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Both gain-and loss-of-function variants of KCNA1 are associated with paroxysmal kinesigenic dyskinesia

Journal of Genetics and Genomics 2024年第8期51卷 801-810页

作者： Wan-Bing Sun Jing-Xin Fu Yu-Lan Chen Hong-Fu Li Zhi-Ying Wu Dian-Fu Chen Department of Medical Genetics and Center for Rare Diseases and Department of Neurologyand Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation in Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Nanhu Brain-computer Interface Institute HangzhouZhejiang 314050China MOE Frontier Science Center for Brain Science and Brain-machine integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang 310012China

KCNA1 is the coding gene for Kv1.1 voltage-gated potassium-channelα*** variants of KCNA1 have been reported to manifest as paroxysmal kinesigenic dyskinesia(PKD),but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD *** the whole exome sequencing followed by Sanger sequencing,we screen for potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese *** proband of one family(c.496G>A,p.A166T)manifests as episodic ataxia type 1,and the other two(c.877G>A,p.V293I and c.1112C>A,p.T371A)manifest as *** pathogenicity of these variants is confirmed by functional studies,suggesting that p.A166T and p.T371A cause a loss-of-function of the channel,while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic *** reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein,we find that these variants tend to cluster around the pore domain,which is similar to ***,our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype–phenotype correlations of KCNA1 channelopathy.

关键词： Paroxysmal kinesigenic dyskinesia KCNA1 Loss-of-function Gain-of-function Channelopathy Episodicataxiatype1

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THREE METHODS FOR ESTIMATING TURBULENT STRESS AND DRAG COEFFICIENT IN TIDAL CURRENTS OF THE HANGZHOU BAY

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Chinese Science Bulletin 1987年第4期32卷 252-257页

作者：方国洪李身铎曹德明 Institute of Occanology Academia SinicaQingdao Estuarine and Coastal Rcscarch Institute East China Normal UniversityShanghai Institute of Occanology Academia SinicaQingdaon this paper we employed three metbods for measuring and estimating the turbulent stress and the results obtained were in good agreement with each other. The first method is a direct application of the momentum equations the second one is based on the integration of momentum equations over an area by which an overall estimate of the stress term for the area can be obtained while the third one makes use of the energy equation and from which the estimate of the drag coefficient is deduced.

In this paper, we employed three metbods for measuring and estimating the turbulent stress and the results obtained were in good agreement with each other. The first method is a direct application of the momentum equations; the second one is based on the integration of momentum equations over an area, by which an overall estimate of the stress term for the area can be obtained; while the third one makes use of the energy equation and from which the estimate of the drag coefficient is deduced.

关键词： momentum turbulent deduced estimating tidal turbulence angular generating coordinates alignment

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An improved calculation method for fiber Raman amplifier equations with multi-wavelength pumping

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Chinese Optics Letters 2004年第8期2卷 441-444页

作者：常建华张明德孙小菡 Department of Electronic Engineering Southeast University Nanjing 210096 Department of Electronic Engineering Southeast University Nanjing 210096 novel numerical method for fiber Raman amplifier (FRA) from standard propagation equations is presented and derived based on the one-step method for ordinary differential equation (ODE). The proposed algorithm is effective in solving FRA equations including all the interactions among pumps signals and noises. Applications of the numerical analysis to practical FRA-based systems show a great reduction in computation time in comparison with the average power method and the fourth-order Runge-Kutta (RK) method under the same condition. Also the proposed method can decrease the computing time over three orders of magnitude with excellent accuracy promises in comparison with the direct integration method.

A novel numerical method for fiber Raman amplifier (FRA) from standard propagation equations is presented and derived based on the one-step method for ordinary differential equation (ODE). The proposed algorithm is effective in solving FRA equations including all the interactions among pumps, signals, and noises. Applications of the numerical analysis to practical FRA-based systems show a great reduction in computation time in comparison with the average power method and the fourth-order Runge-Kutta (RK) method, under the same condition. Also the proposed method can decrease the computing time over three orders of magnitude with excellent accuracy promises in comparison with the direct integration method.

关键词： length FRA An improved calculation method for fiber Raman amplifier equations with multi-wavelength pumping

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Effects of acetylcysteine on micro-inflammation and pulmonary ventilation in chronic obstructive pulmonary disease exacerbation

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World Journal of Clinical Cases 2024年第18期12卷 3482-3490页

作者： Li-Yuan Huang Bin Huang Zheng Lv Xiao-Dan Lu Department of integration of Traditional Chinese and Western Medicine School of Clinical MedicineChangchun University of Chinese MedicineChangchun 130021Jilin ProvinceChina Department of Infectious Diseases Affiliated People's Hospital of Jiangsu UniversityZhenjiang 212002Jiangsu ProvinceChina Department of Zoology School of Life SciencesChangchun Normal UniversityChangchun 130032Jilin ProvinceChina Precision Medical Center Jilin Province General HospitalChangchun 130021Jilin ProvinceChina

