This article explores the characteristics of the average abundance function with mutation on the basis of the multi-player snowdrift evolutionary game model by analytical analysis and numerical simulation.The specific...This article explores the characteristics of the average abundance function with mutation on the basis of the multi-player snowdrift evolutionary game model by analytical analysis and numerical simulation.The specific field of this research concerns the approximate expressions of the average abundance function with mutation on the basis of different levels of selection intensity and an analysis of the results of numerical simulation on the basis of the intuitive expression of the average abundance function.In addition,the biological background of this research lies in research on the effects of mutation,which is regarded as a biological concept and a disturbance to game behavior on the average abundance function.The mutation will make the evolutionary result get closer to the neutral drift state.It can be deduced that this affection is not only related to mutation,but also related to selection intensity and the gap between payoff and aspiration level.The main research findings contain four aspects.First,we have deduced the concrete expression of the expected payoff function.The asymptotic property and change trend of the expected payoff function has been basically obtained.In addition,the intuitive expression of the average abundance function with mutation has been obtained by taking the detailed balance condition as the point of penetration.It can be deduced that the effect of mutation is to make the average abundance function get close to 1/2.In addition,this affection is related to selection intensity and the gap.Secondly,the first-order Taylor expansion of the average abundance function has been deduced for when selection intensity is sufficiently small.The expression of the average abundance function with mutation can be simplified from a composite function to a linear function because of this Taylor expansion.This finding will play a significant role when analyzing the results of the numerical simulation.Thirdly,we have obtained the approximate expressions of the average abundance function corresponding to small and large selection intensity.The significance of the above approximate analysis lies in that we have grasped the basic characteristics of the effect of mutation.The effect is slight and can be neglected when mutation is very small.In addition,the effect begins to increase when mutation rises,and this effect will become more remarkable with the increase of selection intensity.Fourthly,we have explored the influences of parameters on the average abundance function with mutation through numerical simulation.In addition,the corresponding results have been explained on the basis of the expected payoff function.It can be deduced that the influences of parameters on the average abundance function with mutation will be slim when selection intensity is small.Moreover,the corresponding explanation is related to the first-order Taylor expansion.Furthermore,the influences will become notable when selection intensity is large.展开更多
Cyperus difformis L.is a troublesome weed in paddy fields and has attracted attention due to its resistance to acetohydroxyacid synthase(AHAS)inhibitors.It was found that the amino acid mutation in AHAS was the primar...Cyperus difformis L.is a troublesome weed in paddy fields and has attracted attention due to its resistance to acetohydroxyacid synthase(AHAS)inhibitors.It was found that the amino acid mutation in AHAS was the primary cause for the resistance of Cyperus difformis.However,the effect of different mutations on AHAS function is not clear in Cyperus difformis.To confirm the effect of mutations on AHAS function,six biotypes were collected,including Pro197Arg,Pro197Ser,Pro197Leu,Asp376Glu,Trp574Leu and wild type,from Hunan,Anhui,Jiangxi and Jiangsu provinces,China and the function of AHAS was characterized.The AHAS in vitro inhibition assay results indicated that the mutations decreased the sensitivity of AHAS to pyrazosulfuron-ethyl,in which the I_(50)(the half maximal inhibitory concentration)of wild type AHAS was 0.04μmol L^(-1)and Asp376Glu,Pro197Leu,Pro197Arg,Pro197Ser and Trp574Leu mutations were 3.98,11.50,40.38,38.19 and 311.43μmol L^(-1),respectively.In the determination of enzyme kinetics parameters,the Km and the maximum reaction velocity(Vmax)of the wild type were 5.18 mmol L^(-1)and 0.12 nmol mg^(-1)min^(-1),respectively,and the Km values of AHAS with Asp376Glu,Trp574Leu,Pro197Leu and Pro197Ser mutations were 0.38-0.93 times of the wild type.The Km value of the Pro197Arg mutation was 1.14times of the wild type,and the Vmax values of the five mutations were 1.17-3.33-fold compared to the wild type.It was found that the mutations increased the affinity of AHAS to the substrate,except for the Pro197Arg mutation.At a concentration of 0.0032-100 mmol L^(-1)branched-chain amino acids(BCAAs),the sensitivity of the other four mutant AHAS biotypes to feedback inhibition decreased,except for the Pro197Arg mutation.This study elucidated the effect of different mutations on AHAS function in Cyperus difformis and provided ideas for further study of resistance development.展开更多
