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| Open AccessVariability of plasmid fitness effects contributes to plasmid persistence in bacterial communities
The variability of plasmid fitness effects on wild-type bacterial hosts have been largely unknown until this study, which shows that plasmid persistence increases with bacterial diversity and becomes less dependent on conjugation. This could explain why plasmids remain so common in nature.
- Aida Alonso-del Valle
- , Ricardo León-Sampedro
- & Alvaro San Millán
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Article
| Open AccessGenomic analyses of Mycobacterium tuberculosis from human lung resections reveal a high frequency of polyclonal infections
Polyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. Here, Moreno-Molina et al. analyse sputum and surgical resections from tuberculosis patients, showing that the magnitude of polyclonal infections can be underestimated when only testing sputum samples.
- Miguel Moreno-Molina
- , Natalia Shubladze
- & Iñaki Comas
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Article
| Open AccessTaxonomic signatures of cause-specific mortality risk in human gut microbiome
Gut microbiome composition has a role in health and disease. Here the authors show that microbiome signatures related to the Enterobacteriaceae family are associated with cause-specific mortality risk in a well phenotyped Finish population over a 15-year follow-up.
- Aaro Salosensaari
- , Ville Laitinen
- & Teemu Niiranen
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Article
| Open AccessSingle-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines
Ebola virus glycoprotein (GP) is a major target for vaccine design. Here, the authors identify mutations to improve GP stability and yield, design two multilayered nanoparticle carriers, and demonstrate good immunogenicity of the modified GP on nanoparticles in mice and rabbits.
- Linling He
- , Anshul Chaudhary
- & Jiang Zhu
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Article
| Open AccessA SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes
Antibodies against SARS-CoV-2 S protein can provide a treatment strategy for COVID-19. Here, Guo et al. provide the crystal structure of a SARS-CoV2 neutralizing antibody isolated from a convalescent patient and highlight the therapeutic efficacy in a rhesus monkey model of an engineered version with optimized pharmacokinetic and safety profile.
- Yu Guo
- , Lisu Huang
- & Zihe Rao
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Article
| Open AccessThe RNA binding protein FgRbp1 regulates specific pre-mRNA splicing via interacting with U2AF23 in Fusarium
Human RBM42 associates with the spliceosome complex. Here the authors show that the fungus counterpart of RBM42, FgRbp1 regulates splicing by interacting with FgU2AF23.
- Minhui Wang
- , Tianling Ma
- & Zhonghua Ma
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Article
| Open AccessMacrocyclic peptides exhibit antiviral effects against influenza virus HA and prevent pneumonia in animal models
Here, the authors report bi-functional, wide tropic macrocycles that bind the influenza viral envelope protein hemagglutinin and inhibit virus infection by blocking adsorption and fusion and show efficacy in preventing severe pneumonia at later stages of infection in mouse and non-human primate cynomolgus macaque models.
- Makoto Saito
- , Yasushi Itoh
- & Michinori Kohara
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Article
| Open AccessSARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes
The SARS-CoV-2 gene set remains unresolved, hindering dissection of COVID-19 biology. Comparing 44 Sarbecovirus genomes provides a high-confidence protein-coding gene set. The study characterizes protein-level and nucleotide-level evolutionary constraints, and prioritizes functional mutations from the ongoing COVID-19 pandemic.
- Irwin Jungreis
- , Rachel Sealfon
- & Manolis Kellis
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Article
| Open AccessGlobal population structure and genotyping framework for genomic surveillance of the major dysentery pathogen, Shigella sonnei
Whole genome sequencing is increasingly being adopted for Shigella sonnei outbreak investigation and surveillance, but there is no global classification standard. Here, the authors develop and validate a genomic framework implemented using open-source software, and demonstrate its application using surveillance data.
- Jane Hawkey
- , Kalani Paranagama
- & Kathryn E. Holt
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Article
| Open AccessStructural visualization of transcription activated by a multidrug-sensing MerR family regulator
The MerR family of transcriptional regulators, such as EcmrR, activate promoters with a structure that is suboptimal for recognition by RNA polymerase holoenzyme. Structural insights into the EcmrR-dependent transcription process elucidate the mechanisms enabling optimal promoter recognition and transition from initiation to elongation.
- Yang Yang
- , Chang Liu
- & Bin Liu
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Article
| Open AccessA SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation
While SARS-CoV-2 S protein targeting monoclonal antibodies (mAbs) are well studied, little is known about N protein-targeting mAbs. Here, Kang et al. provide the crystal structure of the N protein RNA binding domain with a mAb derived from a convalescent patient and show that it compromises the N protein-induced complement hyperactivation.
