生物力学与基因-献给周培源教授诞辰100周年

生物界包罗万象,其中有力的作用,所以有生物力学.自Galileo,Harvey, Boreli, Hooke, Euler,Young等创始以来,生物力学阐明了鸟飞鱼游,人体运动,血液循环,人工脏器等,对人世社会,有所贡献.生物力学的基础是质点力学,传统地用连续体力学的概念来简化.但近年做生物组织在应力的作用下改造的问题,引起了必须更改传统连续体力学的几个公理的问题.我们将仔细讨论这些公理,然后指出新公理存在的理由,是由于基因在细胞里的日常工作.基因不单主宰遗传,变异;并且忙着控制日常生活.不过,现在仅见其端倪.详细的情形,要等将来来阐发了.      

DNA体外缩合的研究进展

DNA缩合不仅是自然界常见的生理现象,也是非病毒载体介导基因转染的关键步骤。了解DNA体外缩合的性质与特征,将有助于设计出高效的非病毒转基因载体。本文综述了近十几年来以多价阳离子为缩合剂诱发的DNA体外缩合的研究进展,着重介绍了缩合的机理、过程、影响缩合的因素以及应用于转基因的最新成果。     

基质刚性影响声孔效应介导的单细胞基因转染

实验研究了基质刚性对单细胞质粒DNA转染效果的影响。实验采用高声压短脉冲(0.45MPa,10μs)条件的超声对培养在不同硬度凝胶基质(软的凝胶基质：0.2kPa,硬的凝胶基质：40kPa)上的力学敏感细胞NIH 3T3进行质粒DNA转染实验。实验结果表明,培养在硬的凝胶基质上的细胞,质粒DNA转染效率明显高于培养在软的凝胶基质上的细胞。进一步对质粒DNA进行荧光示踪可知培养在不同刚性基质上的细胞导入质粒DNA的方式不同。当细胞被培养在硬的凝胶基质上时,通过声致穿孔产生的小孔进入细胞内的质粒DNA更多,而培养在软的凝胶基质上的细胞,更多的质粒DNA可以通过非声致穿孔作用,例如内吞方式导入细胞。 细胞骨架蛋白分布规律表明,硬的凝胶基质上培养的细胞内有更多的F肌动蛋白微丝,可以更好地支撑起细胞的铺展形态,相对不容易发生内吞作用。而软的凝胶基质上培养的细胞内F肌动蛋白则更多以球形状态存在,细胞形貌骗向圆形,此时更容易发生胞吞作用。     

SVMs在微阵列表达数据分析中的应用

微阵列技术允许同时录制成百万的基因表达水平。但由于经费和工艺的限制,目前研究者获得的表达数据集往往包含少量的样本,而基因表达的测量值却有上万条。很多传统的统计方法无法分析这样的数据,本文结合数据挖掘中统计学习理论的相关知识,详细介绍了一种有监督分析方法———支持向量机(SVMs)在微阵列表达数据分析中的应用。     

Synthesis of a novel multivalent galactoside with high hepatocyte targeting for gene delivery

A novel bifunctional glycolipid which carded a cluster of thiogalactosides as the hepatocyte targeting ligand for gene delivery was prepared. Hexa-antennary alcohol 1 was used as the core scaffold to attach a cholesterol molecule by a poly（ethylene glycol） chain, while its remaining branches were linked with five acetylgalactosides, which would be deacetylated later to produce pentaantennary galactoside. Liposome containing the galactoside showed high affinity and transfection activity in hepatoma cells HepG2.     

Polyethylenimine (PEI)g-comb-poly(ethylene glycol)-transferrin(I): Tumor-targeted Vector for Gene Delivery In-vitro

A new vector, PEG as a core, low Mw PEI was grafted to PEG, and transferrin was conjugated the co-polymer to form PEI-g-PEG-transferrin1,2. NMR, FT-IR and TGA spectroscopy confirmed the structures of activated PEG and the final products. The MW of PEI-g-P…     

Impact of Cationic Charge Density and PEGylated Poly(Amino Acid) Tercopolymer Architecture on Their Use as Gene Delivery Vehicles. Part 2: DNA Protection,Stability, Cytotoxicity,and Transfection Efficiency

The impact of the molecular architecture on the transfection efficiency of PEGylated poly(amino acid) block copolymers was investigated for PEG‐b‐p(l ‐Lys)_x‐b‐p(l ‐Leu)_y, PEG‐b‐p(l ‐Leu)_x‐b‐p(l ‐Lys)_y, and PEG‐b‐p((l ‐Leu)_x‐co‐(l ‐Lys)_y). The block lengths of p(l ‐Lys) and p(l ‐Leu) were varied between 10, 20, and 40; and 10 and 20, respectively, to study the influence of the ionic/hydrophobic balance. The results show that ABC triblock copolymers form smaller and more stable polyplexes with plasmid DNA than AB diblock copolymers—as verified by long‐term aggregation and ethidium bromide exclusion studies—protect the DNA more effectively against nucleases, and provide better transfection efficiencies, as indicated by total protein as well as luciferase expression. More detailed studies revealed that triblock copolymers with p(l ‐Leu) forming the C‐block were most efficient in DNA complexation with a 2.3 times higher transfection rate. Furthermore, increasing the cationic character by increasing the p(l ‐Lys) chain length led to up to 25% higher transfection but at the same time induced some cytotoxicity. Diblock copolymers, where the amino acid–building blocks exist as a random copolymer, bind more loosely with DNA leading to less compact and less stable aggregates with lower transfection efficiencies.     

Chemical Physics in Living Cells-using Light to Visualize and Control Intracellular Signal Transduction?

Cells are crowded microenvironments filled with macromolecules undergoing constant physical and chemical interactions. The physicochemical makeup of the cells affects various cellular responses, determines cell-cell interactions and influences cell decisions. Chemical and physical properties differ between cells and within cells. Moreover, these properties are subject to dynamic changes in response to environmental signals, which often demand adjustments in the chemical or physical states of intracellular molecules. Indeed, cellular responses such as gene expression rely on the faithful relay of information from the outside to the inside of the cell, a process termed signal transduction. The signal often traverses a complex path across subcellular spaces with variable physical chemistry, sometimes even influencing it. Understanding the molecular states of such signaling molecules and their intracellular environments is vital to our understanding of the cell. Exploring such intricate spaces is possible today largely because of experimental and theoretical tools. Here, we focus on one tool that is commonly used in chemical physics studies-light. We summarize recent work which uses light to both visualize the cellular environment and also control intracellular processes along the axis of signal transduction. We highlight recent accomplishments in optical microscopy and optogenetics, an emerging experimental strategy which utilizes light to control the molecular processes in live cells. We believe that optogenetics lends unprecedented spatiotemporal precision to the manipulation of physicochemical properties in biological contexts. We hope to use this work to demonstrate new opportunities for chemical physicists who are interested in pursuing biological and biomedical questions.     

O-羧甲基壳聚糖的制备及应用研究进展

O_羧甲基壳聚糖是壳聚糖的一种衍生物 ,具有比壳聚糖更优良的特性 ,有着更广阔的应用前景。本文对它的制备、性质、应用 ,特别是其在药物释放及基因治疗方面应用的研究进展进行了综述。