BACKGROUND Acute exacerbation of chronic obstructive pulmonary disease(AECOPD)is a serious complication of chronic obstructive pulmonary disease,often characterized by increased morbidity and *** traditional Chinese medicine,AECOPD is linked to phlegm-heat and blood-stasis,presenting symptoms like thick sputum,fever,and chest *** has been shown that acetylcysteine inhalation in conjunction with conventional therapy significantly reduced inflammatory markers and improved lung function parameters in patients with AECOPD,suggesting that acetylcysteine may be an important adjunctive therapy for patients with phlegm-heat-blood stasis type *** To investigate the effect of acetylcysteine on microinflammation and lung ventilation in patients with phlegm-heat and blood-stasis-type *** one hundred patients with phlegm-heat and blood-stasis-type AECOPD were randomly assigned to two *** treatment group received acetylcysteine inhalation(10%solution,5 mL,twice daily)along with conventional therapy,whereas the control group received only conventional *** treatment duration was 14 *** markers(C-reactive protein,interleukin-6,and tumor necrosis factor-alpha)in the serum and sputum as well as lung function parameters(forced expiratory volume in one second,forced vital capacity,and peak expiratory flow)were assessed pre-and *** inhalation led to significant reductions in inflammatory markers and improvements in lung function parameters compared to those in the control group(P<0.05).This suggests that acetylcysteine could serve as an effective adjunct therapy for patients with phlegm-heat and blood-stasis-type *** Acetylcysteine inhalation significantly reduced inflammatory markers in the serum and sputum and improved lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD compared with the control *** differences were statistically significant(P

关键词： Acute exacerbation Chronic obstructive pulmonary disease Traditional Chinese medicine Acetylcysteine Phlegm-heat and blood-stasis Lung ventilation function

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Pathway Matters: Prefrontal Control of Negative Emotions via Distinct Downstream Regions

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Neuroscience Bulletin 2022年第2期38卷 226-228页

作者： Junqiang Zheng Na Liu Han Xu Department of Neurobiology and Department of Neurology of the second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China NHC and CAMS Key Laboratory of Medical Neurobiology MOE Frontier Science Center for Brain Research and Brain-Machine IntegrationSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou 310058China

The infralimbic cortex(IL)is a major subregion of the medial prefrontal cortex(mPFC)that is essential for many advanced brain functions including *** studies have unraveled a critical role of the IL in the processing of negative emotions such as fear and ***,these studies also generate controversial data regarding the precise functions of the IL in the regulation of either fear or *** one hand,pharmacological inactivation of the IL attenuates anxiety-like behaviors and consistently,pharmacological activation of the IL produces anxiety-like behaviors[1].

关键词： inactivation precise Mount

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Improving the Performance and Energy Efficiency of Phase Change Memory Systems

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Journal of Computer Science & Technology 2015年第1期30卷 110-120页

作者：王琪李佳芮王东辉 Digital System integration Laboratory Institute of Acoustics Chinese Academy of Sciences Beijing 100190 China University of Chinese Academy of Sciences Beijing 100049 China

Phase change memory （PCM） is a promising technology for future memory thanks to its better scalability and lower leakage power than DRAM （dynamic random-access memory）. However, adopting PCM as main memory needs to overcome its write issues, such as long write latency and high write power. In this paper, we propose two techniques to improve the performance and energy-efficiency of PCM memory systems. First, we propose a victim cache technique utilizing the existing buffer in the memory controller to reduce PCM memory accesses. The key idea is reorganizing the buffer into a victim cache structure （RBC） to provide additional hits for the LLC （last level cache）. second, we propose a chip parallelism-aware replacement policy （CPAR） for the victim cache to further improve performance. Instead of evicting one cache line once, CPAR evicts multiple cache lines that access different PCM chips. CPAR can reduce the frequent victim cache eviction and improve the write parallelism of PCM chips. The evaluation results show that, compared with the baseline, RBC can improve PCM memory system performance by up to 9.4% and 5.4% on average. Combing CPAR with RBC （RBC＋CPAR） can improve performance by up to 19.0% and 12.1% on average. Moreover, RBC and RBC＋CPAR can reduce memory energy consumption by 8.3% and 6.6% on average, respectively.

关键词： phase change memory systems performance energy efficiency

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A Standardized Protocol for the Induction of Specific Social Fear in Mice

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Neuroscience Bulletin 2021年第12期37卷 1708-1712页

作者： Junqiang Zheng Yuanyuan Tian Haifeng Xu Linfan Gu Han Xu Department of Neurobiology and Department of Neurology of the second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China NHC and CAMS Key Laboratory of Medical Neurobiology MOE Frontier Science Center for Brain Science and BrainMachine IntegrationSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou 310058China

Dear Editor,Social anxiety disorder(SAD)is one of the most common psychiatric *** is characterized by intense and persistent fear of one or more social situations in which one is exposed to possible scrutiny by others[1].The lifetime prevalence of SAD ranges from 0.2%to 13%,with higher prevalence in high-income *** SAD can last a lifetime and is often accompanied by impairments in social life,which severely compromises the quality of ***,SAD is associated with a higher risk of other mental and physical disorders including depressive disor-ders,substance abuse disorders,general anxiety disorders,and cardiovascular diseases[2].

