Epilepsy,one of the most common neurological disorders,is characterized by spon-taneous recurrent seizures.Temporal lobe epilepsy(TLE)is one of the most common medically intractable seizure disorders.Traf2-and NcK-int...Epilepsy,one of the most common neurological disorders,is characterized by spon-taneous recurrent seizures.Temporal lobe epilepsy(TLE)is one of the most common medically intractable seizure disorders.Traf2-and NcK-interacting kinase(TNIK)has recently attracted attention as a critical modulation target of many neurological and psychiatric disorders,but its role in epilepsy remains unclear.In this study,we hypothesized the involvement of TNIK in epilepsy and investigated TNIK expression in patients with intractable TLE and in a pilocarpineinduced rat model of epilepsy by western blotting,immunofluorescence,and immunohistochemistry.A pentylenetetrazole(PTZ)-induced epilepsy rat model was used to determine the effect of the TNIK inhibitor NCB-0846 on behavioral manifestations of epilepsy.Coimmunoprecipitation(Co-IP)/mass spectrometry(MS)was used to identify the potential mechanism.Through Co-IP,we detected and confirmed the main potential TNIK interactors.Subcellular fractionation was used to establish the effect of NCB-0846 on the expression of the main interactors in postsynaptic density(PSD)fractions.We found that TNIK was primarily located in neurons and decreased significantly in epilepsy model rats and TLE patients compared with controls.NCB-0846 delayed kindling progression and decreased seizure severity.Co-IP/MS identified 63 candidate TNIK interactors in rat hippocampi,notably CaMKIl.Co-IP showed that TNIK might correlate with endogenous GRIA1,SYN2,PSD-95,CaMKIV,GABRG1,and GABRG2.In addition,the significant decrease in GRIA1 in hippocampal total lysate and PSDs after NCB-0846 treatment might help modify the progression of PTZ kindling.Our results suggest that TNIK contributes to epileptic pathology and is a potential antiepileptic drug target.展开更多
数量庞大的NORAD(North American Aerospace Defense Command)在轨编目目标轨道通过双行根数(two line elements,TLE)的形式向大众发布,然而由于采用SGP4模型等原因,TLE的轨道预报精度不高,有必要利用相关方法提高预报能力。本文利用长...数量庞大的NORAD(North American Aerospace Defense Command)在轨编目目标轨道通过双行根数(two line elements,TLE)的形式向大众发布,然而由于采用SGP4模型等原因,TLE的轨道预报精度不高,有必要利用相关方法提高预报能力。本文利用长春站光电阵稀疏角度观测数据改进TLE的轨道预报精度,选择了4个NORAD编目目标作为对象进行实验。结果表明,当3 d定轨时段内含至少3个观测弧段时,利用改进后的TLE预报目标7 d后的轨道的精度可以较原始TLE预报精度提升近50%,表明利用稀疏光学测角数据改善目标TLE预报精度是可行的。展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81901324,82001378,82071395)China Postdoctoral Science Foundation(No.2021M693246)+4 种基金joint project of Chongqing Health Commission and Science and Technology Bureau(Chongqing,China)(No.2023QNXM009)Science and Technology Research Program of Chongqing Education Commission of China(No.KJQN202200435)Chongqing Talents:Exceptional Young Talents Project(Chongqing,China)(No.CQYC202005014)Natural Science Foundation of Chongqing,China(No.cstc2021ycjh-bgzxm0035,CSTB2022NSCQ-LZX0038)Key Research and Development Projects of Jining City,Shandong,China(No.2021YXNS057).
文摘Epilepsy,one of the most common neurological disorders,is characterized by spon-taneous recurrent seizures.Temporal lobe epilepsy(TLE)is one of the most common medically intractable seizure disorders.Traf2-and NcK-interacting kinase(TNIK)has recently attracted attention as a critical modulation target of many neurological and psychiatric disorders,but its role in epilepsy remains unclear.In this study,we hypothesized the involvement of TNIK in epilepsy and investigated TNIK expression in patients with intractable TLE and in a pilocarpineinduced rat model of epilepsy by western blotting,immunofluorescence,and immunohistochemistry.A pentylenetetrazole(PTZ)-induced epilepsy rat model was used to determine the effect of the TNIK inhibitor NCB-0846 on behavioral manifestations of epilepsy.Coimmunoprecipitation(Co-IP)/mass spectrometry(MS)was used to identify the potential mechanism.Through Co-IP,we detected and confirmed the main potential TNIK interactors.Subcellular fractionation was used to establish the effect of NCB-0846 on the expression of the main interactors in postsynaptic density(PSD)fractions.We found that TNIK was primarily located in neurons and decreased significantly in epilepsy model rats and TLE patients compared with controls.NCB-0846 delayed kindling progression and decreased seizure severity.Co-IP/MS identified 63 candidate TNIK interactors in rat hippocampi,notably CaMKIl.Co-IP showed that TNIK might correlate with endogenous GRIA1,SYN2,PSD-95,CaMKIV,GABRG1,and GABRG2.In addition,the significant decrease in GRIA1 in hippocampal total lysate and PSDs after NCB-0846 treatment might help modify the progression of PTZ kindling.Our results suggest that TNIK contributes to epileptic pathology and is a potential antiepileptic drug target.
文摘数量庞大的NORAD(North American Aerospace Defense Command)在轨编目目标轨道通过双行根数(two line elements,TLE)的形式向大众发布,然而由于采用SGP4模型等原因,TLE的轨道预报精度不高,有必要利用相关方法提高预报能力。本文利用长春站光电阵稀疏角度观测数据改进TLE的轨道预报精度,选择了4个NORAD编目目标作为对象进行实验。结果表明,当3 d定轨时段内含至少3个观测弧段时,利用改进后的TLE预报目标7 d后的轨道的精度可以较原始TLE预报精度提升近50%,表明利用稀疏光学测角数据改善目标TLE预报精度是可行的。
