1,410 research outputs found
Biochemical Comparison of Anopheles gambiae and Human NADPH P450 Reductases Reveals Different 2âČ-5âČ-ADP and FMN Binding Traits
NADPH-cytochrome P450 oxidoreductase (CPR) plays a central role in chemical
detoxification and insecticide resistance in Anopheles gambiae,
the major vector for malaria. Anopheles gambiae CPR (AgCPR) was
initially expressed in Eschericia coli but failed to bind
2âČ, 5âČ-ADP Sepharose. To investigate this unusual trait, we
expressed and purified a truncated histidine-tagged version for side-by-side
comparisons with human CPR. Close functional similarities were found with
respect to the steady state kinetics of cytochrome c reduction,
with rates (kcat) of 105
sâ1 and 88 sâ1, respectively, for mosquito
and human CPR. However, the inhibitory effects of 2âČ,5âČ-ADP on
activity were different; the IC50 value of AgCPR for 2âČ,
5âČ âADP was significantly higher (6â10 fold) than human CPR
(hCPR) in both phosphate and phosphate-free buffer, indicative of a decrease in
affinity for 2âČ, 5âČ- ADP. This was confirmed by isothermal titration
calorimetry where binding of 2âČ,5âČ-ADP to AgCPR
(Kdâ=â410±18 nM) was
âŒ10 fold weaker than human CPR
(Kdâ=â38 nM). Characterisation
of the individual AgFMN binding domain revealed much weaker binding of FMN
(Kdâ=â83±2.0 nM) than the equivalent
human domain (Kdâ=â23±0.9 nM).
Furthermore, AgCPR was an order of magnitude more sensitive than hCPR to the
reductase inhibitor diphenyliodonium chloride
(IC50â=â28 ”M±2 and 361±31
”M respectively). Taken together, these results reveal unusual biochemical
differences between mosquito CPR and the human form in the binding of small
molecules that may aid the development of âsmartâ insecticides and
synergists that selectively target mosquito CPR
Long acting risperidone in Australian patients with chronic schizophrenia: 24-month data from the e-STAR database
<p>Abstract</p> <p>Background</p> <p>This observational study was designed to collect treatment outcomes data in patients using the electronic Schizophrenia Treatment Adherence Registry (e-STAR).</p> <p>Methods</p> <p>Patients with schizophrenia or schizoaffective disorder in Australia who were prescribed risperidone long-acting injection (RLAI) between 2003 and 2007 were assessed 12-months retrospectively, at baseline and 24-months prospectively at 3-monthly intervals. The intent-to-treat population, defined as all patients who received at least one dose of RLAI at baseline, was used for the efficacy and safety analyses.</p> <p>Results</p> <p>At total of 784 patients (74% with schizophrenia, 69.8% male) with a mean age of 37.1 ± 12.5 years and 10.6 ± 9.5 years since diagnosis were included in this Australian cohort. A significant improvement in mean Clinical Global Impression - severity score was observed at 24-months (4.52 ± 1.04 at baseline, 3.56 ± 1.10 at 24-months). Most of this improvement was seen by 3-months and was also reflected in mean Global Assessment of Functioning score, which improved significantly at 24-months (42.9 ± 14.5 at baseline, 59 ± 15.4 at 24-months). For patients still receiving RLAI at 24-months there was an increase from a mean baseline RLAI dose of 26.4 ± 5 mg to 43.4 ± 15.7 mg. Sixty-six percent of patients discontinued RLAI before the 24-month period--this decreased to 46% once patients lost to follow-up were excluded.</p> <p>Conclusion</p> <p>Over the 24-month period, initiation of RLAI was associated with improved patient functioning and illness severity in patients with schizophrenia or schizoaffective disorder. Improved outcomes were observed early and sustained throughout the study.</p> <p>Trial Registration</p> <p>Clinical Trials Registration Number, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00283517">NCT00283517</a>.</p
