Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes.

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria.

Pleiotropy and the low cost of individual traits promote cooperation.

The evolution of cooperation is thought to be promoted by pleiotropy, whereby cooperative traits are coregulated with traits that are important for personal fitness. However, this hypothesis faces a key challenge: what happens if mutation targets a cooperative trait specifically rather than the pleiotropic regulator? Here, we explore this question with the bacterium Pseudomonas aeruginosa, which cooperatively digests complex proteins using elastase. We empirically measure and theoretically model the fate of two mutants-one missing the whole regulatory circuit behind elastase production and the other with only the elastase gene mutated-relative to the wild-type (WT). We first show that, when elastase is needed, neither of the mutants can grow if the WT is absent. And, consistent with previous findings, we show that regulatory gene mutants can grow faster than the WT when there are no pleiotropic costs. However, we find that mutants only lacking elastase production do not outcompete the WT, because the individual cooperative trait has a low cost. We argue that the intrinsic architecture of molecular networks makes pleiotropy an effective way to stabilize cooperative evolution. Although individual cooperative traits experience loss-of-function mutations, these mutations may result in weak benefits, and need not undermine the protection from pleiotropy.

Monitoring of the training load and recovery parameters in competitive swimmers

Nombreux sont les groupes de recherche qui se sont intéressés, ces dernières années, à la manière de monitorer l'entraînement des sportifs de haut niveau afin d'optimaliser le rendement de ce dernier tout en préservant la santé des athlètes. Un des problèmes cardinaux d'un entraînement sportif mal conduit est le syndrome du surentraînement. La définition du syndrome susmentionné proposée par Kreider et al. est celle qui est actuellement acceptée par le « European College of Sport Science » ainsi que par le « American College of Sports Medicine», à savoir : « An accumulation of training and/or non-training stress resulting in long-term decrement in performance capacity with or without related physiological and psychological signs and symptoms of maladaptation in which restoration of performance capacity may take several weeks or months. » « Une accumulation de stress lié, ou non, à l'entraînement, résultant en une diminution à long terme de la capacité de performance. Cette dernière est associée ou non avec des signes et des symptômes physiologiques et psychologiques d'inadaptation de l'athlète à l'entraînement. La restauration de ladite capacité de performance peut prendre plusieurs semaines ou mois. » Les recommandations actuelles, concernant le monitoring de l'entraînement et la détection précoce du syndrome du surentrainement, préconisent, entre autre, un suivi psychologique à l'aide de questionnaires (tel que le Profile of Mood State (POMS)), un suivi de la charge d'entraînement perçue par l'athlète (p.ex. avec la session rating of perceived exertion (RPE) method selon C. Foster), un suivi des performances des athlètes et des charges d'entraînement effectuées ainsi qu'un suivi des problèmes de santé (blessures et maladies). Le suivi de paramètres sanguins et hormonaux n'est pas recommandé d'une part pour des questions de coût et de faisabilité, d'autre part car la littérature scientifique n'a, jusqu'ici, pas été en mesure de dégager des évidences à ce sujet. A ce jour, peu d'études ont suivi ces paramètres de manière rigoureuse, sur une longue période et chez un nombre d'athlète important. Ceci est précisément le but de notre étude.

The international standardisation arena and the civil society participation stakes : results of the INTERTERM project

International standards are playing an increasingly important role in market governance while frequently exerting direct effects on health, safety and the environment. Yet civil society, more often than not, is absent from the standardisation procedures. The recommendation made here is to foster the participation of civil society actors in standardisation by framing standardisation topics in a way that will encourage the mobilisation of these actors in accordance with their repertoire of actions and interests and by organising the plural expertise required for the effective participation that is necessary if they are to exert an influence.

