29 research outputs found

    Integrating genetic, neuropsychological and neuroimaging data to model early-onset obsessive compulsive disorder severity

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    We propose an integrative approach that combines structural magnetic resonance imaging data (MRI), diffusion tensor imaging data (DTI), neuropsychological data, and genetic data to predict early-onset obsessive compulsive disorder (OCD) severity. From a cohort of 87 patients, 56 with complete information were used in the present analysis. First, we performed a multivariate genetic association analysis of OCD severity with 266 genetic polymorphisms. This association analysis was used to select and prioritize the SNPs that would be included in the model. Second, we split the sample into a training set (N = 38) and a validation set (N = 18). Third, entropy-based measures of information gain were used for feature selection with the training subset. Fourth, the selected features were fed into two supervised methods of class prediction based on machine learning, using the leave-one-out procedure with the train- ing set. Finally, the resulting model was validated with the validation set. Nine variables were used for the creation of the OCD severity predictor, including six genetic polymorphisms and three variables from the neuropsychological data. The developed model classified child and adolescent patients with OCD by disease severity with an accuracy of 0.90 in the testing set and 0.70 in the validation sample. Above its clinical applicability, the combination of particular neuropsychological, neuroimaging, and genetic characteristics could enhance our under- standing of the neurobiological basis of the disorder

    Different modulation of RPS6 phosphorylation by risperidone in striatal cells sub populations: involvement of the mTOR pathway in antipsychotic-induced extrapyramidal symptoms in mice

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    Objective: Acute extrapyramidal symptoms (EPS) are frequent and serious adverse reactions to antipsychotic (AP) drugs. Although the proposed mechanism is an excessive blockade of dopamine D2 receptors in the striatopallidal pathway of the striatum, previous studies implicated the mTOR pathway in the susceptibility to EPS. The objective of the present study is to analyze the mTOR-mediated response to risperidone in subpopulations of striatal neurons and its relationship to risperidone-induced motor side effects. Methods: Two mouse strains (A/J and DBA/2J) with different susceptibility to developing EPS were treated with risperidone 1 mg/kg for three consecutive days. Here we monitored, by double labeling immunohistochemistry, ribosomal protein S6 (rpS6) phosphorylation (Ser235/236 and Ser244/247 sites), a marker of mTOR signaling, in the striatonigral pathway (D1-medium spiny neurons (MSNs)), the striatopallidal pathway (D2-MSNs) and striatal cholinergic interneurons. Results: We found that EPS-resistant DBA/2J mice show higher baseline levels of phosphoactivated rpS6 protein in striatal MSNs, compared with EPS-prone A/J mice. Moreover, risperidone differentially targeted rpS6 phosphorylation in direct and indirect pathway neurons in a strain-specific manner: a significant decrease in the phosphorylation of rpS6 at Ser235/236 and Ser240/244 in DRD1-MSNs EPS-resistant DBA/2J mice after; and a significant increase of phospho-Ser235/236-rpS6 in the striatopallidal pathway of the EPS-prone A/J mice in response to risperidone. Conclusions: Our results reveal the vital role of genetic background in the response to risperidone, and point to the mTOR pathway as an important factor in EPS susceptibility. Keywords: Schizophrenia, Antipsychotic, Risperidone, Extrapyramidal symptoms. mTOR pathway, Striatum, Medium spiny neuron

    Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycotics

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    In previous work we developed a pharmacogenetic predictor of antipsychotic (AP) induced extrapyramidal symptoms (EPS) based on four genes involved in mTOR regulation. The main objective is to improve this predictor by increasing its biological plausibility and replication. We re-sequence the four genes using next-generation sequencing. We predict functionality 'in silico' of all identified SNPs and test it using gene reporter assays. Using functional SNPs, we develop a new predictor utilizing machine learning algorithms (Discovery Cohort, N = 131) and replicate it in two independent cohorts (Replication Cohort 1, N = 113; Replication Cohort 2, N = 113). After prioritization, four SNPs were used to develop the pharmacogenetic predictor of AP-induced EPS. The model constructed using the Naive Bayes algorithm achieved a 66% of accuracy in the Discovery Cohort, and similar performances in the replication cohorts. The result is an improved pharmacogenetic predictor of AP-induced EPS, which is more robust and generalizable than the original

    Engaging stakeholders across a socio-environmentally diverse network of water research sites in North and South America

