Featured
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Article
| Open AccessA ‘through-DNA’ mechanism for co-regulation of metal uptake and efflux
Proteins Zur and ZntR sense intracellular zinc concentrations and regulate zinc transport, respectively, in E. coli. Here the authors show that the proteins coordinate their regulation through DNA, by forming heteromeric complexes that involve protein-DNA and protein-protein interactions.
- Udit Kumar Chakraborty
- , Youngchan Park
- & Peng Chen
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Article
| Open AccessA viral protein activates the MAPK pathway to promote viral infection by downregulating callose deposition in plants
MAPK cascades activate innate immunity to defend against various pathogens. Here the authors show that Nicotiana benthamiana NbMPK3/6 can phosphorylate the tomato chlorosis virus P7 protein leading to suppression of callose-dependent antiviral defence.
- Lixiao Feng
- , Xiangwen Luo
- & Yong Liu
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Article
| Open AccessPotent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages
Here the authors isolate monoclonal antibodies specific for Plasmodium vivax apical membrane antigen 1, and characterize the epitope of one antibody that inhibits invasion of reticulocytes and hepatocytes, and reduces liver infection in a mouse model.
- Anna C. Winnicki
- , Melanie H. Dietrich
- & Christopher L. King
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Article
| Open AccessStreptococcus pyogenes pharyngitis elicits diverse antibody responses to key vaccine antigens influenced by the imprint of past infections
Streptococcus pyogenes is a deadly bacteria without a vaccine. Here, researchers measured antibodies in serum and saliva from a strep throat human challenge trial. Baseline antibodies led to variable responses and affected susceptibility to strep throat.
- Joshua Osowicki
- , Hannah R. Frost
- & Andrew C. Steer
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Article
| Open AccessCryo-EM structure of Nipah virus L-P polymerase complex
The Nipah virus (NiV) polymerase complex is an ideal target for drug development. Here, the authors determine the cryo-EM structures of NiV L-P polymerase complexes and reveal how NiV is resistant to the allosteric L-targeting inhibitor GHP-88309. Furthermore, the authors demonstrate that suramin could inhibit NiV L-P complex at both enzymatic and cellular levels.
- Qi Peng
- , Yingying Dong
- & Yi Shi
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Article
| Open AccessSingle nucleotide polymorphisms are associated with strain-specific virulence differences among clinical isolates of Cryptococcus neoformans
Identification of virulence-associated genes in pathogens is important to understand mechanisms of disease. Here, Jackson et al. use a mouse model and clinical isolates of Cryptococcus neoformans to identify novel gene networks that impact virulence.
- Katrina M. Jackson
- , Thomas J. Y. Kono
- & Kirsten Nielsen
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Article
| Open AccessMechanisms of life cycle simplification in African trypanosomes
African trypanosomes can reduce their requirement for tsetse fly transmission, allowing an expanded geographical range. Here, molecular analyses of field and laboratory selected lines has identified adaptions for the parasite’s simplified life cycle.
- Guy R. Oldrieve
- , Frank Venter
- & Keith R. Matthews
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Article
| Open AccessAn autonomous microbial sensor enables long-term detection of TNT explosive in natural soil
Engineered microbes can detect harmful chemicals, but may not work well in complex environments. Here, the authors built microbial sensors for detection of TNT explosive and tested their response over 28 days in contaminated soil with many natural microbes, achieving stable detection for 21 days.
- Erin A. Essington
- , Grace E. Vezeau
- & Howard M. Salis
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Article
| Open AccessEF-P and its paralog EfpL (YeiP) differentially control translation of proline-containing sequences
EF-P plays an important role in overcoming polyproline sequence-induced stalling in bacteria. Here, the authors show that its paralog, EfpL, can also resolve this type of stalling, and also sense cellular metabolic states via lysine acylation.
- Alina Sieber
- , Marina Parr
- & Jürgen Lassak
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Article
| Open AccessMulti-protomics analysis identified host cellular pathways perturbed by tick-borne encephalitis virus infection
Here, Sui et al. use multi-proteomics to analyse tick-borne encephalitis virus-infected cells and identify host cellular pathways perturbed by viral infection.
- Liyan Sui
- , Wenfang Wang
- & Quan Liu
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Article
| Open AccessParadigm of engineering recalcitrant non-model microorganism with dominant metabolic pathway as a biorefinery chassis
Zymomonas mobilis is an ethanolognic microbial chassis cell for non-food feedstocks biorefinery. Here, the authors report an improved genome-scale metabolic model, develop an intermediate-chassis to bypass the dominant ethanol pathway, and demonstrate the application potential of using lignocellulosic waste for D-lactate production.
