The use of the three genetic models viz. additive, dominant and recessive in </span><span style="font-family:Verdana;">Genome-wide association study (GWAS) is a common and powerful ap</span>...The use of the three genetic models viz. additive, dominant and recessive in </span><span style="font-family:Verdana;">Genome-wide association study (GWAS) is a common and powerful ap</span><span style="font-family:Verdana;">proach to study the association between genetic variants and a trait (disease). The selection of these models depends on the pattern of inheritance and the scope </span><span style="font-family:Verdana;">of the study. GWAS typically focuses on single-nucleotide polymorphism</span><span style="font-family:Verdana;"> (SNPs) and common human diseases in a case-control setup. In order to study this type of association between the risk genotype and the phenotype for a given inheritance pattern, the use of these genetic models helps to identify the disease risk appropriately. This study provides an overview of the existing genetic models (additive, dominant and recessive) and a practical demonstration of these model tests for the contingency tables of SNP genotypes and the disease phenotypes in a case-control setting.展开更多
Parkinson’s disease(PD)relates to defective mitochondrial quality control in the dopaminergic motor network.Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to P...Parkinson’s disease(PD)relates to defective mitochondrial quality control in the dopaminergic motor network.Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to PD onset,pinpointing mitophagy and inflammation as the culprit pathways involved in neuronal loss in the substantia nigra(SNpc).In a reciprocal manner,LRRK2 functions in the regulation of basal flux and inflammatory responses responsible for PINK1/Parkin-dependent mitophagy activation.Pharmacological intervention in these diseasemodifying pathways may facilitate the development of novel PD therapeutics,despite the current lack of an established drug evaluation model.As such,we reviewed the feasibility of employing the versatile global Pink1knockout(KO)rat model as a self-sufficient,spontaneous PD model for investigating both disease etiology and drug pharmacology.These rats retain clinical features encompassing basal mitophagic flux changes with PD progression.We demonstrate the versatility of this PD rat model based on the incorporation of additional experimental insults to recapitulate the proinflammatory responses observed in PD patients.展开更多
Exploring genetic mechanism of the first female flower node and the first male flower node in bitter gourd has practical significance for formulating breeding strategy. In this article, a cross was made between CN19-1...Exploring genetic mechanism of the first female flower node and the first male flower node in bitter gourd has practical significance for formulating breeding strategy. In this article, a cross was made between CN19-1 and Thai4-6, and the F2segregation population was also constructed through F1selfing. The genetic characteristics of the first female flower node and the first male flower node were analyzed by adopting the major gene plus polygene mixed genetic model. The data analysis results showed that the first female flower node and the first male flower node were continuous distribution in the F2segregation population. E-2 model was the most suitable model for the genetic analysis of the first female flower node and the first male flower node. The additive effect values of the 2 pairs of major genes controlling the first female flower node were 2.722 and 1.862 8 respectively, the dominant effect values were-2.721 6 and-0.171 8, respectively. The additive effect value of polygene was-0.839 2, and the dominant effect value of polygene was 2.225 4. The heritability of major genes and polygene were 83.73% and 1.54%, respectively. The additive effect values of the 2 pairs of major genes controlling the first male flower node were 17.746 9 and 3.972, respectively, the dominant effect values were 5.191 6 and-3.972, respectively. The additive effect value of polygene was-20.530 5, and the dominant effect value was-4.141 4. The heritability of major genes and polygene was 92.34% and 4.7%, respectively. This study could provide a theoretical basis for bitter gourd breeding.展开更多
It is recognized that developing valid animal models is essential for the research on the neurobiological mechanisms of (and treatments for) psychiatric disorders, even when these are as complex as schizophrenia. To b...It is recognized that developing valid animal models is essential for the research on the neurobiological mechanisms of (and treatments for) psychiatric disorders, even when these are as complex as schizophrenia. To be considered a valid analogue of the disorder, a given model should present good face validity (i.e. similarity of symptoms), good predictive validity (i.e. similarity of treatment effects and potential for discovering novel treatments) and enough construct validity (i.e. the model should help discover neurobiological mechanisms underlying the disorder or some relevant symptoms). The complexity of symptoms (positive, negative and cognitive) of schizophrenia makes it a very difficult task for a model to mimic all the main features of the disorder, but some rodent (mouse and rat) models have behavioural and even neurobiological phenotype characteristics resembling positive-like symptoms, cognitive symptoms and some neurochemical features of schizophrenia. As several recent works have already reviewed the main behavioural and developmental models, as well as the most used drug-induced, lesion-induced and genetic mouse models, the present review focuses on describing the most relevant genetically-based rat models of schizophrenia-relevant symptoms. Thus, we discuss several selective breeding programs leading to rat lines/strains which present impaired prepulse inhibition (PPI) of the acoustic startle response and (in some cases) latent inhibition deficits (both of which may be considered as endophenotypes of schizophrenia related with pre-attentive processes and attention, respectively), as well as other schizophrenia-relevant symptoms (e.g. learning deficits). Evidence is presented for the effects of genetic background on PPI (and other symptoms/phenotypes), as well as for environmental influences on genetic predisposition to enhanced apomorphine (mixed dopamine receptor agonist) effects. Some of the described rat models appear to present face validity and, to a certain extent, construct validity. While efforts should be made to evaluate the predictive validity of these genetic rat models, we propose that they have the advantage (over mouse knockouts, for example) of better representing “normal” genetic, neurobiological and phenotype variation, thus allowing the study of associations among them by means of genetic mapping or gene expression studies.展开更多
A hyper-ellipsoid model, using genetic algorithm as method of computation, has been proposed to be used in certain metallurgical processes. lt is especially suitable for the modelling of the matallurgical processes wi...A hyper-ellipsoid model, using genetic algorithm as method of computation, has been proposed to be used in certain metallurgical processes. lt is especially suitable for the modelling of the matallurgical processes with data-structure of "inclusion type".展开更多
