Dependence of DNA helix flexibility on base composition

We have used triplet anisotropy decay techniques to study the flexibility of synthetic DNA fragments with different base pair compositions. We have found major differences in the torsional and bending stiffness of poly(dG) . poly(dC), poly(dA) . poly(dT) and poly(dA-dC) . poly(dT-dG). Poly(dG) . poly(dC) has a torsional modulus more than 40 times larger than poly(dA-dC) . poly(dT-dG), and approximately 20 times larger than poly(dA) . poly(dT). These differences imply that the torsional stiffness of DNA can vary greatly with base composition. The Young's modulus (bending stiffness) we have measured for poly(dG) . poly(dC) is at least twice that of poly(dA-dC) . poly(dT-dG) or random sequence DNA, and is at least threefold greater than that of poly(dA) . poly(dT). This implies that the bending stiffness of DNA is also strongly dependent on base composition. In light of this dramatic base composition dependence, we suggest here that such stiffness variation may lead to local variations in the stability of chromatin or other protein complexes that require bending or twisting of the DNA helix.     

Left-handed helical conformation of poly[d(A-m5C).d(G-T)

Poly[d(G-C)] serves as the prototype for the right-to-left (B to Z) transition in he helical sense of DNA, both in solution and inthe crystal form. However, the question remains as to which other synthetic and natural DNAs have the potential to adopt left-handed conformations. One logical candidate is the canonical alternating purine-pyrimidine sequence d(A-C)n.d(G-T)n which seems to be widely disseminated in eukaryotic genomes. Our approach to this question is based on the enzymatic synthesis of poly[d(A-C).d(G-U)] derivatives with systematic methyl and halogen substitutions in the C-5 position of the pyrimidines C and U. Such modifications in poly[d(G-C)] have previously been shown to potentiate the B to Z transition. Here we report a highly cooperative, reversible, salt- and temperature-dependent transition for poly[d(A-m5C).d(G-T)], a repeat of the d(A-m5C) sequence which may occur in natural DNA. Spectroscopic studies and the demonstrated ability to bind anti-Z-DNA antibodies suggest that the new helical conformation is left-handed and shares structural features with known Z-DNA. However, a novel property, not exhibited by poly[d(G-C)], is the profound temperature dependence of the conformational equilibrium.     

Study of-amyloid adsorption and aggregation on graphite by STM and AFM

Alzheimers disease is the major cause of dementia and the fourth leading cause of death in the developed world after heart disease, cancer and stroke. Pathologi-cally, one of major hallmarks of Alzheimers disease is the formation of insoluble deposits of -amyloid (A) both as diffuse and senile plaques in the brain tissue. The plaques are fibrous masses composed primarily of the 40-42 resi-due A peptides. The two most abundant forms of A are, respectively, the 40 and 42 residue peptide -amylo…     

Study of β—amyloid adsorption and aggregation on graphite by STM and AFM

The scanning tunneling microscopy(STM) and the atomic force microscopy(AMF) have been applied to the direct study of the adsorption and aggregation of β-amyloid(1-42)(Aβ42)on the hydrophobic graphite surface.It was found that Aβ42 were preferentially adsorbed on graphite defects such as the edges.Aβ42 peptides self-assembled into intermediate protofibrils,which in turn self-associated to form fibrils.Usually,two or more fibrils intertwined to form the helical structure.These results will provide an important clue to studying the aggregation process of β-amyloid.     

Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase

A functional immune system depends on the production of a wide range of immunoglobulin molecules. Immunoglobulin variable region (IgV) genes are diversified after gene rearrangement by hypermutation. In the DNA deamination model, we have proposed that deamination of dC residues to dU by activation-induced deaminase (AID) triggers this diversification. In hypermutating chicken DT40 B cells, most IgV mutations are dC --> dG/dA or dG --> dC/dT transversions, which are proposed to result from replication over sites of base loss produced by the excision activity of uracil-DNA glycosylase. Blocking the activity of uracil-DNA glycosylase should instead lead to replication over the dU lesion, resulting in dC --> dT (and dG --> dA) transitions. Here we show that expression in DT40 cells of a bacteriophage-encoded protein that inhibits uracil-DNA glycosylase shifts the pattern of IgV gene mutations from transversion dominance to transition dominance. This is good evidence that antibody diversification involves dC --> dU deamination within the immunoglobulin locus itself.     

