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

Generation of integration-free neural progenitor cells from cells in human urine

Human neural stem cells hold great promise for research and therapy in neural disease. We describe the generation of integration-free and expandable human neural progenitor cells (NPCs). We combined an episomal system to deliver reprogramming factors with a chemically defined culture medium to reprogram epithelial-like cells from human urine into NPCs (hUiNPCs). These transgene-free hUiNPCs can self-renew and can differentiate into multiple functional neuronal subtypes and glial cells in vitro. Although functional in vivo analysis is still needed, we report that the cells survive and differentiate upon transplant into newborn rat brain.postprin

A novel library catalogue system

It has become an increasing challenge to apply knowledge management tools in modern library information systems that deliver the most up-to-date and relevant information to end users in a quick, efficient and user-friendly manner. According to a survey on city council libraries in the Sydney area, there is a proliferation of common problems associated with searching speed and accuracy, scalability and the user-friendly interface, all of which are closely related to the performance of the catalogue search scheme. The library information systems currently used in local public council libraries are usually decades old, and therefore cannot meet requirements due to the rapid increase in the amount and categories of library collections. The current marketing price for a library catalogue system (including the maintenance expenses) can be prohibitively high. While a large size organization such as a university can afford to install and maintain such a modern system for superior performance, it could be infeasible for some of the public council libraries and/or primary/high schools to purchase and maintain an existing market product to meet their ever-increasing needs. For those libraries, updating and improving the current information systems using open source software, through collaboration with universities, could provide a better solution. This Master Degree project is proposed to address such a challenge. Apart from such practical motivations, this project also possesses theoretic significance. The algorithms to be developed provide not only a practical solution for library catalogue systems but also a novel methodology applicable to database management system designing with respect to speedy and user-friendly information retrieval. The proposed web-based library system involves client/server architecture with multiple tiers. For performance enhancement in terms of searching speed and error tolerance, two key techniques have been employed: soundexing and adaptive caching. As soundexing is a hashing system with one soundex corresponding many words, a soundex search may bring about irrelevant results and thus reduce the precision of the search. It is just this limitation that has restricted the application of soundexing techniques in general information systems. Some measures have been investigated in our project to ameliorate this limitation, such as to increase the length of the soundex codes, or to use the Metaphone, a phonetic algorithm to produce variable length keys. For database cache, query normalization is adopted to reduce the redundancies existing in the cache and to increase the hitting rate. While there is still room for further improvement of the developed library catalogue system, the testing results are encouraging and meet the expectations of the project

Applications of soundexing retrieval and query caching in an open-source-software based library catalogue system

In some small organizations with limited resources, based on authors’ survey, the library facilities could be decade old. Current marketing prices of library software, including upkeep costs, are prohibitively high. Improving and updating these library information systems by employing open-source-software might provide a better solution. In this paper, the authors present the design of an open source software based library catalogue system that takes multi-tier client/server architecture. Furthermore, techniques of soundexing retrieval and query caching are applied to enhance the system performance with respect to error tolerance, searching speed and scalability. With the support of an appropriately designed soundex algorithm, the catalogue system can largely increase its recall while not compromise the searching precision. The introduced query cache, on the other hand, can increase significantly the system response speed and thus the scalability. The performance of the developed prototype system is verified by simulations using real library data

An open source software based library catalogue system using soundexing retrieval and query caching

It has been a challenge to apply effective knowledge management tools in information systems for modern libraries that deliver the most up-to-date, relevant information to end users in a quick, efficient, and user-friendly manner. In this paper, the authors present the design of a library catalogue system using principally open source software. The integrated web-based library system takes client/server architecture with multiple tiers. For performance enhancement with respect to error tolerance, searching speed and scalability, techniques of soundexing retrieval and query caching were applied. With the support of an appropriately designed soundex algorithm, the catalogue system can largely increase its recall while not compromising the search precision. On the other side, the introduced query cache speeds up the system response significantly