Objective:To summarize the precise association between pulmonary tuberculosis(PTB) and P2x7 A1513 C gene polymorphism.Methods:PubMed and Google Scholar web-databases were searched for the studies reporting the associa...Objective:To summarize the precise association between pulmonary tuberculosis(PTB) and P2x7 A1513 C gene polymorphism.Methods:PubMed and Google Scholar web-databases were searched for the studies reporting the association of P2x7 A1513 C polymorphism and PTB risk.A meta-analysis was performed for the selected case-control studies and pooled odds ratios(ORs) and 95%confidence intervals(95%CIs) were calculated for all the genetic models.Results:Eleven studies comprising 2 678 controls and 2 113 PTB cases were included in this meta-analysis.We observed overall no significant risk in all the five genetic models.When stratified population by the ethnicity,Caucasian population failed to show any risk of PTB in all the genetics models.In Asian ethnicity,variant allele(C vs.A:P=0.001;QR=1.375,95%CI=1.159-1.632) and heterozygous genotype(AC vs.AA:P=0.001;OR=1.570,95%CI=1.269-1.944) demonstrated significant increased risk of PTB.Likewise,recessive genetic model(CC+AC vs.AA:P=0.001;OR=1.540,95%CI= 1.255-1.890) also demonstrated increased risk of PTB in Asians.Conclusions:Our meta-analysis did not suggest the association of P2x7 A1513 C polymorphism with PTB risk in overall or separately in Caucasian population.However,it plays a significant risk factor for predisposing PTB in Asians.Future larger sample and expression studies are needed to validate this association.展开更多
[Objectives]To explore the genetic mechanism that leaf length and leaf width in bitter gourd has realistic guiding significance for formulating breeding strategy.[Methods]In this paper,the cross was made between CN19-...[Objectives]To explore the genetic mechanism that leaf length and leaf width in bitter gourd has realistic guiding significance for formulating breeding strategy.[Methods]In this paper,the cross was made between CN19-1 and Thai4-6 and an F2segregation population was constructed.The genetic characteristics of leaf length and leaf width were analyzed by employing the major gene plus polygene mixed genetic model.[Results]The data analysis results demonstrated that the leaf length and leaf width of the F_(2) segregation population showed continuous distribution.The optimum model for leaf length genetic analysis was A-1,the additive effect value of the major gene was 3.1766,the dominant effect value was-3.1766,and the heritability was 74.51%.The optimum model for leaf width genetic analysis was B-1.The additive effect values of 2 pairs of major genes controlling the leaf width were 3.1917 and 0.9623,respectively.The dominant effect values were-1.3135 and-0.3463,respectively.The additive×additive interaction effect was-0.3591,the additive×dominant interaction effect was-0.2570,the dominant×additive interaction effect was 1.9916,the dominant×dominant interaction effect was 1.9686.The heritability of major genes was 96.67%.[Conclusions]This study is expected to provide a theoretical basis for the breeding of bitter gourd.展开更多
[Objectives]The paper was to verify the genetic mechanism of weight per fruit and fruit length in bitter gourd and to provide guidance for formulating breeding strategy.[Methods]In this study,a cross was made between ...[Objectives]The paper was to verify the genetic mechanism of weight per fruit and fruit length in bitter gourd and to provide guidance for formulating breeding strategy.[Methods]In this study,a cross was made between CN19-1 and Thai4-6,and a Fsegregation population was also constructed.The genetic characteristics of weight per fruit and fruit length were analyzed by employing major gene plus polygene mixed genetic model.[Results]The weight per fruit and fruit length showed continuous distribution in Fsegregation population.The optimal model for weight per fruit and fruit length was the same(A-1 model).The major gene additive effect value of weight per fruit was 46.1474,the dominant effect value was-46.1005,and the major gene heritability was 52.47%.The major gene additive effect value of fruit length was 2.456,the dominant effect value was-2.455,and the major gene heritability was 52.52%.The results showed that weight per fruit and fruit length were mainly controlled by a pair of major genes.[Conclusions]This study can provide a theoretical basis for bitter gourd breeding.展开更多
Performing the genetic mechanism research of internode length in bitter gourd has important guiding significance for making breeding strategy. A cross was made between CN19-1 and Thai4-6, and an F2 segregation populat...Performing the genetic mechanism research of internode length in bitter gourd has important guiding significance for making breeding strategy. A cross was made between CN19-1 and Thai4-6, and an F2 segregation population was constructed. The genetic characteristic of the internode length was analyzed through employing the major gene plus polygene mixed genetic model. The results showed that the internode length was continuous distribution in the F2 population. The optimum model for internode length genetic analysis was B-1. The additive effect values of two pairs of major genes controlling the internode length were 3.206 3 and 2.638 3, respectively, which showed a positive effect. The dominant effect values were-3.434 6 and-1.459 6, respectively, which showed a negative effect. The dominant degree of major genes is-1.07 and-0.55, respectively, indicating that the first pair of major genes was over dominant and the second pair of major genes was incompletely dominant. The heritability of the major gene was 82.25%, indicating the genetic stability was high. This study could provide a theoretical reference for the breeding of bitter gourd.展开更多
Background Chronic otitis media(COM) is a significant clinical problem.Understanding the mechanisms of COM is critical for its control and treatment.However,little is known of the processes leading to COM as a result ...Background Chronic otitis media(COM) is a significant clinical problem.Understanding the mechanisms of COM is critical for its control and treatment.However,little is known of the processes leading to COM as a result of lack of animal models of N-ethyl-N-nitrosourea(ENU) induced mutations in otitis media with effusion(OME).Methods Otoscopy and auditory brain response(ABR) evaluation were carried out under sedation in Nmf391nmf/nmf mice of 2,4,6 and 8 months of age.The mice were killed for study of middle and inner ear pathology.Results Tympanic membrane visualization and ABR thresholds in 1-to 8-month-old Nmf391nmf/nmf mice showed spontaneous OME and inner ear diseases in approximately 100% of the animals.The significant elevation of ABR thresholds suggested a sensorineural component in hearing loss in addition to the conductive loss.Middle and inner ear histology showed various degrees of outer hair cells loss and middle ear inflammation in all the mice,but no inflammation cells in the inner ear.The ABR threshold at 32 kHz was significantly elevated.Conclusions This study shows histopathologic changes in the Nmf391nmf/nmf mouse model of COM with effusion that have not been reported in human COM.This ENU induced mutation model of COM will be valuable for the characterization of middle ear inflammation and inner ear disease processes that are induced by middle ear infections.We propose that COM with effusion in this ENU induced mutation model is the cause of the cochlea hair cells damage.展开更多
