Journal articlemSphere · May 26, 2026
UNLABELLED: During infection, pathogenic mycobacteria reside within phagosomes of varying acidity based on the macrophage activation state. The ESX-1 secretion system (early secreted antigen 6 kilodaltons [ESAT-6] system 1) delivers protein virulence facto ...
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Journal articleSci Adv · January 23, 2026
Mycobacterial granulomas lie at the center of tuberculosis (TB) pathogenesis and represent a unique niche where infecting bacteria survive under nutrient-restricted conditions and in the face of a host immune response. The granuloma's necrotic core, where ...
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Journal articlemBio · December 10, 2025
Animals defend against infections and other diseases by adaptively responding to the microbiota they encounter. These adaptations are driven by changes in gene expression programs; however, our understanding of the transcription factors regulating host res ...
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Journal articlebioRxiv · November 7, 2025
Unlike gene-first approaches to understanding bacterial pathogenesis, molecule-forward discovery can uncover unexpected chemical diversity. Here, new lipidomic analytical methods and quality metrics defined the large scope of unknown lipids in the world's ...
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Journal articlemBio · September 10, 2025
Granulomas are classic manifestations of tuberculosis pathogenesis. They result from an ensemble of immune responses to Mycobacterium tuberculosis infection, but the identities, arrangement, cellular interactions, and regulation of the cells that comprise ...
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Journal articlePLoS Biol · September 2025
Tuberculosis (TB) outcomes vary widely, from asymptomatic infection to mortality, yet most animal models do not recapitulate human phenotypic and genotypic variation. The genetically diverse Collaborative Cross mouse panel models distinct facets of TB dise ...
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Journal articleJ Bacteriol · May 22, 2025
Mycobacterium marinum is a fish pathogen that has become a powerful and well-established model that has accelerated our understanding of the mechanisms of mycobacterial disease. M. marinum is a versatile surrogate for understanding the closely related huma ...
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Journal articlePLoS Pathog · February 2025
Pathogen evolution and genomic diversity are shaped by specific host immune pressures and therapeutic interventions. Analysis of the extant genomes of circulating strains of Mycobacterium tuberculosis, a leading cause of infectious mortality that has co-ev ...
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Journal articlemBio · April 10, 2024
Bacterial pathogens use protein secretion systems to transport virulence factors and regulate gene expression. Among pathogenic mycobacteria, including Mycobacterium tuberculosis and Mycobacterium marinum, the ESAT-6 system 1 (ESX-1) secretion is crucial f ...
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Journal articleTuberculosis (Edinb) · September 2023
The Many Hosts of Mycobacteria (MHM) meeting series brings together basic scientists, clinicians and veterinarians to promote robust discussion and dissemination of recent advances in our knowledge of numerous mycobacterial diseases, including human and bo ...
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Journal articleCell Rep · December 13, 2022
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During mycobacterial infections, pathogenic mycobacteria manipulate both host immune and stromal cells to establish and maintain a productive infection. In humans, non-human primates, and zebrafish models of infection, pathogenic mycobacteria produce and m ...
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Journal articleCell · November 23, 2022
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The human pathogen Mycobacterium tuberculosis typically causes lung disease but can also disseminate to other tissues. We identified a M. tuberculosis (Mtb) outbreak presenting with unusually high rates of extrapulmonary dissemination and bone disease. We ...
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Journal articleCell · September 29, 2022
Necrosis of macrophages in the granuloma, the hallmark immunological structure of tuberculosis, is a major pathogenic event that increases host susceptibility. Through a zebrafish forward genetic screen, we identified the mTOR kinase, a master regulator of ...
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Journal articleDis Model Mech · August 1, 2022
During the current COVID-19 pandemic, there has been renewed scientific and public focus on understanding the pathogenesis of infectious diseases and investigating vaccines and therapies to combat them. In addition to the tragic toll of severe acute respir ...
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Journal articleImmunity · May 10, 2022
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In this issue of Immunity,Gideon et al. (2022) couple sophisticated single-cell analyses with detailed in vivo measurements of Mycobacterium tuberculosis granulomas to define the cellular and transcriptional properties of a successful host immune response ...
