2,584 research outputs found
Leishmaniavirus-dependent metastatic leishmaniasis is prevented by blocking IL-17A
Cutaneous leishmaniasis has various outcomes, ranging from self-healing reddened papules to extensive open ulcerations that metastasise to secondary sites and are often resistant to standard therapies. In the case of L. guyanensis (L.g), about 5-10% of all infections result in metastatic complications. We recently showed that a cytoplasmic virus within L.g parasites (LRV1) is able to act as a potent innate immunogen, worsening disease outcome in a murine model. In this study, we investigated the immunophenotype of human patients infected by L.g and found a significant association between the inflammatory cytokine IL-17A, the presence of LRV1 and disease chronicity. Further, IL-17A was inversely correlated to the protective cytokine IFN-γ. These findings were experimentally corroborated in our murine model, where IL-17A produced in LRV1+ L.g infection contributed to parasite virulence and dissemination in the absence of IFN-γ. Additionally, IL-17A inhibition in mice using digoxin or SR1001, showed therapeutic promise in limiting parasite virulence. Thus, this murine model of LRV1-dependent infectious metastasis validated markers of disease chronicity in humans and elucidated the immunologic mechanism for the dissemination of Leishmania parasites to secondary sites. Moreover, it confirms the prognostic value of LRV1 and IL-17A detection to prevent metastatic leishmaniasis in human patients
Dependence of Quadrupole Strength in the Transition
Models of baryon structure predict a small quadrupole deformation of the
nucleon due to residual tensor forces between quarks or distortions from the
pion cloud. Sensitivity to quark versus pion degrees of freedom occurs through
the dependence of the magnetic (), electric (), and
scalar () multipoles in the
transition. We report new experimental values for the ratios
and over the range = 0.4-1.8 GeV, extracted from
precision data using a truncated multipole expansion.
Results are best described by recent unitary models in which the pion cloud
plays a dominant role.Comment: 5 pages, 5 figures, 1 table. To be published in Phys. Rev. Lett.
(References, figures and table updated, minor changes.
Observation of exclusive DVCS in polarized electron beam asymmetry measurements
We report the first results of the beam spin asymmetry measured in the
reaction e + p -> e + p + gamma at a beam energy of 4.25 GeV. A large asymmetry
with a sin(phi) modulation is observed, as predicted for the interference term
of Deeply Virtual Compton Scattering and the Bethe-Heitler process. The
amplitude of this modulation is alpha = 0.202 +/- 0.028. In leading-order and
leading-twist pQCD, the alpha is directly proportional to the imaginary part of
the DVCS amplitude.Comment: 6 pages, 5 figure
Bypass and hyperbole in soil science:A perspective from the next generation of soil scientists
International audienceWe, the co‐authors of this letter, are an international group of soil scientists at early career stages, from PhD students to postdoctoral researchers, lecturers, and research fellows with permanent positions. Here, we present our collective musings on soil research challenges and opportunities and, in particular, the points raised by Philippe Baveye (Baveye, 2020a, 2020b) and Johan Bouma (Bouma, 2020) on bypass and hyperbole in soil science. Raising awareness about these issues is a first and necessary step. To this end, we would like to thank Philippe Baveye and Johan Bouma for initiating this debate.......
