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Article
| Open AccessCrystal Structures of Wolbachia CidA and CidB Reveal Determinants of Bacteria-induced Cytoplasmic Incompatibility and Rescue
Wolbachia induced cytoplasmic incompatibility (CI) is caused by linked pairs of genes named cifA and cifB. Here, authors show that the residues at interfaces of the CidA-CidB complex is crucial for their binding and contribute to the diversity of CI.
- Haofeng Wang
- , Yunjie Xiao
- & Haitao Yang
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Article
| Open AccessBMP feed-forward loop promotes terminal differentiation in gastric glands and is interrupted by H. pylori-driven inflammation
Helicobacter pylori causes gastric inflammation, gland hyperplasia and is linked to gastric cancer. Here the authors identify a BMP feedback loop between the stomach epithelium and surrounding stroma that controls gland homeostasis and demonstrate its interruption upon infection with H. pylori.
- Marta Kapalczynska
- , Manqiang Lin
- & Michael Sigal
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Article
| Open AccessBiosynthesizing structurally diverse diols via a general route combining oxidative and reductive formations of OH-groups
Diols are important bulk and fine chemicals, but bioproduciton of branch-chain diols is hampered by the unknown biological route. Here, the authors report the expanding of amino acid metabolism for biosynthesis of branch-chain diols via a general route of combined oxidative and reductive formations of hydroxyl groups.
- Yongfei Liu
- , Wei Wang
- & An-Ping Zeng
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Article
| Open AccessComparative effectiveness and safety of homologous two-dose ChAdOx1 versus heterologous vaccination with ChAdOx1 and BNT162b2
Different homologous and heterologous vaccination regimens have been used for COVID-19. Here the authors show in a cohort analysis from Catalonia that heterologous vaccination with ChAdOx1 followed by BNT162b2 has better vaccine effectiveness than two doses of ChAdOx1.
- Eduardo Hermosilla
- , Ermengol Coma
- & Daniel Prieto-Alhambra
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Article
| Open AccessAssessment of global health risk of antibiotic resistance genes
Antibiotic resistance genes (ARGs) have accelerated microbial threats to human health. Here, Zhang et al. analyze 4572 metagenomic samples to illustrate the global patterns of ARG distribution in diverse habitats. They quantitatively evaluate the health risk to humans of 2561 ARGs by integrating human accessibility, mobility, pathogenicity and clinical availability. With the machine learning, they map the antibiotic resistance threats in global marine habitats.
- Zhenyan Zhang
- , Qi Zhang
- & Haifeng Qian
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Article
| Open AccessInhibition of lung microbiota-derived proapoptotic peptides ameliorates acute exacerbation of pulmonary fibrosis
Here, the authors show that treatment with a monoclonal neutralizing antibody against the lung microbiota-derived proapoptotic peptide corisin ameliorates acute exacerbation of pulmonary fibrosis and severity of endotoxin-induced acute lung injury in mice.
- Corina N. D’Alessandro-Gabazza
- , Taro Yasuma
- & Esteban C. Gabazza
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Article
| Open AccessDesign of stable and self-regulated microbial consortia for chemical synthesis
Stability and tunability are two desirable properties of microbial consortia-based bioproduction. Here, the authors integrate a caffeate-responsive biosensor into two and three strains coculture system to achieve autonomous regulation of strain ratios for coniferol and silybin/isosiltbin production, respectively.
- Xianglai Li
- , Zhao Zhou
- & Qipeng Yuan
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Article
| Open AccessIdentification of a protein responsible for the synthesis of archaeal membrane-spanning GDGT lipids
The cell membranes of many archaea contain characteristic membrane-spanning lipids known as glycerol dibiphytanyl glycerol tetraethers. Here, Zeng et al. identify a protein that participates in a key step of the synthesis of these lipids from diether precursors.
- Zhirui Zeng
- , Huahui Chen
- & Paula V. Welander
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Article
| Open AccessStructures of pseudorabies virus capsids
Pseudorabies virus (PRV) is a major etiological agent of swine infectious diseases responsible for significant economic losses in the swine industry. The authors report the structures of the PRV A-capsid and C-capsid, shedding light on PRV’s assembly mechanism.
- Guosong Wang
- , Zhenghui Zha
- & Ningshao Xia
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Article
| Open AccessThe induction of natural competence adapts staphylococcal metabolism to infection
Orthologs of natural competence genes are conserved in non-competent bacterial species, suggesting they have a role other than in transformation. Here, the authors show that competence induction in Staphylococcus aureus occurs in response to reactive oxygen species and host defenses that compromise bacterial respiration during infection, leading to increased DNA and glucose uptake and glycolytic flux.