Through studying several kinds of chaotic mappings' distributions of orbital points, we analyze the capabilityof the chaotic mutations based on these mappings. Nunerical experiments support our conclusions very we...Through studying several kinds of chaotic mappings' distributions of orbital points, we analyze the capabilityof the chaotic mutations based on these mappings. Nunerical experiments support our conclusions very well. Thecapability analysis also led to a self-adaptive mechanism of chaotic mutation. The introducing of the self-adaptivechaotic mutation can improve the performance of genetic algorithm very prominently.展开更多
Despite its apparently simple genetics,cystic fibrosis(CF) is a rather complex genetic disease.A lot of variability in the steps of the path from the cystic fibrosis transmembrane conductance regulator(CFTR) gene to t...Despite its apparently simple genetics,cystic fibrosis(CF) is a rather complex genetic disease.A lot of variability in the steps of the path from the cystic fibrosis transmembrane conductance regulator(CFTR) gene to the clinical manifestations originates an uncertain genotype- phenotype relationship.A major determinant of this uncertainty is the incomplete knowledge of the CFTR mutated genotypes,due to the high number of CFTR mutations and to the higher number of their combinations in trans and in cis.Also the very limited knowledge of functional effects of CFTR mutated alleles severely impairs our diagnostic and prognostic ability.The final phenotypic modulation exerted by CFTR modifier genes and interactome further complicates the framework.The next generation sequencing approach is a rapid,lowcost and high-throughput tool that allows a near complete structural characterization of CFTR mutated genotypes,as well as of genotypes of several other genes cooperating to the final CF clinical manifestations.This powerful method perfectly complements the new personalized therapeutic approach for CF.Drugs active on specific CFTR mutational classes are already available for CF patients or are in phase 3 trials.A complete genetic characterization has been becoming crucial for a correct personalized therapy.However,the need of a functional classification of each CFTR mutation potently arises.Future big efforts towards an ever more detailed knowledge of both structural and functional CFTR defects,coupled to parallel personalized therapeutic interventions decisive for CF cure can be foreseen.展开更多
Through studying several kinds of chaotic mappings' distributions of orbital points, we analyze the capability of the chaotic mutations based on these mappings. Numerical experiments support our conclusions very w...Through studying several kinds of chaotic mappings' distributions of orbital points, we analyze the capability of the chaotic mutations based on these mappings. Numerical experiments support our conclusions very well. The capability analysis also led to a self-adaptive mechanism of chaotic mutation. The introducing of the self-adaptive chaotic mutation can improve the performance of genetic algorithm very prominently.展开更多
As a crucial transcription factor for spermatogenesis,GATA-binding protein 4(GATA4)plays important roles in the functioning of Sertoli and Leydig cells.Conditional knockout of GATA4 in mice results in age-dependent te...As a crucial transcription factor for spermatogenesis,GATA-binding protein 4(GATA4)plays important roles in the functioning of Sertoli and Leydig cells.Conditional knockout of GATA4 in mice results in age-dependent testicular atrophy and loss of fertility.However,whether GATA4 is associated with human azoospermia has not been reported.Herein,we analyzed the GATA4 gene by direct sequencing of samples obtained from 184 Chinese men with idiopathic nonobstructive azoospermia(NOA).We identified a missense mutation(c.191G>A,p.G64E),nine single-nucleotide polymorphisms(SNPs),and one rare variant(c.^(*)84C>T)in the 3′untranslated region(UTR).Functional studies demonstrated that the p.G64E mutation did not affect transactivation ability of GATA4 for spermatogenesis-related genes(claudin-11 and steroidogenic acute regulatory protein,Star),and the 3′UTR rare variant c.^(*)84C>T did not generate microRNA-binding sites to repress GATA4 expression.To our knowledge,this is the first report to investigate the association between GATA4 and azoospermia;our results indicate that mutations in GATA4 may not be pathogenic for NOA in Chinese men.展开更多
