The deposition of amyloid-beta is a pathological hallmark of Alzheimer＇s disease, Amyloid-beta is derived from amyloid precursor protein through sequential proteolytic cleavages by β-secretase （beta-site amyloid pr...The deposition of amyloid-beta is a pathological hallmark of Alzheimer＇s disease, Amyloid-beta is derived from amyloid precursor protein through sequential proteolytic cleavages by β-secretase （beta-site amyloid precursor protein-cleaving enzyme 1） and r-secretase. To further elucidate the roles of beta-site amyloid precursor protein-cleaving enzyme 1 in the development of AIzheimer＇s disease, a yeast two-hybrid system was used to screen a human embryonic brain cDNA library for proteins directly interacting with the intracellular domain of beta-site amyloid precursor protein-cleaving enzyme 1. A potential beta-site amyloid precursor protein-cleaving enzyme 1- interacting protein identified from the positive clones was divalent cation tolerance protein. Immunoprecipitation studies in the neuroblastoma cell line N2a showed that exogenous divalent cation tolerance protein interacts with endogenous beta-site amyloid precursor protein-cleaving enzyme 1. The overexpression of divalent cation tolerance protein did not affect beta-site amyloid precursor protein-cleaving enzyme 1 protein levels, but led to increased amyloid precursor protein levels in N2a/APP695 cells, with a concomitant reduction in the processing product amyloid precursor protein C-terminal fragment, indicating that divalent cation tolerance protein inhibits the processing of amyloid precursor protein. Our experimental findings suggest that divalent cation tolerance protein negatively regulates the function of beta-site amyloid precursor protein-cleaving enzyme 1. Thus, divalent cation tolerance protein could play a protective role in Alzheimer＇s disease.展开更多
Objective:Fragment injury is a type of blast injury that is becoming more and more common in military campaigns and terrorist attacks.Numerical simulation methods investigating the formation of natural fragments and i...Objective:Fragment injury is a type of blast injury that is becoming more and more common in military campaigns and terrorist attacks.Numerical simulation methods investigating the formation of natural fragments and injuries to biological targets are expected to be developed.Methods:A cylindrical warhead model was established and the formation process of natural fragments was simulated using the approach of tied nodes with failure through the explicit finite element(FE)software of LS-DYNA.The interaction between the detonation product and the warhead shell was simulated using the fluidestructure interaction algorithm.A method to simulate the injury of natural fragments to a biological target was presented by transforming Lagrange elements into smooth particle hydrodynamics(SPH)particles after the natural fragments were successfully formed.A computational model of the human thorax was established to simulate the injury induced by natural fragments by the node-to-surface contact algorithm with erosion.Results:The discontinuous velocities of the warhead shell at different locations resulted in the formation of natural fragments with different sizes.The velocities of natural fragments increased rapidly at the initial stage and slowly after the warhead shell fractured.The initial velocities of natural fragments at the central part of the warhead shell were the largest,whereas those at both ends of the warhead shell were the smallest.The natural fragments resulted in bullet holes that were of the same shape as that of the fragments but slightly larger in size than the fragments in the human thorax after they penetrated through.Stress waves propagated in the ribs and enhanced the injury to soft tissues;additionally,ballistic pressure waves ahead of the natural fragments were also an injury factor to the soft tissues.Conclusion:The proposed method is effective in simulating the formation of natural fragments and their injury to biological targets.Moreover,this method will be beneficial for simulating the combined injurie展开更多
基金supported by the National Natural Science Foundation of China, No. 81171192XMU Basic Training Program of Undergraduate, No. CXB2011019Visiting Scholar Fellowship of Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering of Xiamen University, No. 201101
文摘The deposition of amyloid-beta is a pathological hallmark of Alzheimer＇s disease, Amyloid-beta is derived from amyloid precursor protein through sequential proteolytic cleavages by β-secretase （beta-site amyloid precursor protein-cleaving enzyme 1） and r-secretase. To further elucidate the roles of beta-site amyloid precursor protein-cleaving enzyme 1 in the development of AIzheimer＇s disease, a yeast two-hybrid system was used to screen a human embryonic brain cDNA library for proteins directly interacting with the intracellular domain of beta-site amyloid precursor protein-cleaving enzyme 1. A potential beta-site amyloid precursor protein-cleaving enzyme 1- interacting protein identified from the positive clones was divalent cation tolerance protein. Immunoprecipitation studies in the neuroblastoma cell line N2a showed that exogenous divalent cation tolerance protein interacts with endogenous beta-site amyloid precursor protein-cleaving enzyme 1. The overexpression of divalent cation tolerance protein did not affect beta-site amyloid precursor protein-cleaving enzyme 1 protein levels, but led to increased amyloid precursor protein levels in N2a/APP695 cells, with a concomitant reduction in the processing product amyloid precursor protein C-terminal fragment, indicating that divalent cation tolerance protein inhibits the processing of amyloid precursor protein. Our experimental findings suggest that divalent cation tolerance protein negatively regulates the function of beta-site amyloid precursor protein-cleaving enzyme 1. Thus, divalent cation tolerance protein could play a protective role in Alzheimer＇s disease.
基金The work was funded by the National Science Foundation for Young Scientists of China(11902356)China Postdoctoral Science Foundation(2018M633715)+1 种基金Innovation and Cultivation Fund of the Sixth Medical Center of PLA General Hospital(No.CXPY201825)the Army Scientific Research(LB20182D040012).
文摘Objective:Fragment injury is a type of blast injury that is becoming more and more common in military campaigns and terrorist attacks.Numerical simulation methods investigating the formation of natural fragments and injuries to biological targets are expected to be developed.Methods:A cylindrical warhead model was established and the formation process of natural fragments was simulated using the approach of tied nodes with failure through the explicit finite element(FE)software of LS-DYNA.The interaction between the detonation product and the warhead shell was simulated using the fluidestructure interaction algorithm.A method to simulate the injury of natural fragments to a biological target was presented by transforming Lagrange elements into smooth particle hydrodynamics(SPH)particles after the natural fragments were successfully formed.A computational model of the human thorax was established to simulate the injury induced by natural fragments by the node-to-surface contact algorithm with erosion.Results:The discontinuous velocities of the warhead shell at different locations resulted in the formation of natural fragments with different sizes.The velocities of natural fragments increased rapidly at the initial stage and slowly after the warhead shell fractured.The initial velocities of natural fragments at the central part of the warhead shell were the largest,whereas those at both ends of the warhead shell were the smallest.The natural fragments resulted in bullet holes that were of the same shape as that of the fragments but slightly larger in size than the fragments in the human thorax after they penetrated through.Stress waves propagated in the ribs and enhanced the injury to soft tissues;additionally,ballistic pressure waves ahead of the natural fragments were also an injury factor to the soft tissues.Conclusion:The proposed method is effective in simulating the formation of natural fragments and their injury to biological targets.Moreover,this method will be beneficial for simulating the combined injurie