- Mar Cordero
- , Julia García-Fernández
- & Daniel Lopez
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Article
| Open AccessAsymmetric peptidoglycan editing generates cell curvature in Bdellovibrio predatory bacteria
Cells of the predatory bacterium Bdellovibrio bacteriovorus, which invades and replicates within the periplasm of other bacteria, have a characteristic curved rod shape. Here, Banks et al. show that a peptidoglycan hydrolase is required for the curved shape, and this facilitates invasion of prey cells.
- Emma J. Banks
- , Mauricio Valdivia-Delgado
- & R. Elizabeth Sockett
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Article
| Open AccessComparative effectiveness of the BNT162b2 and ChAdOx1 vaccines against Covid-19 in people over 50
Several vaccines have been approved for Covid-19 and effectiveness data could guide public health decisions on vaccine usage. Here, the authors compare effectiveness of BNT162b2 and ChAdOx1 vaccines in people over 50 in the UK and find that BNT162b2 confers lower risk of infection and hospitalization.
- Junqing Xie
- , Shuo Feng
- & Dani Prieto-Alhambra
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Article
| Open AccesscAMP and c-di-GMP synergistically support biofilm maintenance through the direct interaction of their effectors
Nucleotide second messengers, such as cAMP and c-di-GMP, regulate many physiological processes in bacteria, including biofilm formation. Here, the authors provide evidence of cross-talk between cAMP and c-di-GMP pathways through direct interaction of their effectors, showing that the cAMP receptor protein (CRP) can play regulatory roles at the post-translational level.
- Cong Liu
- , Di Sun
- & Weijie Liu
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Article
| Open AccessMicrobiomes in the Challenger Deep slope and bottom-axis sediments
The V-shaped Challenger Deep in the Mariana Trench is the deepest part of the world’s oceans. Using 586 prokaryotic metagenome-assembled genomes and metatranscriptomic data, this study explores metabolic capabilities and activities of microorganisms involved in elemental cycling in hadal sediments, and reveals the different distribution of processes between its bottom-axis and slope.
- Ying-Li Zhou
- , Paraskevi Mara
- & Yong Wang
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Article
| Open AccessAn RNA-binding protein acts as a major post-transcriptional modulator in Bacillus anthracis
HitRS is a two-component system that responds to cell envelope damage in the bacterium Bacillus anthracis. Here, the authors identify an RNA-binding protein that regulates HitRS function by modulating the stability of the hitRS mRNA. In addition, the protein binds to over 70 RNAs and affects the expression of genes involved in multiple cellular processes.
- Hualiang Pi
- , Andy Weiss
- & Eric P. Skaar
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Article
| Open AccessA point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats
HIV-1 integration sites are biased towards actively transcribed genes, likely mediated by binding of the viral integrase (IN) protein to host factors. Here, Winans et al. show that the K258R point mutation in IN eredirects viral DNA integration to the centromeres of host chromosomes, which may affect HIV latency.
- Shelby Winans
- , Hyun Jae Yu
- & Stephen P. Goff
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Article
| Open AccessStructures of a deltacoronavirus spike protein bound to porcine and human receptors
As a potential zoonotic pathogen, porcine deltacoronavirus (PDCoV) has been shown to cause febrile illness in humans. Here, Ji et al. report the structures of PDCoV spike protein bound to porcine and human aminopeptidase receptors, pointing to the likely underlying mechanism of PDCoV zoonotic transmission.
- Weiwei Ji
- , Qi Peng
- & Shuijun Zhang
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Article
| Open AccessDe novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report
Here, the authors identify and validate the emergence of a SARS-CoV-2 resistance mutation to Remdesivir, associated with virological recrudesce in an immunocompromised patient with persistent COVID-19.
- Shiv Gandhi
- , Jonathan Klein
- & Albert I. Ko
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Article
| Open AccessHuman rhinovirus promotes STING trafficking to replication organelles to promote viral replication
Evidence exists that the typically antiviral signaling mediator STING is, counterintuitively, needed for optimal human rhinovirus infection. Here the authors confirm this finding and show how human rhinovirus can reduce stored Ca2+ levels to drive this effect.
- Martha Triantafilou
- , Joshi Ramanjulu
- & Kathy Triantafilou
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Article
| Open AccessRNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection
Understanding the mechanisms of SARS-CoV-2 infection is important to control the pandemic. Here the authors show the biological and pathological role of RNA G-quadruplex structure in both SARS-CoV-2 genome and host factors, particularly TMPRSS2.
