Abscisic acid controls calcium-dependent egress and development in Toxoplasma gondii

Calcium controls a number of critical events, including motility, secretion, cell invasion and egress by apicomplexan parasites. Compared to animal and plant cells, the molecular mechanisms that govern calcium signalling in parasites are poorly understood. Here we show that the production of the phytohormone abscisic acid (ABA) controls calcium signalling within the apicomplexan parasite Toxoplasma gondii, an opportunistic human pathogen. In plants, ABA controls a number of important events, including environmental stress responses, embryo development and seed dormancy. ABA induces production of the second-messenger cyclic ADP ribose (cADPR), which controls release of intracellular calcium stores in plants. cADPR also controls intracellular calcium release in the protozoan parasite T. gondii; however, previous studies have not revealed the molecular basis of this pathway. We found that addition of exogenous ABA induced formation of cADPR in T. gondii, stimulated calcium-dependent protein secretion, and induced parasite egress from the infected host cell in a density-dependent manner. Production of endogenous ABA within the parasite was confirmed by purification (using high-performance liquid chromatography) and analysis (by gas chromatography-mass spectrometry). Selective disruption of ABA synthesis by the inhibitor fluridone delayed egress and induced development of the slow-growing, dormant cyst stage of the parasite. Thus, ABA-mediated calcium signalling controls the decision between lytic and chronic stage growth, a developmental switch that is central in pathogenesis and transmission. The pathway for ABA production was probably acquired with an algal endosymbiont that was retained as a non-photosynthetic plastid known as the apicoplast. The plant-like nature of this pathway may be exploited therapeutically, as shown by the ability of a specific inhibitor of ABA synthesis to prevent toxoplasmosis in the mouse model.     

车削颤振时变可靠性分析

考虑车削加工过程中刀具磨损对切削力系数的影响,用Gamma过程描述了切削力系数随时间的变化过程,并建立了车削颤振时变可靠性模型.提出了主动学习的Kriging模型与基于首次超越的子集模拟相结合的时变可靠性分析方法(AK-SSFP).对某一车床建立车削颤振稳定性模型,分别采用Monte Carlo方法(MCS)、基于主动学习Kriging的Monte Carlo方法(AK-MCS)和AK-SSFP方法计算车削颤振时变可靠度.AK-SSFP方法的结果与MCS方法的结果一致性很好,且AK-SSFP方法减少了真实极限函数的调用次数并缩短了运算时间.AK-SSFP在保证精度的同时提高了计算效率,解决了车削加工系统颤振时变可靠度的计算问题.