Understanding genetic variant functionality is essential for advancing animal genomics and precision breeding.However,the lack of comprehensive functional genomic annotations in animals limits the effectiveness of mos...Understanding genetic variant functionality is essential for advancing animal genomics and precision breeding.However,the lack of comprehensive functional genomic annotations in animals limits the effectiveness of most variant function assessment methods.In this study,we gather 1030 raw epigenomic datasets from 10 animal species and systematically annotate 7 types of key regulatory regions,creating a comprehensive functional annotation map of animal genomic variants.Our findings demonstrate that integrating variants with regulatory annotations can identify tissues and cell types underlying economic traits,underscoring the utility of these annotations in functional variant discovery.Using our functional annotations,we rank the functional potential of genetic variants and classify over 127 million candidate variants into 5 functional confidence categories,with high-confidence variants significantly enriched in eQTLs and trait-associated SNPs.Incorporating these variants into genomic prediction models can improve estimated breeding value accuracy,demonstrating their practical utility in breeding programs.To facilitate the use of our results,we develop the Integrated Functional Mutation(IFmut:http://www.ifmutants.com:8212)platform,enabling researchers to explore regulatory annotations and assess the functional potential of animal variants efficiently.Our study provides a robust framework for functional genomic annotations in farm animals,enhancing variant function assessment and breeding precision.展开更多
BACKGROUND ATP-binding cassette subfamily B member 4(ABCB4)deficiency is associated with cholestatic liver disease primarily because of missense mutations,and many variants remain unidentified.Here,we validate the pat...BACKGROUND ATP-binding cassette subfamily B member 4(ABCB4)deficiency is associated with cholestatic liver disease primarily because of missense mutations,and many variants remain unidentified.Here,we validate the pathogenicity and mechanism of ABCB4 variants in clinical and in vitro trials,hypothesizing that these variants are responsible for impaired biliary function and contribute to the development of cholestatic liver diseases.AIM To clarify the functional features and pathogenicity of ABCB4 variants.METHODS Clinical data were collected from five patients with cholestatic liver disease that was initially not detected by routine examinations.Later,whole-exome sequencing confirmed ABCB4 variants and the patients were treated from January 2017 to December 2023.Pathogenic mechanisms were analyzed using bioinformatics tools,and a cell model in vitro was established to investigate ABCB4 mRNA expression,multidrug resistance protein 3(MDR3)expression,cellular localization,and phosphatidylcholine secretion.Results were compared using Student's t-tests.RESULTS Five missense variants(c.1757T>A,c.1865G>A,c.2362C>T,c.2777C>T and c.3250C>T),one intron variant(c.537-32G>T),and one synonymous(c.C504T)variant were identified.Three of the five patients had various degrees of cholestasis,two presented with liver cirrhosis,and all had elevated gamma-glutamyl transferase.Three of the four patients who underwent a liver biopsy had bile duct dilation,and one had gallstones.Two of the four patients had normal and reduced MDR3 immunohistochemical levels.Bioinformatic analysis indicated that these variants were likely pathogenic except c.C504T variant.None of the missense variants influenced subcellular MDR3 Localization in vitro.However,the c.1865G>A variant significantly decreased ABCB4 mRNA values,and all missense variants down-regulated phosphatidylcholine secretion.CONCLUSION This study uncovered new ABCB4 variants and emphasized the pathogenic potential of specific variants.The findings from five patients provided insight into the pathogenic mechanisms underlying ABCB4-related diseases.展开更多
Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).Ho...Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).However,the detection and screening of transgenic lines remain major bottlenecks,being time-consuming,labor-intensive,and inefficient during transformation and subsequent mutation identification.A simple and efficient visual marker system plays a critical role in addressing these challenges.Recent studies demonstrated that the GmW1 and RUBY reporter systems were used to obtain visual transgenic soybean(Glycine max) plants(Chen L et al.2023;Chen et al.2024).展开更多
