Objective: Detecting the expression and mutation of human telomeric repeat binding factor (hTRF1) in 10 malignant hematopoietic cell line cells on the base of determining its genomic structure and its four pseudoge...Objective: Detecting the expression and mutation of human telomeric repeat binding factor (hTRF1) in 10 malignant hematopoietic cell line cells on the base of determining its genomic structure and its four pseudogenes to clarify ifhTRF1 mutation is one of the factors of the activation of telomerase. Methods: hTRFlcDNA sequences were obtained from GenBank, its genome structure and pseudogenes were forecasted by BLAST and other biology information programs and then testified by sequencing. Real-time RT-PCR was used to detect the expression of h TRFlmRNA in 10 cell line cells, including myelogenous leukemia cell lines K562, HL-60, U-937, NB4, THP-I, HEL and Dami; lymphoblastic leukemia cell lines 6T-CEM, Jurkat and Raji. Telomerase activities of cells were detected by using telomeric repeat amplification (TRAP)-ELISA protocol. PCR and sequencing were used to detect mutation of each exon ofhTRF1 in 10 cell line cells. Results: hTRF1 gene, mapped to 8q13, was divided into 10 exons and spans 38.6 kb. Four processed pseudogenes ofhTRF1 located on chromosome 13, 18, 21 and X respectively, was named as ψhTRFI-13, ψhTRFI-18, ψhTRF1-21 and ψhTRFI-X respectively. All cell line cells showed positive telomerase activity. The expression of hTRF1 was significantly lower in malignant hematopoietic cell lines cells (0.0338, 0.0108-0.0749) than in normal mononuclear cells (0.0493, 0.0369-0.128) (P=0.004). But no significant mutation was found in all exons of hTRF1 in 10 cell line cells. Four variants were found in part ofintron 1, 2 and 8 ofhTRF1. Their infection on gene function is unknown and needs further studies. Conclusion: hTRF1 mutation is probably not one of the main factors for telomerase activation in malignant hematopoietic disease.展开更多
Objective: With the development of peptide-based cancer specific immunotherapy, the prediction of CTL epitopes from insulin-like growth factor-binding protein 7 (IGFBP7) is very important for some research about tu...Objective: With the development of peptide-based cancer specific immunotherapy, the prediction of CTL epitopes from insulin-like growth factor-binding protein 7 (IGFBP7) is very important for some research about tumor metastasis. Because HLA-A2.1-expressing individuals cover 〉50% in the population of China, we aimed at identifying IGFBPT-encoded peptide presented by HLA-A2.1. Methods: In our study, a HLA-A2.1 restricted CTL epitope was identified by using the following two-step procedure: (a) computer-based epitope prediction from the amino acid sequence of IGFBP7 antigen; (b) Validation with epitope molecular modeling. Results: We obtained four epitopes with high immunogenicity scores by all of the three algorithms, i.e., BIMAS, SYFPEITH1 and IMTECH. Each of the four candidates satisfied the criteria of the HLA-A2.1- restricted CTL epitopes in molecular modeling analysis. Conclusion: The combination of BIMAS, SYFPEITHI and IMTECH method can improve the prediction efficiency and accuracy. Due to this research herein, this four epitopes have potential value for further studied, also have potential application in peptide-mediated immunotherapy. These epitopes may be useful in the design of therapeutic peptide vaccine for lung carcinoma and as immunotherapeutic strategies against lung carcinoma after identified by immunology experiment.展开更多
Kynurenine aminotransferases (KATs) catalyze the transamination of kynurenine (KYN) pathway and endogenous KYNs have been suggested to highly correlate to abnormal brain diseases. HKAT3 is a key member of KAT fami...Kynurenine aminotransferases (KATs) catalyze the transamination of kynurenine (KYN) pathway and endogenous KYNs have been suggested to highly correlate to abnormal brain diseases. HKAT3 is a key member of KAT family, while the binding mechanism of KYN and cofactor with HKAT3 has not been determined yet. In this study, we focus on the structure-function relationship among KYN, cofactor and HKAT3. The binding models of KYN complex and KYN&cofactor complex were ob- tained and were studied by molecular dynamics (MD) simulations. We identified several critical residues and influence of conformational changes in human kynurenine aminotransferase 3 (HKAT3) complexes. The cofactor may contribute largely not only to the catalysis, but also to the binding. In addition, a hypothesis is proposed that a strong hydrophobic interaction between Tyr159 and Lys280 may influence the binding mode and the binding region of the substrate and the cofactor. Our re- suits will be a good starting point for further determination of the biological role.展开更多
In the paper, a novel practical approach to construct a composite indicator (CI) is pro- posed. The key idea is to decide the weights of sub-indicators in constructing a composite indicator by maximizing the sum of ...In the paper, a novel practical approach to construct a composite indicator (CI) is pro- posed. The key idea is to decide the weights of sub-indicators in constructing a composite indicator by maximizing the sum of squared correlations between the CI and sub-indicators. The CI obtained in this fashion has the maximum sum of squared correlations among all linear estimators. In addition, the simple, exact and explicit solutions of weights are proposed under the condition of non-negative irreducible matrix. Moreover, under this particular condition, the proposed method will become the principal component analysis. For illustration purpose, the proposed novel approach is utilized to cal- culate Sustainable Energy Index and Human Development Index which are two often-used cases to compare models in the literatures. The results the methods of Hatefi, et al. (2010) and Zhou all sub-indicators' correlations. show that the power of the proposed method outweigh et al. (2007) in terms of the sum of absolute values of展开更多
