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Sample records for article pathogen pathway

  1. FY2003 LDRD Final Annual Report Article: Pathogen Pathway Project

    SciTech Connect

    Fitch, J P; McCutchen-Maloney, S L

    2003-11-10

    Understanding virulence mechanisms of bacterial pathogens is vital to anticipating biological threats and to improving detectors, vaccines, and treatments. This project will characterize factors responsible for virulence of Yersinia pestis, the causative agent of plague and a biothreat agent, which has an inducible Type III secretion virulence mechanism also found in other animal, plant, and human pathogens. Our approach relies on genomic and proteomic characterization of Y. pestis in addition to a bioinformatic infrastructure. Scientific and technical capabilities developed in this project can be applied to other microbes of interest. This work will establish a significant new direction for biodefense at LLNL and expand our national and international scientific collaborations.

  2. Innate immunity in Drosophila: Pathogens and pathways

    PubMed Central

    Govind, Shubha

    2009-01-01

    Following in the footsteps of traditional developmental genetics, research over the last 15 years has shown that innate immunity against bacteria and fungi is governed largely by two NF-κB signal transduction pathways, Toll and IMD. Antiviral immunity appears to stem from RNA interference, whereas resistance against parasitoids is conferred by Toll signaling. The identification of these post-transcriptional regulatory mechanisms and the annotation of most Drosophila immunity genes have derived from functional genomic studies using “model” pathogens, intact animals and cell lines. The D. melanogaster host has thus provided the core information that can be used to study responses to natural microbial and metazoan pathogens as they become identified, as well as to test ideas of selection and evolutionary change. These analyses are of general importance to understanding mechanisms of other insect host–pathogen interactions and determinants of variation in host resistance. PMID:20485470

  3. Phytohormone pathways as targets of pathogens to facilitate infection.

    PubMed

    Ma, Ka-Wai; Ma, Wenbo

    2016-08-01

    Plants are constantly threatened by potential pathogens. In order to optimize the output of defense against pathogens with distinct lifestyles, plants depend on hormonal networks to fine-tune specific responses and regulate growth-defense tradeoffs. To counteract, pathogens have evolved various strategies to disturb hormonal homeostasis and facilitate infection. Many pathogens synthesize plant hormones; more importantly, toxins and effectors are produced to manipulate hormonal crosstalk. Accumulating evidence has shown that pathogens exert extensive effects on plant hormone pathways not only to defeat immunity, but also modify habitat structure, optimize nutrient acquisition, and facilitate pathogen dissemination. In this review, we summarize mechanisms by which a wide array of pathogens gain benefits from manipulating plant hormone pathways.

  4. Intervention of Phytohormone Pathways by Pathogen Effectors[OPEN

    PubMed Central

    Kazan, Kemal; Lyons, Rebecca

    2014-01-01

    The constant struggle between plants and microbes has driven the evolution of multiple defense strategies in the host as well as offense strategies in the pathogen. To defend themselves from pathogen attack, plants often rely on elaborate signaling networks regulated by phytohormones. In turn, pathogens have adopted innovative strategies to manipulate phytohormone-regulated defenses. Tactics frequently employed by plant pathogens involve hijacking, evading, or disrupting hormone signaling pathways and/or crosstalk. As reviewed here, this is achieved mechanistically via pathogen-derived molecules known as effectors, which target phytohormone receptors, transcriptional activators and repressors, and other components of phytohormone signaling in the host plant. Herbivores and sap-sucking insects employ obligate pathogens such as viruses, phytoplasma, or symbiotic bacteria to intervene with phytohormone-regulated defenses. Overall, an improved understanding of phytohormone intervention strategies employed by pests and pathogens during their interactions with plants will ultimately lead to the development of new crop protection strategies. PMID:24920334

  5. Interactions of pathogen-containing compartments with the secretory pathway.

    PubMed

    Canton, Johnathan; Kima, Peter E

    2012-11-01

    A subgroup of intracellular pathogens reside and replicate within membrane-bound compartments often termed pathogen-containing compartments (PCC). PCCs navigate around a wide range of host cell vesicles and organelles. In light of the perils of engaging with vesicles of the endocytic pathway, most PCCs modulate their interactions with endocytic vesicles while a few avoid those interactions. The secretory pathway constitutes another important grouping of vesicles and organelles in host cells. Although the negative consequences of engaging with the secretory pathway are not known, there is evidence that PCCs interact differentially with vesicles and organelles in this pathway as well. In this review, we consider three prokaryote pathogens and two protozoan parasites for which there is information on the interactions of their PCCs with the secretory pathway. Current understandings of the molecular interactions as well as the metabolic benefits that accompany those interactions are discussed. Not unexpectedly, our understanding of the extent of these interactions is variable. An underlying theme that is brought to the fore is that PCCs establish preferential interactions with distinct compartments of the secretory pathway.

  6. Gluconeogenesis, an essential metabolic pathway for pathogenic Francisella.

    PubMed

    Brissac, Terry; Ziveri, Jason; Ramond, Elodie; Tros, Fabiola; Kock, Stephanie; Dupuis, Marion; Brillet, Magali; Barel, Monique; Peyriga, Lindsay; Cahoreau, Edern; Charbit, Alain

    2015-10-01

    Intracellular multiplication and dissemination of the infectious bacterial pathogen Francisella tularensis implies the utilization of multiple host-derived nutrients. Here, we demonstrate that gluconeogenesis constitutes an essential metabolic pathway in Francisella pathogenesis. Indeed, inactivation of gene glpX, encoding the unique fructose 1,6-bisphosphatase of Francisella, severely impaired bacterial intracellular multiplication when cells were supplemented by gluconeogenic substrates such as glycerol or pyruvate. The ΔglpX mutant also showed a severe virulence defect in the mouse model, confirming the importance of this pathway during the in vivo life cycle of the pathogen. Isotopic profiling revealed the major role of the Embden-Meyerhof (glycolysis) pathway in glucose catabolism in Francisella and confirmed the importance of glpX in gluconeogenesis. Altogether, the data presented suggest that gluconeogenesis allows Francisella to cope with the limiting glucose availability it encounters during its infectious cycle by relying on host amino acids. Hence, targeting the gluconeogenic pathway might constitute an interesting therapeutic approach against this pathogen.

  7. Stress Signaling Pathways for the Pathogenicity of Cryptococcus

    PubMed Central

    Jung, Kwang-Woo

    2013-01-01

    Sensing, responding, and adapting to the surrounding environment are crucial for all living organisms to survive, proliferate, and differentiate in their biological niches. This ability is also essential for Cryptococcus neoformans and its sibling species Cryptococcus gattii, as these pathogens have saprobic and parasitic life cycles in natural and animal host environments. The ability of Cryptococcus to cause fatal meningoencephalitis is highly related to its capability to remodel and optimize its metabolic and physiological status according to external cues. These cues act through multiple stress signaling pathways through a panoply of signaling components, including receptors/sensors, small GTPases, secondary messengers, kinases, transcription factors, and other miscellaneous adaptors or regulators. In this minireview, we summarize and highlight the importance of several stress signaling pathways that influence the pathogenicity of Cryptococcus and discuss future challenges in these areas. PMID:24078305

  8. Pathogen-Secreted Proteases Activate a Novel Plant Immune Pathway

    PubMed Central

    Cheng, Zhenyu; Li, Jian-Feng; Niu, Yajie; Zhang, Xue-Cheng; Woody, Owen Z.; Xiong, Yan; Djonović, Slavica; Millet, Yves; Bush, Jenifer; McConkey, Brendan J.; Sheen, Jen; Ausubel, Frederick M.

    2015-01-01

    Mitogen-Activated Protein Kinase (MAPK) cascades play central roles in innate immune signaling networks in plants and animals1,2. In plants, however, the molecular mechanisms of how signal perception is transduced to MAPK activation remain elusive1. We report that pathogen-secreted proteases activate a previously unknown signaling pathway in Arabidopsis thaliana involving the Gα, Gβ and Gγ subunits of heterotrimeric G-protein complexes, which function upstream of a MAPK cascade. In this pathway, Receptor for Activated C Kinase 1 (RACK1) functions as a novel scaffold that binds to the Gβ subunit as well as to all three tiers of the MAPK cascade, thereby linking upstream G protein signaling to downstream activation of a MAPK cascade. The protease-G protein-RACK1-MAPK cascade modules identified in these studies are distinct from previously described plant immune signaling pathways such as the one elicited by bacterial flagellin, in which G proteins function downstream of or in parallel to a MAPK cascade without the involvement of the RACK1 scaffolding protein. The discovery of the novel protease-mediated immune signaling pathway described here was facilitated by the use of the broad host range, opportunistic bacterial pathogen Pseudomonas aeruginosa. The ability of P. aeruginosa to infect both plants and animals makes it an excellent model to identify novel types of immunoregulatory strategies that account for its niche adaptation to diverse host tissues and immune systems. PMID:25731164

  9. The Arginine Decarboxylase Pathways of Host and Pathogen Interact to Impact Inflammatory Pathways in the Lung

    PubMed Central

    Dalluge, Joseph J.; Welchlin, Cole W.; Hughes, John; Han, Wei; Blackwell, Timothy S.; Laguna, Theresa A.; Williams, Bryan J.

    2014-01-01

    The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both humans and most bacterial pathogens. In humans agmatine is a neurotransmitter with affinities towards α2-adrenoreceptors, serotonin receptors, and may inhibit nitric oxide synthase. In bacteria agmatine serves as a precursor to polyamine synthesis and was recently shown to enhance biofilm development in some strains of the respiratory pathogen Pseudomonas aeruginosa. We determined agmatine is at the center of a competing metabolism in the human lung during airways infections and is influenced by the metabolic phenotypes of the infecting pathogens. Ultra performance liquid chromatography with mass spectrometry detection was used to measure agmatine in human sputum samples from patients with cystic fibrosis, spent supernatant from clinical sputum isolates, and from bronchoalvelolar lavage fluid from mice infected with P. aeruginosa agmatine mutants. Agmatine in human sputum peaks during illness, decreased with treatment and is positively correlated with inflammatory cytokines. Analysis of the agmatine metabolic phenotype in clinical sputum isolates revealed most deplete agmatine when grown in its presence; however a minority appeared to generate large amounts of agmatine presumably driving sputum agmatine to high levels. Agmatine exposure to inflammatory cells and in mice demonstrated its role as a direct immune activator with effects on TNF-α production, likely through NF-κB activation. P. aeruginosa mutants for agmatine detection and metabolism were constructed and show the real-time evolution of host-derived agmatine in the airways during acute lung infection. These experiments also demonstrated pathogen agmatine production can upregulate the inflammatory response. As some clinical isolates have adapted to hypersecrete agmatine, these combined data would suggest agmatine is a novel target for immune modulation in the host-pathogen dynamic. PMID:25350753

  10. Bacterium induces cryptic meroterpenoid pathway in the pathogenic fungus Aspergillus fumigatus.

    PubMed

    König, Claudia C; Scherlach, Kirstin; Schroeckh, Volker; Horn, Fabian; Nietzsche, Sandor; Brakhage, Axel A; Hertweck, Christian

    2013-05-27

    Stimulating encounter: The intimate, physical interaction between the soil-derived bacterium Streptomyces rapamycinicus and the human pathogenic fungus Aspergillus fumigatus led to the activation of an otherwise silent polyketide synthase (PKS) gene cluster coding for an unusual prenylated polyphenol (fumicycline A). The meroterpenoid pathway is regulated by a pathway-specific activator gene as well as by epigenetic factors.

  11. Linking multiple pathogenic pathways in Alzheimer’s disease

    PubMed Central

    Bou Khalil, Rami; Khoury, Elie; Koussa, Salam

    2016-01-01

    Alzheimer’s disease (AD) is a chronic neurodegenerative disorder presenting as progressive cognitive decline with dementia that does not, to this day, benefit from any disease-modifying drug. Multiple etiologic pathways have been explored and demonstrate promising solutions. For example, iron ion chelators, such as deferoxamine, are a potential therapeutic solution around which future studies are being directed. Another promising domain is related to thrombin inhibitors. In this minireview, a common pathophysiological pathway is suggested for the pathogenesis of AD to prove that all these mechanisms converge onto the same cascade of neuroinflammatory events. This common pathway is initiated by the presence of vascular risk factors that induce brain tissue hypoxia, which leads to endothelial cell activation. However, the ensuing hypoxia stimulates the production and release of reactive oxygen species and pro-inflammatory proteins. Furthermore, the endothelial activation may become excessive and dysfunctional in predisposed individuals, leading to thrombin activation and iron ion decompartmentalization. The oxidative stress that results from these modifications in the neurovascular unit will eventually lead to neuronal and glial cell death, ultimately leading to the development of AD. Hence, future research in this field should focus on conducting trials with combinations of potentially efficient treatments, such as the combination of intranasal deferoxamine and direct thrombin inhibitors. PMID:27354962

  12. Comparative Analysis of Protein Glycosylation Pathways in Humans and the Fungal Pathogen Candida albicans

    PubMed Central

    Martínez-Duncker, Iván; Díaz-Jímenez, Diana F.; Mora-Montes, Héctor M.

    2014-01-01

    Protein glycosylation pathways are present in all kingdoms of life and are metabolic pathways found in all the life kingdoms. Despite sharing commonalities in their synthesis, glycans attached to glycoproteins have species-specific structures generated by the presence of different sets of enzymes and acceptor substrates in each organism. In this review, we present a comparative analysis of the main glycosylation pathways shared by humans and the fungal pathogen Candida albicans: N-linked glycosylation, O-linked mannosylation and glycosylphosphatidylinositol-anchorage. The knowledge of similarities and divergences between these metabolic pathways could help find new pharmacological targets for C. albicans infection. PMID:25104959

  13. The danger signal S100B integrates pathogen- and danger-sensing pathways to restrain inflammation.

    PubMed

    Sorci, Guglielmo; Giovannini, Gloria; Riuzzi, Francesca; Bonifazi, Pierluigi; Zelante, Teresa; Zagarella, Silvia; Bistoni, Francesco; Donato, Rosario; Romani, Luigina

    2011-03-01

    Humans inhale hundreds of Aspergillus conidia without adverse consequences. Powerful protective mechanisms may ensure prompt control of the pathogen and inflammation. Here we reveal a previously unknown mechanism by which the danger molecule S100B integrates pathogen- and danger-sensing pathways to restrain inflammation. Upon forming complexes with TLR2 ligands, S100B inhibited TLR2 via RAGE, through a paracrine epithelial cells/neutrophil circuit that restrained pathogen-induced inflammation. However, upon binding to nucleic acids, S100B activated intracellular TLRs eventually resolve danger-induced inflammation via transcriptional inhibition of S100B. Thus, the spatiotemporal regulation of TLRs and RAGE by S100B provides evidence for an evolving braking circuit in infection whereby an endogenous danger protects against pathogen-induced inflammation and a pathogen-sensing mechanism resolves danger-induced inflammation.

  14. Immune signaling pathways activated in response to different pathogenic micro-organisms in Bombyx mori.

    PubMed

    Liu, Wei; Liu, Jiabin; Lu, Yahong; Gong, Yongchang; Zhu, Min; Chen, Fei; Liang, Zi; Zhu, Liyuan; Kuang, Sulan; Hu, Xiaolong; Cao, Guangli; Xue, Renyu; Gong, Chengliang

    2015-06-01

    The JAK/STAT, Toll, Imd, and RNAi pathways are the major signaling pathways associated with insect innate immunity. To explore the different immune signaling pathways triggered in response to pathogenic micro-organism infections in the silkworm, Bombyx mori, the expression levels of the signal transducer and activator of transcription (BmSTAT), spatzle-1 (Bmspz-1), peptidoglycan-recognition protein LB (BmPGRP-LB), peptidoglycan-recognition protein LE (BmPGRP-LE), argonaute 2 (Bmago2), and dicer-2 (Bmdcr2) genes after challenge with Escherichia coli (E. coli), Serratiamarcescens (Sm), Bacillus bombyseptieus (Bab), Beauveriabassiana (Beb), nucleopolyhedrovirus (BmNPV), cypovirus (BmCPV), bidensovirus (BmBDV), or Nosemabombycis (Nb) were determined using real-time PCR. We found that the JAK/STAT pathway could be activated by challenge with BmNPV and BmBDV, the Toll pathway could be most robustly induced by challenge with Beb, the Imd pathway was mainly activated in response to infection by E. coli and Sm, and the RNAi pathway was not activated by viral infection, but could be triggered by some bacterial infections. These findings yield insights into the immune signaling pathways activated in response to different pathogenic micro-organisms in the silkworm.

  15. The Stress-Activated Signaling (SAS) Pathways of a Human Fungal Pathogen, Cryptococcus neoformans.

    PubMed

    Jung, Kwang-Woo; Bahn, Yong-Sun

    2009-09-01

    Cryptococcus neoformans is a basidiomycete human fungal pathogen that causes meningoencephalitis in both immunocompromised and immunocompetent individuals. The ability to sense and respond to diverse extracellular signals is essential for the pathogen to infect and cause disease in the host. Four major stress-activated signaling (SAS) pathways have been characterized in C. neoformans, including the HOG (high osmolarity glycerol response), PKC/Mpk1 MAPK (mitogen-activated protein kinase), calcium-dependent calcineurin, and RAS signaling pathways. The HOG pathway in C. neoformans not only controls responses to diverse environmental stresses, including osmotic shock, UV irradiation, oxidative stress, heavy metal stress, antifungal drugs, toxic metabolites, and high temperature, but also regulates ergosterol biosynthesis. The PKC (Protein kinase C)/Mpk1 pathway in C. neoformans is involved in a variety of stress responses, including osmotic, oxidative, and nitrosative stresses and breaches of cell wall integrity. The Ca(2+)/calmodulin- and Ras-signaling pathways also play critical roles in adaptation to certain environmental stresses, such as high temperature and sexual differentiation. Perturbation of the SAS pathways not only impairs the ability of C. neoformans to resist a variety of environmental stresses during host infection, but also affects production of virulence factors, such as capsule and melanin. A drug(s) capable of targeting signaling components of the SAS pathway will be effective for treatment of cryptococcosis.

  16. Endoscopic dacryocystorhinostomy as treatment for lower lacrimal pathway obstructions in adults: Review article

    PubMed Central

    Smirnov, Grigori; Tuomilehto, Henri; Kaarniranta, Kai; Seppä, Juha

    2015-01-01

    Obstruction of the lacrimal pathway is manifested by epiphora, infection, and blurred vision as well as ocular and facial pain. Conservative treatments only achieve temporary relief of symptoms, thus surgery is the treatment of choice. Dacryocystorhinostomy (DCR) is recognized as the most suitable treatment for patients with obstructions of the lacrimal system at the level of the sac or in the nasolacrimal duct. The aim of this operation is to create a bypass between the lacrimal sac and the nasal cavity. During the past 2 decades, advances in rigid endoscopic equipment and other instruments have made it possible to obtain more information about the anatomic landmarks of the nasolacrimal system, which led to the development of less-invasive and safer endoscopic techniques. However, many parts of the treatment process related to endoscopic endonasal dacryocystorhinostomy (EN-DCR) still remain controversial. This article reviews the published literature about the technical issues associated with the success of EN-DCR, and clarifies the pros and cons of different pre- and postoperative procedures in adults with lower lacrimal pathway obstructions. PMID:25860166

  17. Pathogens penetrating the central nervous system: infection pathways and the cellular and molecular mechanisms of invasion.

    PubMed

    Dando, Samantha J; Mackay-Sim, Alan; Norton, Robert; Currie, Bart J; St John, James A; Ekberg, Jenny A K; Batzloff, Michael; Ulett, Glen C; Beacham, Ifor R

    2014-10-01

    The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis.

  18. Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

    PubMed Central

    Dando, Samantha J.; Mackay-Sim, Alan; Norton, Robert; Currie, Bart J.; St. John, James A.; Ekberg, Jenny A. K.; Batzloff, Michael

    2014-01-01

    SUMMARY The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis. PMID:25278572

  19. The renaissance of bacillosamine and its derivatives: pathway characterization and implications in pathogenicity.

    PubMed

    Morrison, Michael J; Imperiali, Barbara

    2014-02-01

    Prokaryote-specific sugars, including N,N'-diacetylbacillosamine (diNAcBac) and pseudaminic acid, have experienced a renaissance in the past decade because of their discovery in glycans related to microbial pathogenicity. DiNAcBac is found at the reducing end of oligosaccharides of N- and O-linked bacterial protein glycosylation pathways of Gram-negative pathogens, including Campylobacter jejuni and Neisseria gonorrhoeae. Further derivatization of diNAcBac results in the nonulosonic acid known as legionaminic acid, which was first characterized in the O-antigen of the lipopolysaccharide (LPS) in Legionella pneumophila. Pseudaminic acid, an isomer of legionaminic acid, is also important in pathogenic bacteria such as Helicobacter pylori because of its occurrence in O-linked glycosylation of flagellin proteins, which plays an important role in flagellar assembly and motility. Here, we present recent advances in the characterization of the biosynthetic pathways leading to these highly modified sugars and investigation of the roles that each plays in bacterial fitness and pathogenicity.

  20. A Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP.

    PubMed

    Spanò, Stefania; Gao, Xiang; Hannemann, Sebastian; Lara-Tejero, María; Galán, Jorge E

    2016-02-10

    Cell-autonomous defense mechanisms are potent strategies that protect individual cells against intracellular pathogens. The Rab-family GTPase Rab32 was previously shown to restrict the intracellular human pathogen Salmonella Typhi, but its potential broader role in antimicrobial defense remains unknown. We show that Rab32 represents a general cell-autonomous, antimicrobial defense that is counteracted by two Salmonella effectors. Mice lacking Rab-32 or its nucleotide exchange factor BLOC-3 are permissive to S. Typhi infection and exhibit increased susceptibility to S. Typhimurium. S. Typhimurium counters this defense pathway by delivering two type III secretion effectors, SopD2, a Rab32 GAP, and GtgE, a specific Rab32 protease. An S. Typhimurium mutant strain lacking these two effectors exhibits markedly reduced virulence, which is fully restored in BLOC-3-deficient mice. These results demonstrate that a cell-autonomous, Rab32-dependent host defense pathway plays a central role in the defense against vacuolar pathogens and describe a mechanism evolved by a bacterial pathogen to counter it.

  1. The N-end rule pathway regulates pathogen responses in plants.

    PubMed

    de Marchi, Rémi; Sorel, Maud; Mooney, Brian; Fudal, Isabelle; Goslin, Kevin; Kwaśniewska, Kamila; Ryan, Patrick T; Pfalz, Marina; Kroymann, Juergen; Pollmann, Stephan; Feechan, Angela; Wellmer, Frank; Rivas, Susana; Graciet, Emmanuelle

    2016-01-01

    To efficiently counteract pathogens, plants rely on a complex set of immune responses that are tightly regulated to allow the timely activation, appropriate duration and adequate amplitude of defense programs. The coordination of the plant immune response is known to require the activity of the ubiquitin/proteasome system, which controls the stability of proteins in eukaryotes. Here, we demonstrate that the N-end rule pathway, a subset of the ubiquitin/proteasome system, regulates the defense against a wide range of bacterial and fungal pathogens in the model plant Arabidopsis thaliana. We show that this pathway positively regulates the biosynthesis of plant-defense metabolites such as glucosinolates, as well as the biosynthesis and response to the phytohormone jasmonic acid, which plays a key role in plant immunity. Our results also suggest that the arginylation branch of the N-end rule pathway regulates the timing and amplitude of the defense program against the model pathogen Pseudomonas syringae AvrRpm1. PMID:27173012

  2. The N-end rule pathway regulates pathogen responses in plants

    PubMed Central

    de Marchi, Rémi; Sorel, Maud; Mooney, Brian; Fudal, Isabelle; Goslin, Kevin; Kwaśniewska, Kamila; Ryan, Patrick T.; Pfalz, Marina; Kroymann, Juergen; Pollmann, Stephan; Feechan, Angela; Wellmer, Frank; Rivas, Susana; Graciet, Emmanuelle

    2016-01-01

    To efficiently counteract pathogens, plants rely on a complex set of immune responses that are tightly regulated to allow the timely activation, appropriate duration and adequate amplitude of defense programs. The coordination of the plant immune response is known to require the activity of the ubiquitin/proteasome system, which controls the stability of proteins in eukaryotes. Here, we demonstrate that the N-end rule pathway, a subset of the ubiquitin/proteasome system, regulates the defense against a wide range of bacterial and fungal pathogens in the model plant Arabidopsis thaliana. We show that this pathway positively regulates the biosynthesis of plant-defense metabolites such as glucosinolates, as well as the biosynthesis and response to the phytohormone jasmonic acid, which plays a key role in plant immunity. Our results also suggest that the arginylation branch of the N-end rule pathway regulates the timing and amplitude of the defense program against the model pathogen Pseudomonas syringae AvrRpm1. PMID:27173012

  3. The hijacking of a receptor kinase–driven pathway by a wheat fungal pathogen leads to disease

    PubMed Central

    Shi, Gongjun; Zhang, Zengcui; Friesen, Timothy L.; Raats, Dina; Fahima, Tzion; Brueggeman, Robert S.; Lu, Shunwen; Trick, Harold N.; Liu, Zhaohui; Chao, Wun; Frenkel, Zeev; Xu, Steven S.; Rasmussen, Jack B.; Faris, Justin D.

    2016-01-01

    Necrotrophic pathogens live and feed on dying tissue, but their interactions with plants are not well understood compared to biotrophic pathogens. The wheat Snn1 gene confers susceptibility to strains of the necrotrophic pathogen Parastagonospora nodorum that produce the SnTox1 protein. We report the positional cloning of Snn1, a member of the wall-associated kinase class of receptors, which are known to drive pathways for biotrophic pathogen resistance. Recognition of SnTox1 by Snn1 activates programmed cell death, which allows this necrotroph to gain nutrients and sporulate. These results demonstrate that necrotrophic pathogens such as P. nodorum hijack host molecular pathways that are typically involved in resistance to biotrophic pathogens, revealing the complex nature of susceptibility and resistance in necrotrophic and biotrophic pathogen interactions with plants.

  4. Population History and Pathways of Spread of the Plant Pathogen Phytophthora plurivora

    PubMed Central

    Schoebel, Corine N.; Stewart, Jane; Gruenwald, Niklaus J.; Rigling, Daniel; Prospero, Simone

    2014-01-01

    Human activity has been shown to considerably affect the spread of dangerous pests and pathogens worldwide. Therefore, strict regulations of international trade exist for particularly harmful pathogenic organisms. Phytophthora plurivora, which is not subject to regulations, is a plant pathogen frequently found on a broad range of host species, both in natural and artificial environments. It is supposed to be native to Europe while resident populations are also present in the US. We characterized a hierarchical sample of isolates from Europe and the US and conducted coalescent-, migration, and population genetic analysis of sequence and microsatellite data, to determine the pathways of spread and the demographic history of this pathogen. We found P. plurivora populations to be moderately diverse but not geographically structured. High levels of gene flow were observed within Europe and unidirectional from Europe to the US. Coalescent analyses revealed a signal of a recent expansion of the global P. plurivora population. Our study shows that P. plurivora has most likely been spread around the world by nursery trade of diseased plant material. In particular, P. plurivora was introduced into the US from Europe. International trade has allowed the pathogen to colonize new environments and/or hosts, resulting in population growth. PMID:24427303

  5. Cyanidin inhibits quorum signalling pathway of a food borne opportunistic pathogen.

    PubMed

    Gopu, Venkadesaperumal; Shetty, Prathapkumar Halady

    2016-02-01

    Quorum sensing (QS) is the process of population dependent cell to cell communication used by bacteria to regulate their phenotypic characteristics. Key virulence factors that determine the bacterial pathogenicity and food spoilage were found to be regulated by QS mechanism. Hence, disrupting the QS signaling pathway could be an attractive strategy to manage food borne pathogens. In the current study, QS inhibitory activity of a naturally occurring anthocyanin-cyanidin and its anti-biofilm property were assessed against an opportunistic pathogen Klebsiella pneumoniae, using a bio-sensor strain. Further, QS inhibitory property of a naturally occurring anthocyanin cyanidin was further confirmed using in-silico techniques like molecular docking and molecular dynamics simulation studies. Cyanidin at sub-lethal dose significantly inhibited QS-dependent phenotypes like violacein production (73.96 %), biofilm formation (72.43 %), and exopolysaccharide production (68.65) in a concentration-dependent manner. Cyanidin enhanced the sensitivity of test pathogen to conventional antibiotics in a synergistic manner. Molecular docking analysis revealed that cyanidin binds more rigidly with LasR receptor protein than the signaling compound with a docking score of -9.13 Kcal/mol. Molecular dynamics simulation predicted that QS inhibitory activity occurs through the conformational changes between the receptor and cyanidin complex. Our results indicate that cyanidin, can be a potential QS based antibiofilm and antibacterial agent for food borne pathogens. PMID:27162376

  6. Understanding pathogenic Burkholderia glumae metabolic and signaling pathways within rice tissues through in vivo transcriptome analyses.

    PubMed

    Kim, Sunyoung; Park, Jungwook; Lee, Jongyun; Shin, Dongjin; Park, Dong-Soo; Lim, Jong-Sung; Choi, Ik-Young; Seo, Young-Su

    2014-08-15

    Burkholderia glumae is a causal agent of rice grain and sheath rot. Similar to other phytopathogens, B. glumae adapts well to the host environment and controls its biology to induce diseases in the host plant; however, its molecular mechanisms are not yet fully understood. To gain a better understating of the actual physiological changes that occur in B. glumae during infection, we analyzed B. glumae transcriptome from infected rice tissues using an RNA-seq technique. To accomplish this, we analyzed differentially expressed genes (DEGs) and identified 2653 transcripts that were significantly altered. We then performed KEGG pathway and module enrichment of the DEGs. Interestingly, most genes involved bacterial chemotaxis-mediated motility, ascorbate and trehalose metabolisms, and sugar transporters including l-arabinose and d-xylose were found to be highly enriched. The in vivo transcriptional profiling of pathogenic B. glumae will facilitate elucidation of unknown plant-pathogenic bacteria interactions, as well as the overall infection processes.

  7. A functional 4-hydroxybenzoate degradation pathway in the phytopathogen Xanthomonas campestris is required for full pathogenicity

    PubMed Central

    Wang, Jia-Yuan; Zhou, Lian; Chen, Bo; Sun, Shuang; Zhang, Wei; Li, Ming; Tang, Hongzhi; Jiang, Bo-Le; Tang, Ji-Liang; He, Ya-Wen

    2015-01-01

    Plants contain significant levels of natural phenolic compounds essential for reproduction and growth, as well as defense mechanisms against pathogens. Xanthomonas campestris pv. campestris (Xcc) is the causal agent of crucifers black rot. Here we showed that genes required for the synthesis, utilization, transportation, and degradation of 4-hydroxybenzoate (4-HBA) are present in Xcc. Xcc rapidly degrades 4-HBA, but has no effect on 2-hydroxybenzoate and 3-hydroxybenzoate when grown in XOLN medium. The genes for 4-HBA degradation are organized in a superoperonic cluster. Bioinformatics, biochemical, and genetic data showed that 4-HBA is hydroxylated by 4-HBA 3-hydroxylase (PobA), which is encoded by Xcc0356, to yield PCA. The resulting PCA is further metabolized via the PCA branches of the β-ketoadipate pathway, including Xcc0364, Xcc0365, and PcaFHGBDCR. Xcc0364 and Xcc0365 encode a new form of β-ketoadipate succinyl-coenzyme A transferase that is required for 4-HBA degradation. pobA expression was induced by 4-HBA via the transcriptional activator, PobR. Radish and cabbage hydrolysates contain 2-HBA, 3-HBA, 4-HBA, and other phenolic compounds. Addition of radish and cabbage hydrolysates to Xcc culture significantly induced the expression of pobA via PobR. The 4-HBA degradation pathway is required for full pathogenicity of Xcc in radish. PMID:26672484

  8. Intracellular periodontal pathogen exploits recycling pathway to exit from infected cells.

    PubMed

    Takeuchi, Hiroki; Takada, Akihiko; Kuboniwa, Masae; Amano, Atsuo

    2016-07-01

    Although human gingival epithelium prevents intrusions by periodontal bacteria, Porphyromonas gingivalis, the most well-known periodontal pathogen, is able to invade gingival epithelial cells and pass through the epithelial barrier into deeper tissues. We previously reported that intracellular P. gingivalis exits from gingival epithelial cells via a recycling pathway. However, the underlying molecular process remains unknown. In the present study, we found that the pathogen localized in early endosomes recruits VAMP2 and Rab4A. VAMP2 was found to be specifically localized in early endosomes, although its localization remained unclear in mammalian cells. A single transmembrane domain of VAMP2 was found to be necessary and sufficient for localizing in early endosomes containing P. gingivalis in gingival epithelial cells. VAMP2 forms a complex with EXOC2/Sec5 and EXOC3/Sec6, whereas Rab4A mediates dissociation of the EXOC complex followed by recruitment of RUFY1/Rabip4, Rab4A effector, and Rab14. Depletion of VAMP2 or Rab4A resulted in accumulation of bacteria in early endosomes and disturbed bacterial exit from infected cells. It is suggested that these novel dynamics allow P. gingivalis to exploit fast recycling pathways promoting further bacterial penetration of gingival tissues.

  9. Dothistroma pini, a Forest Pathogen, Contains Homologs of Aflatoxin Biosynthetic Pathway Genes

    PubMed Central

    Bradshaw, Rosie E.; Bhatnagar, Deepak; Ganley, Rebecca J.; Gillman, Carmel J.; Monahan, Brendon J.; Seconi, Janet M.

    2002-01-01

    Homologs of aflatoxin biosynthetic genes have been identified in the pine needle pathogen Dothistroma pini. D. pini produces dothistromin, a difuranoanthraquinone toxin with structural similarity to the aflatoxin precursor versicolorin B. Previous studies with purified dothistromin suggest a possible role for this toxin in pathogenicity. By using an aflatoxin gene as a hybridization probe, a genomic D. pini clone was identified that contained four dot genes with similarity to genes in aflatoxin and sterigmatocystin gene clusters with predicted activities of a ketoreductase (dotA), oxidase (dotB), major facilitator superfamily transporter (dotC), and thioesterase (dotD). A D. pini dotA mutant was made by targeted gene replacement and shown to be severely impaired in dothistromin production, confirming that dotA is involved in dothistromin biosynthesis. Accumulation of versicolorin A (a precursor of aflatoxin) by the dotA mutant confirms that the dotA gene product is involved in an aflatoxin-like biosynthetic pathway. Since toxin genes have been found to be clustered in fungi in every case analyzed so far, it is speculated that the four dot genes may comprise part of a dothistromin biosynthetic gene cluster. A fifth gene, ddhA, is not a homolog of aflatoxin genes and could be at one end of the dothistromin cluster. These genes will allow comparative biochemical and genetic studies of the aflatoxin and dothistromin biosynthetic pathways and may also lead to new ways to control Dothistroma needle blight. PMID:12039746

  10. Crosstalk between the unfolded protein response and pathways that regulate pathogenic development in Ustilago maydis.

    PubMed

    Heimel, Kai; Freitag, Johannes; Hampel, Martin; Ast, Julia; Bölker, Michael; Kämper, Jörg

    2013-10-01

    The unfolded protein response (UPR) is a conserved eukaryotic signaling pathway regulating endoplasmic reticulum (ER) homeostasis during ER stress, which results, for example, from an increased demand for protein secretion. Here, we characterize the homologs of the central UPR regulatory proteins Hac1 (for Homologous to ATF/CREB1) and Inositol Requiring Enzyme1 in the plant pathogenic fungus Ustilago maydis and demonstrate that the UPR is tightly interlinked with the b mating-type-dependent signaling pathway that regulates pathogenic development. Exact timing of UPR is required for virulence, since premature activation interferes with the b-dependent switch from budding to filamentous growth. In addition, we found crosstalk between UPR and the b target Clampless1 (Clp1), which is essential for cell cycle release and proliferation in planta. The unusual C-terminal extension of the U. maydis Hac1 homolog, Cib1 (for Clp1 interacting bZIP1), mediates direct interaction with Clp1. The interaction between Clp1 and Cib1 promotes stabilization of Clp1, resulting in enhanced ER stress tolerance that prevents deleterious UPR hyperactivation. Thus, the interaction between Cib1 and Clp1 constitutes a checkpoint to time developmental progression and increased secretion of effector proteins at the onset of biotrophic development. Crosstalk between UPR and the b mating-type regulated developmental program adapts ER homeostasis to the changing demands during biotrophy.

  11. The cAMP/protein kinase A signaling pathway in pathogenic basidiomycete fungi: Connections with iron homeostasis

    PubMed Central

    Choi, Jaehyuk; Jung, Won Hee; Kronstad, James W.

    2015-01-01

    A number of pathogenic species of basidiomycete fungi are either life-threatening pathogens of humans or major economic pests for crop production. Sensing the host is a key aspect of pathogen proliferation during disease, and signal transduction pathways are critically important for detecting environmental conditions and facilitating adaptation. This review focuses on the contributions of the cAMP/protein kinase A (PKA) signaling pathway in Cryptococcus neoformans, a species that causes meningitis in humans, and Ustilago maydis, a model phytopathogen that causes a smut disease on maize. Environmental sensing by the cAMP/PKA pathway regulates the production of key virulence traits in C. neoformans including the polysaccharide capsule and melanin. For U. maydis, the pathway controls the dimorphic transition from budding growth to the filamentous cell type required for proliferation in plant tissue. We discuss recent advances in identifying new components of the cAMP/PKA pathway in these pathogens and highlight an emerging theme that pathway signaling influences iron acquisition. PMID:26231374

  12. Aryl hydrocarbon receptor knock-out exacerbates choroidal neovascularization via multiple pathogenic pathways.

    PubMed

    Choudhary, Mayur; Kazmin, Dmitri; Hu, Peng; Thomas, Russell S; McDonnell, Donald P; Malek, Goldis

    2015-01-01

    The aryl hydrocarbon receptor (AhR) is a heterodimeric transcriptional regulator with pleiotropic functions in xenobiotic metabolism and detoxification, vascular development and cancer. Herein, we report a previously undescribed role for the AhR signalling pathway in the pathogenesis of the wet, neovascular subtype of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly in the Western world. Comparative analysis of gene expression profiles of aged AhR(-/-) and wild-type (wt) mice, using high-throughput RNA sequencing, revealed differential modulation of genes belonging to several AMD-related pathogenic pathways, including inflammation, angiogenesis and extracellular matrix regulation. To investigate AhR regulation of these pathways in wet AMD, we experimentally induced choroidal neovascular lesions in AhR(-/-) mice and found that they measured significantly larger in area and volume compared to age-matched wt mice. Furthermore, these lesions displayed a higher number of ionized calcium-binding adaptor molecule 1-positive (Iba1(+) ) microglial cells and a greater amount of collagen type IV deposition, events also seen in human wet AMD pathology specimens. Consistent with our in vivo observations, AhR knock-down was sufficient to increase choroidal endothelial cell migration and tube formation in vitro. Moreover, AhR knock-down caused an increase in collagen type IV production and secretion in both retinal pigment epithelial (RPE) and choroidal endothelial cell cultures, increased expression of angiogenic and inflammatory molecules, including vascular endothelial growth factor A (VEGFA) and chemokine (C-C motif) ligand 2 (CCL2) in RPE cells, and increased expression of secreted phosphoprotein 1 (SPP1) and transforming growth factor-β1 (TGFβ1) in choroidal endothelial cells. Collectively, our findings identify AhR as a regulator of multiple pathogenic pathways in experimentally induced choroidal neovascularization, findings that

  13. Aryl hydrocarbon receptor knock-out exacerbates choroidal neovascularization via multiple pathogenic pathways

    PubMed Central

    Choudhary, Mayur; Kazmin, Dmitri; Hu, Peng; Thomas, Russell S; McDonnell, Donald P; Malek, Goldis

    2015-01-01

    The aryl hydrocarbon receptor (AhR) is a heterodimeric transcriptional regulator with pleiotropic functions in xenobiotic metabolism and detoxification, vascular development and cancer. Herein, we report a previously undescribed role for the AhR signalling pathway in the pathogenesis of the wet, neovascular subtype of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly in the Western world. Comparative analysis of gene expression profiles of aged AhR−/− and wild-type (wt) mice, using high-throughput RNA sequencing, revealed differential modulation of genes belonging to several AMD-related pathogenic pathways, including inflammation, angiogenesis and extracellular matrix regulation. To investigate AhR regulation of these pathways in wet AMD, we experimentally induced choroidal neovascular lesions in AhR−/− mice and found that they measured significantly larger in area and volume compared to age-matched wt mice. Furthermore, these lesions displayed a higher number of ionized calcium-binding adaptor molecule 1-positive (Iba1+) microglial cells and a greater amount of collagen type IV deposition, events also seen in human wet AMD pathology specimens. Consistent with our in vivo observations, AhR knock-down was sufficient to increase choroidal endothelial cell migration and tube formation in vitro. Moreover, AhR knock-down caused an increase in collagen type IV production and secretion in both retinal pigment epithelial (RPE) and choroidal endothelial cell cultures, increased expression of angiogenic and inflammatory molecules, including vascular endothelial growth factor A (VEGFA) and chemokine (C–C motif) ligand 2 (CCL2) in RPE cells, and increased expression of secreted phosphoprotein 1 (SPP1) and transforming growth factor-β1 (TGFβ1) in choroidal endothelial cells. Collectively, our findings identify AhR as a regulator of multiple pathogenic pathways in experimentally induced choroidal neovascularization, findings that

  14. Biosynthetic Pathway for Mannopeptimycins, Lipoglycopeptide Antibiotics Active against Drug-Resistant Gram-Positive Pathogens

    PubMed Central

    Magarvey, Nathan A.; Haltli, Brad; He, Min; Greenstein, Michael; Hucul, John A.

    2006-01-01

    The mannopeptimycins are a novel class of lipoglycopeptide antibiotics active against multidrug-resistant pathogens with potential as clinically useful antibacterials. This report is the first to describe the biosynthesis of this novel class of mannosylated lipoglycopeptides. Included here are the cloning, sequencing, annotation, and manipulation of the mannopeptimycin biosynthetic gene cluster from Streptomyces hygroscopicus NRRL 30439. Encoded by genes within the mannopeptimycin biosynthetic gene cluster are enzymes responsible for the generation of the hexapeptide core (nonribosomal peptide synthetases [NRPS]) and tailoring reactions (mannosylation, isovalerylation, hydroxylation, and methylation). The NRPS system is noncanonical in that it has six modules utilizing only five amino acid-specific adenylation domains and it lacks a prototypical NRPS macrocyclizing thioesterase domain. Analysis of the mannopeptimycin gene cluster and its engineering has elucidated the mannopeptimycin biosynthetic pathway and provides the framework to make new and improved mannopeptimycins biosynthetically. PMID:16723579

  15. A self-lysis pathway that enhances the virulence of a pathogenic bacterium

    PubMed Central

    McFarland, Kirsty A.; Dolben, Emily L.; LeRoux, Michele; Kambara, Tracy K.; Ramsey, Kathryn M.; Kirkpatrick, Robin L.; Mougous, Joseph D.; Hogan, Deborah A.; Dove, Simon L.

    2015-01-01

    In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of the alpA gene, which encodes a positive regulator that activates expression of the alpBCDE lysis cassette. Although this is lethal to the individual cell in which it occurs, we find it benefits the population as a whole during infection of a mammalian host. Thus, host and pathogen each may use PCD as a survival-promoting strategy. We suggest that activation of the Alp cell lysis pathway is a disease-enhancing response to bacterial DNA damage inflicted by the host immune system. PMID:26100878

  16. Characterization of the Complete Uric Acid Degradation Pathway in the Fungal Pathogen Cryptococcus neoformans

    PubMed Central

    Lee, I. Russel; Yang, Liting; Sebetso, Gaseene; Allen, Rebecca; Doan, Thi H. N.; Blundell, Ross; Lui, Edmund Y. L.; Morrow, Carl A.; Fraser, James A.

    2013-01-01

    Degradation of purines to uric acid is generally conserved among organisms, however, the end product of uric acid degradation varies from species to species depending on the presence of active catabolic enzymes. In humans, most higher primates and birds, the urate oxidase gene is non-functional and hence uric acid is not further broken down. Uric acid in human blood plasma serves as an antioxidant and an immune enhancer; conversely, excessive amounts cause the common affliction gout. In contrast, uric acid is completely degraded to ammonia in most fungi. Currently, relatively little is known about uric acid catabolism in the fungal pathogen Cryptococcus neoformans even though this yeast is commonly isolated from uric acid-rich pigeon guano. In addition, uric acid utilization enhances the production of the cryptococcal virulence factors capsule and urease, and may potentially modulate the host immune response during infection. Based on these important observations, we employed both Agrobacterium-mediated insertional mutagenesis and bioinformatics to predict all the uric acid catabolic enzyme-encoding genes in the H99 genome. The candidate C. neoformans uric acid catabolic genes identified were named: URO1 (urate oxidase), URO2 (HIU hydrolase), URO3 (OHCU decarboxylase), DAL1 (allantoinase), DAL2,3,3 (allantoicase-ureidoglycolate hydrolase fusion protein), and URE1 (urease). All six ORFs were then deleted via homologous recombination; assaying of the deletion mutants' ability to assimilate uric acid and its pathway intermediates as the sole nitrogen source validated their enzymatic functions. While Uro1, Uro2, Uro3, Dal1 and Dal2,3,3 were demonstrated to be dispensable for virulence, the significance of using a modified animal model system of cryptococcosis for improved mimicking of human pathogenicity is discussed. PMID:23667704

  17. Metabolic pathways of tetraidothyronine and triidothyronine production by thyroid gland: a review of articles.

    PubMed

    Mansourian, A R

    2011-01-01

    Tetraidothyronine (T4) and Triiodothyronine (T3) are the two vital hormones in human metabolism produced by thyroid gland. The major pathways in thyroid hormone biosynthesis begin with iodine metabolism which occurs in three sequential steps: active iodide transport into thyroid followed by iodide oxidation and subsequent iodination of tyrosyl residues of thyroglobulin (Tg) to produce idotyrosines monoidotyrosine (MIT) and diiodothyrosine (DIT) on Tg. Oxidized iodine and tyrosyle residues which are an aromatic amino acids are integral part of T4 and T3. The thyroid iodine deficiency of either dietary, thyroid malfunction, or disorder of hypothalamus and pituitary to produce enough Thyroid Stimulating Hormone (TSH), eventually lead to hypothyroidism with sever side effects. Iodine oxidation is the initial step for thyroid hormone synthesis within thyroid, is mediated by thyroperoxidase enzyme (TPO), which itself is activated by TSH required for production of MIT and DIT. T4 and T3 are subsequently are synthesized on Tg following MIT and DIT coupling reaction. Thyroid hormones eventually produced and released into circulation through Tg pinocytosis from follicular space and subsequent lysozomal function, a process again stimulated by TSH. The production of T4 and T3 are highly regulated externally by a negative feed-back interrelation between serum T4, T3 and TSH and internally by the elevated iodine within thyroid gland. It is believed the extra iodine concentration within thyroid gland control thyroid hormones synthesis by inhibition of the TPO and hydrogen peroxide (H2O2) formation which is also an essential factor of iodine oxidation, via a complex mechanism. In healthy subjects the entire procedures of T4 and T3 synthesis re-start again following a drop in serum T4 and T3 concentration. On conditions of thyroid disorders, which caused by the distruption of either of above mechanisms, thyroid hormone deficiency and related clinical manifestations eventually begin

  18. Delineation of upstream signaling events in the salmonella pathogenicity island 2 transcriptional activation pathway.

    PubMed

    Kim, Charles C; Falkow, Stanley

    2004-07-01

    Survival and replication in the intracellular environment are critical components of the ability of Salmonella enterica serovar Typhimurium to establish systemic infection in the murine host. Intracellular survival is mediated by a number of genetic loci, including Salmonella pathogenicity island 2 (SPI2). SPI2 is a 40-kb locus encoding a type III secretion system that secretes effector molecules, which permits bacterial survival and replication in the intracellular environment of host cells. A two-component regulatory system, ssrAB, is also encoded in SPI2 and controls expression of the secretion system and effectors. While the environmental signals to which SPI2 responds in vivo are not known, activation of expression is dependent on OmpR and can be stimulated in vitro by chelation of cations or by a shift from rich to acidic minimal medium. In this work, we demonstrated that SPI2 activation is associated with OmpR in the phosphorylated form (OmpR-P). Mutations in envZ and ackA-pta, which disrupted two distinct sources of OmpR phosphorylation, indicated that SPI2 activation by chelators or a shift from rich to acidic minimal medium is largely dependent on functional EnvZ. In contrast, the PhoPQ pathway is not required for SPI2 activation in the presence of OmpR-P. As in the case of in vitro stimulation, SPI2 expression in macrophages correlates with the presence of OmpR-P. Additionally, EnvZ, but not acetyl phosphate, is required for maximal expression of SPI2 in the intracellular environment, suggesting that the in vitro SPI2 activation pathway is the same as that used in vivo.

  19. PATHOGEN TRANSPORT AND FATE MODELING IN THE UPPER SALEM RIVER WATERSHED USING SWAT MODEL - PEER-REVIEWED JOURNAL ARTICLE

    EPA Science Inventory

    Simulation of the fate and transport of pathogen contamination was conducted with SWAT for the Upper Salem River Watershed, located in Salem County, New Jersey. This watershed is 37 km2 and land uses are predominantly agricultural. The watershed drains to a 32 km str...

  20. IL-12 Family Cytokines: General Characteristics, Pathogenic Microorganisms, Receptors, and Signalling Pathways.

    PubMed

    Behzadi, Payam; Behzadi, Elham; Ranjbar, Reza

    2016-03-01

    Among a wide range of cytokines, the Interleukin 12 (IL-12) family has its unique structural, functional, and immunological characteristics that have made this family as important immunological playmakers. Because of the importance of IL-12 heterodimeric cytokines in microbial infections, autoimmune diseases, and cancers, the authors of this literature discuss about the general characteristics of IL-12 family members, the interactions between IL-12 cytokines and pathogenic microorganisms, the interleukins receptors and their strategies for selecting different signalling pathways. IL-12 and IL-23 are similar in p40 subunits and both are involved in proinflammatory responses while, IL-27 and IL-35 contribute to anti-inflammatory activities; however, IL-27 is also involved in pro-inflammatory responses. There are some similarities and dissimilarities among IL-12 family members which make them a unique bridge between innate and adaptive immune systems. The bioactivities of IL-12 family indicate a brilliant promise for their applications in different fields of medicine. The members of IL-12 family are candidate for several therapeutics including gene therapy, cancer therapy, tumour therapy, and vaccination. To have an accurate diagnostic technique and definite treatment regarding to infectious diseases, the playmakers of IL-12 family as effective criteria together with microarray technology are the best choices for current and future applications.

  1. IL-12 Family Cytokines: General Characteristics, Pathogenic Microorganisms, Receptors, and Signalling Pathways.

    PubMed

    Behzadi, Payam; Behzadi, Elham; Ranjbar, Reza

    2016-03-01

    Among a wide range of cytokines, the Interleukin 12 (IL-12) family has its unique structural, functional, and immunological characteristics that have made this family as important immunological playmakers. Because of the importance of IL-12 heterodimeric cytokines in microbial infections, autoimmune diseases, and cancers, the authors of this literature discuss about the general characteristics of IL-12 family members, the interactions between IL-12 cytokines and pathogenic microorganisms, the interleukins receptors and their strategies for selecting different signalling pathways. IL-12 and IL-23 are similar in p40 subunits and both are involved in proinflammatory responses while, IL-27 and IL-35 contribute to anti-inflammatory activities; however, IL-27 is also involved in pro-inflammatory responses. There are some similarities and dissimilarities among IL-12 family members which make them a unique bridge between innate and adaptive immune systems. The bioactivities of IL-12 family indicate a brilliant promise for their applications in different fields of medicine. The members of IL-12 family are candidate for several therapeutics including gene therapy, cancer therapy, tumour therapy, and vaccination. To have an accurate diagnostic technique and definite treatment regarding to infectious diseases, the playmakers of IL-12 family as effective criteria together with microarray technology are the best choices for current and future applications. PMID:27020866

  2. Toward a molecular pathogenic pathway for Yersinia pestis YopM

    PubMed Central

    Uittenbogaard, Annette M.; Chelvarajan, R. Lakshman; Myers-Morales, Tanya; Gorman, Amanda A.; Brickey, W. June; Ye, Zhan; Kaplan, Alan M.; Cohen, Donald A.; Ting, Jenny P.-Y.; Straley, Susan C.

