117 research outputs found

    Epstein-Barr Virus LMP2A Reduces Hyperactivation Induced by LMP1 to Restore Normal B Cell Phenotype in Transgenic Mice

    Get PDF
    Epstein-Barr virus (EBV) latently infects most of the human population and is strongly associated with lymphoproliferative disorders. EBV encodes several latency proteins affecting B cell proliferation and survival, including latent membrane protein 2A (LMP2A) and the EBV oncoprotein LMP1. LMP1 and LMP2A signaling mimics CD40 and BCR signaling, respectively, and has been proposed to alter B cell functions including the ability of latently-infected B cells to access and transit the germinal center. In addition, several studies suggested a role for LMP2A modulation of LMP1 signaling in cell lines by alteration of TRAFs, signaling molecules used by LMP1. In this study, we investigated whether LMP1 and LMP2A co-expression in a transgenic mouse model alters B cell maturation and the response to antigen, and whether LMP2A modulates LMP1 function. NaĂŻve LMP1/2A mice had similar lymphocyte populations and antibody production by flow cytometry and ELISA compared to controls. In the response to antigen, LMP2A expression in LMP1/2A animals rescued the impairment in germinal center generation promoted by LMP1. LMP1/2A animals produced high-affinity, class-switched antibody and plasma cells at levels similar to controls. In vitro, LMP1 upregulated activation markers and promoted B cell hyperproliferation, and co-expression of LMP2A restored a wild-type phenotype. By RT-PCR and immunoblot, LMP1 B cells demonstrated TRAF2 levels four-fold higher than non-transgenic controls, and co-expression of LMP2A restored TRAF2 levels to wild-type levels. No difference in TRAF3 levels was detected. While modulation of other TRAF family members remains to be assessed, normalization of the LMP1-induced B cell phenotype through LMP2A modulation of TRAF2 may be a pathway by which LMP2A controls B cell function. These findings identify an advance in the understanding of how Epstein-Barr virus can access the germinal center in vivo, a site critical for both the genesis of immunological memory and of virus-associated tumors

    Voter Information Campaigns and Political Accountability: Cumulative Findings From a Preregistered Meta-analysis of Coordinated Trials

    Get PDF
    Voters may be unable to hold politicians to account if they lack basic information about their representatives’ performance. Civil society groups and international donors therefore advocate using voter information campaigns to improve democratic accountability. Yet, are these campaigns effective? Limited replication, measurement heterogeneity, and publication biases may undermine the reliability of published research. We implemented a new approach to cumulative learning, coordinating the design of seven randomized controlled trials to be fielded in six countries by independent research teams. Uncommon for multisite trials in the social sciences, we jointly preregistered a meta-analysis of results in advance of seeing the data. We find no evidence overall that typical, nonpartisan voter information campaigns shape voter behavior, although exploratory and subgroup analyses suggest conditions under which informational campaigns could be more effective. Such null estimated effects are too seldom published, yet they can be critical for scientific progress and cumulative, policy-relevant learning.FSW – Publicaties zonder aanstelling Universiteit Leide

    Voter information campaigns and political accountability: cumulative findings from a preregistered meta-analysis of coordinated trials

    Get PDF
    Voters may be unable to hold politicians to account if they lack basic information about their representatives’ performance. Civil society groups and international donors therefore advocate using voter information campaigns to improve democratic accountability. Yet, are these campaigns effective? Limited replication, measurement heterogeneity, and publication biases may undermine the reliability of published research. We implemented a new approach to cumulative learning, coordinating the design of seven randomized controlled trials to be fielded in six countries by independent research teams. Uncommon for multisite trials in the social sciences, we jointly preregistered a meta-analysis of results in advance of seeing the data. We find no evidence overall that typical, nonpartisan voter information campaigns shape voter behavior, although exploratory and subgroup analyses suggest conditions under which informational campaigns could be more effective. Such null estimated effects are too seldom published, yet they can be critical for scientific progress and cumulative, policy-relevant learning

    Funciones de razĂłn para la estimaciĂłn de los volĂşmenes maderables de Pino radiata en PaĂ­s Vasco

    No full text
    En el proyecto de actualización de las tablas de producción para las repoblaciones de Pinus radiata D. Don en el País Vasco se evaluaron los ajustes de cuatro funciones de razón de volumen. Estas funciones permiten estimar los volúmenes de distintos productos a partir de los diámetros finales utilizables, del diámetro normal del árbol y de una función de volumen total de árbol individual. Para los ajustes se utilizó una muestra de 71 árboles. Los árboles se cubicaron con la fórmula de Smalian, y se obtuvo para cada uno el volumen total con corteza y los volúmenes maderables con corteza a puntas finas a delgadas de 7, 10, 15, 20, 25 y 30 cm. A pesar de que todas las funciones tuvieron muy buenas ajustes y demostraron gran precisión en las estimaciones de los volúmenes maderables, mejorando con el aumento del tamaño del árbol, el modelo 1 de Parresol ha sido el que mejores resultados entregó. Este tipo de funciones se consideran novedosas para esta especie en España

    Getting Rich Too Fast? Experimental Evidence on Voters' Reactions to Politicians' Wealth Accumulation in India

    No full text
    Asset declarations requiring politicians to disclose their financial information are becoming increasingly common across the world. The information contained in these disclosures frequently reveals that politicians rapidly accumulate wealth while in office, a fact that may raise suspicion among voters. However, little is known about the ways in which such information may affect voter behavior. To address this gap, we use original experimental and survey data from India to explore voters’ reactions to information about wealth and wealth accumulation. Results suggest that voters strongly disapprove of wealth accumulation in office and associate it with corruption and political violence. Further analyses suggest several mechanisms that may partly explain why many “wealth accumulators” win elections in India despite these negative reactions. Voters generally lack information about disclosures and many weigh wealth accumulation less than some other prominent concerns, such as performance in office or caste-based appeals.The Institutions of Politics; Design, Workings, and implications ( do not use, ended 1-1-2020

    Diagrama de manejo de la densidad de masas de "Pino radiata" en el PaĂ­s Vasco

    No full text
    A partir de alguna de las relaciones entre variables relacionadas con el tamaño y la densidad de los rodales es posible construir los llamados Diagramas de Manejo de la Densidad (DMD), que permiten planificar y describir cuantitativamente las interrelaciones entre producción, densidad y mortalidad en varias etapas del desarrollo del rodal. Con el fin de desarrollar los DMD para Pinus radiata se vincularon las variables Diámetro medio cuadrático y Número de pies, medidas en rodales sin intervenciones, con ello se determinó el nivel de máxima competencia y el indice de densidad del rodal (IDR) y se estableció un algoritmo para la planificación selvícola. Las variables estudiadas mostraron un comportamiento lineal que permitió expresar el nivel de máxima densidad a través de una función lineal logarítmica. El IDR máximo promedio resultó ser de 1.274. El proceso de planificación selvícola se ejemplificó a través de una aplicación práctica
    • …
    corecore