Yeast synaptobrevin homologs are modified posttranslationally by the addition of palmitate.

Yeast possess two homologs of the synaptobrevin family of vesicle-associated membrane proteins that function in membrane recognition and vesicle fusion. Yeast proteins Snc1 and Snc2 localize to secretory vesicles and are required for constitutive exocytosis. They also form a physical complex with a plasma membrane protein, Sec9, which is necessary for vesicle docking and fusion to occur in vivo. Formation of this molecular complex, as a prerequisite for vesicle fusion, appears to have been conserved evolutionarily. Here we demonstrate that Snc proteins undergo a single posttranslational modification with the addition of a palmitate moiety to Cys-95 in Snc1. Modification of Cys-95 (which is located proximal to the transmembrane domain) is rapid, occurs in the endoplasmic reticulum, and is long-lasting. Mutation of Cys-95 to Ser-95 blocks palmitoylation and appears to affect Snc protein stability. This provides evidence that synaptobrevin-like proteins are modified posttranslationally, and we predict that fatty acylation may be common to those found in higher eukaryotes.

The octadecanoic pathway: signal molecules for the regulation of secondary pathways.

Plant defense against microbial pathogens and herbivores relies heavily on the induction of defense proteins and low molecular weight antibiotics. The signals between perception of the aggression, gene activation, and the subsequent biosynthesis of secondary compounds are assumed to be pentacylic oxylipin derivatives. The rapid, but transient, synthesis of cis-jasmonic acid was demonstrated after insect attack on a food plant and by microbial elicitor addition to plant suspension cultures. This effect is highly specific and not caused by a number of environmental stresses such as light, heavy metals, or cold or heat shock. Elicitation of Eschscholtzia cell cultures also led to a rapid alkalinization of the growth medium prior to jasmonate formation. Inhibition of this alkalinization process by the protein kinase inhibitor staurosporine also inhibited jasmonate formation. The induction of specific enzymes in the benzo[c]phenanthridine alkaloid pathway leading to the antimicrobial sanguinarine was induced to a qualitatively and quantitatively similar extent by fungal elicitor, methyl jasmonate, and its linolenic acid-derived precursor 12-oxophytodienoic acid. It is herein proposed that a second oxylipid cascade may exist in plants starting from linoleic acid via 15,16-dihydro-12-oxophytodienoic acid to 9,10-dihydrojasmonate. Experiments with synthetic trihomojasmonate demonstrated that beta-oxidation is not a prerequisite for biological activity and that 12-oxophytodienoic acid and derivatives are most likely fully active as signal transducers. Octadecanoic acid-derived compounds are essential elements in modulating the synthesis of antibiotic compounds and are thus integral to plant defense.

O cérebro sócio-musical: estudo de uma experiência de educação musical

A prática musical tem efeitos positivos no desenvolvimento humano, envolvendo aspectos cognitivos, emocionais, motivacionais e sociais, que implicam em alterações no processamento cerebral. O número de Programas de Educação Musical (PEMs) com enfoque em populações jovens em vulnerabilidade social tem crescido no Brasil e no mundo. Dessa maneira, torna-se importante a realização de estudos que verifiquem os efeitos de PEMs no desenvolvimento destas populações. O objetivo do presente estudo é investigar os impactos de uma experiência de um PEM sobre os aspectos psicológicos de seus estudantes, mais especificamente a autoestima, as habilidades sociais e o funcionamento executivo. A coleta de dados foi realizada em um PEM da cidade de Ribeirão Preto SP e em duas escolas regulares de ensino, uma particular e outra da rede pública. Participaram do estudo 69 crianças e adolescentes com idades entre 10 e 17 anos, divididos em três grupos, a saber: Grupo Iniciante (GI), composto por alunos com até 12 meses de matrícula no PEM; Grupo Experiente (GE), composto por alunos com mais de 24 meses de matrícula no PEM; e Grupo Controle (GC), constituído por participantes sem qualquer envolvimento com aprendizado musical. Cada grupo foi composto por 23 estudantes. Os três grupos de participantes responderam aos seguintes testes psicológicos: Escala de Autoestima de Rosenberg (EAR), Matson Evaluation of Social Skills with Youngsters (MESSY) e Teste de Stroop. Também foram realizadas entrevistas semi-estruturadas com todos os estudantes dos grupos GI e GE, dez estudantes do PEM que não compuseram nenhum grupo por não possuírem o pré-requisito de tempo de matrícula exigido, seis responsáveis legais dos estudantes e doze profissionais do PEM. As entrevistas tiveram a função de fornecerem relatos verbais a respeito dos impactos percebidos nos estudantes pelo envolvimento com o PEM. Os dados dos testes psicológicos foram analisados através dos testes estatísticos ANOVA, Mann-Whitney e t de Student e as entrevistas foram analisadas através da investigação qualitativa em educação. As análises dos testes psicológicos mostraram que os GI e GE não possuem diferenças entre si para nenhuma das variáveis de estudo. O GC apresentou escores inferiores aos GI e GE para a Autoestima e escores superiores para Solidão e Ansiedade Social, indicando que o envolvimento com o PEM pode acarretar em ganhos nessas habilidades. A partir da análise das entrevistas foram construídas três categorias de codificação relacionadas a impactos comportamentais do envolvimento com o PEM, a saber: relacionamento interpessoal, desenvolvimento de habilidades intrapessoais e envolvimento com música e desenvolvimento humano na perspectiva de profissionais e responsáveis legais. A análise das entrevistas indicou que a participação no PEM está relacionada a impactos positivos na autoestima, habilidades sociais e funcionamento executivo dos participantes. Os resultados foram discutidos buscando interrelaciona-los de maneira a integrar os dados colhidos por meio dos testes psicológicos e através das entrevistas. Conclui-se que a participação em PEMs com enfoque no resgate social de populações vulneráveis possui influência no desenvolvimento de crianças e adolescentes, indicando que o uso da educação musical caracteriza uma importante estratégia de intervenção social.

