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A VLPs based vaccine protects against Zika virus infection and prevents cerebral and testicular damage

NPJ vaccines 2025年第1期10卷 107页

作者： Nelson Côrtes Aline Lira Jaqueline D Q Silva Evelyn Carvalho Wasim A Prates-Syed Barbara Hamaguchi Ricardo Durães-Carvalho Andrea Balan Niels O S Câmara Otavio Cabral-Marques Norbert Pardi Ester C Sabino José E Krieger Gustavo Cabral-Miranda Department of Infectious Diseases and Tropical Medicine Laboratory of Medical Investigation 46 Faculty of Medicine University of São Paulo São Paulo Brazil. Department of Immunology Institute of Biomedical Sciences University of São Paulo São Paulo Brazil. Department of Clinical and Toxicological Analyses School of Pharmaceutical Sciences University of Sao Paulo São Paulo Brazil. Department of Biophysics São Paulo School of Medicine Federal University of São Paulo São Paulo SP Brazil. Department of Microbiology Immunology and Parasitology São Paulo School of Medicine Federal University of São Paulo (UNIFESP) São Paulo SP Brazil. Department of Morphology and Genetics Federal University of São Paulo São Paulo Brazil. Interunit Bioinformatics Graduate Program Institute of Chemistry University of Sao Paulo Sao Paulo Brazil. Applied Structural Biology Laboratory Institute of Biomedical Sciences University of São Paulo São Paulo Brazil. Department of Medicine Division of Molecular Medicine Laboratory of Medical Investigation 29 Faculty of Medicine University of São Paulo São Paulo Brazil. DO'R Institute for Research São Paulo Brazil. Department of Microbiology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA. Department of Pathology Laboratory of Medical Investigation 46 Faculty of Medicine University of São Paulo São Paulo Brazil. Laboratory of Genetics and Molecular Cardiology Clinical Hospital Faculty of Medicine University of São Paulo Heart Institute São Paulo Brazil. Department of Infectious Diseases and Tropical Medicine Laboratory of Medical Investigation 46 Faculty of Medicine University of São Paulo São Paulo Brazil. gcabral.miranda@usp.br. Department of Immunology Institute of Biomedical Sciences University of São Paulo São Paulo Brazil. gcabral.miranda@usp.br.

Still, Zika virus (ZIKV) infection poses a substantial public health risk, especially for pregnant women and their fetuses, as it can result in congenital abnormalities and fetal mortality during pregnancy. Despite significant advances in understanding and combating ZIKV, considerable challenges remain in the fight against this flavivirus. A crucial component of this effort is the development of vaccines, none of which have yet been licensed for human use. Here, we present a comprehensive study of a novel ZIKV vaccine candidate based on virus-like particles (VLPs), designed to provide broad immunological protection against viral infection combined with safety, without the need for additional adjuvants. A self-adjuvanted VLPs-based vaccine displaying the envelope protein domain III (EDIII) of ZIKV was built. The EDIII protein was expressed in E. coli and chemically conjugated to QβVLPs. Immunization of C57BL/6 mice with two doses of the EDIII-QβVLPs vaccine elicited strong EDIII-specific Th1-based immune response. Notably, the vaccine induced neutralizing antibodies and conferred protection in type I IFN receptor-deficient (G129) mice against ZIKV challenge. Furthermore, vaccinated male mice were protected from ZIKV-induced cerebral and testicular damage, critical concerns for ZIKV pathogenesis. These findings suggest that the EDIII-QβVLP vaccine is a promising candidate for preventing ZIKV infection, with potential applications in combatting this and other emerging flaviviruses.

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Author Correction: Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

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Nature genetics 2023年第6期55卷 1080页

