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

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

Anti-Metastatic Effects on Melanoma via Intravenous Administration of Anti-NF-κB siRNA Complexed with Functional Peptide-Modified Nano-Micelles

Controlling metastasis is an important strategy in cancer treatment. Nanotechnology and nucleic acids with novel modalities are promising regulators of cancer metastasis. We aimed to develop a small interfering RNA (siRNA) systemic delivery and anti-metastasis system using nanotechnology. We previously reported that polyethylene glycol-polycaprolactone (PEG-PCL) and functional peptide CH2R4H2C nano-micelle (MPEG-PCL-CH2R4H2C) has high siRNA silencing effects, indicated by increased drug accumulation in tumor-bearing mice, and has an anti-tumor effect on solid tumors upon systemic injection. In this study, we aimed to apply our micelles to inhibit metastasis and evaluated the inhibitory effect of anti-RelA siRNA (siRelA), which is a subunit of NF-κB conjugated with MPEG-PCL-CH2R4H2C, via systemic administration. We report that siRelA/MPEG-PCL-CH2R4H2C had a high cellular uptake and suppressed the migration/invasion of cells in B16F10 cells without toxicity. In addition, in a lung metastasis mouse model using intravenous administration of B16F10 cells treated with siRelA/MPEG-PCL-CH2R4H2C, the number of lung nodules in lung tissue significantly decreased compared to naked siRelA and siControl/MPEG-PCL-CH2R4H2C micelle treatments. Hence, we show that RelA expression can reduce cancer metastasis, and MPEG-PCL-CH2R4H2C is an effective siRNA carrier for anti-metastasis cancer therapies

Quantification of speech and synchrony in the conversation of adults with autism spectrum disorder.

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by impairments in social reciprocity and communication together with restricted interest and stereotyped behaviors. The Autism Diagnostic Observation Schedule (ADOS) is considered a 'gold standard' instrument for diagnosis of ASD and mainly depends on subjective assessments made by trained clinicians. To develop a quantitative and objective surrogate marker for ASD symptoms, we investigated speech features including F0, speech rate, speaking time, and turn-taking gaps, extracted from footage recorded during a semi-structured socially interactive situation from ADOS. We calculated not only the statistic values in a whole session of the ADOS activity but also conducted a block analysis, computing the statistical values of the prosodic features in each 8s sliding window. The block analysis identified whether participants changed volume or pitch according to the flow of the conversation. We also measured the synchrony between the participant and the ADOS administrator. Participants with high-functioning ASD showed significantly longer turn-taking gaps and a greater proportion of pause time, less variability and less synchronous changes in blockwise mean of intensity compared with those with typical development (TD) (p<0.05 corrected). In addition, the ASD group had significantly wider distribution than the TD group in the within-participant variability of blockwise mean of log F0 (p<0.05 corrected). The clinical diagnosis could be discriminated using the speech features with 89% accuracy. The features of turn-taking and pausing were significantly correlated with deficits of ASD in reciprocity (p<0.05 corrected). Additionally, regression analysis provided 1.35 of mean absolute error in the prediction of deficits in reciprocity, to which the synchrony of intensity especially contributed. The findings suggest that considering variance of speech features, interaction and synchrony with conversation partner are critical to characterize atypical features in the conversation of people with ASD

労働法 (特集: 2007年 学界回顧)

金沢大学人間社会研究域法学系出版者照会後に全文公

労働法 (特集: 2006年 学界回顧)

金沢大学人間社会研究域法学系出版者照会後に全文公