Structural Polymorphism in Tau Filaments: An Implication for Neurodegenerative Diseases

Tau filaments are the pathological hallmark of >20 neurodegenerative diseases including Alzheimer's disease, Pick's disease, and progressive supranuclear palsy. In the adult human brain, six isoforms of tau are expressed that differ by presence or absence of the second of the four semiconserved repeats. As a consequence, half of the tau isoforms have three repeats (3R tau), whereas the other half has four repeats (4R tau). Site-directed spin labeling of recombinant tau in conjunction with electron paramagnetic resonance spectroscopy was used to obtain structural insights into tau filaments. The studies showed that the filaments of 4R tau and 3R tau share a highly ordered core structure in the third repeat with parallel, in-register arrangement of beta-strands. This structure in 3R and 4R is conserved regardless of whether full-length isoforms (htau40 and htau23) or truncated constructs (K18 and K19) are used. When mixed, 3R tau and 4R tau coassembled into heterogeneous filaments. Hence, these findings indicate that there are at least three compositionally distinct types of filaments: homogeneous 3R tau, homogeneous 4R tau, and heterogeneous 3R/4R tau. In vitro experiments show that the seeded filament growth, a prerequisite for tau spreading in tissue culture and brain, is crucially dependent on the isoform composition of individual seeds. Seeds of 3R tau and 3R/4R tau recruit both types of isoforms whereas seeds of 4R tau can recruit 4R tau, but not 3R tau, establishing an asymmetric barrier. Conformational templating of 4R tau onto 3R tau seeds eliminates this barrier, giving rise to a new type of tau filament. Conformational studies at the molecular level of tau filaments were done using Double electron-electron resonance spectroscopy, which allows the determination of distances between pairs of spin labels. These studies revealed structural differences between filaments of 3R tau and 4R tau. Furthermore, they indicated that 4R tau assumed the conformation of 3R tau when templated on 3R tau seeds. Our measurements have also provided insights into the heterogeneity of tau filament structure. Conformational differences due to variation in filament composition and seeding properties of tau filaments have shown that they are structurally polymorphic in nature. This structural polymorphism of tau filaments has widespread implications in understanding and treatment of neurodegenerative diseases.

Barriers and facilitators to effective coverage of Intimate Partner Violence services for immigrant women in Spain

Objective: To explore service providers’ perceptions in order to identify barriers and facilitators to effective coverage of Intimate Partner Violence (IPV) services for immigrant women in Spain, according to the different categories proposed in Tanahashi's model of effective coverage. Methods: A qualitative study based on 29 in-depth personal interviews and four group interviews with a total of 43 professionals working in public services (social and health-care services, women's refuges, the police force, the judiciary) and NGOs in Barcelona, Madrid, Valencia and Alicante (Spain) in 2011. Findings: Current IPV services in Spain partially fail in their coverage of abused immigrant women due to barriers of (i) availability, such as the inexistence of culturally appropriate services; (ii) accessibility, as having a residence permit is a prerequisite for women's access to different services and rights; (iii) acceptability, such as women's lack of confidence in the effectiveness of services; and (iv) effectiveness, for example, lack of specific training among professionals on the issues of IPV and immigration. However, interviewees also identified facilitators, such as the enabling environment promoted by the Spanish Law on Gender-Based Violence (1/2004), and the impetus it has provided for the development of other specific legislative tools to address IPV in immigrant populations in Spain (availability, accessibility and effectiveness). Conclusion: Whilst not dismissing cultural barriers, aspects related to service structure are identified by providers as the main barriers and facilitators to immigrant women use of IPV services. Despite noteworthy achievements, improvements are still required in terms of mainstreaming assistance tailored to immigrant women's needs in IPV policies and services.

