Impact is a Gcn2 inhibitor that limits lifespan in caenorhabditis elegans

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The General Control Nonderepressible 2 (GCN2) kinase is a conserved member of the integrated stress response (ISR) pathway that represses protein translation and helps cells to adapt to conditions of nutrient shortage. As such, GCN2 is required for longevity and stress resistance induced by dietary restriction (DR). IMPACT is an ancient protein that inhibits GCN2. Results: Here, we tested whether IMPACT down-regulation mimics the effects of DR in C. elegans. Knockdown of the C. elegans IMPACT homolog impt-1 activated the ISR pathway and increased lifespan and stress resistance of worms in a gcn-2-dependent manner. Impt-1 knockdown exacerbated DR-induced longevity and required several DR-activated transcription factors to extend lifespan, among them SKN-1 and DAF-16, which were induced during larval development and adulthood, respectively, in response to impt-1 RNAi. Conclusions: IMPACT inhibits the ISR pathway, thus limiting the activation of stress response factors that are beneficial during aging and required under DR.The General Control Nonderepressible 2 (GCN2) kinase is a conserved member of the integrated stress response (ISR) pathway that represses protein translation and helps cells to adapt to conditions of nutrient shortage. As such, GCN2 is required for longev141115CNQP - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)444424/2014-8474397/2011-42010/52557-02015/01316-72015/04264-82012/24490-42009/52047-52014/17145-42012/04064-02014/25068-02014/25270-32014/10814-8We thank Dr. T. Keith Blackwell and Dr. David Ron for providing the Patf-

Environmental vulnerability assessment of Brazilian Amazon Indigenous Lands

Amazonian Indigenous Lands (ILs) are human-environment systems facing a multitude of environmental threats. Yet, the resulting vulnerability of these systems are to date unknown. We adopt the theoretical vulnerability framework of the IPCC to assess the environmental vulnerability of Brazilian Amazon ILs for two periods (2001–2010 and 2011–2019) and overall (2001–2019). Vulnerability is deemed a function of exposure (EX), sensitivity (SE) and adaptive capacity (AC) of a system to threats. Sensitivity (threats within IL) and exposure (threats in IL's buffer zones) indicators are changes in forest cover, economic activities, and road access, quantified using data of deforestation, forest degradation, land-use, fire, roads and mining. Adaptive capacity indicators represent Indigenous self-organization, education and access to knowledge, land ownership, external incomes, and institutional arrangement. We find a concentration of ILs with high vulnerability in the Arc of Deforestation and South, and advancing in Pará and Roraima states. A strong relationship (Spearman r = 0.79) between EX and SE indicates the strong pressure exerted by external processes. An increase in EX (73.9% of the ILs) and in SE (64.8% of the ILs) in 2011–2019 compared to 2001–2010 signals a worrying rise in vulnerability recently. We advise the adoption of policies by the State, such as combating illegal activities, and strengthening National Policy for Environmental and Territorial Management of ILs. Herein, our vulnerability quantification can prioritize help to certain ILs, and the understanding of the contribution of the underlying dimensions can direct these policies, possibly according to the vulnerability profile of each IL

Effectiveness of different databases in identifying studies for systematic reviews: experience from the WHO systematic review of maternal morbidity and mortality

BACKGROUND: Failure to be comprehensive can distort the results of a systematic review. Conversely, extensive searches may yield unmanageable number of citations of which only few may be relevant. Knowledge of usefulness of each source of information may help to tailor search strategies in systematic reviews. METHODS: We conducted a systematic review of prevalence/incidence of maternal mortality and morbidities from 1997 to 2002. The search strategy included electronic databases, hand searching, screening of reference lists, congress abstract books, contacting experts active in the field and web sites from less developed countries. We evaluated the effectiveness of each source of data and discuss limitations and implications for future research on this topic. RESULTS: Electronic databases identified 64098 different citations of which 2093 were included. Additionally 487 citations were included from other sources. MEDLINE had the highest yield identifying about 62% of the included citations. BIOSIS was the most precise with 13.2% of screened citations included. Considering electronic citations alone (2093), almost 20% were identified uniquely by MEDLINE (400), 7.4% uniquely by EMBASE (154), and 5.6% uniquely by LILACS (117). About 60% of the electronic citations included were identified by two or more databases. CONCLUSIONS: This analysis confirms the need for extending the search to other sources beyond well-known electronic databases in systematic reviews of maternal mortality and morbidity prevalence/incidence. These include regional databases such as LILACS and other topic specific sources such as hand searching of relevant journals not indexed in electronic databases. Guidelines for search strategies for prevalence/incidence studies need to be developed

“Manos a la obra… Manos a la ciencia” Distintos Niveles educativos confluyen para investigar sobre infecciones virales respiratorias