Cancer is a major stress for public well-being and is the most dreadful disease.The models used in the discovery of cancer treatment are continuously changing and extending toward advanced preclinical studies.Cancer m...Cancer is a major stress for public well-being and is the most dreadful disease.The models used in the discovery of cancer treatment are continuously changing and extending toward advanced preclinical studies.Cancer models are either naturally existing or artificially prepared experimental systems that show similar features with human tumors though the heterogeneous nature of the tumor is very familiar.The choice of the most fitting model to best reflect the given tumor system is one of the real difficulties for cancer examination.Therefore,vast studies have been conducted on the cancer models for developing a better understanding of cancer invasion,progression,and early detection.These models give an insight into cancer etiology,molecular basis,host tumor interaction,the role of microenvironment,and tumor heterogeneity in tumor metastasis.These models are also used to predict novel can-cer markers,targeted therapies,and are extremely helpful in drug development.In this review,the potential of cancer models to be used as a platform for drug screening and therapeutic discoveries are highlighted.Although none of the cancer models is regarded as ideal because each is associated with essential caveats that restraint its application yet by bridging the gap between preliminary cancer research and transla-tional medicine.However,they promise a brighter future for cancer treatment.展开更多
Recently,many regression models have been presented for prediction of mechanical parameters of rocks regarding to rock index properties.Although statistical analysis is a common method for developing regression models...Recently,many regression models have been presented for prediction of mechanical parameters of rocks regarding to rock index properties.Although statistical analysis is a common method for developing regression models,but still selection of suitable transformation of the independent variables in a regression model is diffcult.In this paper,a genetic algorithm(GA)has been employed as a heuristic search method for selection of best transformation of the independent variables(some index properties of rocks)in regression models for prediction of uniaxial compressive strength(UCS)and modulus of elasticity(E).Firstly,multiple linear regression(MLR)analysis was performed on a data set to establish predictive models.Then,two GA models were developed in which root mean squared error(RMSE)was defned as ftness function.Results have shown that GA models are more precise than MLR models and are able to explain the relation between the intrinsic strength/elasticity properties and index properties of rocks by simple formulation and accepted accuracy.展开更多
The red swamp crayfish,Procambarus clarkii,is an economically important species especially in China.Their exoskeleton places serious constraints on growth and culture management.Their growth is achieved through interm...The red swamp crayfish,Procambarus clarkii,is an economically important species especially in China.Their exoskeleton places serious constraints on growth and culture management.Their growth is achieved through intermittent molting/ecdysis.The longitudinal genetic dynamics for growth-related traits at different ecdysial points in P.clarkii has been unclear to date.In this study,conditional genetic analysis was carried out for growth-related traits(body weight,body length,chela length,and cephalothorax length)based upon a mixed genetic model with conditional additive,dominance,and genotype by environment effects in P.clarkii.A complete diallel cross was made among three geographic populations of P.clarkii for the genetic mating design.Results of the conditional genetic analysis showed that from 4 th molt to 9 th molt the conditional additive variations were increased significantly whereas the conditional non-additive genetic variations(dominance and genotype by environment interaction)were decreased significantly for these growth-related traits.This indicated that lots of new expression of additive effect genes for body weight,body length,chela length,and cephalothorax length occurred during ontogeny,and environment played a signifi cant role in the expression of genes affecting these growth-related traits.Growth of the four traits was mainly affected by non-additive genetic effects in early developmental stage(prior to 4 th molt).The cumulative conditional additive variation for the growth-related traits from 4 th molt to 9 th molt accounted for a large majority of the total conditional additive variations from 2 nd molt to 9 th molt,indicating that this period was very important for the growth of this species.Using the conditional analysis method,dynamics of growth-related traits during an important ontogenetic phase of red swamp crayfish was uncovered.Our results provide valuable insights into refining production of this species.展开更多
Epithelial ovarian cancer(EOC) is the leading cause of gynecological cancer-related mortality in the developed world. EOC is a heterogeneous disease represented by several histological and molecular subtypes. Therefor...Epithelial ovarian cancer(EOC) is the leading cause of gynecological cancer-related mortality in the developed world. EOC is a heterogeneous disease represented by several histological and molecular subtypes. Therefore, exploration of relevant preclinical animal models that consider the heterogenic nature of EOC is of great importance for the development of novel therapeutic strategies that can be translated clinically to combat this devastating disease. In this review, we discuss recent progress in the development of preclinical mouse models for EOC study as well as their advantages and limitations.展开更多
Scour is a natural phenomenon that is created by the rivers streams or the flood which brings about transferring or eroding of bed materials. To have accurate and safe erosion control structures design, maximum scour ...Scour is a natural phenomenon that is created by the rivers streams or the flood which brings about transferring or eroding of bed materials. To have accurate and safe erosion control structures design, maximum scour depth in downstream of the structures gains specific significance. In the current study, M5 model tree as remedy data mining approaches is suggested to estimate the scour depth around the abutments. To do this, Kayaturk laboratory data (2005), with different hydraulic conditions, are used. Then, the results of M5 model were also compared with genetic programming (GP) and pervious empirical results to investigate the applicability, ability, and accuracy of these procedures. To examine the accuracy of the results yielded from the M5 and GP procedures, two performance indicators (determination coefficient (R2) and root mean square error (RMSE)) were used. The comparison test of results clearly shows that the implementation of M5 technique sounds satisfactory regarding the performance indicators (R<sup>2</sup> = 0.944 and RMSE = 0.126) with less deviation from the numerical values. In addition, M5 tree model, by presenting relationships based on liner regression, has good capability to estimate the depth of scour abutment for engineers in practical terms.展开更多
