A Looming Spatial Localization Neural Network Inspired by MLG1 Neurons in the Crab Neohelice

Similar to most visual animals, the crab Neohelice granulata relies predominantly on visual information to escape from predators, to track prey and for selecting mates. It, therefore, needs specialized neurons to process visual information and determine the spatial location of looming objects. In the crab Neohelice granulata, the Monostratified Lobula Giant type1 (MLG1) neurons have been found to manifest looming sensitivity with finely tuned capabilities of encoding spatial location information. MLG1s neuronal ensemble can not only perceive the location of a looming stimulus, but are also thought to be able to influence the direction of movement continuously, for example, escaping from a threatening, looming target in relation to its position. Such specific characteristics make the MLG1s unique compared to normal looming detection neurons in invertebrates which can not localize spatial looming. Modeling the MLG1s ensemble is not only critical for elucidating the mechanisms underlying the functionality of such neural circuits, but also important for developing new autonomous, efficient, directionally reactive collision avoidance systems for robots and vehicles. However, little computational modeling has been done for implementing looming spatial localization analogous to the specific functionality of MLG1s ensemble. To bridge this gap, we propose a model of MLG1s and their pre-synaptic visual neural network to detect the spatial location of looming objects. The model consists of 16 homogeneous sectors arranged in a circular field inspired by the natural arrangement of 16 MLG1s’ receptive fields to encode and convey spatial information concerning looming objects with dynamic expanding edges in different locations of the visual field. Responses of the proposed model to systematic real-world visual stimuli match many of the biological characteristics of MLG1 neurons. The systematic experiments demonstrate that our proposed MLG1s model works effectively and robustly to perceive and localize looming information, which could be a promising candidate for intelligent machines interacting within dynamic environments free of collision. This study also sheds light upon a new type of neuromorphic visual sensor strategy that can extract looming objects with locational information in a quick and reliable manner

Near-atomic cryo-electron microscopy structures of varicella-zoster virus capsids

VZV是一种广泛存在并且具有高度传染性的人类α-疱疹病毒。初次感染VZV可导致水痘，人群普遍易感（感染率约为61%～100%）。该病毒可在背根神经节潜伏感染，持续终生。夏宁邵教授团队长期开展VZV相关基础与新型疫苗研究，通过系统和精细探索建立了高效的VZV规模化培养和病毒颗粒纯化技术体系，成功获得高质量的VZV颗粒样品。首次揭示了疱疹病毒α家族的水痘-带状疱疹病毒（VZV）不同类型核衣壳的近原子分辨率结构，阐明了VZV核衣壳不同组成蛋白的相互作用网络与衣壳装配机制，可为进一步开展新型载体疫苗设计及抗病毒药物等研究提供重要支持。 我校博士后王玮、高级工程师郑清炳、博士生潘德全和俞海副教授为该论文共同第一作者，我校夏宁邵教授、程通副教授、李少伟教授以及美国罗格斯大学朱桦（Hua Zhu）教授、加利福尼亚大学洛杉矶分校周正洪（Z. Hong Zhou）教授为该论文的共同通讯作者。【Abstract】Varicella-zoster virus (VZV) is a medically important human herpesvirus that causes chickenpox and shingles, but its cell-associated nature has hindered structure studies. Here we report the cryo-electron microscopy structures of purified VZV A-capsid and C-capsid, as well as of the DNA-containing capsid inside the virion. Atomic models derived from these structures show that, despite enclosing a genome that is substantially smaller than those of other human herpesviruses, VZV has a similarly sized capsid, consisting of 955 major capsid protein (MCP), 900 small capsid protein (SCP), 640 triplex dimer (Tri2) and 320 triplex monomer (Tri1) subunits. The VZV capsid has high thermal stability, although with relatively fewer intra- and inter-capsid protein interactions and less stably associated tegument proteins compared with other human herpesviruses. Analysis with antibodies targeting the N and C termini of the VZV SCP indicates that the hexon-capping SCP—the largest among human herpesviruses—uses its N-terminal half to bridge hexon MCP subunits and possesses a C-terminal flexible half emanating from the inner rim of the upper hexon channel into the tegument layer. Correlation of these structural features and functional observations provide insights into VZV assembly and pathogenesis and should help efforts to engineer gene delivery and anticancer vectors based on the currently available VZV vaccine.This research was supported by grants from the National Science and Technology Major Projects for Major New Drugs Innovation and Development (no. 2018ZX09711003-005-003), the National Science and Technology Major Project of Infectious Diseases (no. 2017ZX10304402), the National Natural Science Foundation of China (no. 81871648, 81601762), the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences (no. 2019RU022) and the US National Institutes of Health (DE025567/028583). 该研究获得了国家自然科学基金、新药创制国家科技重大专项和传染病防治国家科技重大专项等资助

