Cis and Trans Effects of Human Genomic Variants on Gene Expression

This work was funded by the Louis-Jeantet Foundation (http://www.jeantet.ch/), the European Research Council (Grant ID: 260927 http://erc.europa.eu/), the Swiss National Foundation (Grant ID: 130342 http://www.snf.ch), NCCR Frontiers In Genetics (http://www.frontiers-in-genetics.org), the UK Medical Research Council (http://www.mrc.ac.uk) and the Wellcome Trust (Grant ID: 092731).

Androgen-regulated transcription of ESRP2 drives alternative splicing patterns in prostate cancer

Prostate is the most frequent cancer in men. Prostate cancer progression is driven by androgen steroid hormones, and delayed by androgen deprivation therapy (ADT). Androgens control transcription by stimulating androgen receptor (AR) activity, yet also control pre-mRNA splicing through less clear mechanisms. Here we find androgens regulate splicing through AR-mediated transcriptional control of the epithelial-specific splicing regulator ESRP2. Both ESRP2 and its close paralog ESRP1 are highly expressed in primary prostate cancer. Androgen stimulation induces splicing switches in many endogenous ESRP2-controlled mRNA isoforms, including splicing switches correlating with disease progression. ESRP2 expression in clinical prostate cancer is repressed by ADT, which may thus inadvertently dampen epithelial splice programmes. Supporting this, treatment with the AR antagonist bicalutamide (Casodex) induced mesenchymal splicing patterns of genes including FLNB and CTNND1. Our data reveals a new mechanism of splicing control in prostate cancer with important implications for disease progression.This article is freely available via Open Access. Click on the Publisher URL to access the full-text via the publisher's site

Biodiversity conservation: history, protected areas and hotspots

Angola is a large country of great physiographic, climatic and habitat diversity, with a corresponding richness in animal and plant species. Legally protected areas (National Parks and Game Reserves) were established from the 1930s and occupied 6% of the country’s terrestrial area at the time of independence in 1975. As a consequence of an extended war, the Protected Areas were exposed to serious neglect, poaching and land invasions. Many habitats of biogeographic importance, and many rare and endemic species came under threat. The recently strengthened administration gives cause for optimism that a new era for biodiversity conservation is at hand. The Protected Areas system was greatly expanded in 2011, and increasing resources are being made available towards achieving management effectivenessinfo:eu-repo/semantics/publishedVersio

Programa de intervención en representaciones de creatividad y motivación académica de adolescentes

Creativity and its promotion are widespread concerns in education. However, few efforts have been made to implement intervention programs designed to promote creativity and other related aspects (e.g., academic motivation). The Future Problem Solving Program International (FPSPI), aimed for training creativity representations and creative problem solving skills in young people, has been one of the most implemented programs. This intervention’s materials and activities were adapted for Portuguese students, and a longitudinal study was conducted. The program was implemented during four months, in weekly sessions, by thirteen teachers. Teachers received previous training for the program and during the program’s implementation. Intervention participants included 77 Basic and Secondary Education students, and control participants included 78 equivalent students. Pretest-posttest measures of academic motivation and creativity representations were collected. Results suggest a significant increase, in the intervention group, in motivation and the appropriate representations of creativity. Practical implications and future research perspectives are presented.A criatividade e sua promoção geram grande preocupação em educação. Contudo, poucos esforços têm existido para implementar programas destinados a sua promoção e de outros aspetos relacionados (e.g., motivação acadêmica). O Future Problem Solving Program International (FPSPI), criado para melhorar as representações de criatividade e a resolução criativa de problemas em jovens, tem sido um dos mais implementados. Os seus materiais e atividades foram adaptados para estudantes portugueses, efetuando-se um estudo longitudinal. O programa foi implementado durante quatro meses, semanalmente, por treze professores, que receberam formação antes e durante a implementação. O grupo experimental incluiu 77 estudantes do Ensino Básico e Secundário, apresentando o grupo de controlo 78 estudantes com características equivalentes. Os dados sobre a motivação e criatividade foram recolhidos num pré e pós-teste. Os resultados sugerem um aumento significativo na motivação e crenças apropriadas de criatividade no grupo experimental. Implicações práticas e perspectivas para investigações futuras são apresentadas.La creatividad y su promoción generan gran preocupación en educación. Sin embargo, han sido llevados a cabo pocos esfuerzos para implementar programas de promoción de la creatividad y otros aspectos (e.g., motivación académica). El Future Problem Solving Program International (FPSPI), creado para mejorar las representaciones de creatividad y la solución creativa de problemas en jóvenes, ha sido bastante implementado. Se adaptaron sus materiales y actividades para estudiantes portugueses, y se desarrolló un estudio longitudinal. El programa se implementó semanalmente durante cuatro meses por trece profesores, que recibieron formación antes y durante la implementación. El grupo experimental incluyó 77 estudiantes de Educación Primaria y Secundaria y el grupo de control incluyó 78 estudiantes con características semejantes. Los datos de motivación y creatividad fueron recogidos en un pre y post-test, sugiriendo un aumento significativo de motivación y creencias apropiadas sobre la creatividad en el grupo experimental. Se presentan implicaciones prácticas y perspectivas para futuras investigaciones.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BPD/80825/201

