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

The reliability of eyetracking to assess attentional bias to threatening words in healthy individuals

Eyetracking is commonly used to investigate attentional bias. Although some studies have investigated the internal consistency of eyetracking, data are scarce on the test–retest reliability and agreement of eyetracking to investigate attentional bias. This study reports the test–retest reliability, measurement error, and internal consistency of 12 commonly used outcome measures thought to reflect the different components of attentional bias: overall attention, early attention, and late attention. Healthy participants completed a preferential-looking eyetracking task that involved the presentation of threatening (sensory words, general threat words, and affective words) and nonthreatening words. We used intraclass correlation coefficients (ICCs) to measure test–retest reliability (ICC \u3e .70 indicates adequate reliability). The ICCs(2, 1) ranged from –.31to.71. Reliability varied according to the outcome measure and threat word category. Sensory words had a lower mean ICC (.08) than either affective words (.32) or general threat words (.29). A longer exposure time was associated with higher test–retest reliability. All of the outcome measures, except second-run dwell time, demonstrated low measurement error (\u3c6%). Most of the outcome measures reported high internal consistency (α \u3e.93). Recommendations are discussed for improving the reliability of eyetracking tasks in future research

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

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

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

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

Development and testing of a practicum matching program for baccalaureate nursing education, a local public health unit

This article describes a novel approach to nursing education, designed to improve the experience of both students in public health nursing, and the local public health unit where they affiliate. Students, faculty, and public health department staff developed a method for matching programs and needs of the local public health unit to the skills and learning needs of nursing students. We describe our experience articulating student competencies, program‐specific functions, and an approach to matching student interests and learning opportunities to agency needs. Students, faculty, and staff rated the program moderately to very high in feasibility, satisfaction, and acceptability. Data suggest the novel program served to improve the quality of the practicum affiliation, to the satisfaction of both the school and agency, while contributing to a robust public health learning experience for emerging professional nurses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162738/2/phn12767.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162738/1/phn12767_am.pd

Correction

n/

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

British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service