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Indoleamides are active against drug-resistant Mycobacterium tuberculosis
New classes of antitubercular drugs are in constant demand as drug-resistant strains of Mycobacterium tuberculosis become more prevalent. Here, the authors characterize a class of drugs that are active against various M. tuberculosisstrains, including those resistant to currently used antituberculars.
- Shichun Lun
- , Haidan Guo
- & William R. Bishai
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Effectors of animal and plant pathogens use a common domain to bind host phosphoinositides
Many Gram-negative bacterial pathogens use the type III secretion system to translocate effectors into the host cell. Here, the authors characterize a bacterial phosphoinositide-binding domain, which is conserved in diverse type III effectors of both plant and animal pathogens and couples membrane localization with refolding.
- Dor Salomon
- , Yirui Guo
- & Kim Orth
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HipA-mediated antibiotic persistence via phosphorylation of the glutamyl-tRNA-synthetase
Bacterial persistence is one of the major causes of failure of antibiotic treatment, and several toxin–antitoxin modules have been linked to the persistent phenotype. Here, the authors show that HipA toxin causes growth arrest and persistence via phosphorylation of the glutamyl-tRNA-synthetase.
- Ilana Kaspy
- , Eitan Rotem
- & Gad Glaser
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A phenylalanine rotameric switch for signal-state control in bacterial chemoreceptors
Bacterial chemoreceptors regulate the kinase CheA via ligand-induced conformational changes. Using long molecular dynamics simulations, Ortega et al.show that these changes are associated with flipping of the stacked aromatic rings of highly conserved phenylalanine residues within the kinase-activating domain.
- Davi R. Ortega
- , Chen Yang
- & Igor B. Zhulin
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| Open AccessMechanisms of molecular transport through the urea channel of Helicobacter pylori
Helicobacter pylori survives in the acidic environment of the stomach by taking up urea and converting it to ammonia and carbon dioxide, which buffer the bacterial periplasm. Using molecular dynamics simulations, McNulty et al. provide insight into the mechanism of urea uptake through the H. pyloriurea transporter.
- Reginald McNulty
- , Jakob P. Ulmschneider
- & Martin B. Ulmschneider
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Highly efficient methane biocatalysis revealed in a methanotrophic bacterium
Methane is a promising renewable carbon source for chemical synthesis, yet methane bio-gas is currently underutilised as a feedstock. Here the authors examine the metabolic processes of methanotrophic bacteria to assess their use for conversion of methane to value-added chemical products.
- M. G. Kalyuzhnaya
- , S. Yang
- & M. E. Lidstrom
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VapC20 of Mycobacterium tuberculosis cleaves the Sarcin–Ricin loop of 23S rRNA
Toxin–antitoxin systems have been implicated in the pathogenicity of Mycobacterium tuberculosis. Here, the authors study the function of the M. tuberculosistoxin VapC20 and show that it can impair protein translation and inhibit bacterial growth by cleaving the Sarcin–Ricin loop of 23S rRNA
- Kristoffer S. Winther
- , Ditlev E. Brodersen
- & Kenn Gerdes
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Deoxygenation alters bacterial diversity and community composition in the ocean’s largest oxygen minimum zone
Oxygen minimum zones in the global ocean have an important role in biogeochemical cycles, yet their response to climate change is poorly understood. Here, the authors show that bacterial community composition is tightly coupled to dissolved oxygen and is likely to fundamentally change as the oceans warm.
- J. Michael Beman
- & Molly T. Carolan
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| Open AccessHorizontal gene transfer converts non-toxigenic Clostridium difficile strains into toxin producers
Clostridium difficile produces potent toxins that are encoded by its pathogenicity locus. Here, Brouwer et al. demonstrate surprising bacterial genome plasticity whereby the pathogenicity locus is transferred from toxigenic to non-toxigenic strains of C. difficileby conjugational transfer.
- Michael S.M. Brouwer
- , Adam P. Roberts
- & Peter Mullany
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Structure of GrlR–GrlA complex that prevents GrlA activation of virulence genes
The locus of enterocyte effacement is a pathogenicity island essential for virulence of some Escherichia colipathogenic serotypes. Here, the authors solve the structure of a regulatory complex that optimizes regulation of this locus during the infection process.