The prediction accuracy of existing models of the rolling force of a thick plate is always very low.To address this problem,a high-precision genetic algorithm-backpropagation network(GA-BP)model of deformation resista...The prediction accuracy of existing models of the rolling force of a thick plate is always very low.To address this problem,a high-precision genetic algorithm-backpropagation network(GA-BP)model of deformation resistance was built,and its integration with the traditional fitted model was further established.Then,a novel rolling force model was obtained by embedding the integration model of deformation resistance in the original model of rolling force.According to this research idea,the industrial data are normalized at first.On this basis,the interactions among the process parameters were disclosed through the variance analysis,and then described by various virtual factors.These factors are set as part of input parameters.Then,the optimal structure of the GA-BP model of deformation resistance was determined and an integration model of deformation resistance was built.Finally,a novel rolling force model is obtained by substituting the traditional fitted deformation resistance into the Sims model with the integration model of the deformation resistance.The results proves that the introduction of virtual factors can increase the hit rate of±5%from 75.8%to 78%and can reduce the root mean square error from 4.72%to 4.48%.Besides,it is found that the mean relative error of the traditional fitted deformation resistance is 0.142,while that of the modified deformation resistance is only 0.03.In addition,the mean relative error in the original rolling force model is 0.145,while that of the present model is only 0.03.展开更多
This study re-evaluates the characteristics of Cu-Pb-Ag and Fe-Mn ore mineralization of the Kombat Mine and Gross Otavi Mine based on field geology, fluid inclusions, petrology, mineralogy, and geochemistry. This is t...This study re-evaluates the characteristics of Cu-Pb-Ag and Fe-Mn ore mineralization of the Kombat Mine and Gross Otavi Mine based on field geology, fluid inclusions, petrology, mineralogy, and geochemistry. This is to determine the genetic relationship between Fe-Mn and Cu-Pb-Ag mineralization. The study has established that the Cu-Pb-Ag ore at the Kombat Mine can be classified as a variant of MVT-type deposit, whereas the Fe-Mn ore can be classified as a stratiform-syn-sedimentary deposit. The formation of the MVT-type deposit is associated with a hydrothermal fluid system with a mean temperature of 183<span style="white-space:nowrap;">°</span>C and mean salinity of 12.85 wt. % NaCl equivalent. The syn-sedimentary Fe-Mn ore, which is largely associated with calc-silicate lithologies, consists mainly of magnetite and hematite with minor pyrite, hausmannite and jacobsite, and was deposited by diagenetic and mixed diagenetic-hydrogenetic processes under changing oxic and anoxic conditions within the sedimentary basin. Acceptable geochemical exploration indicators of the existing mineralization include anomalous values above 0.5% Cu, 0.2% S;0.05% Pb;0.04% As;0.01% Zn;V, W, Mo, and Ag are 0.002%. Mineralogical indicators include chalcopyrite, bornite, covellite and galena with minor chalcocite, sphalerite, and tennantite for the Cu-Pb MVT-type ores at Kombat Mine.展开更多
The leaf area index(LAI)is an important agroecological physiological parameter affecting vegetation growth.To apply the genetic algorithms neural network model(GANNM)to the remote sensing inversion of winter wheat LAI...The leaf area index(LAI)is an important agroecological physiological parameter affecting vegetation growth.To apply the genetic algorithms neural network model(GANNM)to the remote sensing inversion of winter wheat LAI throughout the growth cycle and based on GaoFen-3 Synthetic aperture radar(GF-3 SAR)images and GaoFen-1 Wide Field of View(GF-1 WFV)images,the Xiangfu District in the east of Kaifeng City,Henan Province,was selected as the testing region.Winter wheat LAI data from five growth stages were combined,and optical and microwave polarization decomposition vegetation index models were used.The backscattering coefficient was extracted by modified water cloud model(MWCM),and the LAI was obtained by MWCM inversion as input factors to construct GANNM to invert LAI.The root mean square error(RMSE)and determination coefficient(R2)were used as evaluation indicators of the model.The fitting accuracy of winter wheat LAI in five growth stages by GANNM inversion was better than that of the BP neural network model;the R2 was higher than 0.8,and RMSE was lower than 0.3,indicating that the model could accurately invert the growth status of winter wheat in five growth stages.展开更多
Current pharmacogenetic studies have obtained many genetic models that can predict the therapeutic efficacy of anticancer drugs.Although some of these models are of crucial importance and have been used in clinical pr...Current pharmacogenetic studies have obtained many genetic models that can predict the therapeutic efficacy of anticancer drugs.Although some of these models are of crucial importance and have been used in clinical practice,these very valuable models have not been well adopted into cancer research to promote the development of cancer therapies due to the lack of integration and standards for the existing data of the pharmacogenetic studies.For this purpose,we built a resource investigating genetic model of drug response(iGMDR),which integrates the models from in vitro and in vivo pharmacogenetic studies with different omics data from a variety of technical systems.In this study,we introduced a standardized process for all integrations,and described how users can utilize these models to gain insights into cancer.iGMDR is freely accessible at https://igmdr.modellab.cn.展开更多
Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated death around the world due to advanced clinical stage at diagnosis,high incidence of recurrence and metastasis after surgical treatment.It...Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated death around the world due to advanced clinical stage at diagnosis,high incidence of recurrence and metastasis after surgical treatment.It is in urgent need to create appropriate animal models to explore the mechanism,patterns,risk factors,and therapeutic strategies of HCC metastasis and recurrence.However,most of the established models lack the phenotype of invasion and metastasis in patient,or have unstable phenotype.To establish HCC models with stable metastasis phenotype requires profound understanding in cancer metastasis biology and scientific methodology.Over the past 3 decades,HCC models with stable metastasis have been extensively studied.This paper reviewed the history and development of HCC animal models and cell models,focusing on the screening and maintaining of metastatic potential and phenotype.In-depth studies using these models vastly promote the understanding of cellular and molecular mechanisms and development of therapeutic strategies on HCC metastasis.展开更多
文摘The use of the three genetic models viz. additive, dominant and recessive in </span><span style="font-family:Verdana;">Genome-wide association study (GWAS) is a common and powerful ap</span><span style="font-family:Verdana;">proach to study the association between genetic variants and a trait (disease). The selection of these models depends on the pattern of inheritance and the scope </span><span style="font-family:Verdana;">of the study. GWAS typically focuses on single-nucleotide polymorphism</span><span style="font-family:Verdana;"> (SNPs) and common human diseases in a case-control setup. In order to study this type of association between the risk genotype and the phenotype for a given inheritance pattern, the use of these genetic models helps to identify the disease risk appropriately. This study provides an overview of the existing genetic models (additive, dominant and recessive) and a practical demonstration of these model tests for the contingency tables of SNP genotypes and the disease phenotypes in a case-control setting.
