There are several cofactors which affect body iron metabolism and accelerate iron overload. Alcohol and hepatic viral infections are the most typical examples for clarifying the role of cofactors in iron overload. In ...There are several cofactors which affect body iron metabolism and accelerate iron overload. Alcohol and hepatic viral infections are the most typical examples for clarifying the role of cofactors in iron overload. In these conditions, iron is deposited in hepatocytes and Kupffer cells and reactive oxygen species （ROS） produced through Fenton reaction have key role to facilitate cellular uptake of transferrin-bound iron. Furthermore, hepcidin, antimicrobial peptide produced mainly in the liver is also responsible for intestinal iron absorption and reticuloendothelial iron release. In patients with ceruloplasmin deficiency, anemia and secondary iron overload in liver and neurodegeneration are reported. Furthermore, there is accumulating evidence that fatty acid accumulation without alcohol and obesity itself modifies iron overload states. Ineffective erythropoiesis is also an important factor to accelerate iron overload, which is associated with diseases such as thalassemia and myelodysplastic syndrome. When this condition persists, the dietary iron absorption is increased due to the increment of bone marrow erythropoiesis and tissue iron overload will thereafter occurs. In porphyria cutanea tarda, iron is secondarily accumulated in the liver.展开更多
Two k-hyperconnection expressions of a general k-order cofactor Y<sub>（i,j）</sub> are presentedfor the indefinite parameter matrix Y of a linear system by applying directed hypergraph theory,and based on...Two k-hyperconnection expressions of a general k-order cofactor Y<sub>（i,j）</sub> are presentedfor the indefinite parameter matrix Y of a linear system by applying directed hypergraph theory,and based on it a decomposition theorem of Y<sub>（i,j）</sub> is derived.By this theorem,the multi-leveltearing and analysis can be carried out easily for any linear large system.This is a new mul-tilevel topological analysis method.Using proposed method the scale of systems which can betopologically analysed by a computer will be enlarged.展开更多
Microtubules play important roles in neuronal morphogenesis, including cellular polarization, neurite growth, and branching. A microtubule is a polymer of a- and β-tubulin heterodimers that are formed by a multistep ...Microtubules play important roles in neuronal morphogenesis, including cellular polarization, neurite growth, and branching. A microtubule is a polymer of a- and β-tubulin heterodimers that are formed by a multistep process assisted by at least five tubulin-fold- ing cofactors （TBCA-E） （Lopez-Fanarraga et al., 2001）. Newly syn- thesized α- and β-tubulins associate with the cytosolic chaperonin complex （CCT）, and then the quasi-native tubulins interact with five tubulin-folding cofactors. The α- and β-tubulins first interact with TBCB and TBCA, which are further transferred to TBCE and TBCD, respectively. The α- and β-tubulins, TBCC, TBCD, and TBCE form a supercomplex, and guanosine triphosphate （GTP） hydrolysis occurs within the supercomplex, releasing a tubulin heterodimer. In addition to their functions in tubulin folding and tubulin heterodimer formation, excess amounts of TBCD or TBCE may interact with tubulin heterodimers, leading to their degrada- tion. Thus, tubulin-folding cofactors may play a role in both the synthesis and degradation of tubulin heterodimers.展开更多
Introduction: High grade dysplasia of the cervix has a high incidence and can progress to cervical cancer. The aim was to study cofactors associated with high-grade cervical dysplasia. Methodology: This was a retrospe...Introduction: High grade dysplasia of the cervix has a high incidence and can progress to cervical cancer. The aim was to study cofactors associated with high-grade cervical dysplasia. Methodology: This was a retrospective case-control study without matching. Women with high grade dysplasia were the cases while those with a normal screening test represented the controls. The study took place at the Gabriel Touré University Hospital Center in Bamako. We included 351 cases and 420 controls. The capture and