- Abhilash Padavannil
- , Chacko Jobichen
- & J. Sivaraman
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Implementation of stable and complex biological systems through recombinase-assisted genome engineering
Genetic engineering of bacteria is an important tool in biotechnology and synthetic biology. Here, the authors describe a method for genomic integration of complex, multi-gene sequences into bacteria and use it to create a strain of E. colithat generates ethanol from brown macroalgae.
- Christine Nicole S. Santos
- , Drew D. Regitsky
- & Yasuo Yoshikuni
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| Open AccessStructure of a helicase–helicase loader complex reveals insights into the mechanism of bacterial primosome assembly
During the initiation of bacterial DNA replication, loader proteins transfer the hexameric helicase ring onto replication origin DNA. Liu et al.report the crystal structure of a 570-kDa prepriming complex and suggest that the release of loader proteins is associated with the transition of the helicase ring to a spiral configuration.
- Bin Liu
- , William K. Eliason
- & Thomas A. Steitz
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Single-cell dynamics of the chromosome replication and cell division cycles in mycobacteria
Bacterial cell division requires the coordination of chromosome replication with cell growth and division but how these processes are coordinated in mycobacteria is largely unexplored. Santi et al. use single-cell technologies to describe the cell cycle dynamics of Mycobacterium smegmatisand outline important differences in comparison with other bacterial species.
- Isabella Santi
- , Neeraj Dhar
- & John D. McKinney
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| Open AccessWall teichoic acid structure governs horizontal gene transfer between major bacterial pathogens
Horizontal gene transfer of mobile genetic elements contributes to bacterial evolution and emergence of new pathogens. Here the authors demonstrate that the highly diverse structure of wall teichoic acid polymers governs horizontal gene transfer among Gram-positive pathogens, even across long phylogenetic distances.
- Volker Winstel
- , Chunguang Liang
- & Guoqing Xia
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| Open AccessGenome sequence and functional genomic analysis of the oil-degrading bacterium Oleispira antarctica
Oleispira antarctica is an oil-degrading bacterium found in the cold and deep sea. Here Kube et al. report the genome sequence of O. antarcticaand provide a comprehensive functional genetic and protein structural analysis, revealing insights into how this organism has adapted to its cold environment.
- Michael Kube
- , Tatyana N. Chernikova
- & Peter N. Golyshin
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Selectivity mechanism of the mechanosensitive channel MscS revealed by probing channel subconducting states
The E. colimechanosensitive channel MscS responds to hypoosmotic swelling by opening a weakly anion-selective pore. Here, the authors report that the structural determinants of this selectivity are located not in the pore, but in the large water-filled cytoplasmic domain.
- C. D. Cox
- , T. Nomura
- & B. Martinac
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CRISPR-Cas and restriction–modification systems are compatible and increase phage resistance
CRISPR-Cas and restriction–modification are two distinct bacterial defence systems that protect against phage infection. Dupuis et al. demonstrate that Streptococcus thermophilusemploys both systems simultaneously to cleave invading DNA, thereby providing enhanced phage resistance.
- Marie-Ève Dupuis
- , Manuela Villion
- & Sylvain Moineau
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| Open AccessThe crystal structure of multidrug-resistance regulator RamR with multiple drugs
RamR is an important multidrug-resistance factor, however, its structure and the molecules to which it responds are hitherto unknown. Here, the authors report the crystal structures of RamR complexed with multiple drugs, revealing significant flexibility in its substrate-recognition region.
- Suguru Yamasaki
- , Eiji Nikaido
- & Kunihiko Nishino
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A regulatory role for Staphylococcus aureus toxin–antitoxin system PemIKSa
A role of toxin–antitoxin systems in global regulation of bacterial gene expression has been proposed. Bukowski et al. now demonstrate that a novel toxin–antitoxin system from S. aureusencodes an endoribonuclease that regulates virulence gene expression by targeting translation.
- Michal Bukowski
- , Robert Lyzen
- & Benedykt Wladyka
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Short-time movement of E. coli chromosomal loci depends on coordinate and subcellular localization
The spatial and temporal organization of bacterial chromosomes is important for many cellular functions. Using high-precision measurements of fluorescently labelled chromosomal loci, Javer et al.demonstrate variation in the dynamics of different chromosomal sites, which may either be due to differential organization of the chromosome or spatial variation in molecular noise.
