481 research outputs found

    Temperament & Character account for brain functional connectivity at rest: A diathesis-stress model of functional dysregulation in psychosis

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    The human brain’s resting-state functional connectivity (rsFC) provides stable trait-like measures of differences in the perceptual, cognitive, emotional, and social functioning of individuals. The rsFC of the prefrontal cortex is hypothesized to mediate a person’s rational self-government, as is also measured by personality, so we tested whether its connectivity networks account for vulnerability to psychosis and related personality configurations. Young adults were recruited as outpatients or controls from the same communities around psychiatric clinics. Healthy controls (n = 30) and clinically stable outpatients with bipolar disorder (n = 35) or schizophrenia (n = 27) were diagnosed by structured interviews, and then were assessed with standardized protocols of the Human Connectome Project. Data-driven clustering identified five groups of patients with distinct patterns of rsFC regardless of diagnosis. These groups were distinguished by rsFC networks that regulate specific biopsychosocial aspects of psychosis: sensory hypersensitivity, negative emotional balance, impaired attentional control, avolition, and social mistrust. The rsFc group differences were validated by independent measures of white matter microstructure, personality, and clinical features not used to identify the subjects. We confirmed that each connectivity group was organized by differential collaborative interactions among six prefrontal and eight other automatically-coactivated networks. The temperament and character traits of the members of these groups strongly accounted for the differences in rsFC between groups, indicating that configurations of rsFC are internal representations of personality organization. These representations involve weakly self-regulated emotional drives of fear, irrational desire, and mistrust, which predispose to psychopathology. However, stable outpatients with different diagnoses (bipolar or schizophrenic psychoses) were highly similar in rsFC and personality. This supports a diathesis-stress model in which different complex adaptive systems regulate predisposition (which is similar in stable outpatients despite diagnosis) and stress-induced clinical dysfunction (which differs by diagnosis)

    Emerging Infectious Disease leads to Rapid Population Decline of Common British Birds

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    Emerging infectious diseases are increasingly cited as threats to wildlife, livestock and humans alike. They can threaten geographically isolated or critically endangered wildlife populations; however, relatively few studies have clearly demonstrated the extent to which emerging diseases can impact populations of common wildlife species. Here, we report the impact of an emerging protozoal disease on British populations of greenfinch Carduelis chloris and chaffinch Fringilla coelebs, two of the most common birds in Britain. Morphological and molecular analyses showed this to be due to Trichomonas gallinae. Trichomonosis emerged as a novel fatal disease of finches in Britain in 2005 and rapidly became epidemic within greenfinch, and to a lesser extent chaffinch, populations in 2006. By 2007, breeding populations of greenfinches and chaffinches in the geographic region of highest disease incidence had decreased by 35% and 21% respectively, representing mortality in excess of half a million birds. In contrast, declines were less pronounced or absent in these species in regions where the disease was found in intermediate or low incidence. Also, populations of dunnock Prunella modularis, which similarly feeds in gardens, but in which T. gallinae was rarely recorded, did not decline. This is the first trichomonosis epidemic reported in the scientific literature to negatively impact populations of free-ranging non-columbiform species, and such levels of mortality and decline due to an emerging infectious disease are unprecedented in British wild bird populations. This disease emergence event demonstrates the potential for a protozoan parasite to jump avian host taxonomic groups with dramatic effect over a short time period

    Variability of Individual Platelet Reactivity Over Time in Patients Treated With Clopidogrel Insights From the ELEVATE–TIMI 56 Trial

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    AbstractBackgroundThe degree of antiplatelet response to clopidogrel has been associated with clinical outcomes. Studies have investigated whether adjustment of antiplatelet therapies based on a single platelet function test is beneficial.ObjectivesThe aim of the study was to test the stability of platelet reactivity measurements over time among patients treated with standard and double doses of clopidogrel.MethodsThe ELEVATE–TIMI 56 (Escalating Clopidogrel by Involving a Genetic Strategy–Thrombolysis In Myocardial Infarction 56) investigators genotyped 333 patients with coronary artery disease and randomized them to various clopidogrel regimens. Patients with at least 2 platelet function results on the same maintenance dose of clopidogrel (75 mg or 150 mg) were analyzed. Platelet aggregation was measured using P2Y12 reaction units (PRU).ResultsIn total, the mean platelet reactivity and the total number of nonresponders (PRU ≥230) with clopidogrel did not change between 2 periods for the 75-mg (22.4% vs. 21.9%; p = 0.86) and 150-mg doses of clopidogrel (11.5% vs. 11.5%; p = 1.00). In contrast, when evaluating each patient individually, 15.7% of patients taking clopidogrel 75 mg and 11.4% of patients taking 150 mg had a change in their responder status when tested at 2 different time points (p < 0.001). Despite being treated with the same dose of clopidogrel, >40% of patients had a change in PRU >40 on serial sampling, which approximates the average PRU difference caused by increasing the clopidogrel dose from 75 mg to 150 mg.ConclusionsMeasurements of platelet reactivity vary over time in a significant proportion of patients. Thus, treatment adjustment according to platelet function testing at a single time point might not be sufficient for guiding antiplatelet therapy in clinical or research settings. (Escalating Clopidogrel by Involving a Genetic Strategy–Thrombolysis In Myocardial Infarction 56 [ELEVATE–TIMI 56]; NCT01235351

    Why Reform Fails : The ‘Politics of Policies’ in Costa Rican Telecommunications Liberalization

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    As the \u27Washington Consensus\u27 reforms are losing momentum in Latin America, the Inter- American Development Bank (IDB) is calling for shifting the focus from the content of policy choices to the political process of their implementation. As this paper studies the paradigmatic case of telecommunications reform in Costa Rica it underscores the importance of these \u27politics of policies\u27. The analysis finds, however, that the failure of repeated liberalization initiatives was not only due to policy-makers\u27 errors in steering the project through \u27the messy world of politics\u27 (IDB); instead, as liberalization remained unpopular, policy content indeed mattered, and only the interaction of both explains the outcome. Particular attention is drawn to the political feed-back effects, as the failed reform, precisely because it had been backed by bi-partisan support, became a catalyst for the disintegration of the country\u27s long-standing two-party system.In dem Maße, in dem die mit dem „Washington Consensus“ verbundenen Reformen in Lateinamerika ins Stocken geraten sind, plädiert die Inter-American Development Bank (IDB) für eine stärkere Berücksichtigung nicht nur der Politikinhalte (policies), sondern auch des politischen Prozesses von deren Umsetzung (politics). Die vorliegende Untersuchung zum paradigmatischen Fall der Reform des Telekommunikationssektors in Costa Rica unterstreicht die Bedeutung dieser „politics of policies“. Sie zeigt allerdings auch, dass Ursache für das Scheiten wiederholter Liberalisierungsinitiativen nicht nur Fehler der Politiker sind, das Vorhaben durch „die unordentliche Welt der politics“ (IDB) zu steuern. Die breite gesellschaftliche Opposition gegen den Liberalisierungskurs bleibt. Nur die Interaktion von beiden, politics und policies, erklärt Verlauf und Ergebnis der Reform. Besonderes Augenmerk widmet die Studie den politischen Rückwirkungen der gescheiterten Reform: Sie wurde, just weil sie von beiden etablierten Parteien unterstützt wurde, zum Katalysator für den Zerfall des seit Jahrzehnten etablierten Zweiparteiensystems des Landes

    Three genetic-environmental networks for human personality

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    Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized character profiles (i.e., intentional self-control of emotional conflicts and goals), and (3) creative character profiles (i.e., self-aware appraisal of values and theories), respectively. However, little is known about how these temperament and character components of personality are jointly organized and develop in an integrated manner. In three large independent genome-wide association studies from Finland, Germany, and Korea, we used a data-driven machine learning method to uncover joint phenotypic networks of temperament and character and also the genetic networks with which they are associated. We found three clusters of similar numbers of people with distinct combinations of temperament and character profiles. Their associated genetic and environmental networks were largely disjoint, and differentially related to distinct forms of learning and memory. Of the 972 genes that mapped to the three phenotypic networks, 72% were unique to a single network. The findings in the Finnish discovery sample were blindly and independently replicated in samples of Germans and Koreans. We conclude that temperament and character are integrated within three disjoint networks that regulate healthy longevity and dissociable systems of learning and memory by nearly disjoint sets of genetic and environmental influences.Peer reviewe

    Combining specificity determining and conserved residues improves functional site prediction

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    <p>Abstract</p> <p>Background</p> <p>Predicting the location of functionally important sites from protein sequence and/or structure is a long-standing problem in computational biology. Most current approaches make use of sequence conservation, assuming that amino acid residues conserved within a protein family are most likely to be functionally important. Most often these approaches do not consider many residues that act to define specific sub-functions within a family, or they make no distinction between residues important for function and those more relevant for maintaining structure (e.g. in the hydrophobic core). Many protein families bind and/or act on a variety of ligands, meaning that conserved residues often only bind a common ligand sub-structure or perform general catalytic activities.</p> <p>Results</p> <p>Here we present a novel method for functional site prediction based on identification of conserved positions, as well as those responsible for determining ligand specificity. We define Specificity-Determining Positions (SDPs), as those occupied by conserved residues within sub-groups of proteins in a family having a common specificity, but differ between groups, and are thus likely to account for specific recognition events. We benchmark the approach on enzyme families of known 3D structure with bound substrates, and find that in nearly all families residues predicted by SDPsite are in contact with the bound substrate, and that the addition of SDPs significantly improves functional site prediction accuracy. We apply SDPsite to various families of proteins containing known three-dimensional structures, but lacking clear functional annotations, and discusse several illustrative examples.</p> <p>Conclusion</p> <p>The results suggest a better means to predict functional details for the thousands of protein structures determined prior to a clear understanding of molecular function.</p

    A "masculinização" da produção de leite.

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    O fortalecimento de organizações sociais que possibilitaram fazer da produção de leite uma atividade destinada ao mercado provocou profundas mudanças na divisão sexual do trabalho. A análise sociológica das trocas intradomiciliares nos estabelecimentos rurais familiares mostra que tradições culturais, diferenças de poder entre os gêneros e contextos sociais que ampliam diferenças de acesso aos mercados entre homens e mulheres são as bases sociais e culturais de uma hierarquia estruturada segundo sexo e geração, no qual as mulheres, especialmente as mais jovens, ocupam posições de grande desvantagem. Com o fortalecimento de cooperativas, a produção de leite passou a ocupar um lugar de destaque no provimento de recursos da família, mas o domínio da atividade foi deslocado para o controle masculino. Esse foi um dos resultados não esperados da forma como as organizações conduziram o processo de modernização da produção e de reestruturação dos mercados, que reforçaram ainda mais o domínio masculino sobre a produção familiar e um aumento das desigualdades de gênero no acesso aos recursos
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