AIM: To investigate the biological impacts of 'hot-spot'mutations on genotype B and C HBV X proteins (HBx).METHODS: Five types of'hot-spot' mutations of genotype B or C HBV X genes, which sequentially ...AIM: To investigate the biological impacts of 'hot-spot'mutations on genotype B and C HBV X proteins (HBx).METHODS: Five types of'hot-spot' mutations of genotype B or C HBV X genes, which sequentially lead to the amino acid substitutions of HBx as I127T, F132Y, K130M+V131I,I127T+K130M+V131I, or K130M+V131I+F132Y, respectively,were generated by means of site-directed mutagenesis.To evaluate the anti-proliferative effects, HBx or related mutants' expression vectors were transfected separately to the Chang cells by lipofectamine, and the cells were cultured in hygromycin selective medium for 14 d, drug-resistant colonies were fixed with cold methanol, stained with Giemsa dyes and scored (increase of the colonies indicated the reduction of the anti-proliferation activity,and vice versa). Different types of HBx expression vectors were co-transfected separately with the reporter plasmid pCMVβ to Chang cells, which were lysed 48 h post-transfection and the intra-cellular β-galactosidase activities were monitored (increase of the β-galactosidase activities indicated the reduction of the transactivation activity, and vice versa). All data obtained were calculated by paired-samples t-test.RESULTS: As compared to standard genotype B HBx,mutants of I127T and I127T+K130M+V131I showed higher transactivation and anti-proliferative activities, while the mutants of F132Y, K130M+V131I, and K130M+V131I+F132Y showed lower activities. As compared to standard genotype C HBx, I127T mutant showed higher transactivation activity, while the other four types of mutants showed no differences. With regard to anti-proliferative activity,compared to standard genotype C HBx, F132Y and K130M+V131I mutants showed lower activities, and K130M+V131I +F132Y mutant, on the other hand, showed higher activity,while the mutants of I127T and I127T+K130M+V131I showed no differences.CONCLUSION: 'Hot-spot' mutations affect the antiproliferation and transactivation activities of genotype B and/or C HBx, and the biological impacts of most 'hot-spot' mutations on HBx are genotype B and C differentiated.展开更多
GMO Biosafety Research (ISSN 1925-1955) is a new launched, open access and peer-reviewed journal that dedicates to publish the release of genetically modified organisms (GMOs), GMO safety,
Obsessive-compulsive disorder(OCD)represents a heterogeneous collection of diseases with diverse levels of phenotypic,genetic,and etiologic variability,making it difficult to identify the underlying genetic and biolog...Obsessive-compulsive disorder(OCD)represents a heterogeneous collection of diseases with diverse levels of phenotypic,genetic,and etiologic variability,making it difficult to identify the underlying genetic and biological mechanisms in humans.Domestic dogs exhibit several OCD-like behaviors.Using continuous circling as a representative phenotype for OCD,we screened two independent dog breeds,the Belgian Malinois and Kunming Dog and subsequently sequenced ten circling dogs and ten unaffected dogs for each breed.Using population differentiation analyses,we identified 11 candidate genes in the extreme tail of the differentiated regions between cases and controls.These genes overlap significantly with genes identified in a genome wide association study(GWAS)of human OCD,indicating strong convergence between humans and dogs.Through gene expressional analysis and functional exploration,we found that two candidate OCD risk genes,PPP2R2B and ADAMTSL3,affected the density and morphology of dendritic spines.Therefore,changes in dendritic spine may underlie some common biological and physiological pathways shared between humans and dogs.Our study revealed an unprecedented level of convergence in OCD shared between humans and dogs,and highlighted the importance of using domestic dogs as a model species for many human diseases including OCD.展开更多
Researchers hope that establishing a notion of proximity using topology will help to clarify the biological processes underlying the evolution of living organisms. The simple model presented here, using RNA shapes, ca...Researchers hope that establishing a notion of proximity using topology will help to clarify the biological processes underlying the evolution of living organisms. The simple model presented here, using RNA shapes, can carry over to more general and complex genotype-phenotype systems. Proximity is an important component of continuity, in both real-world and topological terms. Consequently, phenotype spaces provide an appropriate setting for modeling and investigating continuous and discontinuous evolutionary change.展开更多
Alongside recent advances and booming applications of DNA sequencing technologies, a great number of complete genome sequences for animal species are available to researchers. Hundreds of animals have been involved in...Alongside recent advances and booming applications of DNA sequencing technologies, a great number of complete genome sequences for animal species are available to researchers. Hundreds of animals have been involved in whole genome se- quencing, and at least 87 non-human animal species' complete or draft genome sequences have been published since 1998. Based on these technological advances and the subsequent accumulation of large quantity of genomic data, evolutionary genomics has become one of the most rapidly advancing disciplines in biology. Scientists now can perform a number of comparative and evolu- tionary genomic studies for animals, to identify conserved genes or other functional elements among species, genomic elements that confer animals their own specific characteristics and new phenotypes for adaptation. This review deals with the current ge- nomic and evolutionary research on non-human animals, and displays a comprehensive landscape of genomes and the evolution- ary genomics of non-human animals. It is very helpful to a better understanding of the biology and evolution of the myriad forms within the animal kingdom [Current Zoology 59 (1): 87-98, 2013].展开更多