Observation of Orbitally Excited B_s Mesons
We report the first observation of two narrow resonances consistent with
states of orbitally excited (L=1) B_s mesons using 1 fb^{-1} of ppbar
collisions at sqrt{s} = 1.96 TeV collected with the CDF II detector at the
Fermilab Tevatron. We use two-body decays into K^- and B^+ mesons reconstructed
as B^+ \to J/\psi K^+, J/\psi \to \mu^+ \mu^- or B^+ \to \bar{D}^0 \pi^+,
\bar{D}^0 \to K^+ \pi^-. We deduce the masses of the two states to be m(B_{s1})
= 5829.4 +- 0.7 MeV/c^2 and m(B_{s2}^*) = 5839.7 +- 0.7 MeV/c^2.Comment: Version accepted and published by Phys. Rev. Let
Global Search for New Physics with 2.0/fb at CDF
Data collected in Run II of the Fermilab Tevatron are searched for
indications of new electroweak-scale physics. Rather than focusing on
particular new physics scenarios, CDF data are analyzed for discrepancies with
the standard model prediction. A model-independent approach (Vista) considers
gross features of the data, and is sensitive to new large cross-section
physics. Further sensitivity to new physics is provided by two additional
algorithms: a Bump Hunter searches invariant mass distributions for "bumps"
that could indicate resonant production of new particles; and the Sleuth
procedure scans for data excesses at large summed transverse momentum. This
combined global search for new physics in 2.0/fb of ppbar collisions at
sqrt(s)=1.96 TeV reveals no indication of physics beyond the standard model.Comment: 8 pages, 7 figures. Final version which appeared in Physical Review D
Rapid Communication
Performance of the LHC collimation system during 2015
During the long shutdown, a total of 32 collimators were
replaced or installed to improve the Run 1 system, including 18 new collimators with embedded beam position monitors, additional physics debris collimators, additional passive absorbers and the re-installation or displacement of existing collimators. The commissioning experience as well
as the performance of the collimation system in 2015 is
reviewed following these upgrades. In particular, the operational experience with the embedded BPM collimators
is discussed, emphasizing the improvements on alignment
efficiency and the strategy for better orbit monitoring. Improvements of collimation setting validation through an optimized loss map strategy are also presented. Further improvements planned for 2016 are discussed.peer-reviewe
Therapeutic efficacy of sulphadoxine-pyrimethamine and chloroquine for the treatment of uncomplicated malaria in pregnancy in Burkina Faso
BACKGROUND: A reduction in the therapeutic efficacy of chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) has recently been observed in Burkina Faso. As these two drugs are used in pregnancy, their efficacy in pregnant women was studied to directly assess the level of drug resistance in this specific population, rather than to extrapolate results of studies conducted in children < 5 years of age. METHODS: During the malaria transmission season of 2003 in Ouagadougou, the clinical efficacy of SP and CQ, using the WHO 28-day protocol, was assessed in primigravidae and secundigravidae presenting with uncomplicated malaria. RESULTS: PCR-corrected results by day 28 showed that among 62 women treated with SP, eight (12.9%) experienced late parasitological failure, but no clinical failures. Among 60 women treated with CQ, the overall failure rate was 46.7% including 1.7% early treatment failures, 5% late clinical failures and 40% late parasitological failures. SP induced a haemoglobin gain of 0.3 g/dL by day 14 and 0.9 g/dL by day 28. Treatment responses were independent of gravidity, gestational age and prior antenatal care visits. CONCLUSION: While CQ should no longer be used, the efficacy of SP is still compatible with use for intermittent preventive treatment (IPT) in pregnancy. However, given the possible spread of resistance, the drug should be restricted in its use
“A year-long, fortnightly, observational survey in three European countries of patients with respiratory allergies induced by house dust mites: Methodology, demographics and clinical characteristics”
Evaluating genetic markers and neurobiochemical analytes for fluoxetine response using a panel of mouse inbred strains
RationaleIdentification of biomarkers that establish diagnosis or treatment response is critical to the advancement of research and management of patients with depression.ObjectiveOur goal was to identify biomarkers that can potentially assess fluoxetine response and risk to poor treatment outcome.MethodsWe measured behavior, gene expression, and the levels of 36 neurobiochemical analytes across a panel of genetically diverse mouse inbred lines after chronic treatment with water or fluoxetine.ResultsGlyoxylase 1 (GLO1) and guanine nucleotide-binding protein 1 (GNB1) mostly account for baseline anxiety-like and depressive-like behavior, indicating a common biological link between depression and anxiety. Fluoxetine-induced biochemical alterations discriminated positive responders, while baseline neurobiochemical differences differentiated negative responders (p < 0.006). Results show that glial fibrillary acidic protein, S100 beta protein, GLO1, and histone deacetylase 5 contributed most to fluoxetine response. These proteins are linked within a cellular growth/proliferation pathway, suggesting the involvement of cellular genesis in fluoxetine response. Furthermore, a candidate genetic locus that associates with baseline depressive-like behavior contains a gene that encodes for cellular proliferation/adhesion molecule (Cadm1), supporting a genetic basis for the role of neuro/gliogenesis in depression.ConclusionWe provided a comprehensive analysis of behavioral, neurobiochemical, and transcriptome data across 30 mouse inbred strains that has not been accomplished before. We identified biomarkers that influence fluoxetine response, which, altogether, implicate the importance of cellular genesis in fluoxetine treatment. More broadly, this approach can be used to assess a wide range of drug response phenotypes that are challenging to address in human samples.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-011-2574-z) contains supplementary material, which is available to authorized users
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