基金supported by the KIZ-CUHK Joint Lab of Bioresources and Molecular Research of Common Diseases(4750378)the VC Discretionary Fund provided to the Hong Kong Branch of Chinese Academy of Science Center for Excellence in Animal Evolution and Genetics(Acc 8601011)partially by the State Key Laboratory CUHKJinan MOE Key Laboratory for Regenerative medicine(2622009)。
文摘Parkinson’s disease(PD)relates to defective mitochondrial quality control in the dopaminergic motor network.Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to PD onset,pinpointing mitophagy and inflammation as the culprit pathways involved in neuronal loss in the substantia nigra(SNpc).In a reciprocal manner,LRRK2 functions in the regulation of basal flux and inflammatory responses responsible for PINK1/Parkin-dependent mitophagy activation.Pharmacological intervention in these diseasemodifying pathways may facilitate the development of novel PD therapeutics,despite the current lack of an established drug evaluation model.As such,we reviewed the feasibility of employing the versatile global Pink1knockout(KO)rat model as a self-sufficient,spontaneous PD model for investigating both disease etiology and drug pharmacology.These rats retain clinical features encompassing basal mitophagic flux changes with PD progression.We demonstrate the versatility of this PD rat model based on the incorporation of additional experimental insults to recapitulate the proinflammatory responses observed in PD patients.
基金Supported by Hainan Science and Technology Project (No. ZDYF2020229ZDKJ2021010)Scientific Research Program of Hainan Key Laboratory of Vegetable Biology and Hainan Key Laboratory for Quality Regulation of Tropical Horticultural Crops (No. HNZDSYS(YY)-03)。
文摘Exploring genetic mechanism of the first female flower node and the first male flower node in bitter gourd has practical significance for formulating breeding strategy. In this article, a cross was made between CN19-1 and Thai4-6, and the F2segregation population was also constructed through F1selfing. The genetic characteristics of the first female flower node and the first male flower node were analyzed by adopting the major gene plus polygene mixed genetic model. The data analysis results showed that the first female flower node and the first male flower node were continuous distribution in the F2segregation population. E-2 model was the most suitable model for the genetic analysis of the first female flower node and the first male flower node. The additive effect values of the 2 pairs of major genes controlling the first female flower node were 2.722 and 1.862 8 respectively, the dominant effect values were-2.721 6 and-0.171 8, respectively. The additive effect value of polygene was-0.839 2, and the dominant effect value of polygene was 2.225 4. The heritability of major genes and polygene were 83.73% and 1.54%, respectively. The additive effect values of the 2 pairs of major genes controlling the first male flower node were 17.746 9 and 3.972, respectively, the dominant effect values were 5.191 6 and-3.972, respectively. The additive effect value of polygene was-20.530 5, and the dominant effect value was-4.141 4. The heritability of major genes and polygene was 92.34% and 4.7%, respectively. This study could provide a theoretical basis for bitter gourd breeding.
基金Supported by grants for the MICINN(PSI2009-10532)“Fundacio La Marato TV3”(ref.092630/31)and 2009SGR-0051.I.O.is recipient of a PhD FI fellowship(DGR 2014).
文摘It is recognized that developing valid animal models is essential for the research on the neurobiological mechanisms of (and treatments for) psychiatric disorders, even when these are as complex as schizophrenia. To be considered a valid analogue of the disorder, a given model should present good face validity (i.e. similarity of symptoms), good predictive validity (i.e. similarity of treatment effects and potential for discovering novel treatments) and enough construct validity (i.e. the model should help discover neurobiological mechanisms underlying the disorder or some relevant symptoms). The complexity of symptoms (positive, negative and cognitive) of schizophrenia makes it a very difficult task for a model to mimic all the main features of the disorder, but some rodent (mouse and rat) models have behavioural and even neurobiological phenotype characteristics resembling positive-like symptoms, cognitive symptoms and some neurochemical features of schizophrenia. As several recent works have already reviewed the main behavioural and developmental models, as well as the most used drug-induced, lesion-induced and genetic mouse models, the present review focuses on describing the most relevant genetically-based rat models of schizophrenia-relevant symptoms. Thus, we discuss several selective breeding programs leading to rat lines/strains which present impaired prepulse inhibition (PPI) of the acoustic startle response and (in some cases) latent inhibition deficits (both of which may be considered as endophenotypes of schizophrenia related with pre-attentive processes and attention, respectively), as well as other schizophrenia-relevant symptoms (e.g. learning deficits). Evidence is presented for the effects of genetic background on PPI (and other symptoms/phenotypes), as well as for environmental influences on genetic predisposition to enhanced apomorphine (mixed dopamine receptor agonist) effects. Some of the described rat models appear to present face validity and, to a certain extent, construct validity. While efforts should be made to evaluate the predictive validity of these genetic rat models, we propose that they have the advantage (over mouse knockouts, for example) of better representing “normal” genetic, neurobiological and phenotype variation, thus allowing the study of associations among them by means of genetic mapping or gene expression studies.
文摘A hyper-ellipsoid model, using genetic algorithm as method of computation, has been proposed to be used in certain metallurgical processes. lt is especially suitable for the modelling of the matallurgical processes with data-structure of "inclusion type".
