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Cell Research 2001年第3期11卷 217-222页

作者： LU FANG, JIA FANG, CHANG QING CHEN shanghai Research center of Biotechnology, shanghai institutes for biological sciences the chinese academy of sciences, shanghai 200233, china 1shanghai Research center of Biotechnology Shanghai Institutes for Biological Sciences the Chinese Academy of Sciences Shanghai 200233 China. 1shanghai Research center of Biotechnology Shanghai Institutes for Biological Sciences the Chinese Academy of Sciences Shanghai 200233 China. 1shanghai Research center of Biotechnology Shanghai Institutes for Biological Sciences the Chinese Academy of Sciences Shanghai 200233 China.

TNF recepter-55 is the main mediator of TNF-induced apoptosis. TNF receptor-75-dependent induction or enhancement of cytotoxicity has been explained by intracellular signaling, 'ligand passing' , or induction of endogenous TNF. To study the function of human TNF receptor-75 (hTR75) and the interaction between human TNF receptor-55 (hTR55) and hTR75 in hTNFa-induced cytotoxicity, HEp-2 cells were transfected with bicistronic expression vector of hTR75 and its deletion mutants genes. hTNFa-induced cytotoxicity was determined by crystal violet colorimetric method. The expression of hTR75 and its deletion mutants in HEp-2 cells was demonstrated by RT-PCR and indirect ELISA. We found that the overexpressed hTR75 could significantly increase the susceptibility of HEp-2 cells to hTNFa which especially required TRAF2 binding site. hTR75 could not only mediate partial hTNFa-induced cytotoxicity independently but also fulfill an accessory role in enhancing or synergizing hTR55-mediated cytotoxicity

关键词： hTNFa hTNF receptors TRAF2 cytotoxcity signal transduction.

Functional analysis of schistosomes EF-hand domain-containing tegument proteins

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chinese Science Bulletin 2007年第15期52卷 2100-2107页

作者： YU FuDong1,2,3,KANG Bin1,3,LI YuanYuan3,4 & LI YiXue1,3 1 Bioinformatics center,Key Laboratory of Systems Biology,shanghai institutes for biological sciences,chinese academy of Sci-ences,shanghai 2.0031,china 2 Graduate University of chinese academy of sciences,shanghai 2.0031,china 3 shanghai center for bioinformation Technology,shanghai 200235,china 4 Key Laboratory of Systems Biology,shanghai institutes for biological sciences,chinese academy of sciences,shanghai 2.0031,china Bioinformatics center Key Laboratory of Systems Biology Shanghai Institutesfor Biological Sciences Chinese Academy of Sciences Shanghai 200031 China

Schistosomes cause schistosomiasis disease which severely threatens human health. Little is known about the functions of EF-hand domain containing schistosomes tegument proteins other than as an-tigens. More possible functions of these tegument proteins were investigated with in silico analyses including protein-protein functional interaction,site-specific variation and glycosylation modification. The analysis results suggested that schistosomes could actively modulate host immune responses for its own favor through functional interactions with host proteins with immunomodulatory function,and passively regulate host immune responses through sequence variation under positive selection and glycosylating the recognition sites of host immune attack. In addition,the analysis of the C-terminal domain of these tegument proteins indicated that they could assist schistosomes in escaping host immune attacks through inhibiting chemotaxis and non-complement fixing antibody (IgG4) responses. In summary,our results suggested that these tegument antigen proteins could assist schistosomes in escaping and modulating host immune responses for self-protection during the process of host-para-site interaction.

关键词：寄生虫血吸虫皮蛋白质健康

Semantic Search among Heterogeneous biological Databases Based on Gene Ontology

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Acta Biochimica et Biophysica Sinica 2004年第5期36卷 365-370页

作者： Shun-Liang CAO, Lei QIN1, Wei-Zhong HE1, Yang ZHONG2, Yang-Yong ZHU, and Yi-Xue LI1,3* Department of Computing and Information Technology, Fudan University, shanghai 200433, china shanghai center for bioinformation 1 Technology, shanghai 200235, china School of Life sciences, Fudan University, shanghai 200433, china bioinformation center of shanghai institutes for biological sciences, the chinese academy of sciences, shanghai 2.0031, china Department of Computing and Information Technology Fudan University Shanghai China

Semantic search is a key issue in integration of heterogeneous biological databases. In this paper, we present a methodology for implementing semantic search in BioDW, an integrated biological data warehouse. Two tables are presented: the DB2GO table to correlate Gene Ontology (GO) annotated entries from BioDW data sources with GO, and the semantic similarity table to record similarity scores derived from any pair of GO terms. Based on the two tables, multifarious ways for semantic search are provided and the corresponding entries in heterogeneous biological databases in semantic terms can be expediently searched.

