Featured
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| Open AccessA high-resolution temporal atlas of the SARS-CoV-2 translatome and transcriptome
Here, Kim et al. apply various sequencing techniques (RPF-seq, QTI-seq, mRNA-seq, sRNA-seq) to unravel the high-resolution, longitudinal translatome and transcriptome of SARS-CoV-2. They identify a translation initiation site in the leader sequence of all genomic and subgenomic RNAs and show its relevance for the SARS-CoV-2 translatome.
- Doyeon Kim
- , Sukjun Kim
- & Daehyun Baek
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Article
| Open AccessGlobal spread of Salmonella Enteritidis via centralized sourcing and international trade of poultry breeding stocks
Salmonella enterica serotype Enteritidis is a pathogen of poultry that can cause outbreaks in humans. Here the authors use genomic and trade data to investigate a pandemic in the 1980s, finding evidence that international trade of breeding stocks led to global spread of the pathogen.
- Shaoting Li
- , Yingshu He
- & Xiangyu Deng
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Article
| Open AccessA non-enzymatic, isothermal strand displacement and amplification assay for rapid detection of SARS-CoV-2 RNA
The reliance on enzymes in SARS-CoV-2 RNA detection imposes limits on transport and storage conditions. Here the authors use non-enzymatic isothermal amplification to detect RNA with no need for reverse transcription.
- Mohsen Mohammadniaei
- , Ming Zhang
- & Yi Sun
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Article
| Open AccessAn ester bond underlies the mechanical strength of a pathogen surface protein
Bacterial surface adhesion proteins are characterized by unusual mechanical properties. Here, the authors use atomic force microscopy-based technique to study a surface-anchoring protein Cpe0147 from Clostridium perfringens and show that an ester bond can withstand considerable mechanical forces and prevent complete protein unfolding.
- Hai Lei
- , Quan Ma
- & Yi Cao
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Article
| Open AccessThe risk of indoor sports and culture events for the transmission of COVID-19
Mass gathering events represent a risk for transmission of SARS-CoV-2. Here, the authors describe an experimental indoor test event in which individual contacts were measured and use aerosol and epidemiological modelling to evaluate transmission risks of different types of restrictions in the arena.
- Stefan Moritz
- , Cornelia Gottschick
- & Rafael Mikolajczyk
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Article
| Open AccessBacterial cellulose spheroids as building blocks for 3D and patterned living materials and for regeneration
Bacterial cellulose is a promising cheap-to-produce programmable engineered living material. Here the authors present a method for production of spheroids for use as engineerable building blocks able to sense and respond to chemical inputs.
- Joaquin Caro-Astorga
- , Kenneth T. Walker
- & Tom Ellis
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Article
| Open AccessSCOPE enables type III CRISPR-Cas diagnostics using flexible targeting and stringent CARF ribonuclease activation
Type III CRISPR-Cas systems recognize and cleave target RNAs and produce signalling molecules. Here the authors discover that both processes are governed by a flexible seed region, ultimately resulting in SCOPE, a SARSCoV-2 diagnostic assay with atto-molar sensitivity.
- Jurre A. Steens
- , Yifan Zhu
- & Raymond H. J. Staals
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Article
| Open AccessTwo doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern
Understanding the effect of vaccination on emerging SARS-CoV-2 variants of concern is of increasing importance. Here, James et al. report that two doses of vaccination with the Pfizer-BioNTech vaccine induce more robust immune responses to the B.1.1.7 and B.1.351 SARS-CoV-2 lineages than does natural infection.
- Donal T. Skelly
- , Adam C. Harding
- & William S. James
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Article
| Open AccessSARS-CoV-2 disease severity and transmission efficiency is increased for airborne compared to fomite exposure in Syrian hamsters
Here, Port and Yinda et al. directly compare the relative contribution of contact, fomite, and airborne transmission route of SARS-CoV-2 to disease outcome in Syrian hamsters; while intranasal and aerosol inoculation causes severe pathogenesis, fomite exposure is characterized by milder disease.
- Julia R. Port
- , Claude Kwe Yinda
- & Vincent J. Munster
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Article
| Open AccessComplete and efficient conversion of plant cell wall hemicellulose into high-value bioproducts by engineered yeast
Cellulosic hydrolysates contain substantial amounts of acetate, which is toxic to fermenting microorganisms. Here, the authors engineer Baker’s yeast to co-consume xylose and acetate for triacetic acid lactone production from a hemicellulose hydrolysate of switchgrass.