文摘Objective:To summarize the precise association between pulmonary tuberculosis(PTB) and P2x7 A1513 C gene polymorphism.Methods:PubMed and Google Scholar web-databases were searched for the studies reporting the association of P2x7 A1513 C polymorphism and PTB risk.A meta-analysis was performed for the selected case-control studies and pooled odds ratios(ORs) and 95%confidence intervals(95%CIs) were calculated for all the genetic models.Results:Eleven studies comprising 2 678 controls and 2 113 PTB cases were included in this meta-analysis.We observed overall no significant risk in all the five genetic models.When stratified population by the ethnicity,Caucasian population failed to show any risk of PTB in all the genetics models.In Asian ethnicity,variant allele(C vs.A:P=0.001;QR=1.375,95%CI=1.159-1.632) and heterozygous genotype(AC vs.AA:P=0.001;OR=1.570,95%CI=1.269-1.944) demonstrated significant increased risk of PTB.Likewise,recessive genetic model(CC+AC vs.AA:P=0.001;OR=1.540,95%CI= 1.255-1.890) also demonstrated increased risk of PTB in Asians.Conclusions:Our meta-analysis did not suggest the association of P2x7 A1513 C polymorphism with PTB risk in overall or separately in Caucasian population.However,it plays a significant risk factor for predisposing PTB in Asians.Future larger sample and expression studies are needed to validate this association.
基金Hainan Science and Technology Project(ZDYF2020229ZDKJ2021010)Scientific Research Program of Hainan Key Laboratory of Vegetable Biology and Hainan Key Laboratory for Quality Regulation of Tropical Horticultural Crops(HNZDSYS(YY)-03)。
文摘[Objectives]To explore the genetic mechanism that leaf length and leaf width in bitter gourd has realistic guiding significance for formulating breeding strategy.[Methods]In this paper,the cross was made between CN19-1 and Thai4-6 and an F2segregation population was constructed.The genetic characteristics of leaf length and leaf width were analyzed by employing the major gene plus polygene mixed genetic model.[Results]The data analysis results demonstrated that the leaf length and leaf width of the F_(2) segregation population showed continuous distribution.The optimum model for leaf length genetic analysis was A-1,the additive effect value of the major gene was 3.1766,the dominant effect value was-3.1766,and the heritability was 74.51%.The optimum model for leaf width genetic analysis was B-1.The additive effect values of 2 pairs of major genes controlling the leaf width were 3.1917 and 0.9623,respectively.The dominant effect values were-1.3135 and-0.3463,respectively.The additive×additive interaction effect was-0.3591,the additive×dominant interaction effect was-0.2570,the dominant×additive interaction effect was 1.9916,the dominant×dominant interaction effect was 1.9686.The heritability of major genes was 96.67%.[Conclusions]This study is expected to provide a theoretical basis for the breeding of bitter gourd.
基金Hainan Science and Technology Project(ZDYF2020229,ZDKJ2021010)Scientific Research Program of Hainan Key Laboratory of Vegetable Biology and Hainan Key Laboratory for Quality Regulation of Tropical Horticultural Crops[HNZDSYS(YY)-03]。
文摘[Objectives]The paper was to verify the genetic mechanism of weight per fruit and fruit length in bitter gourd and to provide guidance for formulating breeding strategy.[Methods]In this study,a cross was made between CN19-1 and Thai4-6,and a Fsegregation population was also constructed.The genetic characteristics of weight per fruit and fruit length were analyzed by employing major gene plus polygene mixed genetic model.[Results]The weight per fruit and fruit length showed continuous distribution in Fsegregation population.The optimal model for weight per fruit and fruit length was the same(A-1 model).The major gene additive effect value of weight per fruit was 46.1474,the dominant effect value was-46.1005,and the major gene heritability was 52.47%.The major gene additive effect value of fruit length was 2.456,the dominant effect value was-2.455,and the major gene heritability was 52.52%.The results showed that weight per fruit and fruit length were mainly controlled by a pair of major genes.[Conclusions]This study can provide a theoretical basis for bitter gourd breeding.
基金Supported by National Natural Science Foundation of China(31601758)
文摘Performing the genetic mechanism research of internode length in bitter gourd has important guiding significance for making breeding strategy. A cross was made between CN19-1 and Thai4-6, and an F2 segregation population was constructed. The genetic characteristic of the internode length was analyzed through employing the major gene plus polygene mixed genetic model. The results showed that the internode length was continuous distribution in the F2 population. The optimum model for internode length genetic analysis was B-1. The additive effect values of two pairs of major genes controlling the internode length were 3.206 3 and 2.638 3, respectively, which showed a positive effect. The dominant effect values were-3.434 6 and-1.459 6, respectively, which showed a negative effect. The dominant degree of major genes is-1.07 and-0.55, respectively, indicating that the first pair of major genes was over dominant and the second pair of major genes was incompletely dominant. The heritability of the major gene was 82.25%, indicating the genetic stability was high. This study could provide a theoretical reference for the breeding of bitter gourd.
基金supported by National Natural Science Foundation of China(grant no.39970785)International Collaborate Research Foundation of National Natural Science of China(grant no.322200462)National Institutes of Health (grant no.ROIDC007392)
文摘Background Chronic otitis media(COM) is a significant clinical problem.Understanding the mechanisms of COM is critical for its control and treatment.However,little is known of the processes leading to COM as a result of lack of animal models of N-ethyl-N-nitrosourea(ENU) induced mutations in otitis media with effusion(OME).Methods Otoscopy and auditory brain response(ABR) evaluation were carried out under sedation in Nmf391nmf/nmf mice of 2,4,6 and 8 months of age.The mice were killed for study of middle and inner ear pathology.Results Tympanic membrane visualization and ABR thresholds in 1-to 8-month-old Nmf391nmf/nmf mice showed spontaneous OME and inner ear diseases in approximately 100% of the animals.The significant elevation of ABR thresholds suggested a sensorineural component in hearing loss in addition to the conductive loss.Middle and inner ear histology showed various degrees of outer hair cells loss and middle ear inflammation in all the mice,but no inflammation cells in the inner ear.The ABR threshold at 32 kHz was significantly elevated.Conclusions This study shows histopathologic changes in the Nmf391nmf/nmf mouse model of COM with effusion that have not been reported in human COM.This ENU induced mutation model of COM will be valuable for the characterization of middle ear inflammation and inner ear disease processes that are induced by middle ear infections.We propose that COM with effusion in this ENU induced mutation model is the cause of the cochlea hair cells damage.