Prontidão de alunos do ensino superior para a aprendizagem de álgebra linear

Neste artigo estuda-se a prontidão de alunos do ensino superior para a aprendizagem de álgebra linear, salientando a natureza teórica desta área de conhecimento. Participaram no estudo alunos do ensino superior, de uma turma do 1.º ano, de um Instituto Politécnico do norte de Portugal. Os alunos responderam a um teste diagnóstico, cujas questões incorporavam conteúdos lecionados durante os anos escolares anteriores à entrada no ensino superior, considerados como pré-requisito para a aprendizagem de álgebra linear numa vertente mais teórica. Dos resultados do estudo, destacam-se as grandes dificuldades dos alunos em todos os conteúdos avaliados, verificando-se que mais de metade apresentou respostas incorretas ou não respondeu às questões colocadas, donde se conclui que os alunos não apresentam um grau de prontidão adequado para aprendizagem de álgebra linear.

Fraturas do rádio distal : revisão bibliográfica

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Lymphatic vessel function in atherosclerosis

L'athérosclérose est une maladie inflammatoire chronique caractérisée par l'accumulation de cholestérol dans la paroi artérielle et associée à une réponse immunitaire anormale dans laquelle les macrophages jouent un rôle important. Récemment, il a été démontré que les vaisseaux lymphatiques jouent un rôle primordial dans le transport inverse du cholestérol (Martel et al. JCI 2013). L’objectif global de mon stage de maîtrise a été de mieux caractériser la dysfonction lymphatique associée à l’athérosclérose, en étudiant de plus près l’origine physiologique et temporelle de ce mauvais fonctionnement. Notre approche a été d’étudier, depuis l’initiation de l’athérosclérose jusqu’à la progression d’une lésion athérosclérotique tardive, la physiologie des deux constituants principaux qui forment les vaisseaux lymphatiques : les capillaires et collecteurs lymphatiques. En utilisant comme modèle principal des souris Ldlr-/-; hApoB100+/+, nous avons pu démontrer que la dysfonction lymphatique est présente avant même l’apparition de l’athérosclérose, et que cette dysfonction est principalement associée avec un défaut au niveau des vaisseaux collecteurs, limitant ainsi le transport de la lymphe des tissus périphériques vers le sang. De plus, nous avons démontré pour la première fois l’expression du récepteur au LDL par les cellules endothéliales lymphatiques. Nos travaux subséquents démontrent que ce défaut de propulsion de la lymphe pourrait être attribuable à l’absence du récepteur au LDL, et que la dysfonction lymphatique observée précocement dans l’athérosclérose peut être limitée par des injections systémiques de VEGF (vascular endothelial growth factor) –C. Ces résultats suggèrent que la caractérisation fonctionnelle de la capacité de pompage des vaisseaux collecteurs serait une condition préalable à la compréhension de l'interaction entre la fonction du système lymphatique et la progression de l'athérosclérose. Ultimement, nos travaux nous ont amené à considérer de nouvelles cibles thérapeutiques potentielles dans la prévention et le traitement de l’athérosclérose.

Towards a Fragmented Neighbourhood: Policies of the EU and Russia and their consequences for the area that lies in between. CEPS Essay No. 17, 17 October 2014

In the current volatile climate, the EU needs a strategy towards Russia that goes beyond sanctions. In reviewing the European Neighbourhood Policy and the Eastern Partnership, the EU’s incoming leadership should be more sensitive towards the existing political, diplomatic, economic, energy and military ties between Russia and the countries in the common neighbourhood. After all, it is by exploiting these ties that Russia was able to turn this neighbourhood into an area of destructive competition − the primary victim of which is Ukraine. Understanding Russia’s perceptions and being sensitive to these longstanding ties does not mean justifying their use by the Kremlin. Nevertheless, factoring these ties into the EU’s policies vis-à-vis its Eastern neighbourhood is a prerequisite for more reflective, responsive and effective EU policies.