- Liang Sun
- , Jae Won Lee
- & Yong-Su Jin
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Article
| Open AccessStructural basis for the inhibition of HTLV-1 integration inferred from cryo-EM deltaretroviral intasome structures
Human T-cell lymphotropic virus type 1 (HTLV-1) is an oncogenic deltaretrovirus. Here the authors provide structural characterization of the binding mechanism of novel integrase strand transfer inhibitor (INSTI) candidates to limit HTLV-1 infection.
- Michal S. Barski
- , Teresa Vanzo
- & Goedele N. Maertens
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Article
| Open AccessHigh COVID-19 transmission potential associated with re-opening universities can be mitigated with layered interventions
Reopening of universities to students following COVID-19 restrictions risks increased transmission due to high numbers of social contacts and the potential for asymptomatic transmission. Here, the authors use a mathematical model with social contact data to estimate the impacts of reopening a typical non-campus based university in the UK.
- Ellen Brooks-Pollock
- , Hannah Christensen
- & Leon Danon
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Article
| Open AccessPhylogenomics of a new fungal phylum reveals multiple waves of reductive evolution across Holomycota
Unicellular fungi with free-living flagellated stages (zoospores) remain poorly known. Here, Galindo et al. sequence single-cell genomes for two atypical parasitic fungi with amoeboid zoospores, and re-evaluate the branching order of early-diverging fungi and the evolution of fungal multicellularity and flagellum-mediated motility.
- Luis Javier Galindo
- , Purificación López-García
- & David Moreira
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Article
| Open AccessIn situ ultrastructures of two evolutionarily distant apicomplexan rhoptry secretion systems
The rhoptry is an apical secretory organelle of apicomplexan parasites that is essential for host cell invasion. Here, Mageswaran et al. provide in situ ultrastructures of rhoptries from two pathogens, revealing a conserved architecture including luminal filaments and a distinct docking mechanism.
- Shrawan Kumar Mageswaran
- , Amandine Guérin
- & Yi-Wei Chang
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Article
| Open AccessGenome-scale target identification in Escherichia coli for high-titer production of free fatty acids
Identification of gene targets is one of the major challenges to construct superior microbial cell factory for chemical synthesis. Here, the authors employ CRISPRi and omics analyses for genome-scale target genes identification for high-titer production of free fatty acids in E. coli.
- Lixia Fang
- , Jie Fan
- & Hao Song
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Article
| Open AccessOffspring born to influenza A virus infected pregnant mice have increased susceptibility to viral and bacterial infections in early life
Influenza infection during pregnancy can affect health of offspring but it is not clear how this affects immune responses. Here the authors use a mouse model to show that influenza infection during pregnancy can increase susceptibility to secondary infection and alter immune cell function in offspring.
- Henning Jacobsen
- , Kerstin Walendy-Gnirß
- & Gülsah Gabriel
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Article
| Open AccessDecline in plankton diversity and carbon flux with reduced sea ice extent along the Western Antarctic Peninsula
Over the past century, the Western Antarctic Peninsula has experienced rapid warming and a substantial loss of sea ice with important implications for plankton biodiversity and carbon cycling. Using a 5-year DNA metabarcoding dataset, this study assesses how interannual variability in sea-ice conditions impacts biodiversity and biological carbon fluxes in this region.
- Yajuan Lin
- , Carly Moreno
- & Nicolas Cassar
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Article
| Open AccessMetabolome and proteome analyses reveal transcriptional misregulation in glycolysis of engineered E. coli
Synthetic pathways represent a metabolic burden on host cells. Here the authors engineer Cra-binding sites to prevent misregulation in glycerol and carotenoid overproducing E. coli strains.
- Chun-Ying Wang
- , Martin Lempp
- & Hannes Link
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Article
| Open AccessInterferon lambda 4 impairs hepatitis C viral antigen presentation and attenuates T cell responses
A genetic variant in the IFN-lambda 4 gene has been associated with poor hepatitis C virus prognosis but it is not clear how this functions. Here the authors show that IFN-lambda 4 promotes ER stress and inhibits presentation of HCV epitopes to CD8+ T cells.
- Qian Chen
- , Mairene Coto-Llerena
- & Markus H. Heim
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| Open AccessMortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors
Regional differences in SARS-CoV-2 variants may affect treatment outcome. Here, the authors show that near-sourced convalescent plasma has higher efficacy, as defined by death within 30 days of transfusion, than plasma sourced more than 150 miles away.