Bone Biomarkers Help Grading Severity of Coronary Calcifications in Non Dialysis Chronic Kidney Disease Patients
BACKGROUND: Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF23) are recognized as strong risk factors of vascular calcifications in non dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between FGF23, OPG, and coronary artery calcifications (CAC) in this population and to attempt identification of the most powerful biomarker of CAC: FGF23? OPG? METHODOLOGY/PRINCIPAL FINDINGS: 195 ND-CKD patients (112 males/83 females, 70.8 [27.4-94.6] years) were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. Vascular risk markers including FGF23 and OPG were measured. Logistic regression analyses were used to study the potential relationships between CAC and these markers. The fully adjusted-univariate analysis clearly showed high OPG (â„10.71 pmol/L) as the only variable significantly associated with moderate CAC ([100-400[) (ORâ=â2.73 [1.03;7.26]; pâ=â0.04). Such association failed to persist for CAC scoring higher than 400. Indeed, severe CAC was only associated with high phosphate fractional excretion (FEPO(4)) (â„38.71%) (ORâ=â5.47 [1.76;17.0]; pâ=â0.003) and high FGF23 (â„173.30 RU/mL) (ORâ=â5.40 [1.91;15.3]; pâ=â0.002). In addition, the risk to present severe CAC when FGF23 level was high was not significantly different when OPG was normal or high. Conversely, the risk to present moderate CAC when OPG level was high was not significantly different when FGF23 was normal or high. CONCLUSIONS: Our results strongly suggest that OPG is associated to moderate CAC while FGF23 rather represents a biomarker of severe CAC in ND-CKD patients
Study of B0(s)âK0Sh+hâČâ decays with first observation of B0sâK0SK±Ïâ and B0sâK0SÏ+Ïâ
A search for charmless three-body decays of B 0 and B0s mesons with a K0S meson in the final state is performed using the pp collision data, corresponding to an integrated luminosity of 1.0 fbâ1, collected at a centre-of-mass energy of 7 TeV recorded by the LHCb experiment. Branching fractions of the B0(s)âK0Sh+hâČâ decay modes (h (âČ) = Ï, K), relative to the well measured B0âK0SÏ+Ïâ decay, are obtained. First observation of the decay modes B0sâK0SK±Ïâ and B0sâK0SÏ+Ïâ and confirmation of the decay B0âK0SK±Ïâ are reported. The following relative branching fraction measurements or limits are obtained B(B0âK0SK±Ïâ)B(B0âK0SÏ+Ïâ)=0.128±0.017(stat.)±0.009(syst.), B(B0âK0SK+Kâ)B(B0âK0SÏ+Ïâ)=0.385±0.031(stat.)±0.023(syst.), B(B0sâK0SÏ+Ïâ)B(B0âK0SÏ+Ïâ)=0.29±0.06(stat.)±0.03(syst.)±0.02(fs/fd), B(B0sâK0SK±Ïâ)B(B0âK0SÏ+Ïâ)=1.48±0.12(stat.)±0.08(syst.)±0.12(fs/fd)B(B0sâK0SK+Kâ)B(B0âK0SÏ+Ïâ)â[0.004;0.068]at90%CL
Differential branching fraction and angular analysis of decays
The differential branching fraction of the rare decay is measured as a function of , the
square of the dimuon invariant mass. The analysis is performed using
proton-proton collision data, corresponding to an integrated luminosity of 3.0
\mbox{ fb}^{-1}, collected by the LHCb experiment. Evidence of signal is
observed in the region below the square of the mass. Integrating
over 15 < q^{2} < 20 \mbox{ GeV}^2/c^4 the branching fraction is measured as
d\mathcal{B}(\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^-)/dq^2 = (1.18 ^{+
0.09} _{-0.08} \pm 0.03 \pm 0.27) \times 10^{-7} ( \mbox{GeV}^{2}/c^{4})^{-1},
where the uncertainties are statistical, systematic and due to the
normalisation mode, , respectively.
