1,028 research outputs found
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
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
First Tests of the Indiana Silicon Sphere (ISiS)
This research was sponsored by the National Science Foundation Grant NSF PHY-931478
Analytical Results for Individual and Group Selection of Any Intensity
The idea of evolutionary game theory is to relate the payoff of a game to reproductive success (= fitness). An underlying assumption in most models is that fitness is a linear function of the payoff. For stochastic evolutionary dynamics in finite populations, this leads to analytical results in the limit of weak selection, where the game has a small effect on overall fitness. But this linear function makes the analysis of strong selection difficult. Here, we show that analytical results can be obtained for any intensity of selection, if fitness is defined as an exponential function of payoff. This approach also works for group selection (= multi-level selection). We discuss the difference between our approach and that of inclusive fitness theory
Recent Advances in Understanding Particle Acceleration Processes in Solar Flares
We review basic theoretical concepts in particle acceleration, with
particular emphasis on processes likely to occur in regions of magnetic
reconnection. Several new developments are discussed, including detailed
studies of reconnection in three-dimensional magnetic field configurations
(e.g., current sheets, collapsing traps, separatrix regions) and stochastic
acceleration in a turbulent environment. Fluid, test-particle, and
particle-in-cell approaches are used and results compared. While these studies
show considerable promise in accounting for the various observational
manifestations of solar flares, they are limited by a number of factors, mostly
relating to available computational power. Not the least of these issues is the
need to explicitly incorporate the electrodynamic feedback of the accelerated
particles themselves on the environment in which they are accelerated. A brief
prognosis for future advancement is offered.Comment: This is a chapter in a monograph on the physics of solar flares,
inspired by RHESSI observations. The individual articles are to appear in
Space Science Reviews (2011
The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansion
Memory T cells exhibit superior responses to pathogens and tumors compared with their naive counterparts. Memory is typically generated via an immune response to a foreign antigen, but functional memory T cells can also be produced from naive cells by homeostatic mechanisms. Using a recently developed method, we studied CD8 T cells, which are specific for model (ovalbumin) and viral (HSV, vaccinia) antigens, in unimmunized mice and found a subpopulation bearing markers of memory cells. Based on their phenotypic markers and by their presence in germ-free mice, these preexisting memory-like CD44hi CD8 T cells are likely to arise via physiological homeostatic proliferation rather than a response to environmental microbes. These antigen-inexperienced memory phenotype CD8 T cells display several functions that distinguish them from their CD44lo counterparts, including a rapid initiation of proliferation after T cell stimulation and rapid IFN-γ production after exposure to proinflammatory cytokines. Collectively, these data indicate that the unprimed antigen-specific CD8 T cell repertoire contains antigen-inexperienced cells that display phenotypic and functional traits of memory cells
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
Search for lepton-flavor violation at HERA
A search for lepton-flavor-violating interactions and has been performed with the ZEUS detector using the entire HERA I
data sample, corresponding to an integrated luminosity of 130 pb^{-1}. The data
were taken at center-of-mass energies, , of 300 and 318 GeV. No
evidence of lepton-flavor violation was found, and constraints were derived on
leptoquarks (LQs) that could mediate such interactions. For LQ masses below
, limits were set on , where
is the coupling of the LQ to an electron and a
first-generation quark , and is the branching ratio of
the LQ to the final-state lepton ( or ) and a quark . For
LQ masses much larger than , limits were set on the four-fermion
interaction term for LQs that couple to an electron and a quark
and to a lepton and a quark , where and are
quark generation indices. Some of the limits are also applicable to
lepton-flavor-violating processes mediated by squarks in -Parity-violating
supersymmetric models. In some cases, especially when a higher-generation quark
is involved and for the process , the ZEUS limits are the most
stringent to date.Comment: 37 pages, 10 figures, Accepted by EPJC. References and 1 figure (Fig.
6) adde
Multijet production in neutral current deep inelastic scattering at HERA and determination of alpha_s
Multijet production rates in neutral current deep inelastic scattering have
been measured in the range of exchanged boson virtualities 10 < Q2 < 5000 GeV2.
The data were taken at the ep collider HERA with centre-of-mass energy sqrt(s)
= 318 GeV using the ZEUS detector and correspond to an integrated luminosity of
82.2 pb-1. Jets were identified in the Breit frame using the k_T cluster
algorithm in the longitudinally invariant inclusive mode. Measurements of
differential dijet and trijet cross sections are presented as functions of jet
transverse energy E_{T,B}{jet}, pseudorapidity eta_{LAB}{jet} and Q2 with
E_{T,B}{jet} > 5 GeV and -1 < eta_{LAB}{jet} < 2.5. Next-to-leading-order QCD
calculations describe the data well. The value of the strong coupling constant
alpha_s(M_Z), determined from the ratio of the trijet to dijet cross sections,
is alpha_s(M_Z) = 0.1179 pm 0.0013(stat.) {+0.0028}_{-0.0046}(exp.)
{+0.0064}_{-0.0046}(th.)Comment: 22 pages, 5 figure
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