- Katie L. Kunze
- , Patrick W. Johnson
- & Michael J. Joyner
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Article
| Open AccessGut microbiome-mediated metabolism effects on immunity in rural and urban African populations
The authors profile stool metagenomics and plasma metabolomics in Tanzanian individuals and uncover a gradient of gut microbial profiles, from rural through urban Tanzania towards Western populations. Integration with ex vivo blood microbial stimulations reveals immune responses associated with histidine and arginine pathways, mediated by Bifidobacterium longum and Akkermansia muciniphila.
- Martin Stražar
- , Godfrey S. Temba
- & Ramnik J. Xavier
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Article
| Open AccessConversion of dietary inositol into propionate and acetate by commensal Anaerostipes associates with host health
Here, the authors report an anaerobic metabolic pathway from the dominant gut butyrogen Anaerostipes, showing several strains of this genus to be capable of producing propionate from dietary myo-inositol that associates with reduced fasting-glucose levels in mice.
- Thi Phuong Nam Bui
- , Louise Mannerås-Holm
- & Willem M. deVos
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Article
| Open AccessCRISPR/Cas9-engineered inducible gametocyte producer lines as a valuable tool for Plasmodium falciparum malaria transmission research
During each replication cycle of P. falciparum in the human bloodstream, a small proportion of parasites commits to sexual development and differentiates into transmission-relevant gametocytes. Applying CRISPR-based genome editing, Boltryk et al. engineer P. falciparum lines with sexual commitment rates of 75% to promote future studies on gametocyte biology.
- Sylwia D. Boltryk
- , Armin Passecker
- & Till S. Voss
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Article
| Open AccessTracking the introduction and spread of SARS-CoV-2 in coastal Kenya
SARS-CoV-2 was first detected in Kenya in March 2020 and there was evidence of local transmission in the following months. Here, the authors characterise the early stages of the epidemic in coastal Kenya using phylogenetics and find evidence of multiple strain importations from international points of entry.
- George Githinji
- , Zaydah R. de Laurent
- & Charles N. Agoti
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Article
| Open AccessEvolutionary dynamics of multidrug resistant Salmonella enterica serovar 4,[5],12:i:- in Australia
Salmonella enterica serovar 4,[5],12:i:- (Salmonella 4,[5],12:i:-) is a major pathogen of humans and animals with a reported incidence in Australia three times higher than the UK and USA. Here, the authors report the circulation, antimicrobial resistance signatures, and effects on host cells, of three Salmonella4,[5],12:i:- lineages within Australia.
- Danielle J. Ingle
- , Rebecca L. Ambrose
- & Deborah A. Williamson
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Article
| Open AccessIdentification of potent human neutralizing antibodies against SARS-CoV-2 implications for development of therapeutics and prophylactics
Applying neutralizing antibodies against SARS-CoV-2 to infected patients is a promising anti-viral treatment strategy. Here, Zhao et al. derive RBD-targeting monoclonal antibodies from a naïve human phage-displayed Fab library and show their prophylactic and therapeutic potential in hACE2-transgenic mice.
- Shaojuan Zhao
- , Huajun Zhang
- & Rui Gong
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Article
| Open AccessThe cytokines HGF and CXCL13 predict the severity and the mortality in COVID-19 patients
Infection with SARS CoV2 results in the induction of multiple cytokine and inflammatory pathways. Here the authors demonstrate the association of HGF and CXCL13 production with increased severity and mortality in COVID-19 patients.
- Matthieu Perreau
- , Madeleine Suffiotti
- & Giuseppe Pantaleo
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Article
| Open AccessDetection and characterization of the SARS-CoV-2 lineage B.1.526 in New York
West and colleagues develop the Variant Database software tool for examination of changing Spike mutations in SARS-CoV-2 genomes. The authors use this to detect emerging lineages of SARS-CoV-2 in New York and report the rapid spread of the B.1.526 lineage in the city.
- Anthony P. West Jr.
- , Joel O. Wertheim
- & Pamela J. Bjorkman
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Article
| Open AccessAn omics-based framework for assessing the health risk of antimicrobial resistance genes
Antibiotic resistance genes are common but not all are of high risk to human health. Here, the authors develop an omics-based framework for ranking genes by risk that incorporates level of enrichment in human associated environments, gene mobility, and host pathogenicity.