- Xiongying Yan
- , Weiwei Bao
- & Shihui Yang
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Article
| Open AccessSARS-CoV-2 human challenge reveals biomarkers that discriminate early and late phases of respiratory viral infections
It’s not always clear whether blood biomarkers are differentially expressed in the time course of viral infections. In this SARS-CoV-2 human challenge study, the authors identify distinct single-gene blood transcriptional biomarkers for early stages of infection or for symptomatic infection.
- Joshua Rosenheim
- , Rishi K. Gupta
- & Mahdad Noursadeghi
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Article
| Open AccessSubtilase SBT5.2 inactivates flagellin immunogenicity in the plant apoplast
Plants recognize bacteria by perceiving a 22-residue epitope in flagellin. Plant-secreted SBT5.2 subtilases are found to inactivate this epitope, leading to elicitor removal and reducing costly immunity responses while bacteria avoid recognition.
- Pierre Buscaill
- , Nattapong Sanguankiattichai
- & Renier A. L. van der Hoorn
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Article
| Open AccessTRIM7 ubiquitinates SARS-CoV-2 membrane protein to limit apoptosis and viral replication
TRIM7 acts as an antiviral factor during SARS-CoV-2 infection, by ubiquitinating the M protein on K14 and inhibiting caspase-6-dependent apoptosis. The natural K14 mutations in circulating strains support the physiological role of M ubiquitination.
- Maria Gonzalez-Orozco
- , Hsiang-chi Tseng
- & Ricardo Rajsbaum
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Article
| Open AccessBroadly conserved FlgV controls flagellar assembly and Borrelia burgdorferi dissemination in mice
The control of flagellar synthesis and function in the Lyme spirochete Borrelia burgdorferi is poorly understood, as this pathogen lacks the typical flagellar sigma factor and transcriptional regulators. Here, the authors identify a broadly conserved structural flagellar component that modulates flagellar assembly and is important for cell division, motility and virulence.
- Maxime Zamba-Campero
- , Daniel Soliman
- & Philip P. Adams
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Article
| Open AccessTowards a molecular picture of the archaeal cell surface
The model archaeon Sulfolobus acidocaldarius produces several protein filaments with specialised functions, including flagellum-like archaella, Aap pili, and adhesive threads. Here, the authors describe high-resolution structures and distinct glycosylation patterns for the three filaments, and present an integrated model of the filaments in the context of the S-layer.
- Matthew C. Gaines
- , Michail N. Isupov
- & Bertram Daum
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Article
| Open AccessNative RNA nanopore sequencing reveals antibiotic-induced loss of rRNA modifications in the A- and P-sites
It remains unclear whether rRNA modifications can be naturally altered in response to antibiotics in bacteria. Here, the authors analyzed direct RNA nanopore sequencing data with an analytical pipeline Nanoconsensus, to investigate whether bacterial rRNA modifications are modulated upon exposure to various antibiotics.
- Anna Delgado-Tejedor
- , Rebeca Medina
- & Eva Maria Novoa
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Article
| Open AccessThioredoxin 1 moonlights as a chaperone for an interbacterial ADP-ribosyltransferase toxin
Thioredoxin 1 (TrxA) is an enzyme that reduces disulfide bonds in the bacterial cytosol. Here, the AUs show that TrxA can function as a chaperone of the secreted bacterial ADP-ribosyltransferase toxin TreX independent of redox catalysis.
- Baptiste Dumont
- , Laurent Terradot
- & Dukas Jurėnas
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Article
| Open AccessDecoupled responses of plants and soil biota to global change across the world’s land ecosystems
Understanding how global changes affect both aboveground plants and belowground soil organisms is essential for preserving ecosystem functions and biodiversity. This study synthesizes extensive data, revealing decoupled responses in plant and soil biota to global changes across different biomes.
- Qingshui Yu
- , Chenqi He
- & Jingyun Fang
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Article
| Open AccessUse of epigenetically modified bacteriophage and dual beta-lactams to treat a Mycobacterium abscessus sternal wound infection
Cristinziano et al. report the use of bacteriophages and dual beta lactam antibiotics to treat a patient with a Mycobacterium abscessus sternal wound infection. One of the phages was epigenetically modified for specificity to the M. abscessus strain.