Inactivation of the apoptosis effector Apaf-1 in malignant melanoma

Metastatic melanoma is a deadly cancer that fails to respond to conventional chemotherapy and is poorly understood at the molecular level. p53 mutations often occur in aggressive and chemoresistant cancers but are rarely observed in melanoma. Here we show that metastatic melanomas often lose Apaf-1, a cell-death effector that acts with cytochrome c and caspase-9 to mediate p53-dependent apoptosis. Loss of Apaf-1 expression is accompanied by allelic loss in metastatic melanomas, but can be recovered in melanoma cell lines by treatment with the methylation inhibitor 5-aza-2'-deoxycytidine (5aza2dC). Apaf-1-negative melanomas are invariably chemoresistant and are unable to execute a typical apoptotic programme in response to p53 activation. Restoring physiological levels of Apaf-1 through gene transfer or 5aza2dC treatment markedly enhances chemosensitivity and rescues the apoptotic defects associated with Apaf-1 loss. We conclude that Apaf-1 is inactivated in metastatic melanomas, which leads to defects in the execution of apoptotic cell death. Apaf-1 loss may contribute to the low frequency of p53 mutations observed in this highly chemoresistant tumour type.     

AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification

After gene rearrangement, immunoglobulin variable genes are diversified by somatic hypermutation or gene conversion, whereas the constant region is altered by class-switch recombination. All three processes depend on activation-induced cytidine deaminase (AID), a B-cell-specific protein that has been proposed (because of sequence homology) to function by RNA editing. But indications that the three gene diversification processes might be initiated by a common type of DNA lesion, together with the proposal that there is a first phase of hypermutation that targets dC/dG, suggested to us that AID may function directly at dC/dG pairs. Here we show that expression of AID in Escherichia coli gives a mutator phenotype that yields nucleotide transitions at dC/dG in a context-dependent manner. Mutation triggered by AID is enhanced by a deficiency of uracil-DNA glycosylase, which indicates that AID functions by deaminating dC residues in DNA. We propose that diversification of functional immunoglobulin genes is triggered by AID-mediated deamination of dC residues in the immunoglobulin locus with the outcome--that is, hypermutation phases 1 and 2, gene conversion or switch recombination--dependent on the way in which the initiating dU/dG lesion is resolved.     

扫描隧道显微镜畸变图象的校正

从扫描隧道显微镜（STM）的工作原理出发，分析了STM图象畸变产生的原因，建立了一种相应的物理数学模型，利用计算机通过数值解，校正了STM畸变图象，并得到了满意的效果。     

功率谱估计在扫描隧道显微术中的应用

扫描隧道显微镜(简称STM)所采集到的隧道电流信号,不仅包含着表征样品的表面形貌和分子结构的有效信号,而且还隐含着整个扫描隧道显微系统的动态特性.针对STM采集的信号,运用短时傅立叶变换对其波形数据进行功率谱密度估计,对信号在频率域中的特征向量加以提取.结果表明:基于谱空间的特征向量,准确地分辨出了工频在信号中的干扰,也能有效地解释和分析STM系统的动态特性,进而认为存在一小阻尼系统对信号施以影响;此外,分析的结果可以为STM扫描过程的控制,诊断以及扫描图像的重建和解释提供有力的理论指导.     

Self-assembly of 4-（amyloxy） cinnamic acid on HOPG and its photoinduced transformation： An STM study

With the development of the nanoscience and nanotechnology, scientists try to use single molecule to fabricate electronic device, and the so-called “bot- tom-up” technology was considered to be one of the effective methods, which constructs molecular el…     

扫描隧道显微镜的理论研究与应用

根据量子力学中的隧道效应,扫描隧道显微镜已研制成功,在此基础上发展形成了一系列扫描探针显微镜,在各个科学研究领域得到了广泛的应用.本文通过对AJ—I型扫描隧道显微镜的理论与应用研究的阐述,探讨了它在纳米科技的发展中的重要作用.     

表面修饰的金纳米粒子的制作及表征

通过硼氢化钠NaBH4还原金氯酸HAuCl4，成功地制作了羧酸酯表面修饰的金纳米粒子，并用丁二酸硫醇作为硫醇配体稳定剂，抑制了纳米粒子的进一步生长，这种方法有效地把粒径控制在纳米范围内并且粒径分布范围小，只需通过一次反应就可大量地制得1－20nm、具有量子效应的纳米料，用X射线衍射仪、透射式电子显微镜和隧道扫描显微镜对这些粒子进行了检测，证实了大量的粒子都是面心立方结构，硫醇配体在金粒子在表面由化学吸附形成一层单分子膜，隧道扫描显微镜观察到了这一层单分子膜。     

