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| Open AccessProtruding knob-like proteins violate local symmetries in an icosahedral marine virus
Some viruses are spherical particles in which protein components are organized with well-defined icosahedral and local symmetries. Here, Gipson et al. describe a unique arrangement of proteins, breaking all expected local symmetries, in particles of a marine bacterial virus.
- Preeti Gipson
- , Matthew L. Baker
- & Wah Chiu
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Article
| Open AccessPlant genomes enclose footprints of past infections by giant virus relatives
Nucleocytoplasmic large DNA viruses, NCLDVs, are eukaryotic viruses with large genomes, known to infect animals and diverse unicellular eukaryotes. Here, Maumus et al. find NCLDV-like sequences in two land plants and show that they are transcriptionally inactive and highly methylated.
- Florian Maumus
- , Aline Epert
- & Guillaume Blanc
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Glycosphingolipid-functionalized nanoparticles recapitulate CD169-dependent HIV-1 uptake and trafficking in dendritic cells
Ganglioside GM3, a cellular lipid included in the envelope of HIV-1 viral particles, interacts with cellular receptor CD169. Here, the authors develop artificial nanoparticles, consisting of a golden core and a GM3-containing synthetic membrane, that recapitulate the CD169-dependent uptake of viral particles.
- Xinwei Yu
- , Amin Feizpour
- & Björn M. Reinhard
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Article
| Open AccessPredicting the risk of avian influenza A H7N9 infection in live-poultry markets across Asia
An avian influenza virus of the H7N9 type, associated with live-poultry markets, has caused two human epidemics in China. Here, the authors develop a statistical model that predicts the risk of H7N9 infection in live-poultry markets across Asia, as a tool for disease surveillance and control.
- Marius Gilbert
- , Nick Golding
- & Hongjie Yu
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Multi-peaked adaptive landscape for chikungunya virus evolution predicts continued fitness optimization in Aedes albopictus mosquitoes
The ability of a pathogen to adapt to new hosts affects its ability to spread in new environments. Here, Tsetsarkin et al.analysed mutations that enabled the chikungunya virus to adapt to a mosquito vector and predict that specific mutations will result in greater transmission efficiency.
- Konstantin A. Tsetsarkin
- , Rubing Chen
- & Scott C. Weaver
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Stiff filamentous virus translocations through solid-state nanopores
Nanopores are promising tools for the detection and characterization of biomolecules. Here, the authors combine experiments and simulations to study how the passage of rigid viruses through solid-state nanopores differs from more flexible biomolecules.
- Angus McMullen
- , Hendrick W. de Haan
- & Derek Stein
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Membrane deformation and scission by the HSV-1 nuclear egress complex
Two viral proteins form the nuclear egress complex of herpesviruses, which is essential for the exit of nascent viral capsids from the cell nucleus. Here, the authors use synthetic lipid vesicles to show that the complex can mediate membrane budding in the absence of other cellular factors.
- Janna M. Bigalke
- , Thomas Heuser
- & Ekaterina E. Heldwein
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A toggle switch controls the low pH-triggered rearrangement and maturation of the dengue virus envelope proteins
Formation of infectious dengue virus in host cells requires a rearrangement of viral envelope proteins that is triggered by the acidic environment within secretory vesicles. Here, the authors describe the molecular mechanism underlying such rearrangement.
- Aihua Zheng
- , Fei Yuan
- & Margaret Kielian
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Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections
H5N1 avian influenza viruses can be highly pathogenic. Here, the authors show that H5N1 infection leads to increased serum levels of angiotensin II in patients and mice, and that administration of angiotensin-converting enzyme 2 ameliorates lung injury in infected mice.
- Zhen Zou
- , Yiwu Yan
- & Chengyu Jiang
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Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen
Semen-derived peptides can form amyloid fibrils that boost HIV infection in vitro, but the existence of such fibrils in semen remained to be demonstrated. Here, the authors show that human semen contains amyloid fibrils, which can bind HIV particles and increase their infectiveness.
