Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia

Overexpression of the mammalian homolog of the unc-18 gene (munc18-1) has been described in the brain of subjects with schizophrenia. Munc18-1 protein is involved in membrane fusion processes, exocytosis and neurotransmitter release. A transgenic mouse strain that overexpresses the protein isoform munc18-1a in the brain was characterized. This animal displays several schizophrenia-related behaviors, supersensitivity to hallucinogenic drugs and deficits in prepulse inhibition that reverse after antipsychotic treatment. Relevant brain areas (that is, cortex and striatum) exhibit reduced expression of dopamine D-1 receptors and dopamine transporters together with enhanced amphetamine-induced in vivo dopamine release. Magnetic resonance imaging demonstrates decreased gray matter volume in the transgenic animal. In conclusion, the mouse overexpressing brain munc18-1a represents a new valid animal model that resembles functional and structural abnormalities in patients with schizophrenia.

Oligodendrocyte differentiation from adult multipotent stem cells is modulated by glutamate

We used multipotent stem cells (MSCs) derived from the young rat subventricular zone (SVZ) to study the effects of glutamate in oligodendrocyte maturation. Glutamate stimulated oligodendrocyte differentiation from SVZ-derived MSCs through the activation of specific N-methyl-D-aspartate (NMDA) receptor subunits. The effect of glutamate and NMDA on oligodendrocyte differentiation was evident in both the number of newly generated oligodendrocytes and their morphology. In addition, the levels of NMDAR1 and NMDAR2A protein increased during differentiation, whereas NMDAR2B and NMDAR3 protein levels decreased, suggesting differential expression of NMDA receptor subunits during maturation. Microfluorimetry showed that the activation of NMDA receptors during oligodendrocyte differentiation elevated cytosolic calcium levels and promoted myelination in cocultures with neurons. Moreover, we observed that stimulation of MSCs by NMDA receptors induced the generation of reactive oxygen species (ROS), which were negatively modulated by the NADPH inhibitor apocynin, and that the levels of ROS correlated with the degree of differentiation. Taken together, these findings suggest that ROS generated by NADPH oxidase by the activation of NMDA receptors promotes the maturation of oligodendrocytes and favors myelination

Intracellular Ca2+ release through ryanodine receptors contributes to AMPA receptor-mediated mitochondrial dysfunction and ER stress in oligodendrocytes

Overactivation of ionotropic glutamate receptors in oligodendrocytes induces cytosolic Ca2+ overload and excitotoxic death, a process that contributes to demyelination and multiple sclerosis. Excitotoxic insults cause well-characterized mitochondrial alterations and endoplasmic reticulum (ER) dysfunction, which is not fully understood. In this study, we analyzed the contribution of ER-Ca2+ release through ryanodine receptors (RyRs) and inositol triphosphate receptors (IP(3)Rs) to excitotoxicity in oligodendrocytes in vitro. First, we observed that oligodendrocytes express all previously characterized RyRs and IP(3)Rs. Blockade of Ca2+-induced Ca2+ release by TMB-8 following alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor-mediated insults attenuated both oligodendrocyte death and cytosolic Ca2+ overload. In turn, RyR inhibition by ryanodine reduced as well the Ca2+ overload whereas IP3R inhibition was ineffective. Furthermore, AMPA-triggered mitochondrial membrane depolarization, oxidative stress and activation of caspase-3, which in all instances was diminished by RyR inhibition. In addition, we observed that AMPA induced an ER stress response as revealed by alpha subunit of the eukaryotic initiation factor 2 alpha phosphorylation, overexpression of GRP chaperones and RyR-dependent cleavage of caspase-12. Finally, attenuating ER stress with salubrinal protected oligodendrocytes from AMPA excitotoxicity. Together, these results show that Ca2+ release through RyRs contributes to cytosolic Ca2+ overload, mitochondrial dysfunction, ER stress and cell death following AMPA receptor-mediated excitotoxicity in oligodendrocytes. Cell Death and Disease (2010) 1, e54; doi:10.1038/cddis.2010.31; published online 15 July 2010

Entidades Sociales, Inmigrantes y Bienestar Psicológico

La función última de las entidades sociales que atienden a emigrantes es el de promover su integración social y calidad de vida. Potenciar la dimensión cualitativa de la misma implica conocer el nivel de bienestar psicológico subjetivo de las personas usuarias de las mismas. El objetivo principal es el de identificar y evaluar las dimensiones del bienestar subjetivo de las personas inmigrantes adultas usuarias de tres asociaciones ubicadas en Vizcaya. El diseño metodológico empleado es de tipo cualitativo, basado en entrevistas semiestructuradas aplicadas a una muestra intencional compuesta por siete personas inmigrantes adultas residentes en Vizcaya. El análisis de los testimonios desvela diferencias en los niveles de bienestar subjetivo relacionados con su nivel de participación e implicación en la asociación de pertenencia. La principal conclusión extraída del estudio es que la asociación influye de forma positiva en el bienestar de los inmigrantes, mostrando mayor nivel de satisfacción aquellos que además participan como voluntarios.

