Melatonin activate FIS1, DYN1 and DYN2 Plasmodium falciparum related-genes for mitochondria fission: mitoemerald-GFP as a tool to visualize mitochondria structure

Malaria causes millions of deaths worldwide and is considered a huge burden to underdeveloped countries. The number of cases with resistance to all antimalarials is continuously increasing, making the identification of novel drugs a very urgent necessity. A potentially very interesting target for novel therapeutic intervention is the parasite mitochondrion. In this work we studied in P. falciparum three genes coding for proteins homologues of the mammalian FIS1 (Mitochondrial Fission Protein 1) and DRP1 (Dynamin Related Protein 1) involved in mitochondrial fission. We studied the expression of P. falciparum genes that show ample sequence and structural homologies with the mammalian counterparts, namely FIS1, DYN1 and DYN2. The encoded proteins are characterized by a distinct pattern of expression throughout the erythrocytic cycle of Plasmodium falciparum and their mRNAs are modulated by treating the parasite with the host hormone melatonin. We have previously reported that the knock out of the Plasmodium gene that codes for protein kinase 7 is essential for melatonin sensing. We here show that PfPk7 knockout results in major alterations of mitochondrial fission genes expression when compared to wild type parasites, and no change in fission protein expression upon treatment with the host hormone. Finally we have compared the morphological characteristics(using MitoTracker Red CMX Ros. and oxygen consumption properties of P. falciparum mitochondria in wild type parasites and PfPk7 Knockout strains. A novel GFP construct targeted to the mitochondrial matrix to wild type parasites was also developed to visualize Plasmodium falciparum mitochondria. We here show that, the functional characteristics of P. falciparum are profoundly altered in cells lacking protein kinase 7, suggesting that this enzyme plays a major role in the control of mitochondrial morphogenesis and maturation during the intra erythrocyte cell cycle progression. This article is protected by copyright. All rights reserved

Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) in Common Variable Immunodeficiency (CVID): A Multicenter Retrospective Study of Patients From Italian PID Referral Centers

Background: Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) is a severe non-infectious complication of Common Variable Immunodeficiency (CVID), often associated with extrapulmonary involvement. Due to a poorly understood pathogenesis, GLILD diagnosis and management criteria still lack consensus. Accordingly, it is a relevant cause of long-term loss of respiratory function and is closely associated with a markedly reduced survival. The aim of this study was to describe clinical, immunological, laboratory and functional features of GLILD, whose combination in a predictive model might allow a timely diagnosis. Methods: In a multicenter retrospective cross-sectional study we enrolled 73 CVID patients with radiologic features of interstitial lung disease (ILD) associated to CVID (CVID-ILD) and 125 CVID patients without ILD (controls). Of the 73 CVID-ILD patients, 47 received a definite GLILD diagnosis while 26 received a clinical-radiologic diagnosis of CVID related ILD defined as uILD. Results: In GLILD group we found a higher prevalence of splenomegaly (84.8 vs. 39.2%), autoimmune cytopenia (59.6 vs. 6.4%) and bronchiectasis (72.3 vs. 28%), and lower IgA and IgG serum levels at CVID diagnosis. GLILD patients presented lower percentage of switched-memory B cells and marginal zone B cells, and a marked increase in the percentage of circulating CD21lo B cells (14.2 vs. 2.9%). GLILD patients also showed lower total lung capacity (TLC 87.5 vs. 5.0%) and gas transfer (DLCO 61.5 vs. 5.0%) percent of predicted. By univariate logistic regression analysis, we found IgG and IgA levels at CVID diagnosis, presence of splenomegaly and autoimmune cytopenia, CD21lo B cells percentage, TLC and DCLO percent of predicted to be associated to GLILD. The joint analysis of four variables (CD21lo B cells percentage, autoimmune cytopenia, splenomegaly and DLCO percent of predicted), together in a multiple logistic regression model, yielded an area under the ROC curve (AUC) of 0.98 (95% CI: 0.95-1.0). The AUC was only slightly modified when pooling together GLILD and uILD patients (0.92, 95% CI: 0.87-0.97). Conclusions: we propose the combination of two clinical parameters (splenomegaly and autoimmune cytopenia), one lung function index (DLCO%) and one immunologic variable (CD21lo%) as a promising tool for early identification of CVID patients with interstitial lung disease, limiting the use of aggressive diagnostic procedures

The Q2Q^2-dependence of the generalised Gerasimov-Drell-Hearn integral for the deuteron, proton and neutron

The Gerasimov-Drell-Hearn (GDH) sum rule connects the anomalous contribution to the magnetic moment of the target nucleus with an energy-weighted integral of the difference of the helicity-dependent photoabsorption cross sections. The data collected by HERMES with a deuterium target are presented together with a re-analysis of previous measurements on the proton. This provides a measurement of the generalised GDH integral covering simultaneously the nucleon-resonance and the deep inelastic scattering regions. The contribution of the nucleon-resonance region is seen to decrease rapidly with increasing $Q^2$. The DIS contribution is sizeable over the full measured range, even down to the lowest measured $Q^2$. As expected, at higher $Q^2$ the data are found to be in agreement with previous measurements of the first moment of $g_1$. From data on the deuteron and proton, the GDH integral for the neutron has been derived and the proton--neutron difference evaluated. This difference is found to satisfy the fundamental Bjorken sum rule at $Q^2 = 5$ GeV$^2$.Comment: 12 pages, 10 figure