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    Maintaining and restoring freshwater ecosystem services in the face of local and global change requires adaptive research that effectively engages stakeholders. However, there is a lack of understanding and consensus in the research community regarding where, when, and which stakeholders should be engaged and what kind of researcher should do the engaging (e.g., physical, ecological, or social scientists). This paper explores stakeholder engagement across a developing network of aquatic research sites in North and South America with wide ranging cultural norms, social values, resource management paradigms, and eco-physical conditions. With seven sites in six countries, we found different degrees of engagement were explained by differences in the interests of the stakeholders given the history and perceived urgency of water resource problems as well as differences in the capacities of the site teams to effectively engage given their expertise and resources. We categorized engagement activities and applied Hurlbert and Gupta's split ladder of participation to better understand site differences and distill lessons learned for planning comparative socio-hydrological research and systematic evaluations of the effectiveness of stakeholder engagement approaches. We recommend research networks practice deliberate engagement of stakeholders that adaptively accounts for variations and changes in local socio-hydrologic conditions. This, in turn, requires further efforts to foster the development of well-integrated research teams that attract and retain researchers from multiple social science disciplines and enable training on effective engagement strategies for diverse conditions

    Engaging stakeholders across a socio-environmentally diverse network of water research sites in North and South America

    Get PDF
    Maintaining and restoring freshwater ecosystem services in the face of local and global change requires adaptive research that effectively engages stakeholders. However, there is a lack of understanding and consensus in the research community regarding where, when, and which stakeholders should be engaged and what kind of researcher should do the engaging (e.g., physical, ecological, or social scientists). This paper explores stakeholder engagement across a developing network of aquatic research sites in North and South America with wide ranging cultural norms, social values, resource management paradigms, and eco-physical conditions. With seven sites in six countries, we found different degrees of engagement were explained by differences in the interests of the stakeholders given the history and perceived urgency of water resource problems as well as differences in the capacities of the site teams to effectively engage given their expertise and resources. We categorized engagement activities and applied Hurlbert and Gupta's split ladder of participation to better understand site differences and distill lessons learned for planning comparative socio-hydrological research and systematic evaluations of the effectiveness of stakeholder engagement approaches. We recommend research networks practice deliberate engagement of stakeholders that adaptively accounts for variations and changes in local socio-hydrologic conditions. This, in turn, requires further efforts to foster the development of well-integrated research teams that attract and retain researchers from multiple social science disciplines and enable training on effective engagement strategies for diverse conditions.Fil: Smyth, Robyn L.. Bard College; Estados UnidosFil: Fatima, Uroosa. Bard College; Estados UnidosFil: Segarra, Monique. Bard College; Estados UnidosFil: Borre, Lisa. Cary Institute of Ecosystem Studies; Estados UnidosFil: Zilio, Mariana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Económicas y Sociales del Sur. Universidad Nacional del Sur. Departamento de Economía. Instituto de Investigaciones Económicas y Sociales del Sur; ArgentinaFil: Reid, Brian. Universidad Austral de Chile; ChileFil: Pincetl, Stephanie. Institute of the Environment and Sustainability; Estados UnidosFil: Astorga, Anna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Económicas y Sociales del Sur. Universidad Nacional del Sur. Departamento de Economía. Instituto de Investigaciones Económicas y Sociales del Sur; ArgentinaFil: Huamantinco Cisneros, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Geografía y Turismo; ArgentinaFil: Conde, Sergio Daniel. Universidad de la República; UruguayFil: Harmon, Thomas Christopher. University of California Merced; Estados UnidosFil: Hoyos, Natalia. Universidad del Norte; ColombiaFil: Escobar, Jaime. Universidad del Norte; Colombia. Smithsonian Tropical Research Institute; PanamáFil: Lozoya, Juan Pablo. Universidad de la República; UruguayFil: Perillo, Gerardo Miguel E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Geología; ArgentinaFil: Piccolo, Maria Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Geografía y Turismo; ArgentinaFil: Rusak, James A.. Dorset Environmental Science Centre; Canadá. Queens University; CanadáFil: Velez, Maria I.. University of Regina; Canad