文摘Cancer is a major stress for public well-being and is the most dreadful disease.The models used in the discovery of cancer treatment are continuously changing and extending toward advanced preclinical studies.Cancer models are either naturally existing or artificially prepared experimental systems that show similar features with human tumors though the heterogeneous nature of the tumor is very familiar.The choice of the most fitting model to best reflect the given tumor system is one of the real difficulties for cancer examination.Therefore,vast studies have been conducted on the cancer models for developing a better understanding of cancer invasion,progression,and early detection.These models give an insight into cancer etiology,molecular basis,host tumor interaction,the role of microenvironment,and tumor heterogeneity in tumor metastasis.These models are also used to predict novel can-cer markers,targeted therapies,and are extremely helpful in drug development.In this review,the potential of cancer models to be used as a platform for drug screening and therapeutic discoveries are highlighted.Although none of the cancer models is regarded as ideal because each is associated with essential caveats that restraint its application yet by bridging the gap between preliminary cancer research and transla-tional medicine.However,they promise a brighter future for cancer treatment.
文摘Recently,many regression models have been presented for prediction of mechanical parameters of rocks regarding to rock index properties.Although statistical analysis is a common method for developing regression models,but still selection of suitable transformation of the independent variables in a regression model is diffcult.In this paper,a genetic algorithm(GA)has been employed as a heuristic search method for selection of best transformation of the independent variables(some index properties of rocks)in regression models for prediction of uniaxial compressive strength(UCS)and modulus of elasticity(E).Firstly,multiple linear regression(MLR)analysis was performed on a data set to establish predictive models.Then,two GA models were developed in which root mean squared error(RMSE)was defned as ftness function.Results have shown that GA models are more precise than MLR models and are able to explain the relation between the intrinsic strength/elasticity properties and index properties of rocks by simple formulation and accepted accuracy.
基金Supported by the National Natural Science Foundation of China(No.31672648)the Jiangsu Collaborative Innovation Center of Regional Modern Agriculture&Environmental Protection and Huaiyin Normal University(No.HSXT2-107)the Science&Technology Program of Huaiyin Normal University(No.31WH000)。
文摘The red swamp crayfish,Procambarus clarkii,is an economically important species especially in China.Their exoskeleton places serious constraints on growth and culture management.Their growth is achieved through intermittent molting/ecdysis.The longitudinal genetic dynamics for growth-related traits at different ecdysial points in P.clarkii has been unclear to date.In this study,conditional genetic analysis was carried out for growth-related traits(body weight,body length,chela length,and cephalothorax length)based upon a mixed genetic model with conditional additive,dominance,and genotype by environment effects in P.clarkii.A complete diallel cross was made among three geographic populations of P.clarkii for the genetic mating design.Results of the conditional genetic analysis showed that from 4 th molt to 9 th molt the conditional additive variations were increased significantly whereas the conditional non-additive genetic variations(dominance and genotype by environment interaction)were decreased significantly for these growth-related traits.This indicated that lots of new expression of additive effect genes for body weight,body length,chela length,and cephalothorax length occurred during ontogeny,and environment played a signifi cant role in the expression of genes affecting these growth-related traits.Growth of the four traits was mainly affected by non-additive genetic effects in early developmental stage(prior to 4 th molt).The cumulative conditional additive variation for the growth-related traits from 4 th molt to 9 th molt accounted for a large majority of the total conditional additive variations from 2 nd molt to 9 th molt,indicating that this period was very important for the growth of this species.Using the conditional analysis method,dynamics of growth-related traits during an important ontogenetic phase of red swamp crayfish was uncovered.Our results provide valuable insights into refining production of this species.
基金supported by the US National Institutes of Health (R01CA160331, R01CA163377, R01CA202919,R01CA239128, P01AG031862, P50CA228991 to R.G.Z. and K99CA241395 to S.K.)US Department of Defense (OC180109 and OC190181 to R.G.Z.)+2 种基金The Honorable Tina Brozman Foundation for Ovarian Cancer Research (to R.G.Z.)Ovarian Cancer Research Alliance Collaborative Research Development Grant (to R.G.Z.)Core facilities support was provided by a Cancer Centre Support Grant(CA010815) to the Wistar Institute。
文摘Epithelial ovarian cancer(EOC) is the leading cause of gynecological cancer-related mortality in the developed world. EOC is a heterogeneous disease represented by several histological and molecular subtypes. Therefore, exploration of relevant preclinical animal models that consider the heterogenic nature of EOC is of great importance for the development of novel therapeutic strategies that can be translated clinically to combat this devastating disease. In this review, we discuss recent progress in the development of preclinical mouse models for EOC study as well as their advantages and limitations.
文摘Scour is a natural phenomenon that is created by the rivers streams or the flood which brings about transferring or eroding of bed materials. To have accurate and safe erosion control structures design, maximum scour depth in downstream of the structures gains specific significance. In the current study, M5 model tree as remedy data mining approaches is suggested to estimate the scour depth around the abutments. To do this, Kayaturk laboratory data (2005), with different hydraulic conditions, are used. Then, the results of M5 model were also compared with genetic programming (GP) and pervious empirical results to investigate the applicability, ability, and accuracy of these procedures. To examine the accuracy of the results yielded from the M5 and GP procedures, two performance indicators (determination coefficient (R2) and root mean square error (RMSE)) were used. The comparison test of results clearly shows that the implementation of M5 technique sounds satisfactory regarding the performance indicators (R<sup>2</sup> = 0.944 and RMSE = 0.126) with less deviation from the numerical values. In addition, M5 tree model, by presenting relationships based on liner regression, has good capability to estimate the depth of scour abutment for engineers in practical terms.