关键词： prevalence lifetime cardiovascular

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Evolutionary trajectory of TRPM2 channel activation by adenosine diphosphate ribose and calcium

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Science Bulletin 2024年第18期69卷 2892-2905页

作者： Cheng Ma Yanping Luo Congyi Zhang Cheng Cheng Ning Hua Xiaocao Liu Jianan Wu Luying Qin Peilin Yu Jianhong Luo Fan Yang Lin-Hua Jiang Guojie Zhang Wei Yang Department of Biophysics and Department of Neurosurgery The Fourth Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China Protein Facility Core FacilitiesZhejiang University School of MedicineZhejiang UniversityHangzhou 310058China Department of Toxicology and Department of Medical Oncology of The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China Department of Neurobiology Affiliated Mental Health CenterCollege of Brain Science and Brain MedicineZhejiang University School of MedicineHangzhou 310058China Department of Biophysics and Kidney Disease Center of The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province and Department of Physiology and PathophysiologyXinxiang Medical UniversityXinxiang 453004China Henan Collaborative Innovation Center of Prevention and Treatment of Mental Disorder The Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 453004China Evolutionary&Organismal Biology Research Center School of MedicineZhejiang UniversityHangzhou 310058China GuiZhou University Medical College Guiyang 550025China

Ion channel activation upon ligand gating triggers a myriad of biological events and,therefore,evolution of ligand gating mechanism is of fundamental ***2,a typical ancient ion channel,is activated by adenosine diphosphate ribose(ADPR)and calcium and its activation has evolved from a simple mode in invertebrates to a more complex one in vertebrates,but the evolutionary process is still *** evolutionary analysis of TRPM2s from more than 280 different animal species has revealed that,the C-terminal NUDT9-H domain has evolved from an enzyme to a ligand binding site for activation,while the N-terminal MHR domain maintains a conserved ligand binding *** gating pattern has also evolved,from one Ca^(2+)-binding site as in sea anemones to three sites as in ***,we identified a new group represented by olTRPM2,which has a novel gating mode and fills the missing link of the channel gating *** conclude that the TRPM2 ligand binding or activation mode evolved through at least three identifiable stages in the past billion years from simple to complicated and *** findings benefit the evolutionary investigations of other channels and proteins.

关键词： TRPM2 channel Activation mode Molecular evolution

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Production threshold impact on a GEANT4 calculation of the power deposition in a fast domain: MEGAPIE spallation target

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Nuclear Science and Techniques 2019年第5期30卷 40-47页

作者： Abdesslam Lamrabet Abdelmajid Maghnouj Jaouad Tajmouati Mohamed Bencheikh Laboratory of integration of Systems and Advanced Technologies Faculty of Sciences Dhar El mahrazUniversity Sidi Mohamed Ben Abdellah El Hajeb

The calculation time in the Monte Carlo simulations consistently represents an essential issue. It is often very long, and its decrease constitutes a challenge for the simulator. Generally, an MC simulation is qualified as quality or not according to two main criteria: the calculation time and the accuracy of the results. However, in most cases, the optimization of one criterion affects negatively the other. Therefore, a compromise between both of them is always required in this kind of simulation. The present work aims at studying the impact of the production threshold(or cut) of the GEANT4 toolkit on the calculation of the power deposition in the MEGAPIE spallation *** production threshold of secondaries is a GEANT4 intrinsic parameter. It indicates the limit of energy we can reach in the production of secondary particles. This study has allowed us to make the following conclusions. First,the influence of the cut on the calculation of the deposited power depends on the volume size, its arrangement and the importance of the electromagnetic processes occurring within. second, the accuracy of the calculations can be acceptable only below a given value of the cut ***, this accuracy remains almost unchangeable from a certain value of the cut. The study has also made it possible to explore the prevalence of certain interactions in the zone of spallation in the MEGAPIE target.

关键词： Production threshold Power deposition Spallation MEGAPIE GEANT4

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Lighting up Oxytocin Neurons to Nurture the Brain

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Neuroscience Bulletin 2023年第5期39卷 866-868页

作者： Fang Zhou Junqiang Zheng Han Xu Department of Neurobiology and Department of Neurology of the second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China Liangzhu Laboratory MOE Frontier Science Center for Brain Science and Brain-machine IntegrationState Key Laboratory of Brain-machine IntelligenceZhejiang UniversityHangzhou 311121China NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang UniversityHangzhou 310058China

The sensory system develops earlier than the systems responsible for higher brain functions such as language and cognition[1].Moreover,sensory experiences in early life are critical for the development of the ***,how sensory experiences shape brain development is an important yet unresolved question in *** work has demonstrated that deprivation of sensory inputs in the early developmental stage causes synaptic dysfunction in the sensory ***,it has been reported that oxytocin can restore the deficits caused by somatosensory deprivation in neonatal mice,suggesting that oxytocin may play a key role in sensory-mediated synaptogenesis[2].Vision is one of the most important sensory inputs during early development in mammalians including humans[1],but the neural mechanism underlying vision-mediated brain development is still largely unknown.

关键词： neonatal neural sensory

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