Necessary desirability: The inherent contradiction in the European system. EuropEos Commentary No. 11, 9 June 2011

In all political systems there is a gap between the rhetoric of electoral programmes and the practical work of institutions, argues author Riccardo Perissich, but the ‘vision thing’ is often a necessary prerequisite to reaching difficult decisions. When it comes to European institutions, which include the member states acting collectively, the desirable vision – the goal of European unity – has always been there and is still very much alive. Also, the existence of a broadly defined political goal has often facilitated agreements that were in fact purely necessary. However, because we lack a pan-European constituency to debate it, the narrative about this goal has been translated into different languages and is all but common. In fact, we have never seriously tried to unify it. Indeed, Europeans stopped debating what is desirable a long time ago: they simply react to events.

EU Mission in Kosovo (EULEX): Constructing Ambiguity or Constructive Disunity? Transatlantic Security Paper No. 3, June 2011

In which skies should auspices about the future of EU foreign policy be looked for, Libya’s or Kosovo’s? Many commentators have been prompt in digging the grave for EU Security and Defense Policy after Member States’ discordance over taking military action against the Qaddafi regime1. However, as this paper will emphasize through the case of Kosovo, unanimity is not always an indispensable prerequisite – and should not be regarded as the sole criteria – to EU action in regional security. Overly focusing on the ‘speak with one voice’ mantra sometimes leads to stop short of assessing actual outcomes.

Granular computing as a basis of human–data interaction: a cognitive cities use case

The article proposes granular computing as a theoretical, formal and methodological basis for the newly emerging research field of human–data interaction (HDI). We argue that the ability to represent and reason with information granules is a prerequisite for data legibility. As such, it allows for extending the research agenda of HDI to encompass the topic of collective intelligence amplification, which is seen as an opportunity of today’s increasingly pervasive computing environments. As an example of collective intelligence amplification in HDI, we introduce a collaborative urban planning use case in a cognitive city environment and show how an iterative process of user input and human-oriented automated data processing can support collective decision making. As a basis for automated human-oriented data processing, we use the spatial granular calculus of granular geometry.

Mesure de la performance dans les organisations de réadaptation en déficience physique

La présente thèse vise à évaluer le degré d’implantation et d’utilisation de systèmes de mesure de la performance (SMP) par les décideurs des organisations de réadaptation et à comprendre les facteurs contextuels ayant influencé leur implantation. Pour ce faire, une étude de cas multiples a été réalisée comprenant deux sources de données: des entrevues individuelles avec des cadres supérieurs des organisations de réadaptation du Québec et des documents organisationnels. Le cadre conceptuel Consolidated Framework for Implementation Research a été utilisé pour guider la collecte et l’analyse des données. Une analyse intra-cas ainsi qu’une analyse inter-cas ont été réalisées. Nos résultats montrent que le niveau de préparation organisationnelle à l’implantation d’un SMP était élevé et que les SMP ont été implantés avec succès et utilisés de plusieurs façons. Les organisations les ont utilisés de façon passive (comme outil d’information), de façon ciblée (pour tenter d’améliorer des domaines sous-performants) et de façon politique (comme outil de négociation auprès des autorités gouvernementales). Cette utilisation diversifiée des SMP est suscitée par l’interaction complexe de facteurs provenant du contexte interne propre à chaque organisation, des caractéristiques du SMP, du processus d’implantation appliqué et du contexte externe dans lequel évoluent ces organisations. Au niveau du contexte interne, l’engagement continu et le leadership de la haute direction ont été décisifs dans l’implantation du SMP de par leur influence sur l’identification du besoin d’un SMP, l’engagement des utilisateurs visés dans le projet, la priorité organisationnelle accordée au SMP ainsi que les ressources octroyées à son implantation, la qualité des communications et le climat d’apprentissage organisationnel. Toutefois, même si certains de ces facteurs, comme les ressources octroyées à l’implantation, la priorité organisationnelle du SMP et le climat d’apprentissage se sont révélés être des barrières à l’implantation, ultimement, ces barrières n’étaient pas suffisamment importantes pour entraver l’utilisation du SMP. Cette étude a également confirmé l’importance des caractéristiques du SMP, particulièrement la perception de qualité et d’utilité de l’information. Cependant, à elles seules, ces caractéristiques sont insuffisantes pour assurer le succès d’implantation. Cette analyse d’implantation a également révélé que, même si le processus d’implantation ne suit pas des étapes formelles, un plan de développement du SMP, la participation et l’engagement des décideurs ainsi que la désignation d’un responsable de projet ont tous facilité son implantation. Cependant, l’absence d’évaluation et de réflexion collective sur le processus d’implantation a limité le potentiel d’apprentissage organisationnel, un prérequis à l’amélioration de la performance. Quant au contexte externe, le soutien d’un organisme externe s’est avéré un facilitateur indispensable pour favoriser l’implantation de SMP par les organisations de réadaptation malgré l’absence de politiques et incitatifs gouvernementaux à cet effet. Cette étude contribue à accroître les connaissances sur les facteurs contextuels ainsi que sur leurs interactions dans l’utilisation d’innovations tels les SMP et confirme l’importance d’aborder l’analyse de l’implantation avec une perspective systémique.