关键词： Gene Ontology semantic search BioDW

Association between Alcohol, Smoking and HLA-DQA1*0201 Genotype in Psoriasis

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Acta Biochimica et Biophysica Sinica 2004年第9期36卷 597-602页

作者： Guang-Yong ZHENG1,2#, Sheng-Cai WEI3#, Tie-Liu SHI1, and Yi-Xue LI1* 1Bioinformatics center, shanghai institutes for biological sciences, chinese academy of sciences, Graduate School of the chinese academy of sciences, shanghai 2.0031, china Research center for Proteome Analysis, Institute of Biochemistry and Cell Biology, shanghai institutes for biological sciences, chinese academy of sciences, Graduate School of the chinese academy of sciences, shanghai 2.0031, china 3Guangzhou Institute of Dermatology, Guangzhou 510095, china Bioinformatics center Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences

Psoriasis is a chronic skin disease triggered by genetic, environment or other risk factors such as infection, drugs, stress, moisture, alcohol, and smoking. A major psoriasis susceptibility locus at 6p21.3 has been identified. Further studies found that HLA-DQA1*0201 allele was associated with psoriasis. However, there were few data exploring an association between the environmental factors and susceptibility genes. In this study, the samples of 189 patients with psoriasis and 333 healthy controls were collected with their consent and were carried on analysis through polymerase chain reaction sequence-specific primer (PCR- SSP) method. The proportion of male psoriasis patients engaging in the smoking and alcohol was much higher than that of the control group (P6.91, P<1.0×10–4).

关键词： psoriasis HLA-DQA1*0201 allele smoking alcohol association

Recombinant scFv Antibodies against E Protein and N Protein of Severe Acute Respiratory Syndrome Virus

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Acta Biochimica et Biophysica Sinica 2004年第8期36卷 541-547页

作者： Hui LIU , Yan-Li DING, Wei HAN, Mei-Yun LIU, Rui-Yang TIAN, Sheng-Li YANG, and Yi GONGshanghai Research center of Biotechnology, shanghai institutes of biological sciences, chinese academy of sciences,Graduate School of the chinese academy of sciences, shanghai 200233, china shanghai Research center of Biotechnology Shanghai Institutes of Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences Shanghai 200233 China. huiliu@***

Three single chain antibodies (scFv) against the proteins of severe acute respiratory syndrome coronavirus (SARS-CoV) were isolated by phage display from an scFv antibody library. Bio-panning was carried out against immobilized purified envelope (E) and nucleocapsid (N) proteins of SARS-CoV. Their binding activity and specificity to E or N protein of SARS-CoV were characterized by phage-ELISA. Two of them, B10 and C20, could recognize non-overlapping epitopes of the E protein according to the two-site binding test result. Clone A17 could recognize N protein. The sequence of the epitope or overlapping epitope of scFv antibody A17 was PTDSTDNNQNGGRNGARPKQRRPQ. The affinity (equilibrium dissociation constant, Kd) of SARS-CoV E protein was 5.7×10–8 M for B10 and 8.9×10–8 M for C20. The affinity of A17 for N protein was 2.1×10–6 M. All three scFv antibodies were purified with affinity chromatography and determined by Western blot.