- Madison Cristinziano
- , Elena Shashkina
- & Anne Friedland
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Article
| Open AccessA blueprint for broadly effective bacteriophage-antibiotic cocktails against bacterial infections
The application of phage therapy for multidrug-resistant infections is mainly limited to personalized therapy due to the narrow host range of individual phages. Here, Kim et al. identify groups of phages that use non-redundant receptors, and present a blueprint for the development of effective, broad-spectrum phage-antibiotic combinations.
- Minyoung Kevin Kim
- , Qingquan Chen
- & Paul L. Bollyky
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Article
| Open AccessBactericidal antibiotic treatment induces damaging inflammation via TLR9 sensing of bacterial DNA
The immunologic differences induced by bactericidal versus bacteriostatic antibiotics remain unclear. Gross et al. show that, in contrast to static antibiotics, cidal antibiotics may drive harmful inflammation in acute infection via increased DNA release which stimulates TLR9 in mice.
- Julia L. Gross
- , Rahul Basu
- & Iain D. C. Fraser
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Article
| Open AccessMachine learning-enhanced immunopeptidomics applied to T-cell epitope discovery for COVID-19 vaccines
The identification of T cell epitopes is a critical step in understanding the immune response to infection and in designing vaccine based approaches. Here the authors introduce a frame work of antigen discovery called MHCvalidator and Epitrack to identify new antigenic features for T-cell COVID-19 vaccines and characterise a novel non-canonical epitope from a truncated Spike variant and mutation of an immunodominant epitope in the BNT162b4 vaccine.
- Kevin A. Kovalchik
- , David J. Hamelin
- & Etienne Caron
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| Open AccessCOVID-19 progression and convalescence in common variable immunodeficiency patients show dysregulated adaptive immune responses and persistent type I interferon and inflammasome activation
Common variable immunodeficiency (CVID) is a prevalent primary immunodeficiency characterized by hypogammaglobulinemia, poor antibody responses, and enhanced susceptibility to infection. Here the authors examine CVID patients infected by SARS-CoV-2 and describe broad immune dysregulation, sustained type I IFN responses, altered B/T cell signaling, impaired NK cell differentiation, and persistent inflammasome activation.
- Javier Rodríguez-Ubreva
- , Josep Calafell-Segura
- & Esteban Ballestar
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Article
| Open AccessMulti-biome analysis identifies distinct gut microbial signatures and their crosstalk in ulcerative colitis and Crohn’s disease
Here, the authors perform a multi-biome analysis in ulcerative colitis and Crohn’s disease patients from the Japanese 4D cohort, identifying intra- and trans-kingdom interactions including bacteria, phages, and fungi, providing potential candidate therapeutic targets.
- Shintaro Akiyama
- , Suguru Nishijima
- & Naoyoshi Nagata
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Article
| Open AccessCryo-EM structure of single-layered nucleoprotein-RNA complex from Marburg virus
Zinzula et al. reconstituted the helical ribonucleoprotein complex of Marburg virus in vitro, and determined its structure by cryo-electron microscopy in a single-layer conformation that recapitulates the assembly of authentic filovirus particles.
- Luca Zinzula
- , Florian Beck
- & Wolfgang Baumeister
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Article
| Open AccessHigh carriage and possible hidden spread of multidrug-resistant Salmonella among asymptomatic workers in Yulin, China
Salmonella is a significant cause of gastrointestinal infection and asymptomatic carriage can contribute to transmission. Here, the authors investigate the prevalence of asymptomatic carriage of Salmonella in Yulin, China through occupational health screening and find that carriage was higher in food workers.
- Xin Lu
- , Ming Luo
- & Biao Kan
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Article
| Open AccessVirus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability
KSHV modifies paraspeckles during its lytic replication cycle. They enhance virus replication by functioning as hubs for viral RNA processing and their modification is implicated in virus-mediated genomic instability.
- Katherine L. Harper
- , Elena M. Harrington
- & Adrian Whitehouse
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Article
| Open AccessA proteome-wide structural systems approach reveals insights into protein families of all human herpesviruses
The nine human herpesviruses encode hundreds of genes, but the activity and function of many are unclear. Generating protein structure predictions of entire proteomes, the authors could infer the function of many so-far uncharacterized genes.