Les approches de synthèse exploratoire dans le domaine de la santé

Contexte: Les approches de synthèse exploratoire (ou scoping studies) font actuellement l’objet de confusion dans leur appellation, définition et but. Elles continuent aussi de manquer de description méthodologique suffisante ou de détails sur le processus de l’analyse de données. Objectif : Cette synthèse exploratoire fait le point des connaissances sur les approches de synthèse exploratoire utilisées en santé. Plus spécifiquement, ses objectifs sont : 1) d’examiner le volume et l’étendue des synthèses exploratoires ainsi que les domaines d’étude dans lesquels elles ont été conduites; 2) de faire l’inventaire de leurs définitions, buts, forces et faiblesses; et 3) et de faire l’inventaire des approches méthodologiques existantes. Méthodes : Une recherche systématique des synthèses exploratoires a été entreprise jusqu’en avril 2014 dans les bases de données Medline, PubMed, ERIC, PsycINFO, CINAHL, EMBASE, EBM Reviews/Cochrane. Des critères d’inclusion et d’exclusion ont été appliqués afin de ne retenir que des études de langue française et anglaise présentant des définitions, méthodes et écarts de connaissances sur les synthèses exploratoires, ainsi que celles les comparant à d’autres types de revues de littérature. Deux reviseurs ont examiné de façon indépendante les références pertinentes. Une grille d’extraction des données a été conçue afin de recueillir pour chacune des études, les données contextuelles, les étapes méthodologiques ainsi que les définitions, buts et limites des synthèses exploratoires. Les données ont été répertoriées et classées afin de dresser un portrait global des approches de synthèses exploratoires dans un format narratif et tabulaire. Résultats : Sur deux cent cinquante-deux références identifiées, quatre-vingt-douze références pertinentes ont été retenues. Les synthèses exploratoires ont été publiées par 6 pays dans 10 domaines d’études et 73 journaux. Elles ont pour finalité d’être à la fois un support aux connaissances, une aide à la décision et un préalable à une revue systématique de littérature. Cinq auteurs ont été cités en référence et huit autres ont publié sur leur méthodologie. Elles ont 3 étapes importantes de réalisation dont la revue de littérature, la consultation des parties prenantes et la synthèse globale avec ou sans validation des résultats. Les synthèses exploratoires utilisent une méthode systématique, pas toujours exhaustive et sans évaluation formelle des études incluses Des notions claires portant sur leur définition, buts, forces et faiblesses ont été identifiées. Conclusion : Nous suggérons que de nouvelles études soient entreprises afin d’asseoir complètement cette méthode et dégager des lignes directrices pour les chercheurs qui s’y intéresseront.

Geochemistry of Early Toarcian carbonates

The Early Toarcian was characterized by two large perturbations to the carbon cycle: a positive trend associated with increased organic matter burial and ocean anoxia, and a pronounced negative carbon isotope excursion (CIE). We contrast the geochemical evolution in the carbonate phases of two successions: one from the Paris Basin (Sancerre core, comprising black shales), the other from the Lusitanian Basin (Peniche section with very minor lithological expression of bottom water anoxia). Our aim was to identify whether these carbon cycle perturbations were related, and differentiate between the common (global) versus regional expressions of the biogeochemical response and ocean chemistry. Our results highlight contrasts in timing of different phases of anoxia in both locations through the widely documented negative CIE. Widespread anoxic conditions were not a necessary prerequisite for generating a pronounced CIE, as required by the recycling (so-called "Küspert") model. The production of carbonate simultaneously dropped during the d13C negative shift in both locations, likely in response to lowered seawater saturation rate induced by substantial absorption of CO2 from the atmosphere. The recovery interval was accompanied by a rapid reestablishment of seawater alkalinity, and primary and carbonate productivity in epicontinental seas, as evidenced by high d13C and Sr/Ca, in contrast with the more open ocean regime in the Lusitanian Basin. Our results confirm that parallels can be draw between the ocean productivity response and feedback during the Toarcian CIE and the PETM. Both events are characterized by ocean acidification and reduced pelagic calcification followed by a peak in nearshore coccolith productivity, which could have helped the recovery from the perturbation.