Intravenously Injected Amyloid-β Peptide With Isomerized Asp7 and Phosphorylated Ser8 Residues Inhibits Cerebral β-Amyloidosis in AβPP/PS1 Transgenic Mice Model of Alzheimer’s Disease

Cerebral β-amyloidosis, an accumulation in the patient’s brain of aggregated amyloid-β (Aβ) peptides abnormally saturated by divalent biometal ions, is one of the hallmarks of Alzheimer’s disease (AD). Earlier, we found that exogenously administrated synthetic Aβ with isomerized Asp7 (isoD7-Aβ) induces Aβ fibrillar aggregation in the transgenic mice model of AD. IsoD7-Aβ molecules have been implied to act as seeds enforcing endogenous Aβ to undergo pathological aggregation through zinc-mediated interactions. On the basis of our findings on zinc-induced oligomerization of the metal-binding domain of various Aβ species, we hypothesize that upon phosphorylation of Ser8, isoD7-Aβ loses its ability to form zinc-bound oligomeric seeds. In this work, we found that (i) in vitro isoD7-Aβ with phosphorylated Ser8 (isoD7-pS8-Aβ) is less prone to spontaneous and zinc-induced aggregation in comparison with isoD7-Aβ and intact Aβ as shown by thioflavin T fluorimetry and dynamic light scattering data, and (ii) intravenous injections of isoD7-pS8-Aβ significantly slow down the progression of institutional β-amyloidosis in AβPP/PS1 transgenic mice as shown by the reduction of the congophilic amyloid plaques’ number in the hippocampus. The results support the role of the zinc-mediated oligomerization of Aβ species in the modulation of cerebral β-amyloidosis and demonstrate that isoD7-pS8-Aβ can serve as a potential molecular tool to block the aggregation of endogenous Aβ in AD

Phosphorylation of the Amyloid-Beta Peptide Inhibits Zinc-Dependent Aggregation, Prevents Na,K-ATPase Inhibition, and Reduces Cerebral Plaque Deposition

The triggers of late-onset sporadic Alzheimer’s disease (AD) are still poorly understood. Impairment of protein phosphorylation with age is well-known; however, the role of the phosphorylation in β-amyloid peptide (Aβ) is not studied sufficiently. Zinc-induced oligomerization of Aβ represents a potential seeding mechanism for the formation of neurotoxic Aβ oligomers and aggregates. Phosphorylation of Aβ by Ser8 (pS8-Aβ), localized inside the zinc-binding domain of the peptide, may significantly alter its zinc-induced oligomerization. Indeed, using dynamic light scattering, we have shown that phosphorylation by Ser8 dramatically reduces zinc-induced aggregation of Aβ, and moreover pS8-Aβ suppresses zinc-driven aggregation of non-modified Aβ in an equimolar mixture. We have further analyzed the effect of pS8-Aβ on the progression of cerebral amyloidosis with serial retro-orbital injections of the peptide in APPSwe/PSEN1dE9 murine model of AD, followed by histological analysis of amyloid burden in hippocampus. Unlike the non-modified Aβ that has no influence on the amyloidosis progression in murine models of AD, pS8-Aβ injections reduced the number of amyloid plaques in the hippocampus of mice by one-third. Recently shown inhibition of Na+,K+-ATPase activity by Aβ, which is thought to be a major contributor to neuronal dysfunction in AD, is completely reversed by phosphorylation of the peptide. Thus, several AD-associated pathogenic properties of Aβ are neutralized by its phosphorylation

Subchronic Toxicity of Copper Oxide Nanoparticles and Its Attenuation with the Help of a Combination of Bioprotectors

In the copper metallurgy workplace air is polluted with condensation aerosols, which a significant fraction of is presented by copper oxide particles <100 nm. In the scientific literature, there is a lack of their in vivo toxicity characterization and virtually no attempts of enhancing organism’s resistance to their impact. A stable suspension of copper oxide particles with mean (±SD) diameter 20 ± 10 nm was prepared by laser ablation of pure copper in water. It was being injected intraperitoneally to rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water) three times a week up to 19 injections. In parallel, another group of rats was so injected with the same suspension against the background of oral administration of a “bio-protective complex” (BPC) comprising pectin, a multivitamin-multimineral preparation, some amino acids and fish oil rich in ω-3 PUFA. After the termination of injections, many functional and biochemical indices for the organism’s status, as well as pathological changes of liver, spleen, kidneys, and brain microscopic structure were evaluated for signs of toxicity. In the same organs we have measured accumulation of copper while their cells were used for performing the Random Amplification of Polymorphic DNA (RAPD) test for DNA fragmentation. The same features were assessed in control rats infected intraperitoneally with water with or without administration of the BPC. The copper oxide nanoparticles proved adversely bio-active in all respects considered in this study, their active in vivo solubilization in biological fluids playing presumably an important role in both toxicokinetics and toxicodynamics. The BPC proposed and tested by us attenuated systemic and target organs toxicity, as well as genotoxicity of this substance. Judging by experimental data obtained in this investigation, occupational exposures to nano-scale copper oxide particles can present a significant health risk while the further search for its management with the help of innocuous bioprotectors seems to be justified

