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| Open AccessA novel nairovirus associated with acute febrile illness in Hokkaido, Japan
Here, Kodama et al. describe the discovery, isolation and characterization of a novel tick-borne orthonairovirus, designated Yezo virus (YEZV), from patients with an acute febrile illness in Japan. Serological testing of wildlife and molecular screening of ticks suggest an endemic circulation of YEZV in Japan.
- Fumihiro Kodama
- , Hiroki Yamaguchi
- & Keita Matsuno
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Article
| Open AccessStructural basis of RNA polymerase inhibition by viral and host factors
Understanding the structural basis for the inhibition of archaeal eukaryotic-like RNA polymerases (RNAPs) during virus infection is of interest for drug design. Here, the authors present the cryo-EM structures of apo Sulfolobus acidocaldarius RNAP and the RNAP complex structures with two regulatory factors, RIP and TFS4 that inhibit transcription and discuss their inhibitory mechanisms.
- Simona Pilotto
- , Thomas Fouqueau
- & Finn Werner
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Article
| Open AccessA CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses
Rapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Here the authors generate mutant clonal intestinal organoids for 19 host genes previously implicated in coronavirus biology and identify the cell surface protease TMPRSS2 as a potential therapeutic target.
- Joep Beumer
- , Maarten H. Geurts
- & Hans Clevers
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Article
| Open AccessStructure of human cytomegalovirus virion reveals host tRNA binding to capsid-associated tegument protein pp150
Here, cryo-EM reconstructions of human cytomegalovirus (HCMV) virions reveal host tRNAs associated with the virion’s capsid-bound tegument protein, pp150. tRNA recruitment is mediated by the interactions specific for HCMV only, suggesting the explanation for the absence of such tRNA densities in related herpesviruses.
- Yun-Tao Liu
- , David Strugatsky
- & Z. Hong Zhou
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Article
| Open AccessPromoter-proximal elongation regulates transcription in archaea
Transcription in archaea is known to be regulated through the recruitment of RNA polymerase to promoters. Here, the authors show that the archaeon Saccharolobus solfataricus regulates transcription globally through a rate-limiting promoter-proximal elongation step.
- Fabian Blombach
- , Thomas Fouqueau
- & Finn Werner
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Article
| Open AccessPoint-of-care antimicrobial coating protects orthopaedic implants from bacterial challenge
Implant infection is the most common mode of joint replacement failure with serious complications. Here, the authors report on the in vivo application of a prophylactic coating technology that can incorporate a range of antibiotics and be applied in the operating room prior to implantation.
- Weixian Xi
- , Vishal Hegde
- & Tatiana Segura
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Article
| Open AccessCommunity and single cell analyses reveal complex predatory interactions between bacteria in high diversity systems
Studying the role of predator–prey interactions in food-web stability and species coexistence in the environment is arduous. Here, Cohen et al. use a combination of community and single-cell analyses to show that bacterial predators can regulate prey populations in the species-rich environments of wastewater treatment plants.
- Yossi Cohen
- , Zohar Pasternak
- & Edouard Jurkevitch
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Article
| Open AccessThe biogeographic differentiation of algal microbiomes in the upper ocean from pole to pole
Latitudinal ecosystem boundaries in the global upper ocean may be driven by many factors. Here the authors investigate pole-to-pole eukaryotic phytoplankton metatranscriptomes, gene co-expression networks, and beta diversity, finding that geographic patterns are best explained by temperature gradients.
- Kara Martin
- , Katrin Schmidt
- & Thomas Mock
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Article
| Open AccessFatal attraction of Caenorhabditis elegans to predatory fungi through 6-methyl-salicylic acid
Methyl salicylate ester is a plant metabolite involved in plant-insect and plant-plant interactions. Here, Yu et al. show that a nematode-trapping fungus has potential to produce a related compound, 6-methyl salicylate, which attracts its prey (nematodes) and modulates spore germination and trap formation in the fungus.
- Xi Yu
- , Xiaodi Hu
- & Reinhard Fischer
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Article
| Open AccessChlamydia evasion of neutrophil host defense results in NLRP3 dependent myeloid-mediated sterile inflammation through the purinergic P2X7 receptor
Myeloid cells are implicated in the innate immune and inflammatory response during infection with Chlamydia trachomatis. Here the authors show the evasion of the neutrophil response to infection and concomitant induction of sterile immunity via the purinergic P2X7 receptor.