Dear Editor,Cucumber,Cucumis sativus,is a major vegetable crop globally.In addition to being consumed fresh or sliced,pickling cucumber represents a key cultivated type,widely grown in open fields across regions inclu...Dear Editor,Cucumber,Cucumis sativus,is a major vegetable crop globally.In addition to being consumed fresh or sliced,pickling cucumber represents a key cultivated type,widely grown in open fields across regions including the Americas,Europe,and Asia(Shetty and Wehner,2002).展开更多
The Rosenbrock function optimization belongs to unconstrained optimization problems, and its global minimum value is located at the bottom of a smooth and narrow valley of the parabolic shape. It is very difficult to ...The Rosenbrock function optimization belongs to unconstrained optimization problems, and its global minimum value is located at the bottom of a smooth and narrow valley of the parabolic shape. It is very difficult to find the global minimum value of the function because of the little information provided for the optimization algorithm. According to the characteristics of the Rosenbrock function, this paper specifically proposed an improved differential evolution algorithm that adopts the self-adaptive scaling factor F and crossover rate CR with elimination mechanism, which can effectively avoid premature convergence of the algorithm and local optimum. This algorithm can also expand the search range at an early stage to find the global minimum of the Rosenbrock function. Many experimental results show that the algorithm has good performance of function optimization and provides a new idea for optimization problems similar to the Rosenbrock function for some problems of special fields.展开更多
Based on the thermal stress distribution for functionally gradient material (FGM) plates, a Genetic Algorithm (GA) method for the thermal stresses optimum design of FGM plate with computer technologies is given. The m...Based on the thermal stress distribution for functionally gradient material (FGM) plates, a Genetic Algorithm (GA) method for the thermal stresses optimum design of FGM plate with computer technologies is given. The minimum thermal stresses combination distribution for FGM is obtained.展开更多
An adaptive immune-genetic algorithm （AIGA） is proposed to avoid premature convergence and guarantee the diversity of the population. Rapid immune response （secondary response）, adaptive mutation and density opera...An adaptive immune-genetic algorithm （AIGA） is proposed to avoid premature convergence and guarantee the diversity of the population. Rapid immune response （secondary response）, adaptive mutation and density operators in the AIGA are emphatically designed to improve the searching ability, greatly increase the converging speed, and decrease locating the local maxima due to the premature convergence. The simulation results obtained from the global optimization to four multivariable and multi-extreme functions show that AIGA converges rapidly, guarantees the diversity, stability and good searching ability.展开更多
Objective To determine the relationship between TSH receptor gene mutations and autonomously functioning thyroid adenomas (AFTAs). Methods The thyroid samples from 14 cases of diagnosed AFTAs were analyzed, with nor...Objective To determine the relationship between TSH receptor gene mutations and autonomously functioning thyroid adenomas (AFTAs). Methods The thyroid samples from 14 cases of diagnosed AFTAs were analyzed, with normal thyroid specimens adjacent to the tumors as controls. The 155 base pairs DNA fragments which encompassed the third cytoplasmic loop and the sixth transmembrane segments in the TSH receptor gene exon 10 were amplified by Polymerase chain reaction (PCR) and analyzed by the single-strand conformation polymorphism (SSCP). Direct sequencing of the PCR products was performed with Prism Dye Terminator Cycle Sequencing Core Kit. Results 6 of 14 AFTA specimens displayed abnormal migration in SSCP analysis. In sequence analysis of 3 abnormally migrated samples, one base substitution at nucleotide 1957 (A to C) and two same insertion mutations of one adenosine nucleotide between nucleotide 1972 and 1973 were identified. No mutations were found in controls. Conclusion This study confirmed the presence of TSH receptor gene mutations in AFTAs; both one-point substitution mutation and one-base insertion mutation were found to be responsible for the pathogenesis of AFTAs.展开更多
基金Supported by National-Natural Science Found for Distinguished Young Scholars of China （61025015）, the Foundation for Innovative Research Groups of National Natural Science Foundation of China （61321003） and the China Scholarship Council
基金supported by the National Natural Science Foundation of China(71871171,72031009)。