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Journal articlePathog Dis · April 29, 2022
Mycobacterial granuloma formation involves significant stromal remodeling including the growth of leaky, granuloma-associated vasculature. These permeable blood vessels aid mycobacterial growth, as antiangiogenic or vascular normalizing therapies are benef ...
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Journal articleCell Syst · November 17, 2021
Improved therapies for tuberculosis will require the careful revision of complex, multi-drug regimens. In this issue of Cell Systems, Larkins-Ford et al. integrate extensive dose-response measurements of drug combinations, in vivo animal data, and computat ...
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Journal articleClin Infect Dis · June 15, 2021
BACKGROUND: Nontuberculous mycobacteria (NTM) are a rare cause of infectious tenosynovitis of the upper extremity. Using molecular methods, clinical microbiology laboratories are increasingly reporting identification down to the species level. Improved met ...
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Journal articleJ Cell Sci · April 15, 2021
CRISPR/Cas9-based tissue-specific knockout techniques are essential for probing the functions of genes in embryonic development and disease using zebrafish. However, the lack of capacity to perform gene-specific rescue or live imaging in the tissue-specifi ...
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Journal articleCell · April 1, 2021
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The central pathogen-immune interface in tuberculosis is the granuloma, a complex host immune structure that dictates infection trajectory and physiology. Granuloma macrophages undergo a dramatic transition in which entire epithelial modules are induced an ...
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Journal articleProc Natl Acad Sci U S A · March 9, 2021
Adjunctive treatment with antiinflammatory corticosteroids like dexamethasone increases survival in tuberculosis meningitis. Dexamethasone responsiveness associates with a C/T variant in Leukotriene A4 Hydrolase (LTA4H), which regulates expression of the p ...
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Journal articleJ Clin Invest · March 1, 2021
Nearly 140 years after Robert Koch discovered Mycobacterium tuberculosis, tuberculosis (TB) remains a global threat and a deadly human pathogen. M. tuberculosis is notable for complex host-pathogen interactions that lead to poorly understood disease states ...
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Journal article · 2021
Mycobacterial granuloma formation involves significant stromal remodeling and the growth of leaky, granuloma-associated vasculature. These permeable blood vessels aid mycobacterial growth, as anti-angiogenic or vascular normalizing therapies are beneficial ...
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Journal articleJ Leukoc Biol · February 2020
Discussion on an unusual role for a cxcr3 receptor, in which it antagonizes a paralogous receptor to limit macrophage migration. ...
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Journal articlePLoS One · 2020
Lipids represent an important source of nutrition for infecting mycobacteria, accumulating within the necrotic core of granulomas and present in foamy macrophages associated with mycobacterial infection. In order to better understand the timing, process an ...
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Journal article · 2020
Tissue-specific knockout techniques are widely applied in biological studies to probe the tissue-specific roles of specific genes in physiology, development, and disease. CRISPR/Cas9 is a widely used technology to perform fast and efficient genome editing ...
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Journal article · 2020
ABSTRACT Adjunctive treatment with anti-inflammatory corticosteroids like dexamethasone increases survival in tuberculosis meningitis. Dexamethasone responsiveness associates with a C/T variant in Leukotriene A4 Hydrolase (LTA4H ), which regulat ...
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Journal articleProc Natl Acad Sci U S A · August 20, 2019
Intestinal epithelial cell (IEC) shedding is a fundamental response to intestinal damage, yet underlying mechanisms and functions have been difficult to define. Here we model chronic intestinal damage in zebrafish larvae using the nonsteroidal antiinflamma ...
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Journal articleJ Infect Dis · July 2, 2019
BACKGROUND: Infection-induced thrombocytosis is a clinically important complication of tuberculosis infection. Recent studies have highlighted the utility of aspirin as a host-directed therapy modulating the inflammatory response to infection but have not ...