Changes in Channel Trafficking and Protein Stability Caused by LQT2 Mutations in the PAS Domain of the HERG Channel

Inherited human long-QT2 syndrome (LQTS) results from mutations in the gene encoding the HERG channel. Several LQT2-associated mutations have been mapped to the amino terminal cytoplasmic Per-Arnt-Sim (PAS) domain of the HERG1a channel subunit. Here we have characterized the trafficking properties of some LQT2-associated PAS domain mutants and analyzed rescue of the trafficking mutants by low temperature (27°C) or by the pore blocker drug E4031. We show that the LQT2-associated mutations in the PAS domain of the HERG channel display molecular properties that are distinct from the properties of LQT2-associated mutations in the trans-membrane region. Unlike the latter, many of the tested PAS domain LQT2-associated mutations do not result in trafficking deficiency of the channel. Moreover, the majority of the PAS domain mutations that cause trafficking deficiencies are not rescued by a pore blocking drug. We have also explored the in vitro folding stability properties of isolated mutant PAS domain proteins using a thermal unfolding fluorescence assay and a chemical unfolding assay

Diversity of lactic acid bacteria of the bioethanol process

<p>Abstract</p> <p>Background</p> <p>Bacteria may compete with yeast for nutrients during bioethanol production process, potentially causing economic losses. This is the first study aiming at the quantification and identification of Lactic Acid Bacteria (LAB) present in the bioethanol industrial processes in different distilleries of Brazil.</p> <p>Results</p> <p>A total of 489 LAB isolates were obtained from four distilleries in 2007 and 2008. The abundance of LAB in the fermentation tanks varied between 6.0 × 10⁵and 8.9 × 10⁸CFUs/mL. Crude sugar cane juice contained 7.4 × 10⁷to 6.0 × 10⁸LAB CFUs. Most of the LAB isolates belonged to the genus <it>Lactobacillus </it>according to rRNA operon enzyme restriction profiles. A variety of <it>Lactobacillus </it>species occurred throughout the bioethanol process, but the most frequently found species towards the end of the harvest season were <it>L. fermentum </it>and <it>L. vini</it>. The different rep-PCR patterns indicate the co-occurrence of distinct populations of the species <it>L. fermentum </it>and <it>L. vini</it>, suggesting a great intraspecific diversity. Representative isolates of both species had the ability to grow in medium containing up to 10% ethanol, suggesting selection of ethanol tolerant bacteria throughout the process.</p> <p>Conclusions</p> <p>This study served as a first survey of the LAB diversity in the bioethanol process in Brazil. The abundance and diversity of LAB suggest that they have a significant impact in the bioethanol process.</p

Perinatal outcomes associated with low birth weight in a historical cohort

<p>Abstract</p> <p>Objective</p> <p>To identify perinatal outcomes associated with low birth weight (LBW).</p> <p>Methods</p> <p>A retrospective cohort study in a tertiary maternity hospital. Analysis of the database on 43,499 liveborn infants delivered between 1986 and 2004 with low (n = 6,477) and normal (n = 37,467) birth weight. Outcomes associated with LBW were identified through crude and adjusted risk ratio (RR) and 95%CI with bivariate and multivariate analysis. The main outcomes were: onset of labor, mode of delivery, indication for cesarean section; amniotic fluid, fetal heart rate pattern, Apgar score, somatic gestational age, gender and congenital malformation.</p> <p>Results</p> <p>LBW infants showed more frequently signs of perinatal compromise such as abnormal amniotic fluid volume (especially olygohydramnios), nonreassuring patterns of fetal heart rate, malformation, lower Apgar scores and lower gestational age at birth. They were associated with a greater risk of labor induction and cesarean delivery, but lower risk of forceps.</p> <p>Conclusion</p> <p>There was a clear association between LBW and unfavorable perinatal outcomes.</p

Mutation in the xpsD gene of Xanthomonas axonopodis pv. citri affects cellulose degradation and virulence

The Gram-negative bacterium Xanthomonas axonopodis pv. citri, the causal agent of citrus canker, is a major threat to the citrus industry worldwide. Although this is a leaf spot pathogen, it bears genes highly related to degradation of plant cell walls, which are typically found in plant pathogens that cause symptoms of tissue maceration. Little is known on Xac capacity to cause disease and hydrolyze cellulose. We investigated the contribution of various open reading frames on degradation of a cellulose compound by means of a global mutational assay to selectively screen for a defect in carboxymethyl cellulase (CMCase) secretion in X. axonopodis pv. citri. Screening on CMC agar revealed one mutant clone defective in extracellular glycanase activity, out of nearly 3,000 clones. The insertion was located in the xpsD gene, a component of the type II secretion system (T2SS) showing an influence in the ability of Xac to colonize tissues and hydrolyze cellulose. In summary, these data show for the first time, that X. axonopodis pv. citri is capable of hydrolyzing cellulose in a T2SS-dependent process. Furthermore, it was demonstrated that the ability to degrade cellulose contributes to the infection process as a whole