- Sisi Kang
- , Mei Yang
- & Shoudeng Chen
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Article
| Open AccessGut microbiome modulates Drosophila aggression through octopamine signaling
The gut microbiome regulates behaviour in a number of species. Here the authors show that depletion of the gut microbiome in Drosophila reduced aggressive behaviour, in an octopamine-dependent manner.
- Yicong Jia
- , Shan Jin
- & Wei Liu
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Review Article
| Open AccessEmerging concepts in intestinal immune control of obesity-related metabolic disease
At the centre of intestinal health and the fight against obesity and metabolic syndrome is the intestinal microbiota and its interaction with our immune systems. Here the authors Review the current understanding of how these systems interact and how we can capitalize on recent advances to provide better therapeutic options.
- Saad Khan
- , Helen Luck
- & Daniel A. Winer
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Article
| Open AccessAn infection-induced RhoB-Beclin 1-Hsp90 complex enhances clearance of uropathogenic Escherichia coli
Bacterial invasion can lead to multiple host cell responses. Here, the authors show that in a model of uropathogenic E. coli, RhoB is upregulated and induces autophagosome formation in a complex with Beclin1 and Hsp90, promoting bacterial clearance.
- Chunhui Miao
- , Mingyu Yu
- & Quan Wang
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Article
| Open AccessA peptidoglycan storm caused by β-lactam antibiotic’s action on host microbiota drives Candida albicans infection
A risk factor for invasive Candida albicans infection is the use of broad-spectrum antibiotics, but the reasons are poorly understood. Here, the authors show in mice that β-lactam antibiotics cause commensal bacteria to release peptidoglycan fragments that induce the invasive hyphal growth of C. albicans, leading to systemic dissemination.
- Chew Teng Tan
- , Xiaoli Xu
- & Yue Wang
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Article
| Open AccessInterplay of two transcription factors for recruitment of the chromatin remodeling complex modulates fungal nitrosative stress response
Plant and animal tissues produce nitric oxide and reactive nitrogen species that induce nitrosative stress in pathogens. Here, Jian et al. identify two transcriptional regulators in the phytopathogen Fusarium graminearum that control the nitrosative stress response by modulating the recruitment of a chromatin-remodelling complex at the promoters of the response genes.
- Yunqing Jian
- , Zunyong Liu
- & Zhonghua Ma
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Article
| Open AccessStructures of flavivirus RNA promoters suggest two binding modes with NS5 polymerase
Flaviviruses use a ~70 nucleotide stem-loop structure called stem-loop A (SLA) at the 5’ end of the RNA genome as a promoter for RNA synthesis by the viral polymerase NS5. Here the authors describe the structures of dengue and Zika virus SLAs, identify the SLA-binding site on NS5, and propose models for how NS5 recognizes the RNA promoter.
- Eunhye Lee
- , Paul J. Bujalowski
- & Kyung H. Choi
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Article
| Open AccessIFN-γ-dependent NK cell activation is essential to metastasis suppression by engineered Salmonella
Cancer metastasis is one of the major causes of cancer related deaths and there is an urgent need to find more clinically effective metastasis targeting agents. Here, the authors show that Salmonella YB1 inhibits metastasis in multiple mouse models of cancer through a mechanism dependent on IFN-γ and NK cells.
- Qiubin Lin
- , Li Rong
- & Jian-Dong Huang
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Article
| Open AccessHuman kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to acute kidney injury. The authors describe that SARS-COV-2 can directly infect human kidney, possibly mediating tubular pathogenesis.
- Bo Diao
- , Chenhui Wang
- & Yongwen Chen
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Article
| Open AccessPopulation genomics provides insights into the evolution and adaptation to humans of the waterborne pathogen Mycobacterium kansasii
Mycobacterium kansasii can cause serious pulmonary disease. Here, the authors present a population genomics analysis of 358 environmental and clinical isolates from around the world, supporting the idea that municipal water is a main source of infection, and shedding light into the pathogen’s diversity and adaptation to the human host.
- Tao Luo
- , Peng Xu
- & Qian Gao
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Article
| Open AccessSelective cell death in HIV-1-infected cells by DDX3 inhibitors leads to depletion of the inducible reservoir
DEAD-box polypeptide 3 (DDX3) is a host protein belonging to the family of ATP-dependent RNA helicases. Here, the authors demonstrate that DDX3 inhibitors reverse HIV-1 latency and selectively induce cell death in HIV-1-infected cell lines, primary CD4+ T cells and in CD4+ T cells from cART-suppressed people living with HIV-1.
