Plasmodium falciparum glyoxalase II: Theorell-Chance product inhibition patterns, rate-limiting substrate binding via Arg(257)/Lys(260), and unmasking of acid-base catalysis

Glyoxalase II (GloII) is a ubiquitous thioester hydrolase catalyzing the last step of the glutathione-dependent conversion of 2-oxoaldehydes to 2-hydroxycarboxylic acids. Here, we present a detailed structure-function analysis of cGloII from the malaria parasite Plasmodium falciparum. The activity of the enzyme was salt-sensitive and pH-log k(cat) and pH-log k(cat)/K-m profiles revealed acid-base catalysis. An acidic pK(a)(app) value of approximately 6 probably reflects hydroxide formation at the metal center. The glutathione-binding site was analyzed by site-directed mutagenesis. Substitution of residue Arg(154) caused a 2.5-fold increase of K-m(app), whereas replacements of Arg(257) or Lys(260) were far more detrimental. Although the glutathione-binding site and the catalytic center are separated, six of six single mutations at the substrate-binding site decreased the k(cat)(app) value. Furthermore, product inhibition studies support a Theorell-Chance Bi Bi mechanism with glutathione as the second product. We conclude that the substrate is predominantly bound via ionic interactions with the conserved residues Arg(257) and Lys(260), and that correct substrate binding is a pH-and salt-dependent rate-limiting step for catalysis. The presented mechanistic model is presumably also valid for GloII from many other organisms. Our study could be valuable for drug development strategies and enhances the understanding of the chemistry of binuclear metallohydrolases

Rapid diagnostic test for antenatal syphilis screening in low-income and middle-income countries: a systematic review and meta-analysis

OBJECTIVES: To undertake a systematic review and meta-analysis to evaluate the test performance including sensitivity and specificity of rapid immunochromatographic syphilis (ICS) point-of-care (POC) tests at antenatal clinics compared with reference standard tests (non-treponemal (TP) and TP tests) for active syphilis in pregnant women. METHODS: Five electronic databases were searched (PubMed, EMBASE, CRD, Cochrane Library and LILACS) to March 2016 for diagnostic accuracy studies of ICS test and standard reference tests for syphilis in pregnant women. Methodological quality was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). A bivariate meta-analysis was undertaken to generate pooled estimates of diagnostic parameters. Results were presented using a coupled forest plot of sensitivity and specificity and a scatter plot. RESULTS: The methodological quality of the five included studies with regards to risk of bias and applicability concern judgements was either low or unclear. One study was judged as high risk of bias for patient selection due to exclusion of pregnant women with a previous history of syphilis, and one study was judged at high risk of bias for study flow and timing as not all patients were included in the analysis. Five studies contributed to the meta-analysis, providing a pooled sensitivity and specificity for ICS of 0.85 (95% CrI: 0.73 to 0.92) and 0.98 (95% CrI: 0.95 to 0.99), respectively. CONCLUSIONS: This review and meta-analysis observed that rapid ICS POC tests have a high sensitivity and specificity when performed in pregnant women at antenatal clinics. However, the methodological quality of the existing evidence base should be taken into consideration when interpreting these results. PROSPERO REGISTRATION NUMBER: CRD42016036335

Mechanisms for Strong Anisotropy of In-Plane g-Factors in Hole Based Quantum Point Contacts

In-plane hole g factors measured in quantum point contacts based on p-type heterostructures strongly depend on the orientation of the magnetic field with respect to the electric current. This effect, first reported a decade ago and confirmed in a number of publications, has remained an open problem. In this work, we present systematic experimental studies to disentangle different mechanisms contributing to the effect and develop the theory which describes it successfully. We show that there is a new mechanism for the anisotropy related to the existence of an additional Bþk4 −σþ effective Zeeman interaction for holes, which is kinematically different from the standard single Zeeman term B−k2 −σþ considered until now

Competition of charge, orbital, and ferromagnetic correlations in layered manganites

The competition of charge, orbital, and ferromagnetic interactions in layered manganites is investigated by magneto-Raman scattering spectroscopy. We find that the colossal magnetoresistance effect in the layered compounds results from the interplay of the orbital and ferromagnetic double-exchange correlations. Inelastic scattering by charge-order fluctuations dominates the quasiparticle dynamics in the ferromagnetic-metal state. The scattering is suppressed at low frequencies, consistent with the opening of a charge-density wave pseudogap.Comment: 10 pages, 4 figure

BB flavour tagging using charm decays at the LHCb experiment

An algorithm is described for tagging the flavour content at production of neutral $B$ mesons in the LHCb experiment. The algorithm exploits the correlation of the flavour of a $B$ meson with the charge of a reconstructed secondary charm hadron from the decay of the other $b$ hadron produced in the proton-proton collision. Charm hadron candidates are identified in a number of fully or partially reconstructed Cabibbo-favoured decay modes. The algorithm is calibrated on the self-tagged decay modes $B^+ \to J/\psi \, K^+$ and $B^0 \to J/\psi \, K^{*0}$ using $3.0\mathrm{\,fb}^{-1}$ of data collected by the LHCb experiment at $pp$ centre-of-mass energies of $7\mathrm{\,TeV}$ and $8\mathrm{\,TeV}$. Its tagging power on these samples of $B \to J/\psi \, X$ decays is $(0.30 \pm 0.01 \pm 0.01) \%$.Comment: All figures and tables, along with any supplementary material and additional information, are available at http://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-027.htm