- Geng Liu
- , Wenya Du
- & Xianghui Fu
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Article
| Open AccessStructure and function of the soil microbiome underlying N2O emissions from global wetlands
The wetland soil microbiome has a major impact on greenhouse gas emissions. Here the authors characterize how a group of archaea contribute to N2O emissions and find that climate and land use changes could promote these organisms.
- Mohammad Bahram
- , Mikk Espenberg
- & Ülo Mander
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Article
| Open AccessStrain-level characterization of broad host range mobile genetic elements transferring antibiotic resistance from the human microbiome
Here, Forster et al. compare 1354 cultured commensal strains (540 species) to 45,403 pathogen strains (12 species), identifying 64,188 MGE-mediated antibiotic resistance gene transfer events between the two groups, and show that 15 broad host range MGEs are able to transfer between phyla.
- Samuel C. Forster
- , Junyan Liu
- & Trevor D. Lawley
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Article
| Open AccessDynamics of plasmid-mediated niche invasion, immunity to invasion, and pheromone-inducible conjugation in the murine gastrointestinal tract
Microbial communities provide protection to their hosts by excluding colonizing pathogens. Here the authors study plasmid transfer and plasmid-mediated effects on host colonization and persistence of Enterococcus faecalis in the intestinal tract of mice.
- Helmut Hirt
- , Kerryl E. Greenwood-Quaintance
- & Gary M. Dunny
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Article
| Open AccessAntibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab
Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.
- Simeng Lin
- , Nicholas A. Kennedy
- & Jeannie Bishop
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Article
| Open AccessStructure-based design of prefusion-stabilized human metapneumovirus fusion proteins
The degree to which the conformation of the human metapneumovirus fusion (F) protein affects immunogenicity has been debated. Here, Hsieh et al. engineer prefusion-stabilized F variants with enhanced thermostability that elicit higher neutralizing antibody titers in mice than postfusion F.
- Ching-Lin Hsieh
- , Scott A. Rush
- & Jason S. McLellan
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Article
| Open AccessRescuing low frequency variants within intra-host viral populations directly from Oxford Nanopore sequencing data
Tracking low frequency intra-host variants has helped understanding within-host viral population dynamics and transmission. Precise tracking, however, depends partially on the error rate of the sequencing platforms used. Here, Liu et al. present Variabel, a method to rescue low frequency intra-host variants from Oxford Nanopore Technologies (ONT) platforms and validate their approach on Ebola virus, norovirus, and SARS-CoV-2 datasets.
- Yunxi Liu
- , Joshua Kearney
- & Todd J. Treangen
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Article
| Open AccessMucospheres produced by a mixotrophic protist impact ocean carbon cycling
Marine microbes govern ocean productivity and biogeochemistry, regulating global climate. Here the authors describe the sophisticated feeding strategy of a mixotrophic dinoflagellate and show how its behaviour impacts the vertical flux of carbon.
- Michaela E. Larsson
- , Anna R. Bramucci
- & Martina A. Doblin
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Article
| Open AccessCrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT
Pseudomonas aeruginosa secretes the toxin ExoT, which is important for pathogenesis. Here, the authors show that ExoT inhibits NLRC4-dependent inflammatory responses during wound infection.
- Mohamed F. Mohamed
- , Kajal Gupta
- & Sasha H. Shafikhani
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Article
| Open AccessFunctional genomics of RAP proteins and their role in mitoribosome regulation in Plasmodium falciparum
The function of RNA-binding domain abundant in Apicomplexans (RAP) protein family members is largely unknown. Here, using high-throughput functional genomics, including metabolomics, Hollin et al. characterize two RAP proteins that are essential for Plasmodium falciparum survival and control mitochondrial rRNAs.
- Thomas Hollin
- , Steven Abel
- & Karine G. Le Roch
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Article
| Open AccessStructural analysis of 3’UTRs in insect flaviviruses reveals novel determinants of sfRNA biogenesis and provides new insights into flavivirus evolution
Subgenomic flaviviral RNAs (sfRNAs) are produced by pathogenic flaviviruses to counteract the host antiviral response. sfRNAs are products of incomplete degradation of viral RNA by the host exoribonuclease XRN1 which stalls on XRN1-resistant structural elements (xrRNAs) in the 3‟UTR. Here, Slonchak et al. identify xrRNAs for mosquito-specific flaviviruses, characterize their ability to stall XRN1 and produce sfRNAs, and apply structure-based phylogenetic analysis to provide evidence for evolutionary selection of these elements.