- Shringar Rao
- , Cynthia Lungu
- & Tokameh Mahmoudi
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Article
| Open AccessEpididymal epithelium propels early sexual transmission of Zika virus in the absence of interferon signaling
Zika virus can be sexually transmitted. Here, Pletnev et al. show in an immunocompromised mouse model that the epithelial cells of the epididymis, rather than cells of the testis, vas deferens, prostate, or seminal vesicles, are the most likely source of male-to-female sexually transmitted ZIKV genomes.
- Alexander G. Pletnev
- , Olga A. Maximova
- & Konstantin A. Tsetsarkin
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Article
| Open AccessEtiological, epidemiological, and clinical features of acute diarrhea in China
Diarrhoea is a major cause of morbidity and mortality in China. Here, the authors present results from a large sentinel surveillance scheme from 217 hospitals in all 31 provinces in mainland China, including ~150,000 patients with acute diarrhoea and covering years 2009-2018.
- Li-Ping Wang
- , Shi-Xia Zhou
- & Jun Wang
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Article
| Open AccessDecrypting bacterial polyphenol metabolism in an anoxic wetland soil
It is thought that polyphenols inhibit organic matter decomposition in soils devoid of oxygen. Here the authors use metabolomics and genome-resolved metaproteomics to provide experimental evidence of polyphenol biodegradation and maintained soil microbial community metabolism despite anoxia.
- Bridget B. McGivern
- , Malak M. Tfaily
- & Kelly C. Wrighton
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Article
| Open AccessReductive evolution and unique predatory mode in the CPR bacterium Vampirococcus lugosii
The Candidate Phyla Radiation (CPR) constitutes a large group of bacterial lineages with small cell sizes and limited biosynthetic capabilities. Here, Moreira et al. study the biology and genome of Vampirococcus lugosii, an epibiotic parasite of other bacteria, supporting parasitism as a common lifestyle of CPR bacteria.
- David Moreira
- , Yvan Zivanovic
- & Purificación López-García
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Article
| Open AccessRapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection
Here, following a patient with severe acute Pseudomonas aeruginosa infection, the authors combine comprehensive isolate characterization from lung and gut samples (>100 isolates) and patient clinical data to provide insights into bacterial responses to antibiotic therapy.
- Rachel Wheatley
- , Julio Diaz Caballero
- & Craig MacLean
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Comment
| Open AccessBreaking new ground in antimicrobial stewardship in companion animal veterinary practice
Singleton and colleagues publish in Nature Communications an intervention study to reduce antimicrobial usage in companion animal practice. They identify significant reductions in antimicrobial usage with their more active intervention group over approximately a 6-month period. The study offers an exciting way forward to explore further the trial interventions and assess alternative methods to improve antimicrobial stewardship in veterinary practice.
- David Brodbelt
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Article
| Open AccessFtsZ treadmilling is essential for Z-ring condensation and septal constriction initiation in Bacillus subtilis cell division
Bacterial cell division by cell wall synthesis proteins is guided by treadmilling filaments of the cytoskeleton protein FtsZ. Here authors use nanofabrication, advanced microscopy, and microfluidics to resolve the function of FtsZ treadmilling in the Gram-positive model organism Bacillus subtilis.
- Kevin D. Whitley
- , Calum Jukes
- & Séamus Holden
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Article
| Open AccessHigher gametocyte production and mosquito infectivity in chronic compared to incident Plasmodium falciparum infections
In this longitudinal study of an incident (new infections) and chronic (asymptomatic infections) cohort of Plasmodium falciparum infection in children in Burkina Faso, the authors show higher gametocyte production and mosquito infectivity in chronic infections.
- Aissata Barry
- , John Bradley
- & Teun Bousema
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Article
| Open AccessForecasting the dissemination of antibiotic resistance genes across bacterial genomes
Antibiotic resistance spreads among bacteria through horizontal transfer of antibiotic resistance genes (ARGs). Here, Ellabaan et al. use a statistical approach to identify putative mobilisation elements and other features associated with ARG transfer among bacterial clades to predict the potential future dissemination of known ARGs.