- Chunfu Yang
- , Lei Lei
- & Harlan D. Caldwell
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Article
| Open AccessDesigning efficient genetic code expansion in Bacillus subtilis to gain biological insights
B. subtilis is valuable both as a model for cell biology and as an industrial organism. Here the authors use genetic code expansion to enable functional tools for exploring cell division dynamics.
- Devon A. Stork
- , Georgia R. Squyres
- & Aditya M. Kunjapur
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Article
| Open AccessMechanosensitive recruitment of stator units promotes binding of the response regulator CheY-P to the flagellar motor
It is unclear how bacterial cells adapt the reversible switching of flagellar motor rotation to environments of different viscosities. Here, Antani et al. show that flagellar mechanosensors allosterically control the motor’s binding affinity for the chemotaxis response regulator, CheY-P, to adapt flagellar switching over varying viscous loads.
- Jyot D. Antani
- , Rachit Gupta
- & Pushkar P. Lele
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Article
| Open AccessNew-onset IgG autoantibodies in hospitalized patients with COVID-19
Infection with SARS-CoV2 and the development of Coronavirus disease 2019 (COVID-19) has been linked to induction of autoimmunity and autoantibody production. Here the authors characterise the new-onset IgG autoantibody response in hospitalised patients with COVID-19 which they correlate to the magnitude of the SARS-CoV2 response.
- Sarah Esther Chang
- , Allan Feng
- & Paul J. Utz
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Article
| Open AccessStructure and function relationship of OqxB efflux pump from Klebsiella pneumoniae
OqxB is an RND (Resistance-Nodulation-Division) transporter that contributes to the antibiotic resistance in Klebsiella pneumoniae. Here, the authors report structural and functional characterization of OqxB, with insights into its substrate binding pocket and the role in fluoroquinolone resistance.
- Nagakumar Bharatham
- , Purnendu Bhowmik
- & Satoshi Murakami
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Article
| Open AccessContact tracing is an imperfect tool for controlling COVID-19 transmission and relies on population adherence
Evaluations of the UK’s contact tracing programme have shown that it has had limited impact on COVID-19 control. Here, the authors show that with high levels of reporting and adherence, contact tracing could reduce transmission, but it should not be used as the sole control measure.
- Emma L. Davis
- , Tim C. D. Lucas
- & Petra Klepac
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Article
| Open AccessProkaryotic viruses impact functional microorganisms in nutrient removal and carbon cycle in wastewater treatment plants
Activated sludge (AS) systems in wastewater treatment plants (WWTPs) contain high concentration of viruses. Here, the authors apply a systematic metagenomic pipeline and retrieve a catalogue of around 50,000 prokaryotic viruses from samples of six WWTPs, revealing a large and uncharacterized viral diversity in AS communities.
- Yiqiang Chen
- , Yulin Wang
- & Tong Zhang
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Article
| Open AccessOPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection
During herpesvirus infection, most individuals intrinsically suppress a primary infection and therewith preclude potential damage or neurodegeneration of the CNS. Here, Ames et al. show that Optineurin (OPTN), a conserved autophagy receptor, restricts HSV-1 spread, degrades viral VP16 through autophagy and is neuroprotective against HSV infection in vivo.
- Joshua Ames
- , Tejabhiram Yadavalli
- & Deepak Shukla
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Article
| Open AccessTwenty-year trends in antimicrobial resistance from aquaculture and fisheries in Asia
Trends in antimicrobial resistance (AMR) in aquatic food animals are seldom documented, particularly in Asia. Here, Schar et al. review 749 point prevalence surveys, describing AMR trends in Asian aquaculture and fisheries over two decades, and identifying resistance hotspots as well as regions that would benefit most from future surveillance efforts.
- Daniel Schar
- , Cheng Zhao
- & Thomas P. Van Boeckel
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Article
| Open AccessThe gut microbiome in konzo
Here, using metagenomic profiling in 180 individuals from the Democratic Republic of the Congo, the authors find associations between the gut microbiome and konzo, a neurodegenerative disease that mostly affects children and is caused by the consumption improperly processed cassava.
- Matthew S. Bramble
- , Neerja Vashist
- & Eric Vilain
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Article
| Open AccessSequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation
The Spike protein of SARS-CoV-2 has a C-terminal cytoplasmic tail. Here the authors show that this tail binds trafficking machinery via sequences that appear optimised to ensure that Spike accumulates at the site of viral budding in the Golgi but that some can also traffic to the cell surface to induce syncytia formation.
