Hepatitis C virus attenuates mitochondrial lipid β-oxidation by downregulating mitochondrial trifunctional-protein expression

The course of hepatitis C virus (HCV) infection and disease progression involves alterations in lipid metabolism, leading to symptoms such as hypocholesterolemia and steatosis. Steatosis can be induced by multiple mechanisms, including increases in lipid biosynthesis and uptake, impaired lipoprotein secretion, and/or attenuation of lipid β-oxidation. However, little is known about the effects of HCV on lipid β-oxidation. A previous proteomics study revealed that HCV interacted with both the α- and β-subunits of the mitochondrial trifunctional protein (MTP), an enzyme complex which catalyzes the last 3 steps of mitochondrial lipid β-oxidation for cellular energy production. Here we show that in HCV-infected Huh7.5 cells, lipid β-oxidation was significantly attenuated. Consistently with this, MTP protein and mRNA levels were suppressed by HCV infection. A loss-offunction study showed that MTP depletion rendered cells less responsive to alpha interferon (IFN-α) treatment by impairing IFN-stimulated gene expression. These aspects of host-virus interaction explain how HCV alters host energy homeostasis and how it may also contribute to the establishment of persistent infection in the liver

The C terminus of NS5A domain II is a key determinant of hepatitis C virus genome replication, but is not required for virion assembly and release.

The NS5A protein of hepatitis C virus (HCV) plays roles in both virus genome replication and the assembly of infectious virus particles. NS5A comprises three domains, separated by low-complexity sequences. Whilst the function of domain I appears to be predominantly involved with genome replication, the roles of domains II and III are less well defined. It has been reported previously that a deletion spanning the majority of domain II but retaining the C-terminal 35 residues had no effect on virus production; however, deletion of the entire domain II eliminated genome replication, pointing to a key role for the C terminus of this domain. Recent work has also highlighted this region as the potential binding site of the host factor cyclophilin A (CypA). To define this requirement for replication in more detail, and to investigate the involvement of CypA, we conducted a mutagenic study of the C-terminal 30 residues of domain II within the context of both the infectious JFH-1 virus and a JFH-1-derived subgenomic replicon. We showed that 12 of these residues were absolutely required for virus genome replication, whilst mutations of the remainder either had no phenotype or exhibited a partial reduction in genome replication. There was an absolute correlation between the datasets for virus and subgenomic replicon, indicating that this region is involved solely in the process of genome replication. Comparison of our data with a previously published analysis of the same region in genotype 1b revealed some important differences between the two genotypes of HCV

Measurement of tau polarization in e+ e- annihilation at sqrt{s}=58 GeV

The polarization of tau leptons in the reaction e+ e- --> tau+ tau- has been measured using a e+e- collider, TRISTAN, at the center-of-mass energy of 58 GeV. From the kinematical distributions of daughter particles in tau --> e nu nu-bar, mu nu nu-bar, rho nu or pi(K) nu decays, the average polarization of tau- and its forward-backward asymmetry have been evaluated to be 0.012 +- 0.058 and 0.029 +- 0.057, respectively.Comment: 18 pages, 5 figure

Synthesis, Characterization and Magnetic Susceptibility of the Heavy Fermion Transition Metal Oxide LiV_{2}O_{4}

The preparative method, characterization and magnetic susceptibility \chi measurements versus temperature T of the heavy fermion transition metal oxide LiV_{2}O_{4} are reported in detail. The intrinsic \chi(T) shows a nearly T-independent behavior below ~ 30 K with a shallow broad maximum at about 16 K, whereas Curie-Weiss-like behavior is observed above 50-100 K. Field-cooled and zero-field-cooled magnetization M measurements in applied magnetic fields H = 10 to 100 G from 1.8 to 50 K showed no evidence for spin-glass ordering. Crystalline electric field theory for an assumed cubic V point group symmetry is found insufficient to describe the observed temperature variation of the effective magnetic moment. The Kondo and Coqblin-Schrieffer models do not describe the magnitude and T dependence of \chi with realistic parameters. In the high T range, fits of \chi(T) by the predictions of high temperature series expansion calculations provide estimates of the V-V antiferromagnetic exchange coupling constant J/k_{B} ~ 20 K, g-factor g ~ 2 and the T-independent susceptibility. Other possible models to describe the \chi(T) are discussed. The paramagnetic impurities in the samples were characterized using isothermal M(H) measurements with 0 < H <= 5.5 Tesla at 2 to 6 K. These impurities are inferred to have spin S_{imp} ~ 3/2 to 4, g_{imp} ~ 2 and molar concentrations of 0.01 to 0.8 %, depending on the sample.Comment: 19 typeset RevTeX pages, 16 eps figures included, uses epsf; to be published in Phys. Rev.

GEANT4 : a simulation toolkit

Abstract Geant4 is a toolkit for simulating the passage of particles through matter. It includes a complete range of functionality including tracking, geometry, physics models and hits. The physics processes offered cover a comprehensive range, including electromagnetic, hadronic and optical processes, a large set of long-lived particles, materials and elements, over a wide energy range starting, in some cases, from 250 eV and extending in others to the TeV energy range. It has been designed and constructed to expose the physics models utilised, to handle complex geometries, and to enable its easy adaptation for optimal use in different sets of applications. The toolkit is the result of a worldwide collaboration of physicists and software engineers. It has been created exploiting software engineering and object-oriented technology and implemented in the C++ programming language. It has been used in applications in particle physics, nuclear physics, accelerator design, space engineering and medical physics. PACS: 07.05.Tp; 13; 2

Measurements of total and partial charge-changing cross sections for 200-400 MeV/nucleon 12C in water and polycarbonate

We have studied charged nuclear fragments produced by 200 - 400 MeV/nucleon carbon ions, interacting with water and polycarbonate, using a newly developed emulsion detector. Total and partial charge-changing cross sections for the production of B, Be, and Li fragments were measured and compared with both previously published measurements, and model predictions. This study is of importance for validating and improving carbon ion therapy treatment planning systems, and for estimating the radiological risks for personnel on space missions, since carbon is a significant component of the Galactic Cosmic Rays

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson