436 research outputs found

    Exome sequences of multiplex, multigenerational families reveal schizophrenia risk loci with potential implications for neurocognitive performance

    Get PDF
    Schizophrenia is a serious mental illness, involving disruptions in thought and behavior, with a worldwide prevalence of about one percent. Although highly heritable, much of the genetic liability of schizophrenia is yet to be explained. We searched for susceptibility loci in multiplex, multigenerational families affected by schizophrenia, targeting protein-altering variation with in silico predicted functional effects. Exome sequencing was performed on 136 samples from eight European-American families, including 23 individuals diagnosed with schizophrenia or schizoaffective disorder. In total, 11,878 non-synonymous variants from 6,396 genes were tested for their association with schizophrenia spectrum disorders. Pathway enrichment analyses were conducted on gene-based test results, protein-protein interaction (PPI) networks, and epistatic effects. Using a significance threshold of FDR\u3c0.1, association was detected for rs10941112 (P=2.1×10−5; q-value=0.073) in AMACR, a gene involved in fatty acid metabolism and previously implicated in schizophrenia, with significant cis effects on gene expression (P=5.5×10−4), including brain tissue data from the Genotype-Tissue Expression project (minimum P=6.0×10−5). A second SNP, rs10378 located in TMEM176A, also shows risk effects in the exome data (P=2.8×10−5; q-value=0.073). Protein-protein interactions among our top gene-based association results (P\u3c0.05; n=359 genes) reveal significant enrichment of genes involved in NCAM-mediated neurite outgrowth (P=3.0×10−5), while exome-wide SNP-SNP interaction effects for rs10941112 and rs10378 indicate a potential role for kinase-mediated signaling involved in memory and learning. In conclusion, these association results implicate AMACR and TMEM176A in schizophrenia risk, whose effects may be modulated by genes involved in synaptic plasticity and neurocognitive performance

    Palladin Mutation Causes Familial Pancreatic Cancer and Suggests a New Cancer Mechanism

    Get PDF
    BACKGROUND: Pancreatic cancer is a deadly disease. Discovery of the mutated genes that cause the inherited form(s) of the disease may shed light on the mechanism(s) of oncogenesis. Previously we isolated a susceptibility locus for familial pancreatic cancer to chromosome location 4q32–34. In this study, our goal was to discover the identity of the familial pancreatic cancer gene on 4q32 and determine the function of that gene. METHODS AND FINDINGS: A customized microarray of the candidate chromosomal region affecting pancreatic cancer susceptibility revealed the greatest expression change in palladin (PALLD), a gene that encodes a component of the cytoskeleton that controls cell shape and motility. A mutation causing a proline (hydrophobic) to serine (hydrophilic) amino acid change (P239S) in a highly conserved region tracked with all affected family members and was absent in the non-affected members. The mutational change is not a known single nucleotide polymorphism. Palladin RNA, measured by quantitative RT-PCR, was overexpressed in the tissues from precancerous dysplasia and pancreatic adenocarcinoma in both familial and sporadic disease. Transfection of wild-type and P239S mutant palladin gene constructs into HeLa cells revealed a clear phenotypic effect: cells expressing P239S palladin exhibited cytoskeletal changes, abnormal actin bundle assembly, and an increased ability to migrate. CONCLUSIONS: These observations suggest that the presence of an abnormal palladin gene in familial pancreatic cancer and the overexpression of palladin protein in sporadic pancreatic cancer cause cytoskeletal changes in pancreatic cancer and may be responsible for or contribute to the tumor's strong invasive and migratory abilities

    Capillary Channel Flow (CCF) EU2-02 on the International Space Station (ISS): An Experimental Investigation of Passive Bubble Separations in an Open Capillary Channel

    Get PDF
    It would be signicantly easier to design fluid systems for spacecraft if the fluid phases behaved similarly to those on earth. In this research an open 15:8 degree wedge-sectioned channel is employed to separate bubbles from a two-phase flow in a microgravity environment. The bubbles appear to rise in the channel and coalesce with the free surface in much the same way as would bubbles in a terrestrial environment, only the combined effects of surface tension, wetting, and conduit geometry replace the role of buoyancy. The host liquid is drawn along the channel by a pump and noncondensible gas bubbles are injected into it near the channel vertex at the channel inlet. Control parameters include bubble volume, bubble frequency, liquid volumetric flow rate, and channel length. The asymmetrically confined bubbles are driven in the cross-flow direction by capillary forces until they at least become inscribed within the section or until they come in contact with the free surface, whereupon they usually coalesce and leave the flow. The merging of bubbles enhances, but does not guarantee, the latter. The experiments are performed aboard the International Space Station as a subset of the Capillary Channel Flow experiments. The flight hardware is commanded remotely and continuously from ground stations during the tests and an extensive array of experiments is conducted identifying numerous bubble flow regimes and regime transitions depending on the ratio and magnitude of the gas and liquid volumetric flow rates. The breadth of the publicly available experiments is conveyed herein primarily by narrative and by regime maps, where transitions are approximated by simple expressions immediately useful for the purposes of design and deeper analysis

    O processo de implantação do mapa inteligente virtual no território de abrangência no centro de saúde da família EFAPI, situado no município de Chapecó-SC

    Get PDF
    Introdução: A gestão em saúde, de forma participativa, pode ser realizada por meio da confecção de mapas para identificação das necessidades de saúde da comunidade. Neste contexto, o mapa inteligente virtual - (MIV) é uma estratégia criativa que possibilita planejar e compreender o território de forma mais eficiente. Objetivo: Reconhecer o território de abrangência do Centro de Saúde da Família (CSF) - EFAPI, através da confecção de um MIV. Metodologia: Este estudo trata-se de um relato de experiência da confecção de um MIV, realizado pelo grupo PET Interprofissionalidade. A confecção do MIV foi realizada no período de maio e junho de 2019. O grupo manteve contato as Agentes Comunitárias de Saúde (ACS), e a população, realizando reconhecimento do território. A coleta dos dados realizou-se no sistema eletrônico próprio da Secretaria Municipal de Saúde de Chapecó - WinSaúde e a confecção do mapa pela plataforma google maps, registrando em tempo real as informações que foram disponibilizadas pelas equipes do CSF. Resultados: As informações que constaram no MIV retrataram o perfil epidemiológico da comunidade como: número de pacientes com comorbidades crônicas (hipertensos, diabéticos e acamados), número de crianças menores de 2 anos, gestantes, áreas de vulnerabilidade social, focos de mosquito da dengue, locais como escolas e centros comunitários localizados no território. Considerações Finais: A produção do MIV proporcionou exercitar o trabalho efetivo em grupo através de estratégias de territorialização em saúde e obter uma visão holística e humanitária da comunidade.  Ao final da confecção do MIV os estudantes destacaram a disponibilidade e a qualidade do trabalho das ACS, auxiliando e organizando as micro áreas para potencializar a prevenção e promoção da saúde. Além de desenvolver estratégias de intervenção voltadas ao auxílio da população junto ao CSF e ainda poder oferecer maior atenção a população com às suas particularidades. Como existe variação nos dados das condições e necessidades de saúde, é importante que o MIV seja atualizado constantemente, assim possibilitará gerar relatórios de saúde ou levantamentos do comportamento populacional de saúde com dados mais precisos. Palavras-chave: Centro de Saúde. Gestão em Saúde. Agentes Comunitárias da Saúde
    corecore