The mixed lineage kinase domain-like(MLKL)protein is a key factor in tumor necrosis factor-induced necroptosis.Recent studies on necroptosis execution revealed a commitment role of MLKL in membrane disruption.However,...The mixed lineage kinase domain-like(MLKL)protein is a key factor in tumor necrosis factor-induced necroptosis.Recent studies on necroptosis execution revealed a commitment role of MLKL in membrane disruption.However,our knowledge of how MLKL functions on membrane remains very limited.Here we demonstrate that MLKL forms cation channels that are permeable preferential y to Mg2+rather than Ca2+in the presence of Na+and K+.Moreover,the N-terminal domain containing six helices(H1-H6)is sufficient to form channels.Using the substituted cysteine accessibility method,we further determine that helix H1,H2,H3,H5 and H6 are transmembrane segments,while H4 is located in the cytoplasm.Finally,MLKL-induced membrane depolarization and cell death exhibit a positive correlation to its channel activity.The Mg2+-preferred permeability and five transmembrane segment topology distinguish MLKL from previously identified Mg2+-permeable channels and thus establish MLKL as a novel class of cation channels.展开更多
Theoretical design of a neotype fluidic controlling sensor system based on side-polished optical fiber is proposed.Numerical investigations demonstrate that the higher birefringence and resonance coupling can be achie...Theoretical design of a neotype fluidic controlling sensor system based on side-polished optical fiber is proposed.Numerical investigations demonstrate that the higher birefringence and resonance coupling can be achieved by flexible design of the polishing shape and depth in the research wavelength.The fluidic system is beneficial to selective integration of functional materials.The material is integrated into the fluidic system,which can achieve a birefringence up to 6.98×10^-5,and the application of Sagnac thermometer in temperature sensing is studied,and a group of dips with different temperature sensitivities would be observed in the transmission spectra,which is about 1.6 nm/℃by calculating.furthermore,by introducing resonant coupling,single mode single polarization at 1310 nm is realized.The refractive index(RI)response of the sensing system for a low Grange of 1.39-1.37 is approximately linear,and exhibits a sensitivity of 6338 nm/RlU.The results show that the proposed neotype fluidic controlling system can be used as a flexible polarization filter or as a potential two-parameter sensor.展开更多
文摘The mixed lineage kinase domain-like(MLKL)protein is a key factor in tumor necrosis factor-induced necroptosis.Recent studies on necroptosis execution revealed a commitment role of MLKL in membrane disruption.However,our knowledge of how MLKL functions on membrane remains very limited.Here we demonstrate that MLKL forms cation channels that are permeable preferential y to Mg2+rather than Ca2+in the presence of Na+and K+.Moreover,the N-terminal domain containing six helices(H1-H6)is sufficient to form channels.Using the substituted cysteine accessibility method,we further determine that helix H1,H2,H3,H5 and H6 are transmembrane segments,while H4 is located in the cytoplasm.Finally,MLKL-induced membrane depolarization and cell death exhibit a positive correlation to its channel activity.The Mg2+-preferred permeability and five transmembrane segment topology distinguish MLKL from previously identified Mg2+-permeable channels and thus establish MLKL as a novel class of cation channels.
基金supported by the National Key R&D Program of China(Nos.2018YFF01010202 and 2018YFF01010201)the National Natural Science Foundation of China(Nos.61705027 and 11704053)+3 种基金the Government of the Russian Federation(No.08-08)the Innovation Leader Talent Project of Chongqing Science and Technology(No.CSTC-CXLJRC201711)the Basic Research Project of Chongqing Science and Technology Commission(Nos.CSTC-2017csms A40017 and CSTC-2018jcyjax0619)the Science and Technology Project Affiliated to the Education Department of Chongqing Municipality(Nos.KJZH17115 and KJQN201800626)。
文摘Theoretical design of a neotype fluidic controlling sensor system based on side-polished optical fiber is proposed.Numerical investigations demonstrate that the higher birefringence and resonance coupling can be achieved by flexible design of the polishing shape and depth in the research wavelength.The fluidic system is beneficial to selective integration of functional materials.The material is integrated into the fluidic system,which can achieve a birefringence up to 6.98×10^-5,and the application of Sagnac thermometer in temperature sensing is studied,and a group of dips with different temperature sensitivities would be observed in the transmission spectra,which is about 1.6 nm/℃by calculating.furthermore,by introducing resonant coupling,single mode single polarization at 1310 nm is realized.The refractive index(RI)response of the sensing system for a low Grange of 1.39-1.37 is approximately linear,and exhibits a sensitivity of 6338 nm/RlU.The results show that the proposed neotype fluidic controlling system can be used as a flexible polarization filter or as a potential two-parameter sensor.