The Innovation Process – Aiming towards Innovativeness in a Construction Company

The bachelor’s thesis concentrates on the innovativeness in the construction industry. The purpose of the thesis is to define the innovation as a concept reflected on a context of the construction industry. The second objective is to examine how the construction companies could foster and increase the innovativeness. The third objective was to find out tools, methods and phases of the front-end of the innovation process. The construction industry is often considered as a traditional and an old-fashioned manufacturing industry. The innovation or the innovativeness rarely linked to the construction industry. Productivity is a common problem in the construction industry. The construction industry needs to increase the productivity to compete in a globalized world. The productivity can be increased by the innovation. The thesis based on a literature review. The findings from the literature include a description of the innovation as a concept, the innovative culture and the innovation process as a context of the construction industry. The phases of the front-end of the innovation process were explained. Customers centered approach was taken into account in the innovation process. The required tools and methods for managing the front-end of the innovation process were illustrated. The thesis ensures the importance of the innovation facing challenges of the construction industry. Managing the front-end of the innovation is the most important aspect to stand out from the less innovative companies. To take a full advantage of the innovation companies cannot fear of changes. The innovation process requires a full support of the top management of the company. Taking into consideration a theoretical aspect of the thesis a further research is required to respond practical needs of the company. Tools and methods should be considered according the company’s needs and activities. Company’s existing state and culture should be examined before implementing the front-end of the innovation process to ensure the functionality.

Dual Action of BPC194: A Membrane Active Peptide Killing Bacterial Cells

Membrane active peptides can perturb the lipid bilayer in several ways, such as poration and fusion of the target cell membrane, and thereby efficiently kill bacterial cells. We probe here the mechanistic basis of membrane poration and fusion caused by membrane-active, antimicrobial peptides. We show that the cyclic antimicrobial peptide, BPC194, inhibits growth of Gram-negative bacteria and ruptures the outer and inner membrane at the onset of killing, suggesting that not just poration is taking place at the cell envelope. To simplify the system and to better understand the mechanism of action, we performed Förster resonance energy transfer and cryogenic transmission electron microscopy studies in model membranes and show that the BPC194 causes fusion of vesicles. The fusogenic action is accompanied by leakage as probed by dual-color fluorescence burst analysis at a single liposome level. Atomistic molecular dynamics simulations reveal how the peptides are able to simultaneously perturb the membrane towards porated and fused states. We show that the cyclic antimicrobial peptides trigger both fusion and pore formation and that such large membrane perturbations have a similar mechanistic basis

Aplicació Actual de l’Aprenentatge Cooperatiu a la Universitat de Girona : passos cap a l’elaboració d’una guia sobre aprenentatge cooperatiu

The purpose of the present paper is to analyse the present state of thepractical application of cooperative learning methodologies at the University of Girona,to assess its strengths and weaknesses and to extract from that criteria, ideas andprinciples. These materials will be the basis upon which a guide or manual of use oncooperative learning will be drafted. The guide will be at the disposal of the UdGteaching staff and other people interested in it, with the aim of helping them with theirteaching and foster a higher degree of use of cooperative learning at the University. Thepaper presents the survey already conducted, as well as the methodology followed, thehypotheses of the study and the results obtained

A importância do observatório de atividades industriais vis-à-vis tendências em ciência, tecnologia e inovação

Given that innovation is fundamental for competitiveness, and that it is intrinsically linked to knowledge, it has become essential to foster effective interaction between the Brazilian productive sector and universities and R&D centers. This interface should be created by means of the model used in developed countries: Observatory of Industrial Activities and Trends in Science, Technology and Innovation. The present work describes its main functions, using examples of activities undertaken by the Chemical Industry Information System of the Federal University of Rio de Janeiro related to production systems of primary and high-tech industries, examining the diffusion of knowledge to decision-makers.

La infància i la seva protecció

L"article primer de la Convenció de Drets de l"Infant (Nacions Unides, 20 de novembre de 1989) entén per infant tota persona des del seu naixement fins als divuit anys d"edat. El preàmbul d"aquest text jurídic, entre altres aspectes molt importants, reafirma «la necessitat de proporcionar als infants la cura i l"assistència especials a causa de la seva vulnerabilitat».

