High-affinity binding site for a specific nuclear protein in the human IgM gene

Proteins binding to specific regions of DNA with high affinity frequently govern or regulate reactions at the gene level. We have identified a high-affinity binding site in the immunoglobulin mu gene that binds a specific nuclear protein, and have now characterized it fully using nuclear factor 1 (NF-1), a protein purified from the nuclei of HeLa cells and required for the in vitro replication of adenovirus (Ad) DNA. NF-1 protects a 25-base pair (bp) double-stranded segment of DNA which shares a consensus sequence, 5' TGGA/CNNNNNGCCAA 3', with similar binding sites in the Ad-5 terminal repeat and the human c-myc gene. Although this site differs from the enhancer region, a biological function is suggested by the fact that it is DNase I hypersensitive in immunoglobulin-producing lymphoblastoid cells. The binding site for the NF-1 protein in the mu gene, by analogy with the site in the Ad-5 terminal repeat, may represent one component of a cellular origin of replication; alternatively, it may be responsible for the activation of the chromatin in this region.     

核电站结构地震动态响应并行计算研究

为了分析核电站复杂结构地震动态响应,以MPI作为基本并行编程环境,在LINUX操作系统下,开发了核电站结构地震动态响应的并行有限元计算程序。该程序采用黏弹性边界模拟外行波向远域地基的辐射,方程的求解采用时域显式解法,能够模拟包含各类静动荷载以及温度、接触等因素作用下的结构响应。经算例验证,该程序正确可靠。利用该程序对某核电站取水口建筑物进行了动态响应分析,并与ANSYS软件的分析进行比较,所花费时间从单机串行程序的20h40min减少到并行程序下的2h15min。结果证明,该并行程序具有较高的并行度以及良好的并行效率。     

Binding of the SARS-CoV-2 spike protein to glycans

The pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a high number of deaths in the world.To combat it,it is necessary to...     

Binding of disease-associated prion protein to plasminogen

Transmissible spongiform encephalopathies are associated with accumulation of PrP(Sc), a conformer of a cellular protein called PrP(C). PrP(Sc) is thought to replicate by imparting its conformation onto PrP(C) (ref. 1), yet conformational discrimination between PrP(C) and PrP(Sc) has remained elusive. Because deposition of PrP(Sc) alone is not enough to cause neuropathology, PrP(Sc) probably damages the brain by interacting with other cellular constituents. Here we find activities in human and mouse blood which bind PrP(Sc) and prion infectivity, but not PrP(C). We identify plasminogen, a pro-protease implicated in neuronal excitotoxicity, as a PrP(Sc)-binding protein. Binding is abolished if the conformation of PrP(Sc) is disrupted by 6M urea or guanidine. The isolated lysine binding site 1 of plasminogen (kringles I-III) retains this binding activity, and binding can be competed for with lysine. Therefore, plasminogen represents the first endogenous factor discriminating between normal and pathological prion protein. This unexpected property may be exploited for diagnostic purposes.     

Binding of yeast a1 and alpha 2 as a heterodimer to the operator DNA of a haploid-specific gene

The mating-type locus (MAT) encodes several DNA-binding proteins, which determine the three cell types of Saccharomyces cerevisiae: the a and alpha haploid cell types, and the a/alpha diploid cell type. One of the products of MAT, alpha 2, functions in two cell types. In alpha cells, alpha 2 represses the a-specific genes by binding to the operator as a dimer. In a/alpha diploid cells, alpha 2 acts with a1, a product of the other MAT allele, to repress a different set of genes, the haploid-specific genes. Until now, the nature of the interaction between a1 and alpha 2 was not known, although it had been suggested that alpha 2 may form a heterodimer with a1. I show, by using proteins synthesized in vitro, that a1 and alpha 2 bind the operator of a haploid-specific gene as a heterodimer. The ability of alpha 2 to form both homodimers and heterodimers with a1, each with a different DNA-binding specificity, explains the dual regulatory functions of alpha 2. This is the first example of regulation by heterodimerization among homeobox-containing proteins, a class that includes proteins responsible for the specification of segment identity in Drosophila, mammals and other eukaryotes.     

核电厂营运单位应急响应能力评估软件平台

 核电厂营运单位的应急响应能力是核电厂安全运营的重要保障。在核事故中,核电厂营运单位成功实施应急响应是缓解事故进程、控制事故后果,保护人类健康和环境安全的关键途径。因此,核电厂营运单位应急响应能力建设能否支持其成功应对核事故,已成为业界关注的重点。本文在核电厂营运单位应急响应能力评估方法的基础上,研发了核电厂营运单位应急响应能力评估软件平台,用于辅助核电厂营运单位应急响应能力评估方法的推广应用。结合已经形成的应急响应能力评估准则,分析了应急响应能力评估方法运用中的需求、提出的软件功能共含有7 项,包括用户管理、性能指标的计算与数据维护、检查发现的资料管理与评价结果呈现、内部管理流程、综合评价、电厂管理、评估准则和关注点管理,并介绍了功能的软件实现。     

The Caenorhabditis elegans heterochronic gene lin-14 encodes a nuclear protein that forms a temporal developmental switch

During wild-type development, a protein product of the Caenorhabditis elegans heterochronic gene lin-14 is localized to nuclei of specific somatic cells in embryos and early larvae, but is absent in late larvae and adult soma. Gain-of-function lin-14 mutations cause the level of lin-14 protein to remain high throughout development, resulting in developmental reiterations of early cell lineages. The normal down-regulation of the lin-14 nuclear protein level encodes a temporal switch between early and late cell fates.     

Application of a nuclear localization signal gene in transgene mice

Efficient gene transfer by cytoplasm co-injection will offer a powerful means for transgenic animals. Using co-injection in cytoplasm, two independent gene constructs, including bovine α-s1-casein-hG-CSF and a mammal expression vector expressing a nuclear localization signal (mNLS), were introduced into fertilized mouse eggs. The target gene construct was docked into host nucleus probably by the nuclear localization signal. Transgene mice have been obtained at 58% (29/50) of integration ratio. Expression level of the positive transgene mice was detected by Western blotting. Maximal expression of human G-CSF was estimated about 540 mg/L of milk. The expression ratio was up to 75% (9/12). The results here have important practical implications for the generation of mammary gland bioreactors and other transgene studies. Co-injection of a target gene with an expression vector of a mammal nuclear localization signal by cytoplasm appears to be a useful, efficient and easy strategy for generating transgenic animals, which may be able to substitute the routine method of pronucleus-injection of fertilized eggs.