关键词： SARS-CoV antibody scFv phage display affinity chromatography

Sequence analysis of mRNA polyadenylation signals of rice genes

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chinese Science Bulletin 2006年第9期51卷 1069-1077页

作者： LU Ying1, 2, GAO Chenxi1,2,3 & HAN Bin1,3,41. National center for Gene Research, shanghai institutes for biological sciences, chinese academy of sciences, shanghai 200233, china 2. Graduate School of the chinese academy of sciences, Beijing 100039, china 3. Institute of Plant Physiology and Ecology, shanghai institutes for biological sciences, chinese academy of sciences, shanghai 200032, china National center for Gene Research Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200233 China Graduate School of the chinese academy of sciences Beijing 100039 China Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200032 China

The formation of eukaryotic mRNAs involves the cleavage and polyadenylation of pre- mRNAs. To investigate the sequence requirement of putative polyadenylation signals (PASs), poly(A) sites and downstream elements (DUEs) in 3′-end-pro- cessing in rice, we compared expressed sequences tags (ESTs) with poly(A) extremity to full-length cDNA sequences and constructed a database of 12969 pre- mRNA sequences in ?40―+40 nt surrounding the poly(A) sites, which were from 9953 genes. The al- ternative poly(A) sites were revealed in approxi- mately 25% of mRNAs. Nearly 80% of pre-mRNAs showed stringent requirement of the YA (CA or UA) at poly (A) sites for polyadenylation. About 7.9% had the AAUAAA signals on ?40―?1 nt upstream of the poly(A) sites. Over 60% of mRNAs probably used the one- or two-base variants of AAUAAA hexamers as their PASs in 3′ fragments. The single-base variants of AAUGAA revealed the high frequency in 11.5% of 3′ fragments. The DUEs were detected in 90% of pre- mRNAs, especially more than half of the pre-mRNAs with multi-base variants of AAUAAA had the DUEs surrounding the poly(A) site. The location of DUE is also important for defining the cleavage site. Al- though most of the rice pre-mRNAs did not contain AAUAAA signal, the existence of downstream ele- ments ensured the efficiency of cleavage-polyade-

关键词：多聚腺苷酸序列分析 mRNA 水稻基因工程

Progress in the detection of human genome structural variations

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Science china(Life sciences) 2009年第6期52卷 560-567页

作者： WU XueMei1,3 & XIAO HuaSheng1,2 1 center of Functional Genomics,Key Laboratory of System Biology,shanghai institutes for biological sciences,chinese academy of sciences,shanghai 2.0031,china 2 National Engineering center for Biochip at shanghai,shanghai 201203,china 3 Graduate School of the chinese academy of sciences,shanghai 2.0031,china 1. center of Functional Genomics Key Laboratory of System Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China 3. Graduate School of the chinese academy of sciences Shanghai 200031 China 2. National Engineering center for Biochip at shanghai Shanghai 201203 China

The emerging of high-throughput and high-resolution genomic technologies led to the detection of submicroscopic variants ranging from 1 kb to 3 Mb in the human *** variants include copy number variations(CNVs),inversions,insertions,deletions and other complex rearrangements of DNA *** paper briefly reviews the commonly used technologies to discover both genomic structural variants and their potential ***,we highlight the array-based,PCR-based and sequencing-based assays,including array-based comparative genomic hybridization(aCGH),representational oligonucleotide microarray analysis(ROMA),multiplex amplifiable probe hybridization(MAPH),multiplex ligation-dependent probe amplification(MLPA),paired-end mapping(PEM),and next-generation DNA sequencing ***,we discuss the limitations and challenges of current assays and give advices on how to make the database of genomic variations more reliable.

关键词： structural variation cytogenetic microarray PCR paired end mapping(PEM) next-generation sequencing

miRNAs modulate the drug response of tumor cells

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Science china(Life sciences) 2009年第9期52卷 797-801页

作者： WU XueMei1,3 & XIAO HuaSheng1,2 1 center of Functional Genomics,Key Laboratory of System Biology,shanghai institutes for biological sciences,chinese academy of sciences,shanghai 2.0031,china 2 National Engineering center for Biochip at shanghai,shanghai 201203,china 3 Graduate University of chinese academy of sciences,shanghai 2.0031,china center of Functional Genomics Key Laboratory of System Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China National Engineering center for Biochip at shanghai Shanghai 201203 China Graduate University of chinese academy of sciences Shanghai 200031 China

Chemotherapy is one of the major treatments of malignant carcinomas. However,its efficiency is affected by both intrinsic and acquired resistance to anticancer drugs. The cellular mechanisms of drug resistance include the overexpression of energy-dependent transporters that eject anticancer drugs from cells such as p-glycoprotein and multidrug resistance related protein (MRP),the mutation of drug targets,the activation of DNA repair pathways,the defects in cellular death pathways and so on. The genetic and epigenetic changes of these genes can lead to cancer drug resistance. Among these mechanisms,microRNAs (miRNAs) which are critical and essential for many important processes such as development,differentiation,and even carcinogenesis have been reported to regulate the chemosen-sitivity of tumor cells. In this paper we briefly review the relationship between miRNA and cancer drug resistance.