Evidence for Quark-Hadron Duality in the Proton Spin Asymmetry A1A_1

Spin-dependent lepton-nucleon scattering data have been used to investigate the validity of the concept of quark-hadron duality for the spin asymmetry $A_1$. Longitudinally polarised positrons were scattered off a longitudinally polarised hydrogen target for values of $Q^2$ between 1.2 and 12 GeV$^2$ and values of $W^2$ between 1 and 4 GeV$^2$. The average double-spin asymmetry in the nucleon resonance region is found to agree with that measured in deep-inelastic scattering at the same values of the Bjorken scaling variable $x$. This finding implies that the description of $A_1$ in terms of quark degrees of freedom is valid also in the nucleon resonance region for values of $Q^2$ above 1.6 GeV$^2$.Comment: 5 pages, 1 eps figure, table added, new references added, in print in Phys. Rev. Let

The Q^2-Dependence of Nuclear Transparency for Exclusive ρ0\rho^0 Production

Exclusive coherent and incoherent electroproduction of the $\rho^0$ meson from $^1$H and $^{14}$N targets has been studied at the HERMES experiment as a function of coherence length ($l_c$), corresponding to the lifetime of hadronic fluctuations of the virtual photon, and squared four-momentum of the virtual photon ($-Q^2$). The ratio of $^{14}$N to $^1$H cross sections per nucleon, known as nuclear transparency, was found to increase (decrease) with increasing coherence length for coherent (incoherent) $\rho^0$ electroproduction. For fixed coherence length, a rise of nuclear transparency with $Q^2$ is observed for both coherent and incoherent $\rho^0$ production, which is in agreement with theoretical calculations of color transparency.Comment: 5 pages, 4 figure

Exclusive Leptoproduction of rho^0 Mesons from Hydrogen at Intermediate Virtual Photon Energies

Measurements of the cross section for exclusive virtual-photoproduction of rho^0 mesons from hydrogen are reported. The data were collected by the HERMES experiment using 27.5 GeV positrons incident on a hydrogen gas target in the HERA storage ring. The invariant mass W of the photon-nucleon system ranges from 4.0 to 6.0 GeV, while the negative squared four-momentum Q^2 of the virtual photon varies from 0.7 to 5.0 GeV^2. The present data together with most of the previous data at W > 4 GeV are well described by a model that infers the W-dependence of the cross section from the dependence on the Bjorken scaling variable x of the unpolarized structure function for deep-inelastic scattering. In addition, a model calculation based on Off-Forward Parton Distributions gives a fairly good account of the longitudinal component of the rho^0 production cross section for Q^2 > 2 GeV^2.Comment: 10 pages, 6 embedded figures, LaTeX for SVJour(epj) document class. Revisions: curves added to Fig. 1, several clarifications added to tex

Measurement of single-spin azimuthal asymmetries in semi-inclusive electroproduction of pions and kaons on a longitudinally polarised deuterium target

Single-spin asymmetries have been measured for semi-inclusive electroproduction of $\pi^+$, $\pi^-$, $\pi^0$ and $K^+$ mesons in deep-inelastic scattering off a longitudinally polarised deuterium target. The asymmetries appear in the distribution of the hadrons in the azimuthal angle $\phi$ around the virtual photon direction, relative to the lepton scattering plane. The corresponding analysing powers in the $\sin \phi$ moment of the cross section are $0.012 \pm 0.002 {(stat.)} \pm 0.002 {(syst.)}$ for $\pi^+$, $0.006 \pm 0.003 {(stat.)} \pm 0.002 {(syst.)}$ for $\pi^-$, $0.021 \pm 0.005 {(stat.)} \pm 0.003 {(syst.)}$ for $\pi^0$ and $0.013 \pm 0.006 {(stat.)} \pm 0.003 {(syst.)}$ for $K^+$. The $\sin 2\phi$ moments are compatible with zero for all particles.Comment: Revised version shortened 9 pages, 3 tables, 7 figure

Double-Spin Asymmetry in the Cross Section for Exclusive rho^0 Production in Lepton-Proton Scattering

Evidence for a positive longitudinal double-spin asymmetry = 0.24 +-0.11 (stat) +-0.02 (syst) in the cross section for exclusive diffractive rho^0(770) vector meson production in polarised lepton-proton scattering was observed by the HERMES experiment. The longitudinally polarised 27.56 GeV HERA positron beam was scattered off a longitudinally polarised pure hydrogen gas target. The average invariant mass of the photon-proton system has a value of = 4.9 GeV, while the average negative squared four-momentum of the virtual photon is = 1.7 GeV^2. The ratio of the present result to the corresponding spin asymmetry in inclusive deep-inelastic scattering is in agreement with an early theoretical prediction based on the generalised vector meson dominance model.Comment: 10 pages, 4 embedded figures, LaTe

Single-spin Azimuthal Asymmetries in Electroproduction of Neutral Pions in Semi-inclusive Deep-inelastic Scattering

A single-spin asymmetry in the azimuthal distribution of neutral pions relative to the lepton scattering plane has been measured for the first time in deep-inelastic scattering of positrons off longitudinally polarized protons. The analysing power in the sin(phi) moment of the cross section is 0.019 +/- 0.007(stat.) +/- 0.003(syst.). This result is compared to single-spin asymmetries for charged pion production measured in the same kinematic range. The pi^0 asymmetry is of the same size as the pi^+ asymmetry and shows a similar dependence on the relevant kinematic variables. The asymmetry is described by a phenomenological calculation based on a fragmentation function that represents sensitivity to the transverse polarization of the struck quark.Comment: 4 pages, 1 figure, replaced to correct eprint author field, 2nd replacement to correct figure; upper limit of model predictions are corrected. No correction to data or conclusion