- Mostafa M. H. Ellabaan
- , Christian Munck
- & Morten O. A. Sommer
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Article
| Open AccessBrockarchaeota, a novel archaeal phylum with unique and versatile carbon cycling pathways
Geothermal environments are hotspots for carbon cycling. Here, De Anda et al. reconstruct archaeal genomes from terrestrial and deep-sea geothermal sediments, and propose the classification of these microbes as a new phylum, ‘Brockarchaeota’, with unique metabolic capabilities including non-methanogenic anaerobic methylotrophy.
- Valerie De Anda
- , Lin-Xing Chen
- & Brett J. Baker
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Article
| Open AccessNon-additive microbial community responses to environmental complexity
How microbial community properties change under increasingly complex combinations of resources remains unclear. Here, the authors studied hundreds of synthetic consortia to identify the factors that govern how growth and taxonomic diversity scale with environmental complexity.
- Alan R. Pacheco
- , Melisa L. Osborne
- & Daniel Segrè
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Article
| Open AccessLeveraging community mortality indicators to infer COVID-19 mortality and transmission dynamics in Damascus, Syria
Reported COVID-19 mortality rates have been relatively low in Syria, but there has been concern about overwhelmed health systems. Here, the authors use community mortality indicators and estimate that <3% of COVID-19 deaths in Damascus were reported as of 2 September 2020.
- Oliver J. Watson
- , Mervat Alhaffar
- & Patrick Walker
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Article
| Open AccessRNA binding of Hfq monomers promotes RelA-mediated hexamerization in a limiting Hfq environment
RelA stimulates RyhB small RNA–target mRNA interaction by promoting assembly of Hfq monomers into hexamers. Here the authors show that RelA-mediated Hfq hexamerization requires an initial binding of RNA to Hfq monomers.
- Pallabi Basu
- , Maya Elgrably-Weiss
- & Shoshy Altuvia
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Article
| Open AccessCytoplasmic condensation induced by membrane damage is associated with antibiotic lethality
The detailed mechanisms of action of bactericidal antibiotics remain unclear. Here, Wong et al. show that these antibiotics induce cytoplasmic condensation through membrane damage and outflow of cytoplasmic contents, as well as accumulation of reactive metabolic by-products and lipid peroxidation, as part of their lethality.
- Felix Wong
- , Jonathan M. Stokes
- & James J. Collins
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Article
| Open AccessShort-range quorum sensing controls horizontal gene transfer at micron scale in bacterial communities
Bacterial cells often communicate by the release and detection of small diffusible molecules, a process termed quorum-sensing. Here, the authors compare the communication range of quorum-sensing systems, and identify systems that enable cells to accurately detect micron-scale changes in community composition.
- Jordi van Gestel
- , Tasneem Bareia
- & Avigdor Eldar
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Article
| Open AccessOrally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model
While vaccines protecting against SARS-CoV-2 infection are approved, currently, there are no drugs suitable for high-risk exposure use against SARS-CoV-2. Here, Rosenke et al. provide evidence that orally delivered MK-4482, a nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model.
- Kyle Rosenke
- , Frederick Hansen
- & Michael A. Jarvis
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Article
| Open AccessDefective viral genomes as therapeutic interfering particles against flavivirus infection in mammalian and mosquito hosts
Defective viral genomes (DVGs) can interfere with virus replication and provide a potential approach to control infection. Here, Rezelj et al. use a combined experimental evolution and computational approach to identify DVG sequences that optimally interfere with Zika virus infection and show antiviral activity in mice and mosquitoes.
- Veronica V. Rezelj
- , Lucía Carrau
- & Marco Vignuzzi
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Article
| Open AccessField and classroom initiatives for portable sequence-based monitoring of dengue virus in Brazil
Here, the authors present results of the ZiBRA-2 project (https://www.zibra2project.org) which is an arbovirus surveillance project, across the Midwest of Brazil using a mobile genomics laboratory, combined with a genomic surveillance training program that targeted post-graduate students, laboratory technicians, and health practitioners in universities and laboratories.
- Talita Émile Ribeiro Adelino
- , Marta Giovanetti
- & Luiz Carlos Junior Alcantara
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Article
| Open AccessProduction of itaconic acid from alkali pretreated lignin by dynamic two stage bioconversion
Lignin conversion to higher value products is essential to the economic viability of lignocellulosic biorefineries. Here, the authors demonstrate the bioconversion of alkali pretreated lignin to itaconic acid by dynamic two stage fermentation using a signal-amplified nitrogen-limitation biosensor.