作者： Bernardo Rodriguez-Martin Eva G Alvarez Adrian Baez-Ortega Jorge Zamora Fran Supek Jonas Demeulemeester Martin Santamarina Young Seok Ju Javier Temes Daniel Garcia-Souto Harald Detering Yilong Li Jorge Rodriguez-Castro Ana Dueso-Barroso Alicia L Bruzos Stefan C Dentro Miguel G Blanco Gianmarco Contino Daniel Ardeljan Marta Tojo Nicola D Roberts Sonia Zumalave Paul A Edwards Joachim Weischenfeldt Montserrat Puiggròs Zechen Chong Ken Chen Eunjung Alice Lee Jeremiah A Wala Keiran M Raine Adam Butler Sebastian M Waszak Fabio C P Navarro Steven E Schumacher Jean Monlong Francesco Maura Niccolo Bolli Guillaume Bourque Mark Gerstein Peter J Park David C Wedge Rameen Beroukhim David Torrents Jan O Korbel Iñigo Martincorena Rebecca C Fitzgerald Peter Van Loo Haig H Kazazian Kathleen H Burns Peter J Campbell Jose M C Tubio Department of Zoology Genetics and Physical Anthropology Universidade de Santiago de Compostela Santiago de Compostela Spain. Biomedical Research Centre (CINBIO) University of Vigo Vigo Spain. Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain. Transmissible Cancer Group Department of Veterinary Medicine University of Cambridge Cambridge UK. The Biomedical Research Centre (CINBIO) Universidade de Vigo Vigo Spain. Wellcome Sanger Institute Wellcome Genome Campus Cambridge UK. Genome Data Science Institute for Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology (BIST) Barcelona Spain. Institucio Catalana de Recerca i Estudis Avançats (ICREA) Barcelona Spain. The Francis Crick Institute London UK. Department of Human Genetics University of Leuven Leuven Belgium. Genomes and Disease Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain. Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology Daejeon South Korea. Cancer Ageing and Somatic Mutation Programme Wellcome Sanger Institute Cambridge UK. Department of Biochemistry Genetics and Immunology University of Vigo Vigo Spain. Galicia Sur Health Research Institute Vigo Spain. Faculty of Science and Technology University of Vic-Central University of Catalonia (UVic-UCC) Vic Spain. Barcelona Supercomputing Center (BSC) Barcelona Spain. Experimental Cancer Genetics Wellcome Sanger Institute Cambridge UK. Oxford Big Data Institute University of Oxford Oxford UK. DNA Repair and Genome Integrity Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain. Department of Biochemistry and Molecular Biology Universidade de Santiago de Compostela Santiago de Compostela Spain. Medical R

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LifeTime and improving European healthcare through cell-based interceptive medicine (vol 587, pg 377, 2020)

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NATURE 2021年第7852期592卷 E8-E8页

作者： Rajewsky, Nikolaus Almouzni, Genevieve Gorski, Stanislaw A. Aerts, Stein Amit, Ido Bertero, Michela G. Bock, Christoph Bredenoord, Annelien L. Cavalli, Giacomo Chiocca, Susanna Clevers, Hans De Strooper, Bart Eggert, Angelika Ellenberg, Jan Fernandez, Xose M. Figlerowicz, Marek Gasser, Susan M. Hubner, Norbert Kjems, Jorgen Knoblich, Jurgen A. Krabbe, Grietje Lichter, Peter Linnarsson, Sten Marine, Jean-Christophe Marioni, John C. Marti-Renom, Marc A. Netea, Mihai G. Nickel, Dorthe Nollmann, Marcelo Novak, Halina R. Parkinson, Helen Piccolo, Stefano Pinheiro, Ines Pombo, Ana Popp, Christian Reik, Wolf Roman-Roman, Sergio Rosenstiel, Philip Schultze, Joachim L. Stegle, Oliver Tanay, Amos Testa, Giuseppe Thanos, Dimitris Theis, Fabian J. Torres-Padilla, Maria-Elena Valencia, Alfonso Vallot, Celine van Oudenaarden, Alexander Vidal, Marie Voet, Thierry Berlin Institute for Medical Systems Biology Max Delbrück Center for Molecular Medicine in the Helmholtz Association Berlin Germany Charité-Universitätsmedizin Berlin Germany Berlin Institute of Health (BIH) Berlin Germany German Center for Cardiovascular Research (DZHK) Partner Site Berlin Berlin Germany Institute for Biology Humboldt University of Berlin Berlin Germany Cardiovascular and Metabolic Sciences Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) Berlin Germany Department of Pediatric Oncology/Hematology Charité-Universitätsmedizin Berlin Berlin Germany Institut Curie CNRS PSL Research University Sorbonne Université Nuclear Dynamics Unit Equipe Labellisée Ligue contre le cancer Paris France VIB Center for Brain and Disease Research Leuven Belgium Department of Human Genetics KU Leuven Leuven Belgium Department of Neurosciences KU Leuven Leuven Belgium UK Dementia Research Institute at UCL University College London London UK Wellcome Sanger Institute Wellcome Genome Campus Cambridge UK Department of Immunology Weizmann Institute of Science Rehovot Israel Centre for Genomic Regulation (CRG) Barcelona Institute of Science and Technology Barcelona Spain CNAG-CRG Centre for Genomic Regulation Barcelona Institute of Science and Technology Barcelona Spain Universitat Pompeu Fabra Barcelona Spain ICREA Barcelona Spain CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences Vienna Austria Department of Laboratory Medicine Medical University of Vienna Vienna Austria Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases Vienna Austria Department of Medical Humanities Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht The Netherlands Institute of Human Genetics UMR 9002 CNRS and University of Montpellier Montpellier France Department of Experimental Oncology IEO European Institute of Oncology IRCCS Milan Italy Department of Oncology and Hemato

