The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKS...The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.展开更多
The epidemic characters of Omicron(e.g.large-scale transmission)are significantly different from the initial variants of COVID-19.The data generated by large-scale transmission is important to predict the trend of epi...The epidemic characters of Omicron(e.g.large-scale transmission)are significantly different from the initial variants of COVID-19.The data generated by large-scale transmission is important to predict the trend of epidemic characters.However,the re-sults of current prediction models are inaccurate since they are not closely combined with the actual situation of Omicron transmission.In consequence,these inaccurate results have negative impacts on the process of the manufacturing and the service industry,for example,the production of masks and the recovery of the tourism industry.The authors have studied the epidemic characters in two ways,that is,investigation and prediction.First,a large amount of data is collected by utilising the Baidu index and conduct questionnaire survey concerning epidemic characters.Second,theβ-SEIDR model is established,where the population is classified as Susceptible,Exposed,Infected,Dead andβ-Recovered persons,to intelligently predict the epidemic characters of COVID-19.Note thatβ-Recovered persons denote that the Recovered persons may become Sus-ceptible persons with probabilityβ.The simulation results show that the model can accurately predict the epidemic characters.展开更多
Detection of ultralow magnetic field requires magnetic sensors with high sensitivity and low noise level,especially for low operating frequency applications.We investigated the transport properties of tunnel magnetore...Detection of ultralow magnetic field requires magnetic sensors with high sensitivity and low noise level,especially for low operating frequency applications.We investigated the transport properties of tunnel magnetoresistance(TMR)sensors based on the double indirect exchange coupling effect.The TMR ratio of about 150%was obtained in the magnetic tunnel junctions and linear response to an in-plane magnetic field was successfully achieved.A high sensitivity of 1.85%/Oe was achieved due to a designed soft pinned sensing layer of CoFeB/NiFe/Ru/IrMn.Furthermore,the voltage output sensitivity and the noise level of 10.7 mV/V/Oe,10 nT/Hz^(1/2)at 1 Hz and3.3 nT/Hz^(1/2)at 10 Hz were achieved in Full Wheatstone Bridge configuration.This kind of magnetic sensors can be used in the field of smart grid for current detection and sensing.展开更多
基金supported by the National Nature Science Foundation of China,No.32101020(to JL)the Natural Science Foundation of Shandong Province,Nos.ZR2020MC071(to JL),ZR2023MH327(to HZ)+1 种基金the Integrated Project of Major Research Plan of National Natural Science Foundation of China,No.92249303(to PL)the Natural Science Foundation of Qingdao,No.23-2-1-193-zyyd-jch(to HZ)。
文摘The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.
基金Key discipline construction project for traditional Chinese Medicine in Guangdong province,Grant/Award Number:20220104The construction project of inheritance studio of national famous and old traditional Chinese Medicine experts,Grant/Award Number:140000020132。
文摘The epidemic characters of Omicron(e.g.large-scale transmission)are significantly different from the initial variants of COVID-19.The data generated by large-scale transmission is important to predict the trend of epidemic characters.However,the re-sults of current prediction models are inaccurate since they are not closely combined with the actual situation of Omicron transmission.In consequence,these inaccurate results have negative impacts on the process of the manufacturing and the service industry,for example,the production of masks and the recovery of the tourism industry.The authors have studied the epidemic characters in two ways,that is,investigation and prediction.First,a large amount of data is collected by utilising the Baidu index and conduct questionnaire survey concerning epidemic characters.Second,theβ-SEIDR model is established,where the population is classified as Susceptible,Exposed,Infected,Dead andβ-Recovered persons,to intelligently predict the epidemic characters of COVID-19.Note thatβ-Recovered persons denote that the Recovered persons may become Sus-ceptible persons with probabilityβ.The simulation results show that the model can accurately predict the epidemic characters.
基金Supported by the Framework Project of SGCC(Grant No.5700-202058381A-0-0-00)the National Key Research and Development Program of China(Grant No.2017YFA0206200)。
文摘Detection of ultralow magnetic field requires magnetic sensors with high sensitivity and low noise level,especially for low operating frequency applications.We investigated the transport properties of tunnel magnetoresistance(TMR)sensors based on the double indirect exchange coupling effect.The TMR ratio of about 150%was obtained in the magnetic tunnel junctions and linear response to an in-plane magnetic field was successfully achieved.A high sensitivity of 1.85%/Oe was achieved due to a designed soft pinned sensing layer of CoFeB/NiFe/Ru/IrMn.Furthermore,the voltage output sensitivity and the noise level of 10.7 mV/V/Oe,10 nT/Hz^(1/2)at 1 Hz and3.3 nT/Hz^(1/2)at 10 Hz were achieved in Full Wheatstone Bridge configuration.This kind of magnetic sensors can be used in the field of smart grid for current detection and sensing.