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Journal articleDis Model Mech · March 7, 2019
Five years after the launch of the Disease Models & Mechanisms (DMM) Special Issue on zebrafish as a disease model, the field has progressed significantly. Zebrafish have been used to precisely model human genetic variants, to unpick the mechanisms of meta ...
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Journal articlePLoS Pathog · March 2019
The intestinal microbiota influences the development and function of myeloid lineages such as neutrophils, but the underlying molecular mechanisms are unresolved. Using gnotobiotic zebrafish, we identified the immune effector Serum amyloid A (Saa) as one o ...
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Journal articleElife · January 29, 2019
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Mycobacterium tuberculosis is the leading worldwide cause of death due to a single infectious agent. Existing anti-tuberculous therapies require long treatments and are complicated by multi-drug-resistant strains. Host-directed therapies have been proposed ...
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Journal articleFront Immunol · 2019
Over the past 200 years, tuberculosis (TB) has caused more deaths than any other infectious disease, likely infecting more people than it has at any other time in human history. Mycobacterium tuberculosis (Mtb), the etiologic agent of TB, is an obligate hu ...
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Journal articleNat Methods · December 2018
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A central and critical structure in tuberculosis, the mycobacterial granuloma consists of highly organized immune cells, including macrophages that drive granuloma formation through a characteristic epithelioid transformation. Difficulties in imaging withi ...
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Journal articleCell Host Microbe · October 10, 2018
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Mycobacterial infection leads to the formation of characteristic immune aggregates called granulomas, a process accompanied by dramatic remodeling of the host vasculature. As granuloma angiogenesis favors the infecting mycobacteria, it may be actively prom ...
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Journal articleNat Immunol · June 2018
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Tuberculous meningitis is a serious, life-threatening disease affecting vulnerable populations, including HIV-infected individuals and young children. The US National Institutes of Health convened a workshop to identify knowledge gaps in the molecular and ...
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Journal articleGenome Announc · February 15, 2018
Whole-genome sequencing has resulted in new insights into the phylogeography of Mycobacterium tuberculosis However, only limited genomic data are available from M. tuberculosis strains in Guatemala. Here we report 16 complete genomes of clinical strains be ...
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Journal article · 2018
Infection-induced thrombocytosis is a clinically important complication of tuberculosis (TB). Recent studies have separately highlighted a correlation of platelet activation with TB severity and utility of aspirin as a host-directed therapy for TB that mod ...
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Journal article · 2018
The intestinal microbiota influence diverse aspects of host physiology, including the development and function of myeloid lineages. Numerous host and microbial factors are known to poise neutrophils and other granulocytes for response to pathogens and dang ...
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Journal articleNat Rev Neurol · October 2017
Tuberculosis remains a global health problem, with an estimated 10.4 million cases and 1.8 million deaths resulting from the disease in 2015. The most lethal and disabling form of tuberculosis is tuberculous meningitis (TBM), for which more than 100,000 ne ...
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Journal articleProc Natl Acad Sci U S A · September 12, 2017
Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expedit ...
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Journal articleJ Infect Dis · March 1, 2017
Pathogenic mycobacteria trigger formation of organized granulomas. As granulomas mature, they induce angiogenesis and vascular permeability. Here, in a striking parallel to tumor pro-angiogenic signaling, we identify angiopoietin-2 (ANG-2) induction as an ...
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Journal articleMethods Cell Biol · 2017
In recent years, the zebrafish (Danio rerio) has developed as an important alternative to mammalian models for the study of hostpathogen interactions. Because they lack a functional adaptive immune response during the first 4-6weeks of development, zebrafi ...
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Journal articleImmunity · October 18, 2016
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Mycobacterium tuberculosis infection in humans triggers formation of granulomas, which are tightly organized immune cell aggregates that are the central structure of tuberculosis. Infected and uninfected macrophages interdigitate, assuming an altered, flat ...
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Journal articlePathog Dis · October 2016
Macrophages play a central role in mycobacterial pathogenesis. Recent work has highlighted the importance of diverse macrophage types and phenotypes that depend on local environment and developmental origins. In this review, we highlight how distinct macro ...