- Shariq M. Usmani
- , Onofrio Zirafi
- & Jan Münch
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Inhibition of miR-146a prevents enterovirus-induced death by restoring the production of type I interferon
Enterovirus 71 (EV71) is one of the causative agents of hand-food-mouth disease and to date, effective vaccines or antivirals against the disease have not been developed. Here, the authors show that blocking miR-146a upregulation induced upon EV71 infection can have a positive effect on the resolution of infection.
- Bing-Ching Ho
- , I-Shing Yu
- & Sung-Liang Yu
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Article
| Open AccessPopulation genomics supports baculoviruses as vectors of horizontal transfer of insect transposons
Horizontal transfer of DNA is common among eukaryotes but the vectors involved remain elusive. Here, Gilbert et al. show high frequency of in vivotransposition from the cabbage looper moth into genomes of a baculovirus, suggesting that viruses can act as vectors of horizontal transfer between animals.
- Clément Gilbert
- , Aurélien Chateigner
- & Richard Cordaux
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Fragile X mental retardation protein stimulates ribonucleoprotein assembly of influenza A virus
To successfully replicate and propagate, viruses hijack different components of the host cell machinery. Here, Zhou et al.identify the RNA-binding protein Fragile X mental retardation protein as a host factor involved in influenza A virus replication in host cells.
- Zhuo Zhou
- , Mengmeng Cao
- & Tao Deng
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Dynamic reassortments and genetic heterogeneity of the human-infecting influenza A (H7N9) virus
H7N9 influenza A viruses capable of infecting humans have recently emerged in China. Here, the authors show that these viruses remain genetically diverse, suggesting that they are still in the process of adapting to human hosts.
- Lunbiao Cui
- , Di Liu
- & George F. Gao
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Article
| Open AccessDrawing a high-resolution functional map of adeno-associated virus capsid by massively parallel sequencing
Adeno-associated viruses (AAV) are promising gene transfer vectors for human gene therapy. Here, the authors report a high-throughput, sequencing-based method for characterizing amino acid function in AAV capsids and highlight the potential of this method for improving capsid design.
- Kei Adachi
- , Tatsuji Enoki
- & Hiroyuki Nakai
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Continent-wide panmixia of an African fruit bat facilitates transmission of potentially zoonotic viruses
The African straw-coloured fruit bat lives in close proximity to humans and acts as reservoir for Lagos bat virus and henipaviruses. Here, the authors assess viral transmission dynamics in this species and its implications for public health using genetic and serological data.
- Alison J. Peel
- , David R. Sargan
- & Andrew A. Cunningham
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A Ca2+-dependent signalling circuit regulates influenza A virus internalization and infection
Influenza virus can enter host cells through endocytosis, but the molecular pathways involved in this process are not fully understood. Here, the authors dissect these pathways and identify Ca2+as a key regulator of influenza A virus entry via both clathrin-mediated and clathrin-independent endocytosis.
- Yoichiro Fujioka
- , Masumi Tsuda
- & Yusuke Ohba
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Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase
SAMHD1 is a dNTP hydrolase that has been shown to act as a restriction factor against retroviruses such as HIV, and also regulates the retrotransposition of LINE-1 elements. Here the authors reveal the structural basis for dGTP-dependent tetramerization and allosteric activation of the enzyme.
- Chunfeng Zhu
- , Wenying Gao
- & Xiao-Fang Yu
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Chimeric viruses blur the borders between the major groups of eukaryotic single-stranded DNA viruses
Single-stranded DNA viruses are almost ubiquitous and highly diverse. Here, the authors focus on small DNA viruses possessing chimeric genomes with RNA virus-like capsids, disentangling their complex evolutionary history, which challenges the current borders between major groups of eukaryotic ssDNA viruses.
- Simon Roux
- , François Enault
- & Mart Krupovic
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Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides
Cytotoxic CD8+ T cells provide one level of protection against influenza infection. Here, the authors present evidence, in mice and humans, for the emergence and reversion of influenza A virus escape mutants associated with the immune pressure from cytotoxic CD8+ T lymphocytes.
