Cognitive clustering in schizophrenia patients, their first-degree relatives and healthy subjects is associated with anterior cingulate cortex volume

Cognitive impairments are a core feature in schizophrenia patients (SCZ) and are also observed in first-degree relatives (FR) of SCZ. However, substantial variability in the impairments exists within and among SCZ, FR and healthy controls (HC). A cluster-analytic approach can group individuals based on profiles of traits and create more homogeneous groupings than predefined categories. Here, we investigated differences in the Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery (six subscales) among SCZ, unaffected FR and HC. To identify three homogeneous and meaningful cognitive groups regardless of categorical diagnoses (SCZ, FR and HC), cognitive clustering was performed, and differences in the BACS subscales among the cognitive cluster groups were investigated. Finally, the effects of diagnosis and cognition on brain volumes were examined. As expected, there were significant differences in the five BACS subscales among the diagnostic groups. The cluster-analytic approach generated three meaningful subgroups: (i) neuropsychologically normal, (ii) intermediate impaired and (iii) widespread impaired. The cognitive subgroups were mainly affected by the clinical diagnosis, and significant differences in all BACS subscales among clusters were found. The effects of the diagnosis and cognitive clusters on brain volumes overlapped in the frontal, temporal and limbic regions. Frontal and temporal volumes were mainly affected by the diagnosis, whereas the anterior cingulate cortex (ACC) volumes were affected by the additive effects of diagnosis and cognition. Our findings demonstrate a cognitive continuum among SCZ, FR and HC and support the concept of cognitive impairment and the related ACC volumes as intermediate phenotypes in SCZ

White matter microstructural alterations across four major psychiatric disorders : mega-analysis study in 2937 individuals

Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophrenia; however, no similar cross-disorder study has been carried out to date. Here, we conducted mega-analyses comparing white matter microstructural differences between healthy comparison subjects (HCS; N = 1506) and patients with schizophrenia (N = 696), bipolar disorder (N = 211), autism spectrum disorder (N = 126), or major depressive disorder (N = 398; total N = 2937 from 12 sites). In comparison with HCS, we found that schizophrenia, bipolar disorder, and autism spectrum disorder share similar white matter microstructural differences in the body of the corpus callosum; schizophrenia and bipolar disorder featured comparable changes in the limbic system, such as the fornix and cingulum. By comparison, alterations in tracts connecting neocortical areas, such as the uncinate fasciculus, were observed only in schizophrenia. No significant difference was found in major depressive disorder. In a direct comparison between schizophrenia and bipolar disorder, there were no significant differences. Significant differences between schizophrenia/bipolar disorder and major depressive disorder were found in the limbic system, which were similar to the differences in schizophrenia and bipolar disorder relative to HCS. While schizophrenia and bipolar disorder may have similar pathological characteristics, the biological characteristics of major depressive disorder may be close to those of HCS. Our findings provide insights into nosology and encourage further investigations of shared and unique pathophysiology of psychiatric disorders

DNA markers linked to Pga1, an adzuki bean gene that confers resistance to Cadophora gregata race 1

Brown stem rot (BSR) caused by Cadophora gregata f. sp. adzukicola (syn. Phialophora gregata) is a serious soilborne disease of adzuki bean (Vigna angularis) in Japan. Cultivation of resistant cultivars is the most effective disease control method, therefore the selection of resistant lines is a priority for breeders. BSR-resistant adzuki bean lines have been screened in pathogen-infected fields. However, field selection using the pathogen and artificial inoculation methods is time-consuming and labor-intensive. In the present study, we used 105 F-3 lines derived from a cross between a BSR-resistant cultivar 'Syumari' and a susceptible cultivar 'Buchishoryukei-1' for BSR inoculation tests. Amplified fragment-length polymorphism (AFLP) analyses with 1024 primer sets revealed that six fragments were polymorphic between resistance and susceptible bulked groups. Five DNA markers (Pg77, Pg118, Pg138, Pg139 and Pg126) were developed from the nucleotide sequences of polymorphic AFLP markers and their flanking regions. Pg118, which was derived from E-ACT/M-ACT-118, was tightly linked to the resistance gene Pga1 and was converted into a codominant marker for its easier use in marker-assisted selection for adzuki bean BSR resistance. Finally, the applicability of the developed markers for BSR resistance was tested on 32 adzuki bean accessions or cultivars