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Convolutional neural networks for automated annotation of cellular cryo-electron tomograms

arXiv

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arXiv 2017年

作者： Chen, Muyuan Dai, Wei Sun, Stella Y. Jonasch, Darius He, Cynthia Y. Schmid, Michael F. Chiu, Wah Ludtke, Steven J. Graduate Program in Structural and Computational Biology and Molecular Biophysics Baylor College of Medicine HoustonTX77030 United States Verna Marrs and McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine HoustonTX77030 United States Department of Biological Science Centre for BioImaging Sciences National University of Singapore 14 Science Drive 4 Singapore117543 Singapore

Cellular Electron Cryotomography (CryoET) offers the ability to look inside cells and observe macromolecules frozen in action. A primary challenge for this technique is identifying and extracting the molecular components within the crowded cellular environment. We introduce a method using neural networks to dramatically reduce the time and human effort required for subcellular annotation and feature extraction. Subsequent subtomogram classification and averaging yields in-situ structures of molecular components of interest. © 2017, CC BY.

关键词： Cellular neural networks

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Void distributions reveal structural link between jammed packings and protein cores

arXiv

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arXiv 2018年

作者： Treado, John D. Mei, Zhe Regan, Lynne O'Hern, Corey S. Department of Mechanical Engineering & Materials Science Yale University New HavenCT06520 United States Integrated Graduate Program in Physical & Engineering Biology Yale University New HavenCT06520 United States Department of Chemistry Yale University New HavenCT06520 United States Department of Molecular Biophysics & Biochemistry Yale University New HavenCT06520 United States Department of Physics Yale University New HavenCT06520 United States Department of Applied Physics Yale University New HavenCT06520 United States Program in Computational Biology and Bioinformatics Yale University New HavenCT06520 United States

Dense packing of hydrophobic residues in the cores of globular proteins determines their stability. Recently, we have shown that protein cores possess packing fraction φ ≈ 0.56, which is the same as dense, random packing of amino acid-shaped particles. In this article, we compare the structural properties of protein cores and jammed packings of amino acid-shaped particles in much greater depth by measuring their local and connected void regions. We find that the distributions of surface Voronoi cell volumes and local porosities obey similar statistics in both systems. We also measure the probability that accessible, connected void regions percolate as a function of the size of a spherical probe particle and show that both systems possess the same critical probe size. By measuring the critical exponent τ that characterizes the size distribution of connected void clusters at the onset of percolation, we show that void percolation in packings of amino acid-shaped particles and protein cores belong to the same universality class, which is different from that for void percolation in jammed sphere packings. We propose that the connected void regions of proteins are a defining feature of proteins and can be used to differentiate experimentally observed proteins from decoy structures that are generated using computational protein design software. This work emphasizes that jammed packings of amino acid-shaped particles can serve as structural and mechanical analogs of protein cores, and could therefore be useful in modeling the response of protein cores to cavity-expanding and -reducing mutations. Copyright © 2018, The Authors. All rights reserved.

关键词： Amino acids

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Cryo-EM structure and biochemical analysis reveal the basis of the functional difference between human PI3KC3-C1 and-C2

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细胞研究（英文版） 2017年第8期27卷 989-1001页

作者： Meisheng Ma Jun-Jie Liu Yan Li Yuwei Huang Na Ta Yang Chen Hua Fu Ming-Da Ye Yuehe Ding Weijiao Huang Jia Wang Meng-Qiu Dong Li Yu Hong-Wei Wang The State Key Laboratory of Membrane Biology Tsinghua University-Peking University Joint Center for Life Sciences School of Life Sciences Tsinghua University Beijing 100084 China Molecular Biophysics and Integrated Bioimaging Division Lawrence Berkeley National Laboratory Berkeley CA 94720 USA Ministry of Education Key Laboratory of Protein Sciences Tsinghua-Peking Joint Center for Life Sciences Beijing Advanced Innovation Center for Structural Biology School of Life SciencesTsinghua University Beijing 100084 China The State Key Laboratory of Membrane Biology Tsinghua University-Peking University Joint Center for Life Sciences School of Life Sciences Tsinghua University Beijing 100084 China Joint Graduate Program of Peking-Tsinghua-National Institute of Biological Science Tsinghua University Beijing 100084 China MOH Key Laboratory of Systems Biology of Pathogens Institute of Pathogen Biology Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100730 China National Institute of Biological Sciences Beijing 102206 China