- An-Ni Zhang
- , Jeffry M. Gaston
- & Tong Zhang
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Article
| Open AccessLarge-scale computational discovery and analysis of virus-derived microbial nanocompartments
Encapsulins are microbial protein compartments that sequester specific enzymes and are formed by self-assembly of a viral-like capsid protein. Here, Andreas and Giessen carry out a large-scale computational analysis of prokaryotic genomes to present a curated set of over 6,000 encapsulin-like systems, and present hypotheses about their potential biological functions.
- Michael P. Andreas
- & Tobias W. Giessen
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Article
| Open AccessSeven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses
Long-term characterisation of SARS-CoV-2 antibody kinetics is needed to understand the protective role of the immune response. Here the authors describe antibody levels and neutralisation activity in healthcare workers over seven months and investigate the role of immunity to endemic human coronaviruses.
- Natalia Ortega
- , Marta Ribes
- & Carlota Dobaño
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Article
| Open AccessPurple sulfur bacteria fix N2 via molybdenum-nitrogenase in a low molybdenum Proterozoic ocean analogue
N2 fixation was key to the expansion of life on Earth, but which organisms fixed N2 and if Mo-nitrogenase was functional in the low Mo early ocean is unknown. Here, the authors show that purple sulfur bacteria fix N2 using Mo-nitrogenase in a Proterozoic ocean analogue, despite low Mo conditions.
- Miriam Philippi
- , Katharina Kitzinger
- & Marcel M. M. Kuypers
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Article
| Open AccessWhole-genome sequencing of Schistosoma mansoni reveals extensive diversity with limited selection despite mass drug administration
Schistosomiasis control strategies rely on mass drug administration (MDA) using praziquantel. Here, Berger et al. perform whole-genome sequencing of larvae from infected children across Ugandan regions with differing MDA histories. They find extensive gene flow with limited positive selection suggesting minimal change post MDA.
- Duncan J. Berger
- , Thomas Crellen
- & James A. Cotton
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Article
| Open AccessBrown adipose tissue is the key depot for glucose clearance in microbiota depleted mice
Gut microbiota deficient mice demonstrate enhanced glucose clearance, but which tissues are responsible for this improvement are still unclear. Here the authors report that brown adipose tissue contributes to the enhanced glucose clearance in gut microbiota depleted mice and that this response is dissociated from adaptive thermogenesis.
- Min Li
- , Li Li
- & John R. Speakman
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Article
| Open AccessCOVID-19 spread, detection, and dynamics in Bogota, Colombia
Detailed information on SARS-CoV-2 infection rates in Latin America by occupation, socioeconomic group and geographic area are rarely available. Here, the authors provide these estimates for in Bogota, Colombia using data from a sentinel surveillance scheme, and find that over half the population had been infected by March 2021.
- Rachid Laajaj
- , Camilo De Los Rios
- & Duncan Webb
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Article
| Open AccessReversible gene silencing through frameshift indels and frameshift scars provide adaptive plasticity for Mycobacterium tuberculosis
Bacterial adaptation through frame-shifting insertions and deletions (indels) could be reversed by secondary introduction of a frame-restoring indel. Here, the authors develop ScarTrek, a program that scans genomic data for different indels, and analyze 5977 clinical M. tuberculosis isolates for indel frequency.
- Aditi Gupta
- & David Alland
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Article
| Open AccessSalmonella effector SopD promotes plasma membrane scission by inhibiting Rab10
Salmonella secretes the effector protein SopD into the host cell cytoplasm, leading to scission of the plasma membrane through unclear mechanisms. Here, Boddy et al. show that SopD binds to and inhibits the small GTPase Rab10, thus promoting removal of Rab10 and recruitment of dynamin-2 to drive plasma membrane scission.
- Kirsten C. Boddy
- , Hongxian Zhu
- & John H. Brumell
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Article
| Open AccessMechanism of LolCDE as a molecular extruder of bacterial triacylated lipoproteins
In Gram-negative bacteria, lipoproteins are transported from the inner membrane (IM) to the outer membrane (OM) by the ATP-binding cassette (ABC) transporter LolCDE. Here the authors present cryo-EM structures of nanodisc-embedded LolCDE in different states, providing mechanistic insight into the transport mechanism.
- Stuti Sharma
- , Ruoyu Zhou
- & Maofu Liao
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Article
| Open AccessPotent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting diverse and conserved epitopes
Highly potent neutralizing nanobodies (Nbs) are of great interest as potential COVID-19 therapeutics. Here, the authors show that potent neutralizing Nbs targeting the receptor binding domain (RBD) of the SARS-CoV-2 spike protein are also effective against convergent variants of concern of the virus. They determine eight Nb-bound spike protein cryo-EM structures, classify the binding epitopes of the Nbs and discuss their neutralization mechanisms.
