CD81 and claudin 1 coreceptor association: role in hepatitis C virus entry.

Hepatitis C virus (HCV) is an enveloped positive-stranded RNA hepatotropic virus. HCV pseudoparticles infect liver-derived cells, supporting a model in which liver-specific molecules define HCV internalization. Three host cell molecules have been reported to be important entry factors or receptors for HCV internalization: scavenger receptor BI, the tetraspanin CD81, and the tight junction protein claudin-1 (CLDN1). None of the receptors are uniquely expressed within the liver, leading us to hypothesize that their organization within hepatocytes may explain receptor activity. Since CD81 and CLDN1 act as coreceptors during late stages in the entry process, we investigated their association in a variety of cell lines and human liver tissue. Imaging techniques that take advantage of fluorescence resonance energy transfer (FRET) to study protein-protein interactions have been developed. Aequorea coerulescens green fluorescent protein- and Discosoma sp. red-monomer fluorescent protein-tagged forms of CD81 and CLDN1 colocalized, and FRET occurred between the tagged coreceptors at comparable frequencies in permissive and nonpermissive cells, consistent with the formation of coreceptor complexes. FRET occurred between antibodies specific for CD81 and CLDN1 bound to human liver tissue, suggesting the presence of coreceptor complexes in liver tissue. HCV infection and treatment of Huh-7.5 cells with recombinant HCV E1-E2 glycoproteins and anti-CD81 monoclonal antibody modulated homotypic (CD81-CD81) and heterotypic (CD81-CLDN1) coreceptor protein association(s) at specific cellular locations, suggesting distinct roles in the viral entry process

Movement restriction does not modulate sensory and perceptual effects of exercise-induced arm pain

BACKGROUND: Movement restriction has been proposed as an important modulator of changes in sensory and perceptual function and motor imagery performance that are observed in musculoskeletal pain syndromes. There are no empirical data to support this view. PURPOSE: The primary objective of this experiment was to determine the effects of movement restriction on local and widespread sensory, perceptual and motor imagery changes after exercise-induced muscular pain. Further objectives were to investigate whether changes in sensory perception are correlated with pain intensity and tactile acuity or motor imagery performance. METHODS: In forty healthy volunteers, delayed onset muscle soreness (DOMS) of the non-dominant elbow flexors was induced using eccentric contractions until exhaustion. Participants were then randomised into two groups: a movement restriction group (wearing a sling) or a control group (not wearing a sling). Sensory and perceptual functions were measured using a range of sensory tests and a motor imagery performance task (left/right limb judgements). RESULTS: Movement restriction did not modulate any of the measures. We found concurrent mechanical hypoesthesia (p \u3c 0.01), reduced tactile acuity (p = 0.02) and pressure hyperalgesia (p \u3c 0.01) at the painful side. We found evidence of widespread pressure hyperalgesia. Impaired tactile acuity was associated with a decrease in pain threshold to pressure (r = -0.34, p = 0.03). Motor imagery performance was unchanged (p \u3e 0.35) by pain or movement restriction. CONCLUSION: Short-term movement restriction did not influence local and widespread sensory changes induced by experimentally induced muscular pain

VW LMi: tightest quadruple system known. Light-time effect and possible secular changes of orbits

Tightest known quadruple systems VW LMi consists of contact eclipsing binary with P_12 = 0.477551 days and detached binary with P_34 = 7.93063 days revolving in rather tight, 355.0-days orbit. This paper presents new photometric and spectroscopic observations yielding 69 times of minima and 36 disentangled radial velocities for the component stars. All available radial velocities and minima times are combined to better characterize the orbits and to derive absolute parameters of components. The total mass of the quadruple system was estimated at 4.56 M_sun. The detached, non-eclipsing binary with orbital period P = 7.93 days is found to show apsidal motion with U approximately 80 years. Precession period in this binary, caused by the gravitational perturbation of the contact binary, is estimated to be about 120 years. The wide mutual orbit and orbit of the non-eclipsing pair are found to be close to coplanarity, preventing any changes of the inclination angle of the non-eclipsing orbit and excluding occurrence of the second system of eclipses in future. Possibilities of astrometric solution and direct resolving of the wide, mutual orbit are discussed. Nearby star, HD95606, was found to form loose binary with quadruple system VW LMi.Comment: 4 figures. accepted to MNRAS on July 31, 200

