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Peptide backbone-copper ring structure: A molecular insight into copper-induced amyloid toxicity 下载免费PDF全文
Copper ions can promote amyloid diseases that are associated with amyloid peptides, such as type 2 diabetes (T2D), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). However, the underlying molecular mechanism remains obscure. Here we present that Cu2+ is able to specifically bind to the backbone of T2D-related human islet amyloid polypeptide (hIAPP) by forming a ring structure, which causes the reduction of Cu2+ to Cu+ to produce reactive oxygen species (ROS) and the modulation of hIAPP aggregation. Nuclear magnetic resonance spectroscopy showed that Cu2+ bound to the backbone of a turn region, His18—Ser21, which is critical for hIAPP aggregation. Ab initio calculations and x-ray absorption fine structure analyses revealed that Cu2+ simultaneously bound with both the amide nitrogen and carbonyl oxygen on the peptide backbone, resulting in a ring structure, and causing the reduction of Cu2+ to Cu+ to form a hIAPP-Cu+ complex. 2',7'-dichlorodihydrofluorescin diacetate fluorescence measurements further indicated that this complex led to enhanced ROS levels in rat insulinoma cells. Additionally, thioflavin T fluorescence and atomic force microscopy measurements denoted that the backbone-Cu ring structure largely modulated hIAPP aggregation, including the inhibition of hIAPP fibrillation and the promotion of peptide oligomerization. These findings shed new light on the molecular mechanism of Cu2+-induced amyloid toxicity involving both the enhancement of ROS and the modulation of hIAPP aggregation. 相似文献
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The eccentricity of the centre of mass from the geometric centre of a spherical attracting mass in determining the Newtonian gravitational constant G is tested by means of an electronic balance. The experimental result shows that the eccentricity of the sample is about 0.31 μm with uncertainty of 0.05μm. Two density distribution models are discussed to estimate the uncertainty to G by the eccentricities of the attracting masses. 相似文献
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利用MJP-30A滚动磨损与接触疲劳试验机研究了两种水基摩擦改性剂(分别记为FM1和FM2)的最佳涂敷量,分析了FM1和FM2在最佳涂敷量下对轮轨磨损和损伤的影响. 结果表明:FM1和FM2单次的最佳涂敷量分别为14和8 μl. FM1介质下轮轨试样的磨损率明显降低,仅为干态下的23%和41%;FM2介质下车轮试样的磨损率略高于干态下,钢轨试样的磨损率为干态下的64%. 干态和FM2介质下轮轨试样表面出现起皮、剥落及明显的疲劳裂纹,试样剖面出现多层裂纹、支裂纹和次表层裂纹;FM1介质下轮轨试样损伤轻微,试样表面出现轻微起皮和点蚀,试样剖面出现少量的单层微裂纹,FM1可有效减缓轮轨的磨损与损伤. 相似文献
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研究了过共析钢轨焊接接头淬火和正火后不同区域的硬度与微观组织,利用冲击磨损试验机对不同区域进行冲击试验,分析了各区域冲击磨损与损伤特性. 结果表明:钢轨焊接接头分为母材区、焊缝区和热影响区. 母材区微观组织为片层状珠光体,焊缝区为珠光体与先共析铁素体且正火后铁素体含量较多,热影响区淬火后为粒状珠光体而正火后存在少量片层状珠光体. 焊接接头不同区域硬度大小为母材区>淬火焊缝区>正火焊缝区>正火热影响区>淬火热影响区. 硬度越低的区域,冲击深度和磨损体积越大. 母材区冲击损伤轻微,表面呈轻微剥落;焊缝区损伤较严重,出现明显裂纹且正火后损伤较淬火后严重;热影响区损伤最为严重且正火后损伤较淬火后略轻微. 相似文献
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稀土/高分子杂化发光材料的研究 总被引:11,自引:1,他引:10
用SiO2为无机组份和以与SiO2具有相似折射率和优良力学性能的丙烯酸类如甲基丙烯酸甲酯(MMA)和甲基丙烯酸羟乙酯(HEMA),在交联剂3-(三甲氧基硅)丙基甲基丙烯酸酯(MSMA)存在下,快速制备了两种杂化基质材料SiO2/P(MMA-MSMA)和SiO2/P(HEMA-MSMA)。分别以盐酸和六次甲基四胺作为酸性催化剂和碱性催化剂,建立了快速制备透明凝胶的两步溶胶-凝胶法,大大缩短了溶胶的成胶时间,所得杂化材料具有良好的光学透明性,利用此方法制备了掺杂稀土配合物的多种发光杂化材料。采用组装的方法,得到了稀土配合物与层次化合物α-磷酸氢锆(α-ZrP)及中孔分子筛材料MCM-41的组装体,并对所制备的杂化材料进行了表征。另外,将稀土配合物通过共价键嫁接于无机SiO2基质中,得到了含有稀土配合物的分子杂化材料。 相似文献
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通过测量荧光寿命和荧光光谱,研究了1,2-苯并蒽(BA),9,10-二甲基-1,2-苯并蒽(DMBA)与β-环糊精(β-CD)络合过程及荧光猝灭。计算出络合平衡常数和猝灭常数。结果表明,BA与β-CD发生了络合作用,DMBA几乎不与β-CD络合。加入β-CD可使荧光分子的,聚集态与单体间的平衡向生成单体的方向移动,碘离子对BA的猝灭作用也明显减弱。 相似文献
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