文摘This article explores the characteristics of the average abundance function with mutation on the basis of the multi-player snowdrift evolutionary game model by analytical analysis and numerical simulation.The specific field of this research concerns the approximate expressions of the average abundance function with mutation on the basis of different levels of selection intensity and an analysis of the results of numerical simulation on the basis of the intuitive expression of the average abundance function.In addition,the biological background of this research lies in research on the effects of mutation,which is regarded as a biological concept and a disturbance to game behavior on the average abundance function.The mutation will make the evolutionary result get closer to the neutral drift state.It can be deduced that this affection is not only related to mutation,but also related to selection intensity and the gap between payoff and aspiration level.The main research findings contain four aspects.First,we have deduced the concrete expression of the expected payoff function.The asymptotic property and change trend of the expected payoff function has been basically obtained.In addition,the intuitive expression of the average abundance function with mutation has been obtained by taking the detailed balance condition as the point of penetration.It can be deduced that the effect of mutation is to make the average abundance function get close to 1/2.In addition,this affection is related to selection intensity and the gap.Secondly,the first-order Taylor expansion of the average abundance function has been deduced for when selection intensity is sufficiently small.The expression of the average abundance function with mutation can be simplified from a composite function to a linear function because of this Taylor expansion.This finding will play a significant role when analyzing the results of the numerical simulation.Thirdly,we have obtained the approximate expressions of the average abundance function corresponding to small and large selection intensity.The significance of the above approximate analysis lies in that we have grasped the basic characteristics of the effect of mutation.The effect is slight and can be neglected when mutation is very small.In addition,the effect begins to increase when mutation rises,and this effect will become more remarkable with the increase of selection intensity.Fourthly,we have explored the influences of parameters on the average abundance function with mutation through numerical simulation.In addition,the corresponding results have been explained on the basis of the expected payoff function.It can be deduced that the influences of parameters on the average abundance function with mutation will be slim when selection intensity is small.Moreover,the corresponding explanation is related to the first-order Taylor expansion.Furthermore,the influences will become notable when selection intensity is large.
基金funded by the National Natural Science Foundation of China(31972281)。
文摘Cyperus difformis L.is a troublesome weed in paddy fields and has attracted attention due to its resistance to acetohydroxyacid synthase(AHAS)inhibitors.It was found that the amino acid mutation in AHAS was the primary cause for the resistance of Cyperus difformis.However,the effect of different mutations on AHAS function is not clear in Cyperus difformis.To confirm the effect of mutations on AHAS function,six biotypes were collected,including Pro197Arg,Pro197Ser,Pro197Leu,Asp376Glu,Trp574Leu and wild type,from Hunan,Anhui,Jiangxi and Jiangsu provinces,China and the function of AHAS was characterized.The AHAS in vitro inhibition assay results indicated that the mutations decreased the sensitivity of AHAS to pyrazosulfuron-ethyl,in which the I_(50)(the half maximal inhibitory concentration)of wild type AHAS was 0.04μmol L^(-1)and Asp376Glu,Pro197Leu,Pro197Arg,Pro197Ser and Trp574Leu mutations were 3.98,11.50,40.38,38.19 and 311.43μmol L^(-1),respectively.In the determination of enzyme kinetics parameters,the Km and the maximum reaction velocity(Vmax)of the wild type were 5.18 mmol L^(-1)and 0.12 nmol mg^(-1)min^(-1),respectively,and the Km values of AHAS with Asp376Glu,Trp574Leu,Pro197Leu and Pro197Ser mutations were 0.38-0.93 times of the wild type.The Km value of the Pro197Arg mutation was 1.14times of the wild type,and the Vmax values of the five mutations were 1.17-3.33-fold compared to the wild type.It was found that the mutations increased the affinity of AHAS to the substrate,except for the Pro197Arg mutation.At a concentration of 0.0032-100 mmol L^(-1)branched-chain amino acids(BCAAs),the sensitivity of the other four mutant AHAS biotypes to feedback inhibition decreased,except for the Pro197Arg mutation.This study elucidated the effect of different mutations on AHAS function in Cyperus difformis and provided ideas for further study of resistance development.
