Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

An evaluation of the structural validity of the Shoulder Pain and Disability Index (SPADI) using the Rasch model

Purpose: The Shoulder Pain and Disability Index (SPADI) has been extensively evaluated for its psychometric properties using classic test theory (CTT). The purpose of this study was to evaluate its structural validity using Rasch model analysis. Methods: Responses to the SPADI from 1030 patients referred for physiotherapy with shoulder pain and enrolled in a prospective cohort study were available for Rasch model analysis. Overall fit, individual person and item fit, response format, dependence, unidimensionality, targeting, reliability and differential item functioning (DIF) were examined. Results: The SPADI pain subscale initially demonstrated a misfit due to DIF by age and gender. After iterative analysis it showed good fit to the Rasch model with acceptable targeting and unidimensionality (overall fit (chi-square statistic 57.2, p=0.1); mean item fit residual 0.19 (1.5) and mean person fit residual 0.44 (1.1); person separation index (PSI) of 0.83). The disability subscale however shows significant misfit due to uniform DIF even after iterative analyses were used to explore different solutions to the sources of misfit (overall fit (chi-square statistic 57.2, p=0.1); mean item fit residual -0.54 (1.26) and mean person fit residual -0.38 (1.0); PSI 0.84). Conclusions: Rasch Model analysis of the SPADI has identified some strengths and limitations not previously observed using CTT methods. The SPADI should be treated as two separate subscales. The SPADI is a widely used outcome measure in clinical practice and research, however the scores derived from it must be interpreted with caution. The pain subscale fits the Rasch model expectations well. The disability subscale does not fit the Rasch model and its current format does not meet the criteria for true interval-level measurement required for use as a primary endpoint in clinical trials. Clinicians should therefore exercise caution when interpreting score changes on the disability subscale and attempt to compare their scores to age and sex stratified data

Food venue choice, consumer food environment, but not food venue availability within daily travel patterns are associated with dietary intake among adults, Lexington Kentucky 2011

Objective The retail food environment may be one important determinant of dietary intake. However, limited research focuses on individuals’ food shopping behavior and activity within the retail food environment. This study’s aims were to determine the association between six various dietary indicators and 1) food venue availability; 2) food venue choice and frequency; and 3) availability of healthy food within food venue. Methods In Fall, 2011, a cross-sectional survey was conducted among adults (n=121) age 18 years and over in Lexington, Kentucky. Participants wore a global position system (GPS) data logger for 3-days (2 weekdays and 1 weekend day) to track their daily activity space, which was used to assess food activity space. They completed a survey to assess demographics, food shopping behaviors, and dietary outcomes. Food store audits were conducted using the Nutrition Environment Measurement Survey-Store Rudd (NEMS-S) in stores where respondents reported purchasing food (n=22). Multivariate logistic regression was used to examine associations between six dietary variables with food venue availability within activity space; food venue choice; frequency of shopping; and availability of food within food venue. Results 1) Food venue availability within activity space – no significant associations. 2) Food Venue Choice – Shopping at farmers’ markets or specialty grocery stores reported higher odds of consuming fruits and vegetables (OR 1.60 95% CI [1.21, 2.79]). Frequency of shopping - Shopping at a farmers’ markets and specialty stores at least once a week reported higher odds of consumption of fruits and vegetables (OR 1.55 95% CI [1.08, 2.23]). Yet, shopping frequently at a super market had higher odds of consuming sugar-sweetened beverages (OR 1.39 95% CI [1.03, 1.86]). 3) Availability of food within store – those who shop in supermarkets with high availability of healthy food has lower odds of consuming sugar-sweetened beverages (OR 0.65 95% CI [0.14, 0.83]). Conclusion Interventions aimed at improving fruit and vegetable intake need to consider where individuals’ purchase food and the availability within stores as a behavioral and environmental strategy

