Acute inhibition of AMPA receptors by perampanel reduces amyloid β-protein levels by suppressing β-cleavage of APP in Alzheimer's disease models

Hippocampal hyperexcitability is a promising therapeutic target to prevent Aβ deposition in AD since enhanced neuronal activity promotes presynaptic Aβ production and release. This article highlights the potential application of perampanel (PER), an AMPA receptor (AMPAR) antagonist approved for partial seizures, as a therapeutic agent for AD. Using transgenic AD mice combined with in vivo brain microdialysis and primary neurons under oligomeric Aβ-evoked neuronal hyperexcitability, the acute effects of PER on Aβ metabolism were investigated. A single oral administration of PER rapidly decreased ISF Aβ40 and Aβ42 levels in the hippocampus of J20, APP transgenic mice, without affecting the Aβ40 /Aβ42 ratio; 5 mg/kg PER resulted in declines of 20% and 31%, respectively. Moreover, PER-treated J20 manifested a marked decrease in hippocampal APP βCTF levels with increased FL-APP levels. Consistently, acute treatment of PER reduced sAPPβ levels, a direct byproduct of β-cleavage of APP, released to the medium in primary neuronal cultures under oligomeric Aβ-induced neuronal hyperexcitability. To further evaluate the effect of PER on ISF Aβ clearance, a γ-secretase inhibitor was administered to J20 1 h after PER treatment. PER did not influence the elimination of ISF Aβ, indicating that the acute effect of PER is predominantly on Aβ production. In conclusion, acute treatment of PER reduces Aβ production by suppressing β-cleavage of amyloid-β precursor protein effectively, indicating a potential effect of PER against Aβ pathology in AD

Proteome-Wide Prediction of Novel DNA/RNA-Binding Proteins Using Amino Acid Composition and Periodicity in the Hyperthermophilic Archaeon Pyrococcus furiosus

Proteins play a critical role in complex biological systems, yet about half of the proteins in publicly available databases are annotated as functionally unknown. Proteome-wide functional classification using bioinformatics approaches thus is becoming an important method for revealing unknown protein functions. Using the hyperthermophilic archaeon Pyrococcus furiosus as a model species, we used the support vector machine (SVM) method to discriminate DNA/RNA-binding proteins from proteins with other functions, using amino acid composition and periodicities as feature vectors. We defined this value as the composition score (CO) and periodicity score (PD). The P. furiosus proteins were classified into three classes (I–III) on the basis of the two-dimensional correlation analysis of CO score and PD score. As a result, approximately 87% of the functionally known proteins categorized as class I proteins (CO score + PD score > 0.6) were found to be DNA/RNA-binding proteins. Applying the two-dimensional correlation analysis to the 994 hypothetical proteins in P. furiosus, a total of 151 proteins were predicted to be novel DNA/RNA-binding protein candidates. DNA/RNA-binding activities of randomly chosen hypothetical proteins were experimentally verified. Six out of seven candidate proteins in class I possessed DNA/RNA-binding activities, supporting the efficacy of our method

Consideration of Supportive Policy to Improve Health Literacy of Working Women

【目的】 高齢社会が進み生産年齢人口が減少する中、女性が結婚や出産などライフステージが変わっても安心して働き続けることができる環境を実現する必要がある。そのためには、国や自治体、企業が働く女性の健康課題の解決に向けた施策を進めることが求められている。しかしながら、先行研究においては女性特有の健康課題の解決に向けて女性のヘルスリテラシーを向上させることが重要であることが明らかにされているものの、有効な支援施策は必ずしも示されていない。本研究では、社会経済上の諸課題に結びついている女性特有の健康課題をあらためて整理するとともに、ヘルスリテラシー向上のための具体的な支援策を検討する。 【方法】 まず、筆者らが参画した神奈川県立保健福祉大学イノベーション政策研究センター「働く女性の健康プロジェクト」における働く女性を対象とした産学医連携プロジェクトにおけるデータ分析の結果から、本研究における基礎的な知見を整理する。そのうえで、それらの知見に立脚しつつより具体的な支援施策の在り方を検討するべく、ステークホルダーに対するインタビュー調査を実施し、神奈川県がとりうる政策的支援の在り方を提言としてとりまとめた。 【結果】 データ分析の結果からは、女性が自分自身の健康状態を知り行動変容を起こすための効果的なアプローチとして経膣超音波検査の存在が明らかとなった。また、インタビュー調査からは、医療職のなかでも助産師が幅広い年代の女性の健康支援に寄与できることが明らかになった。 【結論】 働く女性における女性特有の健康課題に対するヘルスリテラシーを向上させるための効果的なアプローチとして、①女性の健康に関する啓発資材の活用と経腟超音波検査費用の助成、②顧問助産師派遣の助成と活用の２つを提言する。産官学民が連携し、すべての女性が自分に適した健康づくりに向けて具体的な行動変容を起こし、自分らしくライフプランやキャリアなどの選択ができるような支援が必要であると考えられる。departmental bulletin pape

Recent Results from LHD Experiment with Emphasis on Relation to Theory from Experimentalist’s View

he Large Helical Device (LHD) has been extending an operational regime of net-current free plasmas towardsthe fusion relevant condition with taking advantage of a net current-free heliotron concept and employing a superconducting coil system. Heating capability has exceeded 10 MW and the central ion and electron temperatureshave reached 7 and 10 keV, respectively. The maximum value of β and pulse length have been extended to 3.2% and 150 s, respectively. Many encouraging physical findings have been obtained. Topics from recent experiments, which should be emphasized from the aspect of theoretical approaches, are reviewed. Those are (1) Prominent features in the inward shifted configuration, i.e., mitigation of an ideal interchange mode in the configuration with magnetic hill, and confinement improvement due to suppression of both anomalous and neoclassical transport, (2) Demonstration ofbifurcation of radial electric field and associated formation of an internal transport barrier, and (3) Dynamics of magnetic islands and clarification of the role of separatrix

Periodic Psychosis in Adolescence

Twelve dogs were divided into four groups: Group I-simple interruption of the portal vein for 40 minute

On Schizophrenics with Impotence as Chief Complaint

Three strains of spirochetes, Borrelia duttonii, Treponema pallidum, and Treponema phagedenis, were observed under a scanning electron microscope, and their spiral directiions were described.The right-handed turn in B. duttonii, the left-handed turn in. pallidum were evidenced.The appearance of both types of spiral direction in T. phagedenis was recognized and discussed