Mutations in the NS1 C-terminal tail do not enhance replication or virulence of the 2009 pandemic H1N1 influenza A virus

The ‘classical’ swine H1N1 influenza A virus lineage was established after the devastating 1918 human pandemic virus entered domestic pig herds. A descendent of this lineage recently re-emerged in humans as the 2009 pandemic H1N1 virus. Adaptation in pigs has led to several changes in the multifunctional viral NS1 protein as compared with the parental 1918 virus, most notably a K217E substitution that abolishes binding to host Crk/CrkL signalling adapters, and an 11 aa C-terminal truncation. Using reverse genetics, we reintroduced both these features into a prototype 2009 H1N1 strain, A/California/04/09. Restoration of Crk/CrkL binding or extension of NS1 to 230 aa had no impact on virus replication in human or swine cells. In addition, minimal effects on replication, pathogenicity and transmission were observed in mouse and ferret models. Our data suggest that the currently circulating 2009 H1N1 virus is optimized to replicate efficiently without requiring certain NS1 functions

A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

Asistencia Ventricular definitiva como alternativa al trasplante cardíaco en un paciente ingresado en una unidad de cuidados intensivos: un caso clínico

Rincon-Burgui, R., Jimeno-San Martin, L., Elorza, J., et al. "Asistencia Ventricular definitiva como alternativa al trasplante cardíaco en un paciente ingresado en una unidad de cuidados intensivos: un caso clínico" en XXXVIII Congreso Nacional de la Sociedad Española de Enfermería Intensiva y Unidades Coronarias, celebrado en Santander (España) del 10 de junio de 2012 al 13 de junio de 201

Azithromycin to Prevent Pertussis in Household Contacts, Catalonia and Navarre, Spain, 2012-2013

We retrospectively assessed the effectiveness of azithromycin in preventing transmission of pertussis to a patient's household contacts. We also considered the duration between symptom onset in the primary patient and azithromycin administration. We categorized contacts into 4 groups: those treated within 21 days after illness onset in the primary patient. We studied 476 primary index patients and their 1,975 household contacts, of whom 4.5% were later identified as having pertussis. When contacts started chemoprophylaxis within 14 days after primary patient's symptom onset was less effective. We recommend that contacts of persons with pertussis begin chemoprophylaxis within <14 days after primary patient's symptom onset

Incidence rate trends for colorectal cancer in Navarre (North of Spain) in the 1990-2005 period

Fundamento. En España, se ha observado un aumento de la incidencia de cáncer colorrectal (CCR) en ambos sexos en los últimos años, posiblemente debido a las mejoras diagnósticas, a la occidentalización de la dieta y al empeoramiento de los niveles de obesidad entre otros. En este trabajo se han estudiado las tendencias de la incidencia de CCR en las diferentes áreas de salud de Navarra (norte de España) durante el período 1990-2005. Métodos. Para cada sexo y área, se obtuvieron las tendencias de las tasas de incidencia y los correspondientes intervalos de confianza mediante modelos de P-splines. Resultados. Se observa una tendencia creciente de la incidencia de CCR en la mayoría de las áreas para ambos sexos, siendo menos pronunciada en las mujeres que en los hombres. En la zona centro de Pamplona (la capital) se observa una tendencia decreciente para los hombres durante el período estudiado. Conclusiones. Para cambiar las tendencias crecientes observadas en la mayoría de las áreas de la provincia, la prevención primaria es la mejor estrategia. Sin embargo, adquirir estilos de vida saludables tiene resultados a largo plazo por lo que un programa de detección temprana serviría como estrategia de prevención a más corto plazo.Background. In Spain, an increase in the incidence of colorectal cancer (CRC) has been observed in both sexes in recent years, probably due to an improved diagnostic, the westernization of dietary habits, and worse obesity levels, among others factors. In this work, CRC incidence rate trends in different health areas in Navarre (northern Spain) are studied during the 1990-2005 period. Methods. An estimated incidence trend curve for each health area and the corresponding confidence bands were obtained for each gender using P-spline models. Results. These results show an increasing trend of CRC in most of the areas in both sexes, being less pronounced in women than in men. In the central area of Pamplona (the capital city) a decreasing trend has been observed for men during the studied period. Conclusions. Primary prevention is the best strategy to change the increasing trend observed in most areas of the province of Navarre. However, a healthy lifestyle has long-term results, so it is important to have an early detection program that would serve as a short-term prevention strategy.Este trabajo ha sido financiado por el Ministerio de Ciencia e Innovación (Proyecto MTM2008- 03085 y MTM2011-22664) y por el CIBER de Epidemiología y Salud Pública (CIBERESP)

Communication, development, and social change in Spain: A field between institutionalization and implosion

This paper renders an account of the rapid institutionalization of the academic field of Communication for Development and Social Change (CDCS) in Spain in recent years following a period of neglect and marginalization. The ongoing expansion of the field of CDSC in the Spanish context is understood as a process of implosion, i.e. a collapse inwards, which results from the inconsistencies and weaknesses of fast and late institutionalization. The methodological approach for this inquiry is a documental review of both academic literature and research and institutional reports produced in Spain between 1980 and 2010. Based on this review, the paper contrasts the trajectory of the field in Spain with the debates at the international level, establishing relevant continuities and differences.This article is part of the Research Project (Ministry of Economy and Competitiveness, Spain) CSO2014-52005-R titled ‘Evaluation and Monitoring of Communication for Development and Social Change in Spain: design of indicators to measure its social impact’ (2015–2017)17 página

Translation without eIF2 Promoted by Poliovirus 2A Protease

Poliovirus RNA utilizes eIF2 for the initiation of translation in cell free systems. Remarkably, we now describe that poliovirus translation takes place at late times of infection when eIF2 is inactivated by phosphorylation. By contrast, translation directed by poliovirus RNA is blocked when eIF2 is inactivated at earlier times. Thus, poliovirus RNA translation exhibits a dual mechanism for the initiation of protein synthesis as regards to the requirement for eIF2. Analysis of individual poliovirus non-structural proteins indicates that the presence of 2Apro alone is sufficient to provide eIF2 independence for IRES-driven translation. This effect is not observed with a 2Apro variant unable to cleave eIF4G. The level of 2Apro synthesized in culture cells is crucial for obtaining eIF2 independence. Expression of the N-or C-terminus fragments of eIF4G did not stimulate IRES-driven translation, nor provide eIF2 independence, consistent with the idea that the presence of 2Apro at high concentrations is necessary. The finding that 2Apro provides eIF2-independent translation opens a new and unsuspected area of research in the field of picornavirus protein synthesis