Enhanced Optimization Scheme for Parallel PDE Solver of NSL

Authors have been developing a numerical simulation environment NSL [1], which automatically generates parallel PDE (partial differential equations) solver from high-level description of problem. Two of the notable features of NSL are boundary-fitted coordinate system and multi-block method. Physical domain is mapped onto a group of rectangular computational blocks, each of which is partitioned into one or more congruent sub-blocks. Each processor takes charge of a single sub-block. Static load balancing of such system can be modeled as a combinatorial optimization, which can be solved by branch-and-bound method [2][3]. However, in this model, the number of processors (n) is required to be greater than or equal to the number of blocks (m). This restriction can be a major obstacle to handle many blocks on a modestscale parallel computer. This paper presents an enhanced scheme that works regardless of the relationship between m and n, with additional performance improvement. Basic idea i..

Loss of the BRCA1-interacting helicase BRIP1 results in abnormal mammary acinar morphogenesis

BRIP1 is a DNA helicase that directly interacts with the C-terminal BRCT repeat of the breast cancer susceptibility protein BRCA1 and plays an important role in BRCA1-dependent DNA repair and DNA damage-induced checkpoint control. Recent studies implicate BRIP1 as a moderate/low-penetrance breast cancer susceptibility gene. However, the phenotypic effects of BRIP1 dysfunction and its role in breast cancer tumorigenesis remain unclear. In this study, we used the three-dimensional culture of human mammary epithelial cells as a model of mammary gland morphogenesis, to explore the function of BRIP1 in acinar morphogenesis of mammary epithelial cells. BRIP1 knockdown in non-malignant MCF-10A mammary epithelial cells by RNA interference induced neoplastic-like changes such as abnormal cell adhesion, increased cell proliferation, large and irregular-shaped acini, invasive growth, and defective lumen formation. BRIP1-knockdown cells showed dysregulation of multiple signaling pathways and tumor-associated genes including SATB1, a key transcriptional regulator that promotes tumor growth and metastasis of breast cancer. These results suggest that BRIP1, by regulating multiple tumor-associated genes and signaling pathways, plays important roles not only in the development of mammary glands but also in the neoplastic conversion of mammary epithelial cells.The 22nd Biennial Congress of the European Association for Cancer Researc

Effect of age at exposure on the incidence of thyroid lesions after γ-ray irradiation in mice

Purpose: Since the nuclear accident in Fukushima Daiichi nuclear power plants, long-term low dose rate radiation exposure is concerned about health effects including cancer. There is an increasing interest in the radiation exposure effects of children with particularly high radiation susceptibility. Currently, highest incidence of thyroid cancer by ultrasound thyroid screening has become a serious problem in Fukushima. However, it is not clear whether thyroid carcinogenesis is associated with radiation exposure. The purpose of this study is to clarify the thyroid cancer risk after exposure at childhood using experimental mouse model.Since the nuclear accident in Fukushima, long-term low dose rate radiation exposure is concerned about health effects including cancer. Specially radiation susceptible children have been worried. Currently, ultrasound thyroid screening has revealed increase of thyroid cancer. However, it is not clear whether the thyroid carcinogenesis is associated with radiation exposure. The purpose of this study is to clarify the thyroid cancer risk after exposure at childhood using experimental mouse model.Method: B6C3F1 male and female mice were irradiated at 1 or 7 weeks of age with 0, 0.2Gy ,2Gy or 4Gy γ-ray doses. All mice were sacrificed when they became terminal condition or died. The pathological specimens of all organs and tumors were archived electronically as digital data. We performed the pathological diagnosis of thyroid lesions using archived samples then calculated the risks of thyroid lesion after exposure to radiation, such as dose-response relationship and effect of age at exposure.Results and Conclusions: Histopathological examination of thyroid lesions revealed follicular cell hyperplasia, follicular or papillary adenoma or carcinoma. The incidence of follicular cell hyperplasia was highest than that of adenoma and carcinoma. In mice after irradiation at 1 week of age incidence of tumor (adenoma and carcinoma) shown an increasing tendency compared with mice after irradiated at 7 weeks of age. We will discuss the relation between the risks of each thyroid lesion and dose of radiation or age at exposure.ERR2018(44th European Radiation Research Congress