基金The project supported by National Natural Science Foundation of China under Grant No. 60074020
文摘Through studying several kinds of chaotic mappings' distributions of orbital points, we analyze the capabilityof the chaotic mutations based on these mappings. Nunerical experiments support our conclusions very well. Thecapability analysis also led to a self-adaptive mechanism of chaotic mutation. The introducing of the self-adaptivechaotic mutation can improve the performance of genetic algorithm very prominently.
文摘Despite its apparently simple genetics,cystic fibrosis(CF) is a rather complex genetic disease.A lot of variability in the steps of the path from the cystic fibrosis transmembrane conductance regulator(CFTR) gene to the clinical manifestations originates an uncertain genotype- phenotype relationship.A major determinant of this uncertainty is the incomplete knowledge of the CFTR mutated genotypes,due to the high number of CFTR mutations and to the higher number of their combinations in trans and in cis.Also the very limited knowledge of functional effects of CFTR mutated alleles severely impairs our diagnostic and prognostic ability.The final phenotypic modulation exerted by CFTR modifier genes and interactome further complicates the framework.The next generation sequencing approach is a rapid,lowcost and high-throughput tool that allows a near complete structural characterization of CFTR mutated genotypes,as well as of genotypes of several other genes cooperating to the final CF clinical manifestations.This powerful method perfectly complements the new personalized therapeutic approach for CF.Drugs active on specific CFTR mutational classes are already available for CF patients or are in phase 3 trials.A complete genetic characterization has been becoming crucial for a correct personalized therapy.However,the need of a functional classification of each CFTR mutation potently arises.Future big efforts towards an ever more detailed knowledge of both structural and functional CFTR defects,coupled to parallel personalized therapeutic interventions decisive for CF cure can be foreseen.
文摘Through studying several kinds of chaotic mappings' distributions of orbital points, we analyze the capability of the chaotic mutations based on these mappings. Numerical experiments support our conclusions very well. The capability analysis also led to a self-adaptive mechanism of chaotic mutation. The introducing of the self-adaptive chaotic mutation can improve the performance of genetic algorithm very prominently.
基金This research was supported by the National Natural Science Foundation of China(No.81601337)the Fundamental Research Funds of Shandong University(No.2016HW006)+1 种基金the Key research and development program of Shandong Province(No.2019GSF108237)The authors thank all of the participants involved in this study.
文摘As a crucial transcription factor for spermatogenesis,GATA-binding protein 4(GATA4)plays important roles in the functioning of Sertoli and Leydig cells.Conditional knockout of GATA4 in mice results in age-dependent testicular atrophy and loss of fertility.However,whether GATA4 is associated with human azoospermia has not been reported.Herein,we analyzed the GATA4 gene by direct sequencing of samples obtained from 184 Chinese men with idiopathic nonobstructive azoospermia(NOA).We identified a missense mutation(c.191G>A,p.G64E),nine single-nucleotide polymorphisms(SNPs),and one rare variant(c.^(*)84C>T)in the 3′untranslated region(UTR).Functional studies demonstrated that the p.G64E mutation did not affect transactivation ability of GATA4 for spermatogenesis-related genes(claudin-11 and steroidogenic acute regulatory protein,Star),and the 3′UTR rare variant c.^(*)84C>T did not generate microRNA-binding sites to repress GATA4 expression.To our knowledge,this is the first report to investigate the association between GATA4 and azoospermia;our results indicate that mutations in GATA4 may not be pathogenic for NOA in Chinese men.
