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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
A Case of Pulmonary Sarcoma with Significant Extension into the Right Lung
A female patient in her 30s was referred to us with a mass approximately 8 centimeters in diameter in right lung segment 6. Bronchoscopy was done, and a tumorous lesion obstructing right B6 was found. Biopsy of this lesion supported suspicions of sarcoma or spindle cell carcinoma. Contrast-enhanced CT showed that the mass extended to and obstructed the right main pulmonary artery. A skip lesion was also suspected in the periphery of pulmonary artery trunk. The tumor was removed by right pneumonectomy accompanied by resection of the main and left pulmonary arteries under cardiopulmonary bypass. The pulmonary artery trunk and the left pulmonary artery were reconstructed with a vascular graft. Collectively, intimal sarcoma originating from the right main pulmonary artery with extension into the right lung was diagnosed. Significant extension of pulmonary artery sarcoma into the lung, as was observed in the present case, is considered to be rare, and to our knowledge this is the first report in which the primary lesion was biopsied by bronchoscopy
岡崎100年間の「ていただく」増加傾向 : 受恵表現にみる敬語の民主化
明海大学神戸松蔭女子学院大学Meikai UniversityKobe Shoin Women\u27s Universityこの稿では,対人関係調節のための新表現が実時間の100年間でどのように増加したかを論じる。具体的には,敬語に関わる新表現「ていただく」における進行中の言語変化をみる。岡崎市の55年にわたる計1000人規模の大規模社会言語学的調査に基づき,年齢という見かけの時間を利用する。間隔の異なる3回の調査結果を,時間軸を忠実に反映できるグラフ技法によって提示したところ,「てもらう」「ていただく」が着実に普及しつつあることを,確認できた。これは日本語の補助動詞の発達,授受表現の普及と一致し,岡崎という東海地方の都市の変化が日本語史全体と深く結びついていることが分かった。この背景には敬語変化の普遍性がある。ヨーロッパの二人称代名詞の用法における「力関係から連帯関係へ(from power to solidarity)」と並行的な変化が,現代日本語の敬語でも起こりつつある。つまり地位の上下による使い分けから,親疎による使い分けに変化しつつある。コミュニケーションの民主化・平等化が進んだと考えられる。また,場面による使われ方の違いをみると,依頼表現に伴って多用されるようになった。つまりかつての身分,地位による敬語の使い方と異なった基準が導入され,場面ごとの心理的負担や親疎関係がからむ。このメカニズムも,敬語の民主化・平等化として解釈できる。新表現が個人の一生の間にいかに獲得されるかをみると,若い世代が最初に採用するわけではない。対人関係にかかわる現象に関しては,社会的活躍層が使いはじめる。ポライトネスや敬語などで,30代以上の壮年層が最初に新表現を採用する例,成人後採用の実例が認められた。This paper describes real-time changes in the use of honorifics in Okazaki over nearly 100 years. The tendencies in Okazaki clearly reflect the history of Japanese and also coincide with world trends. Recent developments in real-time analysis of linguistic change in progress have found that linguistic change can occur within an individual long after adolescence. Here we present another example of a phenomenon known as late adoption. The data come from the Okazaki Survey on Honorifics, a 55-year-long repeated survey on change and variation in honorific use, including speaker awareness, in Okazaki City, Japan, with nearly one thousand informants in total. The case in point involves the late adoption of the honorific verb itadaku \u27take, receive\u27, which as part of a serial verb construction, expresses the meaning of humbleness. The -itadaku construction begins to appear late in the Okazaki Survey data, and it was first used not by the youngest speakers, but by middle-age speakers. This late adoption of itadaku is best explained as a consequence of social value of honorifics in Japanese society, where, traditionally, the mastery of honorifics is seen as a passport into the world of adults. The late adoption of itadaku is also a manifestation of a universal of honorific change, as it involves a change from power to solidarity, a tendency that is widely known from the historical change of the second-person pronouns in the Indo-European languages. The spread of the -itadaku construction thus constitutes another example of the democratization of Japanese honorifics
セマイ スキマ ニ オケル キャビテーション ソンショウ ニ オヨボス ポリマー コウカ ニ カンスル ケンキュウ
Cavitation damage tests are undertaken in polymer solutions and water using stationary aluminum in close proximity to the free end of vibratory horn Experimental conditions are resonant frequency 19.5kHz and peak-to-peak amplitude 38.1μm. The mass loss in a 1000wppm polymer solution is lager than in a 100wppm polymer solution and water. ln the 100wppm polymer solution, cavitation bubbles are generated on the vibratory tip, but in the 1000wppm polymer solution, the cavity in the clearance appears on the stationary specimens
Urinary Level of Liver-Type Fatty Acid Binding Protein Reflects the Degree of Tubulointerstitial Damage in Polycystic Kidney Disease
Background/Aims: Polycystic kidney disease (PKD) is a common, progressive, and heritable type of kidney disease. Although certain imaging modalities are useful for the diagnosis and staging of PKD, they cannot adequately monitor the severity of interstitial inflammation and fibrosis. Therefore, the present study evaluated the urinary level of liver-type fatty acid binding protein (L-FABP) as a marker of interstitial inflammation and fibrosis in PKD. Methods: Male PCK/CrljCrl-Pkhd1pck/Crl (PCK) rats (n = 34) were used as an animal model of the PKD. Age-and sex-matched Sprague–Dawley rats (SD) (n = 34) were used as controls. Urine samples were obtained from the rats at 8, 12, 16, 20, and 24 weeks of age, and the sera and kidney tissues were obtained at 8, 16, 20, and 24 weeks of age. Results: All PCK rats developed cysts, and the degrees of tubular epithelial cell proliferation and interstitial inflammation increased linearly with age in these model rats relative to the controls. Interstitial fibrosis tended to increase in the PCK rats from 8 to 20 weeks of age, and revealed a peak level at 20 weeks. The urinary L-FABP levels increased linearly with age in the PCK rats, and the levels at 12, 16, 20, and 24 weeks were significantly higher than those in the controls. The urinary levels of L-FABP in the PCK rats correlated significantly with the severity of tubulointerstitial damage; specifically, we observed a significant correlation of the urinary levels at 16 weeks of age with the total kidney volume at 20 weeks. In contrast, both PCK and SD rats exhibited similar serum levels of L-FABP. Conclusion: Urinary L-FABP reflects the progression of tubulointerstitial damage, and therefore, may be a useful marker for monitoring the progression of PKD
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