Adapter proteins can regulate the gene transcriptions in disparate signaling pathway by interacting with multiple signaling molecules, including T cell activation signaling. Nuclear receptor binding protein （NRBP）, ...Adapter proteins can regulate the gene transcriptions in disparate signaling pathway by interacting with multiple signaling molecules, including T cell activation signaling. Nuclear receptor binding protein （NRBP）, a novel adapter protein, represents a small family of evolutionarily conserved proteins with homologs in Caenorhabditis elegans （C. elegans）, Drosophila melanogaster （i）. melanogaster）, mouse and human. Here, we demonstrated that overexpression of NRBP in Jurkat TAg cells specifically impairs T cell receptor （TCR） or phorbol myristate acetate （PMA） /ionomycin-mediated signaling leading to nuclear factor of activated T cells （NFAT） promoter activation. Furthermore, the N-terminal of NRBP is necessary for its regulation of NFAT activation. Finally, we showed that NRBP has minimal effect on both TCR- and PMA-induced CD69 up-regulation in Jurkat TAg cells, which suggests that NRBP may function downstream of protein kinase C （PKC） /Ras pathway.展开更多
In the present work, the two-dimensional analytical solution for Li diffusion in grains and grain boundaries of a polycrystalline film electrode is established with consideration of Li-segregation at the grain boundar...In the present work, the two-dimensional analytical solution for Li diffusion in grains and grain boundaries of a polycrystalline film electrode is established with consideration of Li-segregation at the grain boundary. The stress field induced by the inhomogeneity of Li con- centration, called chemical stress here for brevity, is analyzed via the finite element simulation. The effects of the grain boundary including its size, its diffusion coefficient as well as the segrega- tion phenomenon on the solute concentration and the chemical stress are examined. It shows that grain boundaries can assist fast diffusion and significantly affect the stress profile in the whole film. It proves that tailoring the grain boundary size or other grain boundary-related parameters may provide an alternative strategy for improving the overall diffusivity and mechanical stability of battery electrodes.展开更多
Schizophrenia is a widespread mental disease with a prevalence of about 1%in the world population,and heritability of up to 80%.Drug therapy is an important approach to treating the disease.However,the curative effect...Schizophrenia is a widespread mental disease with a prevalence of about 1%in the world population,and heritability of up to 80%.Drug therapy is an important approach to treating the disease.However,the curative effect of antipsychotic is far from satisfactory in terms of tolerability and side effects.Many studies have indicated that about 30%of the patients exhibit little or no improvements associated with antipsychotics.The response of individual patients who are given the same dose of the same drug varies considerably.In addition,antipsychotic drugs are often accompanied by adverse drug reactions(ADRs),which can cause considerable financial loss in addition to the obvious societal harm.So,it is strongly recommended that personalized medicine should be implemented both to improve drug efficacy and to minimize adverse events and toxicity.There is therefore a need for pharmacogenomic studies into the factors affecting response of schizophrenia patients to antipsychotic drugs to provide informed guidance for clinicians.Individual differences in drug response is due to a combination of many complex factors including ADEM(absorption,distribution,metabolism,excretion)process,transporting,binding with receptor and intracellular signal transduction.Pharmacogenetic and pharmacogenomic studies have successfully identified genetic variants that contribute to this interindividual variability in antipsychotics response.In addition,epigenetic factors such as methylation of DNA and regulation by miRNA have also been reported to play an important role in the complex interactions between the multiple genes and environmental factors which influence individual drug response phenotypes in patients.In this review,we will focus on the latest research on polymorphisms of candidate genes that code for drug metabolic enzymes(CYP2D6,CYP1A2,CYP3A4,etc.),drug transporters(mainly ABCB1)and neurotransmitter receptors(dopamine receptors and serotonin receptors,etc.).We also discuss the genome-wide pharmacogenomic study of schizophrenia and review the current state of knowledge on epigenetics and potential clinical applications.展开更多
Recent developments in data mining-aided materials discovery and optimization are reviewed in this paper,and an introduction to the materials data mining(MDM)process is provided using case studies.Both qualitative and...Recent developments in data mining-aided materials discovery and optimization are reviewed in this paper,and an introduction to the materials data mining(MDM)process is provided using case studies.Both qualitative and quantitative methods in machine learning can be adopted in the MDM process to accomplish different tasks in materials discovery,design,and optimization.State-of-the-art techniques in data mining-aided materials discovery and optimization are demonstrated by reviewing the controllable synthesis of dendritic Co_(3)O_(4) superstructures,materials design of layered double hydroxide,battery materials discovery,and thermoelectric materials design.The results of the case studies indicate that MDM is a powerful approach for use in materials discovery and innovation,and will play an important role in the development of the Materials Genome Initiative and Materials Informatics.展开更多
