Protein phosphatase 2A(PP2A)is one of the most abundant serine/threonine phosphatases and plays critical roles in regulating cell fate and function.We previously showed that PP2A regulates the differentiation of CD4^(...Protein phosphatase 2A(PP2A)is one of the most abundant serine/threonine phosphatases and plays critical roles in regulating cell fate and function.We previously showed that PP2A regulates the differentiation of CD4^(+)T cells and the development of thymocytes.Nevertheless,its role in CD8^(+)T cells remains elusive.By ablating the catalytic subunit α(Cα)of PP2A in CD8^(+)T cells,we revealed the essential role of PP2A in promoting the effector functions of CD8^(+)T cells.Notably,PP2A Cα-deficient CD8^(+)T cells exhibit reduced proliferation and decreased cytokine production upon stimulation in vitro.In vivo,mice lacking PP2A Cαin T cells displayed defective immune responses against lymphocytic choriomeningitis virus infection,associated with reduced CD8^(+)T cell expansion and decreased cytokine production.Consistently,the ablation of the PP2A Cαsubunit in CD8^(+)T cells results in attenuated antitumor activity in mice.There is a notable decrease in the infiltration of PP2A Cα-deficient CD8^(+)T cells within the tumor microenvironment,and the cells that do infiltrate exhibit diminished effector functions.Mechanistically,PP2A Cα deficiency impedes CD28-induced AKT Ser^(473) phosphorylation,thus impairing CD8^(+)T cell costimulation signal.Collectively,our findings underscore the critical role of phosphatase PP2A as a propeller for CD28-mediated costimulation signaling in CD8^(+)T cell effector function by fine-tuning T cell activation.展开更多
To fulfill the demands for higher quality,efficiency and flexibility in aviation industry,a multi-functional end effector is designed to automate the drilling and riveting processes in assembling carbon fiber reinforc...To fulfill the demands for higher quality,efficiency and flexibility in aviation industry,a multi-functional end effector is designed to automate the drilling and riveting processes in assembling carbon fiber reinforced polymer(CFRP)and aluminum components for a robotic aircraft assembly system.To meet the specific functional requirements for blind rivet installation on CFRP and aluminum materials,additional modules are incorporated on the end effector aside of the basic processing modules for drilling.And all of these processing modules allow for a onestep-drilling-countersinking process,hole inspection,automatic rivet feed,rivet geometry check,sealant application,rivet insertion and installation.Besides,to guarantee the better quality of the hole drilled and joints riveted,several online detection and adjustment measures are applied to this end effector,including the reference detection and perpendicular calibration,which could effectively ensure the positioning precision and perpendicular accuracy as demanded.Finally,the test result shows that this end effector is capable of producing each hole to a positioning precision within ±0.5 mm,aperpendicular accuracy within 0.3°,a diameter tolerance of H8,and a countersink depth tolerance of±0.01 mm.Moreover,it could drill and rivet up to three joints per minute,with acceptable shearing and tensile strength.展开更多
Huanglongbing (HLB) or citrus greening is currently the most important citrus disease, caused by the bacterium </span><i><span style="font-family:Verdana;">Candidatus</span></i>...Huanglongbing (HLB) or citrus greening is currently the most important citrus disease, caused by the bacterium </span><i><span style="font-family:Verdana;">Candidatus</span></i><span style="font-family:Verdana;"> Liberibacter asiaticus (</span><i><span style="font-family:Verdana;">C</span></i><span style="font-family:Verdana;">Las). The impossibility of isolating it causes understanding its pathogenic mechanisms to be a complicated task. Recent studies identified 16 proteins with the signal peptide needed to be secreted in the plant and cause the disease. The present study aims to perform a bioinformatic analysis of these proteins with the function prediction approach by gene ontology (GO) and the detection of conserved domains. It was observed that of the 16 proteins analyzed not all are found in different infective strains reported in the literature. The GO analysis allowed us to relate different proteins with the biological process of energy and pathogenic activity, especially CLIBASIA_03315 and CLIBASIA_05115, respectively. The domain analysis allowed the observation of a </span></span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:""><span style="font-family:Verdana;">-CA domain, tentatively related to the damage caused to the chloroplast and a PAAR domain associated with the T6SS secretory system. Our results provide information on the possible function of potential pathogenicity effectors in </span><i><span style="font-family:Verdana;">C</span></i><span style="font-family:Verdana;">Las.展开更多
基金supported by the China Postdoctoral Science Foundation(2022M720087 to K.Z.)National Natural Science Foundation of China(32300775 to K.Z.,32100718 to X.J.,32141004,32350007,and 31930038 to L.L.)+2 种基金the Provincial Natural Science Foundation of Zhejiang Province(LQ22H030012 to S.H.)the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(LHDMZ24H310001 to X.J.)the Scientific Research Fund of Zhejiang Provincial Education Department(Y202146347 to X.J.).