文摘Objective: Detecting the expression and mutation of human telomeric repeat binding factor (hTRF1) in 10 malignant hematopoietic cell line cells on the base of determining its genomic structure and its four pseudogenes to clarify ifhTRF1 mutation is one of the factors of the activation of telomerase. Methods: hTRFlcDNA sequences were obtained from GenBank, its genome structure and pseudogenes were forecasted by BLAST and other biology information programs and then testified by sequencing. Real-time RT-PCR was used to detect the expression of h TRFlmRNA in 10 cell line cells, including myelogenous leukemia cell lines K562, HL-60, U-937, NB4, THP-I, HEL and Dami; lymphoblastic leukemia cell lines 6T-CEM, Jurkat and Raji. Telomerase activities of cells were detected by using telomeric repeat amplification (TRAP)-ELISA protocol. PCR and sequencing were used to detect mutation of each exon ofhTRF1 in 10 cell line cells. Results: hTRF1 gene, mapped to 8q13, was divided into 10 exons and spans 38.6 kb. Four processed pseudogenes ofhTRF1 located on chromosome 13, 18, 21 and X respectively, was named as ψhTRFI-13, ψhTRFI-18, ψhTRF1-21 and ψhTRFI-X respectively. All cell line cells showed positive telomerase activity. The expression of hTRF1 was significantly lower in malignant hematopoietic cell lines cells (0.0338, 0.0108-0.0749) than in normal mononuclear cells (0.0493, 0.0369-0.128) (P=0.004). But no significant mutation was found in all exons of hTRF1 in 10 cell line cells. Four variants were found in part ofintron 1, 2 and 8 ofhTRF1. Their infection on gene function is unknown and needs further studies. Conclusion: hTRF1 mutation is probably not one of the main factors for telomerase activation in malignant hematopoietic disease.
基金Supported by the Special fund of the National High Technology Research and Development Program of China (863 Program,2007AA02Z129)the National Natural Science Foundation of China (30672076 and 30800506)
文摘Objective: With the development of peptide-based cancer specific immunotherapy, the prediction of CTL epitopes from insulin-like growth factor-binding protein 7 (IGFBP7) is very important for some research about tumor metastasis. Because HLA-A2.1-expressing individuals cover 〉50% in the population of China, we aimed at identifying IGFBPT-encoded peptide presented by HLA-A2.1. Methods: In our study, a HLA-A2.1 restricted CTL epitope was identified by using the following two-step procedure: (a) computer-based epitope prediction from the amino acid sequence of IGFBP7 antigen; (b) Validation with epitope molecular modeling. Results: We obtained four epitopes with high immunogenicity scores by all of the three algorithms, i.e., BIMAS, SYFPEITH1 and IMTECH. Each of the four candidates satisfied the criteria of the HLA-A2.1- restricted CTL epitopes in molecular modeling analysis. Conclusion: The combination of BIMAS, SYFPEITHI and IMTECH method can improve the prediction efficiency and accuracy. Due to this research herein, this four epitopes have potential value for further studied, also have potential application in peptide-mediated immunotherapy. These epitopes may be useful in the design of therapeutic peptide vaccine for lung carcinoma and as immunotherapeutic strategies against lung carcinoma after identified by immunology experiment.
基金supported by the National Natural Science Foundation of ChinaSpecialized Research Fund for the Doctoral Program of Higher EducationSpecialized Fund for the Basic Research of Jilin University (20903045, 20573042, 20070183046,200810018)
文摘Kynurenine aminotransferases (KATs) catalyze the transamination of kynurenine (KYN) pathway and endogenous KYNs have been suggested to highly correlate to abnormal brain diseases. HKAT3 is a key member of KAT family, while the binding mechanism of KYN and cofactor with HKAT3 has not been determined yet. In this study, we focus on the structure-function relationship among KYN, cofactor and HKAT3. The binding models of KYN complex and KYN&cofactor complex were ob- tained and were studied by molecular dynamics (MD) simulations. We identified several critical residues and influence of conformational changes in human kynurenine aminotransferase 3 (HKAT3) complexes. The cofactor may contribute largely not only to the catalysis, but also to the binding. In addition, a hypothesis is proposed that a strong hydrophobic interaction between Tyr159 and Lys280 may influence the binding mode and the binding region of the substrate and the cofactor. Our re- suits will be a good starting point for further determination of the biological role.
基金supported by National Natural Science Foundation of China under Grant No.71003100the Fundamental Research Funds for the Central Universitiesthe Research Funds of Renmin University of China under Grant No.11XNK027
文摘In the paper, a novel practical approach to construct a composite indicator (CI) is pro- posed. The key idea is to decide the weights of sub-indicators in constructing a composite indicator by maximizing the sum of squared correlations between the CI and sub-indicators. The CI obtained in this fashion has the maximum sum of squared correlations among all linear estimators. In addition, the simple, exact and explicit solutions of weights are proposed under the condition of non-negative irreducible matrix. Moreover, under this particular condition, the proposed method will become the principal component analysis. For illustration purpose, the proposed novel approach is utilized to cal- culate Sustainable Energy Index and Human Development Index which are two often-used cases to compare models in the literatures. The results the methods of Hatefi, et al. (2010) and Zhou all sub-indicators' correlations. show that the power of the proposed method outweigh et al. (2007) in terms of the sum of absolute values of