High molecular weight amyloid β1-42 oligomers induce neurotoxicity via plasma membrane damage.

Amyloid β-protein (Aβ) molecules tend to aggregate and subsequently form low MW (LMW) oligomers, high MW (HMW) aggregates such as protofibrils, and ultimately fibrils. These Aβ species can generally form amyloid plaques implicated in the neurodegeneration of Alzheimer disease (AD), but therapies designed to reduce plaque load have not demonstrated clinical efficacy. Recent evidence implicates amyloid oligomers in AD neuropathology, but the precise mechanisms are uncertain. We examined the mechanisms of neuronal dysfunction from HMW-Aβ1-42 exposure by measuring membrane integrity, reactive oxygen species (ROS) generation, membrane lipid peroxidation, membrane fluidity, intracellular calcium regulation, passive membrane electrophysiological properties, and long-term potentiation (LTP). HMW-Aβ1-42 disturbed membrane integrity by inducing ROS generation and lipid peroxidation, resulting in decreased membrane fluidity, intracellular calcium dysregulation, depolarization, and impaired LTP. The damaging effects of HMW-Aβ1-42 were significantly greater than those of LMW-Aβ1-42. Therapeutic reduction of HMW-Aβ1-42 may prevent AD progression by ameliorating direct neuronal membrane damage.-Yasumoto, T., Takamura, Y., Tsuji, M., Watanabe-Nakayama, T., Imamura, K., Inoue, H., Nakamura, S., Inoue, T., Kimura, A., Yano, S., Nishijo, H., Kiuchi, Y., Teplow, D. B., Ono, K. High molecular weight amyloid β1-42 oligomers induce neurotoxicity via plasma membrane damage

わが国の大学における教養体育の開講状況に関する悉皆調査研究

The purpose of this study was to clarify and overview the current status of all colleges and universities (hereinafter, CUs) in Japan offering physical education courses as a component of liberal arts in higher education (hereinafter, PE in higher education) since the first complete survey that was conducted in 2000. Out of the 775 CUs existing as of August 2016, 742 CUs excluding 24 graduate universities and nine PE colleges were included in the survey. The following five items of information were extracted on PE in higher education from the CUs rules，handbook for students and syllabus posted on each CU website: 1) present/not present, 2) course type, 3) compulsory/optional, 4) number of compulsory credits, and 5) integrated title of the courses group. Among the 742 CUs surveyed, 97.7% (725 CUs) offered PE in higher education, except for 17 CUs (2.3%) that did not offer PE in higher education. The 725 CUs offering PE in higher education were categorized into courses comprising mainly practical skills (98.2%; 712 CUs), lectures (63.4%; 460 CUs) and compulsory for all departments (28.0%; 203 CUs), and compulsory for some departments (40.8%; 296 CUs) including practical skills (94.6%; 280 CUs), lectures (31.1% ; 92 CUs), and practical skills and lectures (25.7%; 76 CUs) in undergraduate departments. The number of PE in higher education credits offered as compulsory subjects was 2.15 ± 0.84 (mean ± standard deviation) and 0.5 to 5.0 (minimum - maximum) credits. The terms included in the integrated titles of PE in higher education courses for 725 CUs offering such courses were “Sports” (42.8%; 310 CUs), “Physical education” (39.9%; 289 CUs), “Health” (37.8%; 274 CUs), “Health education” (18.6%; 135 CUs), “Health and physical education” (17.8%; 129 CUs), and “Science” (14.8%; 107 CUs). The results revealed that PE in higher education was offered at approximately 98% of all CUs in Japan, and that the courses were compulsory at approximately 40% of them. Therefore, it can be said that PE in higher education is currently being offered at most CUs. This study has provided an overview of PE in higher education in Japan for the first time since 2000. Future research will involve conducting current status surveys of the curriculum contents focusing on the educational system for PE

Topographic variability of the left atrium and pulmonary veins assessed by 3D-CT predicts the recurrence of atrial fibrillation after catheter ablation

AbstractBackgroundCatheter ablation (CA) is an established therapy for atrial fibrillation (AF). However, the assessment of anatomical information and predictors of AF recurrence remain unclear. We investigated the relationship between anatomical information on the left atrium (LA) and pulmonary veins (PVs) from three-dimensional computed tomography images and the recurrence of AF after CA.MethodsSixty-seven consecutive AF patients (mean age: 62±10 years, median AF history: 42 (12; 60) months, mean LA size: 41±7mm, paroxysmal: 56%) underwent CA and were followed for 19±10 months. The segmented surface areas (antral, posterior, septal, and lateral) and dimensions (between the anterior and posterior walls, the right inferior PV and mitral annulus [MA], the right superior PV and MA, the left superior PV and MA, and the mitral isthmus) of the LA were evaluated three dimensionally using the NavX system. The cross-sectional areas of the PVs were also evaluated.ResultsAfter the follow-up period, 49 patients (73%) remained free from AF. A multivariate analysis showed that the diameter of the mitral isthmus and cross-sectional area of the right upper PV were associated with AF recurrence (odds ratio: 1.070, CI: 1.02–1.12, p=0.001; odds ratio: 0.41, CI: 0.21–0.77, p=0.006).ConclusionEnlargement of the mitral isthmus and a smaller right superior PV cross-sectional area were associated with AF recurrence

Construction of an All-in-one Double-conditional shRNA Expression Vector

Gene silencing by RNA interference （RNAi） is widely used for assessing gene function. An important advance in the RNAi field was the discovery that plasmid-based RNAi can substitute for synthetic small interfering RNA in vitro and in vivo. However, constitutive and ubiquitous knockdown of gene expression by RNAi in mice can limit the scope of experiments because this process can lead to embryonic lethality, or result in compensatory overexpression of other genes such that no phenotypic abnormalities occur. Either way, analyses of the physiological roles of the gene of interest in adult mice are not possible. To overcome these limitations, we previously constructed a double-conditional short-hairpin RNA （shRNA） expression vector that can regulate shRNA expression in a spatio-temporal manner with a tetracycline-inducible floxed stuffer sequence selectively excised by application of Cre recombinase. In this study, we aimed to modify this vector to create an all-in-one vector that produces double-conditional transgenic mice through a single round of gene transfer to fertilized eggs. We added a coding region for nuclear localizing Cre （NCre） recombinase with a multi-cloning site for a cell-specific promoter into the double-conditional short-hairpin RNA （shRNA） expression vector that we previously constructed. Using Escherichia coli, we confirmed successful construction of the vector. First, we confirmed isopropyl-β-D-thiogalactopyranoside-induced expression of NCre recombinase through the lac operon as a specific promoter by western blotting. Second, we confirmed functional recombination of the floxed sequence of loxP-like TATA-lox by analysing restriction enzyme-digested fragments. This all-in-one double-conditional shRNA expression vector will be useful for reversible in vitro and in vivo knockdown of target gene expression, in target cells via promoter-specific expression of NCre, and at specific times by tetracycline application