Nanowires(NWs) exhibit size-dependent mechanical properties due to the high surface/volume ratio, in which temperature also plays an important role. The surface eigenstress model is further developed here to quantitat...Nanowires(NWs) exhibit size-dependent mechanical properties due to the high surface/volume ratio, in which temperature also plays an important role. The surface eigenstress model is further developed here to quantitatively predict the size-dependent mechanical properties of NWs and results in analytic formulas. Molecular dynamics(MD) simulations are conducted to study the size-dependent mechanical of [100], [110] and [111] Ni and Si nanowires within the temperature range of 100–400 K and the MD results verify perfectly the newly developed surface eigenstress model.展开更多
MAP kinase-interacting kinase-2(Mnk2)is one of the downstream kinasesactivated by MAP kinases.It phosphorylates the eukaryotic initiation factor 4E(elF4E),althoughthe role of elF4E phosphorylation and the role of Mnk2...MAP kinase-interacting kinase-2(Mnk2)is one of the downstream kinasesactivated by MAP kinases.It phosphorylates the eukaryotic initiation factor 4E(elF4E),althoughthe role of elF4E phosphorylation and the role of Mnk2 in the process of proteintranslation are notwell understood.Except for elF4E,other physiological substrates of Mnk2 are still unidentified.Tolook for these unidentified substrates and to reveal the physiological function of Mnk2,weperformed a yeast two-hybrid screening with Mnk2 as the bait.The results demonstrated Mnk2 couldinteract with VHL(von Hippel-Lindau tumor suppressor),Rbx1(ring-box1)and Cul2(Cullin2)proteinsin yeast cells.Furthermore,we validated the interaction between Mnk2 and VHL proteins inmammalian cells by co-immunoprecipitation analysis.Because the three proteins VHL,Rbx1 and Cul2are all components of the CBC^(VHL)ubiquitin ligase E3 complex,it has been shown that Mnk2 caninteract with CBC^(VHL)complex,and is probably one of the newsubstrates of the CBC^(VHL)complex.Furthermore,during the interaction of Mnk2 with von Hippel-Lindau(VHL)tumor suppressor-bindingprotein 1(VBP1),it appears that Mnk2 also joins to modulate cell shape as VBP1 plays an importantrole in the process of the maturation of the cytoskeleton and in the process of morphogenesis.展开更多
The coexistence of ferroelectricity,conductivity,and magnetism in a single-phase material has attracted considerable attention due to fundamental interest and tremendous technological potential.However,their mutually ...The coexistence of ferroelectricity,conductivity,and magnetism in a single-phase material has attracted considerable attention due to fundamental interest and tremendous technological potential.However,their mutually exclusive mechanisms hinder the discovery of multifunctional conducting multiferroics.Here,we propose a new material design approach for electron engineering to enable these conflicting properties to coexist.We use first principles calculations to demonstrate that appropriate mechanical strain can turn the excess electrons in doped BaTiO_(3) from a free-carrier configuration to a localized polaronic state by modulating the electron–phonon coupling.The resulting localized spin-polarized electron survives the host ferroelectricity and consequently manifests as a multiferroic polaron.The multiferroic properties coexist with the electronic conductivity arising from the highhopping mobility of the polaron,which enables the doped epitaxial BaTiO_(3) to act as a multiferroic conducting material.This mechanical control over the electron configuration is a potential path toward unusual coexisting properties.展开更多
基金Foundation item: the National Natural Science Foundation (No. 30430630)
文摘Adapter proteins can regulate the gene transcriptions in disparate signaling pathway by interacting with multiple signaling molecules, including T cell activation signaling. Nuclear receptor binding protein （NRBP）, a novel adapter protein, represents a small family of evolutionarily conserved proteins with homologs in Caenorhabditis elegans （C. elegans）, Drosophila melanogaster （i）. melanogaster）, mouse and human. Here, we demonstrated that overexpression of NRBP in Jurkat TAg cells specifically impairs T cell receptor （TCR） or phorbol myristate acetate （PMA） /ionomycin-mediated signaling leading to nuclear factor of activated T cells （NFAT） promoter activation. Furthermore, the N-terminal of NRBP is necessary for its regulation of NFAT activation. Finally, we showed that NRBP has minimal effect on both TCR- and PMA-induced CD69 up-regulation in Jurkat TAg cells, which suggests that NRBP may function downstream of protein kinase C （PKC） /Ras pathway.