analysis were performed using the SPSS 20 software. A univariate and multivariate logistic regression analysis was performed for the analysis of risk cofactors. The statistical tests used were the odds ratio and its confidence interval and the statistical significance threshold was set at p Results: In univariate analysis, the co-factors statistically significantly associated with the occurrence of high-grade dysplasia were parity 0.6 (0.5 - 0.9), gestational 0.7 (0.5 - 0.9), smoking of the spouse 3.4 (1.1 - 11.3), the non-schooling 1.4 (1.2 - 2.1). In multivariate analysis after adjusting for confounding factors, two co-factors have significantly increased the risk of high-grade dysplasia: lack of schooling 1.4 (1.2 - 2.0) and polygamy 1.5 (1.4 - 2.5). Conclusion: At the end of this study, polygamy and lack of schooling were the main risk factors. The prevention of cervical cancer will go through the education of girls and women as well as communication for behavioral change and social change.展开更多
Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-p...Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-prohibitive for biocatalysis at scale yet tightly regulated in host cells.A highly challenging task for P450 catalysis has been to develop an alternative and biocompatible electrondonating system.Here we engineered P450 BM3 to favor reduced nicotinamide cytosine dinucleotide(NCDH)and created non-natural cofactor-dependent P450 catalysis.Two outstanding mutants were identified with over 640-fold NCDH preference improvement and good catalytic efficiencies of over15,000 M^(-1)s^(-1)for the oxidation of the fatty acid probe 12-(para-nitrophenoxy)-dodecanoate.Molecular docking analysis indicated that these mutants bear a compacted cofactor entrance.Upon fusing with an NCD-dependent formate dehydrogenase,fused proteins functioned as NCDH-specific P450catalysts by using formate as the electron donor.Importantly,these mutants and fusions catalyzed NCDH-dependent hydroxylation of fatty acids with similar chain length preference to those by natural P450 BM3 in the presence of NADPH and also similar regioselectivity for subterminal hydroxylation of lauric acid.As P450 BM3 and its variants are catalytically powerful to take diverse substrates and convey different reaction paths,our results offer an exciting opportunity to devise advanced cell factories that convey oxidative biocatalysis with an orthogonal reducing power supply system.展开更多
文摘There are several cofactors which affect body iron metabolism and accelerate iron overload. Alcohol and hepatic viral infections are the most typical examples for clarifying the role of cofactors in iron overload. In these conditions, iron is deposited in hepatocytes and Kupffer cells and reactive oxygen species （ROS） produced through Fenton reaction have key role to facilitate cellular uptake of transferrin-bound iron. Furthermore, hepcidin, antimicrobial peptide produced mainly in the liver is also responsible for intestinal iron absorption and reticuloendothelial iron release. In patients with ceruloplasmin deficiency, anemia and secondary iron overload in liver and neurodegeneration are reported. Furthermore, there is accumulating evidence that fatty acid accumulation without alcohol and obesity itself modifies iron overload states. Ineffective erythropoiesis is also an important factor to accelerate iron overload, which is associated with diseases such as thalassemia and myelodysplastic syndrome. When this condition persists, the dietary iron absorption is increased due to the increment of bone marrow erythropoiesis and tissue iron overload will thereafter occurs. In porphyria cutanea tarda, iron is secondarily accumulated in the liver.
文摘Two k-hyperconnection expressions of a general k-order cofactor Y<sub>（i,j）</sub> are presentedfor the indefinite parameter matrix Y of a linear system by applying directed hypergraph theory,and based on it a decomposition theorem of Y<sub>（i,j）</sub> is derived.By this theorem,the multi-leveltearing and analysis can be carried out easily for any linear large system.This is a new mul-tilevel topological analysis method.Using proposed method the scale of systems which can betopologically analysed by a computer will be enlarged.
