Nonalcoholic fatty liver disease(NAFLD) is associated with obesity,insulin resistance,and type 2 diabetes.NAFLD represents a large spectrum of diseases ranging from(1) fatty liver(hepatic steatosis);(2) steatosis with...Nonalcoholic fatty liver disease(NAFLD) is associated with obesity,insulin resistance,and type 2 diabetes.NAFLD represents a large spectrum of diseases ranging from(1) fatty liver(hepatic steatosis);(2) steatosis with inflammation and necrosis;to(3) cirrhosis.The animal models to study NAFLD/nonalcoholic steatohepatitis(NASH) are extremely useful,as there are still many events to be elucidated in the pathology of NASH.The study of the established animal models has provided many clues in the pathogenesis of steatosis and steatohepatitis,but these remain incompletely understood.The different mouse models can be classified in two large groups.The first one includes genetically modified(transgenic or knockout) mice that spontaneously develop liver disease,and the second one includes mice that acquire the disease after dietary or pharmacological manipulation.Although the molecular mechanism leading to the development of hepatic steatosis in the pathogenesis of NAFLD is complex,genetically modified animal models may be a key for the treatment of NAFLD.Ideal animal models for NASH should closely resemble the pathological characteristics observed in humans.To date,no single animal model has encompassed the full spectrum of human disease progression,but they can imitate particular characteristics of human disease.Therefore,it is important that the researchers choose the appropriate animal model.This review discusses various genetically modified animal models developed and used in research on NAFLD.展开更多
Objective:To establish a systematic framework for selecting the best clustering algorithm and provide an evaluation method for clustering analyses of gene expression data. Methods: Based on data structure (internal in...Objective:To establish a systematic framework for selecting the best clustering algorithm and provide an evaluation method for clustering analyses of gene expression data. Methods: Based on data structure (internal information) and function classification (external information), the evaluation of gene expression data analyses were carried out by using 2 approaches. Firstly, to assess the predictive power of clusteringalgorithms, Entropy was introduced to measure the consistency between the clustering results from different algorithms and the known and validated functional classifications. Secondly, a modified method of figure of merit (adjust-FOM) was used as internal assessment method. In this method, one clustering algorithm was used to analyze all data but one experimental condition, the remaining condition was used to assess the predictive power of the resulting clusters. This method was applied on 3 gene expression data sets (2 from the Lyer's Serum Data Sets, and 1 from the Ferea's Saccharomyces Cerevisiae Data Set). Results: A method based on entropy and figure of merit (FOM) was proposed to explore the results of the 3 data sets obtained by 6 different algorithms, SOM and Fuzzy clustering methods were confirmed to possess the highest ability to cluster. Conclusion: A method based on entropy is firstly brought forward to evaluate clustering analyses.Different results are attained in evaluating same data set due to different function classification. According to the curves of adjust_FOM and Entropy_FOM, SOM and Fuzzy clustering methods show the highest ability to cluster on the 3 data sets.展开更多
The mechanism of ester hydrolysis has been extensively studied; however, the precise function of active-site residues in promoting catalysis is nuclear. We describe here the structural models for the complex of a cata...The mechanism of ester hydrolysis has been extensively studied; however, the precise function of active-site residues in promoting catalysis is nuclear. We describe here the structural models for the complex of a catalytic sntibody Fv fragment with a phosphonate transition -state analogue, constructed by using gene cloning, sequencing and molecular modeling, mainly based on a known X-ray structure of a catalytic atibody. Hydrophobic and electrostatic analyses of the Fv/analog and Fv/substrate interaction suggest the hydrolysis mechanism: In L91 and Tyr H97 play important roles to stabilize the β-naphthyl group of hapten through r-stack; His H35 donates a pair of free electrons at the atom NEZ to an active water and let it to be a partial hydroxide, which attacks the carbon atom of the carbonyl group of the substrate. Both His H35 and Arg L96 can form hydrogen bonds and stabilize the Anoinc tetrahedral intermediate formed during turnover. This mechanism emphasizes that an active water bridge may be formed during hydrolysis process.展开更多