    2012-01-01

    YopM is one of the six “effector Yops” of the human-pathogenic Yersinia, but its mechanism has not been defined. After delivery to J774A.1 monocyte-like cells, YopM can rapidly bind and activate the serine/threonine kinases RSK1 and PRK2. However, in infected mice, effects of Y. pestis YopM have been seen only after 24–48 h post-infection (p.i.). To identify potential direct effects of YopM in-vivo we tested for effects of YopM at 1 h and 16–18 h p.i. in mice infected systemically with 106 bacteria. At 16 h p.i., there was a robust host response to both parent and ΔyopM-1 Y. pestis KIM5. Compared to cells from non-infected mice, CD11b+ cells from spleens of infected mice produced more than 100-fold greater IFNγ. In the corresponding sera there were more than 100-fold greater amounts of IFNγ, G-CSF, and CXCL9, as well as more than 10-fold greater amounts of IL-6, CXCL10, and CXCL1. The only YopM-related differences were slightly lower CXCL10 and IL-6 in sera from mice infected 16 h with parent compared to ΔyopM-1 Y. pestis. Microarray analysis of the CD11b+ cells did not identify consistent transcriptional differences of ≥4-fold at 18 h p.i. However, at 1 h p.i. mRNA for early growth response transcription factor 1 (Egr1) was decreased when YopM was present. Bone marrow-derived macrophages infected for 1 h also expressed lower Egr1 message when YopM was present. Infected J774A.1 cells showed greater expression of Egr1 at 1 h p.i. when YopM was present, but this pattern reversed at 3 h. At 6 h p.i., Cxcl10 mRNA was lower in parent-strain infected cells. We conclude that decreased Egr1 expression is a very early transcriptional effect of YopM and speculate that a pathway may exist from RSK1 through Egr1. These studies revealed novel early transcriptional effects of YopM but point to a time after 18 h of infection when critical transitional events lead to later major effects on cytokine gene transcription. PMID:23248776

  3. Current Understandings of Molecular Biology of Echinococcus multilocularis, a Pathogen for Alveolar Echinococcosis in Humans- a Narrative Review Article

    PubMed Central

    WANG, Xiaoqiang; DING, Juntao; GUO, Xiaola; ZHENG, Yadong

    2015-01-01

    Background: Echinococcus multilocularis is a tiny tapeworm, responsible for 0.3~0.5 million alveolar echinococcosis in humans. Methods: We searched relevant papers published between 1981 and 2013 based on the database sources such as PubMed and Google scholar, and collected and integrated the data for analysis. Results: The parasite is able to use host-originated molecules to modulate its development and has complex signalling pathways than expected previously. E. multilocularis utilizes many types of alternative splicing approaches to generate transcript isoforms. Recently, the genome of E. multilocularis has been deciphered. Conclusion: These data will give us a profound understanding of biology of E. multilocularis, which will promote the use as a model to study helminths. PMID:26622288

  4. Human fecal and pathogen exposure pathways in rural Indian villages and the effect of increased latrine coverage.

    PubMed

    Odagiri, Mitsunori; Schriewer, Alexander; Daniels, Miles E; Wuertz, Stefan; Smith, Woutrina A; Clasen, Thomas; Schmidt, Wolf-Peter; Jin, Yujie; Torondel, Belen; Misra, Pravas R; Panigrahi, Pinaki; Jenkins, Marion W

    2016-09-01

    Efforts to eradicate open defecation and improve sanitation access are unlikely to achieve health benefits unless interventions reduce microbial exposures. This study assessed human fecal contamination and pathogen exposures in rural India, and the effect of increased sanitation coverage on contamination and exposure rates. In a cross-sectional study of 60 villages of a cluster-randomized controlled sanitation trial in Odisha, India, human and domestic animal fecal contamination was measured in community tubewells and ponds (n = 301) and via exposure pathways in homes (n = 354), using Bacteroidales microbial source tracking fecal markers validated in India. Community water sources were further tested for diarrheal pathogens (rotavirus, adenovirus and Vibrio cholerae by quantitative PCR; pathogenic Escherichia coli by multiplex PCR; Cryptosporidium and Giardia by immunomagnetic separation and direct fluorescent antibody microscopy). Exposure pathways in intervention and control villages were compared and relationships with child diarrhea examined. Human fecal markers were rarely detected in tubewells (2.4%, 95%CI: 0.3-4.5%) and ponds (5.6%, 95%CI: 0.8-10.3%), compared to homes (35.4%, 95%CI: 30.4-40.4%). In tubewells, V. cholerae was the most frequently detected pathogen (19.8%, 95%CI: 14.4-25.2%), followed by Giardia (14.8%, 95%CI: 10.0-19.7%). In ponds, Giardia was most often detected (74.5%, 95%CI: 65.7-83.3%), followed by pathogenic E. coli (48.1%, 95%CI: 34.8-61.5%) and rotavirus (44.4%, 95%CI: 34.2-54.7%). At village-level, prevalence of fecal pathogen detection in community drinking water sources was associated with elevated prevalence of child diarrhea within 6 weeks of testing (RR 2.13, 95%CI: 1.25-3.63) while within homes, higher levels of human and animal fecal marker detection were associated with increased risks of subsequent child diarrhea (P = 0.044 and 0.013, respectively). There was no evidence that the intervention, which increased

  5. Human fecal and pathogen exposure pathways in rural Indian villages and the effect of increased latrine coverage.

    PubMed

    Odagiri, Mitsunori; Schriewer, Alexander; Daniels, Miles E; Wuertz, Stefan; Smith, Woutrina A; Clasen, Thomas; Schmidt, Wolf-Peter; Jin, Yujie; Torondel, Belen; Misra, Pravas R; Panigrahi, Pinaki; Jenkins, Marion W

    2016-09-01

    Efforts to eradicate open defecation and improve sanitation access are unlikely to achieve health benefits unless interventions reduce microbial exposures. This study assessed human fecal contamination and pathogen exposures in rural India, and the effect of increased sanitation coverage on contamination and exposure rates. In a cross-sectional study of 60 villages of a cluster-randomized controlled sanitation trial in Odisha, India, human and domestic animal fecal contamination was measured in community tubewells and ponds (n = 301) and via exposure pathways in homes (n = 354), using Bacteroidales microbial source tracking fecal markers validated in India. Community water sources were further tested for diarrheal pathogens (rotavirus, adenovirus and Vibrio cholerae by quantitative PCR; pathogenic Escherichia coli by multiplex PCR; Cryptosporidium and Giardia by immunomagnetic separation and direct fluorescent antibody microscopy). Exposure pathways in intervention and control villages were compared and relationships with child diarrhea examined. Human fecal markers were rarely detected in tubewells (2.4%, 95%CI: 0.3-4.5%) and ponds (5.6%, 95%CI: 0.8-10.3%), compared to homes (35.4%, 95%CI: 30.4-40.4%). In tubewells, V. cholerae was the most frequently detected pathogen (19.8%, 95%CI: 14.4-25.2%), followed by Giardia (14.8%, 95%CI: 10.0-19.7%). In ponds, Giardia was most often detected (74.5%, 95%CI: 65.7-83.3%), followed by pathogenic E. coli (48.1%, 95%CI: 34.8-61.5%) and rotavirus (44.4%, 95%CI: 34.2-54.7%). At village-level, prevalence of fecal pathogen detection in community drinking water sources was associated with elevated prevalence of child diarrhea within 6 weeks of testing (RR 2.13, 95%CI: 1.25-3.63) while within homes, higher levels of human and animal fecal marker detection were associated with increased risks of subsequent child diarrhea (P = 0.044 and 0.013, respectively). There was no evidence that the intervention, which increased

  6. Trafficking and degradation pathways in pathogenic conversion of prions and prion-like proteins in neurodegenerative diseases.

    PubMed

    Victoria, Guiliana Soraya; Zurzolo, Chiara

    2015-09-01

    Several neurodegenerative diseases such as transmissible spongiform encephalopathies, Alzheimer's and Parkinson's diseases are caused by the conversion of cellular proteins to a pathogenic conformer. Despite differences in the primary structure and subcellular localization of these proteins, which include the prion protein, α-synuclein and amyloid precursor protein (APP), striking similarity has been observed in their ability to seed and convert naïve protein molecules as well as transfer between cells. This review aims to cover what is known about the intracellular trafficking of these proteins as well as their degradation mechanisms and highlight similarities in their movement through the endocytic pathway that could contribute to the pathogenic conversion and seeding of these proteins which underlies the basis of these diseases.

  7. Detoxification of nitric oxide by flavohemoglobin and the denitrification pathway in the maize pathogen Fusarium verticillioides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ephemeral nitric oxide (NO) is a free radical, highly reactive, environmentally rare, and a potent signaling molecule in organisms across kingdoms of life. This gaseous small molecule can freely transverse membranes and has been implicated in aspects of pathogenicity both in animal and plant ho...

  8. Metabolic gene clusters encoding the enzymes of two branches of the 3-oxoadipate pathway in the pathogenic yeast Candida albicans.

    PubMed

    Gérecová, Gabriela; Neboháčová, Martina; Zeman, Igor; Pryszcz, Leszek P; Tomáška, Ľubomír; Gabaldón, Toni; Nosek, Jozef

    2015-05-01

    The pathogenic yeast Candida albicans utilizes hydroxyderivatives of benzene via the catechol and hydroxyhydroquinone branches of the 3-oxoadipate pathway. The genetic basis and evolutionary origin of this catabolic pathway in yeasts are unknown. In this study, we identified C. albicans genes encoding the enzymes involved in the degradation of hydroxybenzenes. We found that the genes coding for core components of the 3-oxoadipate pathway are arranged into two metabolic gene clusters. Our results demonstrate that C. albicans cells cultivated in media containing hydroxybenzene substrates highly induce the transcription of these genes as well as the corresponding enzymatic activities. We also found that C. albicans cells assimilating hydroxybenzenes cope with the oxidative stress by upregulation of cellular antioxidant systems such as alternative oxidase and catalase. Moreover, we investigated the evolution of the enzymes encoded by these clusters and found that most of them share a particularly sparse phylogenetic distribution among Saccharomycotina, which is likely to have been caused by extensive gene loss. We exploited this fact to find co-evolving proteins that are suitable candidates for the missing enzymes of the pathway. PMID:25743787

  9. Interplay between pathway-specific and global regulation of the fumonisin gene cluster in the rice pathogen Fusarium fujikuroi.

    PubMed

    Rösler, Sarah M; Sieber, Christian M K; Humpf, Hans-Ulrich; Tudzynski, Bettina

    2016-07-01

    The rice pathogenic fungus Fusarium fujikuroi is known to produce a large variety of secondary metabolites. Besides the gibberellins, causing the bakanae effect in infected rice seedlings, the fungus produces several mycotoxins and pigments. Among the 47 putative secondary metabolite gene clusters identified in the genome of F. fujikuroi, the fumonisin gene cluster (FUM) shows very high homology to the FUM cluster of the main fumonisin producer Fusarium verticillioides, a pathogen of maize. Despite the high level of cluster gene conservation, total fumonisin FB1 and FB2 levels (FBx) produced by F. fujikuroi were only 1-10 % compared to F. verticillioides under inducing conditions. Nitrogen repression was found to be relevant for wild-type strains of both species. However, addition of germinated maize kernels activated the FBx production only in F. verticillioides, reflecting the different host specificity of both wild-type strains. Over-expression of the pathway-specific transcription factor Fum21 in F. fujikuroi strongly activated the FUM cluster genes leading to 1000-fold elevated FBx levels. To gain further insights into the nitrogen metabolite repression of FBx biosynthesis, we studied the impact of the global nitrogen regulators AreA and AreB and demonstrated that both GATA-type transcription factors are essential for full activation of the FUM gene cluster. Loss of one of them obstructs the pathway-specific transcription factor Fum21 to fully activate expression of FUM cluster genes.

  10. The first description of complete invertebrate arginine metabolism pathways implies dose-dependent pathogen regulation in Apostichopus japonicus

    PubMed Central

    Yina, Shao; Chenghua, Li; Weiwei, Zhang; Zhenhui, Wang; Zhimeng, Lv

    2016-01-01

    In this study, three typical members representative of different arginine metabolic pathways were firstly identified from Apostichopus japonicus, including nitric oxide synthase (NOS), arginase, and agmatinase. Spatial expression analysis revealed that the AjNOS transcript presented negative expression patterns relative to those of Ajarginase or Ajagmatinase in most detected tissues. Furthermore, Vibrio splendidus-challenged coelomocytes and intestine, and LPS-exposed primary coelomocytes could significantly induce AjNOS expression, followed by obviously inhibited Arginase and AjAgmatinase transcripts at the most detected time points. Silencing the three members with two specific siRNAs in vivo and in vitro collectively indicated that AjNOS not only compete with Ajarginase but also with Ajagmatinase in arginine metabolism. Interestingly, Ajarginase and Ajagmatinase displayed cooperative expression profiles in arginine utilization. More importantly, live pathogens of V. splendidus and Vibrio parahaemolyticus co-incubated with primary cells also induced NO production and suppressed arginase activity in a time-dependent at an appropriate multiplicity of infection (MOI) of 10, without non-pathogen Escherichia coli. When increasing the pathogen dose (MOI = 100), arginase activity was significantly elevated, and NO production was depressed, with a larger magnitude in V. splendidus co-incubation. The present study expands our understanding of the connection between arginine’s metabolic and immune responses in non-model invertebrates. PMID:27032691

  11. Participation of the p38 pathway in Drosophila host defense against pathogenic bacteria and fungi.

    PubMed

    Chen, Jianming; Xie, Changchuan; Tian, Lili; Hong, Lixin; Wu, Xiurong; Han, Jiahuai

    2010-11-30

    The signaling network of innate immunity in Drosophila is constructed by multiple evolutionarily conserved pathways, including the Toll- or Imd-regulated NF-κB and JNK pathways. The p38 MAPK pathway is evolutionarily conserved in stress responses, but its role in Drosophila host defense is not fully understood. Here we show that the p38 pathway also participates in Drosophila host defense. In comparison with wild-type flies, the sensitivity to microbial infection was slightly higher in the p38a mutant, significantly higher in the p38b mutant, but unchanged in the p38c mutant. The p38b;p38a double-mutant flies were hypersensitive to septic injury. The immunodeficiency of p38b;p38a mutant flies was also demonstrated by hindgut melanization and larvae stage lethality that were induced by microbes naturally presented in fly food. A canonical MAP3K-MKK cascade was found to mediate p38 activation in response to infection in flies. However, neither Toll nor Imd was required for microbe-induced p38 activation. We found that p38-activated heat-shock factor and suppressed JNK collectively contributed to host defense against infection. Together, our data demonstrate that the p38 pathway-mediated stress response contribute to Drosophila host defense against microbial infection.

  12. TrpA1 Regulates Defecation of Food-Borne Pathogens under the Control of the Duox Pathway.

    PubMed

    Du, Eun Jo; Ahn, Tae Jung; Kwon, Ilmin; Lee, Ji Hye; Park, Jeong-Ho; Park, Sun Hwa; Kang, Tong Mook; Cho, Hana; Kim, Tae Jin; Kim, Hyung-Wook; Jun, Youngsoo; Lee, Hee Jae; Lee, Young Sik; Kwon, Jae Young; Kang, KyeongJin

    2016-01-01

    Pathogen expulsion from the gut is an important defense strategy against infection, but little is known about how interaction between the intestinal microbiome and host immunity modulates defecation. In Drosophila melanogaster, dual oxidase (Duox) kills pathogenic microbes by generating the microbicidal reactive oxygen species (ROS), hypochlorous acid (HOCl) in response to bacterially excreted uracil. The physiological function of enzymatically generated HOCl in the gut is, however, unknown aside from its anti-microbial activity. Drosophila TRPA1 is an evolutionarily conserved receptor for reactive chemicals like HOCl, but a role for this molecule in mediating responses to gut microbial content has not been described. Here we identify a molecular mechanism through which bacteria-produced uracil facilitates pathogen-clearing defecation. Ingestion of uracil increases defecation frequency, requiring the Duox pathway and TrpA1. The TrpA1(A) transcript spliced with exon10b (TrpA1(A)10b) that is present in a subset of midgut enteroendocrine cells (EECs) is critical for uracil-dependent defecation. TRPA1(A)10b heterologously expressed in Xenopus oocytes is an excellent HOCl receptor characterized with elevated sensitivity and fast activation kinetics of macroscopic HOCl-evoked currents compared to those of the alternative TRPA1(A)10a isoform. Consistent with TrpA1's role in defecation, uracil-excreting Erwinia carotovora showed higher persistence in TrpA1-deficient guts. Taken together, our results propose that the uracil/Duox pathway promotes bacteria expulsion from the gut through the HOCl-sensitive receptor, TRPA1(A)10b, thereby minimizing the chances that bacteria adapt to survive host defense systems.

  13. TrpA1 Regulates Defecation of Food-Borne Pathogens under the Control of the Duox Pathway

    PubMed Central

    Park, Jeong-Ho; Park, Sun Hwa; Kang, Tong Mook; Cho, Hana; Kim, Tae Jin; Kim, Hyung-Wook; Jun, Youngsoo; Lee, Hee Jae; Lee, Young Sik; Kwon, Jae Young; Kang, KyeongJin

    2016-01-01

    Pathogen expulsion from the gut is an important defense strategy against infection, but little is known about how interaction between the intestinal microbiome and host immunity modulates defecation. In Drosophila melanogaster, dual oxidase (Duox) kills pathogenic microbes by generating the microbicidal reactive oxygen species (ROS), hypochlorous acid (HOCl) in response to bacterially excreted uracil. The physiological function of enzymatically generated HOCl in the gut is, however, unknown aside from its anti-microbial activity. Drosophila TRPA1 is an evolutionarily conserved receptor for reactive chemicals like HOCl, but a role for this molecule in mediating responses to gut microbial content has not been described. Here we identify a molecular mechanism through which bacteria-produced uracil facilitates pathogen-clearing defecation. Ingestion of uracil increases defecation frequency, requiring the Duox pathway and TrpA1. The TrpA1(A) transcript spliced with exon10b (TrpA1(A)10b) that is present in a subset of midgut enteroendocrine cells (EECs) is critical for uracil-dependent defecation. TRPA1(A)10b heterologously expressed in Xenopus oocytes is an excellent HOCl receptor characterized with elevated sensitivity and fast activation kinetics of macroscopic HOCl-evoked currents compared to those of the alternative TRPA1(A)10a isoform. Consistent with TrpA1’s role in defecation, uracil-excreting Erwinia carotovora showed higher persistence in TrpA1-deficient guts. Taken together, our results propose that the uracil/Duox pathway promotes bacteria expulsion from the gut through the HOCl-sensitive receptor, TRPA1(A)10b, thereby minimizing the chances that bacteria adapt to survive host defense systems. PMID:26726767

  14. Conidial Dihydroxynaphthalene Melanin of the Human Pathogenic Fungus Aspergillus fumigatus Interferes with the Host Endocytosis Pathway.

    PubMed

    Thywißen, Andreas; Heinekamp, Thorsten; Dahse, Hans-Martin; Schmaler-Ripcke, Jeannette; Nietzsche, Sandor; Zipfel, Peter F; Brakhage, Axel A

    2011-01-01

    Aspergillus fumigatus is the most important air-borne fungal pathogen of humans. The interaction of the pathogen with the host's immune system represents a key process to understand pathogenicity. For elimination of invading microorganisms, they need to be efficiently phagocytosed and located in acidified phagolysosomes. However, as shown previously, A. fumigatus is able to manipulate the formation of functional phagolysosomes. Here, we demonstrate that in contrast to pigmentless pksP mutant conidia of A. fumigatus, the gray-green wild-type conidia inhibit the acidification of phagolysosomes of alveolar macrophages, monocyte-derived macrophages, and human neutrophil granulocytes. Therefore, this inhibition is independent of the cell type and applies to the major immune effector cells required for defense against A. fumigatus. Studies with melanin ghosts indicate that the inhibitory effect of wild-type conidia is due to their dihydroxynaphthalene (DHN)-melanin covering the conidia, whereas the hydrophobin RodA rodlet layer plays no role in this process. This is also supported by the observation that pksP conidia still exhibit the RodA hydrophobin layer, as shown by scanning electron microscopy. Mutants defective in different steps of the DHN-melanin biosynthesis showed stronger inhibition than pksP mutant conidia but lower inhibition than wild-type conidia. Moreover, A. fumigatus and A. flavus led to a stronger inhibition of phagolysosomal acidification than A. nidulans and A. terreus. These data indicate that a certain type of DHN-melanin that is different in the various Aspergillus species, is required for maximal inhibition of phagolysosomal acidification. Finally, we identified the vacuolar ATPase (vATPase) as potential target for A. fumigatus based on the finding that addition of bafilomycin which inhibits vATPase, led to complete inhibition of the acidification whereas the fusion of phagosomes containing wild-type conidia and lysosomes was not affected.

  15. Macelignan inhibits bee pathogenic fungi Ascophaera apis growth through HOG1 pathway.

    PubMed

    Shin, Y K; Kim, K Y

    2016-07-01

    Ascosphaera apis is a bee pathogen that causes bee larvae infection disease, to which treatment is not yet well investigated. The aim of this study was to investigate antifungal susceptibility in vitro against A. apis and to identify a new antifungal agent for this pathogen through minimal inhibitory concentration (MIC) assay and western blot analysis. Macelignan had 1.56 and 3.125 μg/mL MIC against A. apis after 24 and 48 h, respectively, exhibiting the strongest growth inhibition against A. apis among the tested compounds (corosolic acid, dehydrocostus lactone, loganic acid, tracheloside, fangchinoline and emodin-8-O-β-D-glucopyranoside). Furthermore, macelignan showed a narrow-ranged spectrum against various fungal strains without any mammalian cell cytotoxicity. In spite of miconazole having powerful broad-ranged anti-fungal activity including A. apis, it demonstrated strong cytotoxicity. Therefore, even if macelignan alone was effective as an antifungal agent to treat A. apis, combined treatment with miconazole was more useful to overcome toxicity, drug resistance occurrence and cost effectiveness. Finally, HOG1 was revealed as a target molecule of macelignan in the anti-A. apis activity by inhibiting phosphorylation using S. cerevisiae as a model system. Based on our results, macelignan, a food-grade antimicrobial compound, would be an effective antifungal agent against A. apis infection in bees. PMID:27383123

  16. Macelignan inhibits bee pathogenic fungi Ascophaera apis growth through HOG1 pathway

    PubMed Central

    Shin, Y.K.; Kim, K.Y.

    2016-01-01

    Ascosphaera apis is a bee pathogen that causes bee larvae infection disease, to which treatment is not yet well investigated. The aim of this study was to investigate antifungal susceptibility in vitro against A. apis and to identify a new antifungal agent for this pathogen through minimal inhibitory concentration (MIC) assay and western blot analysis. Macelignan had 1.56 and 3.125 μg/mL MIC against A. apis after 24 and 48 h, respectively, exhibiting the strongest growth inhibition against A. apis among the tested compounds (corosolic acid, dehydrocostus lactone, loganic acid, tracheloside, fangchinoline and emodin-8-O-β-D-glucopyranoside). Furthermore, macelignan showed a narrow-ranged spectrum against various fungal strains without any mammalian cell cytotoxicity. In spite of miconazole having powerful broad-ranged anti-fungal activity including A. apis, it demonstrated strong cytotoxicity. Therefore, even if macelignan alone was effective as an antifungal agent to treat A. apis, combined treatment with miconazole was more useful to overcome toxicity, drug resistance occurrence and cost effectiveness. Finally, HOG1 was revealed as a target molecule of macelignan in the anti-A. apis activity by inhibiting phosphorylation using S. cerevisiae as a model system. Based on our results, macelignan, a food-grade antimicrobial compound, would be an effective antifungal agent against A. apis infection in bees. PMID:27383123

  17. The Steroid Catabolic Pathway of the Intracellular Pathogen Rhodococcus equi Is Important for Pathogenesis and a Target for Vaccine Development

    PubMed Central

    van der Geize, R.; Grommen, A. W. F.; Hessels, G. I.; Jacobs, A. A. C.; Dijkhuizen, L.

    2011-01-01

    Rhodococcus equi causes fatal pyogranulomatous pneumonia in foals and immunocompromised animals and humans. Despite its importance, there is currently no effective vaccine against the disease. The actinobacteria R. equi and the human pathogen Mycobacterium tuberculosis are related, and both cause pulmonary diseases. Recently, we have shown that essential steps in the cholesterol catabolic pathway are involved in the pathogenicity of M. tuberculosis. Bioinformatic analysis revealed the presence of a similar cholesterol catabolic gene cluster in R. equi. Orthologs of predicted M. tuberculosis virulence genes located within this cluster, i.e. ipdA (rv3551), ipdB (rv3552), fadA6 and fadE30, were identified in R. equi RE1 and inactivated. The ipdA and ipdB genes of R. equi RE1 appear to constitute the α-subunit and β-subunit, respectively, of a heterodimeric coenzyme A transferase. Mutant strains RE1ΔipdAB and RE1ΔfadE30, but not RE1ΔfadA6, were impaired in growth on the steroid catabolic pathway intermediates 4-androstene-3,17-dione (AD) and 3aα-H-4α(3′-propionic acid)-5α-hydroxy-7aβ-methylhexahydro-1-indanone (5α-hydroxy-methylhexahydro-1-indanone propionate; 5OH-HIP). Interestingly, RE1ΔipdAB and RE1ΔfadE30, but not RE1ΔfadA6, also displayed an attenuated phenotype in a macrophage infection assay. Gene products important for growth on 5OH-HIP, as part of the steroid catabolic pathway, thus appear to act as factors involved in the pathogenicity of R. equi. Challenge experiments showed that RE1ΔipdAB could be safely administered intratracheally to 2 to 5 week-old foals and oral immunization of foals even elicited a substantial protective immunity against a virulent R. equi strain. Our data show that genes involved in steroid catabolism are promising targets for the development of a live-attenuated vaccine against R. equi infections. PMID:21901092

  18. Linkage of cold acclimation and disease resistance through plant-pathogen interaction pathway in Vitis amurensis grapevine.

    PubMed

    Wu, Jiao; Zhang, Yali; Yin, Ling; Qu, Junjie; Lu, Jiang

    2014-12-01

    Low temperatures cause severe damage to none cold hardy grapevines. A preliminary survey with Solexa sequencing technology was used to analyze gene expression profiles of cold hardy Vitis amurensis 'Zuoshan-1' after cold acclimation at 4 °C for 48 h. A total of 16,750 and 18,068 putative genes were annotated for 4 °C-treated and control library, respectively. Among them, 393 genes were upregulated for at least 20-fold, while 69 genes were downregulated for at least 20-fold under the 4 °C treatment for 48 h. A subset of 101 genes from this survey was investigated further using reverse transcription polymerase chain reaction (RT-PCR). Genes associated with signaling events in pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), including generation of calcium signals (CNGC, CMLs), jasmonic acid signal (JAZ1), oxidative burst (Rboh), and phosphorylation (FLS2, BAK, MEKK1, MKKs) cascades, were upregulated after cold acclimation. Disease resistance genes (RPM1, RPS5, RIN4, PBS1) in the process of effector-triggered immunity (ETI) were also upregulated in the current condition. Defense-related genes (WRKYs, PR1, MIN7) involved in both PTI and ETI processes were abundantly expressed after cold acclimation. Our results indicated that plant-pathogen interaction pathways were linked to the cold acclimation in V. amurensis grapevine. Other biotic- and abiotic-related genes, such as defense (protein phosphatase 2C, U-box domain proteins, NCED1, stilbene synthase), transcription (DREBs, MYBs, ERFs, ZFPs), signal transduction (kinase, calcium, and auxin signaling), transport (ATP-binding cassette (ABC) transporters, auxin:hydrogen symporter), and various metabolism, were also abundantly expressed in the cold acclimation of V. Amurensis 'Zuoshan-1' grapevine. This study revealed a series of critical genes and pathways to delineate important biological processes affected by low temperature in 'Zuoshan-1'.

  19. Entry Mode–Dependent Function of an Indole Glucosinolate Pathway in Arabidopsis for Nonhost Resistance against Anthracnose Pathogens[W

    PubMed Central

    Hiruma, Kei; Onozawa-Komori, Mariko; Takahashi, Fumika; Asakura, Makoto; Bednarek, Paweł; Okuno, Tetsuro; Schulze-Lefert, Paul; Takano, Yoshitaka

    2010-01-01

    When faced with nonadapted fungal pathogens, Arabidopsis thaliana mounts nonhost resistance responses, which typically result in the termination of early pathogenesis steps. We report that nonadapted anthracnose fungi engage two alternative entry modes during pathogenesis on leaves: turgor-mediated invasion beneath melanized appressoria, and a previously undiscovered hyphal tip–based entry (HTE) that is independent of appressorium formation. The frequency of HTE is positively regulated by carbohydrate nutrients and appears to be subject to constitutive inhibition by the fungal mitogen-activated protein kinase (MAPK) cascade of MAPK ESSENTIAL FOR APPRESSORIUM FORMATION1. The same MAPK cascade is essential for appressorium formation. Unexpectedly, the Arabidopsis indole glucosinolate pathway restricts entry of the nonadapted anthracnose fungi only when these pathogens employ HTE. Arabidopsis mutants defective in indole glucosinolate biosynthesis or metabolism support the initiation of postinvasion growth of nonadapted Colletotrichum gloeosporioides and Colletotrichum orbiculare. However, genetic disruption of Colletotrichum appressorium formation does not permit HTE on host plants. Thus, Colletotrichum appressoria play a critical role in the suppression of preinvasion plant defenses, in addition to their previously described role in turgor-mediated plant cell invasion. We also show that HTE is the predominant morphogenetic response of Colletotrichum at wound sites. This implies the existence of a fungal sensing system to trigger appropriate morphogenetic responses during pathogenesis at wound sites and on intact leaf tissue. PMID:20605856

  20. Ras pathway signaling accelerates programmed cell death in the pathogenic fungus Candida albicans.

    PubMed

    Phillips, Andrew J; Crowe, Jonathan D; Ramsdale, Mark

    2006-01-17

    A better understanding of the molecular basis of programmed cell death (PCD) in fungi could provide information that is useful in the design of antifungal drugs that combat life-threatening fungal infections. Harsh environmental stresses, such as acetic acid or hydrogen peroxide, have been shown to induce PCD in the pathogenic fungus Candida albicans. In this study, we show that dying cells progress from an apoptotic state to a secondary necrotic state and that the rate at which this change occurs is proportional to the intensity of the stimulus. Also, we found that the temporal response is modulated by Ras-cAMP-PKA signals. Mutations that block Ras-cAMP-PKA signaling (ras1Delta, cdc35Delta, tpk1Delta, and tpk2Delta) suppress or delay the apoptotic response, whereas mutations that stimulate signaling (RAS1(val13) and pde2Delta) accelerate the rate of entry of cells into apoptosis. Pharmacological stimulation or inhibition of Ras signaling reinforces these findings. Transient increases in endogenous cAMP occur under conditions that stimulate apoptosis but not growth arrest. Death-specific changes in the abundance of different isoforms of the PKA regulatory subunit, Bcy1p, are also observed. Activation of Ras signals may regulate PCD of C. albicans, either by inhibiting antiapoptotic functions (such as stress responses) or by activating proapoptotic functions. PMID:16407097

  1. Opa proteins and CEACAMs: pathways of immune engagement for pathogenic Neisseria.

    PubMed

    Sadarangani, Manish; Pollard, Andrew J; Gray-Owen, Scott D

    2011-05-01

    Neisseria meningitidis and Neisseria gonorrhoeae are globally important pathogens, which in part owe their success to their ability to successfully evade human immune responses over long periods. The phase-variable opacity-associated (Opa) adhesin proteins are a major surface component of these organisms, and are responsible for bacterial adherence and entry into host cells and interactions with the immune system. Most immune interactions are mediated via binding to members of the carcinoembryonic antigen cell adhesion molecule (CEACAM) family. These Opa variants are able to bind to different receptors of the CEACAM family on epithelial cells, neutrophils, and T and B lymphocytes, influencing the innate and adaptive immune responses. Increased epithelial cell adhesion creates the potential for prolonged infection, invasion and dissemination. Furthermore, Opa proteins may inhibit T-lymphocyte activation and proliferation, B-cell antibody production, and innate inflammatory responses by infected epithelia, in addition to conferring increased resistance to antibody-dependent, complement-mediated killing. While vaccines containing Opa proteins could induce adhesion-blocking and bactericidal antibodies, the consequence of CEACAM binding by a candidate Opa-containing vaccine requires further investigation. This review summarizes current knowledge of the immunological consequences of the interaction between meningococcal and gonococcal Opa proteins and human CEACAMs, considering the implications for pathogenesis and vaccine development.

  2. The effector AWR5 from the plant pathogen Ralstonia solanacearum is an inhibitor of the TOR signalling pathway.

    PubMed

    Popa, Crina; Li, Liang; Gil, Sergio; Tatjer, Laura; Hashii, Keisuke; Tabuchi, Mitsuaki; Coll, Núria S; Ariño, Joaquín; Valls, Marc

    2016-01-01

    Bacterial pathogens possess complex type III effector (T3E) repertoires that are translocated inside the host cells to cause disease. However, only a minor proportion of these effectors have been assigned a function. Here, we show that the T3E AWR5 from the phytopathogen Ralstonia solanacearum is an inhibitor of TOR, a central regulator in eukaryotes that controls the switch between cell growth and stress responses in response to nutrient availability. Heterologous expression of AWR5 in yeast caused growth inhibition and autophagy induction coupled to massive transcriptomic changes, unmistakably reminiscent of TOR inhibition by rapamycin or nitrogen starvation. Detailed genetic analysis of these phenotypes in yeast, including suppression of AWR5-induced toxicity by mutation of CDC55 and TPD3, encoding regulatory subunits of the PP2A phosphatase, indicated that AWR5 might exert its function by directly or indirectly inhibiting the TOR pathway upstream PP2A. We present evidence in planta that this T3E caused a decrease in TOR-regulated plant nitrate reductase activity and also that normal levels of TOR and the Cdc55 homologues in plants are required for R. solanacearum virulence. Our results suggest that the TOR pathway is a bona fide T3E target and further prove that yeast is a useful platform for T3E function characterisation. PMID:27257085

  3. The effector AWR5 from the plant pathogen Ralstonia solanacearum is an inhibitor of the TOR signalling pathway

    PubMed Central

    Popa, Crina; Li, Liang; Gil, Sergio; Tatjer, Laura; Hashii, Keisuke; Tabuchi, Mitsuaki; Coll, Núria S.; Ariño, Joaquín; Valls, Marc

    2016-01-01

    Bacterial pathogens possess complex type III effector (T3E) repertoires that are translocated inside the host cells to cause disease. However, only a minor proportion of these effectors have been assigned a function. Here, we show that the T3E AWR5 from the phytopathogen Ralstonia solanacearum is an inhibitor of TOR, a central regulator in eukaryotes that controls the switch between cell growth and stress responses in response to nutrient availability. Heterologous expression of AWR5 in yeast caused growth inhibition and autophagy induction coupled to massive transcriptomic changes, unmistakably reminiscent of TOR inhibition by rapamycin or nitrogen starvation. Detailed genetic analysis of these phenotypes in yeast, including suppression of AWR5-induced toxicity by mutation of CDC55 and TPD3, encoding regulatory subunits of the PP2A phosphatase, indicated that AWR5 might exert its function by directly or indirectly inhibiting the TOR pathway upstream PP2A. We present evidence in planta that this T3E caused a decrease in TOR-regulated plant nitrate reductase activity and also that normal levels of TOR and the Cdc55 homologues in plants are required for R. solanacearum virulence. Our results suggest that the TOR pathway is a bona fide T3E target and further prove that yeast is a useful platform for T3E function characterisation. PMID:27257085

  4. The effector AWR5 from the plant pathogen Ralstonia solanacearum is an inhibitor of the TOR signalling pathway.

    PubMed

    Popa, Crina; Li, Liang; Gil, Sergio; Tatjer, Laura; Hashii, Keisuke; Tabuchi, Mitsuaki; Coll, Núria S; Ariño, Joaquín; Valls, Marc

    2016-06-03

    Bacterial pathogens possess complex type III effector (T3E) repertoires that are translocated inside the host cells to cause disease. However, only a minor proportion of these effectors have been assigned a function. Here, we show that the T3E AWR5 from the phytopathogen Ralstonia solanacearum is an inhibitor of TOR, a central regulator in eukaryotes that controls the switch between cell growth and stress responses in response to nutrient availability. Heterologous expression of AWR5 in yeast caused growth inhibition and autophagy induction coupled to massive transcriptomic changes, unmistakably reminiscent of TOR inhibition by rapamycin or nitrogen starvation. Detailed genetic analysis of these phenotypes in yeast, including suppression of AWR5-induced toxicity by mutation of CDC55 and TPD3, encoding regulatory subunits of the PP2A phosphatase, indicated that AWR5 might exert its function by directly or indirectly inhibiting the TOR pathway upstream PP2A. We present evidence in planta that this T3E caused a decrease in TOR-regulated plant nitrate reductase activity and also that normal levels of TOR and the Cdc55 homologues in plants are required for R. solanacearum virulence. Our results suggest that the TOR pathway is a bona fide T3E target and further prove that yeast is a useful platform for T3E function characterisation.

  5. Functional definition of BirA suggests a biotin utilization pathway in the zoonotic pathogen Streptococcus suis.

    PubMed

    Ye, Huiyan; Cai, Mingzhu; Zhang, Huimin; Li, Zhencui; Wen, Ronghui; Feng, Youjun

    2016-05-24

    Biotin protein ligase is universal in three domains of life. The paradigm version of BPL is the Escherichia coli BirA that is also a repressor for the biotin biosynthesis pathway. Streptococcus suis, a leading bacterial agent for swine diseases, seems to be an increasingly-important opportunistic human pathogen. Unlike the scenario in E. coli, S. suis lacks the de novo biotin biosynthesis pathway. In contrast, it retains a bioY, a biotin transporter-encoding gene, indicating an alternative survival strategy for S. suis to scavenge biotin from its inhabiting niche. Here we report functional definition of S. suis birA homologue. The in vivo functions of the birA paralogue with only 23.6% identity to the counterpart of E. coli, was judged by its ability to complement the conditional lethal mutants of E. coli birA. The recombinant BirA protein of S. suis was overexpressed in E. coli, purified to homogeneity and verified with MS. Both cellulose TLC and MALDI-TOFF-MS assays demonstrated that the S. suis BirA protein catalyzed the biotinylation reaction of its acceptor biotin carboxyl carrier protein. EMSA assays confirmed binding of the bioY gene to the S. suis BirA. The data defined the first example of the bifunctional BirA ligase/repressor in Streptococcus.

  6. Functional definition of BirA suggests a biotin utilization pathway in the zoonotic pathogen Streptococcus suis.

    PubMed

    Ye, Huiyan; Cai, Mingzhu; Zhang, Huimin; Li, Zhencui; Wen, Ronghui; Feng, Youjun

    2016-01-01

    Biotin protein ligase is universal in three domains of life. The paradigm version of BPL is the Escherichia coli BirA that is also a repressor for the biotin biosynthesis pathway. Streptococcus suis, a leading bacterial agent for swine diseases, seems to be an increasingly-important opportunistic human pathogen. Unlike the scenario in E. coli, S. suis lacks the de novo biotin biosynthesis pathway. In contrast, it retains a bioY, a biotin transporter-encoding gene, indicating an alternative survival strategy for S. suis to scavenge biotin from its inhabiting niche. Here we report functional definition of S. suis birA homologue. The in vivo functions of the birA paralogue with only 23.6% identity to the counterpart of E. coli, was judged by its ability to complement the conditional lethal mutants of E. coli birA. The recombinant BirA protein of S. suis was overexpressed in E. coli, purified to homogeneity and verified with MS. Both cellulose TLC and MALDI-TOFF-MS assays demonstrated that the S. suis BirA protein catalyzed the biotinylation reaction of its acceptor biotin carboxyl carrier protein. EMSA assays confirmed binding of the bioY gene to the S. suis BirA. The data defined the first example of the bifunctional BirA ligase/repressor in Streptococcus. PMID:27217336

  7. Functional definition of BirA suggests a biotin utilization pathway in the zoonotic pathogen Streptococcus suis

    PubMed Central

    Ye, Huiyan; Cai, Mingzhu; Zhang, Huimin; Li, Zhencui; Wen, Ronghui; Feng, Youjun

    2016-01-01

    Biotin protein ligase is universal in three domains of life. The paradigm version of BPL is the Escherichia coli BirA that is also a repressor for the biotin biosynthesis pathway. Streptococcus suis, a leading bacterial agent for swine diseases, seems to be an increasingly-important opportunistic human pathogen. Unlike the scenario in E. coli, S. suis lacks the de novo biotin biosynthesis pathway. In contrast, it retains a bioY, a biotin transporter-encoding gene, indicating an alternative survival strategy for S. suis to scavenge biotin from its inhabiting niche. Here we report functional definition of S. suis birA homologue. The in vivo functions of the birA paralogue with only 23.6% identity to the counterpart of E. coli, was judged by its ability to complement the conditional lethal mutants of E. coli birA. The recombinant BirA protein of S. suis was overexpressed in E. coli, purified to homogeneity and verified with MS. Both cellulose TLC and MALDI-TOFF-MS assays demonstrated that the S. suis BirA protein catalyzed the biotinylation reaction of its acceptor biotin carboxyl carrier protein. EMSA assays confirmed binding of the bioY gene to the S. suis BirA. The data defined the first example of the bifunctional BirA ligase/repressor in Streptococcus. PMID:27217336

  8. Identifying host pathogenic pathways in bovine digital dermatitis by RNA-Seq analysis.

    PubMed

    Scholey, R A; Evans, N J; Blowey, R W; Massey, J P; Murray, R D; Smith, R F; Ollier, W E; Carter, S D

    2013-09-01

    Digital dermatitis is a painful foot disease compromising welfare in dairy cattle. The disease has a complex multibacterial aetiology, but little is known about its pathogenesis. In this study, gene expression in skin biopsies from five bovine digital dermatitis lesions and five healthy bovine feet was compared using RNA-Seq technology. Differential gene expression was determined after mapping transcripts to the Btau 4.0 genome. Pathway analysis identified gene networks involving differentially expressed transcripts. Bovine digital dermatitis lesions had increased expression of mRNA for α2-macroglobulin-like 1, a protein potentially involved in bacterial immune evasion and bacterial survival. There was increased expression of keratin 6A and interleukin 1β mRNA in bovine digital dermatitis lesions, but reduced expression of most other keratin and keratin-associated genes. There was little evidence of local immune reactions to the bacterial infection present in lesions.

  9. Towards defining a rigidity-associated pathogenic pathway in idiopathic parkinsonism.

    PubMed

    Dobbs, R John; Charlett, André; Dobbs, Sylvia M; Weller, Clive; Iguodala, Owens; Smee, Cori; Bowthorpe, James; Taylor, David; Bjarnason, Ingvar T

    2012-01-01

    Helicobacter pylori eradication has a differential effect on the facets of idiopathic parkinsonism (IP): brady/hypokinesia improves, but rigidity worsens. Small intestinal bacterial overgrowth is common in IP and has been described as a sequel to Helicobacter eradication. The hyperhomocysteinaemia of IP is, in part, explained by serum vitamin B(12), but the concentration is not explained by Helicobacter status. Moreover, Helicobacter-associated gastric atrophy is uncommon in IP. However, overgrowth both increases B(12) utilization and provides a source of inflammation to drive homocysteine production. It is not a bystander event in IP: clouds of lysosomes are seen in duodenal enterocytes. Its candidature for causality of a rigidity-associated pathway is circumstantial: there are biological gradients of rigidity on natural killer and T-helper blood counts, both being higher with hydrogen breath test positivity for overgrowth.

  10. MdsABC-Mediated Pathway for Pathogenicity in Salmonella enterica Serovar Typhimurium.

    PubMed

    Song, Saemee; Lee, Boeun; Yeom, Ji-Hyun; Hwang, Soonhye; Kang, Ilnam; Cho, Jang-Cheon; Ha, Nam-Chul; Bae, Jeehyeon; Lee, Kangseok; Kim, Yong-Hak

    2015-11-01

    MdsABC is a Salmonella-specific tripartite efflux pump that has been implicated in the virulence of Salmonella enterica serovar Typhimurium; however, little is known about the virulence factors associated with this pump. We observed MdsABC expression-dependent alterations in the degree of resistance to extracellular oxidative stress and macrophage-mediated killing. Thin-layer chromatography and tandem mass spectrometry analyses revealed that overexpression of MdsABC led to increased secretion of 1-palmitoyl-2-stearoyl-phosphatidylserine (PSPS), affecting the ability of the bacteria to invade and survive in host cells. Overexpression of MdsABC and external addition of PSPS similarly rendered the mdsABC deletion strain resistant to diamide. Diagonal gel analysis showed that PSPS treatment reduced the diamide-mediated formation of disulfide bonds, particularly in the membrane fraction of the bacteria. Salmonella infection of macrophages induced the upregulation of MdsABC expression and led to an increase of intracellular bacterial number and host cell death, similar to the effects of MdsABC overexpression and PSPS pretreatment on the mdsABC deletion strain. Our study shows that MdsABC mediates a previously uncharacterized pathway that involves PSPS as a key factor for the survival and virulence of S. Typhimurium in phagocytic cells.

  11. Novel Drug Targets for Food-Borne Pathogen Campylobacter jejuni: An Integrated Subtractive Genomics and Comparative Metabolic Pathway Study

    PubMed Central

    Mehla, Kusum

    2015-01-01

    Abstract Campylobacters are a major global health burden and a cause of food-borne diarrheal illness and economic loss worldwide. In developing countries, Campylobacter infections are frequent in children under age two and may be associated with mortality. In developed countries, they are a common cause of bacterial diarrhea in early adulthood. In the United States, antibiotic resistance against Campylobacter is notably increased from 13% in 1997 to nearly 25% in 2011. Novel drug targets are urgently needed but remain a daunting task to accomplish. We suggest that omics-guided drug discovery is timely and worth considering in this context. The present study employed an integrated subtractive genomics and comparative metabolic pathway analysis approach. We identified 16 unique pathways from Campylobacter when compared against H. sapiens with 326 non-redundant proteins; 115 of these were found to be essential in the Database of Essential Genes. Sixty-six proteins among these were non-homologous to the human proteome. Six membrane proteins, of which four are transporters, have been proposed as potential vaccine candidates. Screening of 66 essential non-homologous proteins against DrugBank resulted in identification of 34 proteins with drug-ability potential, many of which play critical roles in bacterial growth and survival. Out of these, eight proteins had approved drug targets available in DrugBank, the majority serving crucial roles in cell wall synthesis and energy metabolism and therefore having the potential to be utilized as drug targets. We conclude by underscoring that screening against these proteins with inhibitors may aid in future discovery of novel therapeutics against campylobacteriosis in ways that will be pathogen specific, and thus have minimal toxic effect on host. Omics-guided drug discovery and bioinformatics analyses offer the broad potential for veritable advances in global health relevant novel therapeutics. PMID:26061459

  12. Rutin-Mediated Priming of Plant Resistance to Three Bacterial Pathogens Initiating the Early SA Signal Pathway

    PubMed Central

    Li, Yang; Wang, Yingzi; Li, Ming; Wang, Yong; Ding, Xinhua; Chu, Zhaohui

    2016-01-01

    Flavonoids are ubiquitous in the plant kingdom and have many diverse functions, including UV protection, auxin transport inhibition, allelopathy, flower coloring and insect resistance. Here we show that rutin, a proud member of the flavonoid family, could be functional as an activator to improve plant disease resistances. Three plant species pretreated with 2 mM rutin were found to enhance resistance to Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Pseudomonas syringae pv. tomato strain DC3000 in rice, tobacco and Arabidopsis thaliana respectively. While they were normally propagated on the cultural medium supplemented with 2 mM rutin for those pathogenic bacteria. The enhanced resistance was associated with primed expression of several pathogenesis-related genes. We also demonstrated that the rutin-mediated priming resistance was attenuated in npr1, eds1, eds5, pad4-1, ndr1 mutants, and NahG transgenic Arabidopsis plant, while not in either snc1-11, ein2-5 or jar1 mutants. We concluded that the rutin-priming defense signal was modulated by the salicylic acid (SA)-dependent pathway from an early stage upstream of NDR1 and EDS1. PMID:26751786

  13. Rutin-Mediated Priming of Plant Resistance to Three Bacterial Pathogens Initiating the Early SA Signal Pathway.

    PubMed

    Yang, Wei; Xu, Xiaonan; Li, Yang; Wang, Yingzi; Li, Ming; Wang, Yong; Ding, Xinhua; Chu, Zhaohui

    2016-01-01

    Flavonoids are ubiquitous in the plant kingdom and have many diverse functions, including UV protection, auxin transport inhibition, allelopathy, flower coloring and insect resistance. Here we show that rutin, a proud member of the flavonoid family, could be functional as an activator to improve plant disease resistances. Three plant species pretreated with 2 mM rutin were found to enhance resistance to Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Pseudomonas syringae pv. tomato strain DC3000 in rice, tobacco and Arabidopsis thaliana respectively. While they were normally propagated on the cultural medium supplemented with 2 mM rutin for those pathogenic bacteria. The enhanced resistance was associated with primed expression of several pathogenesis-related genes. We also demonstrated that the rutin-mediated priming resistance was attenuated in npr1, eds1, eds5, pad4-1, ndr1 mutants, and NahG transgenic Arabidopsis plant, while not in either snc1-11, ein2-5 or jar1 mutants. We concluded that the rutin-priming defense signal was modulated by the salicylic acid (SA)-dependent pathway from an early stage upstream of NDR1 and EDS1. PMID:26751786

  14. Rutin-Mediated Priming of Plant Resistance to Three Bacterial Pathogens Initiating the Early SA Signal Pathway.

    PubMed

    Yang, Wei; Xu, Xiaonan; Li, Yang; Wang, Yingzi; Li, Ming; Wang, Yong; Ding, Xinhua; Chu, Zhaohui

    2016-01-01

    Flavonoids are ubiquitous in the plant kingdom and have many diverse functions, including UV protection, auxin transport inhibition, allelopathy, flower coloring and insect resistance. Here we show that rutin, a proud member of the flavonoid family, could be functional as an activator to improve plant disease resistances. Three plant species pretreated with 2 mM rutin were found to enhance resistance to Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Pseudomonas syringae pv. tomato strain DC3000 in rice, tobacco and Arabidopsis thaliana respectively. While they were normally propagated on the cultural medium supplemented with 2 mM rutin for those pathogenic bacteria. The enhanced resistance was associated with primed expression of several pathogenesis-related genes. We also demonstrated that the rutin-mediated priming resistance was attenuated in npr1, eds1, eds5, pad4-1, ndr1 mutants, and NahG transgenic Arabidopsis plant, while not in either snc1-11, ein2-5 or jar1 mutants. We concluded that the rutin-priming defense signal was modulated by the salicylic acid (SA)-dependent pathway from an early stage upstream of NDR1 and EDS1.

  15. Gene expression analysis of potential genes and pathways involved in the pathogenic mechanisms of parvovirus B19 in human colorectal cancer

    PubMed Central

    ZHANG, WEI-PING; YANG, HUA; CHEN, HONG; ZHU, HAI-RONG; LEI, QUAN; SONG, YUN-HONG; DAI, ZHONG-MING; SUN, JING-SHAN; JIANG, LI-LI; NIE, ZHAN-GUO

    2014-01-01

    In order to investigate the pathogenic mechanisms of parvovirus B19 in human colorectal cancer, plasmids containing the VP1 or VP2 viral capsid proteins or the NS1 non-structural proteins of parvovirus B19 were constructed and transfected into primary human colorectal epithelial cells and LoVo cells. Differential gene expression was detected using a human genome expression array. Functional gene annotation analyses were performed using Database for Annotation, Visualization and Integrated Discovery v6.7 software. Gene ontology (GO) analyses revealed that VP1-related functions included the immune response, immune system process, defense response and the response to stimulus, while NS1-associated functions were found to include organelle fission, nuclear division, mitosis, the M-phase of the mitotic cell cycle, the mitotic cell cycle, M-phase, cell cycle phase, cell cycle process and cell division. Pathway expression analysis revealed that VP1-associated pathways included cell adhesion molecules, antigen processing and presentation, cytokines and the inflammatory response. Moreover, NS1-associated pathways included the cell cycle, pathways in cancer, colorectal cancer, the wnt signaling pathway and focal adhesion. Among the differential genes detected in the present study, 12 genes were found to participate in general cancer pathways and six genes were observed to participate in colorectal cancer pathways. NS1 is a key molecule in the pathogenic mechanism of parvovirus B19 in colorectal cancer. Several GO categories, pathways and genes were selected and may be the key targets through which parvovirus B19 participates in colorectal cancer pathogenesis. PMID:25013465

  16. Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism.

    PubMed

    De Paepe, Boel; Martin, Jean-Jacques; Herbelet, Sandrine; Jimenez-Mallebrera, Cecilia; Iglesias, Estibaliz; Jou, Cristina; Weis, Joachim; De Bleecker, Jan L

    2016-08-01

    Alongside well-known nuclear factor κB (NFκB) and its associated cytokine networks, nuclear factor of activated T cells 5 (NFAT5), the master regulator of cellular osmoprotective programs, comes forward as an inflammatory regulator. To gain insight into its yet unexplored role in muscle disease, we studied the expression of NFAT5 target proteins involved in osmolyte accumulation: aldose reductase (AR), taurine transporter (TauT), and sodium myo-inositol co-transporter (SMIT). We analyzed idiopathic inflammatory myopathy and Duchenne muscular dystrophy muscle biopsies and myotubes in culture, using immunohistochemistry, immunofluorescence, and western blotting. We report that the level of constitutive AR was upregulated in patients, most strongly so in Duchenne muscular dystrophy. TauT and SMIT expression levels were induced in patients' muscle fibers, mostly representing regenerating and atrophic fibers. In dermatomyositis, strong staining for AR, TauT, and SMIT in atrophic perifascicular fibers was accompanied by staining for other molecular NFAT5 targets, including chaperones, chemokines, and inducible nitric oxide synthase. In these fibers, NFAT5 and NFκB p65 staining coincided, linking both transcription factors with this important pathogenic hallmark. In sporadic inclusion body myositis, SMIT localized to inclusions inside muscle fibers. In addition, SMIT was expressed by a substantial subset of muscle-infiltrating macrophages and T cells in patient biopsies. Our results indicate that osmolyte pathways may contribute to normal muscle functioning, and that activation of AR, TauT, and SMIT in muscle inflammation possibly contributes to the tissue's failing program of damage control. PMID:27322952

  17. Two-Component Signaling Regulates Osmotic Stress Adaptation via SskA and the High-Osmolarity Glycerol MAPK Pathway in the Human Pathogen Talaromyces marneffei.

    PubMed

    Boyce, Kylie J; Cao, Cunwei; Andrianopoulos, Alex

    2016-01-01

    For successful infection to occur, a pathogen must be able to evade or tolerate the host's defense systems. This requires the pathogen to first recognize the host environment and then signal this response to elicit a complex adaptive program in order to activate its own defense strategies. In both prokaryotes and eukaryotes, two-component signaling systems are utilized to sense and respond to changes in the external environment. The hybrid histidine kinases (HHKs) at the start of the two-component signaling pathway have been well characterized in human pathogens. However, how these HHKs regulate processes downstream currently remains unclear. This study describes the role of a response regulator downstream of these HHKs, sskA, in Talaromyces marneffei, a dimorphic human pathogen. sskA is required for asexual reproduction, hyphal morphogenesis, cell wall integrity, osmotic adaptation, and the morphogenesis of yeast cells both in vitro at 37°C and during macrophage infection, but not during dimorphic switching. Comparison of the ΔsskA mutant with a strain in which the mitogen-activated protein kinase (MAPK) of the high-osmolarity glycerol pathway (SakA) has been deleted suggests that SskA acts upstream of this pathway in T. marneffei to regulate these morphogenetic processes. This was confirmed by assessing the amount of phosphorylated SakA in the ΔsskA mutant, antifungal resistance due to a lack of SakA activation, and the ability of a constitutively active sakA allele (sakA(F316L) ) to suppress the ΔsskA mutant phenotypes. We conclude that SskA regulates morphogenesis and osmotic stress adaptation in T. marneffei via phosphorylation of the SakA MAPK of the high-osmolarity glycerol pathway. IMPORTANCE This is the first study in a dimorphic fungal pathogen to investigate the role of a response regulator downstream of two-component signaling systems and its connection to the high-osmolarity glycerol pathway. This study will inspire further research into the

  18. Two-Component Signaling Regulates Osmotic Stress Adaptation via SskA and the High-Osmolarity Glycerol MAPK Pathway in the Human Pathogen Talaromyces marneffei

    PubMed Central

    Cao, Cunwei; Andrianopoulos, Alex

    2016-01-01

    ABSTRACT For successful infection to occur, a pathogen must be able to evade or tolerate the host’s defense systems. This requires the pathogen to first recognize the host environment and then signal this response to elicit a complex adaptive program in order to activate its own defense strategies. In both prokaryotes and eukaryotes, two-component signaling systems are utilized to sense and respond to changes in the external environment. The hybrid histidine kinases (HHKs) at the start of the two-component signaling pathway have been well characterized in human pathogens. However, how these HHKs regulate processes downstream currently remains unclear. This study describes the role of a response regulator downstream of these HHKs, sskA, in Talaromyces marneffei, a dimorphic human pathogen. sskA is required for asexual reproduction, hyphal morphogenesis, cell wall integrity, osmotic adaptation, and the morphogenesis of yeast cells both in vitro at 37°C and during macrophage infection, but not during dimorphic switching. Comparison of the ΔsskA mutant with a strain in which the mitogen-activated protein kinase (MAPK) of the high-osmolarity glycerol pathway (SakA) has been deleted suggests that SskA acts upstream of this pathway in T. marneffei to regulate these morphogenetic processes. This was confirmed by assessing the amount of phosphorylated SakA in the ΔsskA mutant, antifungal resistance due to a lack of SakA activation, and the ability of a constitutively active sakA allele (sakAF316L) to suppress the ΔsskA mutant phenotypes. We conclude that SskA regulates morphogenesis and osmotic stress adaptation in T. marneffei via phosphorylation of the SakA MAPK of the high-osmolarity glycerol pathway. IMPORTANCE This is the first study in a dimorphic fungal pathogen to investigate the role of a response regulator downstream of two-component signaling systems and its connection to the high-osmolarity glycerol pathway. This study will inspire further research into

  19. Gaseous 3-pentanol primes plant immunity against a bacterial speck pathogen, Pseudomonas syringae pv. tomato via salicylic acid and jasmonic acid-dependent signaling pathways in Arabidopsis

    PubMed Central

    Song, Geun C.; Choi, Hye K.; Ryu, Choong-Min

    2015-01-01

    3-Pentanol is an active organic compound produced by plants and is a component of emitted insect sex pheromones. A previous study reported that drench application of 3-pentanol elicited plant immunity against microbial pathogens and an insect pest in crop plants. Here, we evaluated whether 3-pentanol and the derivatives 1-pentanol and 2-pentanol induced plant systemic resistance using the in vitro I-plate system. Exposure of Arabidopsis seedlings to 10 μM and 100 nM 3-pentanol evaporate elicited an immune response to Pseudomonas syringae pv. tomato DC3000. We performed quantitative real-time PCR to investigate the 3-pentanol-mediated Arabidopsis immune responses by determining Pathogenesis-Related (PR) gene expression levels associated with defense signaling through salicylic acid (SA), jasmonic acid (JA), and ethylene signaling pathways. The results show that exposure to 3-pentanol and subsequent pathogen challenge upregulated PDF1.2 and PR1 expression. Selected Arabidopsis mutants confirmed that the 3-pentanol-mediated immune response involved SA and JA signaling pathways and the NPR1 gene. Taken together, this study indicates that gaseous 3-pentanol triggers induced resistance in Arabidopsis by priming SA and JA signaling pathways. To our knowledge, this is the first report that a volatile compound of an insect sex pheromone triggers plant systemic resistance against a bacterial pathogen. PMID:26500665

  20. Comparative genomics of Pseudomonas syringae pathovar tomato reveals novel chemotaxis pathways associated with motility and plant pathogenicity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The majority of bacterial foliar plant pathogens must invade the apoplast of host plants through points of ingress, such as stomata or wounds, replicate to high population density and cause disease. How pathogens navigate plant surfaces to locate invasion sites remains poorly understood. Many bacter...