- Jérôme Cattin-Ortolá
- , Lawrence G. Welch
- & Sean Munro
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Article
| Open AccessFunctional comparison of MERS-coronavirus lineages reveals increased replicative fitness of the recombinant lineage 5
MERS-CoV is enzootic in dromedary camels, can spread to humans but undergoes limited onward transmission. Here, Schroeder et al. compare clinical isolates of MERS-CoV in vitro and show that the predominantly circulating recombinant lineage 5 possess a fitness advantage over parental lineage 3 and 4 due to reduced activation of innate immune signaling.
- Simon Schroeder
- , Christin Mache
- & Christian Drosten
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Comment
| Open AccessGrowth-coupled selection of synthetic modules to accelerate cell factory development
Synthetic biology has brought about a conceptual shift in our ability to redesign microbial metabolic networks. Combining metabolic pathway-modularization with growth-coupled selection schemes is a powerful tool that enables deep rewiring of the cell factories’ biochemistry for rational bioproduction.
- Enrico Orsi
- , Nico J. Claassens
- & Steffen N. Lindner
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Article
| Open AccessComparative genomic analysis reveals metabolic flexibility of Woesearchaeota
The biology of the archaeal phylum Woesearchaeota is poorly understood due to the lack of cultured isolates. Here, the authors analyze datasets of Woesearchaeota 16 S rRNA gene sequences and metagenome-assembled genomes to infer global distribution patterns, ecological preferences and metabolic capabilities.
- Wen-Cong Huang
- , Yang Liu
- & Meng Li
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Article
| Open AccessSingle-cell transcriptomic analysis of bloodstream Trypanosoma brucei reconstructs cell cycle progression and developmental quorum sensing
Trypanosoma brucei undergoes developmental steps during host infection. Here, using oligopeptide-induced differentiation in vitro, authors model replicative ‘slender’ to transmissible ‘stumpy’ bloodstream forms and identify developmental and cell cycle regulators by single cell transcriptomics.
- Emma M. Briggs
- , Federico Rojas
- & Thomas D. Otto
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Article
| Open AccessSmall-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding
Measles virus is highly contagious and outbreaks occur worldwide. Here the authors show that the orally bioavailable small-molecule polymerase inhibitor ERDRP-0519 prevents measles disease in squirrel monkeys and reduces virus shedding.
- Kevin Wittwer
- , Danielle E. Anderson
- & Veronika von Messling
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Article
| Open AccessThe cryo-EM structure of the bd oxidase from M. tuberculosis reveals a unique structural framework and enables rational drug design to combat TB
M. tuberculosis cytochrome bd oxidase is of interest as a TB drug target. Here, the authors present the 2.5 Å cryo-EM structure of M. tuberculosis cytochrome bd oxidase and identify a disulfide bond within the canonical quinol binding and oxidation domain (Q-loop) and a menaquinone-9 binding site at heme b595.
- Schara Safarian
- , Helen K. Opel-Reading
- & Hartmut Michel
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Article
| Open AccessProcessive dynamics of the usher assembly platform during uropathogenic Escherichia coli P pilus biogenesis
Escherichia coli form pili structures in order to initiate infection of the urinary tract. Here, Thanassi et al., have solved the structures of pili assembly intermediates and provided insights into their biogenesis and assembly.
- Minge Du
- , Zuanning Yuan
- & David G. Thanassi
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Article
| Open AccessSpatial rearrangement of the Streptomyces venezuelae linear chromosome during sporogenic development
Streptomyces bacteria have a linear chromosome and a complex life cycle, including development of multi-genomic hyphae that differentiate into mono-genomic exospores. Here, Szafran et al. show that the chromosome of Streptomyces venezuelae undergoes substantial remodelling during sporulation, from an ‘open’ to a ‘closed’ conformation.
- Marcin J. Szafran
- , Tomasz Małecki
- & Dagmara Jakimowicz
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Article
| Open AccessA versatile genetic engineering toolkit for E. coli based on CRISPR-prime editing
CRISPR prime editing enables double-strand break free engineering of the genome. Here the authors present a toolkit for prime editing in E. coli.
- Yaojun Tong
- , Tue S. Jørgensen
- & Sang Yup Lee
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Article
| Open AccessDynamics of the compartmentalized Streptomyces chromosome during metabolic differentiation
Streptomyces bacteria have a linear chromosome, with core genes located in the central region and gene clusters for specialized metabolite biosynthesis found in the ‘arms’. Here, Lioy et al. show that such chromosome structure correlates with genetic compartmentalization, and the onset of metabolic differentiation is accompanied by a rearrangement of chromosome architecture.
