基于AFM成像的DNA长度的计算机统计处理

利用计算机图像处理技术 ,对自然沉积DNA和拉直DNA分子AFM图像的长度进行了自动统计测量 ,并与DNA分子的理论长度进行了比较。该方法在DNA分子的AFM图像的基础上 ,将DNA分子拟合成曲线 ,用插值法求得DNA分子长度 ,整个过程实现了自动化。结果表明 ,该方法测得自然沉积的某DNA分子长度为 (180 .4± 16.4 )nm ,与理论长度 185 .0nm相当符合。该方法与拉直法和直接法求DNA分子长度相比是一次改进 ,也为其它基于AFM图像的线状物体求长度提供了一种新的测量方法。对另一组拉直DNA测量的结果表明 :拉直后DNA分子长度为 (34 3.6± 2 0 .7)nm ,与理论长度 30 7.0nm相比明显变长 ,这表明对自然沉积DNA进行长度测量的必要性 ,保证了DNA分子的长度不受拉直后有所伸长的影响。     

致死剂量辐射诱导小鼠骨髓细胞凋亡特征的研究

经＾６０Ｃｏ γ射线以不同剂量全射照射２１３只ＬＡＣＡ小鼠,于照射后４周内分批 杀,将骨髓标本分别进行Ｈ．Ｅ染色,半薄及超薄切片,并通过原位末端标记和ＤＮＡ交电泳观察其生化特性。结果表明：射后６ｈ,各一组小鼠骨髓造血细胞出现凋亡明显增多,且剂量赵大,凋亡细胞越多。凋亡的细胞形态上表现为染色质深度缩、边移,呈半月型,环状或不规则状,核碎片喜讯发小体形成,电泳下可见ＤＮＡ梯状图谱。在２．５～７．０Ｇ６     

热休克蛋白对电离辐射损伤的保护效应

近年来,热休克蛋白（HSPs）对电离辐射损伤的保护效应成为一个关注的热点。本文综述了热休克蛋白家族及其对电离辐射损伤的保护效应,包括HSPs对细胞凋亡的抑制作用和DNA损伤的保护作用两方面,对热休克蛋白与电离辐射损伤的关系进行了探讨。     

基于混沌映射和DNA编码的图像加密算法

为了有效改进图像的加密效果及安全性,在对已有的图像加密算法进行分析的基础上,提出基于混沌映射的位变换和DNA序列的图像加密算法。首先,采用混沌映射生成置乱序列对图像在位平面进行置乱,同时达到了图像置乱和扩散的双重加密效果。然后,利用DNA编码规则,对置乱后的图像编码,进行DNA运算,实现图像的扩散。实验结果表明,该算法密钥空间足够大,密钥敏感性较强,具有较好的安全性。     

DNA编码限制条件与编码策略

以评价DNA编码的基本限制条件之一——Hamming距离为出发点分析了DNA编码的三个参量：码字个数、码字长度与Watson-Crick Hamming距离,并得到它们之间的内在联系;讨论了Watson-Crick Hamming距离与DNA码字重量之间的关系;在此基础上得到了DNA编码的编码策略;提出了适合DNA编码的改进Watson-Crick Hamming距离及DNA编码模块化的定义,对DNA编码的优化做出了详细分析,为DNA计算的发展注入了活力。     

DNA‐Directed Gold Nanodimers with Tunable Sizes and Interparticle Distances and Their Surface Plasmonic Properties

A quantitative understanding of the localized surface plasmon resonances (LSPRs) of metallic nanostructures has received tremendous interest. However, most of the current studies are concentrated on theoretical calculation due to the difficulty in experimentally obtaining monodisperse discrete metallic nanostructures with high purity. In this work, endeavors to assemble symmetric and asymmetric gold nanoparticle (AuNP) dimer structures with exceptional purity are reported using a DNA self‐assembly strategy through a one‐step gel electrophoresis, which greatly facilitates the preparation process and improves the final purity. In the obtained Au nanodimers, the sizes of AuNPs (13, 20, and 40 nm) and the interparticle distances (5, 10, and 15 nm) are tunable. The size‐ and distance‐dependent plasmon coupling of ensembles of single, isolated dimers in solution are subsequently investigated. The experimental measurements are correlated with the modeled plasmon optical properties of Au nanodimers, showing an expected resonance shift with changing particle sizes and interparticle distances. This new strategy of constructing monodisperse metallic nanodimers will be helpful for building more complicated nanostructures, and our theoretical and experimental understanding of the intrinsic dependence of plasmon property of metallic nanodimer on the sizes and interparticle distances will benefit the future investigation and exploitation of near‐field plasmonic properties.     