El carácter fronterizo de las identidades contemporáneas: el caso de Chiapas

The thesis or hypothesis of this paper is that the multiple connections of explicit andimplicit life styles foster the construction of hybrid, multiple or complex identities. Wemean by hybrid identities the confluence of multiple identifications in the personalbiography. If the globalization and cultural diversity are the fundamental forms ofglobal life, the mobility is its principal ingredient. We describe different cultural traitsin Chiapas. Internet, migration to United States, or the North American Free TradeAgreement (NAFTA), between North America, Canada, and Mexico, were hybridizedwith the heterogeneity of identity (ethnic, linguistic, and religious). It is discussed thesocial and political consequences of the hybrid contemporary societies

Jóvenes que estuvieron en el sistema de protección social a la infancia : reflexiones a partir de una investigación realizada en Girona, España = Young people who were in the child protection system : reflections from a study done in Girona, Spain

Research on residential care is still scarce despite its high implementation in Spain. This article presents the results of a research using qualitative methods. The study analyses the situation experienced by young people who lived in foster care in the province of Girona (1994-2002) based on their opinions and perceptions expressed in a semi-structured interview. The results, clustered into subcategories, show lack of knowledge about the reasons why they needed foster care, if it was better being there than staying with their parents, and the lack of support for transition to adulthood. The study shows implications for children and youth policies, professional practice and research

La separació infant-família i la proposta de mesura com a recurs de protecció infantil en l'Acolliment d'Urgència i Diagnòstic : qüestions ètiques

Aquest treball es proposa reflexionar, des de la mirada de l’ètica aplicada, al voltant de dues qüestions centrals: la demora en els estudis-diagnòstics dels infants en mesura d'acolliment d’Urgència i Diagnòstic, i la incertesa que contenen una bona part de les mesures de protecció que s'acorden posteriorment. Una i altra qüestió poden tenir, en una hipòtesi inicial, conseqüències de gravetat considerable, que afectarien tant els infants - la vida dels quals quedaria fàcilment condicionada pel tipus de decisió que es prengui en aquests moments-, les seves famílies i les famílies acollidores, com, en últim extrem, el propi sistema de protecció. Això, deixant de banda la violència interna que poden arribar a generar en els i les professionals. Però també, des d'una mirada menys conseqüencialista, les dues qüestions tenen a veure amb una forma determinada d'entendre i d'atendre la vulnerabilitat extrema d'aquests infants. Fer-ho be significarà que acollir-lo ara donarà resposta a la necessitat immediata d’atenció i de cura; que respondrem a la seva vulnerabilitat amb les millors condicions possibles. També significarà respondre, en clau de futur, al seu dret a una vida digna, arrelada, estable i en igualtat d'oportunitats

Sistema educativo e igualdad de oportunidades entre los jóvenes tutelados: estudios recientes en el Reino Unido

Educational system and equal opportunities for young people in care: Recent studies in the UK. Publications on research about formal educational itineraries of people who were cared for by the social protection public systems when they were children are scarce, and restricted to a few countries. In recent years, statistics from some European countries have been published, showing that the young people who were cared for are overrepresented in practically all the clusters of people that accumulate indicators of social disadvantage, and it has therefore been argued that they can be considered one of the groups of population with the highest risk for social exclusion. In the present review, the emergence of new data and research results in some European countries —particularly in the United Kingdom, where the fact that less than 5% of this population reaches university studies has been underlined— is tentatively contextualised. Although the extent to which current available data can be extrapolated to other contexts and countries is yet unclear, such results raise important challenges for social intervention and social policies, as well as for psychosocial research, in all countries of the European space

Síntese e caracterização de argilas organofílicas contendo diferentes teores do surfactante catiônico brometo de hexadeciltrimetilamônio

The major applications of organoclays are in adsorption of organic polluents. The objective of this work was the synthesis and characterization of organoclays using differents amounts of cationic surfactant hexadecyltrimethylammonium bromide. The clays were characterized by low angle x-ray diffraction (XRD), scanning electron microscope (SEM), infrared with Fourier tranformation (FTIR), BET surface area, elemental analysis (CHN), Foster swell and adsorption of methylene blue. The surfactant can adsorb in differents forms in the interlamelar region changed the basal spacing. The presence of the surfactant adsorbed can be favorable or not in adsorption of the methylene blue due the different interactions dye-organoclays.