Li Yuping,1,7,* Linlin Guan,2 Isabelle Becher,3 Kira S. Makarova,4 Xueli Cao,2 Surabhi Hareendranath,1 Jingwen Guan,1 Frank Stein,3 Siqi Yang,2 Arne Boergel,3 Karine Lapouge,3 Kim Remans,3 David Agard,5 Mikhail Savitski,3 Athanasios Typas,3 Eugene V. Koonin,4 Yue Feng,2,* and Joseph Bondy-Denomy1,6,8,*
1 Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94403, USA
2 State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
3 European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany
4 Computational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
5 The Chan-Zuckerberg Institute for Advanced Biological Imaging and the Department of Biochemistry, University of California, San Francisco, San Francisco, CA 94143, USA
6 Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94403, USA
7 Present address: Biozentrum, University of Basel, Basel 4056, Switzerland
8 Lead contact
*Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (L.Y.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (Y.F.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J.B.-D.)
https://doi.org/10.1016/j.cell.2025.02.016
SUMMARY
Jumbo bacteriophages of the fKZ-like family assemble a lipid-based early phage infection (EPI) vesicle and a proteinaceous nucleus-like structure during infection. These structures protect the phage from nucleases and may create selective pressure for immunity mechanisms targeting this specific phage family. Here, we identify ‘‘jumbo phage killer’’ (Juk), a two-component immune system that terminates infection of fKZ-like phages, suppressing the expression of early phage genes and preventing phage DNA replication and phage nucleus assembly while saving the cell. JukA (formerly YaaW) rapidly senses the EPI vesicle by binding to an early-expressed phage protein, gp241, and then directly recruits JukB. The JukB effector structurally resembles a pore-forming toxin and destabilizes the EPI vesicle. Functional anti-fKZ JukA homologs are found across bacterial phyla, associated with diverse effectors. These findings reveal a widespread defense system that specifically targets early events executed by fKZ-like jumbo phages prior to phage nucleus assembly.
Sven Klumpe,1,9,* Kirsten A. Senti,2 Florian Beck,1 Jenny Sachweh,3 Bernhard Hampoelz,3 Paolo Ronchi,4 Viola Oorschot,4 Marlene Brandstetter,6 Assa Yeroslaviz,5 John A.G. Briggs,7 Julius Brennecke,2,* Martin Beck,3,8,* and Ju¨ rgen M. Plitzko1,*
1 Research Group CryoEM Technology, Max Planck Institute of Biochemistry, Martinsried, Germany
2 Institute of Molecular Biotechnology Austria (IMBA), Vienna, Austria
3 Department Molecular Sociology, Max Planck Institute of Biophysics, Frankfurt, Germany
4 EMBL EM Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
5 Computational Systems Biochemistry, Bioinformatics Core Facility, Max Planck Institute of Biochemistry, Martinsried, Germany
6 Electron Microscopy Facility, Vienna BioCenter Core Facilities, Vienna, Austria
7 Department of Cell and Virus Structure, Max Planck Institute of Biochemistry, Martinsried, Germany
8 Institute of Biochemistry, Goethe University Frankfurt, Frankfurt, Germany
9 Lead contact
*Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (S.K.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J.B.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (M.B.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J.M.P.)
https://doi.org/10.1016/j.cell.2025.02.003
Long terminal repeat (LTR) retrotransposons belong to the transposable elements (TEs), autonomously replicating genetic elements that integrate into the host,s genome. Among animals, Drosophila melanogaster serves as an important model organism for TE research and contains several LTR retrotransposons, including the Ty1-copia family, which is evolutionarily related to retroviruses and forms viruslike particles (VLPs). In this study, we use cryo-focused ion beam (FIB) milling and lift-out approaches to visualize copia VLPs in ovarian cells and intact egg chambers, resolving the in situ copia capsid structure to 7.7 A˚ resolution by cryoelectron tomography (cryo-ET). Although cytoplasmic copia VLPs vary in size, nuclear VLPs are homogeneous and form densely packed clusters, supporting a model in which nuclear import acts as a size selector. Analyzing flies deficient in the TE-suppressing PIWI-interacting RNA (piRNA) pathway, we observe copia,s translocation into the nucleus during spermatogenesis. Our findings provide insights into the replication cycle and cellular structural biology of an active LTR retrotransposon.
原创： 十六点五 中山二院糖尿病足中心
多学科协作诊疗模式（MDT）是21世纪以来国内外新出现的最重要的医学模式之一。目的是使传统的个体式、经验式的医疗模式转变为小组协作共同决策的模式，其可以针对特定疾病，整合医疗资源，依托多学科团队，以求能够为患者制定最佳的诊断和治疗方案，并在深入交流的过程中提高各个专科的水平。
中山二院糖尿病足中心
一位援疆医生讲述了自己的故事：一天夜里，他接诊了一名遭遇车祸的病人，肝脏破裂，生命垂危。虽经全力抢救，病人终因失血过多而死亡。当医生告诉家属这个坏消息后，家属不仅没有责怪医生，反而向医生道谢，然后要求把切下的破碎肝脏带回去，和死者一起埋葬。丧事办完后，家属又来到医院结清所有费用。此举令这位医生十分感动。从此，每当遇到危重患者，他都没有后顾之忧，总是愿意冒险一搏。
如果说大拇指占了人手功能的50%以上的功能，那么足的大趾的功能并没有那么大的作用，实际上，为了追求足底的平面，这三个支撑点的功能都非常重要。
伤口世界平台生态圈，以“关爱人间所有伤口患者”为愿景，连接、整合和拓展线上和线下的管理慢性伤口的资源，倡导远程、就近和居家管理慢性伤口，解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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