自调节遗传算法的研究

通过对普通遗传算法选择，交叉，变异三个算子的深入分析，揭示了早熟现象产生的原因，并数学证明了选择算子是早熟现象的主要原因，在此基础上设计了一种变异概率可以自调节的基因移民遗传算法，提出了群体相异度指标来衡量多样性，通过相异度的自动地调节变异概率的大小，确保群体的多样性来避免早熟现象的出现，最后，应用马尔可夫链数学工具从理论上证明了该算法是收敛的，实验表明：该算法具有一定的通用性，适合于实际的工程计算。     

新基因ZNF325在人类早期胚胎中的表达

锌指蛋白基因家族是人类最大的基因家族之一，目前已知的很多转录调控因子都是锌指蛋白成员^[1]。初步克隆了一个与RBAK基因有着高度同源性的人类C2H2型锌指蛋白新基因，经国际基因命名委员会批准命名为ZNF325，此基因位于染色体7p22，长2697个碱基，含5个外显子，在基因组DNA上长15kb。它编码的蛋白质全长462个氨基酸，含15个C2H2型的锌指。Northern Bolt分析表明该基因在人类早期胚胎的各个组织中普遍表达，在肺和脑中的表达水平最强，但在肝中的表达随着胚胎的发育而逐渐减少。它的结构和表达特征预示着它编码的是一个具DNA结合功能的转录调控因子。     

关于等位基因型选择中的配子频率变化规律

本文讨论了随机交配群体在链锁条件下,各种基因型出现选择时的频率变化的规律。     

长白蝮蛇类凝血酶基因(Ussurase)的克隆及分析（英文）

从长白蝮蛇（Agkistrodon halys Ussuriensis）毒腺中抽提总RNA,采用RT-PCR扩增其类凝血酶基因,经全序列测定,类凝血酶基因ussurase全长为699个核苷酸,即编码233个氨基酸;根据同源性,推测它的活性中心为His40,Asp85和Ser179;二硫键为Cys7-Cys138,Cys25-Cys41,Cys73-Cys231,Cys117-Cys185,Cys149-Cys164和Cys175-Cys200。该蛇毒类凝血酶cDNA序列及推导的氨基酸序列均为首次报道。     

Where, when and how much: regulation of myelin proteolipid protein gene expression

The myelin proteolipid protein (PLP) gene (Plp) encodes the most abundant protein found in myelin from the central nervous system (CNS). Expression of the gene is regulated in a spatiotemporal manner with maximal levels of expression occurring in oligodendrocytes during the active myelination period of CNS development, although other cell types in the CNS as well as in the periphery can express the gene to a much lower degree. In oligodendrocytes, Plp gene expression is tightly regulated. Underexpression or overexpression of the gene has been shown to have adverse effects in humans and other vertebrates. In light of this strict control, this review provides an overview of the current knowledge of Plp gene regulation.Received 4 August 2003; received after revision 17 September 2003; accepted 24 September 2003     

The genomic basis of the Williams – Beuren syndrome

The Williams-Beuren syndrome is a genomic disorder (prevalence: 1/7,500 to 1/20,000), caused by a hemizygous contiguous gene deletion on chromosome 7q11.23. Typical symptoms comprise supravalvular aortic stenosis, mental retardation, overfriendliness and visuospatial impairment. The common deletion sizes range of 1.5–1.8 mega base pairs (Mb), encompassing app. 28 genes. For a few genes, a genotype-phenotype correlation has been established. The best-explored gene within this region is the elastin gene; its haploinsufficiency causes arterial stenosis. The region of the Williams-Beuren syndrome consists of a single copy gene region (~1.2 Mb) flanked by repetitive sequences – Low Copy Repeats (LCR). The deletions arise as a consequence of misalignment of these repetitive sequences during meiosis and a following unequal crossing over due to high similarity of LCRs. This review presents an overview of the Williams-Beuren syndrome region considering the genomic assembly, chromosomal rearrangements and their mechanisms (i.e. deletions, duplications, inversions) and evolutionary and historical aspects. Received 11 July 2008; received after revision 15 October 2008; accepted 16 October 2008     