  1. Role of the lpxM lipid A biosynthesis pathway gene in pathogenicity of avian pathogenic Escherichia coli strain E058 in a chicken infection model.

    PubMed

    Xu, Huiqing; Ling, Jielu; Gao, Qingqing; He, Hongbo; Mu, Xiaohui; Yan, Zhen; Gao, Song; Liu, Xiufan

    2013-10-25

    Lipopolysaccharide (LPS) is a major surface component of avian pathogenic Escherichia coli (APEC), and is a possible virulence factor in avian infections caused by this organism. The contribution of the lpxM gene, which encodes a myristoyl transferase that catalyzes the final step in lipid A biosynthesis, to the pathogenicity of APEC has not previously been assessed. In this study, an isogenic lpxM mutant, E058ΔlpxM, was constructed in APEC O2 strain E058 and then characterized. Structural analysis of lipid A from the parental strain and derived mutant showed that E058ΔlpxM lacked one myristoyl (C14:0) on its lipid A molecules. No differences were observed between the mutant and wild-type in a series of tests including growth rate in different broths and ability to survive in specific-pathogen-free chicken serum. However, the mutant showed significantly reduced invasion and intracellular survival in the avian macrophage HD11 cell line (P<0.05). Nitric oxide production reduction (P<0.05) and cytokine gene expression downregulation (P<0.05 or P<0.01) also showed in HD11 treated with E058ΔlpxM-derived LPS compared with that in cells treated with E058-derived LPS at different times. Compared to the parental strain E058, E058ΔlpxM had a significant reduction in bacterial load in heart (P<0.01), liver (P<0.01), spleen (P<0.01), lung (P<0.05), and kidney (P<0.05) tissues. The histopathological lesions in visceral organs of birds challenged with the wild-type strain were more severe than in birds infected with the mutant. However, the E058ΔlpxM mutant showed a similar sensitivity pattern to the parental strain following exposure to several hydrophobic reagents. These results indicate that the lpxM gene is important for the pathogenicity and biological activity of APEC strain E058.

  2. Binding of the pathogen receptor HSP90AA1 to avibirnavirus VP2 induces autophagy by inactivating the AKT-MTOR pathway.

    PubMed

    Hu, Boli; Zhang, Yina; Jia, Lu; Wu, Huansheng; Fan, Chengfei; Sun, Yanting; Ye, Chengjin; Liao, Min; Zhou, Jiyong

    2015-01-01

    Autophagy is an essential component of host innate and adaptive immunity. Viruses have developed diverse strategies for evading or utilizing autophagy for survival. The response of the autophagy pathways to virus invasion is poorly documented. Here, we report on the induction of autophagy initiated by the pathogen receptor HSP90AA1 (heat shock protein 90 kDa α [cytosolic], class A member 1) via the AKT-MTOR (mechanistic target of rapamycin)-dependent pathway. Transmission electron microscopy and confocal microscopy revealed that intracellular autolysosomes packaged avibirnavirus particles. Autophagy detection showed that early avibirnavirus infection not only increased the amount of light chain 3 (LC3)-II, but also upregulated AKT-MTOR dephosphorylation. HSP90AA1-AKT-MTOR knockdown by RNA interference resulted in inhibition of autophagy during avibirnavirus infection. Virus titer assays further verified that autophagy inhibition, but not induction, enhanced avibirnavirus replication. Subsequently, we found that HSP90AA1 binding to the viral protein VP2 resulted in induction of autophagy and AKT-MTOR pathway inactivation. Collectively, our findings suggest that the cell surface protein HSP90AA1, an avibirnavirus-binding receptor, induces autophagy through the HSP90AA1-AKT-MTOR pathway in early infection. We reveal that upon viral recognition, a direct connection between HSP90AA1 and the AKT-MTOR pathway trigger autophagy, a critical step for controlling infection.

  3. Genome Content and Phylogenomics Reveal both Ancestral and Lateral Evolutionary Pathways in Plant-Pathogenic Streptomyces Species

    PubMed Central

    Huguet-Tapia, Jose C.; Lefebure, Tristan; Badger, Jonathan H.; Guan, Dongli; Stanhope, Michael J.

    2016-01-01

    Streptomyces spp. are highly differentiated actinomycetes with large, linear chromosomes that encode an arsenal of biologically active molecules and catabolic enzymes. Members of this genus are well equipped for life in nutrient-limited environments and are common soil saprophytes. Out of the hundreds of species in the genus Streptomyces, a small group has evolved the ability to infect plants. The recent availability of Streptomyces genome sequences, including four genomes of pathogenic species, provided an opportunity to characterize the gene content specific to these pathogens and to study phylogenetic relationships among them. Genome sequencing, comparative genomics, and phylogenetic analysis enabled us to discriminate pathogenic from saprophytic Streptomyces strains; moreover, we calculated that the pathogen-specific genome contains 4,662 orthologs. Phylogenetic reconstruction suggested that Streptomyces scabies and S. ipomoeae share an ancestor but that their biosynthetic clusters encoding the required virulence factor thaxtomin have diverged. In contrast, S. turgidiscabies and S. acidiscabies, two relatively unrelated pathogens, possess highly similar thaxtomin biosynthesis clusters, which suggests that the acquisition of these genes was through lateral gene transfer. PMID:26826232

  4. Genome Content and Phylogenomics Reveal both Ancestral and Lateral Evolutionary Pathways in Plant-Pathogenic Streptomyces Species.

    PubMed

    Huguet-Tapia, Jose C; Lefebure, Tristan; Badger, Jonathan H; Guan, Dongli; Pettis, Gregg S; Stanhope, Michael J; Loria, Rosemary

    2016-04-01

    Streptomyces spp. are highly differentiated actinomycetes with large, linear chromosomes that encode an arsenal of biologically active molecules and catabolic enzymes. Members of this genus are well equipped for life in nutrient-limited environments and are common soil saprophytes. Out of the hundreds of species in the genus Streptomyces, a small group has evolved the ability to infect plants. The recent availability of Streptomyces genome sequences, including four genomes of pathogenic species, provided an opportunity to characterize the gene content specific to these pathogens and to study phylogenetic relationships among them. Genome sequencing, comparative genomics, and phylogenetic analysis enabled us to discriminate pathogenic from saprophytic Streptomyces strains; moreover, we calculated that the pathogen-specific genome contains 4,662 orthologs. Phylogenetic reconstruction suggested that Streptomyces scabies and S. ipomoeae share an ancestor but that their biosynthetic clusters encoding the required virulence factor thaxtomin have diverged. In contrast, S. turgidiscabies and S. acidiscabies, two relatively unrelated pathogens, possess highly similar thaxtomin biosynthesis clusters, which suggests that the acquisition of these genes was through lateral gene transfer. PMID:26826232

  5. Pattern Triggered Immunity (PTI) in Tobacco: Isolation of Activated Genes Suggests Role of the Phenylpropanoid Pathway in Inhibition of Bacterial Pathogens

    PubMed Central

    Szatmári, Ágnes; Zvara, Ágnes; Móricz, Ágnes M.; Besenyei, Eszter; Szabó, Erika; Ott, Péter G.; Puskás, László G.; Bozsó, Zoltán

    2014-01-01

    Background Pattern Triggered Immunity (PTI) or Basal Resistance (BR) is a potent, symptomless form of plant resistance. Upon inoculation of a plant with non-pathogens or pathogenicity-mutant bacteria, the induced PTI will prevent bacterial proliferation. Developed PTI is also able to protect the plant from disease or HR (Hypersensitive Response) after a challenging infection with pathogenic bacteria. Our aim was to reveal those PTI-related genes of tobacco (Nicotiana tabacum) that could possibly play a role in the protection of the plant from disease. Methodology/Principal Findings Leaves were infiltrated with Pseudomonas syringae pv. syringae hrcC- mutant bacteria to induce PTI, and samples were taken 6 and 48 hours later. Subtraction Suppressive Hybridization (SSH) resulted in 156 PTI-activated genes. A cDNA microarray was generated from the SSH clone library. Analysis of hybridization data showed that in the early (6 hpi) phase of PTI, among others, genes of peroxidases, signalling elements, heat shock proteins and secondary metabolites were upregulated, while at the late phase (48 hpi) the group of proteolysis genes was newly activated. Microarray data were verified by real time RT-PCR analysis. Almost all members of the phenyl-propanoid pathway (PPP) possibly leading to lignin biosynthesis were activated. Specific inhibition of cinnamic-acid-4-hydroxylase (C4H), rate limiting enzyme of the PPP, decreased the strength of PTI - as shown by the HR-inhibition and electrolyte leakage tests. Quantification of cinnamate and p-coumarate by thin-layer chromatography (TLC)-densitometry supported specific changes in the levels of these metabolites upon elicitation of PTI. Conclusions/Significance We believe to provide first report on PTI-related changes in the levels of these PPP metabolites. Results implicated an actual role of the upregulation of the phenylpropanoid pathway in the inhibition of bacterial pathogenic activity during PTI. PMID:25101956

  6. Comparative genomics of Pseudomonas syringae pathovar tomato reveals novel chemotaxis pathways associated with motility and plant pathogenicity

    PubMed Central

    Hayes, Byron W.; Runde, Brendan J.; Markel, Eric; Swingle, Bryan M.; Vinatzer, Boris A.

    2016-01-01

    The majority of bacterial foliar plant pathogens must invade the apoplast of host plants through points of ingress, such as stomata or wounds, to replicate to high population density and cause disease. How pathogens navigate plant surfaces to locate invasion sites remains poorly understood. Many bacteria use chemical-directed regulation of flagellar rotation, a process known as chemotaxis, to move towards favorable environmental conditions. Chemotactic sensing of the plant surface is a potential mechanism through which foliar plant pathogens home in on wounds or stomata, but chemotactic systems in foliar plant pathogens are not well characterized. Comparative genomics of the plant pathogen Pseudomonas syringae pathovar tomato (Pto) implicated annotated chemotaxis genes in the recent adaptations of one Pto lineage. We therefore characterized the chemosensory system of Pto. The Pto genome contains two primary chemotaxis gene clusters, che1 and che2. The che2 cluster is flanked by flagellar biosynthesis genes and similar to the canonical chemotaxis gene clusters of other bacteria based on sequence and synteny. Disruption of the primary phosphorelay kinase gene of the che2 cluster, cheA2, eliminated all swimming and surface motility at 21 °C but not 28 °C for Pto. The che1 cluster is located next to Type IV pili biosynthesis genes but disruption of cheA1 has no observable effect on twitching motility for Pto. Disruption of cheA2 also alters in planta fitness of the pathogen with strains lacking functional cheA2 being less fit in host plants but more fit in a non-host interaction. PMID:27812402

  7. In Vitro Studies on the Antimicrobial Peptide Human Beta-Defensin 9 (HBD9): Signalling Pathways and Pathogen-Related Response (An American Ophthalmological Society Thesis)

    PubMed Central

    Dua, Harminder S.; Otri, Ahmad Muneer; Hopkinson, Andrew; Mohammed, Imran

    2014-01-01

    Purpose: Human β-defensins (HBDs) are an important part of the innate immune host defense at the ocular surface. Unlike other defensins, expression of HBD9 at the ocular surface is reduced during microbial infection, but activation of toll-like receptor 2 (TLR2) in corneal epithelial cells has been shown to up-regulate HBD9. Our purpose was to test the hypothesis that TLR2 has a key role in the signalling pathway(s) involved in the overexpression or underexpression of HBD9, and accordingly, different pathogens would induce a different expression pattern of HBD9. Methods: The in vitro RNAi silencing method and response to dexamethasone were used to determine key molecules involved in signalling pathways of HBD9 in immortalized human corneal epithelial cells. The techniques included cell culture with exposure to specific transcription factor inhibitors and bacteria, RNA extraction and cDNA synthesis, quantitative real-time polymerase chain reaction, and immunohistology. Results: This study demonstrates that TLR2 induces HBD9 mRNA and protein expression in a time- and dose-dependent manner. Transforming growth factor-β–activated kinase 1 (TAK1) plays a central role in HBD9 induction by TLR2, and transcription factors c-JUN and activating transcription factor 2 are also involved. Dexamethasone reduces TLR2-mediated up-regulation of HBD9 mRNA and protein levels in mitogen-activated protein kinase phosphatase 1 (MKP1)-dependent and c-JUN-independent manner. HBD9 expression differs with gram-negative and gram-positive bacteria. Conclusions: TLR2-mediated MKPs and nuclear factor-κB signalling pathways are involved in HBD9 expression. TAK-1 is a key molecule. These molecules can be potentially targeted to modulate HBD9 expression. Differential expression of HBD9 with different bacteria could be related to differences in pathogen-associated molecular patterns of these organisms. PMID:25646028

  8. Identification of Metabolic Pathways Expressed by Pichia anomala Kh6 in the Presence of the Pathogen Botrytis cinerea on Apple: New Possible Targets for Biocontrol Improvement

    PubMed Central

    Kwasiborski, Anthony; Bajji, Mohammed; Renaut, Jenny; Delaplace, Pierre; Jijakli, M. Haissam

    2014-01-01

    Yeast Pichia anomala strain Kh6 Kurtzman (Saccharomycetales: Endomycetaceae) exhibits biological control properties that provide an alternative to the chemical fungicides currently used by fruit or vegetable producers against main post-harvest pathogens, such as Botrytis cinerea (Helotiales: Sclerotiniaceae). Using an in situ model that takes into account interactions between organisms and a proteomic approach, we aimed to identify P. anomala metabolic pathways influenced by the presence of B. cinerea. A total of 105 and 60 P. anomala proteins were differentially represented in the exponential and stationary growth phases, respectively. In the exponential phase and in the presence of B. cinerea, the pentose phosphate pathway seems to be enhanced and would provide P. anomala with the needed nucleic acids and energy for the wound colonisation. In the stationary phase, P. anomala would use alcoholic fermentation both in the absence and presence of the pathogen. These results would suggest that the competitive colonisation of apple wounds could be implicated in the mode of action of P. anomala against B. cinerea. PMID:24614090

  9. Biosecurity and Vector Behaviour: Evaluating the Potential Threat Posed by Anglers and Canoeists as Pathways for the Spread of Invasive Non-Native Species and Pathogens

    PubMed Central

    Anderson, Lucy G.; White, Piran C. L.; Stebbing, Paul D.; Stentiford, Grant D.; Dunn, Alison M.

    2014-01-01

    Invasive non-native species (INNS) endanger native biodiversity and are a major economic problem. The management of pathways to prevent their introduction and establishment is a key target in the Convention on Biological Diversity's Aichi biodiversity targets for 2020. Freshwater environments are particularly susceptible to invasions as they are exposed to multiple introduction pathways, including non-native fish stocking and the release of boat ballast water. Since many freshwater INNS and aquatic pathogens can survive for several days in damp environments, there is potential for transport between water catchments on the equipment used by recreational anglers and canoeists. To quantify this biosecurity risk, we conducted an online questionnaire with 960 anglers and 599 canoeists to investigate their locations of activity, equipment used, and how frequently equipment was cleaned and/or dried after use. Anglers were also asked about their use and disposal of live bait. Our results indicate that 64% of anglers and 78.5% of canoeists use their equipment/boat in more than one catchment within a fortnight, the survival time of many of the INNS and pathogens considered in this study and that 12% of anglers and 50% of canoeists do so without either cleaning or drying their kit between uses. Furthermore, 8% of anglers and 28% of canoeists had used their equipment overseas without cleaning or drying it after each use which could facilitate both the introduction and secondary spread of INNS in the UK. Our results provide a baseline against which to evaluate the effectiveness of future biosecurity awareness campaigns, and identify groups to target with biosecurity awareness information. Our results also indicate that the biosecurity practices of these groups must improve to reduce the likelihood of inadvertently spreading INNS and pathogens through these activities. PMID:24717714

  10. Hitting the caspofungin salvage pathway of human-pathogenic fungi with the novel lasso peptide humidimycin (MDN-0010).

    PubMed

    Valiante, Vito; Monteiro, Maria Cândida; Martín, Jesús; Altwasser, Robert; El Aouad, Noureddine; González, Ignacio; Kniemeyer, Olaf; Mellado, Emilia; Palomo, Sara; de Pedro, Nuria; Pérez-Victoria, Ignacio; Tormo, José R; Vicente, Francisca; Reyes, Fernando; Genilloud, Olga; Brakhage, Axel A

    2015-09-01

    Fungal infections have increased dramatically in the last 2 decades, and fighting infectious diseases requires innovative approaches such as the combination of two drugs acting on different targets or even targeting a salvage pathway of one of the drugs. The fungal cell wall biosynthesis is inhibited by the clinically used antifungal drug caspofungin. This antifungal activity has been found to be potentiated by humidimycin, a new natural product identified from the screening of a collection of 20,000 microbial extracts, which has no major effect when used alone. An analysis of transcriptomes and selected Aspergillus fumigatus mutants indicated that humidimycin affects the high osmolarity glycerol response pathway. By combining humidimycin and caspofungin, a strong increase in caspofungin efficacy was achieved, demonstrating that targeting different signaling pathways provides an excellent basis to develop novel anti-infective strategies.

  11. Hitting the Caspofungin Salvage Pathway of Human-Pathogenic Fungi with the Novel Lasso Peptide Humidimycin (MDN-0010)

    PubMed Central

    Valiante, Vito; Monteiro, Maria Cândida; Martín, Jesús; Altwasser, Robert; El Aouad, Noureddine; González, Ignacio; Kniemeyer, Olaf; Mellado, Emilia; Palomo, Sara; de Pedro, Nuria; Pérez-Victoria, Ignacio; Tormo, José R.; Vicente, Francisca

    2015-01-01

    Fungal infections have increased dramatically in the last 2 decades, and fighting infectious diseases requires innovative approaches such as the combination of two drugs acting on different targets or even targeting a salvage pathway of one of the drugs. The fungal cell wall biosynthesis is inhibited by the clinically used antifungal drug caspofungin. This antifungal activity has been found to be potentiated by humidimycin, a new natural product identified from the screening of a collection of 20,000 microbial extracts, which has no major effect when used alone. An analysis of transcriptomes and selected Aspergillus fumigatus mutants indicated that humidimycin affects the high osmolarity glycerol response pathway. By combining humidimycin and caspofungin, a strong increase in caspofungin efficacy was achieved, demonstrating that targeting different signaling pathways provides an excellent basis to develop novel anti-infective strategies. PMID:26055366

  12. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

    PubMed Central

    Cordell, Heather J.; Han, Younghun; Mells, George F.; Li, Yafang; Hirschfield, Gideon M.; Greene, Casey S.; Xie, Gang; Juran, Brian D.; Zhu, Dakai; Qian, David C.; Floyd, James A. B.; Morley, Katherine I.; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Schlicht, Erik M; Lammert, Craig; Atkinson, Elizabeth J; Chan, Landon L; de Andrade, Mariza; Balschun, Tobias; Mason, Andrew L; Myers, Robert P; Zhang, Jinyi; Milkiewicz, Piotr; Qu, Jia; Odin, Joseph A; Luketic, Velimir A; Bacon, Bruce R; Bodenheimer Jr, Henry C; Liakina, Valentina; Vincent, Catherine; Levy, Cynthia; Gregersen, Peter K; Almasio, Piero L; Alvaro, Domenico; Andreone, Pietro; Andriulli, Angelo; Barlassina, Cristina; Battezzati, Pier Maria; Benedetti, Antonio; Bernuzzi, Francesca; Bianchi, Ilaria; Bragazzi, Maria Consiglia; Brunetto, Maurizia; Bruno, Savino; Casella, Giovanni; Coco, Barbara; Colli, Agostino; Colombo, Massimo; Colombo, Silvia; Cursaro, Carmela; Crocè, Lory Saveria; Crosignani, Andrea; Donato, Maria Francesca; Elia, Gianfranco; Fabris, Luca; Ferrari, Carlo; Floreani, Annarosa; Foglieni, Barbara; Fontana, Rosanna; Galli, Andrea; Lazzari, Roberta; Macaluso, Fabio; Malinverno, Federica; Marra, Fabio; Marzioni, Marco; Mattalia, Alberto; Montanari, Renzo; Morini, Lorenzo; Morisco, Filomena; Hani S, Mousa; Muratori, Luigi; Muratori, Paolo; Niro, Grazia A; Palmieri, Vincenzo O; Picciotto, Antonio; Podda, Mauro; Portincasa, Piero; Ronca, Vincenzo; Rosina, Floriano; Rossi, Sonia; Sogno, Ilaria; Spinzi, Giancarlo; Spreafico, Marta; Strazzabosco, Mario; Tarallo, Sonia; Tarocchi, Mirko; Tiribelli, Claudio; Toniutto, Pierluigi; Vinci, Maria; Zuin, Massimo; Ch'ng, Chin Lye; Rahman, Mesbah; Yapp, Tom; Sturgess, Richard; Healey, Christopher; Czajkowski, Marek; Gunasekera, Anton; Gyawali, Pranab; Premchand, Purushothaman; Kapur, Kapil; Marley, Richard; Foster, Graham; Watson, Alan; Dias, Aruna; Subhani, Javaid; Harvey, Rory; McCorry, Roger; Ramanaden, David; Gasem, Jaber; Evans, Richard; Mathialahan, Thiriloganathan; Shorrock, Christopher; Lipscomb, George; Southern, Paul; Tibble, Jeremy; Gorard, David; Palegwala, Altaf; Jones, Susan; Carbone, Marco; Dawwas, Mohamed; Alexander, Graeme; Dolwani, Sunil; Prince, Martin; Foxton, Matthew; Elphick, David; Mitchison, Harriet; Gooding, Ian; Karmo, Mazn; Saksena, Sushma; Mendall, Mike; Patel, Minesh; Ede, Roland; Austin, Andrew; Sayer, Joanna; Hankey, Lorraine; Hovell, Christopher; Fisher, Neil; Carter, Martyn; Koss, Konrad; Piotrowicz, Andrzej; Grimley, Charles; Neal, David; Lim, Guan; Levi, Sass; Ala, Aftab; Broad, Andrea; Saeed, Athar; Wood, Gordon; Brown, Jonathan; Wilkinson, Mark; Gordon, Harriet; Ramage, John; Ridpath, Jo; Ngatchu, Theodore; Grover, Bob; Shaukat, Syed; Shidrawi, Ray; Abouda, George; Ali, Faiz; Rees, Ian; Salam, Imroz; Narain, Mark; Brown, Ashley; Taylor-Robinson, Simon; Williams, Simon; Grellier, Leonie; Banim, Paul; Das, Debashis; Chilton, Andrew; Heneghan, Michael; Curtis, Howard; Gess, Markus; Drake, Ian; Aldersley, Mark; Davies, Mervyn; Jones, Rebecca; McNair, Alastair; Srirajaskanthan, Raj; Pitcher, Maxton; Sen, Sambit; Bird, George; Barnardo, Adrian; Kitchen, Paul; Yoong, Kevin; Chirag, Oza; Sivaramakrishnan, Nurani; MacFaul, George; Jones, David; Shah, Amir; Evans, Chris; Saha, Subrata; Pollock, Katharine; Bramley, Peter; Mukhopadhya, Ashis; Fraser, Andrew; Mills, Peter; Shallcross, Christopher; Campbell, Stewart; Bathgate, Andrew; Shepherd, Alan; Dillon, John; Rushbrook, Simon; Przemioslo, Robert; Macdonald, Christopher; Metcalf, Jane; Shmueli, Udi; Davis, Andrew; Naqvi, Asifabbas; Lee, Tom; Ryder, Stephen D; Collier, Jane; Klass, Howard; Ninkovic, Mary; Cramp, Matthew; Sharer, Nicholas; Aspinall, Richard; Goggin, Patrick; Ghosh, Deb; Douds, Andrew; Hoeroldt, Barbara; Booth, Jonathan; Williams, Earl; Hussaini, Hyder; Stableforth, William; Ayres, Reuben; Thorburn, Douglas; Marshall, Eileen; Burroughs, Andrew; Mann, Steven; Lombard, Martin; Richardson, Paul; Patanwala, Imran; Maltby, Julia; Brookes, Matthew; Mathew, Ray; Vyas, Samir; Singhal, Saket; Gleeson, Dermot; Misra, Sharat; Butterworth, Jeff; George, Keith; Harding, Tim; Douglass, Andrew; Panter, Simon; Shearman, Jeremy; Bray, Gary; Butcher, Graham; Forton, Daniel; Mclindon, John; Cowan, Matthew; Whatley, Gregory; Mandal, Aditya; Gupta, Hemant; Sanghi, Pradeep; Jain, Sanjiv; Pereira, Steve; Prasad, Geeta; Watts, Gill; Wright, Mark; Neuberger, James; Gordon, Fiona; Unitt, Esther; Grant, Allister; Delahooke, Toby; Higham, Andrew; Brind, Alison; Cox, Mark; Ramakrishnan, Subramaniam; King, Alistair; Collins, Carole; Whalley, Simon; Li, Andy; Fraser, Jocelyn; Bell, Andrew; Wong, Voi Shim; Singhal, Amit; Gee, Ian; Ang, Yeng; Ransford, Rupert; Gotto, James; Millson, Charles; Bowles, Jane; Thomas, Caradog; Harrison, Melanie; Galaska, Roman; Kendall, Jennie; Whiteman, Jessica; Lawlor, Caroline; Gray, Catherine; Elliott, Keith; Mulvaney-Jones, Caroline; Hobson, Lucie; Van Duyvenvoorde, Greta; Loftus, Alison; Seward, Katie; Penn, Ruth; Maiden, Jane; Damant, Rose; Hails, Janeane; Cloudsdale, Rebecca; Silvestre, Valeria; Glenn, Sue; Dungca, Eleanor; Wheatley, Natalie; Doyle, Helen; Kent, Melanie; Hamilton, Caroline; Braim, Delyth; Wooldridge, Helen; Abrahams, Rachel; Paton, Alison; Lancaster, Nicola; Gibbins, Andrew; Hogben, Karen; Desousa, Phillipa; Muscariu, Florin; Musselwhite, Janine; McKay, Alexandra; Tan, LaiTing; Foale, Carole; Brighton, Jacqueline; Flahive, Kerry; Nambela, Estelle; Townshend, Paula; Ford, Chris; Holder, Sophie; Palmer, Caroline; Featherstone, James; Nasseri, Mariam; Sadeghian, Joy; Williams, Bronwen; Thomas, Carol; Rolls, Sally-Ann; Hynes, Abigail; Duggan, Claire; Jones, Sarah; Crossey, Mary; Stansfield, Glynis; MacNicol, Carolyn; Wilkins, Joy; Wilhelmsen, Elva; Raymode, Parizade; Lee, Hye-Jeong; Durant, Emma; Bishop, Rebecca; Ncube, Noma; Tripoli, Sherill; Casey, Rebecca; Cowley, Caroline; Miller, Richard; Houghton, Kathryn; Ducker, Samantha; Wright, Fiona; Bird, Bridget; Baxter, Gwen; Keggans, Janie; Hughes, Maggie; Grieve, Emma; Young, Karin; Williams, D; Ocker, Kate; Hines, Frances; Martin, Kirsty; Innes, Caron; Valliani, Talal; Fairlamb, Helen; Thornthwaite, Sarah; Eastick, Anne; Tanqueray, Elizabeth; Morrison, Jennifer; Holbrook, Becky; Browning, Julie; Walker, Kirsten; Congreave, Susan; Verheyden, Juliette; Slininger, Susan; Stafford, Lizzie; O'Donnell, Denise; Ainsworth, Mark; Lord, Susan; Kent, Linda; March, Linda; Dickson, Christine; Simpson, Diane; Longhurst, Beverley; Hayes, Maria; Shpuza, Ervin; White, Nikki; Besley, Sarah; Pearson, Sallyanne; Wright, Alice; Jones, Linda; Gunter, Emma; Dewhurst, Hannah; Fouracres, Anna; Farrington, Liz; Graves, Lyn; Marriott, Suzie; Leoni, Marina; Tyrer, David; Martin, Kate; Dali-kemmery, Lola; Lambourne, Victoria; Green, Marie; Sirdefield, Dawn; Amor, Kelly; Colley, Julie; Shinder, Bal; Jones, Jayne; Mills, Marisa; Carnahan, Mandy; Taylor, Natalie; Boulton, Kerenza; Tregonning, Julie; Brown, Carly; Clifford, Gayle; Archer, Emily; Hamilton, Maria; Curtis, Janette; Shewan, Tracey; Walsh, Sue; Warner, Karen; Netherton, Kimberley; Mupudzi, Mcdonald; Gunson, Bridget; Gitahi, Jane; Gocher, Denise; Batham, Sally; Pateman, Hilary; Desmennu, Senayon; Conder, Jill; Clement, Darren; Gallagher, Susan; Orpe, Jacky; Chan, PuiChing; Currie, Lynn; O'Donohoe, Lynn; Oblak, Metod; Morgan, Lisa; Quinn, Marie; Amey, Isobel; Baird, Yolanda; Cotterill, Donna; Cumlat, Lourdes; Winter, Louise; Greer, Sandra; Spurdle, Katie; Allison, Joanna; Dyer, Simon; Sweeting, Helen; Kordula, Jean; Gershwin, M. Eric; Anderson, Carl A.; Lazaridis, Konstantinos N.; Invernizzi, Pietro; Seldin, Michael F.; Sandford, Richard N.; Amos, Christopher I.; Siminovitch, Katherine A.

    2015-01-01

    Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist. PMID:26394269

  13. Pathogenic Lifestyles of E. coli Pathotypes in a Standardized Epithelial Cell Model Influence Inflammatory Signaling Pathways and Cytokines Secretion

    PubMed Central

    Sanchez-Villamil, Javier; Tapia-Pastrana, Gabriela; Navarro-Garcia, Fernando

    2016-01-01

    Inflammatory response is key for the host defense against diarrheagenic Escherichia coli and contributes to the pathogenesis of the disease but there is not a comparative study among different diarrheagenic pathotypes. We analyzed the inflammatory response induced by five diarrheagenic pathotypes in a HT-29 cell infection model. The model was unified to reproduce the pathogenesis of each pathotype. To compare the inflammatory responses we evaluated: (i) nuclear NF-κB and ERK1/2 translocation by confocal microscopy; (ii) kinetics of activation by each pathway detecting p65 and ERK1/2 phosphorylation by Western blotting; (iii) pathways modulation through bacterial infections with or without co-stimulation with TNF-α or EGF; (iv) cytokine profile induced by each pathotype with and without inhibitors of each pathway. EHEC but mainly EPEC inhibited translocation and activation of p65 and ERK1/2 pathways, as well as cytokines secretion; inhibition of p65 and ERK1/2 phosphorylation prevailed in the presence of TNF-α and EGF, respectively. Intracellular strains, EIEC/Shigella flexneri, caused a strong translocation, activation, and cytokines secretion but they could not inhibit TNF-α and EGF stimulation. ETEC and mainly EAEC caused a moderate translocation, but a differential activation, and high cytokines secretion; interestingly TNF-α and EGF stimulation did no modify p65 and ERK1/2 activation. The use of inhibitors of NF-κB and/or ERK1/2 showed that NF-κB is crucial for cytokine induction by the different pathotypes; only partially depended on ERK1/2 activation. Thus, in spite of their differences, the pathotypes can also be divided in three groups according to their inflammatory response as those (i) that inject effectors to cause A/E lesion, which are able to inhibit NF-κB and ERK1/2 pathways, and cytokine secretion; (ii) with fimbrial adherence and toxin secretion with a moderate inhibition of both pathways but high cytokines secretion through autocrine

  14. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

    PubMed

    Cordell, Heather J; Han, Younghun; Mells, George F; Li, Yafang; Hirschfield, Gideon M; Greene, Casey S; Xie, Gang; Juran, Brian D; Zhu, Dakai; Qian, David C; Floyd, James A B; Morley, Katherine I; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Gershwin, M Eric; Anderson, Carl A; Lazaridis, Konstantinos N; Invernizzi, Pietro; Seldin, Michael F; Sandford, Richard N; Amos, Christopher I; Siminovitch, Katherine A

    2015-01-01

    Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist. PMID:26394269

  15. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

    PubMed

    Cordell, Heather J; Han, Younghun; Mells, George F; Li, Yafang; Hirschfield, Gideon M; Greene, Casey S; Xie, Gang; Juran, Brian D; Zhu, Dakai; Qian, David C; Floyd, James A B; Morley, Katherine I; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Gershwin, M Eric; Anderson, Carl A; Lazaridis, Konstantinos N; Invernizzi, Pietro; Seldin, Michael F; Sandford, Richard N; Amos, Christopher I; Siminovitch, Katherine A

    2015-01-01

    Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

  16. Human microRNA-24 modulates highly pathogenic avian-origin H5N1 influenza A virus infection in A549 cells by targeting secretory pathway furin.

    PubMed

    Loveday, Emma-Kate; Diederich, Sandra; Pasick, John; Jean, François

    2015-01-01

    A common critical cellular event that many human enveloped viruses share is the requirement for proteolytic cleavage of the viral glycoprotein by furin in the host secretory pathway. For example, the furin-dependent proteolytic activation of highly pathogenic (HP) influenza A (infA) H5 and H7 haemagglutinin precursor (HA0) subtypes is critical for yielding fusion-competent infectious virions. In this study, we hypothesized that viral hijacking of the furin pathway by HP infA viruses to permit cleavage of HA0 could represent a novel molecular mechanism controlling the dynamic production of fusion-competent infectious virus particles during the viral life cycle. We explored the biological role of a newly identified furin-directed human microRNA, miR-24, in this process as a potential post-transcriptional regulator of the furin-mediated activation of HA0 and production of fusion-competent virions in the host secretory pathway. We report that miR-24 and furin are differentially expressed in human A549 cells infected with HP avian-origin infA H5N1. Using miR-24 mimics, we demonstrated a robust decrease in both furin mRNA levels and intracellular furin activity in A549 cells. Importantly, pretreatment of A549 cells with miR-24 mimicked these results: a robust decrease of H5N1 infectious virions and a complete block of H5N1 virus spread that was not observed in A549 cells infected with low-pathogenicity swine-origin infA H1N1 virus. Our results suggest that viral-specific downregulation of furin-directed microRNAs such as miR-24 during the life cycle of HP infA viruses may represent a novel regulatory mechanism that governs furin-mediated proteolytic activation of HA0 glycoproteins and production of infectious virions.

  17. Pathogen-induced systemic activation of a plant defensin gene in Arabidopsis follows a salicylic acid-independent pathway.

    PubMed Central

    Penninckx, I A; Eggermont, K; Terras, F R; Thomma, B P; De Samblanx, G W; Buchala, A; Métraux, J P; Manners, J M; Broekaert, W F

    1996-01-01

    A 5-kD plant defensin was purified from Arabidopsis leaves challenged with the fungus Alternaria brassicicola and shown to possess antifungal properties in vitro. The corresponding plant defensin gene was induced after treatment of leaves with methyl jasmonate or ethylene but not with salicylic acid or 2,6-dichloroisonicotinic acid. When challenged with A. brassicicola, the levels of the plant defensin protein and mRNA rose both in inoculated leaves and in nontreated leaves of inoculated plants (systemic leaves). These events coincided with an increase in the endogenous jasmonic acid content of both types of leaves. Systemic pathogen-induced expression of the plant defensin gene was unaffected in Arabidopsis transformants (nahG) or mutants (npr1 and cpr1) affected in the salicylic acid response but was strongly reduced in the Arabidopsis mutants eln2 and col1 that are blocked in their response to ethylene and methyl jasmonate, respectively. Our results indicate that systemic pathogen-induced expression of the plant defensin gene in Arabidopsis is independent of salicylic acid but requires components of the ethylene and jasmonic acid response. PMID:8989885

  18. Genes of the de novo and Salvage Biosynthesis Pathways of Vitamin B6 are Regulated under Oxidative Stress in the Plant Pathogen Rhizoctonia solani.

    PubMed

    Samsatly, Jamil; Chamoun, Rony; Gluck-Thaler, Emile; Jabaji, Suha

    2015-01-01

    Vitamin B6 is recognized as an important cofactor required for numerous metabolic enzymes, and has been shown to act as an antioxidant and play a role in stress responses. It can be synthesized through two different routes: salvage and de novo pathways. However, little is known about the possible function of the vitamin B6 pathways in the fungal plant pathogen Rhizoctonia solani. Using genome walking, the de novo biosynthetic pathway genes; RsolPDX1 and RsolPDX2 and the salvage biosynthetic pathway gene, RsolPLR were sequenced. The predicted amino acid sequences of the three genes had high degrees of similarity to other fungal PDX1, PDX2, and PLR proteins and are closely related to other R. solani anastomosis groups. We also examined their regulation when subjected to reactive oxygen species (ROS) stress inducers, the superoxide generator paraquat, or H2O2, and compared it to the well-known antioxidant genes, catalase and glutathione-S-transferase (GST). The genes were differentially regulated with transcript levels as high as 33 fold depending on the gene and type of stress reflecting differences in the type of damage induced by ROS. Exogenous addition of the vitamers PN or PLP in culture medium significantly induced the transcription of the vitamin B6 de novo encoding genes as early as 0.5 hour post treatment (HPT). On the other hand, transcription of RsolPLR was vitamer-specific; a down regulation upon supplementation of PN and upregulation with PLP. Our results suggest that accumulation of ROS in R. solani mycelia is linked to transcriptional regulation of the three genes and implicate the vitamin B6 biosynthesis machinery in R. solani, similar to catalases and GST, as an antioxidant stress protector against oxidative stress.

  19. Genes of the de novo and Salvage Biosynthesis Pathways of Vitamin B6 are Regulated under Oxidative Stress in the Plant Pathogen Rhizoctonia solani

    PubMed Central

    Samsatly, Jamil; Chamoun, Rony; Gluck-Thaler, Emile; Jabaji, Suha

    2016-01-01

    Vitamin B6 is recognized as an important cofactor required for numerous metabolic enzymes, and has been shown to act as an antioxidant and play a role in stress responses. It can be synthesized through two different routes: salvage and de novo pathways. However, little is known about the possible function of the vitamin B6 pathways in the fungal plant pathogen Rhizoctonia solani. Using genome walking, the de novo biosynthetic pathway genes; RsolPDX1 and RsolPDX2 and the salvage biosynthetic pathway gene, RsolPLR were sequenced. The predicted amino acid sequences of the three genes had high degrees of similarity to other fungal PDX1, PDX2, and PLR proteins and are closely related to other R. solani anastomosis groups. We also examined their regulation when subjected to reactive oxygen species (ROS) stress inducers, the superoxide generator paraquat, or H2O2, and compared it to the well-known antioxidant genes, catalase and glutathione-S-transferase (GST). The genes were differentially regulated with transcript levels as high as 33 fold depending on the gene and type of stress reflecting differences in the type of damage induced by ROS. Exogenous addition of the vitamers PN or PLP in culture medium significantly induced the transcription of the vitamin B6 de novo encoding genes as early as 0.5 hour post treatment (HPT). On the other hand, transcription of RsolPLR was vitamer-specific; a down regulation upon supplementation of PN and upregulation with PLP. Our results suggest that accumulation of ROS in R. solani mycelia is linked to transcriptional regulation of the three genes and implicate the vitamin B6 biosynthesis machinery in R. solani, similar to catalases and GST, as an antioxidant stress protector against oxidative stress. PMID:26779127

  20. Modulation of Plant RAB GTPase-Mediated Membrane Trafficking Pathway at the Interface Between Plants and Obligate Biotrophic Pathogens.

    PubMed

    Inada, Noriko; Betsuyaku, Shigeyuki; Shimada, Takashi L; Ebine, Kazuo; Ito, Emi; Kutsuna, Natsumaro; Hasezawa, Seiichiro; Takano, Yoshitaka; Fukuda, Hiroo; Nakano, Akihiko; Ueda, Takashi

    2016-09-01

    RAB5 is a small GTPase that acts in endosomal trafficking. In addition to canonical RAB5 members that are homologous to animal RAB5, land plants harbor a plant-specific RAB5, the ARA6 group, which regulates trafficking events distinct from canonical RAB5 GTPases. Here, we report that plant RAB5, both canonical and plant-specific members, accumulate at the interface between host plants and biotrophic fungal and oomycete pathogens. Biotrophic fungi and oomycetes colonize living plant tissues by establishing specialized infection hyphae, the haustorium, within host plant cells. We found that Arabidopsis thaliana ARA6/RABF1, a plant-specific RAB5, is localized to the specialized membrane that surrounds the haustorium, the extrahaustorial membrane (EHM), formed by the A. thaliana-adapted powdery mildew fungus Golovinomyces orontii Whereas the conventional RAB5 ARA7/RABF2b was also localized to the EHM, endosomal SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) and RAB5-activating proteins were not, which suggests that the EHM has modified endosomal characteristic. The recruitment of host RAB5 to the EHM was a property shared by the barley-adapted powdery mildew fungus Blumeria graminis f.sp. hordei and the oomycete Hyaloperonospora arabidopsidis, but the extrahyphal membrane surrounding the hypha of the hemibiotrophic fungus Colletotrichum higginsianum at the biotrophic stage was devoid of RAB5. The localization of RAB5 to the EHM appears to correlate with the functionality of the haustorium. Our discovery sheds light on a novel relationship between plant RAB5 and obligate biotrophic pathogens. PMID:27318282

  1. Modulation of Plant RAB GTPase-Mediated Membrane Trafficking Pathway at the Interface Between Plants and Obligate Biotrophic Pathogens.

    PubMed

    Inada, Noriko; Betsuyaku, Shigeyuki; Shimada, Takashi L; Ebine, Kazuo; Ito, Emi; Kutsuna, Natsumaro; Hasezawa, Seiichiro; Takano, Yoshitaka; Fukuda, Hiroo; Nakano, Akihiko; Ueda, Takashi

    2016-09-01

    RAB5 is a small GTPase that acts in endosomal trafficking. In addition to canonical RAB5 members that are homologous to animal RAB5, land plants harbor a plant-specific RAB5, the ARA6 group, which regulates trafficking events distinct from canonical RAB5 GTPases. Here, we report that plant RAB5, both canonical and plant-specific members, accumulate at the interface between host plants and biotrophic fungal and oomycete pathogens. Biotrophic fungi and oomycetes colonize living plant tissues by establishing specialized infection hyphae, the haustorium, within host plant cells. We found that Arabidopsis thaliana ARA6/RABF1, a plant-specific RAB5, is localized to the specialized membrane that surrounds the haustorium, the extrahaustorial membrane (EHM), formed by the A. thaliana-adapted powdery mildew fungus Golovinomyces orontii Whereas the conventional RAB5 ARA7/RABF2b was also localized to the EHM, endosomal SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) and RAB5-activating proteins were not, which suggests that the EHM has modified endosomal characteristic. The recruitment of host RAB5 to the EHM was a property shared by the barley-adapted powdery mildew fungus Blumeria graminis f.sp. hordei and the oomycete Hyaloperonospora arabidopsidis, but the extrahyphal membrane surrounding the hypha of the hemibiotrophic fungus Colletotrichum higginsianum at the biotrophic stage was devoid of RAB5. The localization of RAB5 to the EHM appears to correlate with the functionality of the haustorium. Our discovery sheds light on a novel relationship between plant RAB5 and obligate biotrophic pathogens.

  2. Artesunate alleviates hepatic fibrosis induced by multiple pathogenic factors and inflammation through the inhibition of LPS/TLR4/NF-κB signaling pathway in rats.

    PubMed

    Lai, Lina; Chen, Yunxia; Tian, Xiaoxia; Li, Xujiong; Zhang, Xiaojing; Lei, Jingwen; Bi, Yanghui; Fang, Buwu; Song, Xiaoliang

    2015-10-15

    The current study was performed in order to explore the effect of artesunate (Art) on experimental hepatic fibrosis and the potential mechanism involved. Art, a water-soluble hemisuccinate derivative of artemisinin extracted from the Chinese herb Artemisia Annua, is a safe and effective antimalarial drug. Hepatic fibrosis was induced in SD rats by multiple pathogenic factors. Rats were treated concurrently with Art (28.8 mg/kg) given daily by oral gavage for 6 or 8 weeks to evaluate its protective effects. Our data demonstrated that Art treatment obviously attenuated hepatic fibrosis, characterized by less inflammatory infiltration and accumulation of extracellular matrix (ECM). Art remarkably decreased endotoxin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels as well. Art significantly downregulated protein and mRNA expression of α-smooth muscle actin (α-SMA), toll-like receptors 4 (TLR4), myeloid differentiation factor 88 (MyD88) and transforming growth factor beta 1 (TGF-β1). Art also significantly inhibited the nuclear transcription factor kappa B p65 (NF-κB p65) translocation into the nucleus. In addition, there were no remarkable differences between the N group and the NA group. In conclusion, we found that Art could alleviate hepatic fibrosis induced by multiple pathogenic factors and inflammation through the inhibition of LPS/TLR4/NF-κB signaling pathway in rats, suggesting that Art may be a potential candidate for the therapy of hepatic fibrosis. PMID:26318197

  3. High-content image-based screening of a signal transduction pathway inhibitor small-molecule library against highly pathogenic RNA viruses.

    PubMed

    Mudhasani, Rajini; Kota, Krishna P; Retterer, Cary; Tran, Julie P; Tritsch, Sarah R; Zamani, Rouzbeh; Whitehouse, Chris A; Bavari, Sina

    2015-01-01

    High-content image-based screening was developed as an approach to test a small-molecule library of compounds targeting signal transduction pathways for antiviral activity against multiple highly pathogenic RNA viruses. Of the 2843 compounds screened, 120 compounds exhibited ≥60% antiviral activity. Four compounds (E225-0969, E528-0039, G118-0778, and G544-0735), which were most active against Rift Valley fever virus (RVFV) and showed broad-spectrum antiviral activity, were selected for further evaluation for their concentration-response profile and cytotoxicity. These compounds did not show any visible cytotoxicity at the highest concentration of compound tested (200 µM). All four of these compounds were more active than ribavirin against several viruses. One compound, E225-0969, had the lowest effective concentration (EC50 = 1.9-8.92 µM) for all the viruses tested. This compound was 13- and 43-fold more inhibitory against RVFV and Chikungunya virus (CHIKV), respectively, than ribavirin. The highest selectivity index (>106.2) was for E225-0969 against CHIKV. Time-of-addition assays suggested that all four lead compounds targeted early steps in the viral life cycle (entry and/or replication) but not virus egress. Overall, this work demonstrates that high-content image analysis can be used to screen chemical libraries for new antivirals against highly pathogenic viruses.

  4. Nox Complex signal and MAPK cascade pathway are cross-linked and essential for pathogenicity and conidiation of mycoparasite Coniothyrium minitans

    PubMed Central

    Wei, Wei; Zhu, Wenjun; Cheng, Jiasen; Xie, Jiatao; Jiang, Daohong; Li, Guoqing; Chen, Weidong; Fu, Yanping

    2016-01-01

    The NADPH oxidase complex of a sclerotial mycoparasite Coniothyrium minitans, an important biocontrol agent against crop diseases caused by Sclerotinia sclerotiorum, was identified and its functions involved in conidiation and mycoparasitism were studied. Gene knock-out and complementary experiments indicated that CmNox1, but not CmNox2, is necessary for conidiation and parasitism, and its expression could be significantly induced by its host fungus. CmNox1 is regulated by CmRac1-CmNoxR and interacts with CmSlt2, a homolog of Saccharomyces cerevisiae Slt2 encoding cell wall integrity-related MAP kinase. In ΔCmNox1, CmSlt2-GFP fusion protein lost the ability to localize to the cell nucleus accurately. The defect of conidiation in ΔCmRac1 could be partially restored by over-expressing CmSlt2, indicating that CmSlt2 was a downstream regulatory factor of CmNox1 and was involved in conidiation and parasitism. The expressions of mycoparasitism-related genes CmPks1, Cmg1 and CH1 were suppressed in the knock-out mutants of the genes in CmNox1-CmSlt2 signal pathway when cultivated either on PDA. Therefore, our study infers that CmRac1-CmNoxR regulates CmNox1-CmSlt2 pathway in regulating conidiation and pathogenicity of C. minitans. PMID:27066837

  5. The Extracellular Vesicles of the Helminth Pathogen, Fasciola hepatica: Biogenesis Pathways and Cargo Molecules Involved in Parasite Pathogenesis*

    PubMed Central

    Cwiklinski, Krystyna; de la Torre-Escudero, Eduardo; Trelis, Maria; Bernal, Dolores; Dufresne, Philippe J.; Brennan, Gerard P.; O'Neill, Sandra; Tort, Jose; Paterson, Steve; Marcilla, Antonio; Dalton, John P.; Robinson, Mark W.

    2015-01-01

    Extracellular vesicles (EVs) released by parasites have important roles in establishing and maintaining infection. Analysis of the soluble and vesicular secretions of adult Fasciola hepatica has established a definitive characterization of the total secretome of this zoonotic parasite. Fasciola secretes at least two subpopulations of EVs that differ according to size, cargo molecules and site of release from the parasite. The larger EVs are released from the specialized cells that line the parasite gastrodermus and contain the zymogen of the 37 kDa cathepsin L peptidase that performs a digestive function. The smaller exosome-like vesicle population originate from multivesicular bodies within the tegumental syncytium and carry many previously described immunomodulatory molecules that could be delivered into host cells. By integrating our proteomics data with recently available transcriptomic data sets we have detailed the pathways involved with EV biogenesis in F. hepatica and propose that the small exosome biogenesis occurs via ESCRT-dependent MVB formation in the tegumental syncytium before being shed from the apical plasma membrane. Furthermore, we found that the molecular “machinery” required for EV biogenesis is constitutively expressed across the intramammalian development stages of the parasite. By contrast, the cargo molecules packaged within the EVs are developmentally regulated, most likely to facilitate the parasites migration through host tissue and to counteract host immune attack. PMID:26486420

  6. The Extracellular Vesicles of the Helminth Pathogen, Fasciola hepatica: Biogenesis Pathways and Cargo Molecules Involved in Parasite Pathogenesis.

    PubMed

    Cwiklinski, Krystyna; de la Torre-Escudero, Eduardo; Trelis, Maria; Bernal, Dolores; Dufresne, Philippe J; Brennan, Gerard P; O'Neill, Sandra; Tort, Jose; Paterson, Steve; Marcilla, Antonio; Dalton, John P; Robinson, Mark W

    2015-12-01

    Extracellular vesicles (EVs) released by parasites have important roles in establishing and maintaining infection. Analysis of the soluble and vesicular secretions of adult Fasciola hepatica has established a definitive characterization of the total secretome of this zoonotic parasite. Fasciola secretes at least two subpopulations of EVs that differ according to size, cargo molecules and site of release from the parasite. The larger EVs are released from the specialized cells that line the parasite gastrodermus and contain the zymogen of the 37 kDa cathepsin L peptidase that performs a digestive function. The smaller exosome-like vesicle population originate from multivesicular bodies within the tegumental syncytium and carry many previously described immunomodulatory molecules that could be delivered into host cells. By integrating our proteomics data with recently available transcriptomic data sets we have detailed the pathways involved with EV biogenesis in F. hepatica and propose that the small exosome biogenesis occurs via ESCRT-dependent MVB formation in the tegumental syncytium before being shed from the apical plasma membrane. Furthermore, we found that the molecular "machinery" required for EV biogenesis is constitutively expressed across the intramammalian development stages of the parasite. By contrast, the cargo molecules packaged within the EVs are developmentally regulated, most likely to facilitate the parasites migration through host tissue and to counteract host immune attack.

  7. Nonstarch polysaccharides modulate bacterial microbiota, pathways for butyrate production, and abundance of pathogenic Escherichia coli in the pig gastrointestinal tract.

