RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions

The Validity and Structure of Culture-Level Personality Scores: Data From Ratings of Young Adolescents

We examined properties of culture-level personality traits in ratings of targets (N=5,109) ages 12 to 17 in 24 cultures. Aggregate scores were generalizable across gender, age, and relationship groups and showed convergence with culture-level scores from previous studies of self-reports and observer ratings of adults, but they were unrelated to national character stereotypes. Trait profiles also showed cross-study agreement within most cultures, 8 of which had not previously been studied. Multidimensional scaling showed that Western and non-Western cultures clustered along a dimension related to Extraversion. A culture-level factor analysis replicated earlier findings of a broad Extraversion factor but generally resembled the factor structure found in individuals. Continued analysis of aggregate personality scores is warranted. This article is a US Government work and is in the public domain in the USA.Fil: McCrae, Robert R.. National Institute on Ageing; CanadáFil: Terracciano, Antonio. National Institute on Ageing; CanadáFil: De Fruyt, Filip. University of Ghent; BélgicaFil: De Bolle, Marleen. University of Ghent; BélgicaFil: Gelfand, Michele J.. University of Maryland; Estados UnidosFil: Costa Jr., Paul T.. National Institute on Ageing; CanadáFil: Klinkosz, Waldemar. The John Paul II Catholic University of Lublin; PoloniaFil: Knežević, Goran. Belgrade University; SerbiaFil: Leibovich de Figueroa, Nora. Universidad de Buenos Aires; ArgentinaFil: Löckenhoff, Corinna E.. Cornell University; Estados UnidosFil: Martin, Thomas A.. Susquehanna University; Estados UnidosFil: Marušić, Iris. Institute for Social Research; CroaciaFil: Mastor, Khairul Anwar. Universiti Kebangsaan Malaysia; MalasiaFil: Nakazato, Katsuharu. Iwate Prefectural University; AfganistánFil: Nansubuga, Florence. Makerere University; UgandaFil: Porrata, Jose. No especifíca;Fil: Purić, Danka. Belgrade University; SerbiaFil: Realo, aAnu. University of Tartu; EstoniaFil: Reátegui, Norma. Universidad Peruana Cayetano Heredia; PerúFil: Rolland, Jean Pierre. Universite Paris Ouest Nanterre la Defense; FranciaFil: Schmidt, Vanina Ines. Universidad de Buenos Aires. Facultad de Psicología. Instituto de Investigaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sekowski, Andrzej. The John Paul II Catholic University of Lublin; PoloniaFil: Shakespeare Finch, Jane. Queensland University of Technology; AustraliaFil: Shimonaka, Yoshiko. Bunkyo Gakuin University; JapónFil: Simonetti, Franco. Pontificia Universidad Católica de Chile; ChileFil: Siuta, Jerzy. Jagiellonian University;Fil: Szmigielska, Barbara. Jagiellonian University;Fil: Vanno, Vitanya. Srinakharinwirot University; TailandiaFil: Wang, Lei. Peking University; ChinaFil: Yik, Michelle. The Hong Kong University of Science and Technology; Hong Kon

Personality profiles of cultures: aggregate personality traits

Personality profiles of cultures can be operationalized as the mean trait levels of culture members. College students from 51 cultures rated an individual from their country whom they knew well (N = 12, 156). Aggregate scores on Revised NEO Personality Inventory scales generalized across age and gender groups, approximated the individual-level Five-Factor Model, and correlated with aggregate self-report personality scores and other culture-level variables. Results were not attributable to national differences in economic development or to acquiescence. Geographical differences in scale variances and mean levels were replicated, with Europeans and Americans generally scoring higher in Extraversion than Asians and Africans. Findings support the rough scalar equivalence of NEO-PI-R factors and facets across cultures, and suggest that aggregate personality profiles provide insight into cultural differences

Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition

The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects

The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.Peer reviewe

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015

Culture, gender, and the bipolarity of momentary affect

This study examined if the relation between momentary positive and negative affect varies with culture and gender. In eight samples covering five languages (English, Spanish, Chinese, Japanese, and Korean) with 3084 respondents (1305 mates and 1779 females), I tested this proposal through structural equation models that controlled for random and systematic errors of measurement. In all eight samples, female respondents yielded a more negative correlation between positive and negative affect than did male respondents, but the differences were tiny and only two were statistically significant. In a multi-sample confirmatory factor analysis, the correlation was found to be substantial and negative in all five languages (Phi(s) ranging from -80 to -.91). All values from the total samples and from males and females separately were consistent with the bipolarity of positive and negative affect