基金the support of National Natural Science Foundation of China under Grant Nos. 11702164, 11702166, 11672168 and 11332005the Science and Technology Commission of Shanghai Municipality under Grant No. 14DZ2261200Shanghai Sailing Program No. 17YF1406000
文摘In the present work, the two-dimensional analytical solution for Li diffusion in grains and grain boundaries of a polycrystalline film electrode is established with consideration of Li-segregation at the grain boundary. The stress field induced by the inhomogeneity of Li con- centration, called chemical stress here for brevity, is analyzed via the finite element simulation. The effects of the grain boundary including its size, its diffusion coefficient as well as the segrega- tion phenomenon on the solute concentration and the chemical stress are examined. It shows that grain boundaries can assist fast diffusion and significantly affect the stress profile in the whole film. It proves that tailoring the grain boundary size or other grain boundary-related parameters may provide an alternative strategy for improving the overall diffusivity and mechanical stability of battery electrodes.
基金supported by the National High Technology Research and Development Program of China(863 Program,2012AA 02A515)the National Basic Research Program of China(973 Program,2010CB529600)+6 种基金the National Key Technology R&D Program(2012BAI01B09)the National Natural Science Foundation of China(Grant Nos.30900799,30972823,81121001)the Shanghai Jiao Tong University Med-X Fund(YG2010MS61)Public Science and Technology Research Funds(201210056)the Shanghai Jiao Tong University Interdisciplinary Research Fund,the Major Program of Shanghai Committee of Science and Technology(11dz1950300)the Shanghai Municipal Commission of Science and Technology Program(09DJ1400601)the Shanghai Leading Academic Discipline Project(B205).
文摘Schizophrenia is a widespread mental disease with a prevalence of about 1%in the world population,and heritability of up to 80%.Drug therapy is an important approach to treating the disease.However,the curative effect of antipsychotic is far from satisfactory in terms of tolerability and side effects.Many studies have indicated that about 30%of the patients exhibit little or no improvements associated with antipsychotics.The response of individual patients who are given the same dose of the same drug varies considerably.In addition,antipsychotic drugs are often accompanied by adverse drug reactions(ADRs),which can cause considerable financial loss in addition to the obvious societal harm.So,it is strongly recommended that personalized medicine should be implemented both to improve drug efficacy and to minimize adverse events and toxicity.There is therefore a need for pharmacogenomic studies into the factors affecting response of schizophrenia patients to antipsychotic drugs to provide informed guidance for clinicians.Individual differences in drug response is due to a combination of many complex factors including ADEM(absorption,distribution,metabolism,excretion)process,transporting,binding with receptor and intracellular signal transduction.Pharmacogenetic and pharmacogenomic studies have successfully identified genetic variants that contribute to this interindividual variability in antipsychotics response.In addition,epigenetic factors such as methylation of DNA and regulation by miRNA have also been reported to play an important role in the complex interactions between the multiple genes and environmental factors which influence individual drug response phenotypes in patients.In this review,we will focus on the latest research on polymorphisms of candidate genes that code for drug metabolic enzymes(CYP2D6,CYP1A2,CYP3A4,etc.),drug transporters(mainly ABCB1)and neurotransmitter receptors(dopamine receptors and serotonin receptors,etc.).We also discuss the genome-wide pharmacogenomic study of schizophrenia and review the current state of knowledge on epigenetics and potential clinical applications.
基金Financial supports to this work from National Key Research and Development Program of China(No.2016YFB0700504,2017YFB0701600)Science and Technology Commission of Shanghai Municipality of China(No.15DZ2260300 and No.16DZ2260600)are gratefully acknowledged.
