Biosynthesis of selenosubtilisin: A novel way to target selenium into the active site of subtilisin

Glutathione peroxidase （GPx, EC1.11.1.9）, an important anti-oxidative selenoenzyme, can catalyze the reduction of harmful hydroperoxides with concomitant glutathione, thereby protecting cells and other biological issues against oxidative damage. It captures considerable interest in redesign of its function for either the mechanism study or the pharmacological development as an antioxidant. In order to develop a general strategy for specifically targeting and operating selenium in active sites of enzymes, the catalytically essential residue selenocysteine （Sec） was first successfully bioincorporated into the catalytic center of subtilisin by using an auxotrophic expression system. The studies of the catalytic activity and the steady-state kinetics demonstrated that selenosubtilisin is an excellent GPx-like biocatalyst. In comparison with the chemically modified method, biosynthesis exhibits obvious advantages： Sec could be site-directly incorporated into active sites of enzymes to overcome the non-specificity generated by chemical modification. This study provides an important strategy for specifically targeting and operating selenium in the active site of an enzyme.     

Hopf bifurcation and chaos of financial system on condition of specific combination of parameters*

Exponential stability of the first order singular distributed parameter systems is discussed in the light of degenerate semi-group methods, which is described by the abstract developing equation in Hilbert space. The necessary and sufficient conditions concerning the exponential stability of the first order singular distributed parameter systems are given.     

STRATEGIC EXERCISE OF REAL OPTIONS：INVESTMENT DECISIONS IN TECHNOLOGICAL SYSTEMS

Viewing investment projects in new technologies as real options, this paper studies the effects ofendogenous competition and asymmetric information on the strategic exercise of real options. We firstdevelop a multi-period, game-theoretic model and show how competition leads to early exercise andaggressive investment behaviors and how competition erodes option values. We then relax the typicalfull-information assumption found in the literature and allow information asymmetry to exist acrossfirms. Our model shows, in contrast to the literature that payoff is independent of the ordering ofexercise, that the sequential exercise of real options may generate both informational and payoffexternalities. We also find some surpising but interesting results such as having more information isnot necessarily better.     

可微函数鞍点识别的条件

列举了Ｗｉｓｍｅｒ等人所给的鞍点识别充分条件的反例，并给出了正确的鞍点识别条件。     

砼裂纹分析及防治

砼工程中出现裂纹是典型的质量通病，砼裂纹不仅减少砼结构的使用寿命，而且给人们一种观外上的危险感，实践证明，只要严格按施工规范施工，抓好每一道工序质量，完全可以避免砼裂纹的产生，论述了砼裂纹产生的原因和机理，提出了有效的防治措施。     

BOTTLENECKS IN PRODUCTION NETWORKS： AN OVERVIEW

1. Introduction Performances of a production system, such as the throughput, the circle time and the average delay, etc., are affected by the capacities of machines and resources available in the system. Some of them may affect the system performances more than others. Usually, the limitation of a system can be traced to the limitation of one or two machines or one or two kinds of resources, commonly called bottlenecks. From system point of view, bottlenecks are the congestion points of the sy…     

Epigenome analyses using BAC microarrays identify evolutionary conservation of tissue-specific methylation of SHANK3

CpG islands are present in one-half of all human and mouse genes and typically overlap with promoters or exons. We developed a method for high-resolution analysis of the methylation status of CpG islands genome-wide, using arrays of BAC clones and the methylation-sensitive restriction enzyme NotI. Here we demonstrate the accuracy and specificity of the method. By computationally mapping all NotI sites, methylation events can be defined with single-nucleotide precision throughout the genome. We also demonstrate the unique expandability of the array method using a different methylation-sensitive restriction enzyme, BssHII. We identified and validated new CpG island loci that are methylated in a tissue-specific manner in normal human tissues. The methylation status of the CpG islands is associated with gene expression for several genes, including SHANK3, which encodes a structural protein in neuronal postsynaptic densities. Defects in SHANK3 seem to underlie human 22q13 deletion syndrome. Furthermore, these patterns for SHANK3 are conserved in mice and rats.     

带时变时滞的不确定离散奇异系统鲁棒稳定性分析

为了降低不确定离散奇异时变时滞系统稳定性条件的保守性,首先,采用时滞分割方法,获得了新的时滞系统描述方法,并通过综合考虑各时滞分割子区间,提出了分割子区间依赖型Lyapunov函数.其次,采用时滞依赖线性矩阵不等式技术,将研究结果描述成易于求解的严格线性矩阵不等式形式.通过Matlab工具箱求解线性矩阵不等式,即可获得标称系统正则、因果及均方稳定的条件,并将标称系统的研究结果推广至不确定离散奇异时变时滞系统的稳定性分析,获得了不确定离散奇异时变时滞系统鲁棒稳定判定条件.最后通过实例应用说明了所提定理的有效性,且与现有文献结果相比,保守性得到了较大程度的降低.     

ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner

R-spondin proteins strongly potentiate Wnt signalling and function as stem-cell growth factors. Despite the biological and therapeutic significance, the molecular mechanism of R-spondin action remains unclear. Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. Inhibition of ZNRF3 enhances Wnt/β-catenin signalling and disrupts Wnt/planar cell polarity signalling in vivo. Notably, R-spondin mimics ZNRF3 inhibition by increasing the membrane level of Wnt receptors. Mechanistically, R-spondin interacts with the extracellular domain of ZNRF3 and induces the association between ZNRF3 and LGR4, which results in membrane clearance of ZNRF3. These data suggest that R-spondin enhances Wnt signalling by inhibiting ZNRF3. Our study provides new mechanistic insights into the regulation of Wnt receptor turnover, and reveals ZNRF3 as a tractable target for therapeutic exploration.