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Journal articleCell · March 24, 2016
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A zebrafish genetic screen for determinants of susceptibility to Mycobacterium marinum identified a hypersusceptible mutant deficient in lysosomal cysteine cathepsins that manifests hallmarks of human lysosomal storage diseases. Under homeostatic condition ...
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Journal articleMethods Mol Biol · 2016
Zebrafish larvae are a powerful platform for studying the innate immune response to infection. The small size and optical transparency of larval zebrafish allow for multiple subject, multidimensional, and longitudinal imaging experiments. This chapter desc ...
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Journal articleCell Rep · December 15, 2015
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Calcium signaling has long been associated with key events of immunity, including chemotaxis, phagocytosis, and activation. However, imaging and manipulation of calcium flux in motile immune cells in live animals remain challenging. Using light-sheet micro ...
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Journal articleTuberculosis (Edinb) · December 2015
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Limited data are available regarding the molecular epidemiology of Mycobacterium tuberculosis (Mtb) strains circulating in Guatemala. Beijing-lineage Mtb strains have gained prevalence worldwide and are associated with increased virulence and drug resistan ...
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Journal articleDis Model Mech · December 2015
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Visualization of infection and the associated host response has been challenging in adult vertebrates. Owing to their transparency, zebrafish larvae have been used to directly observe infection in vivo; however, such larvae have not yet developed a functio ...
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Journal articlemBio · September 29, 2015
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UNLABELLED: The human fungal pathogen Cryptococcus neoformans is capable of infecting a broad range of hosts, from invertebrates like amoebas and nematodes to standard vertebrate models such as mice and rabbits. Here we have taken advantage of a zebrafish ...
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Journal articleGenome Biol · September 15, 2015
Meta-analyses of genome-wide association studies (GWAS) have demonstrated that the same genetic variants can be associated with multiple diseases and other complex traits. We present software called CPAG (Cross-Phenotype Analysis of GWAS) to look for simil ...
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Journal articleClin Vaccine Immunol · July 2015
The well-established safety profile of the tuberculosis vaccine strain, Mycobacterium bovis bacille Calmette-Guérin (BCG), makes it an attractive vehicle for heterologous expression of antigens from clinically relevant pathogens. However, successful genera ...
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Journal articleCold Spring Harb Perspect Med · May 18, 2015
Host-directed therapies are a relatively new and promising approach to treatment of tuberculosis. Modulation of specific host immune pathways, including those that impact inflammation and immunopathology, can limit mycobacterial infection and pathology, bo ...
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Journal articleProc Natl Acad Sci U S A · March 3, 2015
The intestinal epithelium forms a barrier protecting the organism from microbes and other proinflammatory stimuli. The integrity of this barrier and the proper response to infection requires precise regulation of powerful immune homing signals such as tumo ...
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Journal articleImmunol Rev · March 2015
Recent work in a variety of animal models, including mice, zebrafish, and macaques, as well as in humans, has led to a reassessment of several tenets of mycobacterial infection. In this review, we describe new findings about the composition and dynamics of ...
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Journal articleNature · January 29, 2015
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Pathogenic mycobacteria induce the formation of complex cellular aggregates called granulomas that are the hallmark of tuberculosis. Here we examine the development and consequences of vascularization of the tuberculous granuloma in the zebrafish-Mycobacte ...
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Journal articleNature · January 29, 2015
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Pathogenic mycobacteria induce the formation of complex cellular aggregates called granulomas that are the hallmark of tuberculosis. Here we examine the development and consequences of vascularization of the tuberculous granuloma in the zebrafish-Mycobacte ...
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Journal articlePLoS One · 2015
Transgenic labeling of innate immune cell lineages within the larval zebrafish allows for real-time, in vivo analyses of microbial pathogenesis within a vertebrate host. To date, labeling of zebrafish macrophages has been relatively limited, with the most ...