    The global EPTO database: Worldwide occurrences of aquatic insects

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    Motivation: Aquatic insects comprise 64% of freshwater animal diversity and are widely used as bioindicators to assess water quality impairment and freshwater ecosystem health, as well as to test ecological hypotheses. Despite their importance, a comprehensive, global database of aquatic insect occurrences for mapping freshwater biodiversity in macroecological studies and applied freshwater research is missing. We aim to fill this gap and present the Global EPTO Database, which includes worldwide geo-referenced aquatic insect occurrence records for four major taxa groups: Ephemeroptera, Plecoptera, Trichoptera and Odonata (EPTO). Main type of variables contained: A total of 8,368,467 occurrence records globally, of which 8,319,689 (99%) are publicly available. The records are attributed to the corresponding drainage basin and sub-catchment based on the Hydrography90m dataset and are accompanied by the elevation value, the freshwater ecoregion and the protection status of their location. Spatial location and grain: The database covers the global extent, with 86% of the observation records having coordinates with at least four decimal digits (11.1 m precision at the equator) in the World Geodetic System 1984 (WGS84) coordinate reference system. Time period and grain: Sampling years span from 1951 to 2021. Ninety-nine percent of the records have information on the year of the observation, 95% on the year and month, while 94% have a complete date. In the case of seven sub-datasets, exact dates can be retrieved upon communication with the data contributors.Major taxa and level of measurement: Ephemeroptera, Plecoptera, Trichoptera and Odonata, standardized at the genus taxonomic level. We provide species names for 7,727,980 (93%) records without further taxonomic verification. Software format: The entire tab-separated value (.csv) database can be downloaded and visualized at https://glowa bio.org/proje ct/epto_datab ase/. Fifty individual datasets are also available at https://fred.igb-berlin. de, while six datasets have restricted access. For the latter, we share metadata and the contact details of the authors

    Diversity patterns in marine and freshwater environments:the role of environmental and spatial factors across multiple scales

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    Abstract Recognition of the importance of a regional perspective for understanding the structure and dynamics of local assemblages has stimulated the emergence of the field of macroecology. Most attention has been directed to terrestrial ecosystems, while large-scale patterns in biodiversity of aquatic organisms have received less attention. In this thesis I examined patterns of aquatic diversity across several geographic areas and scales, in an effort to understand some of the environmental and spatial factors determining species diversity in aquatic environments. The main objectives of this thesis were: (i) to examine the latitudinal diversity patterns of marine crustaceans and molluscs and their relationship to large scale environmental gradients, (ii) to study macroinvertebrate species richness in headwater streams at two spatial extents, within and across drainage systems, and assess the relative importance of local, landscape and regional variables, and (iii) to study diversity patterns of macroorganisms vs microorganism, comparing distance decay patterns of stream diatoms, macroinvertebrates and bryophytes. Latitudinal diversity patterns of crustaceans and molluscs were clearly related to larval developmental mode. An increase in species richness towards high latitudes was found for species with direct development, whereas richness of species with planktotrophic development decreased poleward. Sea surface temperature was the most important environmental gradient related to species richness of both phyla and each developmental mode, but with different effects on each mode. Stream macroinvertebrate species richness at the bioregion extent was negatively related to water humic content. Another factor related to species richness at the bioregion extent was elevation range, a variable linked to stream topographic heterogeneity. Local environmental variables explained most of the variation in species richness at the drainage system extent, however high among-region variability was evident. Patterns between macro- and microorganism may not be fundamentally different, but the level of environmental control varied, being strongest for diatoms, while some groups of benthic macroinvertebrates exhibited relatively strong dispersal limitation. The relative importance of niche vs. dispersal processes is not simply a function of organism size but other traits (e.g. life-history type, dispersal capacity) may obscure this relationship

    Watersheds and Trees Fall Together: An Analysis of Intact Forested Watersheds in Southern Patagonia (41–56° S)

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    While intact forests have intrinsic value in terms of conserving biodiversity, they are also important for associated ecosystem services of soil and water conservation, in addition to the biodiversity, function and geomorphology of stream and river ecosystems. In this latter context, the perspective of watershed is more relevant than forest patch, however we are unaware of any landscape assessments of intact forested watersheds (IFWs). We mapped the coverage of forested watersheds with limited intervention for southern Patagonia (Chile, Argentina) using existing forest stand mapping and high resolution stream/watershed delineation (patch size ~ 0.4 km2). Validation and adjusted IFW boundaries was performed using high resolution satellite imagery for three major inland basins representing the north-south range of the study area. For both scales we evaluated size distribution, conservation status, forest type (deciduous vs. evergreen temperate forest) and bio-climatic zones (precipitation range 500 to >6000 mm/year). For the coarse regional analysis potential IFWs covered over 40% of land surface, and included nearly 60% of all forest cover. These figures were significantly reduced following basin scale validation to 6–21% for IFWs and 5–14% of forest contribution to IFW. IFWs identified in the regional analysis were lower elevation (0–100 m) due to abundant coastal drainages, whereas the basin analyses were higher elevation headwaters systems (1000+ m), the largest over 80 km2. Total IFW cover was estimated between 50,000–132,000 km2, the range a reflection of disparate results across these two scales, further highlighting the need for comprehensive revision and field validation. At the same time the difference in areas, defined mostly by minor levels of intervention, indicate the vast potential for management or restoration. Taken together they represent a nationally and globally significant contribution to of intact temperate forests and IFWs. Interactions between forest and stream ecosystems, and their implications for IFW conservation, are discussed in these contexts, based on examples from the region. Finally we used Getis-Ord Gi* statistics to identify hot and cold spots for different attributes, providing an example of a combined index for prioritizing IFW conservation