- Timothy K. Soh
- , Sofia Ognibene
- & Jens B. Bosse
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Article
| Open AccessStreptolysin O accelerates the conversion of plasminogen to plasmin
Group A Streptococcus exploits the human fibrinolytic system to promote infection. Here, the authors reveal that the bacterial toxin streptolysin O binds to plasminogen and accelerates its conversion to plasmin, thereby dismantling blood clots and facilitating the spread within the human host.
- Di Tang
- , Hamed Khakzad
- & Johan Malmström
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Article
| Open AccessBacterial single-cell RNA sequencing captures biofilm transcriptional heterogeneity and differential responses to immune pressure
Microbial biofilms contain subpopulations of cells that display metabolic and transcriptional diversity. Here, Korshoj & Kielian present an optimized bacterial single-cell RNA sequencing method and use it to study Staphylococcus aureus diversity during biofilm growth and transcriptional adaptations following immune cell exposure.
- Lee E. Korshoj
- & Tammy Kielian
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Article
| Open AccessStructural insight into the distinct regulatory mechanism of the HEPN–MNT toxin-antitoxin system in Legionella pneumophila
HEPN–MNT is a bacterial type VII toxin-antitoxin (TA) system, comprising the HEPN toxin and the MNT antitoxin. Crystal structures and functional assays of the HEPN–MNT module suggest that HEPN is a metal-dependent RNase and identify its active site residues and regulatory mechanism.
- Chenglong Jin
- , Cha-Hee Jeon
- & Bong-Jin Lee
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Article
| Open AccessOutcome of SARS-CoV-2 reinfection depends on genetic background in female mice
Genetic disposition can impact response to virus infection. Here, the authors used a reinfection approach with antigenically distinct SARS-CoV-2 variants Omicron and Beta and show that differences in the immune response correlate with disease outcome in mouse models with different genetic background upon reinfection.
- Gagandeep Singh
- , Juan García-Bernalt Diego
- & Michael Schotsaert
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Article
| Open AccessImpact of easing COVID-19 restrictions on antibiotic usage in Eastern China using wastewater-based epidemiology
China’s zero-COVID policy was discontinued in December 2022 and was followed by a wave of COVID-19 infections. Here, the authors demonstrate that the end of this policy also coincided with increased antibiotic use, indicating possible inappropriate prescribing.
- Jinxin Zang
- , Lufang Jiang
- & Helen Lambert
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Article
| Open AccessMembrane lipid homeostasis dually regulates conformational transition of phosphoethanolamine transferase EptA
The phosphoethanolamine transferase modifies lipopolysaccharide structure and confers antibiotic resistance on Gram-negative bacteria. Here the authors reveal how the membrane lipid modulates the conformational transition of this important enzyme.
- Zhenyu Ma
- , Sue C. Nang
- & Xukai Jiang
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Article
| Open AccessPDCD6 regulates lactate metabolism to modulate LC3-associated phagocytosis and antibacterial defense
The molecular mechanism of LAP activation against invading pathogens is not fully understood. Here the authors demonstrate that programmed cell death 6 (PDCD6) negatively regulates LAP formation and the antibacterial response by interacting with lactate dehydrogenase A (LDHA) to downregulate lactate metabolism and RUBCN lactylation-mediated signaling.
- Lulu Sun
- , Sijin Wu
- & Tianliang Li
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Article
| Open AccessDiscovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19
In this work, the authors present novel PLpro inhibitors, with lead compound GZNL-P36 showing potent activity against SARS-CoV-2 variants, improving survival and reducing lung viral loads in a mouse model, offering promise for COVID−19 therapies.
- Yongzhi Lu
- , Qi Yang
- & Jinsai Shang
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Article
| Open AccessQuinolone-mediated metabolic cross-feeding develops aluminium tolerance in soil microbial consortia
The mechanism of soil microbial consortia resistant to aluminium toxicity is unclear. Here, the authors show that the quorum sensing signaling molecular HHQ produced by one member of the consortium can server as the nutritional resource for the other consortium member for aluminium tolerant cell wall component synthesis.
- Zhiyuan Ma
- , Meitong Jiang
- & Yuting Liang
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Article
| Open AccessRe-localization of a repeat-containing fungal effector by apoplastic protein Chitinase-like 1 blocks its toxicity
A toxin identified in Verticillium dahliae, VdTRP, damages cell membranes and causes rapid cell death. As defense, cotton uses chitinase-like 1, a cell wall protein, to keep VdTRP in the apoplastic space and reduce its toxicity to plant cells.