rights and obligations of parties under sale contract in Russian Civil Law

這篇論文的目的是介紹給台灣讀者俄羅斯買賣契約法之基本概念， 本論文特別強調的重點就是買賣契約之效力。 希望本論文給對俄羅斯法有興趣的台灣讀者會有幫助。由於台灣和俄羅斯很多年沒有任何關係，不僅在俄羅斯，有關台灣法律之發展資訊相當欠缺，在台灣有關俄羅斯法律之發展，亦是相同的情況。 雖然本論文不能完全描寫所有有關俄羅斯買賣契約效力之問題，但它涉及所有俄羅斯民法理論關於買賣效力與買賣之總則重要的概念及見解。 本論文還包括俄羅斯買賣之種類以及俄羅斯民法發展之介紹。在結論將與台灣買賣法作基本之比較。 對台灣讀者應該須要解釋一下本論文內容闡述之順序。本論文之內容是按照一般俄羅斯法律書及研究論文的闡述順序而提出。基本上此順序如下﹕首先為買賣契約概念之介紹，然後買賣契約之當事人、買賣契約之標的物之概念、最後為買賣之效力（出賣人之義務與權利和受買人之義務與權利）。 也許，對台灣讀者來講最有趣的是俄羅斯買賣契約之理論沒有跟台灣民法類似的瑕疵擔保概念。另一方面，俄羅斯法之規定比較精細的，例如出賣人之義務包括﹕交付貨物之義務，移轉所有權之義務，交付之貨物須擁有符合法律與契約之規定的數量、種類、品質、完整、包裝與包皮。此應該是受到其它國家買賣法影響之結果，此外尚有國際公約之影響，尤其是1980年的《聯合國國際貨物買賣公約》（《買賣公約》）的影響。 因為新的俄羅斯民法典不是很久以前通過的（第一部分是一九九四年通過的、第二部分是是二○○一年通過的），它可以合併外國法律制度與國際法最新的成果。 其它對於本論文台灣讀者會感到特別的是缺少豐富之法院判決。要強調的是，現代俄羅斯民法之實踐還沒達到台灣民法實踐之豐富。 雖本論文有若干法院判決之腳註（俄羅斯聯邦最高仲裁法院之判決） ，但於俄羅斯民法學說及關於民法法條之評論比判決有更大之影響。現在俄羅斯最受敬重之評論書就是 一九九八年出版的Sadikov O.N.教授俄羅斯聯邦民法法典之評論，本評論書就是在本論文工作上之時候適用的。 除了基本內容以外本論文還有附錄。此附錄包括從俄文翻譯成中文的以及俄文的俄羅斯民法買賣契約之法條。或許，此對學俄文台灣的學生會幫增加他們俄文法律辭典。 本論文之作者希望，他的論文能為台灣與俄羅斯法律學界之交流，作出微薄之貢獻。This thesis focusses on the provisions of Russian civil law which govern all forms of contracts and contractual obligations. In the thesis a reference to the development of the new Russian civil law will be given as well as a final comparison between the Russian provisions for contracts and the contract law of Taiwan.前言 6 俄羅斯民法發達歷史 8 買賣契約意義與使用範圍 10 法規之來源 12 買賣之總則 14 買賣契約之定義 14 買賣契約之當事人 21 買賣契約內容 25 買賣契約之效力 28 契約之條款與雙方之義務 28 出賣人之義務 29 A）財產權移轉 33 B）物之數量 36 C）貨物之種類 38 D）貨物之品質 40 E）貨物之完整 50 F）貨物之包皮與包裝 53 通知出賣人其未適當履行買賣契約 55 買受人之義務 56 A）物之受領 56 B）價金之確定與支 58 買賣契約之類型 63 結論（台俄法之比較） 70 附錄（俄羅斯民法買賣之法條） 中文 75 俄文 94 英文 116 參考文文獻 13

Attendance monitoring of ethnic tourism objects in the Republic of Mordovia in 2017

The Republic of Mordovia is a multinational region of the Russian Federation. For centuries, Russians, Mordovians (Moksha and Erzya), Tatars, and others coexist peacefully on its territory. This necessitates the development of ethnic tourism, the area of tourism with a pronounced ethnic identity in the Republic. It can be distinguished as internal and external ethnic tourism. For the research of the development of ethnic tourism in Mordovia, the authors employed general research analytical methods (comparative, functional, natural history, etc.) and a survey as a tool for collecting primary sociological information. The survey was conducted in all municipal districts of the Republic in September 2017. The most famous objects of ethnic tourism are the ethnographic Museum complex “Mordovian Courtyard” and the Museum of Mordovian folk culture; they are the most visited sites. The percentage of people who know about the Center for National Culture in Old Terizmorga village and Podlesno-Tavlinskoy Children’s Experimental Art School is quite high. The prospects for the development of ethnic tourism can be assessed as favorable, since there is a high percentage of those who would like to visit other objects of ethnic tourism as well. The conclusion is made about further development of internal and external ethnic tourism in Mordovia