    PubMed

    Metzler-Zebeli, Barbara U; Hooda, Seema; Pieper, Robert; Zijlstra, Ruurd T; van Kessel, Andrew G; Mosenthin, Rainer; Gänzle, Michael G

    2010-06-01

    The impact of nonstarch polysaccharides (NSP) differing in their functional properties on intestinal bacterial community composition, prevalence of butyrate production pathway genes, and occurrence of Escherichia coli virulence factors was studied for eight ileum-cannulated growing pigs by use of terminal restriction fragment length polymorphism (TRFLP) and quantitative PCR. A cornstarch- and casein-based diet was supplemented with low-viscosity, low-fermentability cellulose (CEL), with high-viscosity, low-fermentability carboxymethylcellulose (CMC), with low-viscosity, high-fermentability oat beta-glucan (LG), and with high-viscosity, high-fermentability oat beta-glucan (HG). Only minor effects of NSP fractions on the ileal bacterial community were observed, but NSP clearly changed the digestion in the small intestine. Compared to what was observed for CMC, more fermentable substrate was transferred into the large intestine with CEL, LG, and HG, resulting in higher levels of postileal dry-matter disappearance. Linear discriminant analysis of NSP and TRFLP profiles and 16S rRNA gene copy numbers for major bacterial groups revealed that CMC resulted in a distinctive bacterial community in comparison to the other NSP, which was characterized by higher gene copy numbers for total bacteria, Bacteroides-Prevotella-Porphyromonas, Clostridium cluster XIVa, and Enterobacteriaceae and increased prevalences of E. coli virulence factors in feces. The numbers of butyryl-coenzyme A (CoA) CoA transferase gene copies were higher than those of butyrate kinase gene copies in feces, and these quantities were affected by NSP. The present results suggest that the NSP fractions clearly and distinctly affected the taxonomic composition and metabolic features of the fecal microbiota. However, the effects were more linked to the individual NSP and to their effect on nutrient flow into the large intestine than to their shared functional properties.

  8. Silicon-Induced Changes in Antifungal Phenolic Acids, Flavonoids, and Key Phenylpropanoid Pathway Genes during the Interaction between Miniature Roses and the Biotrophic Pathogen Podosphaera pannosa1[W

    PubMed Central

    Shetty, Radhakrishna; Fretté, Xavier; Jensen, Birgit; Shetty, Nandini Prasad; Jensen, Jens Due; Jørgensen, Hans Jørgen Lyngs; Newman, Mari-Anne; Christensen, Lars Porskjær

    2011-01-01

    Application of 3.6 mm silicon (Si+) to the rose (Rosa hybrida) cultivar Smart increased the concentration of antimicrobial phenolic acids and flavonoids in response to infection by rose powdery mildew (Podosphaera pannosa). Simultaneously, the expression of genes coding for key enzymes in the phenylpropanoid pathway (phenylalanine ammonia lyase, cinnamyl alcohol dehydrogenase, and chalcone synthase) was up-regulated. The increase in phenolic compounds correlated with a 46% reduction in disease severity compared with inoculated leaves without Si application (Si−). Furthermore, Si application without pathogen inoculation induced gene expression and primed the accumulation of several phenolics compared with the uninoculated Si− control. Chlorogenic acid was the phenolic acid detected in the highest concentration, with an increase of more than 80% in Si+ inoculated compared with Si− uninoculated plants. Among the quantified flavonoids, rutin and quercitrin were detected in the highest concentrations, and the rutin concentration increased more than 20-fold in Si+ inoculated compared with Si− uninoculated plants. Both rutin and chlorogenic acid had antimicrobial effects on P. pannosa, evidenced by reduced conidial germination and appressorium formation of the pathogen, both after spray application and infiltration into leaves. The application of rutin and chlorogenic acid reduced powdery mildew severity by 40% to 50%, and observation of an effect after leaf infiltration indicated that these two phenolics can be transported to the epidermal surface. In conclusion, we provide evidence that Si plays an active role in disease reduction in rose by inducing the production of antifungal phenolic metabolites as a response to powdery mildew infection. PMID:22021421

  9. Three Articles

    ERIC Educational Resources Information Center

    Renwick, E. M.

    1976-01-01

    These three brief articles concern problems students encounter in solving simple linear equations, children's conceptions of number, and the distinction between adding objects and adding numbers as illustrated by students' problems with Euler's formula. (SD)

  10. Quinolones Induce Partial or Total Loss of Pathogenicity Islands in Uropathogenic Escherichia coli by SOS-Dependent or -Independent Pathways, Respectively

    PubMed Central

    Soto, S. M.; Jimenez de Anta, M. T.; Vila, J.

    2006-01-01

    Escherichia coli is the most common microorganism causing urinary tract infections. Quinolone-resistant E. coli strains have fewer virulence factors than quinolone-susceptible strains. Several urovirulence genes are located in pathogenicity islands (PAIs). We investigated the capacity of quinolones to induce loss of virulence factors such as hemolysin, cytotoxic necrotizing factor 1, P fimbriae, and autotransporter Sat included in PAIs in three uropathogenic E. coli strains. In a multistep selection, all strains lost hemolytic capacity at between 1 and 4 passages when they were incubated with subinhibitory concentrations of ciprofloxacin, showing a partial or total loss of the PAI containing the hly (hemolysin) and cnf-1 (cytotoxic necrotizing factor 1) genes. RecA− mutants were obtained from the two E. coli strains with partial or total loss of the PAI. The inactivation of the RecA protein affected only the partial loss of the PAI induced by quinolones. No spontaneous loss of PAIs was observed on incubation in the absence of quinolones in either the wild-type or mutant E. coli strains. Quinolones induce partial or total loss of PAIs in vitro in uropathogenic E. coli by SOS-dependent or -independent pathways, respectively. PMID:16436722

  11. Siderophore-Based Iron Acquisition and Pathogen Control

    PubMed Central

    Miethke, Marcus; Marahiel, Mohamed A.

    2007-01-01

    Summary: High-affinity iron acquisition is mediated by siderophore-dependent pathways in the majority of pathogenic and nonpathogenic bacteria and fungi. Considerable progress has been made in characterizing and understanding mechanisms of siderophore synthesis, secretion, iron scavenging, and siderophore-delivered iron uptake and its release. The regulation of siderophore pathways reveals multilayer networks at the transcriptional and posttranscriptional levels. Due to the key role of many siderophores during virulence, coevolution led to sophisticated strategies of siderophore neutralization by mammals and (re)utilization by bacterial pathogens. Surprisingly, hosts also developed essential siderophore-based iron delivery and cell conversion pathways, which are of interest for diagnostic and therapeutic studies. In the last decades, natural and synthetic compounds have gained attention as potential therapeutics for iron-dependent treatment of infections and further diseases. Promising results for pathogen inhibition were obtained with various siderophore-antibiotic conjugates acting as “Trojan horse” toxins and siderophore pathway inhibitors. In this article, general aspects of siderophore-mediated iron acquisition, recent findings regarding iron-related pathogen-host interactions, and current strategies for iron-dependent pathogen control will be reviewed. Further concepts including the inhibition of novel siderophore pathway targets are discussed. PMID:17804665

  12. Laminate article

    DOEpatents

    Williams, Robert K.; Paranthaman, Mariappan; Chirayil, Thomas G.; Lee, Dominic F.; Goyal, Amit; Feenstra, Roeland

    2002-01-01

    A laminate article comprises a substrate and a biaxially textured (RE.sub.x A.sub.(1-x)).sub.2 O.sub.2-(x/2) buffer layer over the substrate, wherein 0article can include a layer of YBCO over the (RE.sub.x A.sub.(1-x)).sub.2 O.sub.2-(x/2) buffer layer. A layer of CeO.sub.2 between the YBCO layer and the (RE.sub.x A.sub.(1-x)).sub.2 O.sub.2-(x/2) buffer layer can also be include. Further included can be a layer of YSZ between the CeO.sub.2 layer and the (RE.sub.x A.sub.(1-x)).sub.2 O.sub.2-(x/2) buffer layer. The substrate can be a biaxially textured metal, such as nickel. A method of forming the laminate article is also disclosed.

  13. Pathogenicity islands and the evolution of bacterial pathogens.

    PubMed

    Lee, C A

    1996-01-01

    The term pathogenicity island has been used to refer to large chromosomal regions in pathogenic bacteria that encode virulence genes. This article reviews the recent history of this term and considers what characteristics define a pathogenicity island. It appears that pathogenicity islands can confer complex virulence phenotypes and were acquired by bacteria from unrelated organisms, leading to interesting hypotheses about how bacterial pathogens evolved. It is likely that mechanisms that generate pathogenicity islands continue to operate and may contribute to the emergence of bacterial pathogens with new virulence properties.

  14. The bacterial lipopeptide iturins induce Verticillium dahliae cell death by affecting fungal signalling pathways and mediate plant defence responses involved in pathogen-associated molecular pattern-triggered immunity.

    PubMed

    Han, Qin; Wu, Fengli; Wang, Xiaonan; Qi, Hong; Shi, Liang; Ren, Ang; Liu, Qinghai; Zhao, Mingwen; Tang, Canming

    2015-04-01

    Verticillium wilt in cotton caused by Verticillium dahliae is one of the most serious plant diseases worldwide. Because no known fungicides or cotton cultivars provide sufficient protection against this pathogen, V. dahliae causes major crop yield losses. Here, an isolated cotton endophytic bacterium, designated Bacillus amyloliquefaciens 41B-1, exhibited greater than 50% biocontrol efficacy against V. dahliae in cotton plants under greenhouse conditions. Through high-performance liquid chromatography and mass analysis of the filtrate, we found that the antifungal compounds present in the strain 41B-1 culture filtrate were a series of isoforms of iturins. The purified iturins suppressed V. dahliae microsclerotial germination in the absence or presence of cotton. Treatment with the iturins induced reactive oxygen species bursts, Hog1 mitogen-activated protein kinase (MAPK) activation and defects in cell wall integrity. The oxidative stress response and high-osmolarity glycerol pathway contribute to iturins resistance in V. dahliae. In contrast, the Slt2 MAPK pathway may be involved in iturins sensitivity in this fungus. In addition to antagonism, iturins could induce plant defence responses as activators and mediate pathogen-associated molecular pattern-triggered immunity. These findings suggest that iturins may affect fungal signalling pathways and mediate plant defence responses against V. dahliae.

  15. Bacterial Metabolism Shapes the Host-Pathogen Interface.

    PubMed

    Passalacqua, Karla D; Charbonneau, Marie-Eve; O'Riordan, Mary X D

    2016-06-01

    Bacterial pathogens have evolved to exploit humans as a rich source of nutrients to support survival and replication. The pathways of bacterial metabolism that permit successful colonization are surprisingly varied and highlight remarkable metabolic flexibility. The constraints and immune pressures of distinct niches within the human body set the stage for understanding the mechanisms by which bacteria acquire critical nutrients. In this article we discuss how different bacterial pathogens carry out carbon and energy metabolism in the host and how they obtain or use key nutrients for replication and immune evasion. PMID:27337445

  16. Bloodborne pathogens

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000453.htm Bloodborne pathogens To use the sharing features on this page, please enable JavaScript. A pathogen is something that causes disease. Germs that can ...

  17. Conservation and divergence of the cyclic adenosine monophosphate-protein kinase A (cAMP–PKA) pathway in two plant-pathogenic fungi: Fusarium graminearum and F. verticillioides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cyclic AMP (cAMP)-PKA pathway is a central signaling cascade that transmits extracellular stimuli and governs cell responses through the second messenger cAMP. The importance of cAMP signaling in fungal biology has been well documented. Two key conserved components, adenylate cyclase (AC) and ca...

  18. Conservation and divergence of the cyclic adenosine monophosphate–protein kinase A (cAMP–PKA) pathway in two plant-pathogenic fungi: Fusarium graminearum and F. verticillioides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The importance of cAMP signaling in fungal development and pathogenesis has been well documented in many fungal species including several phytopathogenic Fusarium spp. Two key components of the cAMP-PKA pathway, adenylate cyclase (AC) and catalytic subunit of PKA (CPKA), have been functionally chara...

  19. Lysophosphatidylcholine enhances susceptibility in signaling pathway against pathogen infection through biphasic production of reactive oxygen species and ethylene in tobacco plants.

    PubMed

    Wi, Soo Jin; Seo, So yeon; Cho, Kyoungwon; Nam, Myung Hee; Park, Ky Young

    2014-08-01

    It was previously reported that the amounts of lysophosphatidylcholines (lysoPCs), which are naturally occurring bioactive lipid molecules, significantly increase following pathogen inoculation, as determined using ultraperformance liquid chromatography-quadrupole-time of flight/mass spectrometry analyses. Here, real-time quantitative RT-PCR was performed for the phospholipase A2 (PLA2) genes, Nt1PLA2 and Nt2PLA2, which are responsible for LysoPCs generation. The transcription level of Nt2PLA2 in pathogen-infected tobacco plants transiently peaked at 1h and 36 h, whereas induction of Nt1PLA2 transcription peaked at 36 h. A prominent biphasic ROS accumulation in lysoPC (C18:1(9Z))-treated tobacco leaves was also observed. Transcription of NtRbohD, a gene member of NADPH oxidase, showed biphasic kinetics upon lysoPC 18:1 treatment, as evidenced by an early transient peak in phase I at 1h and a massive peak in phase II at 12h. Each increase in NtACS2 and NtACS4 transcription, gene members of the ACC synthase family, was followed by biphasic peaks of ethylene production after lysoPC 18:1 treatment. This suggested that lysoPC (C18:1)-induced ethylene production was regulated at the transcriptional level of time-dependent gene members. LysoPC 18:1 treatment also rapidly induced cell damage. LysoPC 18:1-induced cell death was almost completely abrogated in ROS generation-impaired transgenic plants (rbohD-as and rbohF-as), ethylene production-impaired transgenic plants (CAS-AS and CAO-AS), and ethylene signaling-impaired transgenic plants (Ein3-AS), respectively. Taken together, pathogen-induced lysoPCs enhance pathogen susceptibility accompanied by ROS and ethylene biosynthesis, resulting in chlorophyll degradation and cell death. Expression of PR genes (PR1-a, PR-3, and PR-4b) and LOX3 was strongly induced in lysoPC 18:1-treated leaves, indicating the involvement of lysoPC 18:1 in the defense response. However, lysoPC 18:1 treatment eventually resulted in cell death, as

  20. The plant pathogen Streptomyces scabies 87-22 has a functional pyochelin biosynthetic pathway that is regulated by TetR- and AfsR-family proteins.

    PubMed

    Seipke, Ryan F; Song, Lijiang; Bicz, Joanna; Laskaris, Paris; Yaxley, Alice M; Challis, Gregory L; Loria, Rosemary

    2011-09-01

    Siderophores are high-affinity iron-chelating compounds produced by bacteria for iron uptake that can act as important virulence determinants for both plant and animal pathogens. Genome sequencing of the plant pathogen Streptomyces scabies 87-22 revealed the presence of a putative pyochelin biosynthetic gene cluster (PBGC). Liquid chromatography (LC)-MS analyses of culture supernatants of S. scabies mutants, in which expression of the cluster is upregulated and which lack a key biosynthetic gene from the cluster, indicated that pyochelin is a product of the PBGC. LC-MS comparisons with authentic standards on a homochiral stationary phase confirmed that pyochelin and not enantio-pyochelin (ent-pyochelin) is produced by S. scabies. Transcription of the S. scabies PBGC occurs via ~19 kb and ~3 kb operons and transcription of the ~19 kb operon is regulated by TetR- and AfsR-family proteins encoded by the cluster. This is the first report, to our knowledge, of pyochelin production by a Gram-positive bacterium; interestingly regulation of pyochelin production is distinct from characterized PBGCs in Gram-negative bacteria. Though pyochelin-mediated iron acquisition by Pseudomonas aeruginosa is important for virulence, in planta bioassays failed to demonstrate that pyochelin production by S. scabies is required for development of disease symptoms on excised potato tuber tissue or radish seedlings. PMID:21757492

  1. The FUS3 MAPK signaling pathway of the citrus pathogen Alternaria alternata functions independently or cooperatively with the fungal redox-responsive AP1 regulator for diverse developmental, physiological and pathogenic processes.

    PubMed

    Lin, Ching-Hsuan; Yang, Siwy Ling; Wang, Nan-Yi; Chung, Kuang-Ren

    2010-04-01

    Alternaria alternata, the fungus that causes citrus brown spot, invades its hosts primarily through the production and action of a host-selective ACT toxin that kills citrus cells prior to invasion. In this study, we show that, in the tangerine pathotype of A. alternata, a mitogen-activated protein kinase (MAPK)-mediated signaling pathway governs a number of biological functions, either separately or in a cooperative manner, with the AaAP1 gene encoding a transcription regulator. The reported MAPK is encoded by the AaFUS3 gene, which we show to be necessary for conidial development, resistance to copper fungicides, melanin biosynthesis, and particularly, for elaboration of the penetration process. In contrast, AaFUS3 negatively controls salt tolerance and production of several hydrolytic enzymes. AaFUS3 has no apparent role in the biosynthesis of host-selective toxin or in resistance to oxidative stress. Both AaAP1 and AaFUS3 are required for fungal resistance to 2,3,5-triiodobenzoic acid (TIBA), 2-chloro-5-hydroxypyridine (CHP), diethyl maleate (DEM), and many pyridine-containing compounds. A strain with mutations in both AaAP1 and AaFUS3 displayed an increased sensitivity to these compounds. Expression of the AaAP1 and AaFUS3 genes and phosphorylation of AaFUS3 were also induced by CHP, DEM, or TIBA. Expression of two genes coding for a putative MFS transporter was coordinately regulated by AaAP1 and AaFUS3. The AaAP1::sGFP (synthetic green fluorescent protein) fusion protein became localized in the nucleus in response to CHP or TIBA. Inactivation of the AaAP1 gene, however, promoted phosphorylation of AaFUS3. Taken together, our results indicate that A. alternata utilizes specialized or synergistic regulatory interactions between the AP1 and MAPK signaling pathways for diverse physiological functions.

  2. FvBck1, a component of cell wall integrity MAP kinase pathway, is required for virulence and oxidative stress response in sugarcane Pokkah Boeng pathogen

    PubMed Central

    Zhang, Chengkang; Wang, Jianqiang; Tao, Hong; Dang, Xie; Wang, Yang; Chen, Miaoping; Zhai, Zhenzhen; Yu, Wenying; Xu, Liping; Shim, Won-Bo; Lu, Guodong; Wang, Zonghua

    2015-01-01

    Fusarium verticillioides (formerly F. moniliforme) is suggested as one of the causal agents of Pokkah Boeng, a serious disease of sugarcane worldwide. Currently, detailed molecular and physiological mechanism of pathogenesis is unknown. In this study, we focused on cell wall integrity MAPK pathway as one of the potential signaling mechanisms associated with Pokkah Boeng pathogenesis. We identified FvBCK1 gene that encodes a MAP kinase kinase kinase homolog and determined that it is not only required for growth, micro- and macro-conidia production, and cell wall integrity but also for response to osmotic and oxidative stresses. The deletion of FvBCK1 caused a significant reduction in virulence and FB1 production, a possibly carcinogenic mycotoxin produced by the fungus. Moreover, we found the expression levels of three genes, which are known to be involved in superoxide scavenging, were down regulated in the mutant. We hypothesized that the loss of superoxide scavenging capacity was one of the reasons for reduced virulence, but overexpression of catalase or peroxidase gene failed to restore the virulence defect in the deletion mutant. When we introduced Magnaporthe oryzae MCK1 into the FvBck1 deletion mutant, while certain phenotypes were restored, the complemented strain failed to gain full virulence. In summary, FvBck1 plays a diverse role in F. verticillioides, and detailed investigation of downstream signaling pathways will lead to a better understanding of how this MAPK pathway regulates Pokkah Boeng on sugarcane. PMID:26500635

  3. Rhamnolipids elicit defense responses and induce disease resistance against biotrophic, hemibiotrophic, and necrotrophic pathogens that require different signaling pathways in Arabidopsis and highlight a central role for salicylic acid.

    PubMed

    Sanchez, Lisa; Courteaux, Barbara; Hubert, Jane; Kauffmann, Serge; Renault, Jean-Hugues; Clément, Christophe; Baillieul, Fabienne; Dorey, Stéphan

    2012-11-01

    Plant resistance to phytopathogenic microorganisms mainly relies on the activation of an innate immune response usually launched after recognition by the plant cells of microbe-associated molecular patterns. The plant hormones, salicylic acid (SA), jasmonic acid, and ethylene have emerged as key players in the signaling networks involved in plant immunity. Rhamnolipids (RLs) are glycolipids produced by bacteria and are involved in surface motility and biofilm development. Here we report that RLs trigger an immune response in Arabidopsis (Arabidopsis thaliana) characterized by signaling molecules accumulation and defense gene activation. This immune response participates to resistance against the hemibiotrophic bacterium Pseudomonas syringae pv tomato, the biotrophic oomycete Hyaloperonospora arabidopsidis, and the necrotrophic fungus Botrytis cinerea. We show that RL-mediated resistance involves different signaling pathways that depend on the type of pathogen. Ethylene is involved in RL-induced resistance to H. arabidopsidis and to P. syringae pv tomato whereas jasmonic acid is essential for the resistance to B. cinerea. SA participates to the restriction of all pathogens. We also show evidence that SA-dependent plant defenses are potentiated by RLs following challenge by B. cinerea or P. syringae pv tomato. These results highlight a central role for SA in RL-mediated resistance. In addition to the activation of plant defense responses, antimicrobial properties of RLs are thought to participate in the protection against the fungus and the oomycete. Our data highlight the intricate mechanisms involved in plant protection triggered by a new type of molecule that can be perceived by plant cells and that can also act directly onto pathogens. PMID:22968829

  4. Arrestins in host-pathogen interactions

    PubMed Central

    Marullo, Stefano; Coureuil, Mathieu

    2014-01-01

    In the context of host-pathogen interaction, host cell receptors and signaling pathways are essential for both invading pathogens, which exploit them at their own profit, and the defending organism, which activates early mechanism of defense, known as innate immunity, to block the aggression. Because of their central role as scaffolding proteins downstream of activated receptors, β-arrestins are involved in multiple signaling pathways activated in host cells by pathogens. Some of these pathways participate to the innate immunity and the inflammatory response. Other β-arrestin-dependent pathways are actually hijacked by microbes and toxins to penetrate into host cells and spread in the organism. PMID:24292839

  5. Activation of an EDS1-mediated R-gene pathway in the snc1 mutant leads to constitutive, NPR1-independent pathogen resistance.

    PubMed

    Li, X; Clarke, J D; Zhang, Y; Dong, X

    2001-10-01

    The Arabidopsis NPR1 protein is an essential regulatory component of systemic acquired resistance (SAR). Mutations in the NPR1 gene completely block the induction of SAR by signals such as salicylic acid (SA). An Arabidopsis mutant, snc1 (suppressor of npr1-1, constitutive 1), was isolated in a screen for suppressors of npr1-1. In the npr1-1 background, the snc1 mutation resulted in constitutive resistance to Pseudomonas syringae maculicola ES4326 and Peronospora parasitica Noco2. High levels of SA were detected in the mutant and shown to be required for manifestation of the snc1 phenotype. The snc1 mutation was mapped to the RPP5 resistance (R) gene cluster and the eds1 mutation that blocks RPP5-mediated resistance suppressed snc1. These data suggest that a RPP5-related resistance pathway is activated constitutively in snc1. This pathway does not employ NPR1 but requires the signal molecule SA and the function of EDS1. Moreover, in snc1, constitutive resistance is conferred in the absence of cell death, which is often associated with R-gene mediated resistance.

  6. N-Acyl-Homoserine Lactone Primes Plants for Cell Wall Reinforcement and Induces Resistance to Bacterial Pathogens via the Salicylic Acid/Oxylipin Pathway[C][W][OPEN

    PubMed Central

    Schenk, Sebastian T.; Hernández-Reyes, Casandra; Samans, Birgit; Stein, Elke; Neumann, Christina; Schikora, Marek; Reichelt, Michael; Mithöfer, Axel; Becker, Annette; Kogel, Karl-Heinz; Schikora, Adam

    2014-01-01

    The ability of plants to monitor their surroundings, for instance the perception of bacteria, is of crucial importance. The perception of microorganism-derived molecules and their effector proteins is the best understood of these monitoring processes. In addition, plants perceive bacterial quorum sensing (QS) molecules used for cell-to-cell communication between bacteria. Here, we propose a mechanism for how N-acyl-homoserine lactones (AHLs), a group of QS molecules, influence host defense and fortify resistance in Arabidopsis thaliana against bacterial pathogens. N-3-oxo-tetradecanoyl-l-homoserine lactone (oxo-C14-HSL) primed plants for enhanced callose deposition, accumulation of phenolic compounds, and lignification of cell walls. Moreover, increased levels of oxylipins and salicylic acid favored closure of stomata in response to Pseudomonas syringae infection. The AHL-induced resistance seems to differ from the systemic acquired and the induced systemic resistances, providing new insight into inter-kingdom communication. Consistent with the observation that short-chain AHLs, unlike oxo-C14-HSL, promote plant growth, treatments with C6-HSL, oxo-C10-HSL, or oxo-C14-HSL resulted in different transcriptional profiles in Arabidopsis. Understanding the priming induced by bacterial QS molecules augments our knowledge of plant reactions to bacteria and suggests strategies for using beneficial bacteria in plant protection. PMID:24963057

  7. Non-nucleoside Inhibitors of BasE, An Adenylating Enzyme in the Siderophore Biosynthetic Pathway of the Opportunistic Pathogen Acinetobacter baumannii

    PubMed Central

    Neres, João; Engelhart, Curtis A.; Drake, Eric J.; Wilson, Daniel J.; Fu, Peng; Boshoff, Helena I.; Barry, Clifton E.; Gulick, Andrew M.; Aldrich, Courtney C.

    2013-01-01

    Siderophores are small-molecule iron chelators produced by bacteria and other microorganisms for survival under iron limiting conditions, such as found in a mammalian host. Siderophore biosynthesis is essential for the virulence of many important Gram-negative pathogens including Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. We performed high-throughput screening of against BasE, which is involved in siderophore biosynthesis in A. baumannii and identified 6-phenyl-1-(pyridin-4-ylmethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid 15. Herein we report the synthesis, biochemical, and microbiological evaluation of a systematic series of analogues of the HTS hit 15. Analogue 67 is the most potent analogue with a KD of 2 nM against BasE. Structural characterization of the inhibitors with BasE reveal they bind in a unique orientation in the active site occupying all three substrate binding sites, and thus can be considered multisubstrate inhibitors. These results provide a foundation for future studies aimed at both increasing enzyme potency and antibacterial activity. PMID:23437866

  8. A Luman/CREB3–ADP-ribosylation factor 4 (ARF4) signaling pathway mediates the response to Golgi stress and susceptibility to pathogens

    PubMed Central

    Reiling, Jan H.; Olive, Andrew J.; Sanyal, Sumana; Carette, Jan E.; Brummelkamp, Thijn R.; Ploegh, Hidde L.; Starnbach, Michael N.; Sabatini, David M.

    2014-01-01

    SUMMARY Treatment of cells with Brefeldin A (BFA) blocks secretory vesicle transport and causes a collapse of the Golgi apparatus. To gain more insight into the cellular mechanisms mediating BFA toxicity, we conducted a genome-wide haploid genetic screen that led to the identification of the small G protein ADP-ribosylation factor 4 (ARF4). ARF4 depletion preserves viability, Golgi integrity and cargo trafficking in the presence of BFA, and these effects depend on the guanine nucleotide exchange factor GBF1 and other ARF isoforms including ARF1 and ARF5. ARF4 knockdown cells show increased resistance to several human pathogens including Chlamydia trachomatis and Shigella flexneri. Furthermore, ARF4 expression is induced when cells are exposed to several Golgi-disturbing agents and requires the CREB3/Luman transcription factor whose downregulation mimics ARF4 loss. Thus, we have uncovered a CREB3–ARF4 signaling cascade that may be part of a Golgi stress response set in motion by stimuli compromising Golgi capacity. PMID:24185178

  9. Enterohaemorrhagic Escherichia coli O157:H7 Shiga-like toxin 1 is required for full pathogenicity and activation of the p38 mitogen-activated protein kinase pathway in Caenorhabditis elegans.

    PubMed

    Chou, T-C; Chiu, H-C; Kuo, C-J; Wu, C-M; Syu, W-J; Chiu, W-T; Chen, C-S

    2013-01-01

    Enterohaemorrhagic Escherichia coli (EHEC) causes life-threatening infections in humans as a consequence of the production of Shiga-like toxins. Lack of a good animal model system currently hinders in vivo study of EHEC virulence by systematic genetic methods. Here we applied the genetically tractable animal, Caenorhabditis elegans, as a surrogate host to study the virulence of EHEC as well as the host immunity to this human pathogen. Our results show that E. coli O157:H7, a serotype of EHEC, infects and kills C. elegans. Bacterial colonization and induction of the characteristic attaching and effacing (A/E) lesions in the intact intestinal epithelium of C. elegans by E. coli O157:H7 were concomitantly demonstrated in vivo. Genetic analysis indicated that the Shiga-like toxin 1 (Stx1) of E. coli O157:H7 is a virulence factor in C. elegans and is required for full toxicity. Moreover, the C. elegans p38 mitogen-activated protein kinase (MAPK) pathway, an evolutionarily conserved innate immune and stress response signalling pathway, is activated in the regulation of host susceptibility to EHEC infection in a Stx1-dependent manner. Our results validate the EHEC-C. elegans interaction as suitable for future comprehensive genetic screens for both novel bacterial and host factors involved in the pathogenesis of EHEC infection.

  10. Activation of Plasmacytoid Dendritic Cells in Colon-Draining Lymph Nodes during Citrobacter rodentium Infection Involves Pathogen-Sensing and Inflammatory Pathways Distinct from Conventional Dendritic Cells.

    PubMed

    Toivonen, Raine; Kong, Lingjia; Rasool, Omid; Lund, Riikka J; Lahesmaa, Riitta; Hänninen, Arno

    2016-06-01

    Dendritic cells (DCs) bear the main responsibility for initiation of adaptive immune responses necessary for antimicrobial immunity. In the small intestine, afferent lymphatics convey Ags and microbial signals to mesenteric lymph nodes (LNs) to induce adaptive immune responses against microbes and food Ags derived from the small intestine. Whether the large intestine is covered by the same lymphatic system or represents its own lymphoid compartment has not been studied until very recently. We identified three small mesenteric LNs, distinct from small intestinal LNs, which drain lymph specifically from the colon, and studied DC responses to the attaching and effacing pathogen Citrobacter rodentium in these. Transcriptional profiling of conventional (CD11c(high)CD103(high)) DC and plasmacytoid (plasmacytoid DC Ag-1(high)B220(+)CD11c(int)) DC (pDC) populations during steady-state conditions revealed activity of distinct sets of genes in these two DC subsets, both in small intestinal and colon-draining LNs. C. rodentium activated DC especially in colon-draining LNs, and gene expression changed in pDC more profoundly than in conventional DC. Among the genes most upregulated in pDC were C-type lectin receptor CLEC4E, IL-1Rs (IL-1R1 and -2), proinflammatory cytokines (IL-1a and IL-6), and TLR6. Our results indicate that colon immune surveillance is distinct from that of the small intestine in terms of draining LNs, and identify pDC as active sentinels of colonic inflammation and/or microbial dysbiosis. PMID:27183629

  11. Subversion of Retrograde Trafficking by Translocated Pathogen Effectors.

    PubMed

    Personnic, Nicolas; Bärlocher, Kevin; Finsel, Ivo; Hilbi, Hubert

    2016-06-01

    Intracellular bacterial pathogens subvert the endocytic bactericidal pathway to form specific replication-permissive compartments termed pathogen vacuoles or inclusions. To this end, the pathogens employ type III or type IV secretion systems, which translocate dozens, if not hundreds, of different effector proteins into their host cells, where they manipulate vesicle trafficking and signaling pathways in favor of the intruders. While the distinct cocktail of effectors defines the specific processes by which a pathogen vacuole is formed, the different pathogens commonly target certain vesicle trafficking routes, including the endocytic or secretory pathway. Recently, the retrograde transport pathway from endosomal compartments to the trans-Golgi network emerged as an important route affecting pathogen vacuole formation. Here, we review current insight into the host cell's retrograde trafficking pathway and how vacuolar pathogens of the genera Legionella, Coxiella, Salmonella, Chlamydia, and Simkania employ mechanistically distinct strategies to subvert this pathway, thus promoting intracellular survival and replication. PMID:26924068

  12. Waterborne Pathogens: The Protozoans.

    PubMed

    Moss, Joseph Anthony

    2016-09-01

    Waterborne diseases associated with polluted recreational and potable waters have been documented for more than a century. Key microbial protozoan parasites, such as Cryptosporidium and Giardia, are causative agents for gastrointestinal disease worldwide. Although not a first-line diagnostic approach for these diseases, medical imaging, such as radiography, computed tomography, magnetic resonance imaging, ultrasonography, and nuclear medicine technologies, can be used to evaluate patients with long-term effects. This article describes protozoan pathogens that affect human health, treatment of common waterborne pathogen-related diseases, and associated medical imaging. PMID:27601690

  13. Arabidopsis CLAVATA1 and CLAVATA2 receptors contribute to Ralstonia solanacearum pathogenicity through a miR169-dependent pathway.

    PubMed

    Hanemian, Mathieu; Barlet, Xavier; Sorin, Céline; Yadeta, Koste A; Keller, Harald; Favery, Bruno; Simon, Rüdiger; Thomma, Bart P H J; Hartmann, Caroline; Crespi, Martin; Marco, Yves; Tremousaygue, Dominique; Deslandes, Laurent

    2016-07-01

    Bacterial wilt caused by Ralstonia solanacearum is one of the most destructive bacterial plant diseases. Although many molecular determinants involved in R. solanacearum adaptation to hosts and pathogenesis have been described, host components required for disease establishment remain poorly characterized. Phenotypical analysis of Arabidopsis mutants for leucine-rich repeat (LRR)-receptor-like proteins revealed that mutations in the CLAVATA1 (CLV1) and CLAVATA2 (CLV2) genes confer enhanced disease resistance to bacterial wilt. We further investigated the underlying mechanisms using genetic, transcriptomic and molecular approaches. The enhanced resistance of both clv1 and clv2 mutants to the bacteria did not require the well characterized CLV signalling modules involved in shoot meristem homeostasis, and was conditioned by neither salicylic acid nor ethylene defence-related hormones. Gene expression microarray analysis performed on clv1 and clv2 revealed deregulation of genes encoding nuclear transcription factor Y subunit alpha (NF-YA) transcription factors whose post-transcriptional regulation is known to involve microRNAs from the miR169 family. Both clv mutants showed a defect in miR169 accumulation. Conversely, overexpression of miR169 abrogated the resistance phenotype of clv mutants. We propose that CLV1 and CLV2, two receptors involved in CLV3 perception during plant development, contribute to bacterial wilt through a signalling pathway involving the miR169/NF-YA module. PMID:26990325

  14. Arabidopsis CLAVATA1 and CLAVATA2 receptors contribute to Ralstonia solanacearum pathogenicity through a miR169-dependent pathway.

    PubMed

    Hanemian, Mathieu; Barlet, Xavier; Sorin, Céline; Yadeta, Koste A; Keller, Harald; Favery, Bruno; Simon, Rüdiger; Thomma, Bart P H J; Hartmann, Caroline; Crespi, Martin; Marco, Yves; Tremousaygue, Dominique; Deslandes, Laurent

    2016-07-01

    Bacterial wilt caused by Ralstonia solanacearum is one of the most destructive bacterial plant diseases. Although many molecular determinants involved in R. solanacearum adaptation to hosts and pathogenesis have been described, host components required for disease establishment remain poorly characterized. Phenotypical analysis of Arabidopsis mutants for leucine-rich repeat (LRR)-receptor-like proteins revealed that mutations in the CLAVATA1 (CLV1) and CLAVATA2 (CLV2) genes confer enhanced disease resistance to bacterial wilt. We further investigated the underlying mechanisms using genetic, transcriptomic and molecular approaches. The enhanced resistance of both clv1 and clv2 mutants to the bacteria did not require the well characterized CLV signalling modules involved in shoot meristem homeostasis, and was conditioned by neither salicylic acid nor ethylene defence-related hormones. Gene expression microarray analysis performed on clv1 and clv2 revealed deregulation of genes encoding nuclear transcription factor Y subunit alpha (NF-YA) transcription factors whose post-transcriptional regulation is known to involve microRNAs from the miR169 family. Both clv mutants showed a defect in miR169 accumulation. Conversely, overexpression of miR169 abrogated the resistance phenotype of clv mutants. We propose that CLV1 and CLV2, two receptors involved in CLV3 perception during plant development, contribute to bacterial wilt through a signalling pathway involving the miR169/NF-YA module.

  15. Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Induces Prostaglandin E2 Production through Cyclooxygenase 1, Which Is Dependent on the ERK1/2-p-C/EBP-β Pathway

    PubMed Central

    Bi, Yanmin; Guo, Xue-kun; Zhao, Haiyan; Gao, Li; Wang, Lianghai; Tang, Jun

    2014-01-01

    ABSTRACT Atypical porcine reproductive and respiratory syndrome (PRRS) caused by highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is characterized by high fever and high mortality. However, the mechanism underlying the fever induction is still unknown. Prostaglandin E2 (PGE2), synthesized by cyclooxygenase type 1/2 (COX-1/2) enzymes, is essential for inducing fever. In this study, we found that PGE2, together with COX-1, was significantly elevated by HP-PRRSV. We subsequently demonstrated that extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK (p-ERK) were the key nodes to trigger COX-1 expression after HP-PRRSV infection. Furthermore, we proved the direct binding of p-C/EBP-β to the COX-1 promoter by luciferase reporter and chromatin immunoprecipitation assays. In addition, silencing of C/EBP-β remarkably impaired the enhancement of COX-1 production induced by HP-PRRSV infection. Taken together, our results indicate that HP-PPRSV elicits the expression of COX-1 through the ERK1/2-p-C/EBP-β signaling pathway, resulting in the increase of PGE2, which might be the cause of high fever in infected pigs. Our findings might provide new insights into the molecular mechanisms underlying the pathogenesis of HP-PRRSV infection. IMPORTANCE The atypical PRRS caused by HP-PRRSV was characterized by high fever, high morbidity, and high mortality in pigs of all ages, yet how HP-PRRSV induces high fever in pigs remains unknown. In the present study, we found out that HP-PRRSV infection could increase PGE2 production by upregulation of COX-1, and we subsequently characterized the underlying mechanisms about how HP-PRRSV enhances COX-1 production. PGE2 plays a critical role in inducing high temperature in hosts during pathogen infections. Thus, our findings here could help us have a better understanding of HP-PRRSV pathogenesis. PMID:24352469

  16. Leukocyte-subset counts in idiopathic parkinsonism provide clues to a pathogenic pathway involving small intestinal bacterial overgrowth. A surveillance study

    PubMed Central

    2012-01-01

    -medication, and not masked by including 13 patients receiving levodopa (except natural-killer count on flexor-rigidity). Cellular associations held after allowing for potentially confounding effect of hydrogen-breath-test or Helicobacter status. Moreover, additional reduction in stride and speed (68 (24, 112) mm & 103 (38, 168) mm.s-1, each p=0.002) was seen with Helicobacter-positivity. Hydrogen-breath-test-positivity, itself, was associated with higher natural-killer and T-helper counts, lower neutrophils (p=0.005, 0.02 & 0.008). Conclusion We propose a rigidity-associated subordinate pathway, flagged by a higher natural-killer count, tempered by a higher T-helper, against which Helicobacter protects by keeping SIBO at bay. PMID:23083400

  17. Pathogen intelligence.

    PubMed

    Steinert, Michael

    2014-01-01

    Different species inhabit different sensory worlds and thus have evolved diverse means of processing information, learning and memory. In the escalated arms race with host defense, each pathogenic bacterium not only has evolved its individual cellular sensing and behavior, but also collective sensing, interbacterial communication, distributed information processing, joint decision making, dissociative behavior, and the phenotypic and genotypic heterogeneity necessary for epidemiologic success. Moreover, pathogenic populations take advantage of dormancy strategies and rapid evolutionary speed, which allow them to save co-generated intelligent traits in a collective genomic memory. This review discusses how these mechanisms add further levels of complexity to bacterial pathogenicity and transmission, and how mining for these mechanisms could help to develop new anti-infective strategies. PMID:24551600

  18. Pathogen intelligence

    PubMed Central

    Steinert, Michael

    2014-01-01

    Different species inhabit different sensory worlds and thus have evolved diverse means of processing information, learning and memory. In the escalated arms race with host defense, each pathogenic bacterium not only has evolved its individual cellular sensing and behavior, but also collective sensing, interbacterial communication, distributed information processing, joint decision making, dissociative behavior, and the phenotypic and genotypic heterogeneity necessary for epidemiologic success. Moreover, pathogenic populations take advantage of dormancy strategies and rapid evolutionary speed, which allow them to save co-generated intelligent traits in a collective genomic memory. This review discusses how these mechanisms add further levels of complexity to bacterial pathogenicity and transmission, and how mining for these mechanisms could help to develop new anti-infective strategies. PMID:24551600

  19. Publishing International Counseling Articles

    ERIC Educational Resources Information Center

    Hohenshil, Thomas H.; Amundson, Norman E.

    2011-01-01

    This article begins with a rationale for including international articles in the "Journal of Counseling & Development." Then, 2 general categories of international articles are described. First are articles that provide a general overview of counseling in a particular country. The 2nd category is more general and might involve international…

  20. Pathways from Poverty.

    ERIC Educational Resources Information Center

    Baldwin, Barbara, Ed.

    1995-01-01

    Articles in this theme issue are based on presentations at the Pathways from Poverty Workshop held in Albuquerque, New Mexico, on May 18-25, 1995. The event aimed to foster development of a network to address rural poverty issues in the Western Rural Development Center (WRDC) region. Articles report on outcomes from the Pathways from Poverty…

  1. Pathogenic agents in freshwater resources

    NASA Astrophysics Data System (ADS)

    Geldreich, Edwin E.

    1996-02-01

    Numerous pathogenic agents have been found in freshwaters used as sources for water supplies, recreational bathing and irrigation. These agents include bacterial pathogens, enteric viruses, several protozoans and parasitic worms more common to tropical waters. Although infected humans are a major source of pathogens, farm animals (cattle, sheep, pigs), animal pets (dogs, cats) and wildlife serve as significant reservoirs and should not be ignored. The range of infected individuals within a given warm-blooded animal group (humans included) may range from 1 to 25%. Survival times for pathogens in the water environment may range from a few days to as much as a year (Ascaris, Taenia eggs), with infective dose levels varying from one viable cell for several primary pathogenic agents to many thousands of cells for a given opportunistic pathogen.As pathogen detection in water is complex and not readily incorporated into routine monitoring, a surrogate is necessary. In general, indicators of faecal contamination provide a positive correlation with intestinal pathogen occurrences only when appropriate sample volumes are examined by sensitive methodology.Pathways by which pathogens reach susceptible water users include ingestion of contaminated water, body contact with polluted recreational waters and consumption of salad crops irrigated by polluted freshwaters. Major contributors to the spread of various water-borne pathogens are sewage, polluted surface waters and stormwater runoff. All of these contributions are intensified during periods of major floods. Several water-borne case histories are cited as examples of breakdowns in public health protection related to water supply, recreational waters and the consumption of contaminated salad crops. In the long term, water resource management must focus on pollution prevention from point sources of waste discharges and the spread of pathogens in watershed stormwater runoff.

  2. [Reading research articles].

    PubMed

    van der Graaf, Yolanda; Zaat, Joost

    2015-01-01

    Keeping up with the latest developments is not easy, but neither is reading articles on research. There are too many medical journals that contain information that is irrelevant to clinical practice. From this mass of articles you have to decide which are important for your own clinical practice and which are not. Most articles naturally fall into the latter category as spectacular findings with important consequences for medical practice do not occur every week. The most important thing in a research article is the research question. If you begin with this, then you can put aside much scientific literature. The methodology section is essential; reading this can save you a lot of time. In this article we take you step-by-step through the process of reading research articles. The articles in our Methodology series can be used as background information. These articles have been combined in a tablet app, which is available via www.ntvg.nl/methodologie.

  3. [Salmonella pathogenicity islands].

    PubMed

    Sırıken, Belgin

    2013-01-01

    Salmonella species are facultative intracellular pathogenic bacteria. They can invade macrophages, dendritic and epithelial cells. The responsible virulence genes for invasion, survival, and extraintestinal spread are located in Salmonella pathogenicity islands (SPIs). SPIs are thought to be acquired by horizontal gene transfer. Some of the SPIs are conserved throughout the Salmonella genus, and some of them are specific for certain serovars. There are differences between Salmonella serotypes in terms of adaptation to host cell, virulence factors and the resulting infection according to SPA presence and characteristics. The most important Salmonella virulence gene clusters are located in 12 pathogenicity islands. Virulence genes that are involved in the intestinal phase of infection are located in SPI-1 and SPI-2 and the remaining SPIs are required for intracellular survival, fimbrial expression, magnesium and iron uptake, multiple antibiotic resistance and the development of systemic infections. In addition SPIs, Sigma ss (RpoS) factors and adaptive acid tolerance response (ATR) are the other two important virulence factors. RpoS and ATR found in virulent Salmonella strains help the bacteria to survive under inappropriate conditions such as gastric acidity, bile salts, inadequate oxygen concentration, lack of nutrients, antimicrobial peptides, mucus and natural microbiota and also to live in phagosomes or phagolysosomes. This review article summarizes the data related to pathogenicity islands in Salmonella serotypes and some factors which play role in the regulation of virulence genes.

  4. Fabrication of boron articles

    DOEpatents

    Benton, Samuel T.

    1976-01-01

    This invention is directed to the fabrication of boron articles by a powder metallurgical method wherein the articles are of a density close to the theoretical density of boron and are essentially crackfree. The method comprises the steps of admixing 1 to 10 weight percent carbon powder with amorphous boron powder, cold pressing the mixture and then hot pressing the cold pressed compact into the desired article. The addition of the carbon to the mixture provides a pressing aid for inhibiting the cracking of the hot pressed article and is of a concentration less than that which would cause the articles to possess significant concentrations of boron carbide.

  5. Conserved Pro-Glu (PE) and Pro-Pro-Glu (PPE) Protein Domains Target LipY Lipases of Pathogenic Mycobacteria to the Cell Surface via the ESX-5 Pathway*

    PubMed Central

    Daleke, Maria H.; Cascioferro, Alessandro; de Punder, Karin; Ummels, Roy; Abdallah, Abdallah M.; van der Wel, Nicole; Peters, Peter J.; Luirink, Joen; Manganelli, Riccardo; Bitter, Wilbert

    2011-01-01

    The type VII secretion system ESX-5 is a major pathway for export of PE and PPE proteins in pathogenic mycobacteria. These mycobacteria-specific protein families are characterized by conserved N-terminal domains of 100 and 180 amino acids, which contain the proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) motifs after which they are named. Here we investigated secretion of the triacylglycerol lipase LipY, which in fast-growing mycobacteria contains a signal sequence, but in slow-growing species appears to have replaced the signal peptide with a PE or PPE domain. Selected LipY homologues were expressed in wild-type Mycobacterium marinum and its corresponding ESX-5 mutant, and localization of the proteins was investigated by immunoblotting and electron microscopy. Our study shows that Mycobacterium tuberculosis PE-LipY (LipYtub) and M. marinum PPE-LipY (LipYmar) are both secreted to the bacterial surface in an ESX-5-dependent fashion. After transport, the PE/PPE domains are removed by proteolytic cleavage. In contrast, Mycobacterium gilvum LipY, which has a signal sequence, is not transported to the cell surface. Furthermore, we show that LipYtub and LipYmar require their respective PE and PPE domains for ESX-5-dependent secretion. The role of the PE domain in ESX-5 secretion was confirmed in a whole cell lipase assay, in which wild-type bacteria expressing full-length LipYtub, but not LipYtub lacking its PE domain, were shown to hydrolyze extracellular lipids. In conclusion, both PE and PPE domains contain a signal required for secretion of LipY by the ESX-5 system, and these domains are proteolytically removed upon translocation. PMID:21471225

  6. Method of drying articles

    DOEpatents

    Janney, Mark A.; Kiggans, Jr., James O.

    1999-01-01

    A method of drying a green particulate article includes the steps of: a. Providing a green article which includes a particulate material and a pore phase material, the pore phase material including a solvent; and b. contacting the green article with a liquid desiccant for a period of time sufficient to remove at least a portion of the solvent from the green article, the pore phase material acting as a semipermeable barrier to allow the solvent to be sorbed into the liquid desiccant, the pore phase material substantially preventing the liquid desiccant from entering the pores.

  7. Method of drying articles

    DOEpatents

    Janney, M.A.; Kiggans, J.O. Jr.

    1999-03-23

    A method of drying a green particulate article includes the steps of: (a) Providing a green article which includes a particulate material and a pore phase material, the pore phase material including a solvent; and (b) contacting the green article with a liquid desiccant for a period of time sufficient to remove at least a portion of the solvent from the green article, the pore phase material acting as a semipermeable barrier to allow the solvent to be sorbed into the liquid desiccant, the pore phase material substantially preventing the liquid desiccant from entering the pores. 3 figs.

  8. Detection of enteric pathogens by the nodosome.

    PubMed

    Keestra, A Marijke; Bäumler, Andreas J

    2014-03-01

    Nucleotide-binding oligomerization domain protein (NOD)1 and NOD2 participate in signaling pathways that detect pathogen-induced processes, such as the presence of peptidoglycan fragments in the host cell cytosol, as danger signals. Recent work suggests that peptidoglycan fragments activate NOD1 indirectly, through activation of the small Rho GTPase Ras-related C3 botulinum toxin substrate 1 (RAC1). Excessive activation of small Rho GTPases by virulence factors of enteric pathogens also triggers the NOD1 signaling pathway. Many enteric pathogens use virulence factors that alter the activation state of small Rho GTPases, thereby manipulating the host cell cytoskeleton of intestinal epithelial cells to promote bacterial attachment or entry. These data suggest that the NOD1 signaling pathway in intestinal epithelial cells provides an important sentinel function for detecting 'breaking and entering' by enteric pathogens. PMID:24268520

  9. Detection of enteric pathogens by the nodosome

    PubMed Central

    Keestra, A. Marijke; Bäumler, Andreas J.

    2014-01-01

    Nucleotide-binding oligomerization domain protein (NOD)1 and NOD2 participate in signaling pathways that detect pathogen-induced processes, such as the presence of peptidoglycan fragments in the host cell cytosol, as danger signals. Recent work suggests that peptidoglycan fragments activate NOD1 indirectly, through activation of the small Rho GTPase Ras-related C3 botulinum toxin substrate 1 (RAC1). Excessive activation of small Rho GTPases by virulence factors of enteric pathogens also triggers the NOD1 signaling pathway. Many enteric pathogens use virulence factors that alter the activation state of small Rho GTPases, thereby manipulating the host cell cytoskeleton of intestinal epithelial cells to promote bacterial attachment or entry. These data suggest that the NOD1 signaling pathway in intestinal epithelial cells provides an important sentinel function for detecting ‘breaking and entering’ by enteric pathogens. PMID:24268520

  10. Trafficking vesicles: pro or contra pathogens?

    PubMed

    Frei dit Frey, Nicolas; Robatzek, Silke

    2009-08-01

    Membrane compartmentalization and trafficking are pivotal for eukaryotic life and demand a higher order of coordination. Even in their resting state, most plant cells exhibit a polarized localization of membrane compartments, which is redirected when plant cells are attacked by microbes. Repositioning of organelles at pathogen penetration sites has been reported since more than a decade; however, only recently has targeted vesicle trafficking upon biotic stress emerged. It has become evident that vesicle secretion and endocytic pathways are engaged in the plant's immune system to actively defend against potential pathogens. By contrast, invasive pathogens have evolved means to utilize these trafficking pathways for the suppression of plant defenses and to the benefit of microbial proliferation. This review summarizes recent findings of host intracellular endomembrane adaptations in response to pathogens and how pathogens exploit them. PMID:19608452

  11. Master Articles List.

    ERIC Educational Resources Information Center

    Indiana Univ., Bloomington.

    Presented are more than 275 articles on 19 topics which can be arranged into readers on selected topics at the request of any educator. Assembled by the Poynter Center at Indiana University, Poynter Readers are compilations of articles that relate to a particular institution, e.g., law, or to several institutions that affect the lives of American…

  12. Waterborne pathogens in urban watersheds.

    PubMed

    Arnone, Russell D; Walling, Joyce Perdek

    2007-03-01

    A serious concern for managers of water resources, pathogens in the urban environment easily enter waters through a number of pathways, including discharge of inadequately treated sewage, stormwater runoff, combined sewer overflows and sanitary sewer overflows. Pathogens in US ambient water bodies are regulated under the Clean Water Act (CWA), while pathogens in drinking water supplies are regulated under the Safe Drinking Water Act. Total maximum daily loads (TMDLs) are developed in accordance with CWA regulations for ambient water bodies with bacterial concentrations exceeding the water quality standard, which generally is a measure of a bacterial indicator organism. However, developing a TMDL for a supplementary indicator or pathogen is also required if a use impairment would still exist even after the water body is in compliance with the standard. This occurs because indicator organisms do not reflect the presence of pathogen contamination with complete certainty. The evaluation of pathogen indicators and summary of epidemiological studies presented are resources for those developing TMDLs to achieve water quality standards and restore water bodies to their intended uses. PMID:17402286

  13. Repositioning of Memantine as a Potential Novel Therapeutic Agent against Meningitic E. coli–Induced Pathogenicities through Disease-Associated Alpha7 Cholinergic Pathway and RNA Sequencing-Based Transcriptome Analysis of Host Inflammatory Responses

    PubMed Central

    Peng, Liang; Wu, Chun-Hua; Cao, Hong; Zhong, John F.; Hoffman, Jill; Huang, Sheng-He

    2015-01-01

    Neonatal sepsis and meningitis (NSM) remains a leading cause worldwide of mortality and morbidity in newborn infants despite the availability of antibiotics over the last several decades. E. coli is the most common gram-negative pathogen causing NSM. Our previous studies show that α7 nicotinic receptor (α7 nAChR), an essential regulator of inflammation, plays a detrimental role in the host defense against NSM. Despite notable successes, there still exists an unmet need for new effective therapeutic approaches to treat this disease. Using the in vitro/in vivo models of the blood-brain barrier (BBB) and RNA-seq, we undertook a drug repositioning study to identify unknown antimicrobial activities for known drugs. We have demonstrated for the first time that memantine (MEM), a FDA-approved drug for treatment of Alzheimer’s disease, could very efficiently block E. coli-caused bacteremia and meningitis in a mouse model of NSM in a manner dependent on α7 nAChR. MEM was able to synergistically enhance the antibacterial activity of ampicillin in HBMEC infected with E. coli K1 (E44) and in neonatal mice with E44-caused bacteremia and meningitis. Differential gene expression analysis of RNA-Seq data from mouse BMEC infected with E. coli K1 showed that several E44-increased inflammatory factors, including IL33, IL18rap, MMP10 and Irs1, were significantly reduced by MEM compared to the infected cells without drug treatment. MEM could also significantly up-regulate anti-inflammatory factors, including Tnfaip3, CISH, Ptgds and Zfp36. Most interestingly, these factors may positively and negatively contribute to regulation of NF-κB, which is a hallmark feature of bacterial meningitis. Furthermore, we have demonstrated that circulating BMEC (cBMEC) are the potential novel biomarkers for NSM. MEM could significantly reduce E44-increased blood level of cBMEC in mice. Taken together, our data suggest that memantine can efficiently block host inflammatory responses to bacterial

  14. Repositioning of Memantine as a Potential Novel Therapeutic Agent against Meningitic E. coli-Induced Pathogenicities through Disease-Associated Alpha7 Cholinergic Pathway and RNA Sequencing-Based Transcriptome Analysis of Host Inflammatory Responses.