- Hanqiao Liu
- , Wenshu Zhang
- & Wangzhen Guo
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Article
| Open AccessPersonalised antimicrobial susceptibility testing with clinical prediction modelling informs appropriate antibiotic use
Authors present a personalised approach to clinical laboratory testing of antibiotics, based on real-time mathematical modelling, that encourages the use of drugs less likely to cause antimicrobial resistance, without compromising on overall antibiotic treatment options for prescribers.
- Alex Howard
- , David M. Hughes
- & William Hope
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Article
| Open AccessMandelonitrile produced by commensal bacteria protects the Colorado potato beetle against predation
The Colorado potato beetle, a major pest of potato crops, displays conspicuous coloration to advertise their toxicity to predators, but the identity of the toxic compounds is unclear. Here, Kang et al. show that the insect releases toxic hydrogen cyanide, which results from the degradation of cyano-compounds produced by commensal bacteria.
- Wei-Nan Kang
- , Yang Pan
- & Guo-Qing Li
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Article
| Open AccessAn evolutionarily conserved metabolite inhibits biofilm formation in Escherichia coli K-12
Methylerythritol cyclodiphosphate is an intermediate in the biosynthesis of isoprenoids in plants and bacteria, and acts as a stress signal in plants. Here, Guo et al. show that, in addition, the metabolite can inhibit biofilm formation in Escherichia coli by modulating the activity of the DNA-binding protein H-NS, thus downregulating the production of adhesive fimbriae.
- Jingzhe Guo
- , Wilhelmina T Van De Ven
- & Katayoon Dehesh
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Article
| Open AccessA widespread accessory protein family diversifies the effector repertoire of the type VI secretion system spike
It is not clear how the conserved components of bacterial type VI secretion systems (T6SSs) recognize and deliver a diverse repertoire of toxic effector proteins. Here, Colautti et al. characterize a widespread family of adaptor proteins that enable the recognition and export of structurally diverse effectors.
- Jake Colautti
- , Huagang Tan
- & John C. Whitney
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Article
| Open AccessGlycan-induced structural activation softens the human papillomavirus capsid for entry through reduction of intercapsomere flexibility
The study shows that HPV activation requires a minimum glycan length, which enlarges and softens the virus. Using virological assays, AFM, and HDX-MS, the authors propose a model explaining HPV structural activation and its role in infection.
- Yuzhen Feng
- , Dominik van Bodegraven
- & Wouter H. Roos
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Article
| Open AccessA potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F protein
In this study, the authors report a potent neutralizing antibody targeting a conserved epitope within RSV pre-F that shows higher antiviral activity against both RSV-A and -B subgroups in vitro and in small animal models than FDA-approved prophylactic agents.
- Yongpeng Sun
- , Liqin Liu
- & Ningshao Xia
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Article
| Open AccessRoot hair developmental regulators orchestrate drought triggered microbiome changes and the interaction with beneficial Rhizobiaceae
Plant microbiome confers fitness benefits upon drought. By integrating plant genetic, microbial genetic and multi-omics approaches, this work reveals the critical role of root hair developmental regulators in shaping drought alleviating microbiome.
- Zhenghong Wang
- , Zewen Li
- & Yi Song
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Article
| Open AccessTranscription regulation of African swine fever virus: dual role of M1249L
African swine fever virus (ASFV) is a contagious DNA virus causing lethal disease in swine. This study reveals structures of ASFV RNA polymerase bound to protein M1249L, showing its vital roles in regulating early transcription and packaging.
- Dongming Zhao
- , Nan Wang
- & Xiangxi Wang
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Article
| Open AccessDual receptor-binding, infectivity, and transmissibility of an emerging H2N2 low pathogenicity avian influenza virus
The authors identify one emerging H2N2 AIV, reveal the molecular basis of human-type receptor binding of the H2N2 AIV and pandemic strains, and evaluate the public risk of H2N2 AIV by its infection, transmission and mammalian-adaptation features.
- Ju Sun
- , Tianyi Zheng
- & Yuhai Bi
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Article
| Open AccessArsenic-induced enhancement of diazotrophic recruitment and nitrogen fixation in Pteris vittata rhizosphere
Elevated arsenic is found to enhance plant nitrogen acquisition and plant growth of the arsenic hyperaccumulator Pteris vittate. Multi-omics analysis reveals the interaction between root metabolites and key diazotrophs underlying this effect.
- Jiahui Lin
- , Hengyi Dai
- & Jianming Xu
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