- Sophie A. Valkenburg
- , Sergio Quiñones-Parra
- & Katherine Kedzierska
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Selection on haemagglutinin imposes a bottleneck during mammalian transmission of reassortant H5N1 influenza viruses
Mutations in the haemagglutinin of H5N1 avian influenza viruses confer transmissibility in ferrets. Here, Wilker et al. show that while within host variability is high, transmitted virus diversity is low suggesting a genetic bottleneck acts during transmission, driven by selection on haemagglutinin genes.
- Peter R. Wilker
- , Jorge M. Dinis
- & Thomas C. Friedrich
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Article
| Open AccessThe landscape of viral expression and host gene fusion and adaptation in human cancer
Viruses contribute to the pathogenesis of certain cancers. Using massively parallel sequencing data from The Cancer Genome Atlas to analyse viral expression in 19 tumour types, Tang et al. both confirm and reject previously described viral associations and present new information on viral integration and host interaction.
- Ka-Wei Tang
- , Babak Alaei-Mahabadi
- & Erik Larsson
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Article
| Open AccessGenome signature-based dissection of human gut metagenomes to extract subliminal viral sequences
Bacteriophages have a significant impact on microbial ecosystems, but additional tools are needed to assess viral communities. Ogilvie et al.present a new strategy to extract viral sequences from metagenomic data sets, and present new insights on their function in the gut ecosystem.
- Lesley A. Ogilvie
- , Lucas D. Bowler
- & Brian V. Jones
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Article
| Open AccessVisualizing influenza virus infection in living mice
Mouse models of influenza infection that permit monitoring of infection in living animals are scarce. Here Pan et al. describe an engineered influenza virus expressing luciferase, which enables real-time in vivovisualization of viral infection and assessment of antiviral drugs.
- Weiqi Pan
- , Zhenyuan Dong
- & Ling Chen
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Axonal and subcellular labelling using modified rabies viral vectors
Viral vectors can be used both to map and manipulate neural circuits in vivo; however, their use is limited by weak expression levels, especially when expression of more than one protein is required. Here, the authors overcome this limitation using deletion-mutant rabies viruses.
- Ian R. Wickersham
- , Heather A. Sullivan
- & H. Sebastian Seung
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HSV-1 exploits the innate immune scavenger receptor MARCO to enhance epithelial adsorption and infection
Herpes simplex virus type 1 infects human skin and mucous membranes. MacLeod and colleagues identify MARCO as a novel cell-surface receptor bound by herpes simplex virus type 1, and show that this interaction enhances infection of keratinocytes and promotes the development of skin lesions in mice.
- Daniel T. MacLeod
- , Teruaki Nakatsuji
- & Richard L. Gallo
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Aerosol transmission is an important mode of influenza A virus spread
Influenza A viruses spread through contact, large and small respiratory droplets (aerosols), but the relative importance of these modes of transmission is unclear. Cowling et al. model data from community trials of face masks and hand hygiene and find that aerosol transmission accounts for half of influenza occurrences.
- Benjamin J. Cowling
- , Dennis K. M. Ip
- & James Mark Simmerman
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Toll-like receptor 3 recognizes incomplete stem structures in single-stranded viral RNA
Toll-like receptor 3 is a sensor of viral infection and sterile tissue necrosis, and is known to be activated by double-stranded RNA. Tatematsu et al. demonstrate that TLR3 also recognizes incomplete stem structures that form in single-stranded poliovirus RNA.
- Megumi Tatematsu
- , Fumiko Nishikawa
- & Misako Matsumoto
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The genome of a Mesozoic paleovirus reveals the evolution of hepatitis B viruses
With paleovirology it is possible to identify ancient endogenous viral elements within eukaryotic genomes. Here Suh and colleagues report a genomic record of hepatitis endogenizations through bird’s evolution; they find a complete hepatitis genome sequence, the first discovery of a Mesozoic paleovirus genome.
- Alexander Suh
- , Jürgen Brosius
- & Jan Ole Kriegs
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Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9
Microglia are specialized immune cells in the brain. Here Åkerblom and colleagues use a microRNA-9-regulated lentiviral vector for the targeted genetic modification of microglia in the rodent brain, presenting a tool that may facilitate functional studies of resident microglia.