    El defensor del pueblo

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    Tesis (Licenciado en Ciencias Jurídicas)El Defensor del Pueblo es una institución antigua, que ha tenido figuras similares en los diferentes pueblos desde muy temprano en la historia de la humanidad, pero fue en Suecia en el año 1809 donde se institucionalizó como un órgano constitucional, en esa época la Institución cumplía la función más propia de un juez representante del Rey. Sin embargo desde el siglo XIX la Institución se ha desarrollado en diferentes países del mundo como una respuesta del intervencionismo estatal, que va invadiendo diferentes aspectos de la vida de las personas hasta el punto de entrar en conflicto con sus derechos. La Administración Pública ha evolucionado rápidamente, se ha vuelto más compleja, más grande, las oportunidades de confrontación de la ciudadanía y la Administración son mayores, por lo que se hacía necesario contar con algún mecanismo ágil, que por medio de procedimientos flexibles, rápidos y poco onerosos pudieran atender las quejas de la ciudadanía. Esta figura se define en la mayoría de las legislaciones como un Defensor de los derechos de las personas, cuya misión es la de proteger a la sociedad de las arbitrariedades y abusos de la Administración del Estado, pero llevando esta defensa desde una perspectiva no judiciaL Con su incorporación a las legislaciones Latinoamericanas, se le otorgaron atribuciones más precisas para la defensa y promoción de los Derechos Humanos, como respuesta a la necesidad de buscar mecanismos que asistieran en el retomo a la democracia y evitar las posibilidades de volver a los antiguos regímenes dictatoriales; hasta llegar su preocupación a la defensa de los intereses difusos, es decir, a aquellos que nos atañen a todos pero nadie defiende, como el medio ambiente, ordenación de transporte etc. La experiencia de otros países nos señalan que la institución, del Defensor del Pueblo, ha sido establecida para la fiscalización de diversas actividades, incluyendo las privadas siendo considerada como una Institución de solución de conflictos menos engorrosa, más económica, rápida y menos dramática que la Solución en el ámbito judicial. En Chile, se ha intentado incorporar la Institución en nuestro ordenamiento jurídico en varias oportunidades a través de los diferentes proyectos presentados por los Gobiernos de la Concertación, sin tener éxito alguno por el momento. El último proyecto de ley fue presentado en el año 2000 por el Gobierno del Presidente Lagos, el que por el instante no ha sido visto por la comisión constitucional del Congreso. En el mes de Mayo del año 2001, el Presidente Lagos frmó un decreto con el cual se creó el Consejo de Defensa del Ciudadano, esta institución comenzó a regir en Agosto del presente año, o sea recientemente. Esta Institución que por el momento ha sido creada en espera del Defensor del Pueblo, tiene una naturaleza completamente diferente a la del Defensor y esperamos que no se cree una confusión por parte de los ciudadanos y legisladores entre las diferentes instituciones

    Data from: Habitat connectivity and in-stream vegetation control temporal variability of benthic invertebrate communities

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    One of the key challenges to understanding patterns of β diversity is to disentangle deterministic patterns from stochastic ones. Stochastic processes may mask the influence of deterministic factors on community dynamics, hindering identification of the mechanisms causing variation in community composition. We studied temporal β diversity (among-year dissimilarity) of macroinvertebrate communities in near-pristine boreal streams across 14 years. To assess whether the observed β diversity deviates from that expected by chance, and to identify processes (deterministic vs. stochastic) through which different explanatory factors affect community variability, we used a null model approach. We observed that at the majority of sites temporal β diversity was low indicating high community stability. When stochastic variation was unaccounted for, connectivity was the only variable explaining temporal β diversity, with weakly connected sites exhibiting higher community variability through time. After accounting for stochastic effects, connectivity lost importance, suggesting that it was related to temporal β diversity via random colonization processes. Instead, β diversity was best explained by in-stream vegetation, community variability decreasing with increasing bryophyte cover. These results highlight the potential of stochastic factors to dampen the influence of deterministic processes, affecting our ability to understand and predict changes in biological communities through time
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