Calcium-release-activated calcium(CARC)channels are one of the major pathways of calcium entry in non-excitable cells.Despite a decade or two of research,its regulatory mechanism is not yet thoroughly understood.The s...Calcium-release-activated calcium(CARC)channels are one of the major pathways of calcium entry in non-excitable cells.Despite a decade or two of research,its regulatory mechanism is not yet thoroughly understood.The slow progress is due to the complexity of its pores(i.e.,Orai)on one hand and the difficulty in capturing its regulatory complex on the other hand.As a result,possible gating mechanisms have often been speculated by exploring the structure and properties of constitutive open mutants.However,there is much debate about how they can truly reflect the gating of CRAC channels under physiological conditions.In the present study,we combined molecular dynamics simulations with free energy calculations to study three dOrai mutants(G170P,H206A,and P288A),and further calculated their current-voltage curves.Results show that these constructs adopt different approaches to maintain their conductive state.Meanwhile they have unique pore structures and distinctive rectification properties and ion selectivity for cations compared to wild-type pores.We conclude that although the mutants may partially capture the gating motion characteristics of wild-type pores,the information obtained from these mutants is likely not a true reflection of CRAC channel gating under physiological conditions.展开更多
The conditional kernel correlation is proposed to measure the relationship between two random variables under covariates for multivariate data.Relying on the framework of reproducing kernel Hilbert spaces,we give the ...The conditional kernel correlation is proposed to measure the relationship between two random variables under covariates for multivariate data.Relying on the framework of reproducing kernel Hilbert spaces,we give the definitions of the conditional kernel covariance and conditional kernel correlation.We also provide their respective sample estimators and give the asymptotic properties,which help us construct a conditional independence test.According to the numerical results,the proposed test is more effective compared to the existing one under the considered scenarios.A real data is further analyzed to illustrate the efficacy of the proposed method.展开更多
基金supported by the National Natural Science Foundation of China(No.21773115,No.21833002,No.11771435,and No.22073110)the Natural Science Foundation of Jiangsu Province(No.BK20190056)the Fundamental Research Funds for the Central Universities(021514380018)。
文摘Calcium-release-activated calcium(CARC)channels are one of the major pathways of calcium entry in non-excitable cells.Despite a decade or two of research,its regulatory mechanism is not yet thoroughly understood.The slow progress is due to the complexity of its pores(i.e.,Orai)on one hand and the difficulty in capturing its regulatory complex on the other hand.As a result,possible gating mechanisms have often been speculated by exploring the structure and properties of constitutive open mutants.However,there is much debate about how they can truly reflect the gating of CRAC channels under physiological conditions.In the present study,we combined molecular dynamics simulations with free energy calculations to study three dOrai mutants(G170P,H206A,and P288A),and further calculated their current-voltage curves.Results show that these constructs adopt different approaches to maintain their conductive state.Meanwhile they have unique pore structures and distinctive rectification properties and ion selectivity for cations compared to wild-type pores.We conclude that although the mutants may partially capture the gating motion characteristics of wild-type pores,the information obtained from these mutants is likely not a true reflection of CRAC channel gating under physiological conditions.
基金partially supported by Knowledge Innovation Program of Hubei Province(No.2019CFB810)partially supported by NSFC(No.12325110)the CAS Project for Young Scientists in Basic Research(No.YSBR-034)。
文摘The conditional kernel correlation is proposed to measure the relationship between two random variables under covariates for multivariate data.Relying on the framework of reproducing kernel Hilbert spaces,we give the definitions of the conditional kernel covariance and conditional kernel correlation.We also provide their respective sample estimators and give the asymptotic properties,which help us construct a conditional independence test.According to the numerical results,the proposed test is more effective compared to the existing one under the considered scenarios.A real data is further analyzed to illustrate the efficacy of the proposed method.