    PubMed

    Yu, Jing-Yi; Zhang, Bao; Peng, Liang; Wu, Chun-Hua; Cao, Hong; Zhong, John F; Hoffman, Jill; Huang, Sheng-He

    2015-01-01

    Neonatal sepsis and meningitis (NSM) remains a leading cause worldwide of mortality and morbidity in newborn infants despite the availability of antibiotics over the last several decades. E. coli is the most common gram-negative pathogen causing NSM. Our previous studies show that α7 nicotinic receptor (α7 nAChR), an essential regulator of inflammation, plays a detrimental role in the host defense against NSM. Despite notable successes, there still exists an unmet need for new effective therapeutic approaches to treat this disease. Using the in vitro/in vivo models of the blood-brain barrier (BBB) and RNA-seq, we undertook a drug repositioning study to identify unknown antimicrobial activities for known drugs. We have demonstrated for the first time that memantine (MEM), a FDA-approved drug for treatment of Alzheimer's disease, could very efficiently block E. coli-caused bacteremia and meningitis in a mouse model of NSM in a manner dependent on α7 nAChR. MEM was able to synergistically enhance the antibacterial activity of ampicillin in HBMEC infected with E. coli K1 (E44) and in neonatal mice with E44-caused bacteremia and meningitis. Differential gene expression analysis of RNA-Seq data from mouse BMEC infected with E. coli K1 showed that several E44-increased inflammatory factors, including IL33, IL18rap, MMP10 and Irs1, were significantly reduced by MEM compared to the infected cells without drug treatment. MEM could also significantly up-regulate anti-inflammatory factors, including Tnfaip3, CISH, Ptgds and Zfp36. Most interestingly, these factors may positively and negatively contribute to regulation of NF-κB, which is a hallmark feature of bacterial meningitis. Furthermore, we have demonstrated that circulating BMEC (cBMEC) are the potential novel biomarkers for NSM. MEM could significantly reduce E44-increased blood level of cBMEC in mice. Taken together, our data suggest that memantine can efficiently block host inflammatory responses to bacterial

  15. Article Watch: September 2015

    PubMed Central

    Slaughter, Clive A.

    2015-01-01

    This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, Georgia Regents University-University of Georgia Medical Partnership, 1425 Prince Ave., Athens, GA 30606, USA. Phone: 706-713-2216; Fax: 706-713-2221; E-mail: cslaught@uga.edu; or to any member of the Editorial Board. Article summaries reflect the reviewer’s opinions and not necessarily those of the association.

  16. Article Watch, April 2012

    PubMed Central

    Slaughter, Clive

    2012-01-01

    This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, Georgia Health Sciences University-University of Georgia Medical Partnership, 279 William St., Athens GA 30607-1777. Phone: 706-369-5945; Fax: 706-369-5936; E-mail: cslaught@uga.edu; or to any member of the editorial board. Article summaries reflect the reviewer's opinions and not necessarily those of the association.

  17. Article Watch, April 2010

    PubMed Central

    Slaughter, Clive

    2010-01-01

    This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information about articles they feel are important and useful to Clive Slaughter, MCG-UGA Medical Partnership, 279 William St., Athens, GA 30607-1777, USA. Tel.: (706) 369-5945: Fax: (706) 369-5936; E-mail: cslaughter@mail.mcg.edu; or to any member of the editorial board. Article summaries reflect the reviewer's opinions and not necessarily those of the association.

  18. Article Watch: July 2015

    PubMed Central

    Slaughter, Clive A.

    2015-01-01

    This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, Georgia Regents University-University of Georgia Medical Partnership, 1425 Prince Ave., Athens, GA 30606, USA. Phone: 706-713-2216; Fax: 706-713-2221; E-mail: cslaught@uga.edu; or to any member of the Editorial Board. Article summaries reflect the reviewer’s opinions and not necessarily those of the association.

  19. Article Watch: September 2016

    PubMed Central

    Slaughter, Clive A.

    2016-01-01

    This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, AU-UGA Medical Partnership, 1425 Prince Ave., Athens, GA 30606, USA. Tel: (706) 713-2216; Fax: (706) 713-2221; E-mail: cslaught@uga.edu, or to any member of the editorial board. Article summaries reflect the reviewer's opinions and not necessarily those of the association. PMID:27582640

  20. Article Watch: December 2016

    PubMed Central

    Slaughter, Clive A.

    2016-01-01

    This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, MCG-UGA Medical Partnership, 1425 Prince Ave., Athens, GA 30606, USA. Tel: (706) 713-2216; Fax: (706) 713-2221; E-mail: cslaught@uga.edu, or to any member of the editorial board. Article summaries reflect the reviewer’s opinions and not necessarily those of the association.

  1. Article Watch: September 2016.

    PubMed

    Slaughter, Clive A

    2016-09-01

    This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, AU-UGA Medical Partnership, 1425 Prince Ave., Athens, GA 30606, USA. Tel: (706) 713-2216; Fax: (706) 713-2221; E-mail: cslaught@uga.edu, or to any member of the editorial board. Article summaries reflect the reviewer's opinions and not necessarily those of the association.

  2. Article Watch: July 2016.

    PubMed

    Slaughter, Clive A

    2016-07-01

    This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, MCG-UGA Medical Partnership, 1425 Prince Ave., Athens, GA 30606, USA. Tel: (706) 713-2216; Fax: (706) 713-2221; E-mail: cslaught@uga.edu, or to any member of the editorial board. Article summaries reflect the reviewer's opinions and not necessarily those of the association.

  3. Article Watch: April 2015

    PubMed Central

    Slaughter, Clive A.

    2015-01-01

    This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, Georgia Regents University-University of Georgia Medical Partnership, 1425 Prince Ave., Athens, GA 30606, USA. Phone: 706-713-2216; Fax: 706-713-2221; E-mail: cslaught@uga.edu; or to any member of the Editorial Board. Article summaries reflect the reviewer’s opinions and not necessarily those of the association.

  4. Article Watch: April 2016

    PubMed Central

    Slaughter, Clive A.

    2016-01-01

    This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, MCG-UGA Medical Partnership, 1425 Prince Ave., Athens, GA 30606, USA; Tel: (706) 713-2216; Fax: (706) 713-2221; E-mail: cslaught@uga.edu, or to any member of the editorial board. Article summaries reflect the reviewer’s opinions and not necessarily those of the association.

  5. Article Watch: July 2014

    PubMed Central

    Slaughter, Clive A.

    2014-01-01

    This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, Georgia Regents University-University of Georgia Medical Partnership, 1425 Prince Ave., Athens, GA 30606, USA. Phone: 706-713-2216; Fax: 706-713-2221; E-mail: cslaught@uga.edu; or to any member of the Editorial Board. Article summaries reflect the reviewer's opinions and not necessarily those of the association.

  6. Article Watch: July 2016

    PubMed Central

    Slaughter, Clive A.

    2016-01-01

    This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, MCG-UGA Medical Partnership, 1425 Prince Ave., Athens, GA 30606, USA. Tel: (706) 713-2216; Fax: (706) 713-2221; E-mail: cslaught@uga.edu, or to any member of the editorial board. Article summaries reflect the reviewer's opinions and not necessarily those of the association. PMID:27257408

  7. Article Watch: April 2014

    PubMed Central

    Slaughter, Clive A.

    2014-01-01

    This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, Georgia Regents University/University of Georgia Medical Partnership, 1425 Prince Ave., Athens, GA 30606, USA (Phone: 706-713-2216; Fax: 706-713-2221; E-mail; cslaught@uga.edu), or to any member of the editorial board. Article summaries reflect the reviewer's opinions and not necessarily those of the association.

  8. Article Watch: December 2015

    PubMed Central

    Slaughter, Clive A.

    2015-01-01

    This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to: Clive Slaughter, GRU-UGA Medical Partnership, 1425 Prince Ave., Athens, GA 30606, USA. Tel: (706) 713-2216; Fax: (706) 713-2221; E-mail: cslaught@uga.edu; or to any member of the editorial board. Article summaries reflect the reviewer’s opinions and not necessarily those of the association.

  9. PFCA Article Testing

    EPA Science Inventory

    The U.S. Environmental Protection Agency (EPA) has established an ongoing effort to quantify possible changes in levels of perfluorinated chemicals (PFCs) in articles of commerce (AOCs). Temporal trends in the concentrations of selected PFCs, including perfluorooctanoic acid (PFO...

  10. Pathogenicity islands and the evolution of microbes.

    PubMed

    Hacker, J; Kaper, J B

    2000-01-01

    Virulence factors of pathogenic bacteria (adhesins, toxins, invasins, protein secretion systems, iron uptake systems, and others) may be encoded by particular regions of the prokaryotic genome termed pathogenicity islands. Pathogenicity islands were first described in human pathogens of the species Escherichia coli, but have recently been found in the genomes of various pathogens of humans, animals, and plants. Pathogenicity islands comprise large genomic regions [10-200 kilobases (kb) in size] that are present on the genomes of pathogenic strains but absent from the genomes of nonpathogenic members of the same or related species. The finding that the G+C content of pathogenicity islands often differs from that of the rest of the genome, the presence of direct repeats at their ends, the association of pathogenicity islands with transfer RNA genes, the presence of integrase determinants and other mobility loci, and their genetic instability argue for the generation of pathogenicity islands by horizontal gene transfer, a process that is well known to contribute to microbial evolution. In this article we review these and other aspects of pathogenicity islands and discuss the concept that they represent a subclass of genomic islands. Genomic islands are present in the majority of genomes of pathogenic as well as nonpathogenic bacteria and may encode accessory functions which have been previously spread among bacterial populations.

  11. Space: A Final Frontier for Vacuolar Pathogens.

    PubMed

    Case, Elizabeth Di Russo; Smith, Judith A; Ficht, Thomas A; Samuel, James E; de Figueiredo, Paul

    2016-05-01

    There is a fundamental gap in our understanding of how a eukaryotic cell apportions the limited space within its cell membrane. Upon infection, a cell competes with intracellular pathogens for control of this same precious resource. The struggle between pathogen and host provides us with an opportunity to uncover the mechanisms regulating subcellular space by understanding how pathogens modulate vesicular traffic and membrane fusion events to create a specialized compartment for replication. By comparing several important intracellular pathogens, we review the molecular mechanisms and trafficking pathways that drive two space allocation strategies, the formation of tight and spacious pathogen-containing vacuoles. Additionally, we discuss the potential advantages of each pathogenic lifestyle, the broader implications these lifestyles might have for cellular biology and outline exciting opportunities for future investigation. PMID:26842840

  12. Space: A Final Frontier for Vacuolar Pathogens.

    PubMed

    Case, Elizabeth Di Russo; Smith, Judith A; Ficht, Thomas A; Samuel, James E; de Figueiredo, Paul

    2016-05-01

    There is a fundamental gap in our understanding of how a eukaryotic cell apportions the limited space within its cell membrane. Upon infection, a cell competes with intracellular pathogens for control of this same precious resource. The struggle between pathogen and host provides us with an opportunity to uncover the mechanisms regulating subcellular space by understanding how pathogens modulate vesicular traffic and membrane fusion events to create a specialized compartment for replication. By comparing several important intracellular pathogens, we review the molecular mechanisms and trafficking pathways that drive two space allocation strategies, the formation of tight and spacious pathogen-containing vacuoles. Additionally, we discuss the potential advantages of each pathogenic lifestyle, the broader implications these lifestyles might have for cellular biology and outline exciting opportunities for future investigation.

  13. Map kinases in fungal pathogens.

    PubMed

    Xu, J R

    2000-12-01

    MAP kinases in eukaryotic cells are well known for transducing a variety of extracellular signals to regulate cell growth and differentiation. Recently, MAP kinases homologous to the yeast Fus3/Kss1 MAP kinases have been identified in several fungal pathogens and found to be important for appressorium formation, invasive hyphal growth, and fungal pathogenesis. This MAP kinase pathway also controls diverse growth or differentiation processes, including conidiation, conidial germination, and female fertility. MAP kinases homologous to yeast Slt2 and Hog1 have also been characterized in Candida albicans and Magnaporthe grisea. Mutants disrupted of the Slt2 homologues have weak cell walls, altered hyphal growth, and reduced virulence. The Hog1 homologues are dispensable for growth but are essential for regulating responses to hyperosmotic stress in C. albicans and M. grisea. Overall, recent studies have indicated that MAP kinase pathways may play important roles in regulating growth, differentiation, survival, and pathogenesis in fungal pathogens. PMID:11273677

  14. Recompressed exfoliated graphite articles

    DOEpatents

    Zhamu, Aruna; Shi, Jinjun; Guo, Jiusheng; Jang, Bor Z

    2013-08-06

    This invention provides an electrically conductive, less anisotropic, recompressed exfoliated graphite article comprising a mixture of (a) expanded or exfoliated graphite flakes; and (b) particles of non-expandable graphite or carbon, wherein the non-expandable graphite or carbon particles are in the amount of between about 3% and about 70% by weight based on the total weight of the particles and the expanded graphite flakes combined; wherein the mixture is compressed to form the article having an apparent bulk density of from about 0.1 g/cm.sup.3 to about 2.0 g/cm.sup.3. The article exhibits a thickness-direction conductivity typically greater than 50 S/cm, more typically greater than 100 S/cm, and most typically greater than 200 S/cm. The article, when used in a thin foil or sheet form, can be a useful component in a sheet molding compound plate used as a fuel cell separator or flow field plate. The article may also be used as a current collector for a battery, supercapacitor, or any other electrochemical cell.

  15. Pathogene Mikroorganismen

    NASA Astrophysics Data System (ADS)

    Wagner, Martin

    Infektionen, die vom Tier auf den Menschen übertragen werden, werden als Zoonosen bezeichnet. Pathogene Mikroorganismen können entweder durch Mensch-Mensch, Mensch-Tier-Kontakt oder durch Kontakt mit kontaminierten Vektoren übertragen werden [39]. Vektoren können einerseits belebt (z. B. blutsaugende Insekten), andererseits unbelebt sein. Kontaminierte Lebensmittel und Wasser gehören zu den wichtigsten unbelebten Vektoren. Neben Lebensmitteln können aber auch kontaminierte Gegenstände oder der Kontakt mit Kontaminationsquellen in der Umwelt Auslöser von Krankheitsfällen sein. Weltweit sind mehr als 1400 krankheitsverursachende biologische Agentien bekannt, von denen über 60 % ein zoonotisches Potenzial aufweisen. Als Ergebnis von Expertengesprächen wurde kürzlich berichtet, dass etwa 3 bis 4, meist virale, neu auftretende Infektionskrankheiten ("emerging diseases“) pro Jahr erwartet werden können [15]. Es handelt sich bei diesen Vorgängen aber nicht nur um das Auftauchen vollkommen neuer oder unbeschriebener Spezies, sondern auch um evolutionsbedingte Anpassungen von mikrobiellen Populationen an neue Bedingungen in ihrem Ökosystem [7]. Molekulare Analysen an Umweltchlamydien erbrachten Hinweise, dass die Evolution erste genetische Pathogenitätsmerkmale in dieser Spezies schon vor 700 Mio. Jahren entstehen ließ [14]. Viele Faktoren befeuern den Prozess der Anpassung, unter anderem auch alle Strategien, mit denen der Mensch seit Jahrtausenden versucht, Lebensmittel sicher und haltbar zu machen. Als die treibenden Kräfte des Auftretens neuer Krankheitserreger werden in der Gegenwart vor allem das sich ändernde Weltklima, die globalen Warenströme und die sich verändernden Konsumgewohnheiten genannt. Es steht auch außer Zweifel, dass viele dieser Erreger Tiere als ihr natürliches Reservoir haben werden, d. h. Zoonosen im klassischen Sinne sind [15].

  16. [Research progress in pathogenicity of Ureaplasma urealyticum].

    PubMed

    Huang, Jun; Zhang, Jun; Song, Tiejun; Xie, Xinyou

    2013-07-01

    Ureaplasma urealyticum (UU) is closely related to human diseases including non-gonococcal urethritis (NGU), infertility, premature membranes and neonatal bronchopulmonary dysplasia. Researches on the pathogenicity of UU have become a hot topic in recent years, and suggest that many potential pathogenicity genes or putative pathogenicity islands are involved in its virulence. Moreover, the biovar and serum types of UU, the infection concentration and the state of the host immune system are also important to determine whether UU can cause human disease or not. In this article the recent progress of researches in the pathogenicity of UU is reviewed.

  17. Why should cell biologists study microbial pathogens?

    PubMed Central

    Welch, Matthew D.

    2015-01-01

    One quarter of all deaths worldwide each year result from infectious diseases caused by microbial pathogens. Pathogens infect and cause disease by producing virulence factors that target host cell molecules. Studying how virulence factors target host cells has revealed fundamental principles of cell biology. These include important advances in our understanding of the cytoskeleton, organelles and membrane-trafficking intermediates, signal transduction pathways, cell cycle regulators, the organelle/protein recycling machinery, and cell-death pathways. Such studies have also revealed cellular pathways crucial for the immune response. Discoveries from basic research on the cell biology of pathogenesis are actively being translated into the development of host-targeted therapies to treat infectious diseases. Thus there are many reasons for cell biologists to incorporate the study of microbial pathogens into their research programs. PMID:26628749

  18. Molded Magnetic Article

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G. (Inventor); Namkung, Min (Inventor); Wincheski, Russell A. (Inventor); Fulton, James P. (Inventor); Fox, Robert L. (Inventor)

    2000-01-01

    A molded magnetic article and fabrication method are provided. Particles of ferromagnetic material embedded in a polymer binder are molded under heat and pressure into a geometric shape. Each particle is an oblate spheroid having a radius-to-thickness aspect ratio approximately in the range of 15-30. Each oblate spheroid has flattened poles that are substantially in perpendicular alignment to a direction of the molding pressure throughout the geometric shape.

  19. Career pathways in research: pharmaceutical.

    PubMed

    Kenkre, J E; Foxcroft, D R

    The pharmaceutical pathway is the final article in this series on career pathways and highlights opportunities for nurses within associated industries. This pathway shows that nurses can use their nursing qualifications, combined with their knowledge, skills and expertise, to develop a career within another sphere of employment.

  20. Ustilago maydis as a Pathogen.

    PubMed

    Brefort, Thomas; Doehlemann, Gunther; Mendoza-Mendoza, Artemio; Reissmann, Stefanie; Djamei, Armin; Kahmann, Regine

    2009-01-01

    The Ustilago maydis-maize pathosystem has emerged as the current model for plant pathogenic basidiomycetes and as one of the few models for a true biotrophic interaction that persists throughout fungal development inside the host plant. This is based on the highly advanced genetic system for both the pathogen and its host, the ability to propagate U. maydis in axenic culture, and its unique capacity to induce prominent disease symptoms (tumors) on all aerial parts of maize within less than a week. The corn smut pathogen, though economically not threatening, will continue to serve as a model for related obligate biotrophic fungi such as the rusts, but also for closely related smut species that induce symptoms only in the flower organs of their hosts. In this review we describe the most prominent features of the U. maydis-maize pathosystem as well as genes and pathways most relevant to disease. We highlight recent developments that place this system at the forefront of understanding the function of secreted effectors in eukaryotic pathogens and describe the expected spin-offs for closely related species exploiting comparative genomics approaches.

  1. Inhibition of death receptor signaling by bacterial gut pathogens.

    PubMed

    Giogha, Cristina; Lung, Tania Wong Fok; Pearson, Jaclyn S; Hartland, Elizabeth L

    2014-04-01

    Gastrointestinal bacterial pathogens such as enteropathogenic Escherichia coli, Salmonella and Shigella control inflammatory and apoptotic signaling in human intestinal cells to establish infection, replicate and disseminate to other hosts. These pathogens manipulate host cell signaling through the translocation of virulence effector proteins directly into the host cell cytoplasm, which then target various signaling pathways. Death receptors such as TNFR1, FAS and TRAIL-R induce signaling cascades that are crucial to the clearance of pathogens, and as such are major targets for inhibition by pathogens. This review focuses on what is known about how bacterial gut pathogens inhibit death receptor signaling to suppress inflammation and prevent apoptosis.

  2. Interferons, Signal Transduction Pathways, and the Central Nervous System

    PubMed Central

    Nallar, Shreeram C.

    2014-01-01

    The interferon (IFN) family of cytokines participates in the development of innate and acquired immune defenses against various pathogens and pathogenic stimuli. Discovered originally as a proteinaceous substance secreted from virus-infected cells that afforded immunity to neighboring cells from virus infection, these cytokines are now implicated in various human pathologies, including control of tumor development, cell differentiation, and autoimmunity. It is now believed that the IFN system (IFN genes and the genes induced by them, and the factors that regulate these processes) is a generalized alarm of cellular stress, including DNA damage. IFNs exert both beneficial and deleterious effects on the central nervous system (CNS). Our knowledge of the IFN-regulated processes in the CNS is far from being clear. In this article, we reviewed the current understanding of IFN signal transduction pathways and gene products that might have potential relevance to diseases of the CNS. PMID:25084173

  3. Interferons, signal transduction pathways, and the central nervous system.

    PubMed

    Nallar, Shreeram C; Kalvakolanu, Dhan V

    2014-08-01

    The interferon (IFN) family of cytokines participates in the development of innate and acquired immune defenses against various pathogens and pathogenic stimuli. Discovered originally as a proteinaceous substance secreted from virus-infected cells that afforded immunity to neighboring cells from virus infection, these cytokines are now implicated in various human pathologies, including control of tumor development, cell differentiation, and autoimmunity. It is now believed that the IFN system (IFN genes and the genes induced by them, and the factors that regulate these processes) is a generalized alarm of cellular stress, including DNA damage. IFNs exert both beneficial and deleterious effects on the central nervous system (CNS). Our knowledge of the IFN-regulated processes in the CNS is far from being clear. In this article, we reviewed the current understanding of IFN signal transduction pathways and gene products that might have potential relevance to diseases of the CNS.

  4. Assembly Test Article (ATA)

    NASA Technical Reports Server (NTRS)

    Ricks, Glen A.

    1988-01-01

    The assembly test article (ATA) consisted of two live loaded redesigned solid rocket motor (RSRM) segments which were assembled and disassembled to simulate the actual flight segment stacking process. The test assembly joint was flight RSRM design, which included the J-joint insulation design and metal capture feature. The ATA test was performed mid-November through 24 December 1987, at Kennedy Space Center (KSC), Florida. The purpose of the test was: certification that vertical RSRM segment mating and separation could be accomplished without any damage; verification and modification of the procedures in the segment stacking/destacking documents; and certification of various GSE to be used for flight assembly and inspection. The RSRM vertical segment assembly/disassembly is possible without any damage to the insulation, metal parts, or seals. The insulation J-joint contact area was very close to the predicted values. Numerous deviations and changes to the planning documents were made to ensure the flight segments are effectively and correctly stacked. Various GSE were also certified for use on flight segments, and are discussed in detail.

  5. Immunity to plant pathogens and iron homeostasis.

    PubMed

    Aznar, Aude; Chen, Nicolas W G; Thomine, Sebastien; Dellagi, Alia

    2015-11-01

    Iron is essential for metabolic processes in most living organisms. Pathogens and their hosts often compete for the acquisition of this nutrient. However, iron can catalyze the formation of deleterious reactive oxygen species. Hosts may use iron to increase local oxidative stress in defense responses against pathogens. Due to this duality, iron plays a complex role in plant-pathogen interactions. Plant defenses against pathogens and plant response to iron deficiency share several features, such as secretion of phenolic compounds, and use common hormone signaling pathways. Moreover, fine tuning of iron localization during infection involves genes coding iron transport and iron storage proteins, which have been shown to contribute to immunity. The influence of the plant iron status on the outcome of a given pathogen attack is strongly dependent on the nature of the pathogen infection strategy and on the host species. Microbial siderophores emerged as important factors as they have the ability to trigger plant defense responses. Depending on the plant species, siderophore perception can be mediated by their strong iron scavenging capacity or possibly via specific recognition as pathogen associated molecular patterns. This review highlights that iron has a key role in several plant-pathogen interactions by modulating immunity. PMID:26475190

  6. Hyphal chemotropism in fungal pathogenicity.

    PubMed

    Turrà, David; Nordzieke, Daniela; Vitale, Stefania; El Ghalid, Mennat; Di Pietro, Antonio

    2016-09-01

    The ability to grow as filamentous hyphae defines the lifestyle of fungi. Hyphae are exposed to a variety of chemical stimuli such as nutrients or signal molecules from mating partners and host organisms. How fungi sense and process this chemical information to steer hyphal growth is poorly understood. Saccharomyces cerevisiae and Neurospora crassa have served as genetic models for the identification of cellular components functioning in chemotropism. A recent study in the pathogen Fusarium oxysporum revealed distinct MAPK pathways governing hyphal growth towards nutrient sources and sex pheromones or plant signals, suggesting an unanticipated complexity of chemosensing during fungus-host interactions. PMID:27150623

  7. Pathogen Tactics to Manipulate Plant Cell Death.

    PubMed

    Mukhtar, M Shahid; McCormack, Maggie E; Argueso, Cristiana T; Pajerowska-Mukhtar, Karolina M

    2016-07-11

    Cell death is a vital process for multicellular organisms. Programmed cell death (PCD) functions in a variety of processes including growth, development, and immune responses for homeostasis maintenance. In particular, plants and animals utilize PCD to control pathogen invasion and infected cell populations. Despite some similarity, there are a number of key differences between how these organisms initiate and regulate cell death. In contrast to animals, plants are sessile, lack a circulatory system, and have additional cellular structures, including cell walls and chloroplasts. Plant cells have the autonomous ability to induce localized cell death using conserved eukaryotic pathways as well as unique plant-specific pathways. Thus, in order to successfully infect host cells, pathogens must subvert immune responses and avoid detection to prevent PCD and allow infection. Here we discuss the roles of cell death in plant immune responses and the tactics pathogens utilize to avert cell death. PMID:27404256

  8. The cuticle and plant defense to pathogens

    PubMed Central

    Serrano, Mario; Coluccia, Fania; Torres, Martha; L’Haridon, Floriane; Métraux, Jean-Pierre

    2014-01-01

    The cuticle provides a physical barrier against water loss and protects against irradiation, xenobiotics, and pathogens. Components of the cuticle are perceived by invading fungi and activate developmental processes during pathogenesis. In addition, cuticle alterations of various types induce a syndrome of reactions that often results in resistance to necrotrophs. This article reviews the current knowledge on the role of the cuticle in relation to the perception of pathogens and activation of defenses. PMID:24982666

  9. Viroid Pathogenicity: One Process, Many Faces

    PubMed Central

    Owens, Robert A.; Hammond, Rosemarie W.

    2009-01-01

    Despite the non-coding nature of their small RNA genomes, the visible symptoms of viroid infection resemble those associated with many plant virus diseases. Recent evidence indicates that viroid-derived small RNAs acting through host RNA silencing pathways play a key role in viroid pathogenicity. Host responses to viroid infection are complex, involving signaling cascades containing host-encoded protein kinases and crosstalk between hormonal and defense-signaling pathways. Studies of viroid-host interaction in the context of entire biochemical or developmental pathways are just beginning, and many working hypotheses have yet to be critically tested. PMID:21994551

  10. Human fungal pathogens: Why should we learn?

    PubMed

    Kim, Jeong-Yoon

    2016-03-01

    Human fungal pathogens that cause invasive infections are hidden killers, taking lives of one and a half million people every year. However, research progress in this field has not been rapid enough to effectively prevent or treat life-threatening fungal diseases. To update recent research progress and promote more active research in the field of human fungal pathogens, eleven review articles concerning the virulence mechanisms and host interactions of four major human fungal pathogens-Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and Histoplasma capsulatum-are presented in this special issue. PMID:26920875

  11. Manipulation of Costimulatory Molecules by Intracellular Pathogens: Veni, Vidi, Vici!!

    PubMed Central

    Pahari, Susanta; Agrewala, Javed N.

    2012-01-01

    Some of the most successful pathogens of human, such as Mycobacterium tuberculosis (Mtb), HIV, and Leishmania donovani not only establish chronic infections but also remain a grave global threat. These pathogens have developed innovative strategies to evade immune responses such as antigenic shift and drift, interference with antigen processing/presentation, subversion of phagocytosis, induction of immune regulatory pathways, and manipulation of the costimulatory molecules. Costimulatory molecules expressed on the surface of various cells play a decisive role in the initiation and sustenance of immunity. Exploitation of the “code of conduct” of costimulation pathways provides evolutionary incentive to the pathogens and thereby abates the functioning of the immune system. Here we review how Mtb, HIV, Leishmania sp., and other pathogens manipulate costimulatory molecules to establish chronic infection. Impairment by pathogens in the signaling events delivered by costimulatory molecules may be responsible for defective T-cell responses; consequently organisms grow unhindered in the host cells. This review summarizes the convergent devices that pathogens employ to tune and tame the immune system using costimulatory molecules. Studying host-pathogen interaction in context with costimulatory signals may unveil the molecular mechanism that will help in understanding the survival/death of the pathogens. We emphasize that the very same pathways can potentially be exploited to develop immunotherapeutic strategies to eliminate intracellular pathogens. PMID:22719245

  12. Bacteriophage biocontrol of foodborne pathogens.

    PubMed

    Kazi, Mustafa; Annapure, Uday S

    2016-03-01

    Bacteriophages are viruses that only infect bacterial cells. Phages are categorized based on the type of their life cycle, the lytic cycle cause lysis of the bacterium with the release of multiple phage particles where as in lysogenic phase the phage DNA is incorporated into the bacterial genome. Lysogeny does not result in lysis of the host. Lytic phages have several potential applications in the food industry as biocontrol agents, biopreservatives and as tools for detecting pathogens. They have also been proposed as alternatives to antibiotics in animal health. Two unique features of phage relevant for food safety are that they are harmless to mammalian cells and high host specificity, keeping the natural microbiota undisturbed. However, the recent approval of bacteriophages as food additives has opened the discussion about 'edible viruses'. This article reviews in detail the application of phages for the control of foodborne pathogens in a process known as "biocontrol". PMID:27570260

  13. Taxonomy of bacterial fish pathogens

    PubMed Central

    2011-01-01

    Bacterial taxonomy has progressed from reliance on highly artificial culture-dependent techniques involving the study of phenotype (including morphological, biochemical and physiological data) to the modern applications of molecular biology, most recently 16S rRNA gene sequencing, which gives an insight into evolutionary pathways (= phylogenetics). The latter is applicable to culture-independent approaches, and has led directly to the recognition of new uncultured bacterial groups, i.e. "Candidatus", which have been associated as the cause of some fish diseases, including rainbow trout summer enteritic syndrome. One immediate benefit is that 16S rRNA gene sequencing has led to increased confidence in the accuracy of names allocated to bacterial pathogens. This is in marked contrast to the previous dominance of phenotyping, and identifications, which have been subsequently challenged in the light of 16S rRNA gene sequencing. To date, there has been some fluidity over the names of bacterial fish pathogens, with some, for example Vibrio anguillarum, being divided into two separate entities (V. anguillarum and V. ordalii). Others have been combined, for example V. carchariae, V. harveyi and V. trachuri as V. harveyi. Confusion may result with some organisms recognized by more than one name; V. anguillarum was reclassified as Beneckea and Listonella, with Vibrio and Listonella persisting in the scientific literature. Notwithstanding, modern methods have permitted real progress in the understanding of the taxonomic relationships of many bacterial fish pathogens. PMID:21314902

  14. Taxonomy of bacterial fish pathogens.

    PubMed

    Austin, Brian

    2011-02-02

    Bacterial taxonomy has progressed from reliance on highly artificial culture-dependent techniques involving the study of phenotype (including morphological, biochemical and physiological data) to the modern applications of molecular biology, most recently 16S rRNA gene sequencing, which gives an insight into evolutionary pathways (= phylogenetics). The latter is applicable to culture-independent approaches, and has led directly to the recognition of new uncultured bacterial groups, i.e. "Candidatus", which have been associated as the cause of some fish diseases, including rainbow trout summer enteritic syndrome. One immediate benefit is that 16S rRNA gene sequencing has led to increased confidence in the accuracy of names allocated to bacterial pathogens. This is in marked contrast to the previous dominance of phenotyping, and identifications, which have been subsequently challenged in the light of 16S rRNA gene sequencing. To date, there has been some fluidity over the names of bacterial fish pathogens, with some, for example Vibrio anguillarum, being divided into two separate entities (V. anguillarum and V. ordalii). Others have been combined, for example V. carchariae, V. harveyi and V. trachuri as V. harveyi. Confusion may result with some organisms recognized by more than one name; V. anguillarum was reclassified as Beneckea and Listonella, with Vibrio and Listonella persisting in the scientific literature. Notwithstanding, modern methods have permitted real progress in the understanding of the taxonomic relationships of many bacterial fish pathogens.

  15. Selected Aquatic Articles. Sports Articles Reprint Series. Second Edition.

    ERIC Educational Resources Information Center

    Clement, Annie, Ed.

    This is a collection of articles from the "DGWS (Division for Girls and Women's Sports) Aquatic Guides" from 1963-1969. All articles, with one exception, were revised to present the most important contributions for that time period in aquatic activity beyond simple swimming. Included in the selection are articles on fear and the non-swimmer, deep…

  16. Article Omission across Child Languages

    ERIC Educational Resources Information Center

    Guasti, Maria Teresa; Gavarro, Anna; de Lange, Joke; Caprin, Claudia

    2008-01-01

    Article omission is known to be a feature of early grammar, although it does not affect all child languages to the same extent. In this article we analyze the production of articles by 12 children, 4 speakers of Catalan, 4 speakers of Italian, and 4 speakers of Dutch. We consider the results in the light of (i) the adult input the children are…

  17. Microwave sintering of multiple articles

    DOEpatents

    Blake, Rodger D.; Katz, Joel D.

    1993-01-01

    Apparatus and method for producing articles of alumina and of alumina and silicon carbide in which the articles are sintered at high temperatures using microwave radiation. The articles are placed in a sintering container which is placed in a microwave cavity for heating. The rates at which heating and cooling take place is controlled.

  18. Mechanisms of bacterial pathogenicity

    PubMed Central

    Wilson, J; Schurr, M; LeBlanc, C; Ramamurthy, R; Buchanan, K; Nickerson, C

    2002-01-01

    Pathogenic bacteria utilise a number of mechanisms to cause disease in human hosts. Bacterial pathogens express a wide range of molecules that bind host cell targets to facilitate a variety of different host responses. The molecular strategies used by bacteria to interact with the host can be unique to specific pathogens or conserved across several different species. A key to fighting bacterial disease is the identification and characterisation of all these different strategies. The availability of complete genome sequences for several bacterial pathogens coupled with bioinformatics will lead to significant advances toward this goal. PMID:11930024

  19. Surface treatment of ceramic articles

    DOEpatents

    Komvopoulos, K.; Brown, I.G.; Wei, B.; Anders, S.; Anders, A.; Bhatia, C.S.

    1998-12-22

    A process is disclosed for producing an article with improved ceramic surface properties including providing an article having a ceramic surface, and placing the article onto a conductive substrate holder in a hermetic enclosure. Thereafter a low pressure ambient is provided in the hermetic enclosure. A plasma including ions of solid materials is produced the ceramic surface of the article being at least partially immersed in a macroparticle free region of the plasma. While the article is immersed in the macroparticle free region, a bias of the substrate holder is biased between a low voltage at which material from the plasma condenses on the surface of the article and a high negative voltage at which ions from the plasma are implanted into the article. 15 figs.

  20. Surface treatment of ceramic articles

    DOEpatents

    Komvopoulos, Kyriakos; Brown, Ian G.; Wei, Bo; Anders, Simone; Anders, Andre; Bhatia, C. Singh

    1998-01-01

    A process for producing an article with improved ceramic surface properties including providing an article having a ceramic surface, and placing the article onto a conductive substrate holder in a hermetic enclosure. Thereafter a low pressure ambient is provided in the hermetic enclosure. A plasma including ions of solid materials is produced the ceramic surface of the article being at least partially immersed in a macroparticle free region of the plasma. While the article is immersed in the macroparticle free region, a bias of the substrate holder is biased between a low voltage at which material from the plasma condenses on the surface of the article and a high negative voltage at which ions from the plasma are implanted into the article.

  1. The interactive effects of simultaneous biotic and abiotic stresses on plants: mechanistic understanding from drought and pathogen combination.

    PubMed

    Ramegowda, Venkategowda; Senthil-Kumar, Muthappa

    2015-03-15

    In nature, plants are simultaneously exposed to a combination of biotic and abiotic stresses that limit crop yields. Only recently, researchers have started understanding the molecular basis of combined biotic and abiotic stress interactions. Evidences suggest that under combined stress plants exhibit tailored physiological and molecular responses, in addition to several shared responses as part of their stress tolerance strategy. These tailored responses are suggested to occur only in plants exposed to simultaneous stresses and this information cannot be inferred from individual stress studies. In this review article, we provide update on the responses of plants to simultaneous biotic and abiotic stresses, in particular drought and pathogen. Simultaneous occurrence of drought and pathogen during plant growth provokes complex pathways controlled by different signaling events resulting in positive or negative impact of one stress over the other. Here, we summarize the effect of combined drought and pathogen infection on plants and highlight the tailored strategies adapted by plants. Besides, we enumerate the evidences from pathogen derived elicitors and ABA response studies for understanding simultaneous drought and pathogen tolerance.

  2. Roles of microRNA and signaling pathway in osteoarthritis pathogenesis*

    PubMed Central

    Xu, Bin; Li, Yao-yao; Ma, Jun; Pei, Fu-xing

    2016-01-01

    Osteoarthritis (OA) is a common chronic degenerative joint disease, with complicated pathogenic factors and undefined pathogenesis. Various signaling pathways play important roles in OA pathogenesis, including genetic expression, matrix synthesis and degradation, cell proliferation, differentiation, apoptosis, and so on. MicroRNA (miRNA) is a class of non-coding RNA in Eukaryon, regulating genetic expression on the post-transcriptional level. A great number of miRNAs are involved in the development of OA, and are closely associated with different signaling pathways. This article reviews the roles of miRNAs and signaling pathways in OA, looking toward having a better understanding of its pathogenesis mechanisms and providing new therapeutic targets for its treatment. PMID:26984840

  3. BACTERIAL WATERBORNE PATHOGENS

    EPA Science Inventory

    Bacterial pathogens are examples of classical etiological agents of waterborne disease. While these agents no longer serve as major threats to U.S. water supplies, they are still important pathogens in areas with substandard sanitation and poor water treatment facilities. In th...

  4. Plant pathogen resistance

    DOEpatents

    Greenberg, Jean T; Jung, Ho Won; Tschaplinski, Timothy

    2012-11-27

    Azelaic acid or its derivatives or analogs induce a robust and a speedier defense response against pathogens in plants. Azelaic acid treatment alone does not induce many of the known defense-related genes but activates a plant's defense signaling upon pathogen exposure.

  5. Plant pathogen resistance

    SciTech Connect

    Greenberg, Jean T.; Jung, Ho Won; Tschaplinski, Timothy

    2015-10-20

    Azelaic acid or its derivatives or analogs induce a robust and a speedier defense response against pathogens in plants. Azelaic acid treatment alone does not induce many of the known defense-related genes but activates a plant's defense signaling upon pathogen exposure.

  6. Emerging foodborne pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The emergence of new foodborne pathogens is due to a number of factors. An important factor is the globalization of the food supply with the possibility of the introduction of foodborne pathogens from other countries. Animal husbandry, food production, food processing, and food distribution system...

  7. Guidelines for evaluating research articles.

    PubMed

    Rumrill, Phillip; Fitzgerald, Shawn; Ware, Megen

    2000-01-01

    The article describes the components and composition of journal articles that report empirical research findings in the field of rehabilitation. The authors delineate technical writing strategies and discuss the contents of research manuscripts, including the Title, Abstract, Introduction, Method, Results, Discussion, and References. The article concludes with a scale that practitioners, manuscript reviewers, educators, and students can use in critically analyzing the content and scientific merits of published rehabilitation research. PMID:12441522

  8. Polyamine metabolism in flax in response to treatment with pathogenic and non–pathogenic Fusarium strains

    PubMed Central

    Wojtasik, Wioleta; Kulma, Anna; Namysł, Katarzyna; Preisner, Marta; Szopa, Jan

    2015-01-01

    Flax crop yield is limited by various environmental stress factors, but the largest crop losses worldwide are caused by Fusarium infection. Polyamines are one of the many plant metabolites possibly involved in the plant response to infection. However, in flax plants the polyamine composition, genes involved in polyamine synthesis, and in particular their regulation, were previously unknown. The aim of this study was to investigate the polyamine synthesis pathway in flax and its involvement in response to pathogen infection. It is well established that polyamines are essential for the growth and development of both plants and fungi, but their role in pathogen infection still remains unknown. In our study we correlated the expression of genes involved in polyamine metabolism with the polyamine levels in plant tissues and compared the results for flax seedlings treated with two pathogenic and one non-pathogenic strains of Fusarium. We observed an increase in the expression of genes participating in polyamine synthesis after fungal infection, and it was reflected in an increase of polyamine content in the plant tissues. The highest level of mRNA was characteristic for ornithine decarboxylase during infection with all tested, pathogenic and non-pathogenic, Fusarium strains and the arginine decarboxylase gene during infection with the pathogenic strain of Fusarium culmorum. The main polyamine identified in the flax seedlings was putrescine, and its level changed the most during infection. Moreover, the considerable increase in the contents of cell wall-bound polyamines compared to the levels of free and conjugated polyamines may indicate that their main role during pathogen infection lies in strengthening of the cell wall. In vitro experiments showed that the polyamines inhibit Fusarium growth, which suggests that they play an important role in plant defense mechanisms. Furthermore, changes in metabolism and content of polyamines indicate different defense mechanisms

  9. Polyamine metabolism in flax in response to treatment with pathogenic and non-pathogenic Fusarium strains.

    PubMed

    Wojtasik, Wioleta; Kulma, Anna; Namysł, Katarzyna; Preisner, Marta; Szopa, Jan

    2015-01-01

    Flax crop yield is limited by various environmental stress factors, but the largest crop losses worldwide are caused by Fusarium infection. Polyamines are one of the many plant metabolites possibly involved in the plant response to infection. However, in flax plants the polyamine composition, genes involved in polyamine synthesis, and in particular their regulation, were previously unknown. The aim of this study was to investigate the polyamine synthesis pathway in flax and its involvement in response to pathogen infection. It is well established that polyamines are essential for the growth and development of both plants and fungi, but their role in pathogen infection still remains unknown. In our study we correlated the expression of genes involved in polyamine metabolism with the polyamine levels in plant tissues and compared the results for flax seedlings treated with two pathogenic and one non-pathogenic strains of Fusarium. We observed an increase in the expression of genes participating in polyamine synthesis after fungal infection, and it was reflected in an increase of polyamine content in the plant tissues. The highest level of mRNA was characteristic for ornithine decarboxylase during infection with all tested, pathogenic and non-pathogenic, Fusarium strains and the arginine decarboxylase gene during infection with the pathogenic strain of Fusarium culmorum. The main polyamine identified in the flax seedlings was putrescine, and its level changed the most during infection. Moreover, the considerable increase in the contents of cell wall-bound polyamines compared to the levels of free and conjugated polyamines may indicate that their main role during pathogen infection lies in strengthening of the cell wall. In vitro experiments showed that the polyamines inhibit Fusarium growth, which suggests that they play an important role in plant defense mechanisms. Furthermore, changes in metabolism and content of polyamines indicate different defense mechanisms

  10. Mobile DNA in the Pathogenic Neisseria.

    PubMed

    Obergfell, Kyle P; Seifert, H Steven

    2015-02-01

    The genus Neisseria contains two pathogenic species of prominant public health concern: Neisseria gonorrhoeae and Neisseria meningitidis. These pathogens display a notable ability to undergo frequent programmed recombination events. The recombination-mediated pathways of transformation and pilin antigenic variation in the Neisseria are well-studied systems that are critical for pathogenesis. Here we will detail the conserved and unique aspects of transformation and antigenic variation in the Neisseria. Transformation will be followed from initial DNA binding through recombination into the genome with consideration to the factors necessary at each step. Additional focus is paid to the unique type IV secretion system that mediates donation of transforming DNA in the pathogenic Neisseria. The pilin antigenic variation system uses programmed recombinations to alter a major surface determinant, which allows immune avoidance and promotes infection. We discuss the trans- and cis- acting factors which facilitate pilin antigenic variation and present the current understanding of the mechanisms involved in the process.

  11. PsAAT3, an oomycete-specific aspartate aminotransferase, is required for full pathogenicity of the oomycete pathogen Phytophthora sojae.

    PubMed

    Wang, Rongbo; Zhang, Meixiang; Liu, Hong; Xu, Jing; Yu, Jia; He, Feng; Zhang, Xiong; Dong, Suomeng; Dou, Daolong

    2016-04-01

    Pathogen nutrient acquisition and metabolism are critical for successful infection and colonization. However, the nutrient requirements and metabolic pathways related to pathogenesis in oomycete pathogens are unknown. In this study, we bioinformatically identified Phytophthora sojae aspartate aminotransferases (AATs), which are key enzymes that coordinate carbon and nitrogen metabolism. We demonstrated that P. sojae encodes more AATs than the analysed fungi. Some of the AATs contained additional prephenate dehydratase and/or prephenate dehydrogenase domains in their N-termini, which are unique to oomycetes. Silencing of PsAAT3, an infection-inducible expression gene, reduced P. sojae pathogenicity on soybean plants and affected the growth under N-starving condition, suggesting that PsAAT3 is involved in pathogen pathogenicity and nitrogen utilisation during infection. Our results suggest that P. sojae and other oomycete pathogens may have distinct amino acid metabolism pathways and that PsAAT3 is important for its full pathogenicity. PMID:27020161

  12. Pathogen mimicry of host protein-protein interfaces modulates immunity.

    PubMed

    Guven-Maiorov, Emine; Tsai, Chung-Jung; Nussinov, Ruth

    2016-10-01

    Signaling pathways shape and transmit the cell's reaction to its changing environment; however, pathogens can circumvent this response by manipulating host signaling. To subvert host defense, they beat it at its own game: they hijack host pathways by mimicking the binding surfaces of host-encoded proteins. For this, it is not necessary to achieve global protein homology; imitating merely the interaction surface is sufficient. Different protein folds often interact via similar protein-protein interface architectures. This similarity in binding surfaces permits the pathogenic protein to compete with a host target protein. Thus, rather than binding a host-encoded partner, the host protein hub binds the pathogenic surrogate. The outcome can be dire: rewiring or repurposing the host pathways, shifting the cell signaling landscape and consequently the immune response. They can also cause persistent infections as well as cancer by modulating key signaling pathways, such as those involving Ras. Mapping the rewired host-pathogen 'superorganism' interaction network - along with its structural details - is critical for in-depth understanding of pathogenic mechanisms and developing efficient therapeutics. Here, we overview the role of molecular mimicry in pathogen host evasion as well as types of molecular mimicry mechanisms that emerged during evolution.

  13. Basic Psychiatric Literature: II. Articles and Article Sources*†

    PubMed Central

    Woods, Joan B.; Pieper, Sam; Frazier, Shervert H.

    1968-01-01

    Widely varying reading lists for general psychiatry residents were obtained from 140 three-year approved training programs. The material recommended for reading was listed on index cards, and the number of programs recommending each item was posted on the cards. Approximately 4,000 articles, 2,800 books, and 200 serials were recommended. A statistical evaluation of the book list appeared in a previous paper (3).* Part II is a similar evaluation of the article list and the limited editions and serials in which the articles appear. PMID:4883158

  14. Citation in Biomedical Journal Articles.

    ERIC Educational Resources Information Center

    Dubois, Betty Lou

    1988-01-01

    Examination of how biomedical scientists cite the published work of others in their own journal articles revealed that subjects tended to summarize or generalize others' articles and used few direct quotations and little paraphrasing. The results suggest ethical and instructional questions relating to which citation forms should be taught to…

  15. Pathogenicity of entamoeba histolytica.

    PubMed

    Kagan, I G

    1975-01-01

    The pathogenicity of Entamoeba histolytica is discussed from an immunologic point of view. The evidence that there is some "trigger" mechanism which converts a commensal dwelling organism into a tissue invasive pathogen is rejected as inadequate. The number of liver abscess cases in comparison with the number of intestinal amebic infections in a population is so low that this in itself suggests that tissue invasion is a rare event in the life history of the ameba. A review is made of the experimental evidence that some type of sensitization is necessary before ameba can invade tissue. In postulating an immunologic basis for the pathogenicity of ameba, a parallel between the behavior of malignant cells in the body and an amebic infection in the gut is made. An appealing hypothesis which deserves further research effort is that an altered immune response is the basis for the pathogenic mechanism in the host. PMID:171223

  16. Articles comprising ferritic stainless steels

    DOEpatents

    Rakowski, James M.

    2016-06-28

    An article of manufacture comprises a ferritic stainless steel that includes a near-surface region depleted of silicon relative to a remainder of the ferritic stainless steel. The article has a reduced tendency to form an electrically resistive silica layer including silicon derived from the steel when the article is subjected to high temperature oxidizing conditions. The ferritic stainless steel is selected from the group comprising AISI Type 430 stainless steel, AISI Type 439 stainless steel, AISI Type 441 stainless steel, AISI Type 444 stainless steel, and E-BRITE.RTM. alloy, also known as UNS 44627 stainless steel. In certain embodiments, the article of manufacture is a fuel cell interconnect for a solid oxide fuel cell.

  17. Global Expression Studies of Yersinia Pestis Pathogenicity

    SciTech Connect

    Garcia, E; Motin, V; Brubaker, R; Fitch, P

    2002-10-15

    The aim of these studies continues to be the investigation into the molecular mechanisms that underlie the virulence process in Yersinia pestis. In particular, the focus of this work centers on the identification of novel genes and pathways responsible for the pathogenic properties of this organism. In spite of more than four decades of intense investigation in this field, the dilemma as to what makes Y. pestis such a virulent and lethal pathogen remains unanswered. The method being employed makes use microarray technology (DNA chip) that enables the examination of the global activities of the whole complement of genes in this pathogen. Two primary resources available to the investigators (one directly obtained from a separate CBNP-funded project) make these studies possible: (1) Whole genome comparisons of the genes in Y. pestis and its near neighbors with attenuated or non pathogenic characteristics, and (2) the ability to duplicate in vitro, conditions that mimic the infection process of this pathogen. This year we have extended our studies from the original work of characterizing the global transcriptional regulation in Y. pestis triggered during temperature transition from 26 C to 37 C (roughly conditions found in the flea vector and the mammalian host, respectively) to studies of regulation encountered during shift between growth from conditions of neutral pH to acidic pH (the latter conditions, those mimic the environment found inside macrophages, a likely environment found by these cells during infection.). For this work, DNA arrays containing some 5,000 genes (the entire genome of Y. pestis plus those genes found uniquely in the enteropathogen, and near neighbor, Y. pseudotuberculosis) are used to monitor the simultaneous expression levels of each gene of known and unknown function in Y. pestis. Those genes that are up-regulate under the experimental conditions represent genes potentially involved in the pathogenic process. The ultimate role in

  18. Prediction of molecular mimicry candidates in human pathogenic bacteria.

    PubMed

    Doxey, Andrew C; McConkey, Brendan J

    2013-08-15

    Molecular mimicry of host proteins is a common strategy adopted by bacterial pathogens to interfere with and exploit host processes. Despite the availability of pathogen genomes, few studies have attempted to predict virulence-associated mimicry relationships directly from genomic sequences. Here, we analyzed the proteomes of 62 pathogenic and 66 non-pathogenic bacterial species, and screened for the top pathogen-specific or pathogen-enriched sequence similarities to human proteins. The screen identified approximately 100 potential mimicry relationships including well-characterized examples among the top-scoring hits (e.g., RalF, internalin, yopH, and others), with about 1/3 of predicted relationships supported by existing literature. Examination of homology to virulence factors, statistically enriched functions, and comparison with literature indicated that the detected mimics target key host structures (e.g., extracellular matrix, ECM) and pathways (e.g., cell adhesion, lipid metabolism, and immune signaling). The top-scoring and most widespread mimicry pattern detected among pathogens consisted of elevated sequence similarities to ECM proteins including collagens and leucine-rich repeat proteins. Unexpectedly, analysis of the pathogen counterparts of these proteins revealed that they have evolved independently in different species of bacterial pathogens from separate repeat amplifications. Thus, our analysis provides evidence for two classes of mimics: complex proteins such as enzymes that have been acquired by eukaryote-to-pathogen horizontal transfer, and simpler repeat proteins that have independently evolved to mimic the host ECM. Ultimately, computational detection of pathogen-specific and pathogen-enriched similarities to host proteins provides insights into potentially novel mimicry-mediated virulence mechanisms of pathogenic bacteria.

  19. Invertebrates as a source of emerging human pathogens.

    PubMed

    Waterfield, Nicholas R; Wren, Brendan W; Ffrench-Constant, Richard H

    2004-10-01

    Despite their importance, little is known about the origins of many emerging human pathogens. However, given the age and current predominance of invertebrates, it is likely that bacteria-invertebrate interactions are not only a present source of human pathogens but have also shaped their evolution. Pathogens of invertebrate and unicellular organisms represent an extensive reservoir of bacterial strains equipped with virulence factors that evolved to overcome the innate immune responses of their hosts. This reservoir might represent a source of new human pathogenic strains and might also foster the spread of novel virulence factors into existing human commensal or pathogenic bacteria. This article examines the available evidence for this concept by examining pairs of closely related bacteria, one of which is benign, but insect associated, and one of which is a human pathogen.

  20. Microbial risk assessment in heterogeneous aquifers: 1. Pathogen transport

    NASA Astrophysics Data System (ADS)

    Molin, S.; Cvetkovic, V.

    2010-05-01

    Pathogen transport in heterogeneous aquifers is investigated for microbial risk assessment. A point source with time-dependent input of pathogens is assumed, exemplified as a simple on-site sanitation installation, intermingled with water supply wells. Any pathogen transmission pathway (realization) to the receptor from a postulated infection hazard is viewed as a random event, with the hydraulic conductivity varying spatially. For aquifers where VAR[lnK] < 1 and the integral scale is finite, we provide relatively simple semianalytical expressions for pathogen transport that incorporate the colloid filtration theory. We test a wide range of Damkohler numbers in order to assess the significance of rate limitations on the aquifer barrier function. Even slow immobile inactivation may notably affect the retention of pathogens. Analytical estimators for microbial peak discharge are evaluated and are shown to be applicable using parameters representative of rotavirus and Hepatitis A with input of 10-20 days duration.

  1. Pathogens and polymers: Microbe–host interactions illuminate the cytoskeleton

    PubMed Central

    Haglund, Cat M.

    2011-01-01

    Intracellular pathogens subvert the host cell cytoskeleton to promote their own survival, replication, and dissemination. Study of these microbes has led to many discoveries about host cell biology, including the identification of cytoskeletal proteins, regulatory pathways, and mechanisms of cytoskeletal function. Actin is a common target of bacterial pathogens, but recent work also highlights the use of microtubules, cytoskeletal motors, intermediate filaments, and septins. The study of pathogen interactions with the cytoskeleton has illuminated key cellular processes such as phagocytosis, macropinocytosis, membrane trafficking, motility, autophagy, and signal transduction. PMID:21969466

  2. [Searching articles and their management].