Phosphatidylinositol 3-phosphate (PI3P) plays essential roles in vesicular trafficking,organelle biogenesis and *** class Ⅲ phosphatidylinositol 3-kinase (PI3KC3) complexes have been identified in mammals,the ATG14L complex (PI3KC3-C1) and the UVRAG complex (PI3KC3-C2).PI3KC3-C1 is crucial for autophagosome biogenesis,and PI3KC3-C2 is involved in various membrane trafficking *** we report the cryo-EM structures of human PI3KC3-C1 and PI3KC3-C2 at sub-nanometer *** two structures share a common L-shaped overall architecture with distinct *** examination revealed that PI3KC3-C1 "stands up" on lipid monolayers,with the ATG14L BATs domain and the VPS34 C-terminal domain (CTD) directly contacting the *** dissection indicated that the ATG14L BATs domain is responsible for membrane anchoring,whereas the CTD of VPS34 determines the ***,PI3KC3-C2 binds much more weakly than PI3KC3-C1 to both PI-containing liposomes and purified endoplasmic reticulum (ER) vesicles,a property that is specifically determined by the ATG14L BATs *** in vivo ER localization analysis indicated that the BATs domain was required for ER localization of *** propose that the different lipid binding capacity is the key factor that differentiates the functions of PI3KC3-C1 and PI3KC3-C2 in autophagy.

关键词： PI3KC3 ATG14L UVRAG autophagy PI cryo-EM

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Transgenic mouse models for studying adult neurogenesis

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Frontiers in biology 2016年第3期11卷 151-167页

作者： Fatih Semerci Mirjana Maletic-Savatic Program in Developmental Biology Baylor College of Medicine Houston TX 77030 USA Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital Houston TX 77030 USA Department of Pediatrics-Neurology Department of Neuroscience and Structural and Computational Biology and Molecular Biophysics Baylor College of Medicine Houston TX 77030 USA

The mammalian hippocampus shows a remarkable capacity for continued neurogenesis throughout life. Newborn neurons, generated by the radial neural stem cells （NSCs）, are important for learning and memory as well as mood control. During aging, the number and responses of NSCs to neurogenic stimuli diminish, leading to decreased neurogenesis and age-associatedcognitive decline and psychiatric disorders. Thus, adult hippocampal neurogenesis has garnered significant interest because targeting it could be a novel potential therapeutic strategy for these disorders. However, if we are to use nenrogenesis to halt or reverse hippocampal-related pathology, we need to understand better the core molecular machinery that governs NSC and their progeny. In this review, we summarize a wide variety of mouse models used in adult neurogenesis field, present their advantages and disadvantages based on specificity and efficiency of labeling of different cell types, and review their contribution to our understanding of the biology and the heterogeneity of different cell types found in adult neurogenic niches.

关键词： adult neurogenesis mouse models neural stem cells neuroprogenitors lineage tracing

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Author Correction: RADICL-seq identifies general and cell type-specific principles of genome-wide RNA-chromatin interactions

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Nature communications 2021年第1期12卷 3128页

作者： Alessandro Bonetti Federico Agostini Ana Maria Suzuki Kosuke Hashimoto Giovanni Pascarella Juliette Gimenez Leonie Roos Alex J Nash Marco Ghilotti Christopher J F Cameron Matthew Valentine Yulia A Medvedeva Shuhei Noguchi Eneritz Agirre Kaori Kashi Joachim Luginbühl Riccardo Cazzoli Saumya Agrawal Nicholas M Luscombe Mathieu Blanchette Takeya Kasukawa Michiel de Hoon Erik Arner Boris Lenhard Charles Plessy Gonçalo Castelo-Branco Valerio Orlando Piero Carninci RIKEN Center for Integrative Medical Sciences Yokohama Kanagawa 230-0045 Japan. alessandro.bonetti@riken.jp. Laboratory of Molecular Neurobiology Department Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden. alessandro.bonetti@riken.jp. The Francis Crick Institute 1 Midland Road London NW1 1AT UK. RIKEN Center for Integrative Medical Sciences Yokohama Kanagawa 230-0045 Japan. Department of Medicine (H7) Karolinska Institutet Stockholm 141 86 Sweden. Epigenetics and Genome Reprogramming Laboratory IRCCS Fondazione Santa Lucia Rome Italy. Faculty of Medicine Imperial College London Institute of Clinical Sciences London W12 0NN UK. MRC London Institute of Medical Sciences London W12 0NN UK. School of Computer Science McGill University Montréal QC Canada. Department of Biochemistry and Goodman Cancer Research Centre McGill University Montréal QC Canada. Institute of Bioengineering Research Centre of Biotechnology Russian Academy of Science 117312 Moscow Russia. Department of Computational Biology Vavilov Institute of General Genetics Russian Academy of Science 119991 Moscow Russia. Department of Biological and Medical Physics Moscow Institute of Physics and Technology 141701 Dolgoprudny Moscow Region Russia. Laboratory of Molecular Neurobiology Department Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden. Department of Experimental Oncology IEO European Institute of Oncology IRCCS Milan Italy. UCL Genetics Institute University College London London WC1E 6BT UK. Okinawa Institute of Science and Technology Graduate University 1919-1 Tancha Onna-son Kunigami-gun Okinawa 904-0495 Japan. Sars International Centre for Marine Molecular Biology University of Bergen 5008 Bergen Norway. Epigenetics and Genome Reprogramming Laboratory IRCCS Fondazione Santa Lucia Rome Italy. valerio.orlando@kaust.edu.sa. KAUST Environmental Epigenetics Program King Abdullah University of Science and Technology (KAUS