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Evidence for the strangeness-changing weak decay Ξb−→Λb0π−\Xi_b^-\to\Lambda_b^0\pi^-

Using a $pp$ collision data sample corresponding to an integrated luminosity of 3.0~fb$^{-1}$, collected by the LHCb detector, we present the first search for the strangeness-changing weak decay $\Xi_b^-\to\Lambda_b^0\pi^-$. No $b$ hadron decay of this type has been seen before. A signal for this decay, corresponding to a significance of 3.2 standard deviations, is reported. The relative rate is measured to be ${{f_{\Xi_b^-}}\over{f_{\Lambda_b^0}}}{\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-) = (5.7\pm1.8^{+0.8}_{-0.9})\times10^{-4}$, where $f_{\Xi_b^-}$ and $f_{\Lambda_b^0}$ are the $b\to\Xi_b^-$ and $b\to\Lambda_b^0$ fragmentation fractions, and ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ is the branching fraction. Assuming $f_{\Xi_b^-}/f_{\Lambda_b^0}$ is bounded between 0.1 and 0.3, the branching fraction ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ would lie in the range from $(0.57\pm0.21)\%$ to $(0.19\pm0.07)\%$.Comment: 7 pages, 2 figures, All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-047.htm

Measurement of D*+/- meson production in jets from pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

This paper reports a measurement of D*+/- meson production in jets from proton-proton collisions at a center-of-mass energy of sqrt(s) = 7 TeV at the CERN Large Hadron Collider. The measurement is based on a data sample recorded with the ATLAS detector with an integrated luminosity of 0.30 pb^-1 for jets with transverse momentum between 25 and 70 GeV in the pseudorapidity range |eta| < 2.5. D*+/- mesons found in jets are fully reconstructed in the decay chain: D*+ -> D0pi+, D0 -> K-pi+, and its charge conjugate. The production rate is found to be N(D*+/-)/N(jet) = 0.025 +/- 0.001(stat.) +/- 0.004(syst.) for D*+/- mesons that carry a fraction z of the jet momentum in the range 0.3 < z < 1. Monte Carlo predictions fail to describe the data at small values of z, and this is most marked at low jet transverse momentum.Comment: 10 pages plus author list (22 pages total), 5 figures, 1 table, matches published version in Physical Review

Forward jet production in deep inelastic ep scattering and low-x parton dynamics at HERA

Differential inclusive jet cross sections in neutral current deep inelastic ep scattering have been measured with the ZEUS detector. Three phase-space regions have been selected in order to study parton dynamics where the effects of BFKL evolution might be present. The measurements have been compared to the predictions of leading-logarithm parton shower Monte Carlo models and fixed-order perturbative QCD calculations. In the forward region, QCD calculations at order alpha_s^1 underestimate the data up to an order of magnitude at low x. An improved description of the data in this region is obtained by including QCD corrections at order alpha_s^2, which account for the lowest-order t-channel gluon-exchange diagrams, highlighting the importance of such terms in parton dynamics at low x.Comment: 25 pages, 4 figure

Time-integrated luminosity recorded by the BABAR detector at the PEP-II e+e- collider

This article is the Preprint version of the final published artcile which can be accessed at the link below.We describe a measurement of the time-integrated luminosity of the data collected by the BABAR experiment at the PEP-II asymmetric-energy e+e- collider at the ϒ(4S), ϒ(3S), and ϒ(2S) resonances and in a continuum region below each resonance. We measure the time-integrated luminosity by counting e+e-→e+e- and (for the ϒ(4S) only) e+e-→μ+μ- candidate events, allowing additional photons in the final state. We use data-corrected simulation to determine the cross-sections and reconstruction efficiencies for these processes, as well as the major backgrounds. Due to the large cross-sections of e+e-→e+e- and e+e-→μ+μ-, the statistical uncertainties of the measurement are substantially smaller than the systematic uncertainties. The dominant systematic uncertainties are due to observed differences between data and simulation, as well as uncertainties on the cross-sections. For data collected on the ϒ(3S) and ϒ(2S) resonances, an additional uncertainty arises due to ϒ→e+e-X background. For data collected off the ϒ resonances, we estimate an additional uncertainty due to time dependent efficiency variations, which can affect the short off-resonance runs. The relative uncertainties on the luminosities of the on-resonance (off-resonance) samples are 0.43% (0.43%) for the ϒ(4S), 0.58% (0.72%) for the ϒ(3S), and 0.68% (0.88%) for the ϒ(2S).This work is supported by the US Department of Energy and National Science Foundation, the Natural Sciences and Engineering Research Council (Canada), the Commissariat à l’Energie Atomique and Institut National de Physique Nucléaire et de Physiquedes Particules (France), the Bundesministerium für Bildung und Forschung and Deutsche Forschungsgemeinschaft (Germany), the Istituto Nazionale di Fisica Nucleare (Italy), the Foundation for Fundamental Research on Matter (The Netherlands), the Research Council of Norway, the Ministry of Education and Science of the Russian Federation, Ministerio de Ciencia e Innovación (Spain), and the Science and Technology Facilities Council (United Kingdom). Individuals have received support from the Marie-Curie IEF program (European Union) and the A.P. Sloan Foundation (USA)