- Avelino Javer
- , Zhicheng Long
- & Marco Cosentino Lagomarsino
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| Open AccessDynamics and stoichiometry of a regulated enhancer-binding protein in live Escherichia coli cells
Cellular adaptive responses require temporal and spatial control of key regulatory protein complexes. Mehta et al. describe the dynamic interaction of a transcriptional activator mediating membrane stress response in E. coliwith its negative regulator, the cell membrane and the transcription machinery.
- Parul Mehta
- , Goran Jovanovic
- & Martin Buck
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Deregulation of translation due to post-transcriptional modification of rRNA explains why erm genes are inducible
Erm methyltransferases confer antimicrobial drug resistance and their expression is induced by macrolides. Gupta et al.show that Erm-catalysed modification of rRNA affects synthesis of some proteins and reduces cell fitness, explaining why expression of Erm is deleterious in the absence of antibiotics.
- Pulkit Gupta
- , Shanmugapriya Sothiselvam
- & Alexander S. Mankin
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Interspecific bacterial sensing through airborne signals modulates locomotion and drug resistance
Microbes use small molecules to sense and communicate with other cells and species. Kim et al. now demonstrate that volatile compounds emitted by Bacillus subtilis can affect Escherichia colimotility and antibiotic resistance through activation of a conserved regulatory mechanism.
- Kwang-sun Kim
- , Soohyun Lee
- & Choong-Min Ryu
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| Open AccessAuto-production of biosurfactants reverses the coffee ring effect in a bacterial system
The coffee ring effect is commonly observed in drying droplets containing suspended matter leading to a deposition at the droplet edge. Sempels et al. show that self-generated biosurfactants in living bacterial systems reverse the coffee ring effect and result in a homogeneous deposition.
- Wouter Sempels
- , Raf De Dier
- & Jan Vermant
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| Open AccessGenomic deletions disrupt nitrogen metabolism pathways of a cyanobacterial diatom symbiont
Cyanobacterial symbionts of marine diatoms can localize intracellularly or externally to their host partners. Here Hilton et al. describe the genomes of two diazotroph cyanobacterial symbionts of diatoms and show that the location of the symbiont affects expression of nitrogen assimilation genes.
- Jason A. Hilton
- , Rachel A. Foster
- & Tracy A. Villareal
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Characterizing the interplay between multiple levels of organization within bacterial sigma factor regulatory networks
Sigma factors are proteins controlling gene expression that allow bacteria to adapt to changing environmental conditions. Qiu and colleagues investigate sigma factor regulatory networks in Geobacter sulfurreducens, providing insights into how sigma factors regulate bacterial growth and energy metabolism.
- Yu Qiu
- , Harish Nagarajan
- & Karsten Zengler
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A light-driven sodium ion pump in marine bacteria
Light-driven proton-pumping rhodopsins are widely distributed in microorganisms and convert sunlight energy into proton gradients. Inoue et al. report the discovery of a light-driven sodium ion pump from marine bacteria.
- Keiichi Inoue
- , Hikaru Ono
- & Hideki Kandori
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| Open Accessβ-lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity
Sub-lethal concentrations of antibiotics are known to promote mutagenesis of bacterial DNA. Here the authors show that β-lactam antibiotics trigger mutagenesis by upregulating the stress-response protein RpoS, which downregulates mismatch-repair activity.
- A. Gutierrez
- , L. Laureti
- & I. Matic
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Engineering the type III secretion system in non-replicating bacterial minicells for antigen delivery
Bacterial type III secretion systems (T3SS) improve the delivery of vaccine antigens and antigen-specific immune responses but require the use of live vaccines. Carleton et al. report the assembly of a functional T3SS in replication-incompetent bacterial minicells that can deliver vaccine antigens in vitro and in vivo.
- Heather A. Carleton
- , María Lara-Tejero
- & Jorge E. Galán
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Actin-based confinement of calcium responses during Shigella invasion
Shigella triggers an increase in intracellular calcium during invasion of host cells. Here the authors show that increased actin polymerization at the invasion site slows the diffusion of signalling mediators, thus sustaining localized calcium influx at invasion sites.