Virus-Free and Live-Cell Visualizing SARS-CoV-2 Cell Entry for Studies of Neutralizing Antibodies and Compound Inhibitors

新型冠状病毒SARS-CoV-2在全球蔓延，给全球公共卫生带来严重威胁。快速研制疫苗、抗体和治疗药物成为科学界面临的重大挑战。由于SARS-CoV-2的高度传染性，采用病毒感染模型进行中和抗体及小分子抑制剂的药效评估需要在高等级生物安全实验室中进行，且常需要数天时间才能完成检测，限制了抗体和药物筛选的效率。发展快速、可视、不依赖于活病毒的新冠病毒入胞检测探针和细胞模型，对于加速新冠病毒抗体和药物的研究有重要意义。夏宁邵教授团队通过CHO真核表达系统高效表达制备出C端融合抗酸荧光蛋白Gamillus的重组新冠病毒spike蛋白STG。STG经SEC分子筛和冷冻电镜确认呈现与天然病毒刺突高度相似的三聚体结构，且与ACE2有很高的亲和力（18.2nM）。STG具备良好的细胞相容性和荧光性质，研究者进一步开发了可定量测定感染恢复期血清、疫苗免疫血清中和抗体（入胞阻断抗体）水平的CSBT检测方法。除了抗体检测评估方面的应用外，该研究发展的探针和模型还可用于筛选分析抑制新冠病毒入胞及胞内转运的小分子化合物。 我校博士后张雅丽，博士生王邵娟、巫洋涛，博士后侯汪衡、袁伦志和深圳市第三人民医院沈晨光博士为共同第一作者。厦门大学夏宁邵教授、袁权教授、程通教授为该论文共同通讯作者。The ongoing corona virus disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2 infection, has resulted in hundreds of thousands of deaths. Cellular entry of SARS-CoV-2, which is mediated by the viral spike protein and ACE2 receptor, is an essential target for the development of vaccines, therapeutic antibodies, and drugs. Using a mammalian cell expression system,a genetically engineered sensor of fluorescent protein (Gamillus)-fused SARS-CoV-2 spike trimer (STG) to probe the viral entry process is developed.In ACE2-expressing cells, it is found that the STG probe has excellent performance in the live-cell visualization of receptor binding, cellular uptake, and intracellular trafficking of SARS-CoV-2 under virus-free conditions. The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. This approach may also be adapted to develop a viral entry visualization system for other viruses.This study was supported by National Natural Science Foundation of China (81993149041 for N.X.; 81902057 for Y.Z.; 81871316 and U1905205 for Q.Y.), the National Science and Technology Major Project of Infectious Diseases (No. 2017ZX10304402‐002‐003 for T.C. and No. 2017ZX10202203‐009 for Q.Y.), the National Science and Technology Major Projects for Major New Drugs Innovation and Development (No. 2018ZX09711003‐005‐003 for T.C.), the Science and Technology Major Project of Fujian (2020YZ014001), the Science and Technology Major Project of Xiamen (3502Z2020YJ01), and the Guangdong Basic and Applied Basic Research Foundation (2020A1515010368 for C.S.). 该研究得到了国家自然科学基金、传染病防治国家科技重大专项、福建省应急科技攻关项目和厦门应急科技攻关项目的支持

Temporal Variations of Spring Water in Karst Areas: A Case Study of Jinan Spring Area, Northern China