基金supported by the National Natural Science Foundation of China(32341051)the grant from Department of Agriculture and Rural Affairs of Hubei Province(HBZY2023B006-02)+2 种基金the National Funding(2023ZD04050)the National Natural Science Foundation of China Outstanding Youth(32125035)the National Key R&D Young Scientists Project(2022YFD1302000).
文摘Understanding genetic variant functionality is essential for advancing animal genomics and precision breeding.However,the lack of comprehensive functional genomic annotations in animals limits the effectiveness of most variant function assessment methods.In this study,we gather 1030 raw epigenomic datasets from 10 animal species and systematically annotate 7 types of key regulatory regions,creating a comprehensive functional annotation map of animal genomic variants.Our findings demonstrate that integrating variants with regulatory annotations can identify tissues and cell types underlying economic traits,underscoring the utility of these annotations in functional variant discovery.Using our functional annotations,we rank the functional potential of genetic variants and classify over 127 million candidate variants into 5 functional confidence categories,with high-confidence variants significantly enriched in eQTLs and trait-associated SNPs.Incorporating these variants into genomic prediction models can improve estimated breeding value accuracy,demonstrating their practical utility in breeding programs.To facilitate the use of our results,we develop the Integrated Functional Mutation(IFmut:http://www.ifmutants.com:8212)platform,enabling researchers to explore regulatory annotations and assess the functional potential of animal variants efficiently.Our study provides a robust framework for functional genomic annotations in farm animals,enhancing variant function assessment and breeding precision.
基金Supported by the National Natural Science Foundation of China,No.81970454.
文摘BACKGROUND ATP-binding cassette subfamily B member 4(ABCB4)deficiency is associated with cholestatic liver disease primarily because of missense mutations,and many variants remain unidentified.Here,we validate the pathogenicity and mechanism of ABCB4 variants in clinical and in vitro trials,hypothesizing that these variants are responsible for impaired biliary function and contribute to the development of cholestatic liver diseases.AIM To clarify the functional features and pathogenicity of ABCB4 variants.METHODS Clinical data were collected from five patients with cholestatic liver disease that was initially not detected by routine examinations.Later,whole-exome sequencing confirmed ABCB4 variants and the patients were treated from January 2017 to December 2023.Pathogenic mechanisms were analyzed using bioinformatics tools,and a cell model in vitro was established to investigate ABCB4 mRNA expression,multidrug resistance protein 3(MDR3)expression,cellular localization,and phosphatidylcholine secretion.Results were compared using Student's t-tests.RESULTS Five missense variants(c.1757T>A,c.1865G>A,c.2362C>T,c.2777C>T and c.3250C>T),one intron variant(c.537-32G>T),and one synonymous(c.C504T)variant were identified.Three of the five patients had various degrees of cholestasis,two presented with liver cirrhosis,and all had elevated gamma-glutamyl transferase.Three of the four patients who underwent a liver biopsy had bile duct dilation,and one had gallstones.Two of the four patients had normal and reduced MDR3 immunohistochemical levels.Bioinformatic analysis indicated that these variants were likely pathogenic except c.C504T variant.None of the missense variants influenced subcellular MDR3 Localization in vitro.However,the c.1865G>A variant significantly decreased ABCB4 mRNA values,and all missense variants down-regulated phosphatidylcholine secretion.CONCLUSION This study uncovered new ABCB4 variants and emphasized the pathogenic potential of specific variants.The findings from five patients provided insight into the pathogenic mechanisms underlying ABCB4-related diseases.