Despite concerted efforts to create employment opportunities and the realized economic growth between 2000 and 2005, the unemployment rate in Namibia currently stands at 27.4%, according to the Labour Force Survey rel...Despite concerted efforts to create employment opportunities and the realized economic growth between 2000 and 2005, the unemployment rate in Namibia currently stands at 27.4%, according to the Labour Force Survey released in April 2013. The percentage of employed males in Namibia stands at 41.6% while that of employed females stand at 28.8% according to the National Human Resources Plan of May 2013. Analysts have put the blame on adverse climatic conditions, limited levels of skills, access to finance, and the structure of the economy. The frustration and discomfort caused by unemployment, especially among the youth, can threaten the country's peace and stability as it negatively impacts on the standard of living, crime rates, family happiness, and drug abuse.To date, studies on employment in Namibia have mainly concentrated on the micro and macro econometric approaches. It is important to examine how bio-demographic characteristics affect employment. This paper uses data from the 2010 Income and expenditure survey to establish the bio-demographic determinants of employment by fitting a binary logistic model. The outcome variable is employment status which is dichotomous. The independent variables which were guided by review of related literature and availability of data in the Income and Expenditure survey data set, included age-group, region, place of residence, marital status, education level, and gender. Results indicated that employment prospects in Namibia were influenced by the region, gender, marital status, and education level.展开更多
The article is an attempt to compile the results of CFD liquid flow simulation through pipeline section containing hydraulic elbow with the results of ultrasonic flow measurements. To carry out the measurements behind...The article is an attempt to compile the results of CFD liquid flow simulation through pipeline section containing hydraulic elbow with the results of ultrasonic flow measurements. To carry out the measurements behind the flow disturbing element(hydraulic elbow), an ultrasonic flowmeter with applied head set in accordance with the Z-type system was used. For comparative purposes, a flow simulation for 3 different turbulence models(k-epsilon, SST and SSG) was performed. It was found that with a proper ultrasonic flowmeter heads configurations, it is possible to measure the flow rate disturbed by the hydraulic elbow at any distance from the source of the disturbance. It has to use appropriate correction factor that can be determined by knowing the flow velocity profile equation. Based on comparison of CFD simulation results with experimental data, the accuracy/purposefulness of using individual turbulence models in the case of discussed hydraulic installation was evaluated.展开更多
The brain of the domestic pig(Sus scrofa domesticus)has drawn considerable attention due to its high similarities to that of humans.However,the cellular compositions of the pig brain(PB)remain elusive.Here we investig...The brain of the domestic pig(Sus scrofa domesticus)has drawn considerable attention due to its high similarities to that of humans.However,the cellular compositions of the pig brain(PB)remain elusive.Here we investigated the single-nucleus transcriptomic profiles of five regions of the PB(frontal lobe,parietal lobe,temporal lobe,occipital lobe,and hypothalamus)and identified 21 cell subpopulations.The cross-species comparison of mouse and pig hypothalamus revealed the shared and specific gene expression patterns at the single-cell resolution.Furthermore,we identified cell types and molecular pathways closely associated with neurological disorders,bridging the gap between gene mutations and pathogenesis.We reported,to our knowledge,the first single-cell atlas of domestic pig cerebral cortex and hypothalamus combined with a comprehensive analysis across species,providing extensive resources for future research regarding neural science,evolutionary developmental biology,and regenerative medicine.展开更多
