Proanthocyanidins prevent tau protein aggregation and disintegrate tau filaments

Occurrence of neurofibrillary tangles of the tau protein is a hallmark of tau-related neurodegenerative diseases, i.e. Alzheimer's disease(AD) and frontotemporal dementia. The pathological mechanism underlying AD remains poorly understood, and effective treatments are still unavailable to mitigate the disease.Inhibiting of tau aggregation and disrupting the existing fibrils are key targets in drug discovery towards preventing or curing AD. In this study, grape seed proanthocyanidins(GSPs) was found to effectively inhibit the repeat domain of tau(tau-RD) aggregation and disaggregate tau-RD fibrils in a concentrationdependent manner by inhibiting β-sheet formation of tau-RD. In cells, GSPs relieved cytotoxicity induced by tau-RD aggregates. Molecular dynamics simulations indicated that strong hydrogen bonding,hydrophobic interaction and π-π stacking between GSPs and tau-RD protein were major reasons why GSPs had high inhibitory activity on tau-RD fibrillogenesis. These results provide preliminary data to develop GSPs into medicines, foodstuffs or nutritional supplements for AD patients, suggesting that GSPs could be a candidate molecule in the drug design for AD therapeutics.

Biggs Theorem for Directed Cycles and Topological Invariants of Digraphs

We generalize Biggs Theorem to the case of directed cycles of multi-digraphs allowing to compute the dimension of the directed cycle space independently of the graph representation with linear runtime complexity. By considering two-dimensional CW complex of elementary cycles and deriving formulas for the Betti numbers of the associated cellular homology groups, we extend the list of representation independent topological inavariants measuring the graph structure. We prove the computation of the 2nd Betti number to be sharp #P hard in general and present specific representation invariant sub-fillings yielding efficiently computable homology groups. Finally, we suggest how to use the provided structural measures to shed new light on graph theoretical problems as graph embeddings, discrete Morse theory and graph clustering.

Opto-fluidically multiplexed assembly and micro-robotics

Techniques for high-definition micromanipulations,such as optical tweezers,hold substantial interest across a wide range of disciplines.However,their applicability remains constrained by material properties and laser exposure.And while microfluidic manipulations have been suggested as an alternative,their inherent capabilities are limited and further hindered by practical challenges of implementation and control.Here we show that the iterative application of laser-induced,localized flow fields can be used for the relative positioning of multiple micro-particles,irrespectively of their material properties.Compared to the standing theoretical proposal,our method keeps particles mobile,and we show that their precision manipulation is non-linearly accelerated via the multiplexing of temperature stimuli below the heat diffusion limit.The resulting flow fields are topologically rich and mathematically predictable.They represent unprecedented microfluidic control capabilities that are illustrated by the actuation of humanoid micro-robots with up to 30 degrees of freedom,whose motions are sufficiently well-defined to reliably communicate personal characteristics such as gender,happiness and nervousness.Our results constitute high-definition micro-fluidic manipulations with transformative potential for assembly,micro-manufacturing,the life sciences,robotics and optohydraulically actuated micro-factories.

小分子伴侣对淀粉样蛋白β聚集抑制作用研究

淀粉样蛋白β(Aβ)的积累和聚集在阿尔茨海默症的致病机理研究中是非常关键的,因而开发能有效抑制Aβ聚集的新型抑制剂具有重要的意义。来源于大肠杆菌分子伴侣GroEL/GroES系统的小分子伴侣(GroEL顶端结构域191-345位残基)可以通过疏水相互作用与目标蛋白结合,具有生物相容性好等特点,是一种潜在的Aβ聚集抑制剂。通过硫代硫磺素T荧光光谱、透射电镜、凝胶过滤色谱分析和细胞毒性实验详细研究了小分子伴侣与Aβ42的相互作用,并与姜黄素、表没食子儿茶素没食子酸酯和槲皮素等多酚类抑制剂的作用进行比较。结果表明小分子伴侣不仅降低了Aβ42的聚集程度,同时也改变了Aβ42的聚集路径,使得其聚集体分子量和纤维形貌发生了显著变化。相较于对照组,添加小分子伴侣后使得Aβ42溶液原位ThT荧光响应值下降了72%,形成的纤维长度从数百纳米下降到小于50 nm,SH-SY5Y的细胞存活率提升了20%。因此,小分子伴侣能有效阻止Aβ纤维聚集体形成,降低其细胞毒性,具有良好的应用前景。

纳米生物学——未来之挑战——中国科学院上海交叉学科研究中心第八次上海圆桌会议

纳米技术是科技部中长期规划基础研究重大专项之一，纳米生物学是其重要的一个分支。我们知道生物细胞已经成为研究纳米技术的重要场所。蛋白装配成纳米机器，它可以转化能量并制造出各种大分子。有些蛋白还可作为一种传感器行使功能。细胞其实就是由各种各样的分子器件组成，其中还有许多未知有待于我们去探索。目前，技术的发展还有赖于那些不可循环利用的资源，如石油、汽油、煤炭、金属等，在今后的几十年中，它们将逐步被取代。未来的工程师创造新技术时，

Highly sensitive force measurements in an optically generated, harmonic hydrodynamic trap

The use of optical tweezers to measure forces acting upon microscopic particles has revolutionised fields from material science to cell biology.However,despite optical control capabilities,this technology is highly constrained by the material properties of the probe,and its use may be limited due to concerns about the effect on biological processes.Here we present a novel,optically controlled trapping method based on light-induced hydrodynamic flows.Specifically,we leverage optical control capabilities to convert a translationally invariant topological defect of a flow field into an attractor for colloids in an effectively one-dimensional harmonic,yet freely rotatable system.Circumventing the need to stabilise particle dynamics along an unstable axis,this novel trap closely resembles the isotropic dynamics of optical tweezers.Using magnetic beads,we explicitly show the existence of a linear force-extension relationship that can be used to detect femtoNewton-range forces with sensitivity close to the thermal limit.Our force measurements remove the need for laser-particle contact,while also lifting material constraints,which renders them a particu-larly interesting tool for the life sciences and engineering.