6D Dyonic String With Active Hyperscalars

We derive the necessary and sufficient conditions for the existence of a Killing spinor in N=(1,0) gauge supergravity in six dimensions coupled to a single tensor multiplet, vector multiplets and hypermultiplets. These are shown to imply most of the field equations and the remaining ones are determined. In this framework, we find a novel 1/8 supersymmetric dyonic string solution with nonvanishing hypermultiplet scalars. The activated scalars parametrize a 4 dimensional submanifold of a quaternionic hyperbolic ball. We employ an identity map between this submanifold and the internal space transverse to the string worldsheet. The internal space forms a 4 dimensional analog of the Gell-Mann-Zwiebach tear-drop which is noncompact with finite volume. While the electric charge carried by the dyonic string is arbitrary, the magnetic charge is fixed in Planckian units, and hence necessarily non-vanishing. The source term needed to balance a delta function type singularity at the origin is determined. The solution is also shown to have 1/4 supersymmetric AdS_3 x S^3 near horizon limit where the radii are proportional to the electric charge.Comment: 28 pages, latex, minor corrections mad

Complexation of lanthanides, actinides and transition metal cations with a 6-(1,2,4-triazin-3-yl)-2,2’:6’,2’’-terpyridine ligand: implications for actinide(III) /lanthanide(III) partitioning

The quadridentate N-heterocyclic ligand 6-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)-2,2’:6’,2’’-terpyridine (CyMe4-hemi-BTBP) has been synthesized and its interactions with Am(III), U(VI), Ln(III) and some transition metal cations have been evaluated by X-ray crystallographic analysis, Am(III)/Eu(III) solvent extraction experiments, UV absorption spectrophotometry, NMR studies and ESI-MS. Structures of the 1:1 complexes with Eu(III), Ce(III) and the linear uranyl (UO22+) ion were obtained by X-ray crystallographic analysis, and showed similar coordination behavior to related BTBP complexes. In methanol, the stability constants of the Ln(III) complexes are slightly lower than those of the analogous quadridentate bis-triazine BTBP ligands, while the stability constant for the Yb(III) complex is higher. 1H NMR titrations and ESI-MS with lanthanide nitrates showed that the ligand forms only 1:1 complexes with Eu(III), Ce(III) and Yb(III), while both 1:1 and 1:2 complexes were formed with La(III) and Y(III) in acetonitrile. A mixture of isomeric chiral 2:2 helical complexes was formed with Cu(I), with a slight preference (1.4:1) for a single directional isomer. In contrast, a 1:1 complex was observed with the larger Ag(I) ion. The ligand was unable to extract Am(III) or Eu(III) from nitric acid solutions into 1-octanol, except in the presence of a synergist at low acidity. The results show that the presence of two outer 1,2,4-triazine rings is required for the efficient extraction and separation of An(III) from Ln(III) by quadridentate N-donor ligand

Absolute properties of the binary system BB Pegasi

We present a ground based photometry of the low-temperature contact binary BB Peg. We collected all times of mid-eclipses available in literature and combined them with those obtained in this study. Analyses of the data indicate a period increase of 3.0(1) x 10^{-8} days/yr. This period increase of BB Peg can be interpreted in terms of the mass transfer 2.4 x 10^{-8} Ms yr^{-1} from the less massive to the more massive component. The physical parameters have been determined as Mc = 1.42 Ms, Mh = 0.53 Ms, Rc = 1.29 Rs, Rh = 0.83 Rs, Lc = 1.86 Ls, and Lh = 0.94 Ls through simultaneous solution of light and of the radial velocity curves. The orbital parameters of the third body, that orbits the contact system in an eccentric orbit, were obtained from the period variation analysis. The system is compared to the similar binaries in the Hertzsprung-Russell and Mass-Radius diagram.Comment: 17 pages, 3 figures, accepted for Astronomical Journa

Highly efficient separation of actinides from lanthanides by a phenanthroline-derived bis-triazine ligand