Jinan is known as “Spring City,” because of its famous 72 artesian springs. Spring water plays an important role in the social and economic development of Jinan. However, the accelerating process of urbanization and more intensive human activities have significantly affected the Jinan springs. Based on the data from four spring groups (2015–2018), the hydrochemical characteristics of spring water were analyzed and 14 parameters were selected to evaluate the quality of spring water. In addition, the main ions variation characteristics of spring water in Jinan from 1958 to 2018 were analyzed, based on the previous studies. Subsequently, the spring flow dynamics of the Jinan spring area from 1958 to 2012 were also discussed. Overall, the water quality of the four spring groups is good. The chemical composition of the spring water is mainly controlled by the dissolution of calcite, followed by dolomite, and de-dolomitization. However, spring water is affected by human activities, and the hydrochemical type tends to evolve from HCO3-Ca to HCO3·SO4-Ca or HCO3-Ca·Mg. From 1958 to 2013, the main ions in spring water increased, while a relatively steady and certain fluctuation trend was observed from 2015 to 2018. Since 1958, the spring water flow in Jinan has experienced four stages, from decline to recovery. The exploitation of karst groundwater, change of land use type, and decrease of atmospheric precipitation are the three most important factors, affecting spring discharge dynamics. The slowdown of the increase of the main ion concentration in Jinan spring water and the resumption of spring water flowing indicate that remarkable achievements have been made to protect spring water, but there is still a long way to go to fully protect Jinan spring water

三峽庫區黃土坡非飽和滑帶土之水-力相互作用之研究

The Huangtupo landslide was one of the largest and most harmful geo-hazards in the Three Gorges Area, China. With the periodical water level fluctuation of the Three Gorges Reservoir, partial regions,especially the sliding zones that are the weakest parts in sliding mass, are under circulating drying and wetting conditions. This study employs the transient water release and imbibition method (TRIM) to test the soil water characteristic curve (SWCC) and hydraulic conductivity function (HFC) of sliding zone soils during drying and wetting paths. Combining suction stress theory and saturated-unsaturated direct shear tests, the soil-water interaction and strength variation properties of sliding zone soils with variable saturation are studied quantitatively. The tests and analysis results indicate that the suction, permeability and suction stress of sliding zone soils are related closely to the water content. The soil water characteristic curve, hydraulic conductivity function and suction stress characteristic curve (SSCC) exhibit significant hysteresis. By calculating the strength of unsaturated sliding zone soils by generalized the Mohr-Coulomb failure criterion based on suction stress theory, researchers can conveniently and accurately assess the unsaturated strength properties of sliding soils in slope stability analysis.黃土坡滑坡是中國三峽庫區範圍最大且社會危害性最嚴重的地質災害之一。隨著三峽水庫水位週期性漲落，黃土坡滑坡部分區域，特別是滑坡體內最軟弱的滑帶區域，將長期處於乾濕迴圈狀態。本研究採用暫態排水和吸水試驗方法 (TWRI) 測試滑帶土乾濕路徑的土壤水分特徵曲線 (SWCC) 和水力傳導函數(HCF)，並結合吸應力理論和飽和-非飽和剪切試驗定量化研究滑帶土不同含水狀態下的土-水相互作用性質與強度變化規律。試驗和分析結果顯示，滑帶土的基質吸力、滲透係數以及吸應力與含水量變化有緊密之關係。土壤水分特徵曲線、水力傳導函數和吸應力特徵曲線 (SSCC) 均存在明顯的遲滯效應。利用基於吸應力理論的擴展莫爾-庫倫破壞準則評估滑帶土非飽和狀態抗剪強度，可以較方便且準確地在滑坡穩定性分析中充分考慮滑動土體非飽和狀態時的強度性質

Near-atomic cryo-electron microscopy structures of varicella-zoster virus capsids

Varicella-zoster virus (VZV) is a medically important human herpesvirus that causes chickenpox and shingles, but its cell-associated nature has hindered structure studies. Here we report the cryo-electron microscopy structures of purified VZV A-capsid and C-capsid, as well as of the DNA-containing capsid inside the virion. Atomic models derived from these structures show that, despite enclosing a genome that is substantially smaller than those of other human herpesviruses, VZV has a similarly sized capsid, consisting of 955 major capsid protein (MCP), 900 small capsid protein (SCP), 640 triplex dimer (Tri2) and 320 triplex monomer (Tri1) subunits. The VZV capsid has high thermal stability, although with relatively fewer intra- and inter-capsid protein interactions and less stably associated tegument proteins compared with other human herpesviruses. Analysis with antibodies targeting the N and C termini of the VZV SCP indicates that the hexon-capping SCP-the largest among human herpesviruses-uses its N-terminal half to bridge hexon MCP subunits and possesses a C-terminal flexible half emanating from the inner rim of the upper hexon channel into the tegument layer. Correlation of these structural features and functional observations provide insights into VZV assembly and pathogenesis and should help efforts to engineer gene delivery and anticancer vectors based on the currently available VZV vaccine