- Andrii Slonchak
- , Rhys Parry
- & Alexander A. Khromykh
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Article
| Open AccessThe core and accessory Hfq interactomes across Pseudomonas aeruginosa lineages
Protein Hfq regulates bacterial mRNA translation and stability by interacting with mRNAs and small noncoding RNAs. Here, the authors identify Hfq-interacting RNAs in three strains representing major phylogenetic lineages of Pseudomonas aeruginosa, highlighting intra-species diversity in post-transcriptional regulatory networks.
- Julian Trouillon
- , Kook Han
- & Stephen Lory
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Article
| Open AccessBacteria eat nanoprobes for aggregation-enhanced imaging and killing diverse microorganisms
The authors demonstrate a strategy for bacterial uptake of gold nanoparticles modified with glucose polymer. The particles aggregate in the bacterial cells upon laser irradiation, resulting in enhanced photoacoustic signal and antibacterial activity, enabling sensitive imaging of bacteria in vivo.
- Yunmin Yang
- , Binbin Chu
- & Yao He
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Article
| Open AccessSynthetic glycans control gut microbiome structure and mitigate colitis in mice
Here, the authors characterize the gut microbiome fermentation properties and therapeutic potential of chemically diverse synthetic glycans (SGs), showing they promote specific shifts in taxonomic and metabolite profiles, and exhibit therapeutic benefits in mouse models of colonic inflammation, together implying SGs as a potential avenue to treat disease by modulating the composition and metabolites produced by the gut microbiome.
- Andrew C. Tolonen
- , Nicholas Beauchemin
- & Johan E. T. van Hylckama Vlieg
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Article
| Open AccessDivergent trajectories of antiviral memory after SARS-CoV-2 infection
The engagement of immunological memory is a key component to the protective anti-SARS-CoV-2 B and T cell responses. Here the authors assess the B and T cells of a cohort of UK healthcare workers in response to infection and longitudinally track the compartment showing distinct trajectories following early priming.
- Adriana Tomic
- , Donal T. Skelly
- & Susanna J. Dunachie
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Article
| Open AccessRapid expansion and extinction of antibiotic resistance mutations during treatment of acute bacterial respiratory infections
It remains unclear how rapid antibiotic switching affects the evolution of antibiotic resistance in individual patients. Here, Chung et al. combine short- and long-read sequencing and resistance phenotyping of 420 serial isolates of Pseudomonas aeruginosa collected from the onset of respiratory infection, and show that rare resistance mutations can increase by nearly 40-fold over 5–12 days in response to antibiotic changes, while mutations conferring resistance to antibiotics not administered diminish and even go to extinction.
- Hattie Chung
- , Christina Merakou
- & Gregory P. Priebe
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Article
| Open AccessSelf-attenuating adenovirus enables production of recombinant adeno-associated virus for high manufacturing yield without contamination
Scalability, yield and quality of recombinant AAVs are a significant issue during manufacture. Here the authors describe a self-inhibiting helper adenovirus strategy that improves outcomes compared to helper-free approaches.
- Weiheng Su
- , Maria I. Patrício
- & Ryan Cawood
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Article
| Open AccessThe indirect effect of mRNA-based COVID-19 vaccination on healthcare workers’ unvaccinated household members
COVID-19 vaccines are effective in preventing disease, but the extent of protection against transmission is unclear. Here, the authors use data from a cohort of healthcare workers in Finland and show that vaccination is associated with reduced infection in their unvaccinated adult household contacts.
- Jussipekka Salo
- , Milla Hägg
- & Lauri Sääksvuori
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Article
| Open AccessEvolution of the SARS-CoV-2 spike protein in the human host
The SARS-CoV-2 spike has been evolving in the human population. The variants of concern alpha and beta evolved to optimise spike openness and so ability to bind its receptor ACE2, the affinity towards the receptor, and stability upon receptor binding.
- Antoni G. Wrobel
- , Donald J. Benton
- & Steven J. Gamblin
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Article
| Open AccessWaning of SARS-CoV-2 booster viral-load reduction effectiveness
The BNT162b2 COVID-19 vaccine has been shown to reduce viral load of breakthrough infections (BTIs). Here, analyzing viral loads of BTIs post third vaccine shot, Levine-Tiefenbrun et al. show waning of the booster’s effectiveness in reducing infectiousness within months, mirroring the rate and magnitude of decline observed post the second shot.