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Building and Validating Atomic Models for Cryo-EM Density Maps

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Microscopy and Microanalysis 2016年第S3期22卷 2080-2081页

作者： Matthew L. Baker Muyuan Chen Tunay Durmaz Phil Baldwin Tao Ju Steven J. Ludtke Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine HoustonTXUSA Program in Structural and Computational Biology and Molecular Biophysics Baylor College of Medicine HoustonTXUSA Department of Computer Science and Engineering Washington University in St. Louis St. LouisMOUSA

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Education for the future

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Science 2018年第6396期360卷 1409-1412页

作者： Cheung, Man Kit Schwendimann, Beat A. Ward, Adrian Pietrzak, Barbara Mollaoglu, Gurkan Duong, Michael Tran Allareddy, Veerasathpurush Ulltveit-Moe, Nils Dutton-Regester, Ken Zhang, Jian Scult, Matthew A. Singh, Poonam C. Yan, Hong Young Naz, Saima Isaacson, Kyle Dennis, Allison F. Beardsley, Felicia Rounds Al-Humaidan, Eyad Ibrahim Lo, Cody Jones, Tyler Sood, Prashant Nieuwenhuis, Rense Ali, Basant A. Yu, Kun-Hsing Arthur, Patrick Kobina Kumar, Brijesh Buschke, Falko Chen, Alexander Cingl, Lubomír O’Mullane, Anthony Peter Coetzee, Vinet Zaidi, Syed Shan-e-Ali Konstantinides, Nikos School of Life Sciences Chinese University of Hong Kong Shatin New Territories Hong Kong Graduate School of Education University of California Berkeley Berkeley 94720 CA United States University of Queensland St. Lucia 4072 QLD Australia Department of Hydrobiology Faculty of Biology Biological and Chemical Research Centre University of Warsaw Warsaw 02-089 Poland Department of Oncological Sciences University of Utah School of Medicine Salt Lake City 84112 UT United States Perelman School of Medicine University of Pennsylvania Philadelphia 19104 PA United States University of Illinois College of Dentistry Chicago 60612 IL United States Department of Information and Communication Technology University of Agder 4879 Grimstad Norway Department of Genetics and Computational Biology QIMR Berghofer Medical Research Institute Brisbane 4006 QLD Australia School of Safety and Environmental Engineering Hunan Institute of Technology Hengyang Hunan 421002 China Lahore 54000 Punjab Pakistan Department of Psychology and Neuroscience Duke University Durham 27708 NC United States National Museum of Marine Biology and Aquarium Chercheng Pingtung County 94450 Taiwan Division of Plant Microbe Interactions CSIR–National Botanical Research Institute Lucknow 226001 Uttar Pradesh India Program in Cell Molecular Developmental Biology and Biophysics (CMDB) Johns Hopkins University Baltimore 21218 MD United States Stem Cell and Tissue Re-Engineering Program King Faisal Specialist Hospital and Research Centre Riyadh Saudi Arabia Department of Sociology and Anthropology University of La Verne La Verne 91750 CA United States Department of Bioengineering University of Utah Salt Lake City 84112 UT United States MRC Centre for Medical Mycology University of Aberdeen Aberdeen AB25 2ZD United Kingdom Faculty of Medicine University of British Columbia Vancouver V6T 1Z2 BC Canada School of Engineering Brown University Providence 02912 RI United States

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