A Plant Virus Movement Protein Regulates the Gcn2p Kinase in Budding Yeast

Virus life cycle heavily depends on their ability to command the host machinery in order to translate their genomes. Animal viruses have been shown to interfere with host translation machinery by expressing viral proteins that either maintain or inhibit eIF2α function by phosphorylation. However, this interference mechanism has not been described for any plant virus yet. Prunnus necrotic ringspot virus (PNRSV) is a serious pathogen of cultivated stone fruit trees. The movement protein (MP) of PNRSV is necessary for the cell-to-cell movement of the virus. By using a yeast-based approach we have found that over-expression of the PNRSV MP caused a severe growth defect in yeast cells. cDNA microarrays analysis carried out to characterise at the molecular level the growth interference phenotype reported the induction of genes related to amino acid deprivation suggesting that expression of MP activates the GCN pathway in yeast cells. Accordingly, PNRSV MP triggered activation of the Gcn2p kinase, as judged by increased eIF2α phosphorylation. Activation of Gcn2p by MP expression required a functional Tor1p kinase, since rapamycin treatment alleviated the yeast cell growth defect and blocked eIF2α phosphorylation triggered by MP expression. Overall, these findings uncover a previously uncharacterised function for PNRSV MP viral protein, and point out at Tor1p and Gcn2p kinases as candidate susceptibility factors for plant viral infections

Microenvironment Eradication of Hepatitis C: A Novel Treatment Paradigm

OBJECTIVES: Prisons are major reservoirs of hepatitis C virus (HCV) in which a therapeutic approach has been particularly difficult so far. Our aim was to create a permanent program of HCV elimination in a prison based on a "test and treat" strategy. METHODS: This open-label clinical trial was conducted in the Spanish prison "El Dueso" between May 2016 and July 2017. Viremic patients were treated with a ledipasvir-sofosbuvir regimen (8-12 weeks) according to the 2015 Spanish Guidelines. A teleconsultation program was established to follow-up patients from the hospital. Non-responders were submitted for a phylogenetic analysis and offered retreatment. An evaluation of new cases of HCV infection was performed every 6 months and upon release in all inmates. RESULTS: 847 (99.5%) inmates accepted to participate. HCV antibodies were present in 110 (13.0%) and 86 (10.2%) had detectable viremia. Most of them were genotype 1 or 3 (82.6%) and had <F2 fibrosis (52.2%). Treatment was started in the 69 inmates whose stay in prison was longer than 30 days. Sustained virological response was achieved in 64 out of 66 patients (96.9%), three of whom were successfully rescued with a salvage regimen after treatment failure. Two patients were lost to follow-up and three are currently on treatment without viremia. As a result, by July 2017 none of the 409 imprisoned was viremic, and neither reinfections nor de novo infections were detected. CONCLUSIONS: A sustained "test-and-treat" strategy against HCV in prisons is feasible and beneficial. Spreading this strategy should entail a public health impact.Supported by Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad, cofinanced by European Development Regional Fund “A way to achieve Europe”,Operative program Intelligent Growth 2014–2020 and grant PIE15/00079. This study received funding assistance from Gilead Sciences, Spain (IN-ES-337-2089), C/Vía de los Poblados, 3, 28033 Madrid, Spain, http://www.gilead. com/about/worldwide-operations/europe/spain; phone number: +34 913789830), who played no part in study design, data analysis, or in the preparation of the manuscript. All study investigators declare to be independent from funders

Influence of the functionalisation of mesoporous silica material UVM-7 on polyphenol oxidase enzyme capture and enzymatic browning

The authors are grateful to the Spanish Government (Projects RTI2018-100910-B-C44 and MAT2015-64139-C4-1) and the Generalitat Valencia (Project PROMETEO/2018/024) for supportMuñoz-Pina, S.; Ros-Lis, JV.; Argüelles Foix, AL.; Martínez-Máñez, R.; Andrés Grau, AM. (2020). Influence of the functionalisation of mesoporous silica material UVM-7 on polyphenol oxidase enzyme capture and enzymatic browning. Food Chemistry. 310:1-8. https://doi.org/10.1016/j.foodchem.2019.125741S1831

Cuantificación de la variabilidad de la repolarización ventricular en pacientes con cardiopatía isquémica

Se propuso un nuevo indicador que se denomina: Relación de desviaciones estándar (DERI) para cuantificar la variabilidad de la repolarización ventricular (VRV). Este indicador tiene en cuenta la variación de las componentes rápidas y lentas de variación de los intervalos RR, RTm (pico de R a pico de T) y RTe (pico de R a final de T). Se ha evaluado en 20 sujetos sanos, 12 sujetos con cardiopatía isquémica (no infartados) y 13 sujetos que sufrieron infarto de miocardio agudo. El indicador DERI es menor en sujetos sanos que en infartados (p We propose the standard deviation ratio index (DERI) to quantify ventricular repolarization variability (VRV). This new index takes into account the changes in the fast and slow components of the RR, RTm (from R peak to T peak) and RTe (from R peak to T end) cardiac intervals. DERI has been evaluated in 20 healthy subjects, 12 subjects with coronary artery disease (CAD) and 13 subjects with acute myocardial infarction (AMI). The DERI index is lower in healthy subjects than in AMI subjects (p < 1,68 &acute; 10-4 for RTm and p < 4,46 &acute; 10-4 for RTe) and in CAD subjects (p < 3,23 &acute; 10-5 for RTm and p < 0,02 for RTe). Breathing patterns affect the DERI index. In order to reduce that influence, we propose to record signals in periods with uniform breathing patterns, such as during sleep