In the intervals where the signal is observed, angular distributions are
studied and the forward-backward asymmetries in the dimuon ()
and hadron () systems are measured for the first time. In the
range 15 < q^2 < 20 \mbox{ GeV}^2/c^4 they are found to be A^{l}_{\rm FB} =
-0.05 \pm 0.09 \mbox{ (stat)} \pm 0.03 \mbox{ (syst)} and A^{h}_{\rm FB} =
-0.29 \pm 0.07 \mbox{ (stat)} \pm 0.03 \mbox{ (syst)}.Comment: 27 pages, 10 figures, Erratum adde
Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV
We report on the rapidity and centrality dependence of proton and anti-proton
transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as
measured by the STAR experiment at RHIC. Our results are from the rapidity and
transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons
and anti-protons, transverse mass distributions become more convex from
peripheral to central collisions demonstrating characteristics of collective
expansion. The measured rapidity distributions and the mean transverse momenta
versus rapidity are flat within |y|<0.5. Comparisons of our data with results
from model calculations indicate that in order to obtain a consistent picture
of the proton(anti-proton) yields and transverse mass distributions the
possibility of pre-hadronic collective expansion may have to be taken into
account.Comment: 4 pages, 3 figures, 1 table, submitted to PR
Lack of the Long Pentraxin PTX3 Promotes Autoimmune Lung Disease but not Glomerulonephritis in Murine Systemic Lupus Erythematosus
The long pentraxin PTX3 has multiple roles in innate immunity. For example, PTX3 regulates C1q binding to pathogens and dead cells and regulates their uptake by phagocytes. It also inhibits P-selectin-mediated recruitment of leukocytes. Both of these mechanisms are known to be involved in autoimmunity and autoimmune tissue injury, e.g. in systemic lupus erythematosus, but a contribution of PTX3 is hypothetical. To evaluate a potential immunoregulatory role of PTX3 in autoimmunity we crossed Ptx3-deficient mice with Fas-deficient (lpr) C57BL/6 (B6) mice with mild lupus-like autoimmunity. PTX3 was found to be increasingly expressed in kidneys and lungs of B6lpr along disease progression. Lack of PTX3 impaired the phagocytic uptake of apoptotic T cells into peritoneal macrophages and selectively expanded CD4/CD8 double negative T cells while other immune cell subsets and lupus autoantibody production remained unaffected. Lack of PTX3 also aggravated autoimmune lung disease, i.e. peribronchial and perivascular CD3+ T cell and macrophage infiltrates of B6lpr mice. In contrast, histomorphological and functional parameters of lupus nephritis remained unaffected by the Ptx3 genotype. Together, PTX3 specifically suppresses autoimmune lung disease that is associated with systemic lupus erythematosus. Vice versa, loss-of-function mutations in the Ptx3 gene might represent a genetic risk factor for pulmonary (but not renal) manifestations of systemic lupus or other autoimmune diseases
Observation of associated near-side and away-side long-range correlations in âsNN=5.02ââTeV proton-lead collisions with the ATLAS detector
Two-particle correlations in relative azimuthal angle (ÎÏ) and pseudorapidity (Îη) are measured in âsNN=5.02ââTeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1ââÎŒb-1 of data as a function of transverse momentum (pT) and the transverse energy (ÎŁETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Îη|<5) ânear-sideâ (ÎÏâŒ0) correlation that grows rapidly with increasing ÎŁETPb. A long-range âaway-sideâ (ÎÏâŒÏ) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ÎŁETPb, is found to match the near-side correlation in magnitude, shape (in Îη and ÎÏ) and ÎŁETPb dependence. The resultant ÎÏ correlation is approximately symmetric about Ï/2, and is consistent with a dominant cosâĄ2ÎÏ modulation for all ÎŁETPb ranges and particle pT
Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at âs = 7 TeV with the ATLAS detector
This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of âs = 7 TeV;{\rm Te}{\rm V}4.6\;{\rm f}{{{\rm b}}^{-1}}{{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}|\eta |\lt 1.9{{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques
Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector
The inclusive and dijet production cross-sections have been measured for jets
containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass
energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The
measurements use data corresponding to an integrated luminosity of 34 pb^-1.
The b-jets are identified using either a lifetime-based method, where secondary
decay vertices of b-hadrons in jets are reconstructed using information from
the tracking detectors, or a muon-based method where the presence of a muon is
used to identify semileptonic decays of b-hadrons inside jets. The inclusive
b-jet cross-section is measured as a function of transverse momentum in the
range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet
cross-section is measured as a function of the dijet invariant mass in the
range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets
and the angular variable chi in two dijet mass regions. The results are
compared with next-to-leading-order QCD predictions. Good agreement is observed
between the measured cross-sections and the predictions obtained using POWHEG +
Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet
cross-section. However, it does not reproduce the measured inclusive
cross-section well, particularly for central b-jets with large transverse
momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final
version published in European Physical Journal
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