基金Supported by the Foundation for the Author of National Excellent Doctoral Dissertation of PR China, No. 200359Fujian Natural Science Key Foundation, No, 2002F005Fujian Science and Technology Innovation Foundation for Young Scientists, No.2001J058
文摘AIM: To investigate the biological impacts of 'hot-spot'mutations on genotype B and C HBV X proteins (HBx).METHODS: Five types of'hot-spot' mutations of genotype B or C HBV X genes, which sequentially lead to the amino acid substitutions of HBx as I127T, F132Y, K130M+V131I,I127T+K130M+V131I, or K130M+V131I+F132Y, respectively,were generated by means of site-directed mutagenesis.To evaluate the anti-proliferative effects, HBx or related mutants' expression vectors were transfected separately to the Chang cells by lipofectamine, and the cells were cultured in hygromycin selective medium for 14 d, drug-resistant colonies were fixed with cold methanol, stained with Giemsa dyes and scored (increase of the colonies indicated the reduction of the anti-proliferation activity,and vice versa). Different types of HBx expression vectors were co-transfected separately with the reporter plasmid pCMVβ to Chang cells, which were lysed 48 h post-transfection and the intra-cellular β-galactosidase activities were monitored (increase of the β-galactosidase activities indicated the reduction of the transactivation activity, and vice versa). All data obtained were calculated by paired-samples t-test.RESULTS: As compared to standard genotype B HBx,mutants of I127T and I127T+K130M+V131I showed higher transactivation and anti-proliferative activities, while the mutants of F132Y, K130M+V131I, and K130M+V131I+F132Y showed lower activities. As compared to standard genotype C HBx, I127T mutant showed higher transactivation activity, while the other four types of mutants showed no differences. With regard to anti-proliferative activity,compared to standard genotype C HBx, F132Y and K130M+V131I mutants showed lower activities, and K130M+V131I +F132Y mutant, on the other hand, showed higher activity,while the mutants of I127T and I127T+K130M+V131I showed no differences.CONCLUSION: 'Hot-spot' mutations affect the antiproliferation and transactivation activities of genotype B and/or C HBx, and the biological impacts of most 'hot-spot' mutations on HBx are genotype B and C differentiated.
文摘GMO Biosafety Research (ISSN 1925-1955) is a new launched, open access and peer-reviewed journal that dedicates to publish the release of genetically modified organisms (GMOs), GMO safety,
基金supported by the National Key Research and Development Program of China(2019YFA0707101)the Key Research Program of Frontier Sciences of the Chinese Academy of Sciences(2019YFA0707101)+5 种基金the Innovative Research Team(in Science and Technology)of Yunnan Province(201905E160019)the National Natural Science Foundation of China(81860255,31701133,81722019,and 31201712)Yunnan Applied Basic Research Projects for Kunming Medicine University Special Fund(2017FE468(-134))the Animal Branch of the Germplasm Bank of Wild Species,Chinese Academy of Sciences(the Large Research Infrastructure Funding)supported by the National Youth Talent Support Programsupported by the Hundred-Talent Program of Kunming Medical University。
文摘Obsessive-compulsive disorder(OCD)represents a heterogeneous collection of diseases with diverse levels of phenotypic,genetic,and etiologic variability,making it difficult to identify the underlying genetic and biological mechanisms in humans.Domestic dogs exhibit several OCD-like behaviors.Using continuous circling as a representative phenotype for OCD,we screened two independent dog breeds,the Belgian Malinois and Kunming Dog and subsequently sequenced ten circling dogs and ten unaffected dogs for each breed.Using population differentiation analyses,we identified 11 candidate genes in the extreme tail of the differentiated regions between cases and controls.These genes overlap significantly with genes identified in a genome wide association study(GWAS)of human OCD,indicating strong convergence between humans and dogs.Through gene expressional analysis and functional exploration,we found that two candidate OCD risk genes,PPP2R2B and ADAMTSL3,affected the density and morphology of dendritic spines.Therefore,changes in dendritic spine may underlie some common biological and physiological pathways shared between humans and dogs.Our study revealed an unprecedented level of convergence in OCD shared between humans and dogs,and highlighted the importance of using domestic dogs as a model species for many human diseases including OCD.
文摘Researchers hope that establishing a notion of proximity using topology will help to clarify the biological processes underlying the evolution of living organisms. The simple model presented here, using RNA shapes, can carry over to more general and complex genotype-phenotype systems. Proximity is an important component of continuity, in both real-world and topological terms. Consequently, phenotype spaces provide an appropriate setting for modeling and investigating continuous and discontinuous evolutionary change.
文摘Alongside recent advances and booming applications of DNA sequencing technologies, a great number of complete genome sequences for animal species are available to researchers. Hundreds of animals have been involved in whole genome se- quencing, and at least 87 non-human animal species' complete or draft genome sequences have been published since 1998. Based on these technological advances and the subsequent accumulation of large quantity of genomic data, evolutionary genomics has become one of the most rapidly advancing disciplines in biology. Scientists now can perform a number of comparative and evolu- tionary genomic studies for animals, to identify conserved genes or other functional elements among species, genomic elements that confer animals their own specific characteristics and new phenotypes for adaptation. This review deals with the current ge- nomic and evolutionary research on non-human animals, and displays a comprehensive landscape of genomes and the evolution- ary genomics of non-human animals. It is very helpful to a better understanding of the biology and evolution of the myriad forms within the animal kingdom [Current Zoology 59 (1): 87-98, 2013].