Porcine factor V: cDNA cloning, gene mapping, three-dimensional protein modeling of membrane binding sites and comparative anatomy of domains

Factor V is a plasma protein essential for blood coagulation. This protein is involved in activated protein C resistance, the most common inherited thrombotic disorder known. We utilized the polymerase chain reaction to clone the porcine factor V gene by generating overlapping clones amplified with primers chosen by comparison with known nucleotide sequences. The porcine factor V cDNA contig encodes a predicted 2258-amino acid protein, making it the largest in comparison to the bovine, human, and murine proteins. Porcine factor V has the highest level of homology with bovine factor V, but also has high levels of conservation of important residues with all the species. Radiation hybrid mapping assigned the porcine factor V gene to chromosome 4. Three-dimensional models of factor V were generated and used to analyze membrane-binding sites in terms of conserved, and therefore likely important residues. Received 3 October 2000; revised 23 November 2000; accepted 6 December 2000     

Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines

In the context of developing a safe genetic vaccination strategy we tested and studied globin-stabilized mRNA-based vaccination in mice. This vaccination strategy has the advantages of genetic vaccination (easy production, adaptability to any disease and inexpensive storage when lyophilized), but not the drawbacks of DNA vaccination (long-term uncontrolled expression of a transgene, possibility of integration into the host genome and possible induction of anti-DNA antibodies). We report here that injection of naked -globin untranslated region (UTR)-stabilized mRNA coding for -galactosidase is followed by detectable translation in vivo. In addition, we show that such a vaccination strategy primes a T helper 2 (Th2) type of response which can be enhanced and shifted to a Th1-type immune response by application of recombinant granulocyte/macrophage colony-stimulating factor 1 day after mRNA injection. Our data demonstrate that the administration of globin UTR-stabilized mRNA is a versatile vaccination strategy that can be manipulated to fit the requirement of antiviral, antibacterial or antitumor immunity.Received 14 June 2004; received after revision 19 July 2004; accepted 9 August 2004     

Cholera toxin structure, gene regulation and pathophysiological and immunological aspects

Many notions regarding the function, structure and regulation of cholera toxin expression have remained essentially unaltered in the last 15 years. At the same time, recent findings have generated additional perspectives. For example, the cholera toxin genes are now known to be carried by a non-lytic bacteriophage, a previously unsuspected condition. Understanding of how the expression of cholera toxin genes is controlled by the bacterium at the molecular level has advanced significantly and relationships with cell-density-associated (quorum-sensing) responses have recently been discovered. Regarding the cell intoxication process, the mode of entry and intracellular transport of cholera toxin are becoming clearer. In the immunological field, the strong oral immunogenicity of the non-toxic B subunit of cholera toxin (CTB) has been exploited in the development of a now widely licensed oral cholera vaccine. Additionally, CTB has been shown to induce tolerance against co-administered (linked) foreign antigens in some autoimmune and allergic diseases. Received 25 October 2007; accepted 12 December 2007     

Mechanisms of sperm-egg interactions emerging from gene-manipulated animals

Untangling the molecular nature of sperm-egg interactions is fundamental if we are to understand fertilization. These phenomena have been studied for many years using biochemical approaches such as antibodies and ligands that interact with sperm or with eggs and their vestments. However, when homologous genetic recombination techniques were applied, most of the phenotypic factors of the gene-manipulated animals believed “essential” for fertilization were found to be dispensable. Of course, all biological systems contain redundancies and compensatory mechanisms, but as a whole the old model of fertilization clearly requires significant modification. In this review, we use the results of gene manipulation experiments in animals to propose the basis for a new vision. Received 26 January 2007; received after revision 7 March 2007; accepted 17 April 2007