Article:Langton, M.J., Keymeulen, F., Ciaccia, M. et al. (2 more authors) (2016) Controlled membrane translocation provides a mechanism for signal transduction and amplification. Nature Chemistry. ISSN 1755-4330 https://doi.org/10.1038/nchem.2678 eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request.Controlled membrane translocation provides a mechanism for signal transduction and amplification Matthew AbstractTransmission and amplification of chemical signals across lipid bilayer membranes is of profound significance in many biological processes, from the development of multi-cellular organisms to information processing in the nervous system. In biology, membrane-spanning proteins are responsible for transmission of chemical signals across membranes, and signal transduction is often associated with an amplified signaling cascade. The ability to reproduce such processes in artificial systems has potential applications in sensing, controlled drug delivery and communication between compartments in tissue-like constructs of synthetic vesicles. Here we describe a new mechanism for transmitting chemical signals across membranes based on controlled translocation of a synthetic molecular transducer from one side of a lipid bilayer membrane to the other. The controlled molecular motion has been coupled to activation of a catalyst on the inside of a vesicle, which leads to a signal amplification process analogous to the biological counterpart. MainLipid bilayer membranes in biological systems enable the formation of compartments, allowing chemical processes on either side of the bilayer to be physically decoupled. An essential feature of such compartmentalized systems is the communication of chemical information between the two sides of a bilayer, mediated by membrane spanning proteins, without uncontrolled mixing of the two solutions. 1 In nature there are two mechanisms by which these signaling proteins transduce and amplify chemical signals across bilayer membranes. Binding of a ligand to the extra-cellular region of a membrane-spanning protein receptor induces either a global conformational change (Fig. 1a), as exemplified by the G-coupled receptors, 2 or dimerization of two proteins (Fig. 1b)...

Chronic hepatitis C is a global health problem with infected individuals at risk of developing liver disease that can progress to hepatocellular carcinoma. Autotaxin generates the biologically active lipid lysophosphatidic acid that has been reported to play a tumorigenic role in a wide number of cancers. In this study we show that hepatitis C virus infection increases autotaxin expression via hypoxia inducible transcription factor and provides an environment in the liver that promotes fibrosis and liver injury. Importantly, we show a new role for lysophosphatidic acid in positively regulating hepatitis C virus replication.

Objective: To evaluate the prevalence of scoliosis and the risk factors in elementary school students.Methods: A cross-sectional study was carried out in 954 students in 2015. The instrument involved was a questionnaire on postural habits, socioeconomic conditions, and demographic factors. The anthropometric measurements, including height and weight, a visual inspection of the deformity of the vertebral column, the leveling of shoulders, and the Adam’s test were obtained. The sample was calculated in the expected frequency of 12.3%, acceptable error rate of 2.0% and confidence level of 95.0%. To compare the proportions, the chi-square test or Fisher’s exact test was applied. The association between scoliosis and risk factors was evaluated by logistic regression, being significant p <0.05.Results: The prevalence of scoliosis was 24.3%, higher in obese patients and students who adopted a sitting position for a long period of time. Obese students showed a 1.8 times higher chance of testing positive Adam’s Forward Bend Test when compared to normal-weight/lean and 2.1 times higher chance compared to overweight students. The sitting position for watching television increases the chance of testing positive Adam’s test in 38.0%, when compared to the lying position. Obesity increases the risk of testing positive Adam’s test in 74.0 and 98.0%, when compared, respectively, to the underweight/normal weight and overweight. Conclusions: There was a high prevalence of scoliosis in students from public elementary schools in Santos. The most influential factors for this deviation of the spine were obesity and the position adopted by students to watch television.

Objective: To evaluate the prevalence of genu valgum and associated factors in elementary school students. Methods: Cross-sectional study, carried out in 2015, with 1,050 children and adolescents enrolled in an elementary school in Santos, Southeast Brazil. Misalignment of the knee was assessed by intermalleolar distance, considering ≥8 cm or <8 cm. Inter-examiners reliability was measured by Kappa coefficient, resulting in 0.94. Nutritional status was evaluated according to the World Health Organization 2006 references. Logistic regression model was applied to analyze variables associated with genu valgum. Results: Among schoolchildren, 7.1% had genu valgum. The frequency was higher among overweight or obese schoolchildren. On average, students with genu valgum are older than those without it. There was no association with gender. Upon logistic regression model, only nutritional status was significantly associated with this condition. The chance of occurrence of valgus knee in overweight and obese schoolchildren was, respectively, 6.0 and 75.7 times greater than among thin or eutrophic subjects.Conclusions: The prevalence of genu valgum in elementary school children and adolescents was 7.1%, being higher among overweight/obese students and presenting no association with gender or age.

CONTEXT AND OBJECTIVE: Viral hepatitis A is still a concern at public health level in Brazil and around the world, due both to the number of affected subjects and the possibility of complications in the acute forms. The Brazilian Ministry of Health estimates that at least 70% of this country' s population has already had contact with the hepatitis A virus (HAV). The aim here was to discover the prevalence of serological markers for the hepatitis A virus among children and teenagers at daycare facilities, kindergartens and elementary schools in the city of Santos. DESIGN AND SETTING: Cross-sectional study in kindergartens and elementary schools within the municipal education network in several regions of the city of Santos. METHOD: Students' family members were surveyed using a questionnaire and 4,680 finger-prick blood samples were taken and assayed by means of the ELISA technique. RESULTS:The general prevalence of anti-HAV IgG was 9.72% and, of these cases, 74.6% were reactive to anti-HAV IgM. There was higher prevalence of anti-HAV IgG among older children, females, children who played in streams, those whose homes were not connected to the sewage system, those whose parents had low education levels, those with low household income and those who did not live along the seashore. The prevalence of anti-HAV IgM peaked in the early years and subsequently fell, and it was lower on the hills and in the Northwestern Zone. CONCLUSION: The general prevalence of serological markers for hepatitis A was low in Santos. RESUMO CONTEXTO E OBJETIVO:A hepatite viral A continua sendo uma preocupação em nível de saúde pública no Brasil e no mundo, tanto pelo número de indivíduos atingidos, como pela possibilidade de complicação das formas agudas. O Ministério da Saúde estima que pelo menos 70% da população do Brasil já tiveram contato com o vírus da hepatite A. O objetivo foi conhecer a prevalência de marcadores sorológicos do vírus da hepatite A em crianças e adolescentes de creches e escolas de ensino infantil e fundamental na cidade de Santos. TIPO DE ESTUDO E LOCAL: Estudo transversal em pré-escolas e de ensino fundamental da rede municipal em diversas regiões da cidade de Santos. MÉTODO: Foi aplicado um questionário aos familiares dos estudantes e coletadas 4.680 amostras de sangue através de punção capilar para realização da sorologia pela técnica ELISA. RESULTADOS: A prevalência geral do anti-HVA IgG foi de 9,72% e, desses, 74,6% foram anti-HVA IgM reagentes. A prevalência de anti-HVA IgG foi maior entre as crianças mais velhas, meninas, aquelas que brincavam em córregos, sem rede de coleta de esgoto em sua moradia, de pais com baixa instrução, de baixa renda familiar e aquelas que não eram moradoras da orla. A prevalência de anti-HVA IgM teve pico nos primeiros anos e posterior queda e, no morro e Zona Noroeste, foi mais baixa. CONCLUSÃO: A prevalência geral dos marcadores sorológicos para hepatite A foi baixa em Santos.