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Journal articleDis Model Mech · July 2014
Despite efforts to generate new vaccines and antibiotics for tuberculosis, the disease remains a public health problem worldwide. The zebrafish Danio rerio has emerged as a useful model to investigate mycobacterial pathogenesis and treatment. Infection of ...
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Journal articleZebrafish · February 2014
Mycobacterium chelonae is widespread in aquatic environments and can cause mycobacteriosis with low virulence in zebrafish. The risk of infection in zebrafish is exacerbated in closed-recirculating aquatic systems where rapidly growing mycobacteria can liv ...
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Journal articleNature · January 9, 2014
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The evolutionary survival of Mycobacterium tuberculosis, the cause of human tuberculosis, depends on its ability to invade the host, replicate, and transmit infection. At its initial peripheral infection site in the distal lung airways, M. tuberculosis inf ...
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Journal articleNature · 2014
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The evolutionary survival of Mycobacterium tuberculosis, the cause of human tuberculosis, depends on its ability to invade the host, replicate, and transmit infection. At its initial peripheral infection site in the distal lung airways, M. tuberculosis inf ...
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Journal articlePLoS One · 2014
MicroRNAs are expressed by all multicellular organisms and play a critical role as post-transcriptional regulators of gene expression. Moreover, different microRNA species are known to influence the progression of a range of different diseases, including c ...
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Journal articleCurr Opin Pharmacol · August 2013
There is a growing appreciation of the diverse roles that lipid mediators play in modulating inflammatory responses during infection. In the case of tuberculosis, virulent mycobacteria induce host production of anti-inflammatory mediators, including lipoxi ...
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Journal articlePLoS One · 2013
While tuberculosis susceptibility has historically been ascribed to failed inflammation, it is now known that an excess of leukotriene A4 hydrolase (LTA4H), which catalyzes the final step in leukotriene B4 (LTB4) synthesis, produces a hyperinflammatory sta ...
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Journal articleCell · February 3, 2012
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Susceptibility to tuberculosis is historically ascribed to an inadequate immune response that fails to control infecting mycobacteria. In zebrafish, we find that susceptibility to Mycobacterium marinum can result from either inadequate or excessive acute i ...
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Journal articleCell · March 5, 2010
Exposure to Mycobacterium tuberculosis produces varied early outcomes, ranging from resistance to infection to progressive disease. Here we report results from a forward genetic screen in zebrafish larvae that identify multiple mutant classes with distinct ...
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Journal articleCell Microbiol · May 2008
A thorough understanding of Mycobacterium tuberculosis pathogenesis in humans has been elusive in part because of imperfect surrogate laboratory hosts, each with its own idiosyncrasies. Mycobacterium marinum is the closest genetic relative of the M. tuberc ...
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Journal articleJ Neurobiol · October 2004
Genetic analysis of nociceptive behaviors in the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster has led to the discovery of conserved sensory transduction channels and signaling molecules. These are embedded in neurons and circui ...
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Journal articleProc Natl Acad Sci U S A · November 25, 2003
All animals detect osmotic and mechanical stimuli, but the molecular basis for these responses is incompletely understood. The vertebrate transient receptor potential channel vanilloid subfamily 4 (TRPV4) (VR-OAC) cation channel has been suggested to be an ...
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Journal articleNature · October 31, 2002
Natural Caenorhabditis elegans isolates exhibit either social or solitary feeding on bacteria. We show here that social feeding is induced by nociceptive neurons that detect adverse or stressful conditions. Ablation of the nociceptive neurons ASH and ADL t ...
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Journal articleNeuron · July 18, 2002
C. elegans OSM-9 is a TRPV channel protein involved in sensory transduction and adaptation. Here, we show that distinct sensory functions arise from different combinations of OSM-9 and related OCR TRPV proteins. Both OSM-9 and OCR-2 are essential for sever ...
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Journal articleMol Biol Cell · September 2000
The Caenorhabditis elegans sax-1 gene regulates several aspects of neuronal cell shape. sax-1 mutants have expanded cell bodies and ectopic neurites in many classes of neurons, suggesting that SAX-1 functions to restrict cell and neurite growth. The ectopi ...
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