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Recent schizophrenia (SCZ) studies have reported an increased burden of de novocopy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10−9, 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novoCNVs (e.g., MBD5deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novoCNVs and variable expressivity of CNVs.

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

The proliferative activity of 91 canine mast cell tumours was assessed on the basis of the Ki-67 positive index (Ki-67 PI) and mitotic index (MI) and, in 15 cases, also by the labelling index of bromodeoxyuridine (BrdU; an analogue of tritiated thymidine) incorporated in vivointo S-phase cells. BrdU and Ki-67 were detected immunohistochemically. The tumours were graded histologically (I, II or III). The BrdU labelling index (BrdU LI) tended to increase as the grade became higher. In terms of the mean values of Ki-67 PI, significant differences were found between histological tumour grades I and II (P<0·01) and between grades II and III (P<0·01). In terms of mean MI, grades I and II were found to differ significantly (P<0·05). With Spearman rank correlation coefficient and linear regression analysis, the BrdU LI and Ki-67 PI showed a highly significant correlation. This strong correlation indicated that Ki-67 was, like BrdU, a useful marker for proliferative potential in canine mast cell tumours; moreover, its use did not require the prior administration of any reagent to the live animal.

—The Nikko region, in northern Kanto, central Japan, which is a high seismicity region, is located near the volcanic front. Many seismic observations have been carried out around the Nikko region because the seismograms of the shallow earthquakes occurring in this region show an S-wave reflected phase (SxS)and an S-to-Pmode-converted and reflected phase (SxP)from a mid-crustal seismic velocity discontinuity. The depth of the mid-crustal reflector was estimated to be about 9–16 km. From the amplitude analyses of SxSand SxPphases, the material of the mid-crustal layer just beneath the reflector was expected to be a low rigidity layer, which was interpreted as partially molten rocks. No evidence has been shown for the internal properties of the material of the reflector. The Vp/Vsratio is a good measure to distinguish between the two candidates for seismic reflectors; i.e., partially molten rocks and rocks containing water. We investigate the Vp/Vsratio of the reflector using the spectrum analyses of the data observed by a seismic array. From spectrum analysis of the data, we indicate that the Vp/Vsratio of 2.5 is better than that of 1.8 to explain the observed data, which shows that the material beneath the reflector consists of partially molten rocks.

In the Kanto-Tokai district of central Japan, the configuration of the subducting Philippine Sea plate has been estimated using three-dimensional velocity inversions of the seismic wave velocity structure and the distribution of microearthquakes. However, it is difficult to show the configuration of the Philippine Sea plate from the distribution of microearthquakes beneath the western Kanto region, i.e. the Yamanashi and Nagano prefectures, because seismic activity is quite low there.