基金supported by the Jilin Science and Technology Development Program,China (20240602032RC)the Jilin Agricultural Science and Technology Innovation Project,China (CXGC2024ZD001)+1 种基金the Jilin Agricultural Science and Technology Innovation Project,China (CXGC2024ZY012)the Jilin Province Development and Reform Commission-Project for Improving the Independent Innovation Capacity of Major Grain Crops,China (2024C002)。
文摘Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).However,the detection and screening of transgenic lines remain major bottlenecks,being time-consuming,labor-intensive,and inefficient during transformation and subsequent mutation identification.A simple and efficient visual marker system plays a critical role in addressing these challenges.Recent studies demonstrated that the GmW1 and RUBY reporter systems were used to obtain visual transgenic soybean(Glycine max) plants(Chen L et al.2023;Chen et al.2024).
基金supported by the Provincial Technology Innovation Program of Shandong,Ningbo Science and Technology Innovation Project 2021Z132Weifang Seed Innovation Group.
文摘Dear Editor,Cucumber,Cucumis sativus,is a major vegetable crop globally.In addition to being consumed fresh or sliced,pickling cucumber represents a key cultivated type,widely grown in open fields across regions including the Americas,Europe,and Asia(Shetty and Wehner,2002).
文摘The Rosenbrock function optimization belongs to unconstrained optimization problems, and its global minimum value is located at the bottom of a smooth and narrow valley of the parabolic shape. It is very difficult to find the global minimum value of the function because of the little information provided for the optimization algorithm. According to the characteristics of the Rosenbrock function, this paper specifically proposed an improved differential evolution algorithm that adopts the self-adaptive scaling factor F and crossover rate CR with elimination mechanism, which can effectively avoid premature convergence of the algorithm and local optimum. This algorithm can also expand the search range at an early stage to find the global minimum of the Rosenbrock function. Many experimental results show that the algorithm has good performance of function optimization and provides a new idea for optimization problems similar to the Rosenbrock function for some problems of special fields.
文摘Based on the thermal stress distribution for functionally gradient material (FGM) plates, a Genetic Algorithm (GA) method for the thermal stresses optimum design of FGM plate with computer technologies is given. The minimum thermal stresses combination distribution for FGM is obtained.
基金the Research Fund for the Doctoral Program of Higher Education of China (20020008004).
文摘An adaptive immune-genetic algorithm （AIGA） is proposed to avoid premature convergence and guarantee the diversity of the population. Rapid immune response （secondary response）, adaptive mutation and density operators in the AIGA are emphatically designed to improve the searching ability, greatly increase the converging speed, and decrease locating the local maxima due to the premature convergence. The simulation results obtained from the global optimization to four multivariable and multi-extreme functions show that AIGA converges rapidly, guarantees the diversity, stability and good searching ability.
文摘Objective To determine the relationship between TSH receptor gene mutations and autonomously functioning thyroid adenomas (AFTAs). Methods The thyroid samples from 14 cases of diagnosed AFTAs were analyzed, with normal thyroid specimens adjacent to the tumors as controls. The 155 base pairs DNA fragments which encompassed the third cytoplasmic loop and the sixth transmembrane segments in the TSH receptor gene exon 10 were amplified by Polymerase chain reaction (PCR) and analyzed by the single-strand conformation polymorphism (SSCP). Direct sequencing of the PCR products was performed with Prism Dye Terminator Cycle Sequencing Core Kit. Results 6 of 14 AFTA specimens displayed abnormal migration in SSCP analysis. In sequence analysis of 3 abnormally migrated samples, one base substitution at nucleotide 1957 (A to C) and two same insertion mutations of one adenosine nucleotide between nucleotide 1972 and 1973 were identified. No mutations were found in controls. Conclusion This study confirmed the presence of TSH receptor gene mutations in AFTAs; both one-point substitution mutation and one-base insertion mutation were found to be responsible for the pathogenesis of AFTAs.