- Virginia S. Lioy
- , Jean-Noël Lorenzi
- & Stéphanie Bury-Moné
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Article
| Open AccessTargeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques
In this study, Marlin et al. provide insights into the potential use of subunit vaccines that induce a high level of protection against SARS-CoV-2 in animal models.
- Romain Marlin
- , Veronique Godot
- & Roger Le Grand
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Article
| Open AccessChanges in the distribution of fitness effects and adaptive mutational spectra following a single first step towards adaptation
Analyses of both natural and experimental evolution suggest that adaptation depends on the evolutionary past and adaptive potential decreases over time. Here, by tracking yeast adaptation with DNA barcoding, the authors show that such evolutionary phenomena can be observed even after a single adaptive step.
- Dimitra Aggeli
- , Yuping Li
- & Gavin Sherlock
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Article
| Open AccessThe structure of the bacterial DNA segregation ATPase filament reveals the conformational plasticity of ParA upon DNA binding
ParA is an ATPase involved in the segregation of newly replicated DNA in bacteria. Here, structures of a ParA filament bound to DNA and of ParA in various nucleotide states offer insight into its conformational changes upon DNA binding and filament assembly, including the basis for ParA’s cooperative binding to DNA.
- Alexandra V. Parker
- , Daniel Mann
- & Julien R. C. Bergeron
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Article
| Open AccessA pre-registered short-term forecasting study of COVID-19 in Germany and Poland during the second wave
Forecasting models have been used extensively to inform decision making during the COVID-19 pandemic. In this preregistered and prospective study, the authors evaluated 14 short-term models for Germany and Poland, finding considerable heterogeneity in predictions and highlighting the benefits of combined forecasts.
- J. Bracher
- , D. Wolffram
- & Frost Tianjian Xu
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Perspective
| Open AccessThe microbiome extends host evolutionary potential
The microbiome is becoming recognized as a key determinant of host phenotype. Here, Henry et al. present a framework for building our understanding of how the microbiome also influences host evolution, review empirical examples and research approaches, and highlight emerging questions.
- Lucas P. Henry
- , Marjolein Bruijning
- & Julien F. Ayroles
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Article
| Open AccessGlobal phylogenomic analyses of Mycobacterium abscessus provide context for non cystic fibrosis infections and the evolution of antibiotic resistance
Mycobacterium abscessus is an emerging infection that usually affects patients with structural lung diseases such as cystic fibrosis (CF). Here, the authors use phylogenetic analyses to demonstrate close relationships between isolates from CF and non-CF patients and identify antibiotic resistance markers.
- Ryan A. Bronson
- , Chhavi Gupta
- & Keira A. Cohen
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Article
| Open AccessDistinct patterns of within-host virus populations between two subgroups of human respiratory syncytial virus
Respiratory syncytial virus (RSV) is a common infection in children and older adults but little is known about within-host viral population diversity. Here, the authors perform deep sequencing and find that RSV subgroup B exhibited more diversity than subgroup A, with implications for development of therapeutics and vaccines.
- Gu-Lung Lin
- , Simon B. Drysdale
- & Andrew J. Pollard
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Article
| Open AccessA guanidine-degrading enzyme controls genomic stability of ethylene-producing cyanobacteria
The metabolic pathways used by microbes to degrade guanidine or mitigate its toxicity remain unclear. Here, the authors report a guanidine degrading enzyme that controls genomic stability of ethylene producing cyanobacterial strains.
- Bo Wang
- , Yao Xu
- & Jianping Yu
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Article
| Open AccessTracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS
Here, the authors perform transcriptional profiling on tracheal aspirates of adults requiring mechanical ventilation for SARS-CoV2-induced acute respiratory distress syndrome (ARDS) and identify a dysregulated host response predicted to predicted to be potentially modulated by dexamethasone.
- Aartik Sarma
- , Stephanie A. Christenson
- & Charles R. Langelier
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Article
| Open AccessNeutralization of SARS-CoV-2 variants by convalescent and BNT162b2 vaccinated serum
Here, the authors show that neutralization of human sera from both BNT162b2 vaccine recipients and from convalescent COVID-19 patients is less efficient against SARS- CoV-2 variants B.1.1.7 and B.1.351 and negatively associated with patient age.
- Timothy A. Bates
- , Hans C. Leier
- & Fikadu G. Tafesse
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Article
| Open AccessComprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions
Here, Yang et al. apply different RNA sequencing approaches to characterize the secondary structure of SARS-CoV-2 viral RNAs, report on long-range interactions along the viral genome, and uncover the virus-host RNA interactome in cells.
- Siwy Ling Yang
- , Louis DeFalco
- & Yue Wan
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Article
| 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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