To explore how the intrinsic apoptosis pathway is controlled in the spontaneous fog （forebrain overgrowth） mutant mice with an Apafl splicing deficiency, we examined spleen and bone marrow cells from Apafl＋/＋ （＋...To explore how the intrinsic apoptosis pathway is controlled in the spontaneous fog （forebrain overgrowth） mutant mice with an Apafl splicing deficiency, we examined spleen and bone marrow cells from Apafl＋/＋ （＋/＋） and Apafl^fog/fog （fog/fog） mice for initiator caspase-9 activation by cellular stresses. When the mitochondrial inner membrane potential （△ψm） was disrupted by staurosporine, ＋/＋ cells but not fog/fog cells activated caspase-9 to cause apoptosis, indicating the lack of apoptosome （apoptosis protease activating factor 1 （Apaf-l）/cytochrome c/（d）ATP/procaspase-9） function in fog/fog cells. However, when a marginal （-20%） decrease in △ψm was caused by hydrogen peroxide （0.1 mM）, peroxynitrite donor 3-morpholinosydnonimine （0.1 mM） and UV-C irradiation （20 J/m^2）, both ＋/＋ and fog/fog cells triggered procaspase-9 auto-processing and its downstream cascade activation. Supporting our previous results, procaspase-9 pre-existing in the mitochondria induced its auto-processing before the cytosolic caspase activation regardless of the genotypes. Cellular ATP concentration significantly decreased under the hypoactive △ψm condition. Furthermore, we detected accumulation of citrate, a kosmotrope known to facilitate procaspase-9 dimerization, probably due to a feedback control of the Krebs cycle by the electron transfer system. Thus, mitochondrial in situ caspase-9 activation may be caused by the major metabolic reactions in response to physiological stresses, which may represent a mode of Apaf-l-independent apoptosis hypothesized from recent genetic studies.展开更多
Supersonic gas jets generated via a conical nozzle are widely applied in the laser wakefield acceleration of electrons.The stability of the gas jet is critical to the electron injection and the reproducibility of the ...Supersonic gas jets generated via a conical nozzle are widely applied in the laser wakefield acceleration of electrons.The stability of the gas jet is critical to the electron injection and the reproducibility of the wakefield acceleration.Here we discussed the role of the stilling chamber in a modified converging-diverging nozzle to dissipate the turbulence and to stabilize the gas jets.By the fluid dynamics simulations and the Mach-Zehnder interferometer measurements,the instability originating from the nonlinear turbulence is studied and the mechanism to suppress the instability is proposed.Both the numerical and experimental results prove that the carefully designed nozzle with a stilling chamber is able to reduce the perturbation by more than 10% compared with a simple-conical nozzle.展开更多
文摘To explore how the intrinsic apoptosis pathway is controlled in the spontaneous fog （forebrain overgrowth） mutant mice with an Apafl splicing deficiency, we examined spleen and bone marrow cells from Apafl＋/＋ （＋/＋） and Apafl^fog/fog （fog/fog） mice for initiator caspase-9 activation by cellular stresses. When the mitochondrial inner membrane potential （△ψm） was disrupted by staurosporine, ＋/＋ cells but not fog/fog cells activated caspase-9 to cause apoptosis, indicating the lack of apoptosome （apoptosis protease activating factor 1 （Apaf-l）/cytochrome c/（d）ATP/procaspase-9） function in fog/fog cells. However, when a marginal （-20%） decrease in △ψm was caused by hydrogen peroxide （0.1 mM）, peroxynitrite donor 3-morpholinosydnonimine （0.1 mM） and UV-C irradiation （20 J/m^2）, both ＋/＋ and fog/fog cells triggered procaspase-9 auto-processing and its downstream cascade activation. Supporting our previous results, procaspase-9 pre-existing in the mitochondria induced its auto-processing before the cytosolic caspase activation regardless of the genotypes. Cellular ATP concentration significantly decreased under the hypoactive △ψm condition. Furthermore, we detected accumulation of citrate, a kosmotrope known to facilitate procaspase-9 dimerization, probably due to a feedback control of the Krebs cycle by the electron transfer system. Thus, mitochondrial in situ caspase-9 activation may be caused by the major metabolic reactions in response to physiological stresses, which may represent a mode of Apaf-l-independent apoptosis hypothesized from recent genetic studies.
基金funded by the JST-MIRAI program,grant No.JPMJMI17A1.
文摘Supersonic gas jets generated via a conical nozzle are widely applied in the laser wakefield acceleration of electrons.The stability of the gas jet is critical to the electron injection and the reproducibility of the wakefield acceleration.Here we discussed the role of the stilling chamber in a modified converging-diverging nozzle to dissipate the turbulence and to stabilize the gas jets.By the fluid dynamics simulations and the Mach-Zehnder interferometer measurements,the instability originating from the nonlinear turbulence is studied and the mechanism to suppress the instability is proposed.Both the numerical and experimental results prove that the carefully designed nozzle with a stilling chamber is able to reduce the perturbation by more than 10% compared with a simple-conical nozzle.