The orchestrated expression of thousands of genes gives rise to the complexity of the human brain.However,the structures governing these myriad gene-gene interactions remain unclear.By analyzing transcription data fro...The orchestrated expression of thousands of genes gives rise to the complexity of the human brain.However,the structures governing these myriad gene-gene interactions remain unclear.By analyzing transcription data from more than 2000 sites in six human brains,we found that pairwise interactions between genes,without considering any higher-order interactions,are sufficient to predict the transcriptional pattern of the genome for individual brain regions and the transcriptional profile of the entire brain consisting of more than 200 areas.These findings suggest a quadratic complexity of transcriptional patterns in the human brain,which is much simpler than expected.In addition,using a pairwise interaction model,we revealed that the strength of gene-gene interactions in the human brain gives rise to the nearly maximal number of transcriptional clusters,which may account for the functional and structural richness of the brain.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
文摘Nonalcoholic fatty liver disease(NAFLD) is associated with obesity,insulin resistance,and type 2 diabetes.NAFLD represents a large spectrum of diseases ranging from(1) fatty liver(hepatic steatosis);(2) steatosis with inflammation and necrosis;to(3) cirrhosis.The animal models to study NAFLD/nonalcoholic steatohepatitis(NASH) are extremely useful,as there are still many events to be elucidated in the pathology of NASH.The study of the established animal models has provided many clues in the pathogenesis of steatosis and steatohepatitis,but these remain incompletely understood.The different mouse models can be classified in two large groups.The first one includes genetically modified(transgenic or knockout) mice that spontaneously develop liver disease,and the second one includes mice that acquire the disease after dietary or pharmacological manipulation.Although the molecular mechanism leading to the development of hepatic steatosis in the pathogenesis of NAFLD is complex,genetically modified animal models may be a key for the treatment of NAFLD.Ideal animal models for NASH should closely resemble the pathological characteristics observed in humans.To date,no single animal model has encompassed the full spectrum of human disease progression,but they can imitate particular characteristics of human disease.Therefore,it is important that the researchers choose the appropriate animal model.This review discusses various genetically modified animal models developed and used in research on NAFLD.
文摘Objective:To establish a systematic framework for selecting the best clustering algorithm and provide an evaluation method for clustering analyses of gene expression data. Methods: Based on data structure (internal information) and function classification (external information), the evaluation of gene expression data analyses were carried out by using 2 approaches. Firstly, to assess the predictive power of clusteringalgorithms, Entropy was introduced to measure the consistency between the clustering results from different algorithms and the known and validated functional classifications. Secondly, a modified method of figure of merit (adjust-FOM) was used as internal assessment method. In this method, one clustering algorithm was used to analyze all data but one experimental condition, the remaining condition was used to assess the predictive power of the resulting clusters. This method was applied on 3 gene expression data sets (2 from the Lyer's Serum Data Sets, and 1 from the Ferea's Saccharomyces Cerevisiae Data Set). Results: A method based on entropy and figure of merit (FOM) was proposed to explore the results of the 3 data sets obtained by 6 different algorithms, SOM and Fuzzy clustering methods were confirmed to possess the highest ability to cluster. Conclusion: A method based on entropy is firstly brought forward to evaluate clustering analyses.Different results are attained in evaluating same data set due to different function classification. According to the curves of adjust_FOM and Entropy_FOM, SOM and Fuzzy clustering methods show the highest ability to cluster on the 3 data sets.
文摘The mechanism of ester hydrolysis has been extensively studied; however, the precise function of active-site residues in promoting catalysis is nuclear. We describe here the structural models for the complex of a catalytic sntibody Fv fragment with a phosphonate transition -state analogue, constructed by using gene cloning, sequencing and molecular modeling, mainly based on a known X-ray structure of a catalytic atibody. Hydrophobic and electrostatic analyses of the Fv/analog and Fv/substrate interaction suggest the hydrolysis mechanism: In L91 and Tyr H97 play important roles to stabilize the β-naphthyl group of hapten through r-stack; His H35 donates a pair of free electrons at the atom NEZ to an active water and let it to be a partial hydroxide, which attacks the carbon atom of the carbonyl group of the substrate. Both His H35 and Arg L96 can form hydrogen bonds and stabilize the Anoinc tetrahedral intermediate formed during turnover. This mechanism emphasizes that an active water bridge may be formed during hydrolysis process.