DDME分子在石墨(HOPG)表面吸附

用扫描隧道显微镜(STM)研究了用真空沉积法在高定向有序石墨(HOPG)上制备的1, 1dicyano-2, 2-(4-dimethylaminophenyl) ethylene(DDME)薄膜。DDME在石墨表面形成十分平整的分子柱状堆积二维有序结构。还观察到了随覆盖度降低转变成为其他二维有序结构,并对其形成机理进行了研究。     

色氨酸分子在石墨表面吸附的扫描隧道显微镜研究

用扫描隧道显微镜(STM)研究了室温下色氨酸分子(L-Tryptophane)在石墨(HOPG)表面的吸附行为。实验发现,在室温下色氨酸分子可以在石墨表面形成均匀的吸附层,并形成二维条状结构和二维单斜晶格两种有序结构。针对这2种结构给出了可能的吸附模型。这2种有序结构的形成原因被认为与相邻色氨酸分子侧链之间的π堆积相互作用有关。     

Structure of neurofilaments studied with scanning tunneling microscopy

Neurofilaments (NFs) were isolated from bovine spinal cord. The structure of purified NFs was studied by scanning tunneling microscopy (STM). The STM images showed that NF was composed of a long core filament and numerous sidearms flanking the rod regularly. The diameter of the rod was about 10 nm (10.2 ± 0.8 nm). Most of the sidearms were short and the distance between two adjacent sidearms was approximately 10 nm. There were some long sidearms between two proximal core filaments. The distance between two adjacent long sidearms was 21 nm. A three-quarter-staggered fashion of native NF structure was put forward.     

Carbon Nanotube Transistor with Short-Term Memory

Short-Term Memory(STM) is a primary capability of the human brain. Humans use STM to remember a small amount of information, like someone’s phone number, for a short period of time. Usually the duration of STM is less than 1 minute. Synapses, the connections between neurons, are of vital importance to memory in biological brains. For mimicking the memory function of synapses, Carbon Nanotube(CNT) networks based thinfilm transistors with Electric Double Layers(EDL) at the dielectric/channel interface were researched in this work.A response characteristic of pre-synaptic potential pulses on the gate electrode of this CNT synaptic transistor was shown remarkably similar to Excitatory Post-Synaptic Current(EPSC) of biological synapses. Also a multi-level modulatable STM of CNT synaptic transistors was investigated. Post-synaptic current was shown with tunable peak values, on-off ratio, and relaxation time.     

Radio-frequency scanning tunnelling microscopy

The scanning tunnelling microscope (STM) relies on localized electron tunnelling between a sharp probe tip and a conducting sample to attain atomic-scale spatial resolution. In the 25-year period since its invention, the STM has helped uncover a wealth of phenomena in diverse physical systems--ranging from semiconductors to superconductors to atomic and molecular nanosystems. A severe limitation in scanning tunnelling microscopy is the low temporal resolution, originating from the diminished high-frequency response of the tunnel current readout circuitry. Here we overcome this limitation by measuring the reflection from a resonant inductor-capacitor circuit in which the tunnel junction is embedded, and demonstrate electronic bandwidths as high as 10 MHz. This approximately 100-fold bandwidth improvement on the state of the art translates into fast surface topography as well as delicate measurements in mesoscopic electronics and mechanics. Broadband noise measurements across the tunnel junction using this radio-frequency STM have allowed us to perform thermometry at the nanometre scale. Furthermore, we have detected high-frequency mechanical motion with a sensitivity approaching approximately 15 fm Hz(-1/2). This sensitivity is on par with the highest available from nanoscale optical and electrical displacement detection techniques, and the radio-frequency STM is expected to be capable of quantum-limited position measurements.     

扫描隧道显微镜诱导吸附有甘氨酸的Cu(111)表面铜台阶的产生和运动

氨基酸是蛋白质的构成单元,它在金属表面的吸附为研究蛋白质同金属相互作用奠定了基础。吸附了氨基酸的金属表面会发生诸如重构改变或小面化等形貌的变化,但这些变化在吸附了氨基酸的全部金属表面都能够发生。在较大负偏压(|V_b|＞2.5V)的条件下使用扫描隧道显微镜(STM)扫描吸附有甘氨酸的Cu(111)表面,在扫描区域内原有铜台阶的形状发生了变化并产生了新的铜台阶。本文对甘氨酸在铜表面形貌变化中所起的作用进行了讨论。     

扫描隧道显微镜针尖的电化学腐蚀制备方法

本文利用电化学腐蚀方法设计并搭建了一种扫描隧道显微镜（ＳＴＭ）针尖制备的直流腐蚀电路。电路中使用了９０１３三极管和ＬＭ３１１快速比较器，使电解池切断时间低于５００ｎｓ。成功地制备了质量较高的钨针类。