Rab27a and Rab27b control different steps of the exosome secretion pathway

Exosomes are secreted membrane vesicles that share structural and biochemical characteristics with intraluminal vesicles of multivesicular endosomes (MVEs). Exosomes could be involved in intercellular communication and in the pathogenesis of infectious and degenerative diseases. The molecular mechanisms of exosome biogenesis and secretion are, however, poorly understood. Using an RNA interference (RNAi) screen, we identified five Rab GTPases that promote exosome secretion in HeLa cells. Among these, Rab27a and Rab27b were found to function in MVE docking at the plasma membrane. The size of MVEs was strongly increased by Rab27a silencing, whereas MVEs were redistributed towards the perinuclear region upon Rab27b silencing. Thus, the two Rab27 isoforms have different roles in the exosomal pathway. In addition, silencing two known Rab27 effectors, Slp4 (also known as SYTL4, synaptotagmin-like 4) and Slac2b (also known as EXPH5, exophilin 5), inhibited exosome secretion and phenocopied silencing of Rab27a and Rab27b, respectively. Our results therefore strengthen the link between MVEs and exosomes, and introduce ways of manipulating exosome secretion in vivo

Effect of age, sex and gender on pain sensitivity: A narrative review

© 2017 Eltumi And Tashani. Introduction: An increasing body of literature on sex and gender differences in pain sensitivity has been accumulated in recent years. There is also evidence from epidemiological research that painful conditions are more prevalent in older people. The aim of this narrative review is to critically appraise the relevant literature investigating the presence of age and sex differences in clinical and experimental pain conditions. Methods: A scoping search of the literature identifying relevant peer reviewed articles was conducted on May 2016. Information and evidence from the key articles were narratively described and data was quantitatively synthesised to identify gaps of knowledge in the research literature concerning age and sex differences in pain responses. Results: This critical appraisal of the literature suggests that the results of the experimental and clinical studies regarding age and sex differences in pain contain some contradictions as far as age differences in pain are concerned. While data from the clinical studies are more consistent and seem to point towards the fact that chronic pain prevalence increases in the elderly findings from the experimental studies on the other hand were inconsistent, with pain threshold increasing with age in some studies and decreasing with age in others. Conclusion: There is a need for further research using the latest advanced quantitative sensory testing protocols to measure the function of small nerve fibres that are involved in nociception and pain sensitivity across the human life span. Implications: Findings from these studies should feed into and inform evidence emerging from other types of studies (e.g. brain imaging technique and psychometrics) suggesting that pain in the older humans may have unique characteristics that affect how old patients respond to intervention

The role of diet in the aetiopathogenesis of inflammatory bowel disease

Crohn’s disease and ulcerative colitis, collectively known as IBD, are chronic inflammatory disorders of the gastrointestinal tract. Although the aetiopathogenesis of IBD is largely unknown, it is widely thought that diet has a crucial role in the development and progression of IBD. Indeed, epidemiological and genetic association studies have identified a number of promising dietary and genetic risk factors for IBD. These preliminary studies have led to major interest in investigating the complex interaction between diet, host genetics, the gut microbiota and immune function in the pathogenesis of IBD. In this Review, we discuss the recent epidemiological, gene–environment interaction, microbiome and animal studies that have explored the relationship between diet and the risk of IBD. In addition, we highlight the limitations of these prior studies, in part by explaining their contradictory findings, and review future directions

LUX-ZEPLIN (LZ) Technical Design Report

In this Technical Design Report (TDR) we describe the LZ detector to be built at the Sanford Underground Research Facility (SURF). The LZ dark matter experiment is designed to achieve sensitivity to a WIMP-nucleon spin-independent cross section of three times ten to the negative forty-eighth square centimeters

Estimation and inference under economic restrictions

Estimation of economic relationships often requires imposition of constraints such as positivity or monotonicity on each observation. Methods to impose such constraints, however, vary depending upon the estimation technique employed. We describe a general methodology to impose (observation-specific) constraints for the class of linear regression estimators using a method known as constraint weighted bootstrapping. While this method has received attention in the nonparametric regression literature, we show how it can be applied for both parametric and nonparametric estimators. A benefit of this method is that imposing numerous constraints simultaneously can be performed seamlessly. We apply this method to Norwegian dairy farm data to estimate both unconstrained and constrained parametric and nonparametric models

A Population-Based Evaluation of a Publicly Funded, School-Based HPV Vaccine Program in British Columbia, Canada: Parental Factors Associated with HPV Vaccine Receipt

Analysis of a telephone survey by Gina Ogilvie and colleagues identifies the parental factors associated with HPV vaccine uptake in a school-based program in Canada