- Dapeng Sun
- , Zhe Sang
- & Yi Shi
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Article
| Open AccessTime-varying optimization of COVID-19 vaccine prioritization in the context of limited vaccination capacity
In the context of limited supply, strategies for optimising allocation of COVID-19 vaccines are needed. Here, the authors explore time-varying strategies that adapt to the epidemiological situation and simultaneously optimise for multiple objectives including reducing numbers of infections, hospitalisations, and deaths.
- Shasha Han
- , Jun Cai
- & Hongjie Yu
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Article
| Open AccessSARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation
SARS-CoV-2 infection has been shown to drive NLRP3 inflammasome activation and thereby cytokine storm, but how it does so is unclear. Here the authors show that the viral N protein can bind to NLRP3, resulting in enhanced interaction with ASC and thereby with the NLRP3 inflammasome.
- Pan Pan
- , Miaomiao Shen
- & Jianguo Wu
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Article
| Open AccessToxin import through the antibiotic efflux channel TolC
Bacteria can secrete diffusible protein toxins that kill competing bacteria. Here, the authors use biochemical, biophysical and structural analyses to show how one of these toxins exploits TolC (a major antibiotic efflux channel) to transport itself across the outer membrane of target cells.
- Nicholas G. Housden
- , Melissa N. Webby
- & Colin Kleanthous
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Article
| Open AccessA fructose/H+ symporter controlled by a LacI-type regulator promotes survival of pandemic Vibrio cholerae in seawater
The bacterium Vibrio cholerae can colonize the human intestine and cause cholera, but spends much of its life cycle in seawater. Here, Liu et al. identify a fructose uptake system that is important for the growth of the bacteria in seawater, where fructose concentrations are low.
- Yutao Liu
- , Bin Liu
- & Lei Wang
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Article
| Open AccessCorrelative multi-scale cryo-imaging unveils SARS-CoV-2 assembly and egress
In this study, Peijun Zhang and colleagues use cryoFIB/SEM volume imaging and soft x-ray cryo-tomography with cryo-electron tomography (cryoET) of cellular periphery, lamellae, and subtomogram averaging to place critical structural events in the SARS-CoV-2 infection cycle in the context of whole-cell images.
- Luiza Mendonça
- , Andrew Howe
- & Peijun Zhang
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Article
| Open AccessLytic archaeal viruses infect abundant primary producers in Earth’s crust
Little is known about viral-host interactions in the continental subsurface. Here, the authors use a combination of metagenomics, fluorescence in situ hybridization, and electron microscopy to show infections of abundant C-fixing subsurface archaea by lytic viruses.
- Janina Rahlff
- , Victoria Turzynski
- & Alexander J. Probst
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Article
| Open AccessA single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial
Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that has caused outbreaks in various regions of the world. Here the authors present safety and immunogenicity data from a phase 1 trial with the simian adenovirus vectored vaccine ChAdOx1 Chik, showing induction of neutralizing antibodies to four CHIKV lineages.
- Pedro M. Folegatti
- , Kate Harrison
- & Arturo Reyes-Sandoval
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Article
| Open AccessPlasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes
To understand malaria symptoms, several studies investigate association between parasite’s transcriptome and disease severity. Here, Thomson-Luque et al. reanalyze available transcriptomic data of P. falciparum and find that longer circulation of infected erythrocytes without sequestering to endothelial cells associates with decreasing parasitaemia and less severe disease.
- Richard Thomson-Luque
- , Lasse Votborg-Novél
- & Silvia Portugal
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Article
| Open AccessA synthetic nanobody targeting RBD protects hamsters from SARS-CoV-2 infection
Here, the authors report the engineering, structural and biological characterization of synthetic nanobodies (sybodies) that display potent therapeutic activity against SARS-CoV-2 infection in animal models via targeting the virus receptor-binding domain.
- Tingting Li
- , Hongmin Cai
- & Dianfan Li
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Article
| Open AccessPseudomonas aeruginosa PA14 produces R-bodies, extendable protein polymers with roles in host colonization and virulence
R-bodies are long, extendable protein polymers formed in the cytoplasm of some bacteria. Here, Wang et al. show that Pseudomonas aeruginosa produces R-bodies during colonization of plant and nematode hosts, and R-bodies induce ribosome cleavage and translational inhibition in nematodes.
- Bryan Wang
- , Yu-Cheng Lin
- & Lars E. P. Dietrich
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