Schizophrenia (SCZ) is known to be a heritable disorder; however, its multifactorial nature has significantly hampered attempts to establish its pathogenesis. Therefore, in this study, we performed genome-wide copy-number variation (CNV) analysis of 2940 patients with SCZ and 2402 control subjects and identified a statistically significant association between SCZ and exonic CNVs in the
ARHGAP10
gene.
ARHGAP10
encodes a member of the RhoGAP superfamily of proteins that is involved in small GTPase signaling. This signaling pathway is one of the SCZ-associated pathways and may contribute to neural development and function. However, the
ARHGAP10
gene is often confused with
ARHGAP21
, thus, the significance of
ARHGAP10
in the molecular pathology of SCZ, including the expression profile of the ARHGAP10 protein, remains poorly understood. To address this issue, we focused on one patient identified to have both an exonic deletion and a missense variant (p.S490P) in
ARHGAP10
. The missense variant was found to be located in the RhoGAP domain and was determined to be relevant to the association between
ARHGAP10
and the active form of RhoA. We evaluated ARHGAP10 protein expression in the brains of reporter mice and generated a mouse model to mimic the patient case. The model exhibited abnormal emotional behaviors, along with reduced spine density in the medial prefrontal cortex (mPFC). In addition, primary cultured neurons prepared from the mouse model brain exhibited immature neurites in vitro. Furthermore, we established induced pluripotent stem cells (iPSCs) from this patient, and differentiated them into tyrosine hydroxylase (TH)-positive neurons in order to analyze their morphological phenotypes. TH-positive neurons differentiated from the patient-derived iPSCs exhibited severe defects in both neurite length and branch number; these defects were restored by the addition of the Rho-kinase inhibitor, Y-27632. Collectively, our findings suggest that rare
ARHGAP10
variants may be genetically and biologically associated with SCZ and indicate that Rho signaling represents a promising drug discovery target for SCZ treatment.
PACS 71.55. Gs, 78.55.Et Cu-doped p-type CdS (CdS : Cu) and non-doped n-type CdS films were fabricated by the vacuum deposition process. Photoluminescence (PL) spectra of CdS : Cu and CdS films were measured between 8.7 K and room temperature. Free excitonic emission (FX), neutral acceptor-bound excitonic emission (I 1 ), and donor-acceptor pair emission (DAP) were observed from CdS:Cu films. These results suggest that crystallinity of CdS films was improved by Cu doping and that Cu atoms in CdS behave as acceptors and form shallow levels (about 80 meV above the valence band edge) in CdS.
PACS 71.35.-y, 78.55.Et Photoluminescence (PL) was circumstantially measured for ZnO single crystals with polar and non-polar faces. PL spectra of ZnO single crystals depended on the sector and polarity of ZnO single crystals. Emissions due to excitons from c-plane substrates sliced from the +c sector were strong, and FWHMs of the emissions were smaller than those from substrates sliced from the -c sector. An emission due to neutraldonor-bound exicitons (D 0 X) at 3.361 eV was dominantly observed on all surfaces of ZnO single crystals, and an emission due to ionized-donor-bound excitons (D + X) around 3.366 eV was observed on the O-face but not on the Zn-face at 4.2 K. It is thought that surface state densities due to oxygen caused this difference in PL emission for polarity of ZnO.
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