文摘Despite concerted efforts to create employment opportunities and the realized economic growth between 2000 and 2005, the unemployment rate in Namibia currently stands at 27.4%, according to the Labour Force Survey released in April 2013. The percentage of employed males in Namibia stands at 41.6% while that of employed females stand at 28.8% according to the National Human Resources Plan of May 2013. Analysts have put the blame on adverse climatic conditions, limited levels of skills, access to finance, and the structure of the economy. The frustration and discomfort caused by unemployment, especially among the youth, can threaten the country's peace and stability as it negatively impacts on the standard of living, crime rates, family happiness, and drug abuse.To date, studies on employment in Namibia have mainly concentrated on the micro and macro econometric approaches. It is important to examine how bio-demographic characteristics affect employment. This paper uses data from the 2010 Income and expenditure survey to establish the bio-demographic determinants of employment by fitting a binary logistic model. The outcome variable is employment status which is dichotomous. The independent variables which were guided by review of related literature and availability of data in the Income and Expenditure survey data set, included age-group, region, place of residence, marital status, education level, and gender. Results indicated that employment prospects in Namibia were influenced by the region, gender, marital status, and education level.
文摘The article is an attempt to compile the results of CFD liquid flow simulation through pipeline section containing hydraulic elbow with the results of ultrasonic flow measurements. To carry out the measurements behind the flow disturbing element(hydraulic elbow), an ultrasonic flowmeter with applied head set in accordance with the Z-type system was used. For comparative purposes, a flow simulation for 3 different turbulence models(k-epsilon, SST and SSG) was performed. It was found that with a proper ultrasonic flowmeter heads configurations, it is possible to measure the flow rate disturbed by the hydraulic elbow at any distance from the source of the disturbance. It has to use appropriate correction factor that can be determined by knowing the flow velocity profile equation. Based on comparison of CFD simulation results with experimental data, the accuracy/purposefulness of using individual turbulence models in the case of discussed hydraulic installation was evaluated.
基金the China Postdoctoral Science Foundation(2017M622795)the Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ20180507183628543)the Fundamental Research Funds for the Central Universities(2662018PY025 and 2662017PY105)。
文摘The brain of the domestic pig(Sus scrofa domesticus)has drawn considerable attention due to its high similarities to that of humans.However,the cellular compositions of the pig brain(PB)remain elusive.Here we investigated the single-nucleus transcriptomic profiles of five regions of the PB(frontal lobe,parietal lobe,temporal lobe,occipital lobe,and hypothalamus)and identified 21 cell subpopulations.The cross-species comparison of mouse and pig hypothalamus revealed the shared and specific gene expression patterns at the single-cell resolution.Furthermore,we identified cell types and molecular pathways closely associated with neurological disorders,bridging the gap between gene mutations and pathogenesis.We reported,to our knowledge,the first single-cell atlas of domestic pig cerebral cortex and hypothalamus combined with a comprehensive analysis across species,providing extensive resources for future research regarding neural science,evolutionary developmental biology,and regenerative medicine.
基金the National Key Research and Development Program of China(2017YFA0105203)the National Natural Science Foundation of China(81671855)+1 种基金Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32040200)Beijing Academy of Artificial Intelligence,and Beijing Advanced Discipline Fund。
文摘The orchestrated expression of thousands of genes gives rise to the complexity of the human brain.However,the structures governing these myriad gene-gene interactions remain unclear.By analyzing transcription data from more than 2000 sites in six human brains,we found that pairwise interactions between genes,without considering any higher-order interactions,are sufficient to predict the transcriptional pattern of the genome for individual brain regions and the transcriptional profile of the entire brain consisting of more than 200 areas.These findings suggest a quadratic complexity of transcriptional patterns in the human brain,which is much simpler than expected.In addition,using a pairwise interaction model,we revealed that the strength of gene-gene interactions in the human brain gives rise to the nearly maximal number of transcriptional clusters,which may account for the functional and structural richness of the brain.
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.