微米级PVDAT@PS微球的制备及生物应用研究

该研究首次利用功能单体2-乙烯基-4,6-二氨基-1,3,5-三嗪(VDAT)在水相中合成具有生物应用前景的微米级核壳微球。首先,我们利用分散聚合制备出了微米级,单分散,且表面带有足够负电荷的聚苯乙烯微球(PS)模板。再利用半连续无皂乳液聚合法在阳离子引发剂的作用下,于水相中将微溶于热水的单体VDAT引发聚合。通过静电作用将带正电荷的VDAT聚合物(PVDAT)包覆于带负电荷的PS微球表面,成功合成PVDAT@PS功能微球。最后利用该功能微球对不同双链DNA的吸附,初步研究其在生物领域的应用。     

Metallic Conductive Nanowires Elaborated by PVD Metal Deposition on Suspended DNA Bundles

Metallic conductive nanowires (NWs) with DNA bundle core are achieved, thanks to an original process relying on double‐stranded DNA alignment and physical vapor deposition (PVD) metallization steps involving a silicon substrate. First, bundles of DNA are suspended with a repeatable process between 2 µm high parallel electrodes with separating gaps ranging from 800 nm to 2 µm. The process consists in the drop deposition of a DNA lambda‐phage solution on the electrodes followed by a naturally evaporation step. The deposition process is controlled by the DNA concentration within the buffer solution, the drop volume, and the electrode hydrophobicity. The suspended bundles are finally metallized with various thicknesses of titanium and gold by a PVD e‐beam evaporation process. The achieved NWs have a width ranging from a few nanometers up to 100 nm. The electrical behavior of the achieved 60 and 80 nm width metallic NWs is shown to be Ohmic and their intrinsic resistance is estimated according to different geometrical models of the NW section area. For the 80 nm width NWs, a resistance of about few ohms is established, opening exploration fields for applications in microelectronics.     

Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases MUTYH and hOGG1 in Colorectal Cancer Patients

Oxidative stress, oxidative DNA damage and resulting mutations play a role in colorectal carcinogenesis. Impaired equilibrium between DNA damage formation, antioxidant status, and DNA repair capacity is responsible for the accumulation of genetic mutations and genomic instability. The lesion-specific DNA glycosylases, e.g., hOGG1 and MUTYH, initiate the repair of oxidative DNA damage. Hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome) with germline mutations causing a loss-of-function in base excision repair glycosylases, serve as straight forward evidence on the role of oxidative DNA damage and its repair. Altered or inhibited function of above glycosylases result in an accumulation of oxidative DNA damage and contribute to the adenoma-adenocarcinoma transition. Oxidative DNA damage, unless repaired, often gives rise G:C > T:A mutations in tumor suppressor genes and proto-oncogenes with subsequent occurrence of chromosomal copy-neutral loss of heterozygosity. For instance, G>T transversions in position c.34 of a KRAS gene serves as a pre-screening tool for MUTYH-associated polyposis diagnosis. Since sporadic colorectal cancer represents more complex and heterogenous disease, the situation is more complicated. In the present study we focused on the roles of base excision repair glycosylases (hOGG1, MUTYH) in colorectal cancer patients by investigating tumor and adjacent mucosa tissues. Although we found downregulation of both glycosylases and significantly lower expression of hOGG1 in tumor tissues, accompanied with G>T mutations in KRAS gene, oxidative DNA damage and its repair cannot solely explain the onset of sporadic colorectal cancer. In this respect, other factors (especially microenvironment) per se or in combination with oxidative DNA damage warrant further attention. Base excision repair characteristics determined in colorectal cancer tissues and their association with disease prognosis have been discussed as well.     

Multiplexed-Based Assessment of DNA Damage Response to Chemotherapies Using Cell Imaging Cytometry

The current methods for measuring the DNA damage response (DDR) are relatively labor-intensive and usually based on Western blotting, flow cytometry, and/or confocal immunofluorescence analyses. They require many cells and are often limited to the assessment of a single or few proteins. Here, we used the Celigo^® image cytometer to evaluate the cell response to DNA-damaging agents based on a panel of biomarkers associated with the main DDR signaling pathways. We investigated the cytostatic or/and the cytotoxic effects of these drugs using simultaneous propidium iodide and calcein-AM staining. We also describe new dedicated multiplexed protocols to investigate the qualitative (phosphorylation) or the quantitative changes of eleven DDR markers (H2AX, DNA-PKcs, ATR, ATM, CHK1, CHK2, 53BP1, NBS1, RAD51, P53, P21). The results of our study clearly show the advantage of using this methodology because the multiplexed-based evaluation of these markers can be performed in a single experiment using the standard 384-well plate format. The analyses of multiple DDR markers together with the cell cycle status provide valuable insights into the mechanism of action of investigational drugs that induce DNA damage in a time- and cost-effective manner due to the low amounts of antibodies and reagents required.