The synthesis, lanthanide complexation, and solvent ex- traction of actinide(III) and lanthanide(III) radiotracers from nitric acid solutions by a phenanthroline-derived quadridentate bis-triazine ligand are described. The ligand separates Am(III) and Cm(III) from the lanthanides with remarkably high efficiency, high selectivity, and fast extraction kinetics compared to its 2,2'-bipyridine counterpart. Structures of the 1:2 bis-complexes of the ligand with Eu(III) and Yb(III) were elucidated by X-ray crystallography and force field calculations, respec-tively. The Eu(III) bis-complex is the first 1:2 bis-complex of a quadridentate bis-triazine ligand to be characterized by crystallography. The faster rates of extraction were verified by kinetics measurements using the rotating membrane cell technique in several diluents. The improved kinetics of metal ion extraction are related to the higher surface activity of the ligand at the phase interface. The improvement in the ligand's properties on replacing the bipyridine unit with a phenanthroline unit far exceeds what was anticipated based on ligand design alone

Ethics and social responsibility in practice: interpreters and translators engaging with and beyond the professions

Interpreting and translation are unregulated activities in most countries, yet interpreters and translators perform challenging work in sensitive domains, such as the law, medicine and social work. Other professionals working in these sectors must complete formal ethics training to qualify, then subscribe to Codes of Practice or Ethics. When they face ethical challenges in their work, they can access ongoing support. They must undertake regular refresher training in ethics. Interpreters and translators rarely have access to this sort of ethical infrastructure. This places the onus on interpreters and translators to reflect on ethical aspects of their practice, for reasons related to both professional performance and social responsibility. This contribution presents original UK-based research with one type of professional ‘clients’ who rely on interpreters and translators, social workers and social work students prior to their first work experience placement. Findings suggest that insufficient attention has been paid to such professional clients and that ethical aspects of professional communication can be compromised as a result. By framing ethics training and ongoing support in terms of social responsibility, we point to some ways in which the different professional groups might communicate and work more effectively with one another and with service users

Targeted Selection of Stimulation Parameters for Restoration of Motor and Autonomic Function in Individuals With Spinal Cord Injury

Study Design: This is a report of methods and tools for selection of task and individual configurations targeted for voluntary movement, standing, stepping, blood pressure stabilization, and facilitation of bladder storage and emptying using tonic-interleaved excitation of the lumbosacral spinal cord. Objectives: This study aimed to present strategies used for selection of stimulation parameters for various motor and autonomic functions. Conclusions: Tonic-interleaved functionally focused neuromodulation targets a myriad of consequences from spinal cord injury with surgical implantation of the epidural electrode at a single location. This approach indicates the sophistication of the human spinal cord circuitry and its important role in the regulation of motor and autonomic functions in humans

Collagen proportionate area correlates with histological stage and predicts clinical events in primary sclerosing cholangitis

Background & Aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease in need of accurate biomarkers for stratification and as surrogates for clinical endpoints in trials. Quantitative liver fibrosis assessment by collagen proportionate area (CPA) measurement has been demonstrated to correlate with clinical outcomes in chronic hepatitis C, alcohol-related and non-alcoholic fatty liver disease. We aimed to investigate the ability of CPA to quantify liver fibrosis and predict clinical events in PSC. Methods: Biopsies from 101 PSC patients from two European centres were retrospectively assessed by two expert pathologists in tandem, using grading (Ishak and Nakanuma) and staging (Ishak, Nakanuma, Ludwig) systems recently validated to predict clinical events in PSC. CPA was determined by image analysis of picro-Sirius red-stained sections following a standard protocol. We assessed the correlations between CPA, staging and grading and their associations with three outcomes: (1) time to PSC-related death, liver transplant or primary liver cancer; (2) liver transplant-free survival; (3) occurrence of cirrhosis-related clinical manifestations. Results: CPA correlated strongly with histological stage determined by each scoring system (P < .001) and was significantly associated with the three endpoints. Median time to endpoint-1, endpoint-2 and endpoint-3 was shorter in patients with higher CPA, on Kaplan-Meier analyses (P = .011, P = .034 and P = .001, respectively). Conclusion: Quantitative fibrosis assessment by CPA has utility in PSC. It correlates with established histological staging systems and predicts clinical events. CPA may be a useful tool for staging fibrosis and for risk stratification in PSC and should be evaluated further within prospective clinical trials