- Guy Tran Van Nhieu
- , Bing Kai Liu
- & Laurent Combettes
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| Open AccessCell wall elongation mode in Gram-negative bacteria is determined by peptidoglycan architecture
Bacterial cell wall peptidoglycan is essential for viability and shape determination. Using high-resolution microscopy, Foster and colleagues elucidate the peptidoglycan architecture and insertion pattern in Escherichia coliand other Gram-negative bacteria, and propose a new model for cell wall elongation.
- Robert D. Turner
- , Alexander F. Hurd
- & Simon J. Foster
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Mechanism of tetracycline resistance by ribosomal protection protein Tet(O)
The bacterial tetracycline resistance protein Tet(O) binds to the ribosome, preventing tetracycline from inhibiting translation. Using cryo-electron microscopic reconstruction, the authors present an atomic model of Tet(O) bound to the 70S ribosome, and reveal how Tet(O) promotes antibiotic resistance.
- Wen Li
- , Gemma C. Atkinson
- & Joachim Frank
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Bacteroides fragilis polysaccharide A is necessary and sufficient for acute activation of intestinal sensory neurons
Commensal bacteria in gut lumen are known to interact with the enteric nervous system. Mao and colleagues test the effects of Lactobacillus rhamnosus and Bacteroides fragilis ex vivo, in the myenteric plexus, and find that the polysaccharide A is necessary for intestinal sensory neuron sensitization.
- Yu-Kang Mao
- , Dennis L. Kasper
- & Wolfgang A. Kunze
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Cytotoxicity of botulinum neurotoxins reveals a direct role of syntaxin 1 and SNAP-25 in neuron survival
Botulinum toxins can cause substantial neurodegeneration. Peng et al. study cultured rat hippocampal neurons and find that botulinum toxin-induced cytotoxicity occurs only when there is effective cleavage of the SNARE proteins, syntaxin 1 or SNAP-25, by type C and type E botulinum toxins.
- Lisheng Peng
- , Huisheng Liu
- & Min Dong
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Modular optimization of multi-gene pathways for fatty acids production in E. coli
Microbial fatty acid-derived fuels represent promising alternatives to the traditionally used fossil fuels. Koffas and colleagues report that E. colicentral metabolism can be modified to produce large quantities of fatty acids through a modular pathway engineering strategy.
- Peng Xu
- , Qin Gu
- & Mattheos A.G. Koffas
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Environmental conditions and community evenness determine the outcome of biological invasion
Biological invasion varies under different environmental stressors. Here, using a fully controlled system of bacterial communities, De Roy et al. find that community evenness affects the level of invasion, and that the community’s response depends on specific environmental conditions as well as the community evenness.
- Karen De Roy
- , Massimo Marzorati
- & Nico Boon
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Predator richness increases the effect of prey diversity on prey yield
The functioning of bacterial communities is affected by selection, but the role of predation by single or multiple predators is unclear. In a study of 465 bacterial microcosms, Saleem et al.find that multiple predation causes positive bacterial diversity effects due to increased evenness among bacterial species.
- Muhammad Saleem
- , Ingo Fetzer
- & Antonis Chatzinotas
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| Open AccessProteome-wide selected reaction monitoring assays for the human pathogen Streptococcus pyogenes
Selected reaction monitoring mass spectrometry (SRM-MS) can quantify dynamic changes in protein expression with high sensitivity. Karlsson et al. define optimal detection parameters for 10,412 distinct group A Streptococcus pyogenespeptides, which facilitates proteome-wide SRM-MS studies in this bacterium.
- Christofer Karlsson
- , Lars Malmström
- & Johan Malmström
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Competition–colonization dynamics in experimental bacterial metacommunities
Species coexistence can be explained by the competition–colonization trade-off theory. Here, Livingston et al. illustrate this theory in a metacommunity experiment using two bacterial strains, finding a negative correlation between diversity and productivity when scaled to full metacommunities.