文摘Protein phosphatase 2A(PP2A)is one of the most abundant serine/threonine phosphatases and plays critical roles in regulating cell fate and function.We previously showed that PP2A regulates the differentiation of CD4^(+)T cells and the development of thymocytes.Nevertheless,its role in CD8^(+)T cells remains elusive.By ablating the catalytic subunit α(Cα)of PP2A in CD8^(+)T cells,we revealed the essential role of PP2A in promoting the effector functions of CD8^(+)T cells.Notably,PP2A Cα-deficient CD8^(+)T cells exhibit reduced proliferation and decreased cytokine production upon stimulation in vitro.In vivo,mice lacking PP2A Cαin T cells displayed defective immune responses against lymphocytic choriomeningitis virus infection,associated with reduced CD8^(+)T cell expansion and decreased cytokine production.Consistently,the ablation of the PP2A Cαsubunit in CD8^(+)T cells results in attenuated antitumor activity in mice.There is a notable decrease in the infiltration of PP2A Cα-deficient CD8^(+)T cells within the tumor microenvironment,and the cells that do infiltrate exhibit diminished effector functions.Mechanistically,PP2A Cα deficiency impedes CD28-induced AKT Ser^(473) phosphorylation,thus impairing CD8^(+)T cell costimulation signal.Collectively,our findings underscore the critical role of phosphatase PP2A as a propeller for CD28-mediated costimulation signaling in CD8^(+)T cell effector function by fine-tuning T cell activation.
基金supported by the National Natural Science Foundations of China(Nos.5157051626,51475225)
文摘To fulfill the demands for higher quality,efficiency and flexibility in aviation industry,a multi-functional end effector is designed to automate the drilling and riveting processes in assembling carbon fiber reinforced polymer(CFRP)and aluminum components for a robotic aircraft assembly system.To meet the specific functional requirements for blind rivet installation on CFRP and aluminum materials,additional modules are incorporated on the end effector aside of the basic processing modules for drilling.And all of these processing modules allow for a onestep-drilling-countersinking process,hole inspection,automatic rivet feed,rivet geometry check,sealant application,rivet insertion and installation.Besides,to guarantee the better quality of the hole drilled and joints riveted,several online detection and adjustment measures are applied to this end effector,including the reference detection and perpendicular calibration,which could effectively ensure the positioning precision and perpendicular accuracy as demanded.Finally,the test result shows that this end effector is capable of producing each hole to a positioning precision within ±0.5 mm,aperpendicular accuracy within 0.3°,a diameter tolerance of H8,and a countersink depth tolerance of±0.01 mm.Moreover,it could drill and rivet up to three joints per minute,with acceptable shearing and tensile strength.
文摘Huanglongbing (HLB) or citrus greening is currently the most important citrus disease, caused by the bacterium </span><i><span style="font-family:Verdana;">Candidatus</span></i><span style="font-family:Verdana;"> Liberibacter asiaticus (</span><i><span style="font-family:Verdana;">C</span></i><span style="font-family:Verdana;">Las). The impossibility of isolating it causes understanding its pathogenic mechanisms to be a complicated task. Recent studies identified 16 proteins with the signal peptide needed to be secreted in the plant and cause the disease. The present study aims to perform a bioinformatic analysis of these proteins with the function prediction approach by gene ontology (GO) and the detection of conserved domains. It was observed that of the 16 proteins analyzed not all are found in different infective strains reported in the literature. The GO analysis allowed us to relate different proteins with the biological process of energy and pathogenic activity, especially CLIBASIA_03315 and CLIBASIA_05115, respectively. The domain analysis allowed the observation of a </span></span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:""><span style="font-family:Verdana;">-CA domain, tentatively related to the damage caused to the chloroplast and a PAAR domain associated with the T6SS secretory system. Our results provide information on the possible function of potential pathogenicity effectors in </span><i><span style="font-family:Verdana;">C</span></i><span style="font-family:Verdana;">Las.
文摘免疫球蛋白G(immunoglobulin G,Ig G)是免疫系统的重要成分,是B细胞产生的糖蛋白,糖基化位点位于Fc段第297位氨基酸天冬酰胺上。糖链组成具有不均一性,末端组分变化可以影响抗体功能,并受多种因素的调节,如疫苗接种可以调节Fc段糖链修饰,进而影响抗体与Fc受体或补体的结合,从而对抗体的功能产生影响。本文就Ig G Fc糖链的组成、糖链与功能的关系、疫苗接种对糖链修饰的调节及对功能的影响作一综述。