    PubMed

    Tomizawa, Yasuko

    2010-05-01

    The development of digitalizing technology and the Internet has enabled medical doctors and researchers in medicine to search and read the latest articles at their desk without visiting a library. As a result of the time and effort spent for searching articles can be extremely reduced by learning how to use effective tools in combination, the time for the research activity will certainly be greatly saved. It is promising that the advancement of science database, online journals, evaluating system of the journal impact will be great help for researchers. PMID:20446610

  3. Stomata and pathogens

    PubMed Central

    Gudesblat, Gustavo E; Torres, Pablo S

    2009-01-01

    Bacteria and fungi are capable of triggering stomatal closure through pathogen-associated molecular patterns (PAMPs), which prevents penetration through these pores. Therefore, the stomata can be considered part of the plant innate immune response. Some pathogens have evolved mechanisms to evade stomatal defense. The bacterial pathogen Xanthomonas campestris pv. campestris (Xcc), which infects plants of the Brassicaceae family mainly through hydathodes, has also been reported to infect plants through stomata. A recent report shows that penetration of Xcc in Arabidopsis leaves through stomata depends on a secreted small molecule whose synthesis is under control of the rpf/diffusible signal factor (DSF) cell-to-cell signaling system, which also controls genes involved in biofilm formation and pathogenesis. The same reports shows that Arabidopsis ROS- and PAMP-activated MAP kinase 3 (MPK3) is essential for stomatal innate response. Other recent and past findings about modulation of stomatal behaviour by pathogens are also discussed. In all, these findings support the idea that PAMP-triggered stomatal closure might be a more effective and widespread barrier against phytopathogens than previously thought, which has in turn led to the evolution in pathogens of several mechanisms to evade stomatal defense. PMID:20514224

  4. Pathogenic Network Analysis Predicts Candidate Genes for Cervical Cancer

    PubMed Central

    Zhang, Yun-Xia

    2016-01-01

    Purpose. The objective of our study was to predicate candidate genes in cervical cancer (CC) using a network-based strategy and to understand the pathogenic process of CC. Methods. A pathogenic network of CC was extracted based on known pathogenic genes (seed genes) and differentially expressed genes (DEGs) between CC and normal controls. Subsequently, cluster analysis was performed to identify the subnetworks in the pathogenic network using ClusterONE. Each gene in the pathogenic network was assigned a weight value, and then candidate genes were obtained based on the weight distribution. Eventually, pathway enrichment analysis for candidate genes was performed. Results. In this work, a total of 330 DEGs were identified between CC and normal controls. From the pathogenic network, 2 intensely connected clusters were extracted, and a total of 52 candidate genes were detected under the weight values greater than 0.10. Among these candidate genes, VIM had the highest weight value. Moreover, candidate genes MMP1, CDC45, and CAT were, respectively, enriched in pathway in cancer, cell cycle, and methane metabolism. Conclusion. Candidate pathogenic genes including MMP1, CDC45, CAT, and VIM might be involved in the pathogenesis of CC. We believe that our results can provide theoretical guidelines for future clinical application. PMID:27034707

  5. Subverting Toll-Like Receptor Signaling by Bacterial Pathogens

    PubMed Central

    McGuire, Victoria A.; Arthur, J. Simon C.

    2015-01-01

    Pathogenic bacteria are detected by pattern-recognition receptors (PRRs) expressed on innate immune cells, which activate intracellular signal transduction pathways to elicit an immune response. Toll-like receptors are, perhaps, the most studied of the PRRs and can activate the mitogen-activated protein kinase (MAPK) and Nuclear Factor-κB (NF-κB) pathways. These pathways are critical for mounting an effective immune response. In order to evade detection and promote virulence, many pathogens subvert the host immune response by targeting components of these signal transduction pathways. This mini-review highlights the diverse mechanisms that bacterial pathogens have evolved to manipulate the innate immune response, with a particular focus on those that target MAPK and NF-κB signaling pathways. Understanding the elaborate strategies that pathogens employ to subvert the immune response not only highlights the importance of these proteins in mounting effective immune responses, but may also identify novel approaches for treatment or prevention of infection. PMID:26648936

  6. Ophthalmic parasitosis: a review article.

    PubMed

    Nimir, Amal R; Saliem, Ahmed; Ibrahim, Ibrahim Abdel Aziz

    2012-01-01

    Ocular parasitosis in human is more prevalent in geographical areas where environmental factors and poor sanitary conditions favor the parasitism between man and animals. Lesions in the eye can be due to damage directly caused by the infectious pathogen, indirect pathology caused by toxic products, or the immune response incited by infections or ectopic parasitism. The epidemiology of parasitic ocular diseases reflects the habitat of the causative parasites as well as the habits and health status of the patient. An ocular examination may provide clues to the underlying disease/infection, and an awareness of the possibilities of travel-related pathology may shed light on an ocular presentation. This paper is a comprehensive review of the parasitic diseases of the eye. The majority of the clinically important species of parasites involved in eye infection are reviewed in this paper. Parasites are discussed by the disease or infection they cause.

  7. Ophthalmic Parasitosis: A Review Article

    PubMed Central

    Nimir, Amal R.; Saliem, Ahmed; Ibrahim, Ibrahim Abdel Aziz

    2012-01-01

    Ocular parasitosis in human is more prevalent in geographical areas where environmental factors and poor sanitary conditions favor the parasitism between man and animals. Lesions in the eye can be due to damage directly caused by the infectious pathogen, indirect pathology caused by toxic products, or the immune response incited by infections or ectopic parasitism. The epidemiology of parasitic ocular diseases reflects the habitat of the causative parasites as well as the habits and health status of the patient. An ocular examination may provide clues to the underlying disease/infection, and an awareness of the possibilities of travel-related pathology may shed light on an ocular presentation. This paper is a comprehensive review of the parasitic diseases of the eye. The majority of the clinically important species of parasites involved in eye infection are reviewed in this paper. Parasites are discussed by the disease or infection they cause. PMID:23024652

  8. Bioterrorism: pathogens as weapons.

    PubMed

    Anderson, Peter D; Bokor, Gyula

    2012-10-01

    Biowarfare has been used for centuries. The use of biological weapons in terrorism remains a threat. Biological weapons include infectious agents (pathogens) and toxins. The most devastating bioterrorism scenario would be the airborne dispersal of pathogens over a concentrated population area. Characteristics that make a specific pathogen a high-risk for bioterrorism include a low infective dose, ability to be aerosolized, high contagiousness, and survival in a variety of environmental conditions. The most dangerous potential bioterrorism agents include the microorganisms that produce anthrax, plague, tularemia, and smallpox. Other diseases of interest to bioterrorism include brucellosis, glanders, melioidosis, Q fever, and viral encephalitis. Food safety and water safety threats are another area of concern.

  9. Bioterrorism: pathogens as weapons.

    PubMed

    Anderson, Peter D; Bokor, Gyula

    2012-10-01

    Biowarfare has been used for centuries. The use of biological weapons in terrorism remains a threat. Biological weapons include infectious agents (pathogens) and toxins. The most devastating bioterrorism scenario would be the airborne dispersal of pathogens over a concentrated population area. Characteristics that make a specific pathogen a high-risk for bioterrorism include a low infective dose, ability to be aerosolized, high contagiousness, and survival in a variety of environmental conditions. The most dangerous potential bioterrorism agents include the microorganisms that produce anthrax, plague, tularemia, and smallpox. Other diseases of interest to bioterrorism include brucellosis, glanders, melioidosis, Q fever, and viral encephalitis. Food safety and water safety threats are another area of concern. PMID:23011963

  10. "Developmental Review's" Most Influential Articles

    ERIC Educational Resources Information Center

    Brainerd, C. J.

    2006-01-01

    "Developmental Review" is a journal of literature reviews and theoretical analyses for developmental scientists. During its first quarter-century of publication, the quality of those articles resulted in a journal whose level of impact on the scientific literature is extremely high, currently in the top 10% of all journals indexed by "Social…

  11. Commentary on Albert Ellis' Article

    ERIC Educational Resources Information Center

    Kleiner, Frederic B.

    1977-01-01

    In a response to Albert Ellis' feature article, the author agrees with Ellis but feels that less time should be spent proving which counseling method is better than the next, and more time spent in comparative research as per clients' gains. (HMV)

  12. Anterior cruciate ligament - updating article.

    PubMed

    Luzo, Marcus Vinicius Malheiros; Franciozi, Carlos Eduardo da Silveira; Rezende, Fernando Cury; Gracitelli, Guilherme Conforto; Debieux, Pedro; Cohen, Moisés

    2016-01-01

    This updating article on the anterior cruciate ligament (ACL) has the aim of addressing some of the most interesting current topics in this field. Within this stratified approach, it contains the following sections: ACL remnant; anterolateral ligament and combined intra and extra-articular reconstruction; fixation devices; and ACL femoral tunnel creation techniques. PMID:27517015

  13. Anterior cruciate ligament - updating article.

    PubMed

    Luzo, Marcus Vinicius Malheiros; Franciozi, Carlos Eduardo da Silveira; Rezende, Fernando Cury; Gracitelli, Guilherme Conforto; Debieux, Pedro; Cohen, Moisés

    2016-01-01

    This updating article on the anterior cruciate ligament (ACL) has the aim of addressing some of the most interesting current topics in this field. Within this stratified approach, it contains the following sections: ACL remnant; anterolateral ligament and combined intra and extra-articular reconstruction; fixation devices; and ACL femoral tunnel creation techniques.

  14. Enteric pathogens and soil: a short review.

    PubMed

    Santamaría, Johanna; Toranzos, Gary A

    2003-03-01

    It is known that soil is a recipient of solid wastes able to contain enteric pathogens in high concentrations. Although the role of soil as a reservoir of certain bacterial pathogens is not in question, recent findings show that soil may have a larger role in the transmission of enteric diseases than previously thought. Many of the diseases caused by agents from soil have been well characterized, although enteric diseases and their link to soil have not been so well studied. Gastrointestinal infections are the most common diseases caused by enteric bacteria. Some examples are salmonellosis ( Salmonella sp.), cholera ( Vibrio cholerae), dysentery ( Shigella sp.) and other infections caused by Campylobacter jejuni, Yersinia sp. and Escherichia coli O157:H7 and many other strains. Viruses are the most hazardous and have some of the lowest infectious doses of any of the enteric pathogens. Hepatitis A, hepatitis E, enteric adenoviruses, poliovirus types 1 and 2, multiple strains of echoviruses and coxsackievirus are enteric viruses associated with human wastewater. Among the most commonly detected protozoa in sewage are Entamoeba histolytica, Giardia intestinalis and Cryptosporidium parvum. This article reviews the existing literature of more than two decades on waste disposal practices that favor the entry of enteric pathogens to soil and the possible consequent role of the soil as a vector and reservoir of enteric pathogens.

  15. Highly pathogenic avian influenza.

    PubMed

    Swayne, D E; Suarez, D L

    2000-08-01

    Highly pathogenic (HP) avian influenza (AI) (HPAI) is an extremely contagious, multi-organ systemic disease of poultry leading to high mortality, and caused by some H5 and H7 subtypes of type A influenza virus, family Orthomyxoviridae. However, most AI virus strains are mildly pathogenic (MP) and produce either subclinical infections or respiratory and/or reproductive diseases in a variety of domestic and wild bird species. Highly pathogenic avian influenza is a List A disease of the Office International des Epizooties, while MPAI is neither a List A nor List B disease. Eighteen outbreaks of HPAI have been documented since the identification of AI virus as the cause of fowl plague in 1955. Mildly pathogenic avian influenza viruses are maintained in wild aquatic bird reservoirs, occasionally crossing over to domestic poultry and causing outbreaks of mild disease. Highly pathogenic avian influenza viruses do not have a recognised wild bird reservoir, but can occasionally be isolated from wild birds during outbreaks in domestic poultry. Highly pathogenic avian influenza viruses have been documented to arise from MPAI viruses through mutations in the haemagglutinin surface protein. Prevention of exposure to the virus and eradication are the accepted methods for dealing with HPAI. Control programmes, which imply allowing a low incidence of infection, are not an acceptable method for managing HPAI, but have been used during some outbreaks of MPAI. The components of a strategy to deal with MPAI or HPAI include surveillance and diagnosis, biosecurity, education, quarantine and depopulation. Vaccination has been used in some control and eradication programmes for AI.

  16. Bloodborne Pathogens Program

    NASA Technical Reports Server (NTRS)

    Blasdell, Sharon

    1993-01-01

    The final rule on the Occupational Exposure to Bloodborne Pathogens was published in the Federal Register on Dec. 6, 1991. This Standard, 29 CFR Part 1910.130, is expected to prevent 8,900 hepatitis B infections and nearly 200 deaths a year in healthcare workers in the U.S. The Occupational Medicine and Environmental Health Services at KSC has been planning to implement this standard for several years. Various aspects of this standard and its Bloodborne Pathogens Program at KSC are discussed.

  17. Pathogens and gene product normalization in the biomedical literature.

    PubMed

    Vishnyakova, Dina; Pasche, Emilie; Teodoro, Douglas; Lovis, Christian; Ruch, Patrick

    2012-01-01

    We present a new approach for pathogens and gene product normalization in the biomedical literature. The idea of this approach was motivated by needs such as literature curation, in particular applied to the field of infectious diseases thus, variants of bacterial species (S. aureus, Staphyloccocus aureus, ...) and their gene products (protein ArsC, Arsenical pump modifier, Arsenate reductase, ...). Our approach is based on the use of an Ontology Look-up Service, a Gene Ontology Categorizer (GOCat) and Gene Normalization methods. In the pathogen detection task the use of OLS disambiguates found pathogen names. GOCat results are incorporated into overall score system to support and to confirm the decisionmaking in normalization process of pathogens and their genomes. The evaluation was done on two test sets of BioCreativeIII benchmark: gold standard of manual curation (50 articles) and silver standard (507 articles) curated by collective results of BCIII participants. For the cross-species GN we achieved the precision of 46% for silver and 27% for gold sets. Pathogen normalization results showed 95% of precision and 93% of recall. The impact of GOCat explicitly improves results of pathogen and gene normalization, basically confirming identified pathogens and boosting correct gene identifiers on the top of the results' list ranked by confidence. A correct identification of the pathogen is able to improve significantly normalization effectiveness and to solve the disambiguation problem of genes.

  18. Emerging Pathogens – How Safe is Blood?

    PubMed Central

    Schmidt, Michael; Geilenkeuser, Wolf-Jochen; Sireis, Walid; Seifried, Erhard; Hourfar, Kai

    2014-01-01

    Summary During the last few decades, blood safety efforts were mainly focused on preventing viral infections. However, humanity's increased mobility and improved migration pathways necessitate a global perspective regarding other transfusion-transmitted pathogens. This review focuses on the general infection risk of blood components for malaria, dengue virus, Trypanosoma cruzi (Chagas disease) and Babesia spp. Approximately 250 million people become infected by Plasmodium spp. per year. Dengue virus affects more than 50 million people annually in more than 100 countries; clinically, it can cause serious diseases, such as dengue haemorrhagic fever and dengue shock syndrome. Chagas disease, which is caused by Trypanosoma cruzi, mainly occurs in South America and infects approximately 10 million people annually. Babesia spp. is a parasitic infection that infects red blood cells; although many infections are asymptomatic, severe clinical disease has been reported, especially in the elderly. Screening assays are available for all considered pathogens but make screening strategies more complex and more expensive. A general pathogen inactivation for all blood components (whole blood) promises to be a long-term, sustainable solution for both known and unknown pathogens. Transfusion medicine therefore eagerly awaits such a system. PMID:24659943

  19. Emerging Pathogens - How Safe is Blood?

    PubMed

    Schmidt, Michael; Geilenkeuser, Wolf-Jochen; Sireis, Walid; Seifried, Erhard; Hourfar, Kai

    2014-02-01

    During the last few decades, blood safety efforts were mainly focused on preventing viral infections. However, humanity's increased mobility and improved migration pathways necessitate a global perspective regarding other transfusion-transmitted pathogens. This review focuses on the general infection risk of blood components for malaria, dengue virus, Trypanosoma cruzi (Chagas disease) and Babesia spp. Approximately 250 million people become infected by Plasmodium spp. per year. Dengue virus affects more than 50 million people annually in more than 100 countries; clinically, it can cause serious diseases, such as dengue haemorrhagic fever and dengue shock syndrome. Chagas disease, which is caused by Trypanosoma cruzi, mainly occurs in South America and infects approximately 10 million people annually. Babesia spp. is a parasitic infection that infects red blood cells; although many infections are asymptomatic, severe clinical disease has been reported, especially in the elderly. Screening assays are available for all considered pathogens but make screening strategies more complex and more expensive. A general pathogen inactivation for all blood components (whole blood) promises to be a long-term, sustainable solution for both known and unknown pathogens. Transfusion medicine therefore eagerly awaits such a system. PMID:24659943

  20. Pathways of Antigen Processing

    PubMed Central

    Blum, Janice S.; Wearsch, Pamela A.; Cresswell, Peter

    2014-01-01

    T cell recognition of antigen presenting cells depends on their expression of a spectrum of peptides bound to Major Histocompatibility Complex class I (MHC-I) and class II (MHC-II) molecules. Conversion of antigens from pathogens or transformed cells into MHC-I and MHC-II-bound peptides is critical for mounting protective T cell responses, and similar processing of self proteins is necessary to establish and maintain tolerance. Cells use a variety of mechanisms to acquire protein antigens, from translation in the cytosol to variations on the theme of endocytosis, and to degrade them once acquired. In this review we highlight the aspects of MHC-I and MHC-II biosynthesis and assembly that have evolved to intersect these pathways and sample the peptides that are produced. PMID:23298205

  1. A more flexible lipoprotein sorting pathway.

    PubMed

    Chahales, Peter; Thanassi, David G

    2015-05-01

    Lipoprotein biogenesis in Gram-negative bacteria occurs by a conserved pathway, each step of which is considered essential. In contrast to this model, LoVullo and colleagues demonstrate that the N-acyl transferase Lnt is not required in Francisella tularensis or Neisseria gonorrhoeae. This suggests the existence of a more flexible lipoprotein pathway, likely due to a modified Lol transporter complex, and raises the possibility that pathogens may regulate lipoprotein processing to modulate interactions with the host. PMID:25755190

  2. Main Propulsion Test Article (MPTA)

    NASA Technical Reports Server (NTRS)

    Snoddy, Cynthia

    2010-01-01

    Scope: The Main Propulsion Test Article integrated the main propulsion subsystem with the clustered Space Shuttle Main Engines, the External Tank and associated GSE. The test program consisted of cryogenic tanking tests and short- and long duration static firings including gimbaling and throttling. The test program was conducted on the S1-C test stand (Position B-2) at the National Space Technology Laboratories (NSTL)/Stennis Space Center. 3 tanking tests and 20 hot fire tests conducted between December 21 1 1977 and December 17, 1980 Configuration: The main propulsion test article consisted of the three space shuttle main engines, flightweight external tank, flightweight aft fuselage, interface section and a boilerplate mid/fwd fuselage truss structure.

  3. Article removal device for glovebox

    DOEpatents

    Guyer, R.H.; Leebl, R.G.

    1973-12-01

    An article removal device for a glovebox is described comprising a conduit extending through a glovebox wall which may be closed by a plug within the glovebox, and a fire-resistant container closing the outer end of the conduit and housing a removable container for receiving pyrophoric or otherwise hazardous material without disturbing the interior environment of the glovebox or adversely affecting the environment outside of the glovebox. (Official Gazette)

  4. PATHOGEN EQUIVALENCY COMMITTEE (PEC)

    EPA Science Inventory

    The U.S. Environmental Protection Agency created the PEC in 1985 to make recommendations to EPA and State managers on the equivalency of unproven sewage sludge disinfection technologies/processes to either a Process to Significantly Reduce Pathogens (PSRP) or a Process to Further...

  5. DISINFECTION OF EMERGING PATHOGENS

    EPA Science Inventory

    There is a growing awareness of the need to control waterborne microbial pathogens. This presentation will concentate on the role of chemical inactivation, using chlorine, chloramines and ozone as a means of controlling bacterial and protozoan species. Information will be present...

  6. Leafhopper viral pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four newly discovered viral pathogens in leafhopper vectors of Pierce’s disease of grapes, have been shown to replicate in sharpshooter leafhoppers; the glassy-winged sharpshooter, GWSS, Homalodisca vitripennis, and Oncometopia nigricans (Hemiptera: Cicadellidae). The viruses were classified as memb...

  7. Bacterial genomes: evolution of pathogenicity.

    PubMed

    Arnold, Dawn L; Jackson, Robert W

    2011-08-01

    Bacterial pathogens continue to pose a major threat to economically important plant resources. Disease outbreaks can occur through rapid evolution of a pathogen to overcome host defences. The advent of genome sequencing, especially next-generation technologies, has seen a revolution in the study of plant pathogen evolution over the past five years. This review highlights recent developments in understanding bacterial plant pathogen evolution, enabled by genomics and specifically focusing on type III protein effectors. The genotypic changes and mechanisms involved in pathogen evolution are now much better understood. However, there is still much to be learned about the drivers of pathogen evolution, both in terms of plant resistance and bacterial lifestyle.

  8. Stress adaptation in a pathogenic fungus

    PubMed Central

    Brown, Alistair J. P.; Budge, Susan; Kaloriti, Despoina; Tillmann, Anna; Jacobsen, Mette D.; Yin, Zhikang; Ene, Iuliana V.; Bohovych, Iryna; Sandai, Doblin; Kastora, Stavroula; Potrykus, Joanna; Ballou, Elizabeth R.; Childers, Delma S.; Shahana, Shahida; Leach, Michelle D.

    2014-01-01

    Candida albicans is a major fungal pathogen of humans. This yeast is carried by many individuals as a harmless commensal, but when immune defences are perturbed it causes mucosal infections (thrush). Additionally, when the immune system becomes severely compromised, C. albicans often causes life-threatening systemic infections. A battery of virulence factors and fitness attributes promote the pathogenicity of C. albicans. Fitness attributes include robust responses to local environmental stresses, the inactivation of which attenuates virulence. Stress signalling pathways in C. albicans include evolutionarily conserved modules. However, there has been rewiring of some stress regulatory circuitry such that the roles of a number of regulators in C. albicans have diverged relative to the benign model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. This reflects the specific evolution of C. albicans as an opportunistic pathogen obligately associated with warm-blooded animals, compared with other yeasts that are found across diverse environmental niches. Our understanding of C. albicans stress signalling is based primarily on the in vitro responses of glucose-grown cells to individual stresses. However, in vivo this pathogen occupies complex and dynamic host niches characterised by alternative carbon sources and simultaneous exposure to combinations of stresses (rather than individual stresses). It has become apparent that changes in carbon source strongly influence stress resistance, and that some combinatorial stresses exert non-additive effects upon C. albicans. These effects, which are relevant to fungus–host interactions during disease progression, are mediated by multiple mechanisms that include signalling and chemical crosstalk, stress pathway interference and a biological transistor. PMID:24353214

  9. Publishing Scientific Articles in XML.

    NASA Astrophysics Data System (ADS)

    Shaya, E.; Borne, K.; Thomas, B.; Cheung, C. Y.

    2001-12-01

    Most publication houses are using SGML for electronic mark up of pages intended for hardcopy. Since XML is a major subset of SGML with W3C backing and greater database compatibility, many publication houses are naturally considering switching to or including XML. Now, if authors were also to switch to XML for their manuscripts, it would greatly reduce the work load at the publication houses and reduce the number of errors that are introduced in the translation process. XML is also a logical progression for authors since it is rapidly becoming incorporated into editors such as Word Perfect, Notepad, Emacs, etc. There is an XML standard for equation markup, MathML, and equation editors exist for it. It is easy to put these manuscripts onto the Web; all one needs is to link to a standard cascade style sheet (CSS2). Leveraging our experience with encapsulating scientific data in XML the ADC (Astronomical Data Center) staff are working out details of a scientific XML article format called "AXML" (Article XML Markup Language). We foresee using AXML eventually as an end to end solution for data from experiment/observation through analysis to publication. With fewer transformations needed on article text, equations, and tables, less human intervention will be required and fewer human errors will be introduced, for example, proofing of XML documents by publication houses could someday be unnecessary or (at least) vastly more efficient. In this poster we discuss examine several important aspects of this technology, give the technical details of AXML (including a DTD) and give examples which show the power of AXML.

  10. AlzPathway, an Updated Map of Curated Signaling Pathways: Towards Deciphering Alzheimer's Disease Pathogenesis.

    PubMed

    Ogishima, Soichi; Mizuno, Satoshi; Kikuchi, Masataka; Miyashita, Akinori; Kuwano, Ryozo; Tanaka, Hiroshi; Nakaya, Jun

    2016-01-01

    Alzheimer's disease (AD) is a complex neurodegenerative disorder in which loss of neurons and synaptic function causes dementia in the elderly. To clarify AD pathogenesis and develop drugs for AD, thousands of studies have elucidated signaling pathways involved. However, knowledge of AD signaling pathways has not been compiled as a pathway map. In this chapter, we introduce the manual construction of a pathway map in AD which we call "AlzPathway", that comprehensively catalogs signaling pathways in the field of AD. We have collected and manually curated over 100 review articles related to AD, and have built the AD pathway map. AlzPathway is currently composed of thousands of molecules and reactions in neurons, brain blood barrier, presynaptic, postsynaptic, astrocyte, and microglial cells, with their cellular localizations. AlzPathway provides a systems-biology platform of comprehensive AD signaling and related pathways which is expected to contribute to clarification of AD pathogenesis and AD drug development.

  11. Contributions of host cellular trafficking and organization to the outcomes of plant-pathogen interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In recent years it has become increasingly apparent that dynamic changes in protein localization, membrane trafficking pathways, and cellular organization play a major role in determining the outcome of interactions between plants and pathogenic microorganisms. Plants have evolved sophisticated perc...

  12. Maintenance of vacuole integrity by bacterial pathogens.

    PubMed

    Creasey, Elizabeth A; Isberg, Ralph R

    2014-02-01

    Many intracellular bacterial pathogens reside within a membrane-bound compartment. The biogenesis of these vacuolar compartments is complex, involving subversion of host cell secretory pathways by bacterial proteins. In recent years it has become clear that disruption of vacuole biogenesis may result in membrane rupture and escape of bacteria into the host cell cytosol. Correct modulation of the host cell cytoskeleton, signalling molecules such as small GTPases and the lipids of the vacuole membrane have all been shown to be critical in the maintenance of vacuole integrity. Increasing evidence suggests that vacuole rupture may result from aberrant mechanical forces exerted on the vacuole, possibly due to a defect in vacuole expansion.

  13. Application of microfluidics in waterborne pathogen monitoring: a review.

    PubMed

    Bridle, Helen; Miller, Brian; Desmulliez, Marc P Y

    2014-05-15

    A review of the recent advances in microfluidics based systems for the monitoring of waterborne pathogens is provided in this article. Emphasis has been made on existing, commercial and state-of-the-art systems and research activities in laboratories worldwide. The review separates sample processing systems and monitoring systems, highlighting the slow progress made in automated sample processing for monitoring of pathogens in waterworks and in the field. Future potential directions of research are also highlighted in the conclusions.

  14. Multiplex detection of agricultural pathogens

    DOEpatents

    Siezak, Thomas R.; Gardner, Shea; Torres, Clinton; Vitalis, Elizabeth; Lenhoff, Raymond J.

    2013-01-15

    Described are kits and methods useful for detection of agricultural pathogens in a sample. Genomic sequence information from agricultural pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay and/or an array assay to successfully identify the presence or absence of pathogens in a sample.

  15. Multiplex detection of agricultural pathogens

    DOEpatents

    McBride, Mary Teresa; Slezak, Thomas Richard; Messenger, Sharon Lee

    2010-09-14

    Described are kits and methods useful for detection of seven agricultural pathogens (BPSV; BHV; BVD; FMDV; BTV; SVD; and VESV) in a sample. Genomic sequence information from 7 agricultural pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay to successfully identify the presence or absence of pathogens in a sample.

  16. Opportunistic Pathogenic Yeasts

    NASA Astrophysics Data System (ADS)

    Banerjee, Uma

    Advances in medical research, made during the last few decades, have improved the prophylactic, diagnostic and therapeutic capabilities for variety of infections/diseases. However, many of the prophylactic and therapeutic procedures have been seen in many instances to exact a price of host-vulnerability to an expanding group of opportunistic pathogens and yeasts are one of the important members in it. Fortunately amongst the vast majority of yeasts present in nature only few are considered to have the capability to cause infections when certain opportunities predisposes and these are termed as ‘opportunistic pathogenic yeasts.’ However, the term ‘pathogenic’ is quite tricky, as it depends of various factors of the host, the ‘bug’ and the environment to manifest the clinical infection. The borderline is expanding. In the present century with unprecedented increase in number of immune-compromised host in various disciplines of health care settings, where any yeast, which has the capability to grow at 37 ° C (normal body temperature of human), can be pathogenic and cause infection in particular situation

  17. Extraintestinal pathogenic Escherichia coli.

    PubMed

    Smith, James L; Fratamico, Pina M; Gunther, Nereus W

    2007-01-01

    Extraintestinal pathogenic Escherichia coli (ExPEC) possesses virulence traits that allow it to invade, colonize, and induce disease in bodily sites outside of the gastrointestinal tract. Human diseases caused by ExPEC include urinary tract infections, neonatal meningitis, sepsis, pneumonia, surgical site infections, as well as infections in other extraintestinal locations. ExPEC-induced diseases represent a large burden in terms of medical costs and productivity losses. In addition to human illnesses, ExPEC strains also cause extraintestinal infections in domestic animals and pets. A commonality of virulence factors has been demonstrated between human and animal ExPEC, suggesting that the organisms are zoonotic pathogens. ExPEC strains have been isolated from food products, in particular from raw meats and poultry, indicating that these organisms potentially represent a new class of foodborne pathogens. This review discusses various aspects of ExPEC, including its presence in food products, in animals used for food or as companion pets; the diseases ExPEC can cause; and the virulence factors and virulence mechanisms that cause disease.

  18. Pathogenicity islands in bacterial pathogenesis.

    PubMed

    Schmidt, Herbert; Hensel, Michael

    2004-01-01

    In this review, we focus on a group of mobile genetic elements designated pathogenicity islands (PAI). These elements play a pivotal role in the virulence of bacterial pathogens of humans and are also essential for virulence in pathogens of animals and plants. Characteristic molecular features of PAI of important human pathogens and their role in pathogenesis are described. The availability of a large number of genome sequences of pathogenic bacteria and their benign relatives currently offers a unique opportunity for the identification of novel pathogen-specific genomic islands. However, this knowledge has to be complemented by improved model systems for the analysis of virulence functions of bacterial pathogens. PAI apparently have been acquired during the speciation of pathogens from their nonpathogenic or environmental ancestors. The acquisition of PAI not only is an ancient evolutionary event that led to the appearance of bacterial pathogens on a timescale of millions of years but also may represent a mechanism that contributes to the appearance of new pathogens within a human life span. The acquisition of knowledge about PAI, their structure, their mobility, and the pathogenicity factors they encode not only is helpful in gaining a better understanding of bacterial evolution and interactions of pathogens with eukaryotic host cells but also may have important practical implications such as providing delivery systems for vaccination, tools for cell biology, and tools for the development of new strategies for therapy of bacterial infections.

  19. Pathogenicity Islands in Bacterial Pathogenesis

    PubMed Central

    Schmidt, Herbert; Hensel, Michael

    2004-01-01

    In this review, we focus on a group of mobile genetic elements designated pathogenicity islands (PAI). These elements play a pivotal role in the virulence of bacterial pathogens of humans and are also essential for virulence in pathogens of animals and plants. Characteristic molecular features of PAI of important human pathogens and their role in pathogenesis are described. The availability of a large number of genome sequences of pathogenic bacteria and their benign relatives currently offers a unique opportunity for the identification of novel pathogen-specific genomic islands. However, this knowledge has to be complemented by improved model systems for the analysis of virulence functions of bacterial pathogens. PAI apparently have been acquired during the speciation of pathogens from their nonpathogenic or environmental ancestors. The acquisition of PAI not only is an ancient evolutionary event that led to the appearance of bacterial pathogens on a timescale of millions of years but also may represent a mechanism that contributes to the appearance of new pathogens within a human life span. The acquisition of knowledge about PAI, their structure, their mobility, and the pathogenicity factors they encode not only is helpful in gaining a better understanding of bacterial evolution and interactions of pathogens with eukaryotic host cells but also may have important practical implications such as providing delivery systems for vaccination, tools for cell biology, and tools for the development of new strategies for therapy of bacterial infections. PMID:14726454

  20. 14-3-3 proteins in plant-pathogen interactions.

    PubMed

    Lozano-Durán, Rosa; Robatzek, Silke

    2015-05-01

    14-3-3 proteins define a eukaryotic-specific protein family with a general role in signal transduction. Primarily, 14-3-3 proteins act as phosphosensors, binding phosphorylated client proteins and modulating their functions. Since phosphorylation regulates a plethora of different physiological responses in plants, 14-3-3 proteins play roles in multiple signaling pathways, including those controlling metabolism, hormone signaling, cell division, and responses to abiotic and biotic stimuli. Increasing evidence supports a prominent role of 14-3-3 proteins in regulating plant immunity against pathogens at various levels. In this review, potential links between 14-3-3 function and the regulation of plant-pathogen interactions are discussed, with a special focus on the regulation of 14-3-3 proteins in response to pathogen perception, interactions between 14-3-3 proteins and defense-related proteins, and 14-3-3 proteins as targets of pathogen effectors.

  1. Microbial Pathogens in the Fungal Kingdom

    PubMed Central

    Heitman, Joseph

    2011-01-01

    The fungal kingdom is vast, spanning ~1.5 to as many as 5 million species diverse as unicellular yeasts, filamentous fungi, mushrooms, lichens, and both plant and animal pathogens. The fungi are closely aligned with animals in one of the six to eight supergroups of eukaryotes, the opisthokonts. The animal and fungal kingdoms last shared a common ancestor ~1 billion years ago, more recently than other groups of eukaryotes. As a consequence of their close evolutionary history and shared cellular machinery with metazoans, fungi are exceptional models for mammalian biology, but prove more difficult to treat in infected animals. The last common ancestor to the fungal/metazoan lineages is thought to have been unicellular, aquatic, and motile with a posterior flagellum, and certain extant species closely resemble this hypothesized ancestor. Species within the fungal kingdom were traditionally assigned to four phyla, including the basal fungi (Chytridiomycota, Zygomycota) and the more recently derived monophyletic lineage, the dikarya (Ascomycota, Basidiomycota). The fungal tree of life project has revealed that the basal lineages are polyphyletic, and thus there are as many as eight to ten fungal phyla. Fungi that infect vertebrates are found in all of the major lineages, and virulence arose multiple times independently. A sobering recent development involves the species Batrachochytrium dendrobatidis from the basal fungal phylum, the Chytridiomycota, which has emerged to cause global amphibian declines and extinctions. Genomics is revolutionizing our view of the fungal kingdom, and genome sequences for zygomycete pathogens (Rhizopus, Mucor), skin-associated fungi (dermatophytes, Malassezia), and the Candida pathogenic species clade promise to provide insights into the origins of virulence. Here we survey the diversity of fungal pathogens and illustrate key principles revealed by genomics involving sexual reproduction and sex determination, loss of conserved pathways in

  2. Aptamer-Based Technologies in Foodborne Pathogen Detection

    PubMed Central

    Teng, Jun; Yuan, Fang; Ye, Yingwang; Zheng, Lei; Yao, Li; Xue, Feng; Chen, Wei; Li, Baoguang

    2016-01-01

    Aptamers are single stranded DNA or RNA ligands, which can be selected by a method called systematic evolution of ligands by exponential enrichment (SELEX); and they can specifically recognize and bind to their targets. These unique characteristics of aptamers offer great potentials in applications such as pathogen detection and biomolecular screening. Pathogen detection is the critical means in detecting and identifying the problems related to public health and food safety; and only the rapid, sensitive and efficient detection technologies can enable the users to make the accurate assessments on the risks of infections (humans and animals) or contaminations (foods and other commodities) caused by various pathogens. This article reviews the development in the field of the aptamer-based approaches for pathogen detection, including whole-cell SELEX and Genomic SELEX. Nowadays, a variety of aptamer-based biosensors have been developed for pathogen detection. Thus, in this review, we also cover the development in aptamer-based biosensors including optical biosensors for multiple pathogen detection by multiple-labeling or label-free models such as fluorescence detection and surface plasmon resonance, electrochemical biosensors and lateral chromatography test strips, and their applications in pathogen detection and biomolecular screening. While notable progress has been made in the field in the last decade, challenges or drawbacks in their applications such as pathogen detection and biomolecular screening remain to be overcome.

  3. Aptamer-Based Technologies in Foodborne Pathogen Detection.

    PubMed

    Teng, Jun; Yuan, Fang; Ye, Yingwang; Zheng, Lei; Yao, Li; Xue, Feng; Chen, Wei; Li, Baoguang

    2016-01-01

    Aptamers are single stranded DNA or RNA ligands, which can be selected by a method called systematic evolution of ligands by exponential enrichment (SELEX); and they can specifically recognize and bind to their targets. These unique characteristics of aptamers offer great potentials in applications such as pathogen detection and biomolecular screening. Pathogen detection is the critical means in detecting and identifying the problems related to public health and food safety; and only the rapid, sensitive and efficient detection technologies can enable the users to make the accurate assessments on the risks of infections (humans and animals) or contaminations (foods and other commodities) caused by various pathogens. This article reviews the development in the field of the aptamer-based approaches for pathogen detection, including whole-cell SELEX and Genomic SELEX. Nowadays, a variety of aptamer-based biosensors have been developed for pathogen detection. Thus, in this review, we also cover the development in aptamer-based biosensors including optical biosensors for multiple pathogen detection by multiple-labeling or label-free models such as fluorescence detection and surface plasmon resonance, electrochemical biosensors and lateral chromatography test strips, and their applications in pathogen detection and biomolecular screening. While notable progress has been made in the field in the last decade, challenges or drawbacks in their applications such as pathogen detection and biomolecular screening remain to be overcome.

  4. A guide to in silico vaccine discovery for eukaryotic pathogens.

    PubMed

    Goodswen, Stephen J; Kennedy, Paul J; Ellis, John T

    2013-11-01

    In this article, a framework for an in silico pipeline is presented as a guide to high-throughput vaccine candidate discovery for eukaryotic pathogens, such as helminths and protozoa. Eukaryotic pathogens are mostly parasitic and cause some of the most damaging and difficult to treat diseases in humans and livestock. Consequently, these parasitic pathogens have a significant impact on economy and human health. The pipeline is based on the principle of reverse vaccinology and is constructed from freely available bioinformatics programs. There are several successful applications of reverse vaccinology to the discovery of subunit vaccines against prokaryotic pathogens but not yet against eukaryotic pathogens. The overriding aim of the pipeline, which focuses on eukaryotic pathogens, is to generate through computational processes of elimination and evidence gathering a ranked list of proteins based on a scoring system. These proteins are either surface components of the target pathogen or are secreted by the pathogen and are of a type known to be antigenic. No perfect predictive method is yet available; therefore, the highest-scoring proteins from the list require laboratory validation.

  5. Aptamer-Based Technologies in Foodborne Pathogen Detection

    PubMed Central

    Teng, Jun; Yuan, Fang; Ye, Yingwang; Zheng, Lei; Yao, Li; Xue, Feng; Chen, Wei; Li, Baoguang

    2016-01-01

    Aptamers are single stranded DNA or RNA ligands, which can be selected by a method called systematic evolution of ligands by exponential enrichment (SELEX); and they can specifically recognize and bind to their targets. These unique characteristics of aptamers offer great potentials in applications such as pathogen detection and biomolecular screening. Pathogen detection is the critical means in detecting and identifying the problems related to public health and food safety; and only the rapid, sensitive and efficient detection technologies can enable the users to make the accurate assessments on the risks of infections (humans and animals) or contaminations (foods and other commodities) caused by various pathogens. This article reviews the development in the field of the aptamer-based approaches for pathogen detection, including whole-cell SELEX and Genomic SELEX. Nowadays, a variety of aptamer-based biosensors have been developed for pathogen detection. Thus, in this review, we also cover the development in aptamer-based biosensors including optical biosensors for multiple pathogen detection by multiple-labeling or label-free models such as fluorescence detection and surface plasmon resonance, electrochemical biosensors and lateral chromatography test strips, and their applications in pathogen detection and biomolecular screening. While notable progress has been made in the field in the last decade, challenges or drawbacks in their applications such as pathogen detection and biomolecular screening remain to be overcome. PMID:27672383

  6. Aptamer-Based Technologies in Foodborne Pathogen Detection.

    PubMed

    Teng, Jun; Yuan, Fang; Ye, Yingwang; Zheng, Lei; Yao, Li; Xue, Feng; Chen, Wei; Li, Baoguang

    2016-01-01

    Aptamers are single stranded DNA or RNA ligands, which can be selected by a method called systematic evolution of ligands by exponential enrichment (SELEX); and they can specifically recognize and bind to their targets. These unique characteristics of aptamers offer great potentials in applications such as pathogen detection and biomolecular screening. Pathogen detection is the critical means in detecting and identifying the problems related to public health and food safety; and only the rapid, sensitive and efficient detection technologies can enable the users to make the accurate assessments on the risks of infections (humans and animals) or contaminations (foods and other commodities) caused by various pathogens. This article reviews the development in the field of the aptamer-based approaches for pathogen detection, including whole-cell SELEX and Genomic SELEX. Nowadays, a variety of aptamer-based biosensors have been developed for pathogen detection. Thus, in this review, we also cover the development in aptamer-based biosensors including optical biosensors for multiple pathogen detection by multiple-labeling or label-free models such as fluorescence detection and surface plasmon resonance, electrochemical biosensors and lateral chromatography test strips, and their applications in pathogen detection and biomolecular screening. While notable progress has been made in the field in the last decade, challenges or drawbacks in their applications such as pathogen detection and biomolecular screening remain to be overcome. PMID:27672383

  7. The multilevel and dynamic interplay between plant and pathogen

    PubMed Central

    Yang, Yifei; Zhou, Jian-Min

    2009-01-01

    Phytopathogens invade into plant apoplast and proliferate by assimilating nutrition from plant cells. Plants depend on sophisticated defensive strategies to resist this invasion. Therefore, pathogenic disease and plant disease resistance are two opposite phases. Fascinating molecular mechanisms uncovered that interactions between plant and pathogen are multilevel and dynamic processes. On one side, plant immunity system contains multiple layers mainly including the perception of common pathogen- associated molecular patterns (PAMPs) using distinct cell-surface pattern-recognition receptors (PRRs) to activate intracellular signaling pathways for broad-spectrum immunity, and the recognition of pathogen virulence proteins by the specific intracellular disease resistance (R) proteins for cultivar-specific immunity. On the opposite side, the bacterial pathogens employ virulence factors, such as phytotoxin and type III effectors (T3SEs) to interfere with the host immunity in different levels. Meanwhile, natural selection drives plants and pathogens to evolve new strategies to confront with each other constantly. The present review highlights recent insights about Arabidopsis immunity and mechanisms for Pseudomonas syringae to counteract this immunity to give a full understanding of plant-pathogen interactions. PMID:19794843

  8. Purification and proteomics of pathogen-modified vacuoles and membranes

    PubMed Central

    Herweg, Jo-Ana; Hansmeier, Nicole; Otto, Andreas; Geffken, Anna C.; Subbarayal, Prema; Prusty, Bhupesh K.; Becher, Dörte; Hensel, Michael; Schaible, Ulrich E.; Rudel, Thomas; Hilbi, Hubert

    2015-01-01

    Certain pathogenic bacteria adopt an intracellular lifestyle and proliferate in eukaryotic host cells. The intracellular niche protects the bacteria from cellular and humoral components of the mammalian immune system, and at the same time, allows the bacteria to gain access to otherwise restricted nutrient sources. Yet, intracellular protection and access to nutrients comes with a price, i.e., the bacteria need to overcome cell-autonomous defense mechanisms, such as the bactericidal endocytic pathway. While a few bacteria rupture the early phagosome and escape into the host cytoplasm, most intracellular pathogens form a distinct, degradation-resistant and replication-permissive membranous compartment. Intracellular bacteria that form unique pathogen vacuoles include Legionella, Mycobacterium, Chlamydia, Simkania, and Salmonella species. In order to understand the formation of these pathogen niches on a global scale and in a comprehensive and quantitative manner, an inventory of compartment-associated host factors is required. To this end, the intact pathogen compartments need to be isolated, purified and biochemically characterized. Here, we review recent progress on the isolation and purification of pathogen-modified vacuoles and membranes, as well as their proteomic characterization by mass spectrometry and different validation approaches. These studies provide the basis for further investigations on the specific mechanisms of pathogen-driven compartment formation. PMID:26082896

  9. Purification and proteomics of pathogen-modified vacuoles and membranes.

    PubMed

    Herweg, Jo-Ana; Hansmeier, Nicole; Otto, Andreas; Geffken, Anna C; Subbarayal, Prema; Prusty, Bhupesh K; Becher, Dörte; Hensel, Michael; Schaible, Ulrich E; Rudel, Thomas; Hilbi, Hubert

    2015-01-01

    Certain pathogenic bacteria adopt an intracellular lifestyle and proliferate in eukaryotic host cells. The intracellular niche protects the bacteria from cellular and humoral components of the mammalian immune system, and at the same time, allows the bacteria to gain access to otherwise restricted nutrient sources. Yet, intracellular protection and access to nutrients comes with a price, i.e., the bacteria need to overcome cell-autonomous defense mechanisms, such as the bactericidal endocytic pathway. While a few bacteria rupture the early phagosome and escape into the host cytoplasm, most intracellular pathogens form a distinct, degradation-resistant and replication-permissive membranous compartment. Intracellular bacteria that form unique pathogen vacuoles include Legionella, Mycobacterium, Chlamydia, Simkania, and Salmonella species. In order to understand the formation of these pathogen niches on a global scale and in a comprehensive and quantitative manner, an inventory of compartment-associated host factors is required. To this end, the intact pathogen compartments need to be isolated, purified and biochemically characterized. Here, we review recent progress on the isolation and purification of pathogen-modified vacuoles and membranes, as well as their proteomic characterization by mass spectrometry and different validation approaches. These studies provide the basis for further investigations on the specific mechanisms of pathogen-driven compartment formation.

  10. When pathogenic bacteria meet the intestinal microbiota.

    PubMed

    Rolhion, Nathalie; Chassaing, Benoit

    2016-11-01

    The intestinal microbiota is a large and diverse microbial community that inhabits the intestinal tract, containing about 100 trillion bacteria from 500-1000 distinct species that, collectively, provide multiple benefits to the host. The gut microbiota contributes to nutrient absorption and maturation of the immune system, and also plays a central role in protection of the host from enteric bacterial infection. On the other hand, many enteric pathogens have developed strategies in order to be able to outcompete the intestinal community, leading to infection and/or chronic diseases. This review will summarize findings describing the complex relationship occurring between the intestinal microbiota and enteric pathogens, as well as how future therapies can ultimately benefit from such discoveries.This article is part of the themed issue 'The new bacteriology'. PMID:27672153

  11. Career pathways in research: clinical practice.

    PubMed

    Foxcroft, K J

    This article, the first in a five-part series on career pathways, discusses the facility for nurses to develop their clinical expertise to consultant level, which is an exciting development on the career pathway for nurses in clinical practice. The introduction of consultant nurses has re-emphasised the need for experienced leadership in research and practice development in clinical settings.

  12. BK polyomavirus: emerging pathogen.

    PubMed

    Bennett, Shauna M; Broekema, Nicole M; Imperiale, Michael J

    2012-08-01

    BK polyomavirus (BKPyV) is a small double-stranded DNA virus that is an emerging pathogen in immunocompromised individuals. BKPyV is widespread in the general population, but primarily causes disease when immune suppression leads to reactivation of latent virus. Polyomavirus-associated nephropathy and hemorrhagic cystitis in renal and bone marrow transplant patients, respectively, are the most common diseases associated with BKPyV reactivation and lytic infection. In this review, we discuss the clinical relevance, effects on the host, virus life cycle, and current treatment protocols. PMID:22402031

  13. Portable pathogen detection system

    SciTech Connect

    Colston, Billy W.; Everett, Matthew; Milanovich, Fred P.; Brown, Steve B.; Vendateswaran, Kodumudi; Simon, Jonathan N.

    2005-06-14

    A portable pathogen detection system that accomplishes on-site multiplex detection of targets in biological samples. The system includes: microbead specific reagents, incubation/mixing chambers, a disposable microbead capture substrate, and an optical measurement and decoding arrangement. The basis of this system is a highly flexible Liquid Array that utilizes optically encoded microbeads as the templates for biological assays. Target biological samples are optically labeled and captured on the microbeads, which are in turn captured on an ordered array or disordered array disposable capture substrate and then optically read.

  14. The Keystone Pathogen Hypothesis

    PubMed Central

    Hajishengallis, George; Darveau, Richard P.; Curtis, Michael A.

    2012-01-01

    Recent studies have highlighted the importance of the human microbiome in host health and disease. However, for the most part the mechanisms by which the microbiome mediates disease, or protection from it, remain poorly understood. The “keystone pathogen” hypothesis holds that certain low-abundance microbial pathogens can orchestrate inflammatory disease by remodelling a normally benign microbiota into a dysbiotic one. In this Opinion, we critically assess the available literature in support of this hypothesis, which may provide a novel conceptual basis for the development of targeted diagnostic and treatment modalities for complex dysbiotic diseases. PMID:22941505

  15. Tomato transcriptional responses to a foliar and a vascular fungal pathogen are distinct.

    PubMed

    van Esse, H Peter; Fradin, Emilie F; de Groot, Philip J; de Wit, Pierre J G M; Thomma, Bart P H J

    2009-03-01

    Plant activation of host defense against pathogenic microbes requires significant host transcriptional reprogramming. In this study, we compared transcriptional changes in tomato during compatible and incompatible interactions with the foliar fungal pathogen Cladosporium fulvum and the vascular fungal pathogen Verticillium dahliae. Although both pathogens colonize different host tissues, they display distinct commonalities in their infection strategy; both pathogens penetrate natural openings and grow strictly extracellular. Furthermore, resistance against both pathogens is conveyed by the same class of resistance proteins, the receptor-like proteins. For each individual pathogen, the expression profile of the compatible and incompatible interaction largely overlaps. However, when comparing between the two pathogens, the C. fulvum-induced transcriptional changes show little overlap with those induced by V. dahliae. Moreover, within the subset of genes that are regulated by both pathogens, many genes show inverse regulation. With pathway reconstruction, networks of tomato genes implicated in photorespiration, hypoxia, and glycoxylate metabolism were identified that are repressed upon infection with C. fulvum and induced by V. dahliae. Similarly, auxin signaling is differentially affected by the two pathogens. Thus, differentially regulated pathways were identified with novel strategies that allowed the use of state-of-the-art tools, even though tomato is not a genetic model organism.

  16. Finding and Recommending Scholarly Articles

    NASA Astrophysics Data System (ADS)

    Kurtz, Michael J.; Henneken, Edwin A.

    2014-05-01

    The rate at which scholarly literature is being produced has been increasing at approximately 3.5 percent per year for decades. This means that during a typical 40 year career the amount of new literature produced each year increases by a factor of four. The methods scholars use to discover relevant literature must change. Just like everybody else involved in information discovery, scholars are confronted with information overload. Two decades ago, this discovery process essentially consisted of paging through abstract books, talking to colleagues and librarians, and browsing journals. A time-consuming process, which could even be longer if material had to be shipped from elsewhere. Now much of this discovery process is mediated by online scholarly information systems. All these systems are relatively new, and all are still changing. They all share a common goal: to provide their users with access to the literature relevant to their specific needs. To achieve this each system responds to actions by the user by displaying articles which the system judges relevant to the user's current needs. Recently search systems which use particularly sophisticated methodologies to recommend a few specific papers to the user have been called "recommender systems". These methods are in line with the current use of the term "recommender system" in computer science. We do not adopt this definition, rather we view systems like these as components in a larger whole, which is presented by the scholarly information systems themselves. In what follows we view the recommender system as an aspect of the entire information system; one which combines the massive memory capacities of the machine with the cognitive abilities of the human user to achieve a human-machine synergy.

  17. Clerkship pathway

    PubMed Central

    MacLellan, Anne-Marie; Brailovsky, Carlos; Miller, François; Leboeuf, Sylvie

    2012-01-01

    Abstract Objective To identify factors that help predict success for international medical graduates (IMGs) who train in Canadian residency programs and pass the Canadian certification examinations. Design A retrospective analysis of 58 variables in the files of IMGs who applied to the Collège des médecins du Québec between 2000 and 2008. Setting Quebec. Participants Eight hundred ten IMGs who applied to the Collège des médecins du Québec through either the “equivalency pathway” (ie, starting training at a residency level) or the “clerkship pathway” (ie, relearning at the level of a medical student in the last 2 years of the MD diploma). Main outcome measures Success factors in achieving certification. Data were analyzed using descriptive statistics and ANOVA (analysis of variance). Results International medical graduates who chose the “clerkship pathway” had greater success on certification examinations than those who started at the residency level did. Conclusion There are several factors that influence IMGs’ success on certification examinations, including integration issues, the acquisition of clinical decision-making skills, and the varied educational backgrounds. These factors perhaps can be better addressed by a regular clerkship pathway, in which IMGs benefit from learner-centred teaching and have more time for reflection on and understanding of the North American approach to medical education. The clerkship pathway is a useful strategy for assuring the integration of IMGs in the North American health care system. A 2-year relearning period in medical school at a clinical clerkship level deserves careful consideration. PMID:22859630

  18. Cryptosporidium Pathogenicity and Virulence

    PubMed Central

    Bouzid, Maha; Chalmers, Rachel M.; Tyler, Kevin M.

