49 research outputs found

    Fabp7 Maps to a Quantitative Trait Locus for a Schizophrenia Endophenotype

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    Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain), a gene with functional links to the N-methyl-D-aspartic acid (NMDA) receptor and expression in astrocytes. Fabp7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL's proposed effects. A quantitative complementation test supported Fabp7 as a potential PPI-QTL gene, particularly in male mice. Disruption of Fabp7 attenuated neurogenesis in vivo. Human FABP7 showed altered expression in schizophrenic brains and genetic association with schizophrenia, which were both evident in males when samples were divided by sex. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of schizophrenia pathology and the PPI endophenotype, with larger or overt effects in males. We also discuss the results from the perspective of fetal programming

    精神疾患におけるマイクログリア由来ニューレグリン発現

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    Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD. Intriguingly, microglial NRG expression significantly increased in BTBR and socially-isolated mice, while maternal immune activation (MIA) mice exhibited identical NRG expression to controls. Furthermore, we observed a positive correlation between NRG expression in microglia and peripheral blood mononuclear cells (PBMCs) in mice, suggesting that NRG expression in human PBMCs may mirror microglia-derived NRG expression in the human brain. To translate these findings for application in clinical psychiatry, we measured levels of NRG1 splice-variant expression in clinically available PBMCs of patients with ASD. Levels of NRG1 type III expression in PBMCs were positively correlated with impairments in social interaction in children with ASD (as assessed using the Autistic Diagnostic Interview-Revised test: ADI-R). These findings suggest that immune cell-derived NRGs may be implicated in the pathobiology of psychiatric disorders such as ASD.博士(医学)・乙第1404号・平成29年6月28日Copyright © 2017 Elsevier Inc. All rights reserved

    Real-time observation of X-ray-induced intramolecular and interatomic electronic decay in CH2I2

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    The increasing availability of X-ray free-electron lasers (XFELs) has catalyzed the development of single-object structural determination and of structural dynamics tracking in realtime. Disentangling the molecular-level reactions triggered by the interaction with an XFEL pulse is a fundamental step towards developing such applications. Here we report real-time observations of XFEL-induced electronic decay via short-lived transient electronic states in the diiodomethane molecule, using a femtosecond near-infrared probe laser. We determine the lifetimes of the transient states populated during the XFEL-induced Auger cascades and find that multiply charged iodine ions are issued from short-lived (similar to 20 fs) transient states, whereas the singly charged ones originate from significantly longer-lived states (similar to 100 fs). We identify the mechanisms behind these different time scales: contrary to the short-lived transient states which relax by molecular Auger decay, the long-lived ones decay by an interatomic Coulombic decay between two iodine atoms, during the molecular fragmentation

    Development and improvement of Bragg coherent diffraction imaging for expanding observable particle-size range

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    SPring-8のコヒーレントX線とBL22XUビームラインのBraggコヒーレント回折イメージング (Bragg-CDI) 装置を用いて、Pd微結晶とBaTiO3微結晶の外形、サイズ、内部歪の可視化を行なった。真空槽の導入やShrink-wrapの適用により、観測可能粒子サイズをこれまでの100~300 nmから40~500 nmへと大幅に拡張することに成功した。この成果を国際結晶学連合International Union of CrystallographyのカンファレンスであるTwenty-Fifth Congress and General Assembly of the International Union of Crystallographyにて発表するものである。Twenty-Fifth Congress and General Assembly of the International Union of Crystallograph

    Mesoscopic hierarchic polarization structure in relaxor ferroelectrics Pb[(Mg1/3Nb2/3)1-xTix]O3

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    Mesoscopic polarization structures such as polar nanoregions and polarization domain walls are the key factors that connecting microscopic fundamental polarization structures with macroscopic practical dielectric properties. Snapshot observation of domain in the relaxor-ferroelectrics PMN-x%PT just vicinity of morphotropic phase boundary region was performed by use of 7 ps single shot soft X-ray laser pulse. A self-assembled evolution of oblique polarization domain was observed in PMN-27.8%PT under the sample temperature decreased with thermal equilibrium condition. Based on energetic discussion, anti-phase shift of domain wall pairs keeping with flat boundaries was proposed for the dielectric response. A sharp enhancement in dielectric response at the vicinity of morphotropic phase boundary region reported previously was recognized as an evidence for hierarchic nature of the present oblique polarization domain wall
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