San Francisco : a city reinvented by creative innovation

The aim of this paper is to analyse the recent evolution of the city of San Francisco to outline the major features that have made it possible this continuing process of creative innovation in the city. In order to meet this objective, the project is framed around answering two key research questions: (1) what are the main economic and social elements that characterise urban change in the city of San Francisco and (2) which is the role of public strategies in the continuing economic success of San Francisco. The paper concludes that the successful performance of San Francisco is the result of the actions taken by many agents in the city, but the role of public authorities, especially the City and County, must be stressed, both through direct intervention and by coordinating, fostering and supporting the private and non-profit sectors. This is especially relevant in a country like the US where private initiative has been seen in many occasions as the greatest driver of economic and social success. Yet, the performance of San Francisco City cannot be explained without the role played by the public sector, in coordination with the civil society

A bibliography of works for the identification of freshwater invertebrates in the British Isles

This bibliography covers the literature up to the end of 1978. The criteria used in the selection of references were that they should aid identification of invertebrates directly; thus, works solely concerned with the taxonomy of a particular group are in general omitted unless they contain a key. Some check-lists are however included where they give current nomenclature. The references are arranged alphabetically within each group and deal mainly with macro-invertebrates but include available keys to some microscopic invertebrates. Internal parasites and hymenopterous parasitoids are omitted. For insects the life stages to which the key applies are given where this is not clear in the reference. A number of keys to non-aquatic stages have been included in the hope that they may prove useful in certain circumstances. In addition, under a general head, latest check-lists are referred to together with bibliographies of algal keys and a guide for the identification of British water plants.

Implementation of the nursing process in a health area: models and assessment structures used

Objective: to analyze what nursing models and nursing assessment structures have been used in the implementation of the nursing process at the public and private centers in the health area Gipuzkoa (Basque Country). Method: a retrospective study was undertaken, based on the analysis of the nursing records used at the 158 centers studied. Results: the Henderson model, Carpenito's bifocal structure, Gordon's assessment structure and the Resident Assessment Instrument Nursing Home 2.0 have been used as nursing models and assessment structures to implement the nursing process. At some centers, the selected model or assessment structure has varied over time. Conclusion: Henderson's model has been the most used to implement the nursing process. Furthermore, the trend is observed to complement or replace Henderson's model by nursing assessment structures.

Prediction of Multi-Target Networks of Neuroprotective Compounds with Entropy Indices and Synthesis, Assay, and Theoretical Study of New Asymmetric 1,2-Rasagiline Carbamates

In a multi-target complex network, the links (L-ij) represent the interactions between the drug (d(i)) and the target (t(j)), characterized by different experimental measures (K-i, K-m, IC50, etc.) obtained in pharmacological assays under diverse boundary conditions (c(j)). In this work, we handle Shannon entropy measures for developing a model encompassing a multi-target network of neuroprotective/neurotoxic compounds reported in the CHEMBL database. The model predicts correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80%-90% on training and external validation series. Indeed, the model can calculate different outcomes for >30 experimental measures in >400 different experimental protocolsin relation with >150 molecular and cellular targets on 11 different organisms (including human). Hereafter, we reported by the first time the synthesis, characterization, and experimental assays of a new series of chiral 1,2-rasagiline carbamate derivatives not reported in previous works. The experimental tests included: (1) assay in absence of neurotoxic agents; (2) in the presence of glutamate; and (3) in the presence of H2O2. Lastly, we used the new Assessing Links with Moving Averages (ALMA)-entropy model to predict possible outcomes for the new compounds in a high number of pharmacological tests not carried out experimentally.