    2013-01-01

    Cryptosporidium is a protozoan parasite of medical and veterinary importance that causes gastroenteritis in a variety of vertebrate hosts. Several studies have reported different degrees of pathogenicity and virulence among Cryptosporidium species and isolates of the same species as well as evidence of variation in host susceptibility to infection. The identification and validation of Cryptosporidium virulence factors have been hindered by the renowned difficulties pertaining to the in vitro culture and genetic manipulation of this parasite. Nevertheless, substantial progress has been made in identifying putative virulence factors for Cryptosporidium. This progress has been accelerated since the publication of the Cryptosporidium parvum and C. hominis genomes, with the characterization of over 25 putative virulence factors identified by using a variety of immunological and molecular techniques and which are proposed to be involved in aspects of host-pathogen interactions from adhesion and locomotion to invasion and proliferation. Progress has also been made in the contribution of host factors that are associated with variations in both the severity and risk of infection. Here we provide a review comprised of the current state of knowledge on Cryptosporidium infectivity, pathogenesis, and transmissibility in light of our contemporary understanding of microbial virulence. PMID:23297262

  19. PathoPlant: a database on plant-pathogen interactions.

    PubMed

    Bülow, Lorenz; Schindler, Martin; Choi, Claudia; Hehl, Reinhard

    2004-01-01

    Pathogen recognition and signal transduction during plant pathogenesis is essential for the activation of plant defense mechanisms. To facilitate easy access to published data and to permit comparative studies of different pathogen response pathways, a database is indispensable to give a broad overview of the components and reactions so far known. PathoPlant has been developed as a relational database to display relevant components and reactions involved in signal transduction related to plant-pathogen interactions. On the organism level, the tables 'plant', 'pathogen' and 'interaction' are used to describe incompatible interactions between plants and pathogens or diseases. On the molecular level, plant pathogenesis related information is organized in PathoPlant's main tables 'molecule', 'reaction' and 'location'. Signal transduction pathways are modeled as consecutive sequences of known molecules and corresponding reactions. PathoPlant entries are linked to associated internal records as well as to entries in external databases such as SWISS-PROT, GenBank, PubMed, and TRANSFAC. PathoPlant is available as a web-based service at http://www.pathoplant.de. PMID:15752070

  20. Signaling Pathways in Cartilage Repair

    PubMed Central

    Mariani, Erminia; Pulsatelli, Lia; Facchini, Andrea

    2014-01-01

    In adult healthy cartilage, chondrocytes are in a quiescent phase characterized by a fine balance between anabolic and catabolic activities. In ageing, degenerative joint diseases and traumatic injuries of cartilage, a loss of homeostatic conditions and an up-regulation of catabolic pathways occur. Since cartilage differentiation and maintenance of homeostasis are finely tuned by a complex network of signaling molecules and biophysical factors, shedding light on these mechanisms appears to be extremely relevant for both the identification of pathogenic key factors, as specific therapeutic targets, and the development of biological approaches for cartilage regeneration. This review will focus on the main signaling pathways that can activate cellular and molecular processes, regulating the functional behavior of cartilage in both physiological and pathological conditions. These networks may be relevant in the crosstalk among joint compartments and increased knowledge in this field may lead to the development of more effective strategies for inducing cartilage repair. PMID:24837833

  1. Fusobacterium nucleatum: a commensal-turned pathogen.

    PubMed

    Han, Yiping W

    2015-02-01

    Fusobacterium nucleatum is an anaerobic oral commensal and a periodontal pathogen associated with a wide spectrum of human diseases. This article reviews its implication in adverse pregnancy outcomes (chorioamnionitis, preterm birth, stillbirth, neonatal sepsis, preeclampsia), GI disorders (colorectal cancer, inflammatory bowel disease, appendicitis), cardiovascular disease, rheumatoid arthritis, respiratory tract infections, Lemierre's syndrome and Alzheimer's disease. The virulence mechanisms involved in the diseases are discussed, with emphasis on its colonization, systemic dissemination, and induction of host inflammatory and tumorigenic responses. The FadA adhesin/invasin conserved in F. nucleatum is a key virulence factor and a potential diagnostic marker for F. nucleatum-associated diseases.

  2. Innate immune sensing of nucleic acids from pathogens.

    PubMed

    Oliveira, Sergio C

    2014-12-01

    The innate immune system is important as the first line of defense to sense invading pathogens. Nucleic acids represent critical pathogen signatures that trigger a host proinflammatory immune response. Much progress has been made in understanding how DNA and RNA trigger host defense countermeasures, however, several aspects of how cytosolic nucleic acids are sensed remain unclear. This special issue reviews how the host innate immune system senses nucleic acids from Brucella abortus, Mycobacterium sp and Legionella pneumophila, viral DNA, the role of STING in DNA sensing and inflammatory diseases and the mechanism of viral RNA recognition by the small interfering RNA pathway in Drosophila melanogaster.

  3. Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms

    PubMed Central

    Mansilla Pareja, Maria Eugenia; Colombo, Maria I.

    2013-01-01

    Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will describe the means used by diverse bacterial pathogens to survive intracellularly and how they are recognized by the autophagic molecular machinery, as well as the mechanisms used to avoid autophagic clearance. PMID:24137567

  4. Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms.

    PubMed

    Pareja, Maria Eugenia Mansilla; Colombo, Maria I

    2013-01-01

    Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will describe the means used by diverse bacterial pathogens to survive intracellularly and how they are recognized by the autophagic molecular machinery, as well as the mechanisms used to avoid autophagic clearance.

  5. [Streptococcus pyogenes pathogenic factors].

    PubMed

    Bidet, Ph; Bonacorsi, S

    2014-11-01

    The pathogenicity of ß-hemolytic group A streptococcus (GAS) is particularly diverse, ranging from mild infections, such as pharyngitis or impetigo, to potentially debilitating poststreptococcal diseases, and up to severe invasive infections such as necrotizing fasciitis or the dreaded streptococcal toxic shock syndrome. This variety of clinical expressions, often radically different in individuals infected with the same strain, results from a complex interaction between the bacterial virulence factors, the mode of infection and the immune system of the host. Advances in comparative genomics have led to a better understanding of how, following this confrontation, GAS adapts to the immune system's pressure, either peacefully by reducing the expression of certain virulence factors to achieve an asymptomatic carriage, or on the contrary, by overexpressing them disproportionately, resulting in the most severe forms of invasive infection. PMID:25456681

  6. Flagella and bacterial pathogenicity.

    PubMed

    Duan, Qiangde; Zhou, Mingxu; Zhu, Liqian; Zhu, Guoqiang

    2013-01-01

    As locomotive organelles, flagella allow bacteria to move toward favorable environments. A flagellum consists of three parts: the basal structure (rotary motor), the hook (universal joint), and the filament (helical propeller). For ages, flagella have been generally regarded as important virulence factors, mainly because of their motility property. However, flagella are getting recognized to play multiple roles with more functions besides motility and chemotaxis. Recent evidence has pinpointed that the bacterial flagella participate in many additional processes including adhesion, biofilm formation, virulence factor secretion, and modulation of the immune system of eukaryotic cells. This mini-review summarizes data from recent studies that elucidated how flagella, as a virulence factor, contribute to bacterial pathogenicity.

  7. Flagella and bacterial pathogenicity.

    PubMed

    Duan, Qiangde; Zhou, Mingxu; Zhu, Liqian; Zhu, Guoqiang

    2013-01-01

    As locomotive organelles, flagella allow bacteria to move toward favorable environments. A flagellum consists of three parts: the basal structure (rotary motor), the hook (universal joint), and the filament (helical propeller). For ages, flagella have been generally regarded as important virulence factors, mainly because of their motility property. However, flagella are getting recognized to play multiple roles with more functions besides motility and chemotaxis. Recent evidence has pinpointed that the bacterial flagella participate in many additional processes including adhesion, biofilm formation, virulence factor secretion, and modulation of the immune system of eukaryotic cells. This mini-review summarizes data from recent studies that elucidated how flagella, as a virulence factor, contribute to bacterial pathogenicity. PMID:22359233

  8. Pathogenic effects of asbestos.

    PubMed

    Kannerstein, M; Churg, J; McCaughey, E; Selikoff, I J

    1977-12-01

    The enormous increase in the use of asbestos during this century has necessitated the intensive study of its pathogenic effects. The occurrence of pulmonary parenchymal and pleural fibrosis and an increased prevalence of pulmonary and gastrointestinal carcinoma and of pleural and peritoneal mesothelioma have been established. A relationship, also, to laryngeal carcinoma is probable. Mesothelioma has been associated with indirect occupational, domestic, and neighborhood exposure, and the possibility of a similar correlation of pulmonary carcinoma with low exposure has been suggested. Pulmonary fibrosis and pleural plaques have been demonstrated under these circumstances. The physical characteristics of the asbestos fiber appear to be the principal factors in its carcinogenic action. The ability of fine, short fibers, especially fragmented chrysotile, to reach the pleura would appear to account for many of the pathogenetic and anatomical features of asbestos-related disease.

  9. Rapid Detection of Pathogens

    SciTech Connect

    David Perlin

    2005-08-14

    Pathogen identification is a crucial first defense against bioterrorism. A major emphasis of our national biodefense strategy is to establish fast, accurate and sensitive assays for diagnosis of infectious diseases agents. Such assays will ensure early and appropriate treatment of infected patients. Rapid diagnostics can also support infection control measures, which monitor and limit the spread of infectious diseases agents. Many select agents are highly transmissible in the early stages of disease, and it is critical to identify infected patients and limit the risk to the remainder of the population and to stem potential panic in the general population. Nucleic acid-based molecular approaches for identification overcome many of the deficiencies associated with conventional culture methods by exploiting both large- and small-scale genomic differences between organisms. PCR-based amplification of highly conserved ribosomal RNA (rRNA) genes, intergenic sequences, and specific toxin genes is currently the most reliable approach for bacterial, fungal and many viral pathogenic agents. When combined with fluorescence-based oligonucleotide detection systems, this approach provides real-time, quantitative, high fidelity analysis capable of single nucleotide allelic discrimination (4). These probe systems offer rapid turn around time (<2 h) and are suitable for high throughput, automated multiplex operations that are critical for clinical diagnostic laboratories. In this pilot program, we have used molecular beacon technology invented at the Public health Research Institute to develop a new generation of molecular probes to rapidly detect important agents of infectious diseases. We have also developed protocols to rapidly extract nucleic acids from a variety of clinical specimen including and blood and tissue to for detection in the molecular assays. This work represented a cooperative research development program between the Kramer-Tyagi/Perlin labs on probe development

  10. Microsporidia: emerging pathogenic protists.

    PubMed

    Weiss, L M

    2001-02-23

    Microsporidia are eukaryotic spore forming obligate intracellular protozoan parasites first recognized over 100 years ago. These organisms infect all of the major animal groups and are now recognized as opportunistic pathogens of humans. Microsporidian spores are common in the environment and microsporidia pathogenic to humans have been found in water supplies. The genera Nosema, Vittaforma, Brachiola, Pleistophora, Encephalitozoon, Enterocytozoon, Septata (reclassified to Encephalitozoon) and Trachipleistophora have been found in human infections. These organisms have the smallest known eukaryotic genomes. Microsporidian ribosomal RNA sequences have proven useful as diagnostic tools as well as for phylogenetic analysis. Recent phylogenetic analysis suggests that Microsporidia are related to the fungi. These organisms are defined by the presence of a unique invasion organelle consisting of a single polar tube that coils around the interior of the spore. All microsporidia exhibit the same response to stimuli, that is, the polar tube discharges from the anterior pole of the spore in an explosive reaction. If the polar tube is discharged next to a cell, it can pierce the cell and transfer its sporoplasm into the cell. A technique was developed for the purification of polar tube proteins (PTPs) using differential extraction followed by reverse phase HPLC. This method was used to purify the PTPs from Glugea americanus, Encephalitozoon cuniculi, Enc. hellem and Enc. intestinalis. These PTPs demonstrate conserved characteristics such as solubility, hydrophobicity, mass, proline content and immunologic epitopes. The major PTP gene from Enc. cuniculi and Enc. hellem has been cloned and expressed in vitro. The gene sequences support the importance of ER and in the formation of the polar tube as suggested by morphologic studies. Analysis of the cloned proteins also indicates that secondary structural characteristics are conserved. These characteristics are probably important

  11. Fungal pathogens of Proteaceae.

    PubMed

    Crous, P W; Summerell, B A; Swart, L; Denman, S; Taylor, J E; Bezuidenhout, C M; Palm, M E; Marincowitz, S; Groenewald, J Z

    2011-12-01

    Species of Leucadendron, Leucospermum and Protea (Proteaceae) are in high demand for the international floriculture market due to their brightly coloured and textured flowers or bracts. Fungal pathogens, however, create a serious problem in cultivating flawless blooms. The aim of the present study was to characterise several of these pathogens using morphology, culture characteristics, and DNA sequence data of the rRNA-ITS and LSU genes. In some cases additional genes such as TEF 1-α and CHS were also sequenced. Based on the results of this study, several novel species and genera are described. Brunneosphaerella leaf blight is shown to be caused by three species, namely B. jonkershoekensis on Protea repens, B. nitidae sp. nov. on Protea nitida and B. protearum on a wide host range of Protea spp. (South Africa). Coniothyrium-like species associated with Coniothyrium leaf spot are allocated to other genera, namely Curreya grandicipis on Protea grandiceps, and Microsphaeropsis proteae on P. nitida (South Africa). Diaporthe leucospermi is described on Leucospermum sp. (Australia), and Diplodina microsperma newly reported on Protea sp. (New Zealand). Pyrenophora blight is caused by a novel species, Pyrenophora leucospermi, and not Drechslera biseptata or D. dematoidea as previously reported. Fusicladium proteae is described on Protea sp. (South Africa), Pestalotiopsis protearum on Leucospermum cuneiforme (Zimbabwe), Ramularia vizellae and R. stellenboschensis on Protea spp. (South Africa), and Teratosphaeria capensis on Protea spp. (Portugal, South Africa). Aureobasidium leaf spot is shown to be caused by two species, namely A. proteae comb. nov. on Protea spp. (South Africa), and A. leucospermi sp. nov. on Leucospermum spp. (Indonesia, Portugal, South Africa). Novel genera and species elucidated in this study include Gordonomyces mucovaginatus and Pseudopassalora gouriqua (hyphomycetes), and Xenoconiothyrium catenata (coelomycete), all on Protea spp. (South Africa).

  12. Multiplex detection of respiratory pathogens

    DOEpatents

    McBride, Mary; Slezak, Thomas; Birch, James M.

    2012-07-31

    Described are kits and methods useful for detection of respiratory pathogens (influenza A (including subtyping capability for H1, H3, H5 and H7 subtypes) influenza B, parainfluenza (type 2), respiratory syncytial virus, and adenovirus) in a sample. Genomic sequence information from the respiratory pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay to successfully identify the presence or absence of pathogens in a sample.

  13. Host Specificity of Bacterial Pathogens

    PubMed Central

    Bäumler, Andreas; Fang, Ferric C.

    2013-01-01

    Most pathogens are able to infect multiple hosts but some are highly adapted to a single-host species. A detailed understanding of the basis of host specificity can provide important insights into molecular pathogenesis, the evolution of pathogenic microbes, and the potential for pathogens to cross the species barrier to infect new hosts. Comparative genomics and the development of humanized mouse models have provided important new tools with which to explore the basis of generalism and specialism. This review will examine host specificity of bacterial pathogens with a focus on generalist and specialist serovars of Salmonella enterica. PMID:24296346

  14. 42 CFR 35.35 - Unsalable articles.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Unsalable articles. 35.35 Section 35.35 Public... HOSPITAL AND STATION MANAGEMENT Disposition of Articles Produced by Patients § 35.35 Unsalable articles. Articles having no commercial value shall be stored, destroyed, or otherwise disposed of as the officer...

  15. 27 CFR 46.208 - Unmerchantable articles.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Unmerchantable articles. 46... Tubes Held for Sale on April 1, 2009 Inventories § 46.208 Unmerchantable articles. Articles that the.... However, the dealer must segregate any such unmerchantable articles and include them in a separate...

  16. 42 CFR 35.35 - Unsalable articles.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Unsalable articles. 35.35 Section 35.35 Public... HOSPITAL AND STATION MANAGEMENT Disposition of Articles Produced by Patients § 35.35 Unsalable articles. Articles having no commercial value shall be stored, destroyed, or otherwise disposed of as the officer...

  17. 27 CFR 46.208 - Unmerchantable articles.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Unmerchantable articles... Tubes Held for Sale on April 1, 2009 Inventories § 46.208 Unmerchantable articles. Articles that the.... However, the dealer must segregate any such unmerchantable articles and include them in a separate...

  18. 27 CFR 46.208 - Unmerchantable articles.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Unmerchantable articles... Tubes Held for Sale on April 1, 2009 Inventories § 46.208 Unmerchantable articles. Articles that the.... However, the dealer must segregate any such unmerchantable articles and include them in a separate...

  19. 42 CFR 35.35 - Unsalable articles.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Unsalable articles. 35.35 Section 35.35 Public... HOSPITAL AND STATION MANAGEMENT Disposition of Articles Produced by Patients § 35.35 Unsalable articles. Articles having no commercial value shall be stored, destroyed, or otherwise disposed of as the officer...

  20. 27 CFR 46.208 - Unmerchantable articles.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Unmerchantable articles... Tubes Held for Sale on April 1, 2009 Inventories § 46.208 Unmerchantable articles. Articles that the.... However, the dealer must segregate any such unmerchantable articles and include them in a separate...

  1. 42 CFR 35.35 - Unsalable articles.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Unsalable articles. 35.35 Section 35.35 Public... HOSPITAL AND STATION MANAGEMENT Disposition of Articles Produced by Patients § 35.35 Unsalable articles. Articles having no commercial value shall be stored, destroyed, or otherwise disposed of as the officer...

  2. On Reviewing and Writing a Scholarly Article

    ERIC Educational Resources Information Center

    Bettis, Jerry L., Sr.

    2012-01-01

    This article provides guidelines for reviewing and writing scholarly articles for the professional who reads and writes them for his/her own work and/or for publication in scientific journals. It outlines the purpose and contents of each section of a research article and provides a checklist for reviewing and writing a research article. This…

  3. 42 CFR 35.35 - Unsalable articles.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Unsalable articles. 35.35 Section 35.35 Public... HOSPITAL AND STATION MANAGEMENT Disposition of Articles Produced by Patients § 35.35 Unsalable articles. Articles having no commercial value shall be stored, destroyed, or otherwise disposed of as the officer...

  4. 27 CFR 46.208 - Unmerchantable articles.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Unmerchantable articles... Tubes Held for Sale on April 1, 2009 Inventories § 46.208 Unmerchantable articles. Articles that the.... However, the dealer must segregate any such unmerchantable articles and include them in a separate...

  5. Tick vaccines and the control of tick-borne pathogens.

    PubMed

    Merino, Octavio; Alberdi, Pilar; Pérez de la Lastra, José M; de la Fuente, José

    2013-01-01

    Ticks are obligate hematophagous ectoparasites that transmit a wide variety of pathogens to humans and animals. The incidence of tick-borne diseases has increased worldwide in both humans and domestic animals over the past years resulting in greater interest in the study of tick-host-pathogen interactions. Advances in vector and pathogen genomics and proteomics have moved forward our knowledge of the vector-pathogen interactions that take place during the colonization and transmission of arthropod-borne microbes. Tick-borne pathogens adapt from the vector to the mammalian host by differential gene expression thus modulating host processes. In recent years, studies have shown that targeting tick proteins by vaccination can not only reduce tick feeding and reproduction, but also the infection and transmission of pathogens from the tick to the vertebrate host. In this article, we review the tick-protective antigens that have been identified for the formulation of tick vaccines and the effect of these vaccines on the control of tick-borne pathogens.

  6. Tick vaccines and the control of tick-borne pathogens

    PubMed Central

    Merino, Octavio; Alberdi, Pilar; Pérez de la Lastra, José M.; de la Fuente, José

    2013-01-01

    Ticks are obligate hematophagous ectoparasites that transmit a wide variety of pathogens to humans and animals. The incidence of tick-borne diseases has increased worldwide in both humans and domestic animals over the past years resulting in greater interest in the study of tick-host-pathogen interactions. Advances in vector and pathogen genomics and proteomics have moved forward our knowledge of the vector-pathogen interactions that take place during the colonization and transmission of arthropod-borne microbes. Tick-borne pathogens adapt from the vector to the mammalian host by differential gene expression thus modulating host processes. In recent years, studies have shown that targeting tick proteins by vaccination can not only reduce tick feeding and reproduction, but also the infection and transmission of pathogens from the tick to the vertebrate host. In this article, we review the tick-protective antigens that have been identified for the formulation of tick vaccines and the effect of these vaccines on the control of tick-borne pathogens. PMID:23847771

  7. Production of Eicosanoids and Other Oxylipins by Pathogenic Eukaryotic Microbes

    PubMed Central

    Noverr, Mairi C.; Erb-Downward, John R.; Huffnagle, Gary B.

    2003-01-01

    Oxylipins are oxygenated metabolites of fatty acids. Eicosanoids are a subset of oxylipins and include the prostaglandins and leukotrienes, which are potent regulators of host immune responses. Host cells are one source of eicosanoids and oxylipins during infection; however, another potential source of eicosanoids is the pathogen itself. A broad range of pathogenic fungi, protozoa, and helminths produce eicosanoids and other oxylipins by novel synthesis pathways. Why do these organisms produce oxylipins? Accumulating data suggest that phase change and differentiation in these organisms are controlled by oxylipins, including prostaglandins and lipoxygenase products. The precise role of pathogen-derived eicosanoids in pathogenesis remains to be determined, but the potential link between pathogen eicosanoids and the development of TH2 responses in the host is intriguing. Mammalian prostaglandins and leukotrienes have been studied extensively, and these molecules can modulate Th1 versus Th2 immune responses, chemokine production, phagocytosis, lymphocyte proliferation, and leukocyte chemotaxis. Thus, eicosanoids and oxylipins (host or microbe) may be mediators of a direct host-pathogen “cross-talk” that promotes chronic infection and hypersensitivity disease, common features of infection by eukaryotic pathogens. PMID:12857780

  8. Developing cryotherapy to eliminate graft-transmissible pathogens in citrus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This article summarizes research being conducted as part of a project funded by the California Citrus Research Board to develop cryotherapy (freezing buds in liquid nitrogen, and then recovering them) as a viable method for elimination of graft transmissible pathogens from Citrus. There are current...

  9. HealthPathways: creating a pathway for health systems reform.

    PubMed

    Robinson, Suzanne; Varhol, Richard; Bell, Colin; Quirk, Frances; Durrington, Learne

    2015-02-01

    Inefficiencies in the co-ordination and integration of primary and secondary care services in Australia, have led to increases in waiting times, unnecessary presentations to emergency departments and issues around poor discharge of patients. HealthPathways is a program developed in Canterbury, New Zealand, that builds relationships between General Practitioners and Specialists and uses information technology so that efficiency is maximised and the right patient is given the right care at the right time. Healthpathways is being implemented by a number of Medicare Locals across Australia however, little is known about the impact HealthPathways may have in Australia. This article provides a short description of HealthPathways and considers what it may offer in the Australian context and some of the barriers and facilitators to implementation. PMID:25433515

  10. HealthPathways: creating a pathway for health systems reform.

    PubMed

    Robinson, Suzanne; Varhol, Richard; Bell, Colin; Quirk, Frances; Durrington, Learne

    2015-02-01

    Inefficiencies in the co-ordination and integration of primary and secondary care services in Australia, have led to increases in waiting times, unnecessary presentations to emergency departments and issues around poor discharge of patients. HealthPathways is a program developed in Canterbury, New Zealand, that builds relationships between General Practitioners and Specialists and uses information technology so that efficiency is maximised and the right patient is given the right care at the right time. Healthpathways is being implemented by a number of Medicare Locals across Australia however, little is known about the impact HealthPathways may have in Australia. This article provides a short description of HealthPathways and considers what it may offer in the Australian context and some of the barriers and facilitators to implementation.

  11. Promiscuous Pathogenicity Islands and Phylogeny of Pathogenic Streptomyces spp.

    PubMed

    Zhang, Yucheng; Bignell, Dawn R D; Zuo, Ran; Fan, Qiurong; Huguet-Tapia, Jose C; Ding, Yousong; Loria, Rosemary

    2016-08-01

    Approximately 10 Streptomyces species cause disease on underground plant structures. The most economically important of these is potato scab, and the most studied of these pathogens is Streptomyces scabiei (syn. S. scabies). The main pathogenicity determinant of scab-causing Streptomyces species is a nitrated diketopiperazine, known as thaxtomin A (ThxA). In the pathogenic species Streptomyces turgidiscabies, ThxA biosynthetic genes reside on a mobile pathogenicity island (PAI). However, the mobilization of PAIs in other Streptomyces species remains uncharacterized. Here, we investigated the mobilization of the PAI of S. scabiei 87-22. Based on whole genome sequences, we inferred the evolutionary relationships of pathogenic Streptomyces species and discovered that Streptomyces sp. strain 96-12, a novel pathogenic species isolated from potatoes in Egypt, was phylogenetically grouped with nonpathogenic species rather than with known pathogenic species. We also found that Streptomyces sp. strain 96-12 contains a PAI that is almost identical to the PAI in S. scabiei 87-22, despite significant differences in their genome sequences. This suggested direct or indirect in vivo mobilization of the PAI between S. scabiei and nonpathogenic Streptomyces species. To test whether the S. scabiei 87-22 PAI could, indeed, be mobilized, S. scabiei 87-22 deletion mutants containing antibiotic resistance markers in the PAI were mated with Streptomyces diastatochromogenes, a nonpathogenic species. The PAI of S. scabiei was site-specifically inserted into the aviX1 gene of S. diastatochromogenes and conferred pathogenicity in radish seedling assays. Our results demonstrated that S. scabiei, the earliest described Streptomyces pathogen, could be the source of a PAI responsible for the emergence of novel pathogenic species. PMID:27502745

  12. Cell wall integrity signalling in human pathogenic fungi.

    PubMed

    Dichtl, Karl; Samantaray, Sweta; Wagener, Johannes

    2016-09-01

    Fungi are surrounded by a rigid structure, the fungal cell wall. Its plasticity and composition depend on active regulation of the underlying biosynthesis and restructuring processes. This involves specialised signalling pathways that control gene expression and activities of biosynthetic enzymes. The cell wall integrity (CWI) pathway is the central signalling cascade required for the adaptation to a wide spectrum of cell wall perturbing conditions, including heat, oxidative stress and antifungals. In the recent years, great efforts were made to analyse the CWI pathway of diverse fungi. It turned out that the CWI signalling cascade is mostly conserved in the fungal kingdom. In this review, we summarise as well as compare the current knowledge on the canonical CWI pathway in the human pathogenic fungi Candida albicans, Candida glabrata, Aspergillus fumigatus and Cryptococcus neoformans. Understanding the differences and similarities in the stress responses of these organisms could become a key to improving existing or developing new antifungal therapies. PMID:27155139

  13. How Salmonella became a pathogen.

    PubMed

    Groisman, E A; Ochman, H

    1997-09-01

    In many pathogens, virulence can be conferred by a single region of the genome. In contrast, the facultative intracellular lifestyle of Salmonella demands a large number of genes distributed around the chromosome. The evolution of Salmonella has been marked by the acquisition of several 'pathogenicity islands', each contributing to the unique virulence properties of this microorganism.

  14. Common themes in microbial pathogenicity.

    PubMed Central

    Finlay, B B; Falkow, S

    1989-01-01

    A bacterial pathogen is a highly adapted microorganism which has the capacity to cause disease. The mechanisms used by pathogenic bacteria to cause infection and disease usually include an interactive group of virulence determinants, sometimes coregulated, which are suited for the interaction of a particular microorganism with a specific host. Because pathogens must overcome similar host barriers, common themes in microbial pathogenesis have evolved. However, these mechanisms are diverse between species and not necessarily conserved; instead, convergent evolution has developed several different mechanisms to overcome host barriers. The success of a bacterial pathogen can be measured by the degree with which it replicates after entering the host and reaching its specific niche. Successful microbial infection reflects persistence within a host and avoidance or neutralization of the specific and nonspecific defense mechanisms of the host. The degree of success of a pathogen is dependent upon the status of the host. As pathogens pass through a host, they are exposed to new environments. Highly adapted pathogenic organisms have developed biochemical sensors exquisitely designed to measure and respond to such environmental stimuli and accordingly to regulate a cascade of virulence determinants essential for life within the host. The pathogenic state is the product of dynamic selective pressures on microbial populations. PMID:2569162

  15. USEPA PATHOGEN EQUIVALENCY COMMITTEE RETREAT

    EPA Science Inventory

    The Pathogen Equivalency Committee held its retreat from September 20-21, 2005 at Hueston Woods State Park in College Corner, Ohio. This presentation will update the PEC’s membership on emerging pathogens, analytical methods, disinfection techniques, risk analysis, preparat...

  16. Developmental Pathways in Juvenile Externalizing and Internalizing Problems

    ERIC Educational Resources Information Center

    Loeber, Rolf; Burke, Jeffrey D.

    2011-01-01

    This article summarizes the empirical studies showing pathways in the development of externalizing and delinquent behaviors. Pathways are defined as the orderly temporal development between more than two problem behaviors. The paper addresses the following questions: (1) What are the developmental pathways between different diagnoses of Disruptive…

  17. Physical constraints for pathogen movement.

    PubMed

    Schwarz, Ulrich S

    2015-10-01

    In this pedagogical review, we discuss the physical constraints that pathogens experience when they move in their host environment. Due to their small size, pathogens are living in a low Reynolds number world dominated by viscosity. For swimming pathogens, the so-called scallop theorem determines which kinds of shape changes can lead to productive motility. For crawling or gliding cells, the main resistance to movement comes from protein friction at the cell-environment interface. Viruses and pathogenic bacteria can also exploit intracellular host processes such as actin polymerization and motor-based transport, if they present the appropriate factors on their surfaces. Similar to cancer cells that also tend to cross various barriers, pathogens often combine several of these strategies in order to increase their motility and therefore their chances to replicate and spread.

  18. Modulation of Host miRNAs by Intracellular Bacterial Pathogens

    PubMed Central

    Das, Kishore; Garnica, Omar; Dhandayuthapani, Subramanian

    2016-01-01

    MicroRNAs (miRNAs) are short non-coding RNAs that regulate the expression of protein coding genes of viruses and eukaryotes at the post-transcriptional level. The eukaryotic genes regulated by miRNAs include those whose products are critical for biological processes such as cell proliferation, metabolic pathways, immune response, and development. It is now increasingly recognized that modulation of miRNAs associated with biological processes is one of the strategies adopted by bacterial pathogens to survive inside host cells. In this review, we present an overview of the recent findings on alterations of miRNAs in the host cells by facultative intracellular bacterial pathogens. In addition, we discuss how the altered miRNAs help in the survival of these pathogens in the intracellular environment. PMID:27536558

  19. Tubercle bacilli rely on a type VII army for pathogenicity.

    PubMed

    Stoop, Esther J M; Bitter, Wilbert; van der Sar, Astrid M

    2012-10-01

    Mycobacteria, such as the major human pathogen Mycobacterium tuberculosis, have a highly unusual and characteristic diderm cell envelope that protects them against harmful conditions. Protein secretion across this hydrophobic barrier requires specialized secretion systems. Recently, a type VII secretion (T7S) pathway has been identified that fulfills this function. Pathogenic mycobacteria have up to five different T7S systems, some of which play a crucial role in virulence. The interactions between secreted substrates and host molecules are only starting to become clear and will help in furthering our understanding of the persistence of these enigmatic pathogens. In this review, we discuss current knowledge on the role of T7S systems in mycobacterial virulence.

  20. Alterations of host cell ubiquitination machinery by pathogenic bacteria

    PubMed Central

    Alomairi, Jaafar; Bonacci, Thomas; Ghigo, Eric; Soubeyran, Philippe

    2015-01-01

    Response of immune and non-immune cells to pathogens infections is a very dynamic process. It involves the activation/modulation of many pathways leading to actin remodeling, membrane engulfing, phagocytosis, vesicle trafficking, phagolysosome formation, aiming at the destruction of the intruder. These sophisticated and rapid mechanisms rely on post-translational modifications (PTMs) of key host cells' factors, and bacteria have developed various strategies to manipulate them to favor their survival. Among these important PTMs, ubiquitination has emerged as a major mediator/modulator/regulator of host cells response to infections that pathogens have also learned to use for their own benefit. In this mini-review, we summarize our current knowledge about the normal functions of ubiquitination during host cell infection, and we detail its hijacking by model pathogens to escape clearance and to proliferate. PMID:25774357

  1. Finding all BRCA pathogenic mutation carriers: best practice models.

    PubMed

    Hoogerbrugge, Nicoline; Jongmans, Marjolijn Cj

    2016-09-01

    Identifying germline BRCA pathogenic mutations in patients with ovarian or breast cancer is a crucial component in the medical management of affected patients. Furthermore, the relatives of affected patients can be offered genetic testing. Relatives who test positive for a germline BRCA pathogenic mutation can take appropriate action to prevent cancer or have cancer diagnosed as early as possible for better treatment options. The recent discovery that BRCA pathogenic mutation status can inform treatment decisions in patients with ovarian cancer has led to an increased demand for BRCA testing, with testing taking place earlier in the patient care pathway. New approaches to genetic counselling may be required to meet this greater demand for BRCA testing. This review discusses the need for best practices for genetic counselling and BRCA testing; it examines the challenges facing current practice and looks at adapted models of genetic counselling. PMID:27514840

  2. Modulation of Host miRNAs by Intracellular Bacterial Pathogens.

    PubMed

    Das, Kishore; Garnica, Omar; Dhandayuthapani, Subramanian

    2016-01-01

    MicroRNAs (miRNAs) are short non-coding RNAs that regulate the expression of protein coding genes of viruses and eukaryotes at the post-transcriptional level. The eukaryotic genes regulated by miRNAs include those whose products are critical for biological processes such as cell proliferation, metabolic pathways, immune response, and development. It is now increasingly recognized that modulation of miRNAs associated with biological processes is one of the strategies adopted by bacterial pathogens to survive inside host cells. In this review, we present an overview of the recent findings on alterations of miRNAs in the host cells by facultative intracellular bacterial pathogens. In addition, we discuss how the altered miRNAs help in the survival of these pathogens in the intracellular environment. PMID:27536558

  3. Pathogens in water: value and limits of correlation with microbial indicators.

    PubMed

    Payment, Pierre; Locas, Annie

    2011-01-01

    This article discusses the value and limitations of using microbial indicators to predict occurrence of enteric pathogens in water. Raw or treated sewage is a primary source of fecal contamination of the receiving surface water or groundwater; hence, understanding the relationship between pathogens and indicators in sewage is an important step in understanding the correlation in receiving waters. This article presents three different datasets representing different concentrations of pathogens and microbial indicators: sewage containing high concentrations of pathogens and indicators, surface water with variable concentrations, and groundwater with low concentrations. In sewage, even with very high levels of microorganisms, no mathematical correlation can predict the type or concentration of any pathogen. After discharge in the environment, direct correlation becomes biologically improbable as dilution, transport, and different inactivation rates occur in various environments. In surface waters, advanced statistical methods such as logistic regression have provided some level of predictability of the occurrence of pathogens but not specific counts. In groundwater, the continuous absence of indicators indicates an improbable occurrence of pathogen. In contrast, when these indicators are detected, pathogen occurrence probability increases significantly. In groundwater, given the nature and dissemination pattern of pathogenic microorganisms, a direct correlation with fecal microbial indicators is not observed and should not be expected. However, the indicators are still useful as a measure of risk. In summary, many pathogens of public health importance do not behave like fecal microbial indicators, and there is still no absolute indicator of their presence, only a probability of their co-occurrence.

  4. Pyrimidine salvage pathway in Mycobacterium tuberculosis.

    PubMed

    Villela, A D; Sánchez-Quitian, Z A; Ducati, R G; Santos, D S; Basso, L A

    2011-01-01

    The causative agent of tuberculosis (TB), Mycobacterium tuberculosis, infects one-third of the world population. TB remains the leading cause of mortality due to a single bacterial pathogen. The worldwide increase in incidence of M. tuberculosis has been attributed to the high proliferation rates of multi and extensively drug-resistant strains, and to co-infection with the human immunodeficiency virus. There is thus a continuous requirement for studies on mycobacterial metabolism to identify promising targets for the development of new agents to combat TB. Singular characteristics of this pathogen, such as functional and structural features of enzymes involved in fundamental metabolic pathways, can be evaluated to identify possible targets for drug development. Enzymes involved in the pyrimidine salvage pathway might be attractive targets for rational drug design against TB, since this pathway is vital for all bacterial cells, and is composed of enzymes considerably different from those present in humans. Moreover, the enzymes of the pyrimidine salvage pathway might have an important role in the mycobacterial latent state, since M. tuberculosis has to recycle bases and/or nucleosides to survive in the hostile environment imposed by the host. The present review describes the enzymes of M. tuberculosis pyrimidine salvage pathway as attractive targets for the development of new antimycobacterial agents. Enzyme functional and structural data have been included to provide a broader knowledge on which to base the search for compounds with selective biological activity.

  5. Method of nitriding refractory metal articles

    DOEpatents

    Tiegs, T.N.; Holcombe, C.E.; Dykes, N.L.; Omatete, O.O.; Young, A.C.

    1994-03-15

    A method of nitriding a refractory-nitride forming metal or metalloid articles and composite articles. A consolidated metal or metalloid article or composite is placed inside a microwave oven and nitrogen containing gas is introduced into the microwave oven. The metal or metalloid article or composite is heated to a temperature sufficient to react the metal or metalloid with the nitrogen by applying a microwave energy within the microwave oven. The metal or metalloid article or composite is maintained at that temperature for a period of time sufficient to convert the article of metal or metalloid or composite to an article or composite of refractory nitride. In addition, a method of applying a coating, such as a coating of an oxide, a carbide, or a carbo-nitride, to an article of metal or metalloid by microwave heating.

  6. Method of nitriding refractory metal articles

    DOEpatents

    Tiegs, Terry N.; Holcombe, Cressie E.; Dykes, Norman L.; Omatete, Ogbemi O.; Young, Albert C.

    1994-01-01

    A method of nitriding a refractory-nitride forming metal or metalloid articles and composite articles. A consolidated metal or metalloid article or composite is placed inside a microwave oven and nitrogen containing gas is introduced into the microwave oven. The metal or metalloid article or composite is heated to a temperature sufficient to react the metal or metalloid with the nitrogen by applying a microwave energy within the microwave oven. The metal or metalloid article or composite is maintained at that temperature for a period of time sufficient to convert the article of metal or metalloid or composite to an article or composite of refractory nitride. In addition, a method of applying a coating, such as a coating of an oxide, a carbide, or a carbo-nitride, to an article of metal or metalloid by microwave heating.

  7. Glacial Refugia in Pathogens: European Genetic Structure of Anther Smut Pathogens on Silene latifolia and Silene dioica

    PubMed Central

    Vercken, Elodie; Fontaine, Michael C.; Gladieux, Pierre; Hood, Michael E.; Jonot, Odile; Giraud, Tatiana

    2010-01-01

    Climate warming is predicted to increase the frequency of invasions by pathogens and to cause the large-scale redistribution of native host species, with dramatic consequences on the health of domesticated and wild populations of plants and animals. The study of historic range shifts in response to climate change, such as during interglacial cycles, can help in the prediction of the routes and dynamics of infectious diseases during the impending ecosystem changes. Here we studied the population structure in Europe of two Microbotryum species causing anther smut disease on the plants Silene latifolia and Silene dioica. Clustering analyses revealed the existence of genetically distinct groups for the pathogen on S. latifolia, providing a clear-cut example of European phylogeography reflecting recolonization from southern refugia after glaciation. The pathogen genetic structure was congruent with the genetic structure of its host species S. latifolia, suggesting dependence of the migration pathway of the anther smut fungus on its host. The fungus, however, appeared to have persisted in more numerous and smaller refugia than its host and to have experienced fewer events of large-scale dispersal. The anther smut pathogen on S. dioica also showed a strong phylogeographic structure that might be related to more northern glacial refugia. Differences in host ecology probably played a role in these differences in the pathogen population structure. Very high selfing rates were inferred in both fungal species, explaining the low levels of admixture between the genetic clusters. The systems studied here indicate that migration patterns caused by climate change can be expected to include pathogen invasions that follow the redistribution of their host species at continental scales, but also that the recolonization by pathogens is not simply a mirror of their hosts, even for obligate biotrophs, and that the ecology of hosts and pathogen mating systems likely affects recolonization

  8. Glacial refugia in pathogens: European genetic structure of anther smut pathogens on Silene latifolia and Silene dioica.

    PubMed

    Vercken, Elodie; Fontaine, Michael C; Gladieux, Pierre; Hood, Michael E; Jonot, Odile; Giraud, Tatiana

    2010-01-01

    Climate warming is predicted to increase the frequency of invasions by pathogens and to cause the large-scale redistribution of native host species, with dramatic consequences on the health of domesticated and wild populations of plants and animals. The study of historic range shifts in response to climate change, such as during interglacial cycles, can help in the prediction of the routes and dynamics of infectious diseases during the impending ecosystem changes. Here we studied the population structure in Europe of two Microbotryum species causing anther smut disease on the plants Silene latifolia and Silene dioica. Clustering analyses revealed the existence of genetically distinct groups for the pathogen on S. latifolia, providing a clear-cut example of European phylogeography reflecting recolonization from southern refugia after glaciation. The pathogen genetic structure was congruent with the genetic structure of its host species S. latifolia, suggesting dependence of the migration pathway of the anther smut fungus on its host. The fungus, however, appeared to have persisted in more numerous and smaller refugia than its host and to have experienced fewer events of large-scale dispersal. The anther smut pathogen on S. dioica also showed a strong phylogeographic structure that might be related to more northern glacial refugia. Differences in host ecology probably played a role in these differences in the pathogen population structure. Very high selfing rates were inferred in both fungal species, explaining the low levels of admixture between the genetic clusters. The systems studied here indicate that migration patterns caused by climate change can be expected to include pathogen invasions that follow the redistribution of their host species at continental scales, but also that the recolonization by pathogens is not simply a mirror of their hosts, even for obligate biotrophs, and that the ecology of hosts and pathogen mating systems likely affects recolonization

  9. Sweet new world: glycoproteins in bacterial pathogens.

    PubMed

    Schmidt, M Alexander; Riley, Lee W; Benz, Inga

    2003-12-01

    In eukaryotes, the combinatorial potential of carbohydrates is used for the modulation of protein function. However, despite the wealth of cell wall and surface-associated carbohydrates and glycoconjugates, the accepted dogma has been that prokaryotes are not able to glycosylate proteins. This has now changed and protein glycosylation in prokaryotes is an accepted fact. Intriguingly, in Gram-negative bacteria most glycoproteins are associated with virulence factors of medically significant pathogens. Also, important steps in pathogenesis have been linked to the glycan substitution of surface proteins, indicating that the glycosylation of bacterial proteins might serve specific functions in infection and pathogenesis and interfere with inflammatory immune responses. Therefore, the carbohydrate modifications and glycosylation pathways of bacterial proteins will become new targets for therapeutic and prophylactic measures. Here we discuss recent findings on the structure, genetics and function of glycoproteins of medically important bacteria and potential applications of bacterial glycosylation systems for the generation of novel glycoconjugates.

  10. Algodystrophy: recent insight into the pathogenic framework

    PubMed Central

    Varenna, Massimo; Zucchi, Francesca

    2015-01-01

    Summary Algodystrophy, nowadays called CRPS I, is a painful syndrome characterized by sensory and vasomotor disturbance, edema and functional impairment. Significant progress in knowledge about the pathogenic mechanisms of the disease have been recently achieved, but they are not yet fully understood and some clinical aspects are still lacking of a whole pathogenetic comprehension. The local release of pro-inflammatory neuropeptides and some cytokines may be the event that triggers and maintains the disease, causing hyperalgesia and allodynia. In the following phases, the impaired capillary permeability, the interstitial edema and the consequent hypoxia and local acidosis have been proposed as possible pathophysiological pathways. The local hyperactivity of the sympathetic nervous system supposed in the past has not be confirmed and the hypothesis of an altered nociceptive processing at CNS level has limited evidences in acute phases of the disease. The steady bone involvement could be confirmed by the efficacy of bisphosphonates in the treatment of early disease. PMID:26136792

  11. Infection strategies of enteric pathogenic Escherichia coli

    PubMed Central

    Clements, Abigail; Young, Joanna C.; Constantinou, Nicholas; Frankel, Gad

    2012-01-01

    Enteric Escherichia coli (E. coli) are both natural flora of humans and important pathogens causing significant morbidity and mortality worldwide. Traditionally enteric E. coli have been divided into 6 pathotypes, with further pathotypes often proposed. In this review we suggest expansion of the enteric E. coli into 8 pathotypes to include the emerging pathotypes of adherent invasive E. coli (AIEC) and Shiga-toxin producing enteroaggregative E. coli (STEAEC). The molecular mechanisms that allow enteric E. coli to colonize and cause disease in the human host are examined and for two of the pathotypes that express a type 3 secretion system (T3SS) we discuss the complex interplay between translocated effectors and manipulation of host cell signaling pathways that occurs during infection. PMID:22555463

  12. Tips and tricks in writing review article.

    PubMed

    Syam, Ari Fahrial

    2007-01-01

    Review article or literature review actually is the simplest form of writing compared to a case report or study report. The writing process begins at pointing out topics to be written and informed to readers. The next step after the topic has been selected is to find literatures related to the article review writing. Principally, article writing plays an essential part in a doctor's life, whether as a specialist or consultant. And the most important is the desire to publish the article review.

  13. Authoring Newspaper Science Articles: A Rewarding Experience

    ERIC Educational Resources Information Center

    Gonzalez-Espada, Wilson J.

    2009-01-01

    In this article, the author summarizes the rationale for using science articles in K-16 education and addresses some of its limitations. The author also encourages scientists and college science faculty to contribute contextually relevant articles that might include selected literary techniques to their local or state newspapers.

  14. 22 CFR 120.6 - Defense article.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Defense article. 120.6 Section 120.6 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.6 Defense article. Defense article means any item or technical data designated in § 121.1 of this...

  15. 48 CFR 225.104 - Nonavailable articles.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Nonavailable articles. 225..., DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Supplies 225.104 Nonavailable articles. (a) DoD has determined that the following articles also are nonavailable in accordance with FAR...

  16. 19 CFR 148.4 - Accompanying articles.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Accompanying articles. 148.4 Section 148.4 Customs... (CONTINUED) PERSONAL DECLARATIONS AND EXEMPTIONS General Provisions § 148.4 Accompanying articles. (a) Generally. Articles shall be considered as accompanying a passenger or brought in by him if the...

  17. 48 CFR 825.104 - Nonavailable articles.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Nonavailable articles. 825... SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Buy American Act-Supplies 825.104 Nonavailable articles. The following items are added to the list of nonavailable articles contained in FAR 25.104: Glass, lead...

  18. 19 CFR 148.4 - Accompanying articles.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Accompanying articles. 148.4 Section 148.4 Customs... (CONTINUED) PERSONAL DECLARATIONS AND EXEMPTIONS General Provisions § 148.4 Accompanying articles. (a) Generally. Articles shall be considered as accompanying a passenger or brought in by him if the...

  19. 22 CFR 120.6 - Defense article.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Defense article. 120.6 Section 120.6 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.6 Defense article. Defense article means any item or technical data designated in § 121.1 of this...

  20. 27 CFR 20.191 - Bulk articles.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Bulk articles. 20.191... Users of Specially Denatured Spirits Operations by Users § 20.191 Bulk articles. Users who convey articles in containers exceeding one gallon may provide the recipient with a photocopy of subpart G of...

  1. 27 CFR 20.191 - Bulk articles.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Bulk articles. 20.191... Users of Specially Denatured Spirits Operations by Users § 20.191 Bulk articles. Users who convey articles in containers exceeding one gallon may provide the recipient with a photocopy of subpart G of...

  2. 48 CFR 225.104 - Nonavailable articles.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Nonavailable articles. 225.104 Section 225.104 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Nonavailable articles. (a) DoD has determined that the following articles also are nonavailable in...

  3. Referent Salience Affects Second Language Article Use

    ERIC Educational Resources Information Center

    Trenkic, Danijela; Pongpairoj, Nattama

    2013-01-01

    The effect of referent salience on second language (L2) article production in real time was explored. Thai (-articles) and French (+articles) learners of English described dynamic events involving two referents, one visually cued to be more salient at the point of utterance formulation. Definiteness marking was made communicatively redundant with…

  4. 48 CFR 825.104 - Nonavailable articles.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Nonavailable articles. 825... SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Buy American Act-Supplies 825.104 Nonavailable articles. The following items are added to the list of nonavailable articles contained in FAR 25.104: Glass, lead...

  5. 27 CFR 20.191 - Bulk articles.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Bulk articles. 20.191... Users of Specially Denatured Spirits Operations by Users § 20.191 Bulk articles. Users who convey articles in containers exceeding one gallon may provide the recipient with a photocopy of subpart G of...

  6. 27 CFR 20.191 - Bulk articles.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Bulk articles. 20.191... Users of Specially Denatured Spirits Operations by Users § 20.191 Bulk articles. Users who convey articles in containers exceeding one gallon may provide the recipient with a photocopy of subpart G of...

  7. 22 CFR 120.6 - Defense article.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Defense article. 120.6 Section 120.6 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.6 Defense article. Defense article means any item or technical data designated in § 121.1 of this...

  8. 48 CFR 225.104 - Nonavailable articles.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Nonavailable articles. 225.104 Section 225.104 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Nonavailable articles. (a) DoD has determined that the following articles also are nonavailable in...

  9. 22 CFR 120.6 - Defense article.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Defense article. 120.6 Section 120.6 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.6 Defense article. Defense article means any item or technical data designated in § 121.1 of this...

  10. 19 CFR 148.4 - Accompanying articles.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Accompanying articles. 148.4 Section 148.4 Customs... (CONTINUED) PERSONAL DECLARATIONS AND EXEMPTIONS General Provisions § 148.4 Accompanying articles. (a) Generally. Articles shall be considered as accompanying a passenger or brought in by him if the...

  11. 48 CFR 825.104 - Nonavailable articles.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Nonavailable articles. 825... SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Buy American Act-Supplies 825.104 Nonavailable articles. The following items are added to the list of nonavailable articles contained in FAR 25.104: Glass, lead...

  12. 48 CFR 825.104 - Nonavailable articles.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Nonavailable articles. 825... SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Buy American Act-Supplies 825.104 Nonavailable articles. The following items are added to the list of nonavailable articles contained in FAR 25.104: Glass, lead...

  13. 22 CFR 120.6 - Defense article.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Defense article. 120.6 Section 120.6 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.6 Defense article. Defense article means any item or technical data designated in § 121.1 of this...

  14. 48 CFR 225.104 - Nonavailable articles.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Nonavailable articles. 225..., DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Supplies 225.104 Nonavailable articles. (a) DoD has determined that the following articles also are nonavailable in accordance with FAR...

  15. 19 CFR 148.4 - Accompanying articles.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 2 2014-04-01 2014-04-01 false Accompanying articles. 148.4 Section 148.4 Customs... (CONTINUED) PERSONAL DECLARATIONS AND EXEMPTIONS General Provisions § 148.4 Accompanying articles. (a) Generally. Articles shall be considered as accompanying a passenger or brought in by him if the...

  16. 27 CFR 20.191 - Bulk articles.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Bulk articles. 20.191... Users of Specially Denatured Spirits Operations by Users § 20.191 Bulk articles. Users who convey articles in containers exceeding one gallon may provide the recipient with a photocopy of subpart G of...

  17. 48 CFR 825.104 - Nonavailable articles.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Nonavailable articles. 825... SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Buy American Act-Supplies 825.104 Nonavailable articles. The following items are added to the list of nonavailable articles contained in FAR 25.104: Glass, lead...

  18. 19 CFR 148.4 - Accompanying articles.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Accompanying articles. 148.4 Section 148.4 Customs... (CONTINUED) PERSONAL DECLARATIONS AND EXEMPTIONS General Provisions § 148.4 Accompanying articles. (a) Generally. Articles shall be considered as accompanying a passenger or brought in by him if the...

  19. Measuring the Interestingness of News Articles

    SciTech Connect

    Pon, R K; Cardenas, A F; Buttler, D J

    2007-09-24

    An explosive growth of online news has taken place. Users are inundated with thousands of news articles, only some of which are interesting. A system to filter out uninteresting articles would aid users that need to read and analyze many articles daily, such as financial analysts and government officials. The most obvious approach for reducing the amount of information overload is to learn keywords of interest for a user (Carreira et al., 2004). Although filtering articles based on keywords removes many irrelevant articles, there are still many uninteresting articles that are highly relevant to keyword searches. A relevant article may not be interesting for various reasons, such as the article's age or if it discusses an event that the user has already read about in other articles. Although it has been shown that collaborative filtering can aid in personalized recommendation systems (Wang et al., 2006), a large number of users is needed. In a limited user environment, such as a small group of analysts monitoring news events, collaborative filtering would be ineffective. The definition of what makes an article interesting--or its 'interestingness'--varies from user to user and is continually evolving, calling for adaptable user personalization. Furthermore, due to the nature of news, most articles are uninteresting since many are similar or report events outside the scope of an individual's concerns. There has been much work in news recommendation systems, but none have yet addressed the question of what makes an article interesting.

  20. How to Write an Article for Publication.

    ERIC Educational Resources Information Center

    Berger, Allen

    The suggestions for writing for publication given in this paper include writing with honesty, thinking clearly, considering the potential audience, sharing the article with friends, revising the article, and sending the article to the appropriate journal. Empathy for the difficulty of writing is given and illustrated with examples from Eric…

  1. Evaluating and understanding articles about treatment.

    PubMed

    Shaughnessy, Allen F

    2009-04-15

    Each year physicians must decide which of the thousands of newly published articles they will take time to read. To determine which articles are the most clinically useful, physicians should assess their relevance, validity, and clinical importance. Using these criteria can drastically decrease the number of articles physicians need to read. PMID:19405410

  2. Host-Pathogen Interactions

    PubMed Central

    English, Patricia D.; Jurale, Joseph Byrne; Albersheim, Peter

    1971-01-01

    The effect of a number of physiological variables on the secretion of polysaccharide-degrading enzymes by culture-grown Colletotrichum lindemuthianum (Saccardo and Magnus) Scribner was determined. The number of spores used to inoculate cultures grown on isolated bean hypocotyl cell walls affects the time after inoculation at which enzyme secretion occurs, but has no significant effect on the maximal amount of enzyme ultimately secreted. Cell walls isolated from bean leaves, first internodes, or hypocotyls (susceptible to C. lindemuthianum infection), when used as carbon source for C. lindemuthianum growth, stimulate the fungus to secrete more α-galactosidase than do cell walls isolated from roots (resistant to infection). The concentration of carbon source used for fungal growth determines the final level of enzyme activity in the culture fluid. The level of enzyme secretion is not proportional to fungal growth; rather, enzyme secretion is induced. Maximal α-galactosidase activity in the culture medium is found when the concentration of cell walls used as carbon source is 1% or greater. A higher concentration of cell walls is necessary for maximal α-arabinosidase activity. Galactose, when used as the carbon source, stimulates α-galactosidase secretion but, at comparable concentrations, is less effective in doing so than are cell walls. Polysaccharide-degrading enzymes are secreted by C. lindemuthianum at different times during growth of the pathogen on isolated cell walls. Pectinase and α-arabinosidase are secreted first, followed by β-xylosidase and cellulase, then β-glucosidase, and, finally, α-galactosidase. PMID:16657562

  3. Opportunistic Premise Plumbing Pathogens: Increasingly Important Pathogens in Drinking Water.

    PubMed

    Falkinham, Joseph O; Pruden, Amy; Edwards, Marc

    2015-06-09

    Opportunistic premise plumbing pathogens are responsible for a significant number of infections whose origin has been traced to drinking water. These opportunistic pathogens represent an emerging water borne disease problem with a major economic cost of at least $1 billion annually. The common features of this group of waterborne pathogens include: disinfectant-resistance, pipe surface adherence and biofilm formation, growth in amoebae, growth on low organic concentrations, and growth at low oxygen levels. Their emergence is due to the fact that conditions resulting from drinking water treatment select for them. As such, there is a need for novel approaches to reduce exposure to these pathogens. In addition to much-needed research, controls to reduce numbers and human exposure can be instituted independently by utilities and homeowners and hospital- and building-operators.