- Matan Levine-Tiefenbrun
- , Idan Yelin
- & Roy Kishony
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Article
| Open AccessStructural insight into Marburg virus nucleoprotein–RNA complex formation
Marburg virus causes severe hemorrhagic fever in humans. Here, the authors determine the structure of Marburg virus nucleoprotein–RNA complex by cryo-electron microscopy and provide mechanistic insight into the helical assembly of the nucleocapsid.
- Yoko Fujita-Fujiharu
- , Yukihiko Sugita
- & Takeshi Noda
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Article
| Open AccessThe molecular basis of FimT-mediated DNA uptake during bacterial natural transformation
Many bacteria can take up exogenous DNA, in a process that often requires surface appendages composed of thousands of protein subunits called pilins. Here, Braus et al. show that a minor pilin binds directly to DNA and is important for DNA uptake in the pathogen Legionella pneumophila.
- Sebastian A. G. Braus
- , Francesca L. Short
- & Manuela K. Hospenthal
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Article
| Open AccessIn vitro maturation of Toxoplasma gondii bradyzoites in human myotubes and their metabolomic characterization
Bradyzoites are a quiescent form of Toxoplasma gondii enclosed in cysts during chronic infections. Here, Christiansen et al. develop a human myotube-based in vitro culture model of cysts that are infectious to mice and characterize their metabolism in comparison to fast replicating tachyzoites.
- Céline Christiansen
- , Deborah Maus
- & Martin Blume
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Article
| Open AccessCryo-EM structure of a SARS-CoV-2 omicron spike protein ectodomain
This study determined the structure of the spike protein of the SARS-CoV-2 omicron variant, revealing a predominantly open conformation of the molecule that may help omicron infect cells more efficiently than do previous variants.
- Gang Ye
- , Bin Liu
- & Fang Li
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Article
| Open AccessRole of mobile genetic elements in the global dissemination of the carbapenem resistance gene blaNDM
Gene blaNDM, conferring resistance to carbapenem antibiotics, is globally distributed across Gram-negative bacteria on multiple plasmids. Here, Acman et al. study the dynamics underlying blaNDM dissemination across over 6000 bacterial genomes, and identify mobile genetic elements and specific mobilisation events likely involved in the gene’s global spread.
- Mislav Acman
- , Ruobing Wang
- & Francois Balloux
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Article
| Open AccessIncorporating temporal distribution of population-level viral load enables real-time estimation of COVID-19 transmission
The time-varying effective reproductive number (Rt) is useful for monitoring transmission of infections such as COVID-19, but reporting delays impact case count-based estimation methods. Here, the authors demonstrate and validate a method for estimation of Rt based on viral load data from Hong Kong that does not require accurate daily counts.
- Yun Lin
- , Bingyi Yang
- & Benjamin J. Cowling
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Article
| Open AccessMechanism of cooperative N-glycan processing by the multi-modular endoglycosidase EndoE
EndoE is a multi-domain glycoside hydrolase of the human pathogen Enterococcus faecalis. Here, the authors present crystal structures of EndoE and provide biochemical insights into the molecular basis of EndoE’s substrate specificity and catalytic mechanism.
- Mikel García-Alija
- , Jonathan J. Du
- & Marcelo E. Guerin
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Article
| Open AccessChanges to gut amino acid transporters and microbiome associated with increased E/I ratio in Chd8+/− mouse model of ASD-like behavior
The gut microbiota has been shown to modulate the neural function via the microbiota-gut-brain axis. Here, the authors show that Bacteroides uniformis, a gut commensal bacterium, restores the ASD-like phenotypes by reducing intestinal amino acid transport in an ASD mouse model.
- You Yu
- , Bing Zhang
- & Fangqing Zhao
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Article
| Open AccessXenogeneic silencing strategies in bacteria are dictated by RNA polymerase promiscuity
Bacteria use specific silencing proteins to prevent spurious transcription of horizontally acquired DNA. Here, Forrest et al. describe differences in silencing strategies between E. coli and Bacillus subtilis, driven by the respective specificities of the silencing protein and the RNA polymerase in each organism.
- David Forrest
- , Emily A. Warman
- & David C. Grainger
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Article
| Open AccessAntibody escape and global spread of SARS-CoV-2 lineage A.27
The A.27 SARS-CoV-2 lineage spread globally in 2021 but did not become dominant. Here, the authors show that A.27 shares some mutations in the spike gene that are present in variants of concern, but lacks the D614G mutation, indicating independent evolution of immune escape properties.
- Tamara Kaleta
- , Lisa Kern
- & Jonas Fuchs
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