基金funded by the National Natural Science Foundation of China(Grant Nos.52274388,U1960105 and 52074187)the authors express gratitude to reviewers for precious suggestions.
文摘The prediction accuracy of existing models of the rolling force of a thick plate is always very low.To address this problem,a high-precision genetic algorithm-backpropagation network(GA-BP)model of deformation resistance was built,and its integration with the traditional fitted model was further established.Then,a novel rolling force model was obtained by embedding the integration model of deformation resistance in the original model of rolling force.According to this research idea,the industrial data are normalized at first.On this basis,the interactions among the process parameters were disclosed through the variance analysis,and then described by various virtual factors.These factors are set as part of input parameters.Then,the optimal structure of the GA-BP model of deformation resistance was determined and an integration model of deformation resistance was built.Finally,a novel rolling force model is obtained by substituting the traditional fitted deformation resistance into the Sims model with the integration model of the deformation resistance.The results proves that the introduction of virtual factors can increase the hit rate of±5%from 75.8%to 78%and can reduce the root mean square error from 4.72%to 4.48%.Besides,it is found that the mean relative error of the traditional fitted deformation resistance is 0.142,while that of the modified deformation resistance is only 0.03.In addition,the mean relative error in the original rolling force model is 0.145,while that of the present model is only 0.03.
文摘This study re-evaluates the characteristics of Cu-Pb-Ag and Fe-Mn ore mineralization of the Kombat Mine and Gross Otavi Mine based on field geology, fluid inclusions, petrology, mineralogy, and geochemistry. This is to determine the genetic relationship between Fe-Mn and Cu-Pb-Ag mineralization. The study has established that the Cu-Pb-Ag ore at the Kombat Mine can be classified as a variant of MVT-type deposit, whereas the Fe-Mn ore can be classified as a stratiform-syn-sedimentary deposit. The formation of the MVT-type deposit is associated with a hydrothermal fluid system with a mean temperature of 183<span style="white-space:nowrap;">°</span>C and mean salinity of 12.85 wt. % NaCl equivalent. The syn-sedimentary Fe-Mn ore, which is largely associated with calc-silicate lithologies, consists mainly of magnetite and hematite with minor pyrite, hausmannite and jacobsite, and was deposited by diagenetic and mixed diagenetic-hydrogenetic processes under changing oxic and anoxic conditions within the sedimentary basin. Acceptable geochemical exploration indicators of the existing mineralization include anomalous values above 0.5% Cu, 0.2% S;0.05% Pb;0.04% As;0.01% Zn;V, W, Mo, and Ag are 0.002%. Mineralogical indicators include chalcopyrite, bornite, covellite and galena with minor chalcocite, sphalerite, and tennantite for the Cu-Pb MVT-type ores at Kombat Mine.
基金funded by 2016 National Key Research and Development Plan(grant number 2016YFC0803103)Research on Key Technology of Agricultural Remote Sensing Monitoring(grant number 12210243)and Henan Provincial University Innovation Team Support Plan(grant number 14IRTSTHN026).
文摘The leaf area index(LAI)is an important agroecological physiological parameter affecting vegetation growth.To apply the genetic algorithms neural network model(GANNM)to the remote sensing inversion of winter wheat LAI throughout the growth cycle and based on GaoFen-3 Synthetic aperture radar(GF-3 SAR)images and GaoFen-1 Wide Field of View(GF-1 WFV)images,the Xiangfu District in the east of Kaifeng City,Henan Province,was selected as the testing region.Winter wheat LAI data from five growth stages were combined,and optical and microwave polarization decomposition vegetation index models were used.The backscattering coefficient was extracted by modified water cloud model(MWCM),and the LAI was obtained by MWCM inversion as input factors to construct GANNM to invert LAI.The root mean square error(RMSE)and determination coefficient(R2)were used as evaluation indicators of the model.The fitting accuracy of winter wheat LAI in five growth stages by GANNM inversion was better than that of the BP neural network model;the R2 was higher than 0.8,and RMSE was lower than 0.3,indicating that the model could accurately invert the growth status of winter wheat in five growth stages.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.81830073 and 31571356)
文摘Current pharmacogenetic studies have obtained many genetic models that can predict the therapeutic efficacy of anticancer drugs.Although some of these models are of crucial importance and have been used in clinical practice,these very valuable models have not been well adopted into cancer research to promote the development of cancer therapies due to the lack of integration and standards for the existing data of the pharmacogenetic studies.For this purpose,we built a resource investigating genetic model of drug response(iGMDR),which integrates the models from in vitro and in vivo pharmacogenetic studies with different omics data from a variety of technical systems.In this study,we introduced a standardized process for all integrations,and described how users can utilize these models to gain insights into cancer.iGMDR is freely accessible at https://igmdr.modellab.cn.
基金This work was supported by Beijing Municipal Administration of Hospitals’Ascent Plan[grant number DFL20180701]Special Fund for the Capital Characteristic Clinical Medicine Development Project[grant number Z161100000516077]+1 种基金Beijing Municipal Grant for Medical Talents Group on Peritoneal Surface Oncology[grant number 2017400003235J007]Beijing Health and Science Technology Achievement and Appropriate Technology Promotion Project[grant number 2018-TG-27]Beijing Natural Science Foundation[grant number 7172108].
文摘Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated death around the world due to advanced clinical stage at diagnosis,high incidence of recurrence and metastasis after surgical treatment.It is in urgent need to create appropriate animal models to explore the mechanism,patterns,risk factors,and therapeutic strategies of HCC metastasis and recurrence.However,most of the established models lack the phenotype of invasion and metastasis in patient,or have unstable phenotype.To establish HCC models with stable metastasis phenotype requires profound understanding in cancer metastasis biology and scientific methodology.Over the past 3 decades,HCC models with stable metastasis have been extensively studied.This paper reviewed the history and development of HCC animal models and cell models,focusing on the screening and maintaining of metastatic potential and phenotype.In-depth studies using these models vastly promote the understanding of cellular and molecular mechanisms and development of therapeutic strategies on HCC metastasis.
