Crystallization and preliminary X-ray crystallographic analysis of spruce budworm antifreeze protein.

Antifreeze proteins have the ability to bind to ice with high affinity and inhibit further crystal growth. The insect antifreeze protein from spruce budworm exhibits very high thermal hysteresis activity and is implicated in the protection of overwintering larvae from freezing. This protein has been crystallized in 20-25% polyethylene glycol (Mr 6000), 0.4 M NaCl, 0.1 M Tris-HCl, pH 8.5, by vapor diffusion using the hanging drop method. The resulting crystals are very thin (typically <0.01 mm in the shortest dimension), and only after repeated seeding could crystals be grown large enough for data collection using synchrotron radiation. The crystals belong to the monoclinic space group C2, with cell dimensions a = 82.28 A, b = 62.29 A, c = 63.63 A, and beta = 113.7 degrees. Molecules in the asymmetric unit are related by a twofold axis of symmetry with two molecules present. Native data to a resolution of 2.6 A have been collected with 90.3% completeness and a Rsym of 6.9%.     

The role of GSK3beta in the development of the central nervous system

Glycogen synthase kinase 3β (GSK3β) is a multifunctional serine/threonine kinase.It is particularly abundant in the developing central nervous system (CNS).Since GSK3β has diverse substrates ranging fr...     

切应力对内皮细胞膜微粘度的影响

目的：研究切应力对内皮细胞（EC）膜微粘度的影响。材料和方法：将EC置于脉动循环装置中,分别施加15dyne/cm^2,50dyne/cm^2,30Odyne/cm^2切应力,作用Oh,1h,2h,4h,6h,10h后,利用带偏振器的荧光分光光度计测量膜微粘度,结果：切应力使膜微粘度增加,且切应力越高,膜微粘度增加幅度越大。切应力作用4h,EC膜微粘度升至最高,4h-10h,膜微粘度开始缓慢恢复,但仍比静态对照显著升高,结论：在切应力作用下,EC膜微粘度增加,切应力是AS的致病因素,动脉狭窄处和大中动脉分叉处是AS好发的危险部位,也是防治的重点。     

Peptide models of four possible insulin folding intermediates with two disulfides

The single-chain insulin (PIP) can spontaneously fold into native structure through preferred kinetic intermediates. During refolding, pairing of the first disulfide A20-B19 is highly specific, whereas pairing of the second disulfide is likely random because two two-disulfide intermediates have been trapped. To get more details of pairing property of the second disulfide, four model peptides of possible folding intermediates with two disulfides were prepared by protein engineering, and their properties were analyzed. The four model peptides were named [A20-B19, A7-B7]PIP, [A20-B19, A6-B7]PIP, [A20-B19, A6-A11]PIP, and [A20-B19, A7-A11]PIP according to their remaining disulfides. The four model peptides all adopt partially folded structure with moderate conformational differences. In redox buffer, the disulfides of the model peptides are more easily reduced than those of the wild-type PIP. During in vitro refolding, the reduced model peptides share similar relative folding rates but different folding yields: The refolding efficiency of the reduced [A20-B19, A7-A11]PIP is about threefold lower than that of the other three peptides. The present results indicate that the folding intermediates corresponding to the present model peptides all adopt partially folded conformation, and can be formed during PIP refolding, but the chance of forming the intermediate with disulfide [A20-B19, A7-A11] is much lower than that of forming the other three intermediates.     

中药调节肠道菌群防治高血压的研究进展

肠道菌群是人体内环境的重要组成部分,可影响机体的代谢、免疫和炎症反应,与原发性高血压的发生发展密切相关,已成为防治高血压的研究热点。中药在临床用于原发性高血压的治疗且疗效显著。研究表明中药可被肠道菌群分解代谢为易于吸收的活性物质,而这些活性物质又可通过调节肠道菌群结构及其代谢产物防治高血压。本文以肠道菌群作为切入点,通过分析肠道菌群与原发性高血压发生发展的关系和中药在调节原发性高血压肠道菌群方面的研究,总结中药通过调节肠道菌群防治原发性高血压的作用和机制,以期为中药防治高血压及药物研发提供新的研究思路。     

Identification,Design and Bio-Evaluation of Novel Hsp90 Inhibitors by Ligand-Based Virtual Screening

Heat shock protein 90 (Hsp90), whose inhibitors have shown promising activity in clinical trials, is an attractive anticancer target. In this work, we first explored the significant pharmacophore features needed for Hsp90 inhibitors by generating a 3D-QSAR pharmacophore model. It was then used to virtually screen the SPECS databases, identifying 17 hits. Compound S1 and S13 exhibited the most potent inhibitory activity against Hsp90, with IC₅₀ value 1.61±0.28 μM and 2.83±0.67 μM, respectively. Binding patterns analysis of the two compounds with Hsp90 revealed reasonable interaction modes. Further evaluation showed that the compounds exhibited good anti-proliferative effects against a series of cancer cell lines with high expression level of Hsp90. Meanwhile, S13 induced cell apoptosis in a dose-dependent manner in different cell lines. Based on the consideration of binding affinities, physicochemical properties and toxicities, 24 derivatives of S13 were designed, leading to the more promising compound S40, which deserves further optimization.     

Taxonomy and phylogeny of Ceriporia (Polyporales,Basidiomycota) with an emphasis of Chinese collections

Ceriporia accommodates a kind of wood-inhabiting polypores producing resupinate basidiocarps and causing a white rot. More than 30 species of this genus have been described; however, only a few species were referred to molecular phylogeny. In this study, a total of 203 specimens of Ceriporia were studied morphologically, and the ITS and/or nLSU regions from 42 samples, representing 18 species, were sequenced for phylogenetic analysis. Based on both morphological and phylogenetic analyses, three new species of Ceriporia, C. bubalinomarginata, C. pseudocystidiata and C. variegata, are described and illustrated. An annotated identification key is provided for all 20 species of this genus thus far known in China. Our phylogeny shows that (1) Ceriporia is not monophyletic, (2) C. spissa and C. viridans as morphologically circumscribed are polyphyletic, (3) C. inflata is retained for both C. inflata and C. jiangxiensis, and (4) presence or absence of hymenial cystidia is not a useful character in delimiting species relationships in Ceriporia.