Vacunación de la hepatitis B. Indicaciones del test serológico postvacunal y la dosis de refuerzo

En relación con la hepatitis B, la vacunación estándar permite, en la gran mayoría de los casos, un título de anti-HBs protector (>10 UI/l). Sin embargo, la duración efectiva de la memoria inmunológica no es bien conocida todavía. Como consecuencia de ello, las recomendaciones en el seguimiento postvacunal han sido dispares: desde no realizar seguimiento hasta realizar tests serológicos postvacunales (título de anti-HBs) de manera regular. En los sujetos no protegidos tras la vacunación primaria, la dosis de refuerzo ha demostrado ser efectiva. Pero el procedimiento más adecuado para su utilización en función del título de anti-HBs alcanzado no está bien establecido. Se recomienda el test postvacunal y la monitorización serológica periódica únicamente en determinados grupos de riesgo, fundamentalmente en personal sanitario y en personas inmunodeprimidas. En estos casos la dosis de refuerzo se debe aplicar en los sujetos no respondedores, utilizando incluso el doble de la dosis habitual. No existe todavía un estado de consenso respecto a la temporalidad más adecuada para administrar la dosis de refuerzo

Vacunación de la hepatitis B. Indicaciones del test serológico postvacunal y la dosis de refuerzo

En relación con la hepatitis B, la vacunación estándar permite, en la gran mayoría de los casos, un título de anti-HBs protector (>10 UI/l). Sin embargo, la duración efectiva de la memoria inmunológica no es bien conocida todavía. Como consecuencia de ello, las recomendaciones en el seguimiento postvacunal han sido dispares: desde no realizar seguimiento hasta realizar tests serológicos postvacunales (título de anti-HBs) de manera regular. En los sujetos no protegidos tras la vacunación primaria, la dosis de refuerzo ha demostrado ser efectiva. Pero el procedimiento más adecuado para su utilización en función del título de anti-HBs alcanzado no está bien establecido. Se recomienda el test postvacunal y la monitorización serológica periódica únicamente en determinados grupos de riesgo, fundamentalmente en personal sanitario y en personas inmunodeprimidas. En estos casos la dosis de refuerzo se debe aplicar en los sujetos no respondedores, utilizando incluso el doble de la dosis habitual. No existe todavía un estado de consenso respecto a la temporalidad más adecuada para administrar la dosis de refuerzo

Vacunación de la hepatitis B. Indicaciones del test serológico postvacunal y la dosis de refuerzo

The standard anti-HBV vaccination elicits protective anti-HBs levels (above 10 UI/l) in most people. However, the effective duration of immunologic memory is not well-known. Consequently, the recommendations on the post-vaccination follow-up are not uniform: from vaccination with no follow-up blood test (anti-HBs levels) to regular follow-up blood tests for all vaccinees. In unresponsive subjects a booster dose has been demonstrated to be effective. However, the optimal procedure for management depending anti-HBs levels has not been well established. Postvaccination antibody testing and regular testing for antibodies is recommended only to high-risk subjects, especially to health care workers and subjects with immunodeficiency. In these cases, the booster dose should be administered in nonresponders, and might include double doses. Unanimous consensus does not exist about to the appropriate timing for booster dose administration.En relación con la hepatitis B, la vacunación estándar permite, en la gran mayoría de los casos, un título de anti-HBs protector (>10 UI/l). Sin embargo, la duración efectiva de la memoria inmunológica no es bien conocida todavía. Como consecuencia de ello, las recomendaciones en el seguimiento postvacunal han sido dispares: desde no realizar seguimiento hasta realizar tests serológicos postvacunales (título de anti-HBs) de manera regular. En los sujetos no protegidos tras la vacunación primaria, la dosis de refuerzo ha demostrado ser efectiva. Pero el procedimiento más adecuado para su utilización en función del título de anti-HBs alcanzado no está bien establecido. Se recomienda el test postvacunal y la monitorización serológica periódica únicamente en determinados grupos de riesgo, fundamentalmente en personal sanitario y en personas inmunodeprimidas. En estos casos la dosis de refuerzo se debe aplicar en los sujetos no respondedores, utilizando incluso el doble de la dosis habitual. No existe todavía un estado de consenso respecto a la temporalidad más adecuada para administrar la dosis de refuerzo

The flow of a free water table about a tunnel

Translated from French (Mitt. Schweizerischen Gesellschaft fuer Boden und Felsmechanik 1987 (115) p 3-7)Available from British Library Document Supply Centre- DSC:9057.2457(TRRL-Trans--3514)T / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Evaluation of an automated luminescent bacteria assay for in situ aquatic toxicity determination

A new system for monitoring toxicity TOXcontrol® (MicroLAN BV, The Netherlands) has been used to assess the toxicity of a selection of priority or emergent compounds in the laboratory. In this study, inhibition curves and EC50 – Effective Concentration causing 50% inhibition – of selected compounds (including pesticides, pharmaceuticals, surfactants and metals commonly detected in surface or drinking waters) were determined. This new technology is based on the measurement of Vibrio fischeri bioluminescence inhibition (ISO 11348). The main advantage of this equipment, compared to other laboratory assays, is the fully automation of the procedure. The instrument can be operated online in a simple, rapid and reproducible way. The variability of the results obtained with the TOXcontrol® biomonitoring system has been studied. A comparison with standardised technology based in V. fischeri (Microtox®) and additional test with Daphnia magna for selected organic compounds is presented. The results show that the methodology based on the TOXcontrol® system being validated is accurate and reproducible enough enabling this system to be used as an on-line automatic alert system to detect abnormal concentrations of toxic compound