Este proyecto extensionista tiene como objetivos vincular instituciones de distintos niveles educativos en torno a la investigación científica de infecciones virales respiratorias, y promover la actividad empírica y científica en el Laboratorio escolar. Los investigadores de la UNC y los docentes del secundario organizaron una conferencia con expertos, para padres y alumnos. Los docentes de primaria realizaron  la publicidad, promoción y comunicación de las actividades mediante afiches, y gestionaban los espacios y tiempos. La conferencia se llevó a cabo en junio, donde los expertos explicaron sobre el proceso salud-enfermedad referida a virus respiratorios. El circuito que recorre este proceso desde la visita al médico, la toma de muestra, su diagnóstico y tratamiento. En  agosto, en las aulas se impartieron las clases teóricas sobre el proceso de salud-enfermedad de las infecciones virales respiratorias, a los alumnos de  4º y 6º grados  del primario y a los de 5º año  del secundario. Los temas desarrollados fueron: bioseguridad, metodología de la investigación en salud, autocuidado, ciclos de infección, epidemiología haciendo hincapié en enfermedades respiratorias.  Los alumnos realizaron investigación bibliográfica y efectuaron análisis estadísticos. También visitaron laboratorios del Instituto de Virología. Además, se puso gran énfasis en recuperación de las actividades prácticas en el laboratorio del primario con el asesoramiento de los docentes e investigadores. En este punto se extrajeron muestras a los alumnos que participaron voluntariamente con el consentimiento firmado por sus padres. Este proyecto titulado “Manos a la Obra…Manos a la Ciencia” fue aprobado y subsidiado por el Ministerio de Ciencia y Tecnología de la Provincia de Córdoba (Mincyt), dentro del Programa “Innovaciones en el aula 2011”. Teniendo en cuenta que algunas de las actividades propuestas  están aún en desarrollo durante 2012, como completar la parte de materiales y métodos, contamos con algunos resultados que nos permiten elaborar conclusiones preliminares. Los resultados fueron un 4%  de detecciones de un tipo de virus respiratorio, aún cuando se consideró esta población escolar sana como control negativo. Reportándose entonces que esta infección respiratoria se presentó como un mini brote asintomático. Cabe aclarar que las detecciones virales  no fueron el fin buscado, sino la comprensión de todo el proceso de investigación que se lleva a cabo y del cual forman parte. Finalmente apostamos que desarrollar este tipo de proyectos es muy importante para promover la integración entre la Comunidad Educativa y la Científica, a través de actividades vinculadas con la investigación en salud.

Electrostatic Effects in the Folding of the SH3 Domain of the c-Src Tyrosine Kinase: pH-Dependence in 3D-Domain Swapping and Amyloid Formation

The SH3 domain of the c-Src tyrosine kinase (c-Src-SH3) aggregates to form intertwined dimers and amyloid fibrils at mild acid pHs. In this work, we show that a single mutation of residue Gln128 of this SH3 domain has a significant effect on: (i) its thermal stability; and (ii) its propensity to form amyloid fibrils. The Gln128Glu mutant forms amyloid fibrils at neutral pH but not at mild acid pH, while Gln128Lys and Gln128Arg mutants do not form these aggregates under any of the conditions assayed. We have also solved the crystallographic structures of the wild-type (WT) and Gln128Glu, Gln128Lys and Gln128Arg mutants from crystals obtained at different pHs. At pH 5.0, crystals belong to the hexagonal space group P6522 and the asymmetric unit is formed by one chain of the protomer of the c-Src-SH3 domain in an open conformation. At pH 7.0, crystals belong to the orthorhombic space group P212121, with two molecules at the asymmetric unit showing the characteristic fold of the SH3 domain. Analysis of these crystallographic structures shows that the residue at position 128 is connected to Glu106 at the diverging β-turn through a cluster of water molecules. Changes in this hydrogen-bond network lead to the displacement of the c-Src-SH3 distal loop, resulting also in conformational changes of Leu100 that might be related to the binding of proline rich motifs. Our findings show that electrostatic interactions and solvation of residues close to the folding nucleation site of the c-Src-SH3 domain might play an important role during the folding reaction and the amyloid fibril formation.This research was funded by the Spanish Ministry of Science and Innovation and Ministry of Economy and Competitiveness and FEDER (EU): BIO2009-13261-C02-01/02 (ACA); BIO2012-39922-C02-01/02 (ACA); CTQ2013-4493 (JLN) and CSD2008-00005 (JLN); Andalusian Regional Government (Spain) and FEDER (EU): P09-CVI-5063 (ACA); and Valentian Regional Government (Spain) and FEDER (EU): Prometeo 2013/018 (JLN). Data collection was supported by European Synchrotron Radiation Facility (ESRF), Grenoble, France: BAG proposals MX-1406 (ACA) and MX-1541 (ACA); and ALBA (Barcelona, Spain) proposals 2012010072 (ACA) and 2012100378 (ACA)

Use of AFLP and RAPD molecular genetic markers and cytogenetic analysis to explore relationships among taxa of the Patagonian Bromus setifolius complex

Bromus setifolius var. pictus (Hook) Skottsb., B. setifolius var. setifolius Presl. and B.setifolius var. brevifolius Ness are three native Patagonian taxa in the section Pnigma Dumort of the genus Bromus L. AFLP and RAPD analysis, in conjunction with genetic distance measurements and statistical techniques, revealed variation within this group and indicated that B. setifolius var. brevifolius was closely related to B. setifolius var. pictus, with both taxa being more distantly related to B. setifolius var. setifolius. Cytogenetic analysis confirmed the chromosomal number of B. setifolius var. pictus (2n = 70) and B. setifolius var. setifolius (2n = 28) and showed for the first time that B. setifolius var. brevifolius had 2n = 70. The combination of molecular genetic and cytogenetic evidence supported a species status for two of the three taxa and suggested hypotheses for the evolutionary origin of these complex taxa. Species status was also indicated for B. setifolius var. setifolius. Based on these findings, we suggest that B. setifolius var. pictus be referred to as B. pictus Hook var. pictus, and B. setifolius var brevifolius as B. pictus Hook var brevifolius. The correlation between AFLP diversity and variation in ecological parameters suggested that this marker system could be used to assess breeding progress and to monitor the domestication of Patagonian Bromus species for agronomic use