- Malin Åkerblom
- , Rohit Sachdeva
- & Johan Jakobsson
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Structure of the full-length HCV IRES in solution
The hepatitis C virus RNA genome is translated via an internal ribosome entry site. Pérard et al. present an atomic model of this site, and using molecular dynamics simulations, identify conformational flexibility that may underlie its function during translation initiation.
- Julien Pérard
- , Cédric Leyrat
- & Marc Jamin
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The role and assembly mechanism of nucleoprotein in influenza A virus ribonucleoprotein complexes
The nucleoprotein of negative-strand RNA viruses forms a part of the ribonucleoprotein complex. Here Turrell et al.show that nucleoprotein does not regulate the initiation and termination of transcription and replication by the viral RNA polymerase, suggesting that nucleoprotein instead is an elongation factor.
- Lauren Turrell
- , Jon W. Lyall
- & Frank T. Vreede
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A synthetic nanomaterial for virus recognition produced by surface imprinting
The recognition of viruses by synthetic materials is historically difficult. Here, a templating procedure using silica nanoparticles coated with organosilanes is used to form virus-imprinted particles, possessing both shape and chemical imprints, capable of virus recognition at picomolar concentrations.
- Alessandro Cumbo
- , Bernard Lorber
- & Patrick Shahgaldian
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Influenza neuraminidase operates via a nucleophilic mechanism and can be targeted by covalent inhibitors
New influenza neuramidase inhibitors may increase preparedness against influenza outbreaks. Vavricka et al.confirm the catalytic mechanism of neuramidase and show that it can be inhibited irreversibly with covalent inhibitors.
- Christopher J. Vavricka
- , Yue Liu
- & George F. Gao
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Self-organization of the vesicular stomatitis virus nucleocapsid into a bullet shape
The bullet shape of Rhabdoviruses is thought to depend on their matrix protein, which stabilizes the nucleocapsid coil. Desfosses and colleagues show that the nucleoprotein of the vesicular stomatitis virus can fold the genome into a bullet-shaped skeleton in the absence of other viral components.
- Ambroise Desfosses
- , Euripedes A. Ribeiro Jr
- & Irina Gutsche
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Strong bias in the bacterial CRISPR elements that confer immunity to phage
Bacterial CRISPR–Cas systems provide adaptive immunity against phage by transcribing interfering RNA from phage DNA inserted into the bacterial genome. Using deep-sequencing, the authors detect a bias in the phage genome locations sampled, suggestive of selection.
- David Paez-Espino
- , Wesley Morovic
- & Jillian F. Banfield
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Article
| Open AccessInterferon-induced transmembrane protein-3 genetic variant rs12252-C is associated with severe influenza in Chinese individuals
A variant in the IFITM3gene increases the risk of severe influenza, but homozygosity is rare in Caucasians. The authors show that the variant gene is homozygous in 25% of healthy Chinese people, and 69% of those with severe pandemic influenza, suggesting that this gene influences the epidemiology of influenza in South-East Asia.
- Yong-Hong Zhang
- , Yan Zhao
- & Tao Dong
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In vivo imaging of virological synapses
In vitro, retroviruses spread between cells via structures resembling synapses. Sewaldet al. now demonstrate that virological synapses can also be observed in living mice by intravital microscopy, validating this concept in vivo.
- Xaver Sewald
- , David G. Gonzalez
- & Walther Mothes
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Article
| Open AccessVirus-like glycodendrinanoparticles displaying quasi-equivalent nested polyvalency upon glycoprotein platforms potently block viral infection
Host–pathogen relationships can be mediated by polyvalent glycan ligand–protein interactions. Here well-defined highly valent glycodendrimeric constructs are synthesized that can mimic pathogens, and can inhibit a model of infection by the Ebola virus.
- Renato Ribeiro-Viana
- , Macarena Sánchez-Navarro
- & Benjamin G. Davis
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Cooperation between different RNA virus genomes produces a new phenotype
RNA viruses are known to rapidly evolve new features through errors in replication and reshuffling of genomic segments. These authors report another strategy used by the measles virus to improve infectivity; the cooperation between wild-type and mutant fusion proteins in the same viral particle.