- Joshua R. Elmore
- , Gara N. Dexter
- & Adam M. Guss
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Article
| Open AccessPrimary and secondary clarithromycin resistance in Helicobacter pylori and mathematical modeling of the role of macrolides
Clarithromycin is a macrolide antibiotic widely used for eradication of Helicobacter pylori infection. Here, Kocsmár et al. study clarithromycin resistance and previous macrolide consumption in 4,744 H. pylori-infected patients, shedding light into the sources of primary resistant cases and the role played by prior consumption of macrolides for non-eradication purposes.
- Éva Kocsmár
- , György Miklós Buzás
- & Gábor Lotz
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Article
| Open AccessDiet and gut microbiome enterotype are associated at the population level in African buffalo
There are stable relationships between diet and microbiome in humans and lab animals. A study on African buffalo finds that diet influences microbiome variation and enterotype formation. Three pathogens may associate with microbiome depending on host diet, suggesting nutrition impacts relationships between gut microbiome and host health.
- Claire E. Couch
- , Keaton Stagaman
- & Anna E. Jolles
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Article
| Open AccessThe effect of eviction moratoria on the transmission of SARS-CoV-2
Massive unemployment during the COVID-19 pandemic could result in an eviction crisis in US cities. Here, the authors model the effect of evictions on SARS-CoV-2 epidemics, simulating viral transmission within and among households in a theoretical and applied urban settings.
- Anjalika Nande
- , Justin Sheen
- & Alison L. Hill
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Article
| Open AccessMicrobiota-based markers predictive of development of Clostridioides difficile infection
Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhoea (AAD); however, markers predictive of CDI or AAD development are as yet lacking. Here, to identify markers predictive of CDI, the authors profile the intestinal microbiota of 945 hospitalised patients from 34 hospitals in 6 different European countries and show distinct microbiota enriched in Enterococcus and depleted of Ruminococcus, Blautia, Prevotella and Bifidobacterium compared to non-CDI patients.
- Matilda Berkell
- , Mohamed Mysara
- & Odile Launay
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Article
| Open AccessDirect 1,3-butadiene biosynthesis in Escherichia coli via a tailored ferulic acid decarboxylase mutant
Microorganisms cannot naturally produce 1,3-butadiene, an important monomer for synthetic rubber and plastic production, using glucose as carbon source. Here, the authors combine the cis,cis-muconic acid-production pathway and tailor ferulic acid decarboxylase mutations to achieve its production in E. coli.
- Yutaro Mori
- , Shuhei Noda
- & Akihiko Kondo
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Article
| Open AccessOrganic matter mineralization in modern and ancient ferruginous sediments
The conditions that shaped Earth’s evolution during the Archaean and Proterozoic Eons remain unknown. Using Lake Towuti in Indonesia as an analog of early oceans the authors find that microbial methanogenesis exerts a strong influence with important implications for the composition of Earth’s early atmosphere.
- André Friese
- , Kohen Bauer
- & Jens Kallmeyer
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Article
| Open AccessThe Botrytis cinerea Crh1 transglycosylase is a cytoplasmic effector triggering plant cell death and defense response
Crh proteins catalyze crosslinking of chitin and glucan polymers in fungal cell walls. Here, Bi et al. show that a Crh protein from the phytopathogenic fungus Botrytis cinerea acts as a cytoplasmic effector and elicitor of plant defense, and plants expressing this gene exhibit reduced sensitivity to the pathogen.
- Kai Bi
- , Loredana Scalschi
- & Amir Sharon
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Article
| Open AccessHuman anogenital monocyte-derived dendritic cells and langerin+cDC2 are major HIV target cells
Epithelial tissue mononuclear phagocytes (MNP) can transmit HIV to CD4 T cells, but less is known about sub-epithelial cells. Here, the authors describe MNPs in human anogenital and colorectal tissues and find that CD14+CD1c+ monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 preferentially take up and transmit HIV.
- Jake W. Rhodes
- , Rachel A. Botting
- & Andrew N. Harman
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Article
| Open AccessActivation mechanism of a small prototypic Rec-GGDEF diguanylate cyclase
As part of two-component systems, diguanylate cyclases (DGCs) are activated by phosphorylation. Structural and computational analyses of DgcR, a model DGC, reveal the phosphorylation-induced conformational changes and the activation mechanism likely shared by many DGCs with N-terminal coiled-coil linkers.
- Raphael D. Teixeira
- , Fabian Holzschuh
- & Tilman Schirmer
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