基金supported by grants from the Ministry of Education,Culture,Sports,Science and Technology in Japan to MM and TCthe Japan Society for the Promotion of Science to MO,MM,and TCthe Japan Science and Technology Agency to M.M.and TC
文摘Microtubules play important roles in neuronal morphogenesis, including cellular polarization, neurite growth, and branching. A microtubule is a polymer of a- and β-tubulin heterodimers that are formed by a multistep process assisted by at least five tubulin-fold- ing cofactors （TBCA-E） （Lopez-Fanarraga et al., 2001）. Newly syn- thesized α- and β-tubulins associate with the cytosolic chaperonin complex （CCT）, and then the quasi-native tubulins interact with five tubulin-folding cofactors. The α- and β-tubulins first interact with TBCB and TBCA, which are further transferred to TBCE and TBCD, respectively. The α- and β-tubulins, TBCC, TBCD, and TBCE form a supercomplex, and guanosine triphosphate （GTP） hydrolysis occurs within the supercomplex, releasing a tubulin heterodimer. In addition to their functions in tubulin folding and tubulin heterodimer formation, excess amounts of TBCD or TBCE may interact with tubulin heterodimers, leading to their degrada- tion. Thus, tubulin-folding cofactors may play a role in both the synthesis and degradation of tubulin heterodimers.
文摘Introduction: High grade dysplasia of the cervix has a high incidence and can progress to cervical cancer. The aim was to study cofactors associated with high-grade cervical dysplasia. Methodology: This was a retrospective case-control study without matching. Women with high grade dysplasia were the cases while those with a normal screening test represented the controls. The study took place at the Gabriel Touré University Hospital Center in Bamako. We included 351 cases and 420 controls. The capture and analysis were performed using the SPSS 20 software. A univariate and multivariate logistic regression analysis was performed for the analysis of risk cofactors. The statistical tests used were the odds ratio and its confidence interval and the statistical significance threshold was set at p Results: In univariate analysis, the co-factors statistically significantly associated with the occurrence of high-grade dysplasia were parity 0.6 (0.5 - 0.9), gestational 0.7 (0.5 - 0.9), smoking of the spouse 3.4 (1.1 - 11.3), the non-schooling 1.4 (1.2 - 2.1). In multivariate analysis after adjusting for confounding factors, two co-factors have significantly increased the risk of high-grade dysplasia: lack of schooling 1.4 (1.2 - 2.0) and polygamy 1.5 (1.4 - 2.5). Conclusion: At the end of this study, polygamy and lack of schooling were the main risk factors. The prevention of cervical cancer will go through the education of girls and women as well as communication for behavioral change and social change.
基金supported by the National Key R&D Program of China(2019YFA0904900)the National Natural Science Foundation of China(21877112,21837002,21721004)。
文摘Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-prohibitive for biocatalysis at scale yet tightly regulated in host cells.A highly challenging task for P450 catalysis has been to develop an alternative and biocompatible electrondonating system.Here we engineered P450 BM3 to favor reduced nicotinamide cytosine dinucleotide(NCDH)and created non-natural cofactor-dependent P450 catalysis.Two outstanding mutants were identified with over 640-fold NCDH preference improvement and good catalytic efficiencies of over15,000 M^(-1)s^(-1)for the oxidation of the fatty acid probe 12-(para-nitrophenoxy)-dodecanoate.Molecular docking analysis indicated that these mutants bear a compacted cofactor entrance.Upon fusing with an NCD-dependent formate dehydrogenase,fused proteins functioned as NCDH-specific P450catalysts by using formate as the electron donor.Importantly,these mutants and fusions catalyzed NCDH-dependent hydroxylation of fatty acids with similar chain length preference to those by natural P450 BM3 in the presence of NADPH and also similar regioselectivity for subterminal hydroxylation of lauric acid.As P450 BM3 and its variants are catalytically powerful to take diverse substrates and convey different reaction paths,our results offer an exciting opportunity to devise advanced cell factories that convey oxidative biocatalysis with an orthogonal reducing power supply system.