Machado de Assis e o exercício dos gêneros da intimidade

Observando o crescente interesse pela escrita do eu e levando em conta a afirmação de Jorge de Sena no ensaio Machado de Assis e o seu quinteto carioca, que declara haver como unidade entre as cinco obras finais de Machado de Assis o questionamento dos gêneros que expressam a subjetividade moderna, buscamos investigar, nesta dissertação, a maneira como Machado de Assis lida com alguns desses gêneros da intimidade, dentro e fora do espaço ficcional. Para tanto, selecionamos duas das obras finais que empregam mais diretamente a escrita do eu e que, do mesmo modo, mais transgridem essa escrita: Memórias Póstumas de Brás Cubas, uma autobiografia escrita por um defunto autor; e Memorial de Aires, um diário que registra mais frequentemente a vida dos outros do que a do próprio diarista Aires. Além das obras ficcionais, trazemos para a análise as missivas machadianas, observando como o escritor constrói a imagem de si na troca de cartas com intelectuais de seu convívio. Refletindo sobre o exercício desses gêneros da intimidade, por parte de Machado de Assis, observamos que este, na sua correspondência, não ultrapassou os limites que, à época, regiam a troca de confidências entre pares e amigos. Comedido e discreto, assume, de modo geral, o papel de mestre e aconselhador, apresentando em suas cartas um projeto literário de cunho pedagógico, conduzindo os mais jovens na direção da literatura. Já na ficção, ao fazer um uso engenhoso e criativo das retóricas da autobiografia e do diário, o escritor utilizou tais gêneros para, ao mesmo tempo, recobrir e agudizar a crítica corrosiva à sociedade de seu tempo

Relativistic force between fast electrons and planar targets

The full retarded electromagnetic force experienced by swift electrons moving parallel to planar boundaries is revisited, for both metallic and dielectric targets, with special emphasis on the consequences in electron microscopy experiments. The focus is placed on the sign of the transverse force experienced by the electron beam as a function of the impact parameter. For point probes, the force is found to be always attractive. The contribution of the induced magnetic field and the causality requirements of the target dielectric response, given by the Kramers-Kronig (K-K) relations, prove to be crucial issues at small impact parameters. For spatially extended probes, repulsive forces are predicted for close trajectories, in agreement with previous works. The force experienced by the target is also explored, with the finding that in insulators, the momentum associated to Cherenkov radiation (CR) is relevant at large impact parameters.

Structural Synthesis of 3-DoF Spatial Fully Parallel Manipulators

In this paper, the architectures of three degrees of freedom (3-DoF) spatial, fully parallel manipulators (PMs), whose limbs are structurally identical, are obtained systematically. To do this, the methodology followed makes use of the concepts of the displacement group theory of rigid body motion. This theory works with so-called 'motion generators'. That is, every limb is a kinematic chain that produces a certain type of displacement in the mobile platform or end-effector. The laws of group algebra will determine the actual motion pattern of the end-effector. The structural synthesis is a combinatorial process of different kinematic chains' topologies employed in order to get all of the 3-DoF motion pattern possibilities in the end-effector of the fully parallel manipulator.

Modos de subjetivação em redes de saúde, vistos através das narrativas sobre fantasmas das Termas de Araxá: um estudo de caso

Mediante narrativas de casos de aparição de fantasmas em um complexo de águas termais localizado no Barreiro de Araxá, em Minas Gerais, que mudou sua imagem de lugar de cura e saúde para ambiente de lazer e beleza, este trabalho buscou seguir pistas sobre: a ascensão, queda e renascimento do termalismo no Brasil; o problema da contaminação das águas minerais do Barreiro; as incongruências nas ações das Políticas Públicas. Tais aspectos produziram efeitos múltiplos nos trabalhadores das Termas e na população local, tais como: fantasmas, medos, silêncios, disputas e adoecimentos. A pesquisa toma como inspiração metodológica os trabalhos de Alessandro Portelli com a História Oral, para obter e acompanhar as narrativas; a genealogia de Michel Foucault, para apresentar as mudanças no conceito de saúde e de terapêutica no tempo; a Teoria do ator-rede de Bruno Latour, para seguir os actantes, humanos e não-humanos. Chama atenção para o cuidado de si como forma ética de estar no mundo, tendente a tornar a vida potente, criativa, abrindo uma possibilidade de alguém se tornar médico de si mesmo. Entende, nesse sentido, que podem ser viáveis, desde que em ruptura com meras práticas de renovado controle da vida das populações, as novas terapêuticas implantadas no SUS ? Terapias Alternativas e Complementares, dentre elas, em particular, o Termalismo Social.