- George Livingston
- , Miguel Matias
- & Nicolas Mouquet
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Chimpanzees and humans harbour compositionally similar gut enterotypes
Humans tend to adopt one of a limited number of different bacterial community structures in the gut, known as enterotypes. Moeller et al.now show that these microbial fingerprints are conserved in chimpanzees, and that individuals can switch between enterotypes over periods of several years.
- Andrew H. Moeller
- , Patrick H. Degnan
- & Howard Ochman
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Tyrosine sulfation in a Gram-negative bacterium
The sulfation of protein tyrosine residues is a common post-translational modification in eukaryotes. Here, Han et al.show that the protein RaxST, produced by a plant bacterium, has tyrosine sulfotransferase activity, demonstrating for the first time tyrosine sulfation in prokaryotes.
- Sang-Wook Han
- , Sang-Won Lee
- & Pamela C. Ronald
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Phylogenetic constraints on ecosystem functioning
It has been proposed that phylogenetic diversity can be used as a proxy to estimate functional diversity and to predict ecosystem functioning. Here, the rapid evolutionary response of marine bacteria is used to study the positive effects of evolutionary history and species diversity on ecosystem productivity.
- Dominique Gravel
- , Thomas Bell
- & Nicolas Mouquet
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Article
| Open AccessStructure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing
Sodium-gated ion channels open and close in response to the flow of ions. Here, McCusker et al.report the open structure of a sodium-gated ion channel pore from a bacterial homologue, and show, by comparison with the closed structure, that the movement of a C-terminal helix is sufficient to open the channel.
- Emily C. McCusker
- , Claire Bagnéris
- & B.A. Wallace
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Controlled delivery of bioactive molecules into live cells using the bacterial mechanosensitive channel MscL
The bacterial channel protein MscL opens in response to mechanical forces and could be exploited for vesicular-based drug delivery. Doerneret al. show that functional MscL can be expressed in mammalian cells and facilitate the controlled cellular uptake of relatively large, membrane-impermeable bioactive molecules.
- Julia F. Doerner
- , Sebastien Febvay
- & David E. Clapham
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Genomics of DNA cytosine methylation in Escherichia coli reveals its role in stationary phase transcription
How DNA cytosine methylation affects gene expression inEscherichia coli is poorly understood. Here, the first genome-wide study of cytosine methylation in E. coliat single-base resolution reveals that cytosine methylation controls the expression of genes during the stationary growth phase.
- Christina Kahramanoglou
- , Ana I. Prieto
- & Aswin S.N. Seshasayee
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Article
| Open AccessThe C-terminal helical bundle of the tetrameric prokaryotic sodium channel accelerates the inactivation rate
Many channels have cytosolic domains which regulate channel function. Irieet al. show that the cytosolic C-terminal region of NavSulP, a prokaryotic voltage-gated sodium channel, forms a four-helix bundle which stabilises the tetrameric channel and accelerates channel inactivation.
- Katsumasa Irie
- , Takushi Shimomura
- & Yoshinori Fujiyoshi
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Growth of non-phototrophic microorganisms using solar energy through mineral photocatalysis
Microbial metabolism is usually considered to be phototrophic or chemotrophic. By showing that light-induced photoelectrons from metal oxide and metal sulfides can stimulate the growth of chemoautotrophic and heterotrophic bacteria, this study indicates that light may be involved in non-phototrophic microbial activity.
- Anhuai Lu
- , Yan Li
- & Hailiang Dong
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Graphene-based wireless bacteria detection on tooth enamel
Graphene is characterized by unique physical properties that offer substantial promise, most notably for electronic applications. Mannooret al. present a wireless graphene-based sensor for detecting bacteria on a range of biological tissues.
- Manu S. Mannoor
- , Hu Tao
- & Michael C. McAlpine
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The GOLD domain-containing protein TMED7 inhibits TLR4 signalling from the endosome upon LPS stimulation
TLRs have a role in innate immunity and TLR4 recognizes lipopolysaccharide on the cell wall of Gram-negative bacteria. Now, Doyle and colleagues show that a transmembrane protein TMED7, similar to aDrosophilahomologue, can negatively control TLR4 signalling, suggesting a conserved role in innate immunity.
- Sarah L. Doyle
- , Harald Husebye
- & Anne F. McGettrick
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