It is well known that α-synuclein (αS) plays an important role in the pathogenesis of Parkinson’s disease (PD). Moreover, oxidative stress is also thought to be an important factor in PD due to induction of dopamin...It is well known that α-synuclein (αS) plays an important role in the pathogenesis of Parkinson’s disease (PD). Moreover, oxidative stress is also thought to be an important factor in PD due to induction of dopaminergic neuronal cell death by free radicals and enhancement of αS fibrillation by oxidized stress. In the present study, to clarify the role of glutathione (GSH), an intracellular antioxidant, on the molecular mechanism of αS-induced cell injury, we examined the effects of L-buthionine-SR-sulfoximine (BSO), a GSH synthase inhibitor, with or without N-acetyl-L-cysteine (NAC), a source of GSH, on αS-induced cell injury in human neuroblastoma SH-SY5Y cells. Treatment with BSO significantly reduced the cell viability of both empty-vector- and αS-transfected SH-SY5Y cells in a dose-dependent manner (p < 0.01), although the ratio of αS-induced reduction of cell viability in α-syn-transfected cells was much greater than that in empty-vector-transfected cells. Moreover, BSO significantly reduced the intracellular total GSH level in both types of transformant cells. However, NAC significantly prevented BSO-induced reduction of both cell viability and GSH level in the αS-transfected cells. These findings suggest that GSH plays an important role in αS-induced cell injury by reducing cell viability.展开更多
Zonisamide (ZNS), a commonly used anticonvulsant, scavenged hydroxyl radicals at a clinically relevant concentration. Reactants of ZNS with hydrogen peroxide and with hydrogen peroxide plus UV irradiation, yielding hy...Zonisamide (ZNS), a commonly used anticonvulsant, scavenged hydroxyl radicals at a clinically relevant concentration. Reactants of ZNS with hydrogen peroxide and with hydrogen peroxide plus UV irradiation, yielding hydroxyl radicals, were analyzed by the LC/MS technique. Many small fragments were found in the both reactions, suggesting that ZNS was decomposed not only by hydroxyl radicals but also by hydrogen peroxide. Furthermore, mass-fragment-grams showed that m/z: 213 (ZNS itself) was decreased markedly and m/z: 118 (may be a decomposed product by ring cleavage of ZNS) was detected specifically by treatment with hydroxyl radical. These data suggested that ZNS may react directly with free radicals.展开更多
An assembly robot needs to be capable of executing an assembly task robustly under various uncertainties.To attain this goal,we use a task sequence tree model originally proposed for manual assembly.This model regards...An assembly robot needs to be capable of executing an assembly task robustly under various uncertainties.To attain this goal,we use a task sequence tree model originally proposed for manual assembly.This model regards an assembly task under uncertainties as a transformation of the contact state concept.The concept may contain several contact states with probabilities but these are transformed through a series of task elements into the contact state concept having only the goal state at the end.The transformed contact state concept can be classified according to the terminal condition of each task element.Thus,the whole assembly task can be designed as a tree-shaped contingent strategy called a task sequence tree.This paper proposes a systematic approach for reconfiguring a task sequence tree model for application to a robotic assembly task.In addition,by taking a 2D peg-in-hole insertion task to be performed by a robot equipped with a force sensor as an example,we confirm that the proposed approach can provide a robust motion strategy for the task and that the robot can actually execute the task robustly under bounded uncertainty according to the strategy.展开更多
文摘It is well known that α-synuclein (αS) plays an important role in the pathogenesis of Parkinson’s disease (PD). Moreover, oxidative stress is also thought to be an important factor in PD due to induction of dopaminergic neuronal cell death by free radicals and enhancement of αS fibrillation by oxidized stress. In the present study, to clarify the role of glutathione (GSH), an intracellular antioxidant, on the molecular mechanism of αS-induced cell injury, we examined the effects of L-buthionine-SR-sulfoximine (BSO), a GSH synthase inhibitor, with or without N-acetyl-L-cysteine (NAC), a source of GSH, on αS-induced cell injury in human neuroblastoma SH-SY5Y cells. Treatment with BSO significantly reduced the cell viability of both empty-vector- and αS-transfected SH-SY5Y cells in a dose-dependent manner (p < 0.01), although the ratio of αS-induced reduction of cell viability in α-syn-transfected cells was much greater than that in empty-vector-transfected cells. Moreover, BSO significantly reduced the intracellular total GSH level in both types of transformant cells. However, NAC significantly prevented BSO-induced reduction of both cell viability and GSH level in the αS-transfected cells. These findings suggest that GSH plays an important role in αS-induced cell injury by reducing cell viability.
文摘Zonisamide (ZNS), a commonly used anticonvulsant, scavenged hydroxyl radicals at a clinically relevant concentration. Reactants of ZNS with hydrogen peroxide and with hydrogen peroxide plus UV irradiation, yielding hydroxyl radicals, were analyzed by the LC/MS technique. Many small fragments were found in the both reactions, suggesting that ZNS was decomposed not only by hydroxyl radicals but also by hydrogen peroxide. Furthermore, mass-fragment-grams showed that m/z: 213 (ZNS itself) was decreased markedly and m/z: 118 (may be a decomposed product by ring cleavage of ZNS) was detected specifically by treatment with hydroxyl radical. These data suggested that ZNS may react directly with free radicals.
基金Project (No.19GS0208) supported by the Grant-in-Aid for Creative Scientific Research 2007–2011 funded by the Ministry of Education,Culture,Sports,Science and Technology,Japan
文摘An assembly robot needs to be capable of executing an assembly task robustly under various uncertainties.To attain this goal,we use a task sequence tree model originally proposed for manual assembly.This model regards an assembly task under uncertainties as a transformation of the contact state concept.The concept may contain several contact states with probabilities but these are transformed through a series of task elements into the contact state concept having only the goal state at the end.The transformed contact state concept can be classified according to the terminal condition of each task element.Thus,the whole assembly task can be designed as a tree-shaped contingent strategy called a task sequence tree.This paper proposes a systematic approach for reconfiguring a task sequence tree model for application to a robotic assembly task.In addition,by taking a 2D peg-in-hole insertion task to be performed by a robot equipped with a force sensor as an example,we confirm that the proposed approach can provide a robust motion strategy for the task and that the robot can actually execute the task robustly under bounded uncertainty according to the strategy.