文摘Recent developments in data mining-aided materials discovery and optimization are reviewed in this paper,and an introduction to the materials data mining(MDM)process is provided using case studies.Both qualitative and quantitative methods in machine learning can be adopted in the MDM process to accomplish different tasks in materials discovery,design,and optimization.State-of-the-art techniques in data mining-aided materials discovery and optimization are demonstrated by reviewing the controllable synthesis of dendritic Co_(3)O_(4) superstructures,materials design of layered double hydroxide,battery materials discovery,and thermoelectric materials design.The results of the case studies indicate that MDM is a powerful approach for use in materials discovery and innovation,and will play an important role in the development of the Materials Genome Initiative and Materials Informatics.
基金supported by the National Key R&D Program of China (Grant No. 2017YFB0701600)the National Natural Science Foundation of China (Grant No. 11672168)the Science and Technology Commission of Shanghai Municipality (Grant Nos. 15DZ2260300 and 16DZ2260600)
文摘Nanowires(NWs) exhibit size-dependent mechanical properties due to the high surface/volume ratio, in which temperature also plays an important role. The surface eigenstress model is further developed here to quantitatively predict the size-dependent mechanical properties of NWs and results in analytic formulas. Molecular dynamics(MD) simulations are conducted to study the size-dependent mechanical of [100], [110] and [111] Ni and Si nanowires within the temperature range of 100–400 K and the MD results verify perfectly the newly developed surface eigenstress model.
基金supported by the National High Tech Develop-ment Project of China(863 Program)(Grant No.2001AA221231).
文摘MAP kinase-interacting kinase-2(Mnk2)is one of the downstream kinasesactivated by MAP kinases.It phosphorylates the eukaryotic initiation factor 4E(elF4E),althoughthe role of elF4E phosphorylation and the role of Mnk2 in the process of proteintranslation are notwell understood.Except for elF4E,other physiological substrates of Mnk2 are still unidentified.Tolook for these unidentified substrates and to reveal the physiological function of Mnk2,weperformed a yeast two-hybrid screening with Mnk2 as the bait.The results demonstrated Mnk2 couldinteract with VHL(von Hippel-Lindau tumor suppressor),Rbx1(ring-box1)and Cul2(Cullin2)proteinsin yeast cells.Furthermore,we validated the interaction between Mnk2 and VHL proteins inmammalian cells by co-immunoprecipitation analysis.Because the three proteins VHL,Rbx1 and Cul2are all components of the CBC^(VHL)ubiquitin ligase E3 complex,it has been shown that Mnk2 caninteract with CBC^(VHL)complex,and is probably one of the newsubstrates of the CBC^(VHL)complex.Furthermore,during the interaction of Mnk2 with von Hippel-Lindau(VHL)tumor suppressor-bindingprotein 1(VBP1),it appears that Mnk2 also joins to modulate cell shape as VBP1 plays an importantrole in the process of the maturation of the cytoskeleton and in the process of morphogenesis.
基金The authors acknowledge the financial support for T.X.by the National Natural Science Foundation of China(Grant no.11802169)for T.S.and T.K.by JSPS KAKENHI(25000012,26289006,15K13831,and 17H03145)for J.W.by the Fundamental Research Funds for the Central Universities 2018XZZX001-05,and for T.Y.Z.by the 111 project(No.D16002)from the State Administration of Foreign Experts Affairs and the Ministry of Education,PRC.
文摘The coexistence of ferroelectricity,conductivity,and magnetism in a single-phase material has attracted considerable attention due to fundamental interest and tremendous technological potential.However,their mutually exclusive mechanisms hinder the discovery of multifunctional conducting multiferroics.Here,we propose a new material design approach for electron engineering to enable these conflicting properties to coexist.We use first principles calculations to demonstrate that appropriate mechanical strain can turn the excess electrons in doped BaTiO_(3) from a free-carrier configuration to a localized polaronic state by modulating the electron–phonon coupling.The resulting localized spin-polarized electron survives the host ferroelectricity and consequently manifests as a multiferroic polaron.The multiferroic properties coexist with the electronic conductivity arising from the highhopping mobility of the polaron,which enables the doped epitaxial BaTiO_(3) to act as a multiferroic conducting material.This mechanical control over the electron configuration is a potential path toward unusual coexisting properties.