关键词： cancer drug resistance miRNAs

Fusion Protein of Interleukin 4 and Diphtherial Toxin with High Cytotoxicity to Cancer Cells

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Acta Biochimica et Biophysica Sinica 2004年第6期36卷 437-442页

作者： Yu-Jian ZHANG, Xiao-BoHU, Su-Xia LI1, Li-Ping TIAN, Sheng-Li YANG, and Yi GONG* Research center of Biotechnology, shanghai institutes for biological sciences,chinese academy of sciences, Graduate School of the chinese academy of sciences, shanghai 200233, china State Key Laboratory of Bioreactor Engineering, East china University of Science and Technology, shanghai 200237, china Research center of Biotechnology Shanghai Institutes for Biological SciencesChinese Academy of Sciences Graduate School of the Chinese Academy of SciencesShanghai 200233 China State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237 China

Receptor of human interleukin 4 (hIL4R) has been found to be present on many types of cancer, so it may be a good target for cancer therapy. Here, fusion toxin gene DT4H has been constructed by fusing DNA sequence encoding the first 389 amino acids of diphtherial toxin (DT), which can not bind its own receptor, to human interleukin 4 (hIL4) gene. In order to improve the affinity of fusion toxin for hIL4R, a circularly permuted form of hIL4 (cpIL4) was used. The fusion gene was expressed in Escherichia coli where the fusion toxin DT4H was highly expressed. Purified DT4H was very cytotoxic to cancer cell line U251 cells, and moderate cytotoxic to HepG2 and MCF-7 cells. SGC-7901 cells were insensitive to it. The cytotoxic action of DT4H was specific because it was blocked by excess hIL4. These results suggest that DT4H may be a useful agent in the treatment of certain malignancies.

关键词： fusion toxin diphtherial toxin cancer therapy interleukin 4 IL-4 receptor

Overexpression of a novel gene , Cms1, can rescue the growth arrest of a Saccharomyces cerevisiae mcm10 suppressor

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Cell Research 2001年第4期11卷 285-291页

作者： WANG JI WU, JIA RUI WU State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, shanghai Research center of Life Science, shanghai institutes for biological sciences, chinese academy of sciences, 320 Yue- Yang Road, shanghai 1State Key Laboratory of Molecular Biology Institute of Biochemistry and Cell Biology Shanghai Research Center of Life Science Shanghai Institutes for Biological Sciences Chinese Academy of Sciences 320 Yue-Yang Road Shanghai 200031 China 1State Key Laboratory of Molecular Biology Institute of Biochemistry and Cell Biology Shanghai Research Center of Life Science Shanghai Institutes for Biological Sciences Chinese Academy of Sciences 320 Yue-Yang Road Shanghai 200031 China

MCM10 protein is an essential replication factor involved in the initiation of DNA replication. A mcm10 mutan (mcm10-1) of budding yeast shows a growth arrest at 37 C. In the present work, we have isolated a mcm10-1 suppressor strain, which grows at 37 C. Interestingly, this mcm10-1 suppressor undergoes cell Cycle arrest at 14 C. A novel gene, YLR003c, is identified by high-copy complementation of this suppressor. We called it as Cms1 (Complementation of Mcm 10 Suppressor). Furthermore, the experiments of trans- formation show that cells of mcm10-1 suppressor with high-copy plasmid but not low-copy plasmid grow at 14 C, indicating that overexpression of Cms1 can rescue the growth arrest of this mcm10 suppressor at non-permissive temperature. These results suggest that CMS1 protein may functionally interact with MCM10 protein and play a role in the regulation of DNA replication and cell cycle control.

关键词： Saccharomyces cerevisiae DNA replication Mcm10 Cms1 cell cycle.