- Yuta Shirogane
- , Shumpei Watanabe
- & Yusuke Yanagi
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Article
| Open AccessMolecular memory of prior infections activates the CRISPR/Cas adaptive bacterial immunity system
The clustered regularly interspaced short palindromic repeats (CRISPR) system protects prokaryotes from foreign DNA. Here, bacteriophage DNA containing mutations that can circumvent this response are shown to be incorporated into the CRISPR locus, allowing bacteria to remember previous infections in an adaptive manner.
- Kirill A. Datsenko
- , Ksenia Pougach
- & Ekaterina Semenova
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Article |
Adaptive mutations in NEP compensate for defective H5N1 RNA replication in cultured human cells
Adaptive mutations in the avian influenza virus permit replication in mammals but how these mutations enable this effect is unclear. In this study, mutations found in the nuclear export protein of human isolates of H5N1 are shown to enhance the replication of viral RNA in human cells in culture.
- Benjamin Mänz
- , Linda Brunotte
- & Martin Schwemmle
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Host factors dictate control of viral replication in two HIV-1 controller/chronic progressor transmission pairs
Human immunodeficiency virus patients who maintain low levels of virus or have undetectable levels of virus exist. In this study, the HIV found in two of these patients is shown to replicatein vitro, suggesting that host factors have a role in suppressing virus levels.
- Robert W. Buckheit III
- , Tracy G. Allen
- & Joel N. Blankson
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Mapping of H3N2 influenza antigenic evolution in China reveals a strategy for vaccine strain recommendation
Influenza vaccines are updated frequently to accommodate changing influenza antigenicity. Here, the authors develop a new computational method for predicting the antigenicity of H3N2 influenza strains based on the HA sequence.
- Xiangjun Du
- , Libo Dong
- & Taijiao Jiang
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Article
| Open AccessModification of the carboxy-terminal flanking region of a universal influenza epitope alters CD4+ T-cell repertoire selection
Epitopes presented by MHC-II molecules bind to T-cell receptors to activate CD4+ T cells. In this study, changes in the carboxy-terminal region of the influenza hemagglutinin epitope HA305-320alters the strength of binding to the T-cell receptor, thus modulating T-cell receptor usage and activation.
- David K. Cole
- , Kathleen Gallagher
- & Andrew Godkin
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Article
| Open AccessThree-dimensional analysis of ribonucleoprotein complexes in influenza A virus
The influenza A virus genome consists of eight RNA segments, which permits genetic reassortment and contributes to the emergence of novel strains with pandemic potential. Here, electron tomography is used to study the three-dimensional structure of ribonucleoprotein complexes within progeny virions.
- Takeshi Noda
- , Yukihiko Sugita
- & Yoshihiro Kawaoka
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Binding of herpes simplex virus glycoprotein D to nectin-1 exploits host cell adhesion
Herpesvirus glycoprotein D binds to nectin 1 and the herpes virus entry mediator protein on the surface of host cells. In this study, Zhanget al. report the crystal structure of glycoprotein D in complex with the immunoglobulin-like domains of nectin 1, which suggests that binding of glycoprotein D to nectin 1 prevents nectin 1 dimerization.
- Na Zhang
- , Jinghua Yan
- & George F Gao
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Location-specific patterns of exposure to recent pre-pandemic strains of influenza A in southern China
Population demographics affect influenza transmission at large spatial scales. Here, influenza immunity is shown to vary spatially in a way unexplained by differences in demographics, suggesting that there are aspects of locations that drive influenza transmission other than individual and household risk factors.
- Justin Lessler
- , Derek A.T. Cummings
- & Steven Riley
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Article
| Open AccessMechanism of 150-cavity formation in influenza neuraminidase
Group-1 influenza A neuramidase proteins have a 150-cavity that can be targeted by drugs, but the 2009 H1N1 virus neuramidase is not thought to have a 150-cavity. Here, biophysical simulations show that the 2009 H1N1 neuramidase exists in solution with an open 150-cavity, which is stabilized by a salt bridge.
- Rommie E. Amaro
- , Robert V. Swift
- & Robin M. Bush
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