催化剂分子设计专家系统中数据库和知识库的建立

从建造专家系统的理论体系出发，结合作者以前在计算机辅助催化剂分子设计方面所做的工作，确立了复合催化剂组分子设计专家系统的基本结构，并探讨了这一系统的任务功能、体系结构与支持界面、性质数据库与知识规则库的建立．以甲烷氧化偶联反应为例，说明了数据库的构成和领域知识的分类以及相应的知识表示技术．     

随机扰动下DNA三核苷酸重复序列的弯曲和柔性

利用统计力学模型讨论了与人类遗传病有关的DNA三核苷酸重复序列的弯曲和柔性,提出随机成动模型来近似表示DNA序列和蛋白质的相互作用,发现弯曲很小的三核苷重复序列在有随机扰动的情况下,可以出现大角度的弯曲,且随扰动强度的加大出现大角度弯曲的概率增加,求出了十二种三核苷重复序列的柔性及其长度依赖,发现当序列长度大于150 bp时,柔性的变化开始显,CTG和CGG具有最大的柔性,研究了柔性在有随机扰动时下的变化,发现在序列上不同位置施加扰动,柔性的变化程度不同,对于600bp长的序列,在390bp处的柔性变化程度最大。     

Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome

We show that haploinsufficiency of KANSL1 is sufficient to cause the 17q21.31 microdeletion syndrome, a multisystem disorder characterized by intellectual disability, hypotonia and distinctive facial features. The KANSL1 protein is an evolutionarily conserved regulator of the chromatin modifier KAT8, which influences gene expression through histone H4 lysine 16 (H4K16) acetylation. RNA sequencing studies in cell lines derived from affected individuals and the presence of learning deficits in Drosophila melanogaster mutants suggest a role for KANSL1 in neuronal processes.     

Aryl-hydrocarbon receptor-dependent alteration of FAK/RhoA in the inhibition of HUVEC motility by 3-methylcholanthrene

We previously demonstrated the antiproliferative and antiangiogenic effects of 3-methylcholanthrene (3MC), an aryl-hydrocarbon receptor (AhR) agonist, in human umbilical vascular endothelial cells (HUVECs). Herein, we unraveled its molecular mechanisms in inhibiting HUVEC motility. 3MC down-regulated FAK, but up-regulated RhoA, which was rescued by AhR knockdown. It led us to identify novel AhR binding sites in the FAK/RhoA promoters. Additionally, 3MC increased RhoA activity via suppression of a negative feedback pathway of FAK/p190RhoGAP. With an increase in membrane-bound RhoA, subsequent stress fiber and focal adhesion complex formation was observed in 3MC-treated cells, and this was reversed by a RhoA inhibitor and AhR antagonists. Notably, these compounds significantly reversed 3MC-mediated anti-migration in a transwell assay. The in vitro findings were further confirmed using an animal model of Matrigel formation in Balb/c mice. Collectively, AhR’s genomic regulation of FAK/RhoA, together with RhoA activation, is ascribable to the anti-migration effect of 3MC in HUVECs.     

Physiogenomic resources for rat models of heart, lung and blood disorders

Cardiovascular disorders are influenced by genetic and environmental factors. The TIGR rodent expression web-based resource (TREX) contains over 2,200 microarray hybridizations, involving over 800 animals from 18 different rat strains. These strains comprise genetically diverse parental animals and a panel of chromosomal substitution strains derived by introgressing individual chromosomes from normotensive Brown Norway (BN/NHsdMcwi) rats into the background of Dahl salt sensitive (SS/JrHsdMcwi) rats. The profiles document gene-expression changes in both genders, four tissues (heart, lung, liver, kidney) and two environmental conditions (normoxia, hypoxia). This translates into almost 400 high-quality direct comparisons (not including replicates) and over 100,000 pairwise comparisons. As each individual chromosomal substitution strain represents on average less than a 5% change from the parental genome, consomic strains provide a useful mechanism to dissect complex traits and identify causative genes. We performed a variety of data-mining manipulations on the profiles and used complementary physiological data from the PhysGen resource to demonstrate how TREX can be used by the cardiovascular community for hypothesis generation.     

Inhibition of Rho-associated kinase relieves C5a-induced proteinuria in murine nephrotic syndrome

Childhood nephrotic syndrome is mainly caused by minimal change disease which is named because only subtle ultrastructural alteration could be observed at electron microscopic level in the pathological kidney. Glomerular podocytes are presumed to be the target cells whose protein sieving capability is compromised by a yet unidentified permeability perturbing factor. In a cohort of children with non-hereditary idiopathic nephrotic syndrome, we found the complement fragment C5a was elevated in their sera during active disease. Administration of recombinant C5a induced profound proteinuria and minimal change nephrotic syndrome in mice. Purified glomerular endothelial cells, instead of podocytes, were demonstrated to be responsible for the proteinuric effect elicited by C5a. Further studies depicted a signaling pathway involving Rho/Rho-associated kinase/myosin activation leading to endothelial cell contraction and cell adhesion complex breakdown. Significantly, application of Rho-associated kinase inhibitor, Y27632, prevented the protein leaking effects observed in both C5a-treated purified endothelial cells and mice. Taken together, our study identifies a previously unknown mechanism underlying nephrotic syndrome and provides a new insight toward identifying Rho-associated kinase inhibition as an alternative therapeutic option for nephrotic syndrome.     

铑催化剂上CO的吸附态及其加氢反应

用红外光谱法测定表明：各种硅胶负载仲进型铑催化剂上，线ＣＯ／桥ＣＯ红外吸收强度比值与金属助剂（Ｍ）的关系变化顺序为（５０：１）（Ｒｈ－Ｍｎ）〉（２２：１）（Ｒｈ－Ｌｉ）〉（９．１：１）（Ｒｈ－Ｍｎ－Ｆｅ－Ｌｉ）〉（３．５：１）（Ｒｈ－Ｆｅ）〉２．８：１）（Ｒｈ）。在各种Ｒｈ－Ｍ／ＳｉＯ２催化剂上，线、桥ＣＯ吸附态的加氢原位ＦＴＩＲ跟踪实验表明：随着加氢的进行，线ＣＯ／桥ＣＯ吸收强度比值均逐渐减少…     

改进型铜基甲醇合成催化剂的制备研究

在三组分铜基催化剂Ｃｕ－Ｚｎ－Ａｌ中添加少量第四组分金属氧化物助剂ＭＯ＿ｘ，制得改进型四组分铜基甲醇合成催化剂Ｃｕ－Ｚｎ－Ａｌ－Ｍ（ＸＨ４０２）；５．０ＭＰａ压力下的活性评价结果表明ＸＨ４０２催化剂合成甲醇时空得率比工业甲醇合成催化剂Ｃ３０１提高２５％。催化剂的ＸＲＤ表征显示，工作态ＸＨ４０２催化剂的活性相特征峰２θ＝４３．３２°的强度比Ｃ３０１的提高约３０％。