Interaction of coxsackievirus A21 with its cellular receptor, ICAM-1

Coxsackievirus A21 (CAV21), like human rhinoviruses (HRVs), is a causative agent of the common cold. It uses the same cellular receptor, intercellular adhesion molecule 1 (ICAM-1), as does the major group of HRVs; unlike HRVs, however, it is stable at acid pH. The cryoelectron microscopy (cryoEM) image reconstruction of CAV21 is consistent with the highly homologous crystal structure of poliovirus 1; like other enteroviruses and HRVs, CAV21 has a canyon-like depression around each of the 12 fivefold vertices. A cryoEM reconstruction of CAV21 complexed with ICAM-1 shows all five domains of the extracellular component of ICAM-1. The known atomic structure of the ICAM-1 amino-terminal domains D1 and D2 has been fitted into the cryoEM density of the complex. The site of ICAM-1 binding within the canyon of CAV21 overlaps the site of receptor recognition utilized by rhinoviruses and polioviruses. Interactions within this common region may be essential for triggering viral destabilization after attachment to susceptible cells.     

Modeling and analysis of a predator-prey model with disease in the prey

A system of retarded functional differential equations is proposed as a predator-prey model with disease in the prey. Mathematical analyses of the model equations with regard to invariance of non-negativity, boundedness of solutions, nature of equilibria, permanence and global stability are analyzed. If the coefficient in conversing prey into predator k=k(0) is constant (independent of delay tau;, gestation period), we show that positive equilibrium is locally asymptotically stable when time delay tau; is suitable small, while a loss of stability by a Hopf bifurcation can occur as the delay increases. If k=k(0)e(-dtau;) (d is the death rate of predator), numerical simulation suggests that time delay has both destabilizing and stabilizing effects, that is, positive equilibrium, if it exists, will become stable again for large time delay. A concluding discussion is then presented.     

Crystal structure of Escherichia coli uracil DNA glycosylase and its complexes with uracil and glycerol: structure and glycosylase mechanism revisited

The DNA repair enzyme uracil DNA glycosylase (UDG) catalyzes the hydrolysis of premutagenic uracil residues from single-stranded or duplex DNA, producing free uracil and abasic DNA. Here we report the high-resolution crystal structures of free UDG from Escherichia coli strain B (1.60 A), its complex with uracil (1.50 A), and a second active-site complex with glycerol (1.43 A). These represent the first high-resolution structures of a prokaryotic UDG to be reported. The overall structure of the E. coli enzyme is more similar to the human UDG than the herpes virus enzyme. Significant differences between the bacterial and viral structures are seen in the side-chain positions of the putative general-acid (His187) and base (Asp64), similar to differences previously observed between the viral and human enzymes. In general, the active-site loop that contains His187 appears preorganized in comparison with the viral and human enzymes, requiring smaller substrate-induced conformational changes to bring active-site groups into catalytic position. These structural differences may be related to the large differences in the mechanism of uracil recognition used by the E. coli and viral enzymes. The pH dependence of k(cat) for wild-type UDG and the D64N and H187Q mutant enzymes is consistent with general-base catalysis by Asp64, but provides no evidence for a general-acid catalyst. The catalytic mechanism of UDG is critically discussed with respect to these results.     

肿瘤血管生成抑制剂的作用机制研究进展

肿瘤血管生成抑制剂批能破坏或抑制血管生成,有效地阻止肿瘤生长和转移的药物,可分为特异性和非特异性两大类。其作用机制主要有：（１）调控血管形成生长因子;（２）抑制基底膜降解;（３）影响信号转导通路;（４）调控细胞生长周期;（５）调控肿瘤机关基因。本文对其作用机制的进展作一综述。     

Comparison of Erysiphe cichoracearum and E. cruciferarum and a survey of 360 Arabidopsis thaliana accessions for resistance to these two powdery mildew pathogens

In previous work, UEA1 and UCSC1, two geographically distinct, powdery mildew isolates, were recognized for their ability to infect Arabidopsis thaliana. We have clarified the identity of these isolates by determining their host ranges, reexamining their morphology, and comparing their DNA sequences for the 5.8S ribosomal RNA and two flanking internal transcribed spacer sequences. These experiments confirm that UEA1 is a member of Erysiphe cruciferarum and that UCSC1 belongs to E. cichoracearum. Interactions of the two Erysiphe isolates with 360 A. thaliana accessions were examined to provide a comprehensive profile of naturally occurring powdery mildew resistance in this weedy species. The majority of A. thaliana accessions (213) were susceptible to both isolates. Among the accessions exhibiting some degree of resistance, most (84) responded differentially to UEA1 and UCSC1 and the remainder were resistant to both isolates. Notably, resistance to UCSC1 cosegregated with RPW7, a locus previously demonstrated to confer resistance to UEA1 in Ms-0 x Landsberg (erecta) crosses. With this large collection of resistant accessions, questions about species specificity, genetic diversity and the evolution of resistance to powdery mildews can be addressed.     

Numerical simulations of surface plasmon resonance system for monitoring DNA hybridization and detecting protein-lipid film interactions

This paper presents a simple method to extract information about thin organic films from surface plasmon resonance (SPR) spectra. From numerical simulations it was found that a shift (Δθ _SPR) of an absorption peak in the SPR spectrum was directly proportional to the product of the thin organic film thickness and the refractive index difference between the thin organic film and a buffer soaking the sample. It was also found that Δθ _SPR was not sensitive to the thin organic film support of a gold film and a glass cover slip. Relationships between Δθ _SPR and distributions of macromolecule structures, in the thin organic films were theoretically established. Formulae were derived for a homemade SPR system to calculate length, transverse area, density and surface concentration of macromolecules in the thin organic film. The validity of these treatments was checked by precisely measuring the size of a single distearoylphosphatidylcholine molecule on a gold-supported phospholipid film; by quantitatively monitoring hybridization of synthesized oligonucleotides strands based on a biotin/avidin system; and by quantitatively detecting the steric hindrance of rabbit C-reactive protein specifically bound to phospholipid monolayers composed of synthesized lipids. Received: 4 May 1998 / Revised version: 27 July 1998 / Accepted: 27 August 1998     

小鞘指环虫种群的聚集性研究

本文中建立了一个衡量聚集性的指标－聚集度Ａ,并用该指标结合方差／均数和负二项分布的参数ｋ值分析了小鞘指环虫（Ｄａｃｔｙｌｏｇｙｒｕｓｖａｇｉｎｕｌａｔｕｓ）种群在其宿主鲢（Ｈｙｐｏｐｈｔｈａｌｍｉｃｈｔｈｙｓｍｏｌｉｔｒｉｘ）种群中分布的聚集程度与感染率和丰度的关系。结果表明该虫种群的聚集程度随感染率及丰度的上升而呈现下降的特点,作为衡量聚集性的指标,聚集度要优于ｋ值,而后者又优于方差与均数之比,