Background:Spinocerebellar ataxia type 2(SCA2)is a neurodegenerative disease marked by significant clinical and genetic heterogeneity,primarily caused by expanded CAG mutations in the ATXN2 gene.The unstable expansion...Background:Spinocerebellar ataxia type 2(SCA2)is a neurodegenerative disease marked by significant clinical and genetic heterogeneity,primarily caused by expanded CAG mutations in the ATXN2 gene.The unstable expansion of CAG repeats disrupts the genetic stability of animal models,which is detrimental to disease research.Methods:In this study,we established a mouse model in which CAG repeats do not undergo microsatellite instability(MSI)across generations.A humanized ATXN2 cDNA with four CAA interruptions within 73 CAG expansions was inserted into the Rosa26 locus of C57BL/6J mice.A 23 CAG control mouse model was also generated to verify ATXN2 integration and expression.Results:In our model,the number of CAG repeats remained stable during transmission,with no CAG repeat expansion observed in 64 parent-to-offspring transmissions.Compared with SCA2-Q23 mice,SCA2-Q73 mice exhibited progressive motor impairment,reduced Purkinje cell count and volume(indicative of cell atrophy),and muscle atrophy.These observations in the mice suggest that the behavioral and neuropathological phenotypes may reflect the features of SCA2 patients.RNA-seq analysis of the gastrocnemius muscle in SCA2-Q73 mice showed significant changes in muscle differentiation and development gene expression at 56 weeks,with no significant differences at 16 weeks compared to SCA2-Q23 mice.The expression level of the Myf6 gene significantly changed in the muscles of aged mice.Conclusion:In summary,the establishment of this model not only provides a stable animal model for studying CAG transmission in SCA2 but also indicates that the lack of long-term neural stimulation leads to muscle atrophy.展开更多
The design of landing gear is complicated due to the numerous considered elements.And the initial elements related to each other can also be influenced by different factors.Landing gear design often involves a very la...The design of landing gear is complicated due to the numerous considered elements.And the initial elements related to each other can also be influenced by different factors.Landing gear design often involves a very large variety of configurations,especially in the conceptual design phase.However,traditional method costs more time to complete the whole procedure for suitable configurations of landing gears.Therefore,the parametric modeling of component library for landing gear based on computer aided three-dimensional interface application/component application architecutre(CATIA/CAA)is proposed.According to the analysis of the characteristics of landing gear components,a method is presented to extract the primary parameters of landing gear components so that a systematic classification can be established.Further,the related theories and methods,including receiving geometrical parameters of the components and updating the parametrical model,displaying the component parts,are also illustrated.Finally,the development technology for component library is explained.The proposed modeling method can improve the efficiency of the whole design cycle for landing gear.展开更多
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:CIFMS,2021-I2M-1-024The Joint Fund for the Department of Science and Technology of Yunnan Province-Kunming Medical University,Grant/Award Number:202201AY070001-007+1 种基金Open Research Fund Project of Yunnan Provincial Key Laboratory of Pharmacology of Natural Medicines,Grant/Award Number:YKLPNP-G2403The Science and Technology Leading Talent Program of Yunnan Province,Grant/Award Number:202405AB350002。
文摘Background:Spinocerebellar ataxia type 2(SCA2)is a neurodegenerative disease marked by significant clinical and genetic heterogeneity,primarily caused by expanded CAG mutations in the ATXN2 gene.The unstable expansion of CAG repeats disrupts the genetic stability of animal models,which is detrimental to disease research.Methods:In this study,we established a mouse model in which CAG repeats do not undergo microsatellite instability(MSI)across generations.A humanized ATXN2 cDNA with four CAA interruptions within 73 CAG expansions was inserted into the Rosa26 locus of C57BL/6J mice.A 23 CAG control mouse model was also generated to verify ATXN2 integration and expression.Results:In our model,the number of CAG repeats remained stable during transmission,with no CAG repeat expansion observed in 64 parent-to-offspring transmissions.Compared with SCA2-Q23 mice,SCA2-Q73 mice exhibited progressive motor impairment,reduced Purkinje cell count and volume(indicative of cell atrophy),and muscle atrophy.These observations in the mice suggest that the behavioral and neuropathological phenotypes may reflect the features of SCA2 patients.RNA-seq analysis of the gastrocnemius muscle in SCA2-Q73 mice showed significant changes in muscle differentiation and development gene expression at 56 weeks,with no significant differences at 16 weeks compared to SCA2-Q23 mice.The expression level of the Myf6 gene significantly changed in the muscles of aged mice.Conclusion:In summary,the establishment of this model not only provides a stable animal model for studying CAG transmission in SCA2 but also indicates that the lack of long-term neural stimulation leads to muscle atrophy.
基金Supported by the National Natural Science Foundation of China(51075203,51105197)the Nanjing University of Aeronautics and Astronautics Research Funding(NS2010023)
文摘The design of landing gear is complicated due to the numerous considered elements.And the initial elements related to each other can also be influenced by different factors.Landing gear design often involves a very large variety of configurations,especially in the conceptual design phase.However,traditional method costs more time to complete the whole procedure for suitable configurations of landing gears.Therefore,the parametric modeling of component library for landing gear based on computer aided three-dimensional interface application/component application architecutre(CATIA/CAA)is proposed.According to the analysis of the characteristics of landing gear components,a method is presented to extract the primary parameters of landing gear components so that a systematic classification can be established.Further,the related theories and methods,including receiving geometrical parameters of the components and updating the parametrical model,displaying the component parts,are also illustrated.Finally,the development technology for component library is explained.The proposed modeling method can improve the efficiency of the whole design cycle for landing gear.