  4. Opportunistic Premise Plumbing Pathogens: Increasingly Important Pathogens in Drinking Water

    PubMed Central

    Falkinham, Joseph O.; Pruden, Amy; Edwards, Marc

    2015-01-01

    Opportunistic premise plumbing pathogens are responsible for a significant number of infections whose origin has been traced to drinking water. These opportunistic pathogens represent an emerging water borne disease problem with a major economic cost of at least $1 billion annually. The common features of this group of waterborne pathogens include: disinfectant-resistance, pipe surface adherence and biofilm formation, growth in amoebae, growth on low organic concentrations, and growth at low oxygen levels. Their emergence is due to the fact that conditions resulting from drinking water treatment select for them. As such, there is a need for novel approaches to reduce exposure to these pathogens. In addition to much-needed research, controls to reduce numbers and human exposure can be instituted independently by utilities and homeowners and hospital- and building-operators. PMID:26066311

  5. Firefox Extension Framework for News Article Tagging

    2006-08-08

    FEFNAT is a Firefox extension that is used to collect information about user interests when viewing new articles. When a user is reading a news article on a web-page, he can vote whether the article was interesting or not interesting by clicking the appropriate button on the extension's tool-bar. The purpose of this extension is to collet user interests and behavior while viewing new articles so that it can be used in my research formore » predicting how interesting future news article may be for the user.« less

  6. Functional genomics of pathogenic bacteria.

    PubMed Central

    Moxon, E R; Hood, D W; Saunders, N J; Schweda, E K H; Richards, J C

    2002-01-01

    Microbial diseases remain the commonest cause of global mortality and morbidity. Automated-DNA sequencing has revolutionized the investigation of pathogenic microbes by making the immense fund of information contained in their genomes available at reasonable cost. The challenge is how this information can be used to increase current understanding of the biology of commensal and virulence behaviour of pathogens with particular emphasis on in vivo function and novel approaches to prevention. One example of the application of whole-genome-sequence information is afforded by investigations of the pathogenic role of Haemophilus influenzae lipopolysaccharide and its candidacy as a vaccine. PMID:11839188

  7. Roadmap for future research on plant pathogen effectors

    PubMed Central

    Alfano, James R.

    2009-01-01

    SUMMARY Bacterial and eukaryotic plant pathogens deliver effector proteins into plant cells to promote pathogenesis. Bacterial pathogens containing type III protein secretion systems are known to inject many of these effectors into plant cells. More recently, oomycete pathogens have been shown to possess a large family of effectors containing the RXLR motif, and many effectors are also being discovered in fungal pathogens. Although effector activities are largely unknown, at least a subset suppress plant immunity. A plethora of new plant pathogen genomes that will soon be available thanks to next-generation sequencing technologies will allow the identification of many more effectors. This article summarizes the key approaches used to identify plant pathogen effectors, many of which will continue to be useful for future effector discovery. Thus, it can be viewed as a ‘roadmap’ for effector and effector target identification. Because effectors can be used as tools to elucidate components of innate immunity, advances in our understanding of effectors and their targets should lead to improvements in agriculture. PMID:19849786

  8. A critical role of autophagy in plant resistance to necrotrophic fungal pathogens.

    PubMed

    Lai, Zhibing; Wang, Fei; Zheng, Zuyu; Fan, Baofang; Chen, Zhixiang

    2011-06-01

    Autophagy is a pathway for degradation of cytoplasmic components. In plants, autophagy plays an important role in nutrient recycling during nitrogen or carbon starvation, and in responses to abiotic stress. Autophagy also regulates age- and immunity-related programmed cell death, which is important in plant defense against biotrophic pathogens. Here we show that autophagy plays a critical role in plant resistance to necrotrophic pathogens. ATG18a, a critical autophagy protein in Arabidopsis, interacts with WRKY33, a transcription factor that is required for resistance to necrotrophic pathogens. Expression of autophagy genes and formation of autophagosomes are induced in Arabidopsis by the necrotrophic fungal pathogen Botrytis cinerea. Induction of ATG18a and autophagy by B. cinerea was compromised in the wrky33 mutant, which is highly susceptible to necrotrophic pathogens. Arabidopsis mutants defective in autophagy exhibit enhanced susceptibility to the necrotrophic fungal pathogens B. cinerea and Alternaria brassicicola based on increased pathogen growth in the mutants. The hypersusceptibility of the autophagy mutants was associated with reduced expression of the jasmonate-regulated PFD1.2 gene, accelerated development of senescence-like chlorotic symptoms, and increased protein degradation in infected plant tissues. These results strongly suggest that autophagy cooperates with jasmonate- and WRKY33-mediated signaling pathways in the regulation of plant defense responses to necrotrophic pathogens.

  9. 14 CFR 45.15 - Marking requirements for PMA articles, TSO articles, and Critical parts.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Marking requirements for PMA articles, TSO articles, and Critical parts. 45.15 Section 45.15 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... Articles § 45.15 Marking requirements for PMA articles, TSO articles, and Critical parts. (a) PMA...

  10. 7 CFR 319.37-12 - Prohibited articles accompanying restricted articles.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Prohibited articles accompanying restricted articles... Stock, Plants, Roots, Bulbs, Seeds, and Other Plant Products 1,2 § 319.37-12 Prohibited articles accompanying restricted articles. A restricted article for importation into the United States shall not...

  11. 14 CFR 45.15 - Marking requirements for PMA articles, TSO articles, and Critical parts.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Marking requirements for PMA articles, TSO articles, and Critical parts. 45.15 Section 45.15 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... Articles § 45.15 Marking requirements for PMA articles, TSO articles, and Critical parts. (a) PMA...

  12. 7 CFR 319.37-12 - Prohibited articles accompanying restricted articles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Prohibited articles accompanying restricted articles... Stock, Plants, Roots, Bulbs, Seeds, and Other Plant Products 1,2 § 319.37-12 Prohibited articles accompanying restricted articles. A restricted article for importation into the United States shall not...

  13. 14 CFR 45.15 - Marking requirements for PMA articles, TSO articles, and Critical parts.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Marking requirements for PMA articles, TSO articles, and Critical parts. 45.15 Section 45.15 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... Articles § 45.15 Marking requirements for PMA articles, TSO articles, and Critical parts. (a) PMA...

  14. [PATHOGENIC MIKO,- AND MICROFLORA OF FRAXINUS EXCELSIOR IN PODOLYA UKRAINE].

    PubMed

    Kulbanska, I N; Goychuk, A F

    2015-01-01

    The article summarizes our research results of pathogenic myco- and microflora, as well as harmful entomofauna on European Ash. It is shown that the most common and harmful diseaseis tuberculosis (its causal agent--bacteria Pseudomonas syringae pv.savastanoi (Smith 1908), which affects trunks, branches, twigs and buds of European Ash. It describes a number of pathogens and representatives mikofitozov malicious entomofauna that by virtue of its activities significantly weaken the growth, development and underestimate the qualitative characteristics of wood European Ash. PMID:26638486

  15. Multiplex polymerase chain reaction tests for detection of pathogens associated with gastroenteritis.

    PubMed

    Zhang, Hongwei; Morrison, Scott; Tang, Yi-Wei

    2015-06-01

    A wide range of enteric pathogens can cause infectious gastroenteritis. Conventional diagnostic algorithms are time-consuming and often lack sensitivity and specificity. Advances in molecular technology have provided new clinical diagnostic tools. Multiplex polymerase chain reaction (PCR)-based testing has been used in gastroenterology diagnostics in recent years. This article presents a review of recent laboratory-developed multiplex PCR tests and current commercial multiplex gastrointestinal pathogen tests. It focuses on two commercial syndromic multiplex tests: Luminex xTAG Gastrointestinal Pathogen Panel and BioFire FilmArray gastrointestinal test. Multiplex PCR tests have shown superior sensitivity to conventional methods for detection of most pathogens.

  16. Mining biological networks from full-text articles.

    PubMed

    Czarnecki, Jan; Shepherd, Adrian J

    2014-01-01

    The study of biological networks is playing an increasingly important role in the life sciences. Many different kinds of biological system can be modelled as networks; perhaps the most important examples are protein-protein interaction (PPI) networks, metabolic pathways, gene regulatory networks, and signalling networks. Although much useful information is easily accessible in publicly databases, a lot of extra relevant data lies scattered in numerous published papers. Hence there is a pressing need for automated text-mining methods capable of extracting such information from full-text articles. Here we present practical guidelines for constructing a text-mining pipeline from existing code and software components capable of extracting PPI networks from full-text articles. This approach can be adapted to tackle other types of biological network.

  17. Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses

    PubMed Central

    Mogensen, Trine H.

    2009-01-01

    Summary: The innate immune system constitutes the first line of defense against invading microbial pathogens and relies on a large family of pattern recognition receptors (PRRs), which detect distinct evolutionarily conserved structures on pathogens, termed pathogen-associated molecular patterns (PAMPs). Among the PRRs, the Toll-like receptors have been studied most extensively. Upon PAMP engagement, PRRs trigger intracellular signaling cascades ultimately culminating in the expression of a variety of proinflammatory molecules, which together orchestrate the early host response to infection, and also is a prerequisite for the subsequent activation and shaping of adaptive immunity. In order to avoid immunopathology, this system is tightly regulated by a number of endogenous molecules that limit the magnitude and duration of the inflammatory response. Moreover, pathogenic microbes have developed sophisticated molecular strategies to subvert host defenses by interfering with molecules involved in inflammatory signaling. This review presents current knowledge on pathogen recognition through different families of PRRs and the increasingly complex signaling pathways responsible for activation of an inflammatory and antimicrobial response. Moreover, medical implications are discussed, including the role of PRRs in primary immunodeficiencies and in the pathogenesis of infectious and autoimmune diseases, as well as the possibilities for translation into clinical and therapeutic applications. PMID:19366914

  18. Lectins in human pathogenic fungi.

    PubMed

    Gallegos, Belém; Martínez, Ruth; Pérez, Laura; Del Socorro Pina, María; Perez, Eduardo; Hernández, Pedro

    2014-01-01

    Lectins are carbohydrate-binding proteins widely distributed in nature. They constitute a highly diverse group of proteins consisting of many different protein families that are, in general, structurally unrelated. In the last few years, mushroom and other fungal lectins have attracted wide attention due to their antitumour, antiproliferative and immunomodulatory activities. The present mini-review provides concise information about recent developments in understanding lectins from human pathogenic fungi. A bibliographic search was performed in the Science Direct and PubMed databases, using the following keywords "lectin", "fungi", "human" and "pathogenic". Lectins present in fungi have been classified; however, the role played by lectins derived from human pathogenic fungi in infectious processes remains uncertain; thus, this is a scientific field requiring more research. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012).

  19. Pathogen detection using engineered bacteriophages.

    PubMed

    Smartt, Abby E; Xu, Tingting; Jegier, Patricia; Carswell, Jessica J; Blount, Samuel A; Sayler, Gary S; Ripp, Steven

    2012-04-01

    Bacteriophages, or phages, are bacterial viruses that can infect a broad or narrow range of host organisms. Knowing the host range of a phage allows it to be exploited in targeting various pathogens. Applying phages for the identification of microorganisms related to food and waterborne pathogens and pathogens of clinical significance to humans and animals has a long history, and there has to some extent been a recent revival in these applications as phages have become more extensively integrated into novel detection, identification, and monitoring technologies. Biotechnological and genetic engineering strategies applied to phages are responsible for some of these new methods, but even natural unmodified phages are widely applicable when paired with appropriate innovative detector platforms. This review highlights the use of phages as pathogen detector interfaces to provide the reader with an up-to-date inventory of phage-based biodetection strategies.

  20. Molecular Soybean-Pathogen Interactions.

    PubMed

    Whitham, Steven A; Qi, Mingsheng; Innes, Roger W; Ma, Wenbo; Lopes-Caitar, Valéria; Hewezi, Tarek

    2016-08-01

    Soybean hosts a wide variety of pathogens that cause significant yield losses. The importance of soybean as a major oilseed crop has led to research focused on its interactions with pathogens, such as Soybean mosaic virus, Pseudomonas syringae, Phytophthora sojae, Phakopsora pachyrhizi, and Heterodera glycines. Pioneering work on soybean's interactions with these organisms, which represent the five major pathogen groups (viruses, bacteria, oomycetes, fungi, and nematodes), has contributed to our understanding of the molecular mechanisms underlying virulence and immunity. These mechanisms involve conserved and unique features that validate the need for research in both soybean and homologous model systems. In this review, we discuss identification of effectors and their functions as well as resistance gene-mediated recognition and signaling. We also point out areas in which model systems and recent advances in resources and tools have provided opportunities to gain deeper insights into soybean-pathogen interactions. PMID:27359370

  1. Lectins in human pathogenic fungi.

    PubMed

    Gallegos, Belém; Martínez, Ruth; Pérez, Laura; Del Socorro Pina, María; Perez, Eduardo; Hernández, Pedro

    2014-01-01

    Lectins are carbohydrate-binding proteins widely distributed in nature. They constitute a highly diverse group of proteins consisting of many different protein families that are, in general, structurally unrelated. In the last few years, mushroom and other fungal lectins have attracted wide attention due to their antitumour, antiproliferative and immunomodulatory activities. The present mini-review provides concise information about recent developments in understanding lectins from human pathogenic fungi. A bibliographic search was performed in the Science Direct and PubMed databases, using the following keywords "lectin", "fungi", "human" and "pathogenic". Lectins present in fungi have been classified; however, the role played by lectins derived from human pathogenic fungi in infectious processes remains uncertain; thus, this is a scientific field requiring more research. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). PMID:24270074

  2. 100 most cited articles in fracture surgery.

    PubMed

    Baldwin, Keith; Namdari, Surena; Donegan, Derek; Kovatch, Kevin; Ahn, Jaimo; Mehta, Samir

    2013-12-01

    Citation density is an important method by which to assess an article's impact on a field. We sought to identify the 100 most cited articles in fracture surgery, and highlight their characteristics. We used the ISI web of science's cited reference search to identify the most cited articles in orthopedic surgery. We then used multiple reviewers to identify the articles that pertained specifically to fracture surgery. Differences were resolved by discussion. We then characterized the level of evidence, decade of publication, type of design, and citation density for each article. All of the top 100 articles were published in English, the majority (69%) originated from the United States. Sixty-six percent of articles were clinical articles; the remainder were basic science. The most represented topic in the top 100 was hip fractures (12/100 articles). Over half of the clinical articles were level IV. Level of evidence was negatively correlated with date of publication. Citation number-based identification of important papers will help current practitioners gain insight into past and current trends in their respective fields and provides the foundation for further investigations.

  3. Impact of the UPR on the virulence of the plant fungal pathogen A. brassicicola

    PubMed Central

    Guillemette, Thomas; Calmes, Benoit; Simoneau, Philippe

    2014-01-01

    The fungal genus Alternaria contains many destructive plant pathogens, including Alternaria brassicicola, which causes black spot disease on a wide range of Brassicaceae plants and which is routinely used as a model necrotrophic pathogen in studies with Arabidopsis thaliana. During host infection, many fungal proteins that are critical for disease progression are processed in the endoplasmic reticulum (ER)/Golgi system and secreted in planta. The unfolded protein response (UPR) is an essential part of ER protein quality control that ensures efficient maturation of secreted and membrane-bound proteins in eukaryotes. This review highlights the importance of the UPR signaling pathway with respect to the ability of A. brassicicola to efficiently accomplish key steps of its pathogenic life cycle. Understanding the pathogenicity mechanisms that fungi uses during infection is crucial for the development of new antifungal therapies. Therefore the UPR pathway has emerged as a promising drug target for plant disease control. PMID:24189567

  4. Optimization of proteomic sample preparation procedures for comprehensive protein characterization of pathogenic systems

    SciTech Connect

    Brewer, Heather M.; Norbeck, Angela D.; Adkins, Joshua N.; Manes, Nathan P.; Ansong, Charles; Shi, Liang; Rikihisa, Yasuko; Kikuchi, Takane; Wong, Scott; Estep, Ryan D.; Heffron, Fred; Pasa-Tolic, Ljiljana; Smith, Richard D.

    2008-12-19

    The elucidation of critical functional pathways employed by pathogens and hosts during an infectious cycle is both challenging and central to our understanding of infectious diseases. In recent years, mass spectrometry-based proteomics has been used as a powerful tool to identify key pathogenesis-related proteins and pathways. Despite the analytical power of mass spectrometry-based technologies, samples must be appropriately prepared to characterize the functions of interest (e.g. host-response to a pathogen or a pathogen-response to a host). The preparation of these protein samples requires multiple decisions about what aspect of infection is being studied, and it may require the isolation of either host and/or pathogen cellular material.

  5. Pathogens in Dairy Farming: Source Characterization and Groundwater Impacts

    NASA Astrophysics Data System (ADS)

    Atwill, E. R.; Watanabe, N.; Li, X.; Hou, L.; Harter, T.; Bergamaschi, B.

    2007-12-01

    Intense animal husbandry is of growing concern as a potential contamination source of enteric pathogens as well as antibiotics. To assess the public health risk from pathogens and their hydrologic pathways, we hypothesize that the animal farm is not a homogeneous diffuse source, but that pathogen loading to the soil and, therefore, to groundwater varies significantly between the various management units of a farm. A dairy farm, for example, may include an area with calf hutches, corrals for heifers of various ages, freestalls and exercise yards for milking cows, separate freestalls for dry cows, a hospital barn, a yard for collection of solid manure, a liquid manure storage lagoon, and fields receiving various amounts of liquid and solid manure. Pathogen shedding and, hence, therapeutic and preventive pharmaceutical treatments vary between these management units. We are implementing a field reconnaissance program to determine the occurrence of three different pathogens ( E. coli, Salmonella, Campylobacter) and one indicator organism ( Enterococcus) at the ground-surface and in shallow groundwater of seven different management units on each of two farms, and in each of four seasons (spring/dry season, summer/irrigation season, fall/dry season, winter/rainy season). Initial results indicate that significant differences exist in the occurrence of these pathogens between management units and between organisms. These differences are weakly reflected in their occurrence in groundwater, despite the similarity of the shallow geologic environment across these sites. Our results indicate the importance of differentiating sources within a dairy farm and the importance of understanding subsurface transport processes for these pathogens.

  6. Protein Sialylation Regulates a Gene Expression Signature that Promotes Breast Cancer Cell Pathogenicity

    PubMed Central

    2016-01-01

    Many mechanisms have been proposed for how heightened aerobic glycolytic metabolism fuels cancer pathogenicity, but there are still many unexplored pathways. Here, we have performed metabolomic profiling to map glucose incorporation into metabolic pathways upon transformation of mammary epithelial cells by 11 commonly mutated human oncogenes. We show that transformation of mammary epithelial cells by oncogenic stimuli commonly shunts glucose-derived carbons into synthesis of sialic acid, a hexosamine pathway metabolite that is converted to CMP-sialic acid by cytidine monophosphate N-acetylneuraminic acid synthase (CMAS) as a precursor to glycoprotein and glycolipid sialylation. We show that CMAS knockdown leads to elevations in intracellular sialic acid levels, a depletion of cellular sialylation, and alterations in the expression of many cancer-relevant genes to impair breast cancer pathogenicity. Our study reveals the heretofore unrecognized role of sialic acid metabolism and protein sialylation in regulating the expression of genes that maintain breast cancer pathogenicity. PMID:27380425

  7. Protein Sialylation Regulates a Gene Expression Signature that Promotes Breast Cancer Cell Pathogenicity.

    PubMed

    Kohnz, Rebecca A; Roberts, Lindsay S; DeTomaso, David; Bideyan, Lara; Yan, Peter; Bandyopadhyay, Sourav; Goga, Andrei; Yosef, Nir; Nomura, Daniel K

    2016-08-19

    Many mechanisms have been proposed for how heightened aerobic glycolytic metabolism fuels cancer pathogenicity, but there are still many unexplored pathways. Here, we have performed metabolomic profiling to map glucose incorporation into metabolic pathways upon transformation of mammary epithelial cells by 11 commonly mutated human oncogenes. We show that transformation of mammary epithelial cells by oncogenic stimuli commonly shunts glucose-derived carbons into synthesis of sialic acid, a hexosamine pathway metabolite that is converted to CMP-sialic acid by cytidine monophosphate N-acetylneuraminic acid synthase (CMAS) as a precursor to glycoprotein and glycolipid sialylation. We show that CMAS knockdown leads to elevations in intracellular sialic acid levels, a depletion of cellular sialylation, and alterations in the expression of many cancer-relevant genes to impair breast cancer pathogenicity. Our study reveals the heretofore unrecognized role of sialic acid metabolism and protein sialylation in regulating the expression of genes that maintain breast cancer pathogenicity.

  8. Inactivation of conserved C. elegans genes engages pathogen- and xenobiotic-associated defenses.

    PubMed

    Melo, Justine A; Ruvkun, Gary

    2012-04-13

    The nematode C. elegans is attracted to nutritious bacteria and is repelled by pathogens and toxins. Here we show that RNAi and toxin-mediated disruption of core cellular activities, including translation, respiration, and protein turnover, stimulate behavioral avoidance of normally attractive bacteria. RNAi of these and other essential processes induces expression of detoxification and innate immune effectors, even in the absence of toxins or pathogens. Disruption of core processes in non-neuronal tissues was sufficient to stimulate aversion behavior, revealing a neuroendocrine axis of control that additionally required serotonergic and Jnk kinase signaling pathways. We propose that surveillance pathways overseeing core cellular activities allow animals to detect invading pathogens that deploy toxins and virulence factors to undermine vital host functions. Variation in cellular surveillance and endocrine pathways controlling behavior, detoxification, and immunity selected by past toxin or microbial interactions could underlie aberrant responses to foods, medicines, and microbes. PMID:22500807

  9. Method of producing silicon carbide articles

    DOEpatents

    Milewski, John V.

    1985-01-01

    A method of producing articles comprising reaction-bonded silicon carbide (SiC) and graphite (and/or carbon) is given. The process converts the graphite (and/or carbon) in situ to SiC, thus providing the capability of economically obtaining articles made up wholly or partially of SiC having any size and shape in which graphite (and/or carbon) can be found or made. When the produced articles are made of an inner graphite (and/or carbon) substrate to which SiC is reaction bonded, these articles distinguish SiC-coated graphite articles found in the prior art by the feature of a strong bond having a gradual (as opposed to a sharply defined) interface which extends over a distance of mils. A method for forming SiC whisker-reinforced ceramic matrices is also given. The whisker-reinforced articles comprise SiC whiskers which substantially retain their structural integrity.

  10. Strip of heat-recoverable articles

    SciTech Connect

    McLoughlin, R.H.; Kirkham, S.W.

    1985-01-29

    A strip of hollow heat-recoverable articles formed side-by-side by tear welding two lengths of polymeric material together at intervals so that individual articles may be torn off. A preferred method of making the strip involves cross-linking after the tear welding, heating the strip, and inflating the hollow articles to render them heat-recoverable by introducing pressure via an interconnecting passage formed for that purpose during the tear welding.

  11. Biaxially textured articles formed by powder metallurgy

    DOEpatents

    Goyal, Amit; Williams, Robert K.

    2001-01-01

    A biaxially textured alloy article comprises Ni powder and at least one powder selected from the group consisting of Cr, W, V, Mo, Cu, Al, Ce, YSZ, Y, Rare Earths, (RE), MgO, CeO.sub.2, and Y.sub.2 O.sub.3 ; compacted and heat treated, then rapidly recrystallized to produce a biaxial texture on the article. In some embodiments the alloy article further comprises electromagnetic or electro-optical devices and possesses superconducting properties.

  12. Tips for writing and publishing an article.

    PubMed

    Nahata, Milap C

    2008-02-01

    Peer reviewed publications are the primary source of important new information. This editorial provides tips for writing various sections of research papers, review articles, and case reports. Additional topics discussed include making decisions about authorship, selecting a journal for submission of an article, understanding the peer review process and expectations of editors and reviewers, and revising the article. Successful authors combine appropriate knowledge and experience, personal attributes, and effective collaborations to produce insightful and important contributions to the literature.

  13. The classic. Review article: Traffic accidents. 1966.

    PubMed

    Tscherne, H

    2013-09-01

    This Classic Article is a translation of the original work by Prof. Harald Tscherne, Der Straßenunfall [Traffic Accidents]. An accompanying biographical sketch of Prof. Tscherne is available at DOI 10.1007/s11999-013-3011-x . An online version of the original German article is available as supplemental material. The Classic Article is reproduced with permission from Brüder Hollinek & Co. GesmbH, Purkersdorf, Austria. The original article was published in Wien Med Wochenschr. 1966;116:105-108. (Translated by Dr. Roman Pfeifer.).

  14. Biaxially textured articles formed by powder metallurgy

    DOEpatents

    Goyal, Amit; Williams, Robert K.; Kroeger, Donald M.

    2004-09-14

    A biaxially textured alloy article having a magnetism less than pure Ni includes a rolled and annealed compacted and sintered powder-metallurgy preform article, the preform article having been formed from a powder mixture selected from the group of mixtures consisting of: at least 60 at % Ni powder and at least one of Cr powder, W powder, V powder, Mo powder, Cu powder, Al powder, Ce powder, YSZ powder, Y powder, Mg powder, and RE powder; the article having a fine and homogeneous grain structure; and having a dominant cube oriented {100}<100> orientation texture; and further having a Curie temperature less than that of pure Ni.

  15. Biaxially textured articles formed by powder metallurgy

    DOEpatents

    Goyal, Amit; Williams, Robert K.; Kroeger, Donald M.

    2005-05-10

    A biaxially textured alloy article having a magnetism less than pure Ni includes a rolled and annealed compacted and sintered powder-metallurgy preform article, the preform article having been formed from a powder mixture selected from the group of mixtures consisting of at least 60 at % Ni powder and at least one of Cr powder, W powder, V powder, Mo powder, Cu powder, Al powder, Ce powder, YSZ powder, Y powder, Mg powder, and RE powder; the article having a fine and homogeneous grain structure; and having a dominant cube oriented {100}<100> orientation texture; and further having a Curie temperature less than that of pure Ni.

  16. Biaxially textured articles formed by power metallurgy

    DOEpatents

    Goyal, Amit; Williams, Robert K.; Kroeger, Donald M.

    2003-08-26

    A biaxially textured alloy article having a magnetism less than pure Ni includes a rolled and annealed compacted and sintered powder-metallurgy preform article, the preform article having been formed from a powder mixture selected from the group of mixtures consisting of: at least 60 at % Ni powder and at least one of Cr powder, W powder, V powder, Mo powder, Cu powder, Al powder, Ce powder, YSZ powder, Y powder, Mg powder, and RE powder; the article having a fine and homogeneous grain structure; and having a dominant cube oriented {100}<100> orientation texture; and further having a Curie temperature less than that of pure Ni.

  17. Biaxially textured articles formed by powder metallurgy

    DOEpatents

    Goyal, Amit; Williams, Robert K.; Kroeger, Donald M.

    2003-07-29

    A biaxially textured alloy article having a magnetism less than pure Ni includes a rolled and annealed compacted and sintered powder-metallurgy preform article, the preform article having been formed from a powder mixture selected from the group of mixtures consisting of: at least 60 at % Ni powder and at least one of Cr powder, W powder, V powder, Mo powder, Cu powder, Al powder, Ce powder, YSZ powder, Y powder, Mg powder, and RE powder; the article having a fine and homogeneous grain structure; and having a dominant cube oriented {100}<100> orientation texture; and further having a Curie temperature less than that of pure Ni.

  18. Biaxially textured articles formed by powder metallurgy

    DOEpatents

    Goyal, Amit; Williams, Robert K.; Kroeger, Donald M.

    2003-08-26

    A biaxially textured alloy article having a magnetism less than pure Ni includes a rolled and annealed compacted and sintered powder-metallurgy preform article, the preform article having been formed from a powder mixture selected from the group of mixtures consisting of: at least 60 at % Ni powder and at least one of Cr powder, W powder, V powder, Mo powder, Cu powder, Al powder, Ce powder, YSZ powder, Y powder, Mg powder, and RE powder; the article having a fine and homogeneous grain structure; and having a dominant cube oriented {100}<100> orientation texture; and further having a Curie temperature less than that of pure Ni.

  19. Biaxially textured articles formed by powder metallurgy

    DOEpatents

    Goyal, Amit; Williams, Robert K.; Kroeger, Donald M.

    2005-01-25

    A biaxially textured alloy article having a magnetism less than pure Ni includes a rolled and annealed compacted and sintered powder-metallurgy preform article, the preform article having been formed from a powder mixture selected from the group of mixtures consisting of: at least 60 at % Ni powder and at least one of Cr powder, W powder, V powder, Mo powder, Cu powder, Al powder, Ce powder, YSZ powder, Y powder, Mg powder, and RE powder; the article having a fine and homogeneous grain structure; and having a dominant cube oriented {100}<100> orientation texture; and further having a Curie temperature less than that of pure Ni.

  20. Biaxially textured articles formed by powder metallurgy

    DOEpatents

    Goval, Amit; Williams, Robert K.; Kroeger, Donald M.

    2005-06-07

    A biaxially textured alloy article having a magnetism less than pure Ni includes a rolled and annealed compacted and sintered powder-metallurgy preform article, the preform article having been formed from a powder mixture selected from the group of mixtures consisting of: at least 60 at % Ni powder and at least one of Cr powder, W powder, V powder, Mo powder, Cu powder, Al powder, Ce powder, YSZ powder, Y powder, Mg powder, and RE powder; the article having a fine and homogeneous grain structure; and having a dominant cube oriented {100}<100> orientation texture; and further having a Curie temperature less than that of pure Ni.

  1. Biaxially textured articles formed by powder metallurgy

    DOEpatents

    Goyal, Amit; Williams, Robert K.; Kroeger, Donald M.

    2003-08-05

    A biaxially textured alloy article having a magnetism less than pure Ni includes a rolled and annealed compacted and sintered powder-metallurgy preform article, the preform article having been formed from a powder mixture selected from the group of ternary mixtures consisting of: Ni powder, Cu powder, and Al powder, Ni powder, Cr powder, and Al powder; Ni powder, W powder and Al powder; Ni powder, V powder, and Al powder; Ni powder, Mo powder, and Al powder; the article having a fine and homogeneous grain structure; and having a dominant cube oriented {100}<100> orientation texture; and further having a Curie temperature less than that of pure Ni.

  2. Biaxially textured articles formed by powder metallurgy

    DOEpatents

    Goyal, Amit; Williams, Robert K.; Kroeger, Donald M.

    2003-08-19

    A biaxially textured alloy article having a magnetism less than pure Ni includes a rolled and annealed compacted and sintered powder-metallurgy preform article, the preform article having been formed from a powder mixture selected from the group of mixtures consisting of: at least 60 at % Ni powder and at least one of Cr powder, W powder, V powder, Mo powder, Cu powder, Al powder, Ce powder, YSZ powder, Y powder, Mg powder, and RE powder; the article having a fine and homogeneous grain structure; and having a dominant cube oriented {100}<100> orientation texture; and further having a Curie temperature less than that of pure Ni.

  3. Biaxially textured articles formed by powder metallurgy

    DOEpatents

    Goyal, Amit; Williams, Robert K.; Kroeger, Donald M.

    2004-09-28

    A biaxially textured alloy article having a magnetism less than pure Ni includes a rolled and annealed compacted and sintered powder-metallurgy preform article, the preform article having been formed from a powder mixture selected from the group of mixtures consisting of: at least 60 at % Ni powder and at least one of Cr powder, W powder, V powder, Mo powder, Cu powder, Al powder, Ce powder, YSZ powder, Y powder, Mg powder, and RE powder; the article having a fine and homogeneous grain structure; and having a dominant cube oriented {100}<100> orientation texture; and further having a Curie temperature less than that of pure Ni.

  4. Volatile Metabolites of Pathogens: A Systematic Review

    PubMed Central

    Bos, Lieuwe D. J.; Sterk, Peter J.; Schultz, Marcus J.

    2013-01-01

    Ideally, invading bacteria are detected as early as possible in critically ill patients: the strain of morbific pathogens is identified rapidly, and antimicrobial sensitivity is known well before the start of new antimicrobial therapy. Bacteria have a distinct metabolism, part of which results in the production of bacteria-specific volatile organic compounds (VOCs), which might be used for diagnostic purposes. Volatile metabolites can be investigated directly in exhaled air, allowing for noninvasive monitoring. The aim of this review is to provide an overview of VOCs produced by the six most abundant and pathogenic bacteria in sepsis, including Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Such VOCs could be used as biological markers in the diagnostic approach of critically ill patients. A systematic review of existing literature revealed 31 articles. All six bacteria of interest produce isopentanol, formaldehyde, methyl mercaptan, and trimethylamine. Since humans do not produce these VOCs, they could serve as biological markers for presence of these pathogens. The following volatile biomarkers were found for identification of specific strains: isovaleric acid and 2-methyl-butanal for Staphylococcus aureus; 1-undecene, 2,4-dimethyl-1-heptane, 2-butanone, 4-methyl-quinazoline, hydrogen cyanide, and methyl thiocyanide for Pseudomonas aeruginosa; and methanol, pentanol, ethyl acetate, and indole for Escherichia coli. Notably, several factors that may effect VOC production were not controlled for, including used culture media, bacterial growth phase, and genomic variation within bacterial strains. In conclusion, VOCs produced by bacteria may serve as biological markers for their presence. Goal-targeted studies should be performed to identify potential sets of volatile biological markers and evaluate the diagnostic accuracy of these markers in critically ill patients. PMID

  5. Role of care pathways in interprofessional teamwork.

    PubMed

    Scaria, Minimol Kulakkottu

    2016-08-24

    Cohesive interprofessional teamwork is essential to successful healthcare services. Interprofessional teamwork is the means by which different healthcare professionals - with diverse knowledge, skills and talents - collaborate to achieve a common goal. Several interventions are available to improve teamwork in the healthcare setting. This article explores the role of care pathways in improving interprofessional teamwork. Care pathways enhance teamwork by promoting coordination, collaboration, communication and decision making to achieve optimal healthcare outcomes. They result in improved staff knowledge, communication, documentation and interprofessional relations. Care pathways also contribute to patient-centred care and increase patient satisfaction.

  6. The Evolution of the Wnt Pathway

    PubMed Central

    Holstein, Thomas W.

    2012-01-01

    Wnt genes are important regulators of embryogenesis and cell differentiation in vertebrates and insects. New data revealed by comparative genomics have now shown that members of the Wnt signaling pathway can be found in all clades of metazoans, but not in fungi, plants, or unicellular eukaryotes. This article focuses on new data from recent genomic analyses of several basal metazoan organisms, providing evidence that the Wnt pathway was a primordial signaling pathway during evolution. The formation of a Wnt signaling center at the site of gastrulation was instrumental for the formation of a primary, anterior–posterior body axis, which can be traced throughout animal evolution. PMID:22751150

  7. Role of care pathways in interprofessional teamwork.

    PubMed

    Scaria, Minimol Kulakkottu

    2016-08-24

    Cohesive interprofessional teamwork is essential to successful healthcare services. Interprofessional teamwork is the means by which different healthcare professionals - with diverse knowledge, skills and talents - collaborate to achieve a common goal. Several interventions are available to improve teamwork in the healthcare setting. This article explores the role of care pathways in improving interprofessional teamwork. Care pathways enhance teamwork by promoting coordination, collaboration, communication and decision making to achieve optimal healthcare outcomes. They result in improved staff knowledge, communication, documentation and interprofessional relations. Care pathways also contribute to patient-centred care and increase patient satisfaction. PMID:27641591

  8. Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1.

    PubMed

    Keestra, A Marijke; Winter, Maria G; Auburger, Josef J; Frässle, Simon P; Xavier, Mariana N; Winter, Sebastian E; Kim, Anita; Poon, Victor; Ravesloot, Mariëtta M; Waldenmaier, Julian F T; Tsolis, Renée M; Eigenheer, Richard A; Bäumler, Andreas J

    2013-04-11

    Our innate immune system distinguishes microbes from self by detecting conserved pathogen-associated molecular patterns. However, these are produced by all microbes, regardless of their pathogenic potential. To distinguish virulent microbes from those with lower disease-causing potential the innate immune system detects conserved pathogen-induced processes, such as the presence of microbial products in the host cytosol, by mechanisms that are not fully resolved. Here we show that NOD1 senses cytosolic microbial products by monitoring the activation state of small Rho GTPases. Activation of RAC1 and CDC42 by bacterial delivery or ectopic expression of SopE, a virulence factor of the enteric pathogen Salmonella, triggered the NOD1 signalling pathway, with consequent RIP2 (also known as RIPK2)-mediated induction of NF-κB-dependent inflammatory responses. Similarly, activation of the NOD1 signalling pathway by peptidoglycan required RAC1 activity. Furthermore, constitutively active forms of RAC1, CDC42 and RHOA activated the NOD1 signalling pathway. Our data identify the activation of small Rho GTPases as a pathogen-induced process sensed through the NOD1 signalling pathway. PMID:23542589

  9. Structural Basis for the Function of Complement Component C4 within the Classical and Lectin Pathways of Complement.

    PubMed

    Mortensen, Sofia; Kidmose, Rune T; Petersen, Steen V; Szilágyi, Ágnes; Prohászka, Zoltan; Andersen, Gregers R

    2015-06-01

    Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During activation of complement, its major fragment C4b becomes covalently attached to the surface of pathogens and altered self-tissue, where it acts as an opsonin marking the surface for removal. Moreover, C4b provides a platform for assembly of the proteolytically active convertases that mediate downstream complement activation by cleavage of C3 and C5. In this article, we present the crystal and solution structures of the 195-kDa C4b. Our results provide the molecular details of the rearrangement accompanying C4 cleavage and suggest intramolecular flexibility of C4b. The conformations of C4b and its paralogue C3b are shown to be remarkably conserved, suggesting that the convertases from the classical and alternative pathways are likely to share their overall architecture and mode of substrate recognition. We propose an overall molecular model for the classical pathway C5 convertase in complex with C5, suggesting that C3b increases the affinity for the substrate by inducing conformational changes in C4b rather than a direct interaction with C5. C4b-specific features revealed by our structural studies are probably involved in the assembly of the classical pathway C3/C5 convertases and C4b binding to regulators.

  10. Article retracted, but the message lives on.

    PubMed

    Greitemeyer, Tobias

    2014-04-01

    The retraction of an original article aims to ensure that readers are alerted to the fact that the findings are not trustworthy. However, the present research suggests that individuals still believe in the findings of an article even though they were later told that the data were fabricated and that the article was retracted. Participants in a debriefing condition and a no-debriefing condition learned about the scientific finding of an empirical article, whereas participants in a control condition did not. Afterward, participants in the debriefing condition were told that the article had been retracted because of fabricated data. Results showed that participants in the debriefing condition were less likely to believe in the findings than participants in the no-debriefing condition but were more likely to believe in the findings than participants in the control condition, suggesting that individuals do adjust their beliefs in the perceived truth of a scientific finding after debriefing-but insufficiently. Mediational analyses revealed that the availability of generated causal arguments underlies belief perseverance. These results suggest that a retraction note of an empirical article in a scientific journal is not sufficient to ensure that readers of the original article no longer believe in the article's conclusions.

  11. 48 CFR 425.104 - Nonavailable articles.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Nonavailable articles. 425.104 Section 425.104 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Buy American Act-Supplies 425.104 Nonavailable articles. Information...

  12. 48 CFR 425.104 - Nonavailable articles.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Nonavailable articles. 425.104 Section 425.104 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Buy American Act-Supplies 425.104 Nonavailable articles. Information...

  13. Teaching Critical Appraisal of Articles on Psychopharmacology

    ERIC Educational Resources Information Center

    Mohr, Pavel; Hoschl, Cyril; Volavka, Jan

    2012-01-01

    Objective: Psychiatrists and other physicians sometimes read publications superficially, relying excessively on abstracts. The authors addressed this problem by teaching critical appraisal of individual articles. Method: The authors developed a 23-item appraisal instrument to assess articles in the area of psychopharmacology. The results were…

  14. 48 CFR 425.104 - Nonavailable articles.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Nonavailable articles. 425.104 Section 425.104 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Buy American Act-Supplies 425.104 Nonavailable articles. Information...

  15. 48 CFR 425.104 - Nonavailable articles.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Nonavailable articles. 425.104 Section 425.104 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Buy American Act-Supplies 425.104 Nonavailable articles. Information...

  16. Suggestions for Structuring a Research Article

    ERIC Educational Resources Information Center

    Klein, James D.; Reiser, Robert A.

    2014-01-01

    Researchers often experience difficulty as they attempt to prepare journal articles that describe their work. The purpose of this article is to provide researchers in the field of education with a series of suggestions as to how to clearly structure each section of a research manuscript that they intend to submit for publication in a scholarly…

  17. 48 CFR 425.104 - Nonavailable articles.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Nonavailable articles. 425.104 Section 425.104 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Buy American Act-Supplies 425.104 Nonavailable articles. Information...

  18. Method of manufacturing ceramic shaped articles

    NASA Technical Reports Server (NTRS)

    Inoue, K.

    1983-01-01

    A method of manufacturing ceramic shaped articles, wherein tapes of ceramic powder material in mixture with a binder material and special additives are shaped and then articles are stamped out from said tapes and sintered in a sintering furnace is described.

  19. Gymnastics. Selected Coaching Articles. Officiating Techniques.

    ERIC Educational Resources Information Center

    Niccollai, Rene, Ed.

    This publication is a compilation of articles directed toward providing a better understanding of the various aspects of gymnastics and to promote a greater proficiency among educators, coaches, judges, leaders, and participants of sport programs for girls and women. Articles in the first section cover the technical aspects of gymnastics: (1)…

  20. Periodical Articles of School Historical Interest.

    ERIC Educational Resources Information Center

    Norgaard, Ellen

    1981-01-01

    This translation from the "Yearbook of Danish School History" summarizes nine articles from Danish educational journals. Six describe past changes in primary education, teacher training and salaries, the Greenland schools, and the definitions of deviant behavior. The remaining three articles present background information on current problems. (AM)

  1. Valued Youth Anthology: Articles on Dropout Prevention.

    ERIC Educational Resources Information Center

    Intercultural Development Research Association, San Antonio, TX.

    This document contains, in chronological order, all articles related to dropouts that have appeared in the Intercultural Development Research Association (IDRA) Newsletter from 1986 to 1989. The articles are: (1) "The Prevention and Recovery of Dropouts: An Action Agenda" (Robledo); (2) "Coca Cola Valued Youth Partnership Program Results of Second…

  2. Understanding Student Article Retrieval Behaviors: Instructional Implications

    ERIC Educational Resources Information Center

    Cook-Cottone, Catherine P.; Dutt-Doner, Karen; Schoen, David

    2005-01-01

    This study evaluates the use of full-text databases amongst 425 undergraduate and graduate students in western New York. A review of literature implicated convenience, time issues, article retrieval option knowledge, and the appreciation and understanding of research article quality as potential predictors of full-text reliance. These variables…

  3. Improved zein articles using polyethylenemaleic anhydride

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Developing corn protein (zein) articles with improved physical properties and solvent resistance will have a beneficial impact on companies that use corn. The effect of using the crosslinking reagent polyethylenemaleic anhydride (PEMA) on the properties and solubility of zein articles were studied. ...

  4. Method for fabricating boron carbide articles

    DOEpatents

    Ardary, Zane L.; Reynolds, Carl D.

    1980-01-01

    The present invention is directed to the fabrication of boron carbide articles having length-to-diameter or width ratios greater than 2 to 1. The process of the present invention is practiced by the steps comprising hot pressing boron carbide powder into article segments or portions in which the segments have a length-to-diameter or width ratio less than 1.5, aligning a plurality of the initially hot-pressed segments in a hot-pressing die with the end surfaces of the segments placed in intimate contact with one another, and then hot pressing the aligned segments into an article of the desired configuration. The resulting article exhibits essentially uniform density throughout the structure with the bonds between the segments being equivalent in hardness, strength, and density to the remainder of the article.

  5. Manned remote work station development article

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The two prime objectives of the Manned Remote Work Station (MRWS) Development Article Study are to first, evaluate the MRWS flight article roles and associated design concepts for fundamental requirements and embody key technology developments into a simulation program; and to provide detail manufacturing drawings and schedules for a simulator development test article. An approach is outlined which establishes flight article requirements based on past studies of Solar Power Satellite, orbital construction support equipments, construction bases and near term shuttle operations. Simulation objectives are established for those technology issues that can best be addressed on a simulator. Concepts for full-scale and sub-scale simulators are then studied to establish an overall approach to studying MRWS requirements. Emphasis then shifts to design and specification of a full-scale development test article.

  6. The genus Aeromonas: taxonomy, pathogenicity, and infection.

    PubMed

    Janda, J Michael; Abbott, Sharon L

    2010-01-01

    Over the past decade, the genus Aeromonas has undergone a number of significant changes of practical importance to clinical microbiologists and scientists alike. In parallel with the molecular revolution in microbiology, several new species have been identified on a phylogenetic basis, and the genome of the type species, A. hydrophila ATCC 7966, has been sequenced. In addition to established disease associations, Aeromonas has been shown to be a significant cause of infections associated with natural disasters (hurricanes, tsunamis, and earthquakes) and has been linked to emerging or new illnesses, including near-drowning events, prostatitis, and hemolytic-uremic syndrome. Despite these achievements, issues still remain regarding the role that Aeromonas plays in bacterial gastroenteritis, the extent to which species identification should be attempted in the clinical laboratory, and laboratory reporting of test results from contaminated body sites containing aeromonads. This article provides an extensive review of these topics, in addition to others, such as taxonomic issues, microbial pathogenicity, and antimicrobial resistance markers.

  7. Cell biology of Zymoseptoria tritici: Pathogen cell organization and wheat infection

    PubMed Central

    Steinberg, Gero

    2015-01-01

    Cell biological research in the wheat pathogen Zymoseptoria tritici (formerly Mycosphaerella graminicola) has led to a good understanding of the histology of the infection process. Expression profiling and bioinformatic approaches, combined with molecular studies on signaling pathways, effectors and potential necrosis factors provides first insight into the complex interplay between the host and the pathogen. Cell biological studies will help to further our understanding of the infection strategy of the fungus. The cellular organization and intracellular dynamics of the fungus itself is largely unexplored. Insight into essential cellular processes within the pathogen will expand our knowledge of the basic biology of Z. tritici, thereby providing putative new anti-fungal targets. PMID:26092785

  8. Characterization of Pathogenicity, Virulence and Host-Pathogen Interractions

    SciTech Connect

    Krishnan, A; Folta, P

    2006-07-27

    The threats of bio-terrorism and newly emerging infectious diseases pose serious challenges to the national security infrastructure. Rapid detection and diagnosis of infectious disease in human populations, as well as characterizing pathogen biology, are critical for reducing the morbidity and mortality associated with such threats. One of the key challenges in managing an infectious disease outbreak, whether through natural causes or acts of overt terrorism, is detection early enough to initiate effective countermeasures. Much recent attention has been directed towards the utility of biomarkers or molecular signatures that result from the interaction of the pathogen with the host for improving our ability to diagnose and mitigate the impact of a developing infection during the time window when effective countermeasures can be instituted. Host responses may provide early signals in blood even from localized infections. Multiple innate and adaptive immune molecules, in combination with other biochemical markers, may provide disease-specific information and new targets for countermeasures. The presence of pathogen specific markers and an understanding of the molecular capabilities and adaptations of the pathogen when it interacts with its host may likewise assist in early detection and provide opportunities for targeting countermeasures. An important question that needs to be addressed is whether these molecular-based approaches will prove useful for early diagnosis, complement current methods of direct agent detection, and aid development and use of countermeasures. Lawrence Livermore National Laboratory (LLNL) will host a workshop to explore the utility of host- and pathogen-based molecular diagnostics, prioritize key research issues, and determine the critical steps needed to transition host-pathogen research to tools that can be applied towards a more effective national bio-defense strategy. The workshop will bring together leading researchers/scientists in the

  9. Finding the sweet spot: how human fungal pathogens acquire and turn the sugar inositol against their hosts.

    PubMed

    Xue, Chaoyang

    2015-03-03

    Inositol is an essential nutrient with important structural and signaling functions in eukaryotes. Its role in microbial pathogenesis has been reported in fungi, protozoans, and eubacteria. In a recent article, Porollo et al. [mBio 5(6):e01834-14, 2014, doi:10.1128/mBio.01834-14] demonstrated the importance of inositol metabolism in the development and viability of Pneumocystis species--obligate fungal pathogens that remain unculturable in vitro. To understand their obligate nature, the authors used innovative comparative genomic approaches and discovered that Pneumocystis spp. are inositol auxotrophs due to the lack of inositol biosynthetic enzymes and that inositol insufficiency is a contributing factor preventing fungal growth in vitro. This work is in accord with other studies suggesting that inositol plays a conserved role in microbial pathogenesis. Inositol uptake and metabolism therefore may represent novel antimicrobial drug targets. Using comparative genomics to analyze metabolic pathways offers a powerful tool to gain new insights into nutrient utilization in microbes, especially obligate pathogens.

  10. Contributions of host cellular trafficking and organization to the outcomes of plant-pathogen interactions.

    PubMed

    Underwood, William

    2016-08-01

    In recent years it has become increasingly apparent that dynamic changes in protein localization, membrane trafficking pathways, and cellular organization play a major role in determining the outcome of interactions between plants and pathogenic microorganisms. Plants have evolved sophisticated perception systems to recognize the presence of potentially pathogenic microorganisms via the detection of non-self or modified-self elicitor molecules, pathogen virulence factors, or the activities of such virulence factors. Dynamic changes to host cellular organization and membrane trafficking pathways play pivotal roles in detection and signaling by plant immune receptors and are vital for the execution of spatially targeted defense responses to thwart invasion by potential pathogens. Conversely, from the perspective of the pathogen, the ability to manipulate plant cellular organization and trafficking processes to establish infection structures and deliver virulence factors is a major determinant of pathogen success. This review summarizes selected topics that illustrate how dynamic changes in host cellular trafficking and organization shape the outcomes of diverse plant-pathogen interactions and addresses ways in which our rapidly expanding knowledge of the cell biological processes that contribute to immunity or infection may influence efforts to improve plant disease resistance. PMID:27216829

  11. Contributions of host cellular trafficking and organization to the outcomes of plant-pathogen interactions.

    PubMed

    Underwood, William

    2016-08-01

    In recent years it has become increasingly apparent that dynamic changes in protein localization, membrane trafficking pathways, and cellular organization play a major role in determining the outcome of interactions between plants and pathogenic microorganisms. Plants have evolved sophisticated perception systems to recognize the presence of potentially pathogenic microorganisms via the detection of non-self or modified-self elicitor molecules, pathogen virulence factors, or the activities of such virulence factors. Dynamic changes to host cellular organization and membrane trafficking pathways play pivotal roles in detection and signaling by plant immune receptors and are vital for the execution of spatially targeted defense responses to thwart invasion by potential pathogens. Conversely, from the perspective of the pathogen, the ability to manipulate plant cellular organization and trafficking processes to establish infection structures and deliver virulence factors is a major determinant of pathogen success. This review summarizes selected topics that illustrate how dynamic changes in host cellular trafficking and organization shape the outcomes of diverse plant-pathogen interactions and addresses ways in which our rapidly expanding knowledge of the cell biological processes that contribute to immunity or infection may influence efforts to improve plant disease resistance.

  12. Update on the proteomics of major arthropod vectors of human and animal pathogens.

    PubMed

    Patramool, Sirilaksana; Choumet, Valérie; Surasombatpattana, Pornapat; Sabatier, Laurence; Thomas, Frédéric; Thongrungkiat, Supatra; Rabilloud, Thierry; Boulanger, Nathalie; Biron, David G; Missé, Dorothée

    2012-12-01

    Vector-borne diseases (VBDs) are defined as infectious diseases of humans and animals caused by pathogenic agents such as viruses, protists, bacteria, and helminths transmitted by the bite of blood-feeding arthropod (BFA) vectors. VBDs represent a major public health threat in endemic areas, generally subtropical zones, and many are considered to be neglected diseases. Genome sequencing of some arthropod vectors as well as modern proteomic and genomic technologies are expanding our knowledge of arthropod-pathogen interactions. This review describes the proteomic approaches that have been used to investigate diverse biological questions about arthropod vectors, including the interplay between vectors and pathogens. Proteomic studies have identified proteins and biochemical pathways that may be involved in molecular crosstalk in BFA-pathogen associations. Future work can build upon this promising start and functional analyses coupled with interactome bioassays will be carried out to investigate the role of candidate peptides and proteins in BFA-human pathogen associations. Dissection of the host-pathogen interactome will be key to understanding the strategies and biochemical pathways used by BFAs to cope with pathogens.

  13. Compositions and methods for pathogen transport

    DOEpatents

    El-Etr, Sahar; Farquar, George R.

    2016-01-26

    This disclosure provides a method for transporting a pathogen under ambient conditions, by culturing the pathogen with an amoeba under conditions that favor the incorporation of the pathogen into a trophozoite, starving the amoeba until it encysts, then culturing under conditions that favor conversion of the amoeba back to a trophozoite. In one aspect, the conditions that favor incorporation of the pathogen into the cyst of the amoeba comprises contacting the pathogen with the amoeba in an iron rich environment. Virus and/or bacteria are pathogens that can be transported by the disclosed method. Amoeba that are useful in the disclosed methods include, without limitation Acanthamoeba castellanii, Hartmannella vermiformis and Naegleria gruberi. The disclosed methods have utility in: transporting pathogens from military field hospitals and clinics to the laboratory; transporting pathogens from global satellite laboratories to clinical laboratories; long term storage of pathogens; enriching contaminated patient samples for pathogens of interest; biosurveillance and detection efforts.

  14. Pathogen evolution and the immunological niche

    PubMed Central

    Cobey, Sarah

    2014-01-01

    Host immunity is a major driver of pathogen evolution and thus a major determinant of pathogen diversity. Explanations for pathogen diversity traditionally assume simple interactions between pathogens and the immune system, a view encapsulated by the susceptible–infected–recovered (SIR) model. However, there is growing evidence that the complexity of many host–pathogen interactions is dynamically important. This revised perspective requires broadening the definition of a pathogen's immunological phenotype, or what can be thought of as its immunological niche. After reviewing evidence that interactions between pathogens and host immunity drive much of pathogen evolution, I introduce the concept of a pathogen's immunological phenotype. Models that depart from the SIR paradigm demonstrate the utility of this perspective and show that it is particularly useful in understanding vaccine-induced evolution. This paper highlights questions in immunology, evolution, and ecology that must be answered to advance theories of pathogen diversity. PMID:25040161

  15. Directionally solidified article with weld repair

    NASA Technical Reports Server (NTRS)

    Smashey, Russell W. (Inventor); Snyder, John H. (Inventor); Borne, Bruce L. (Inventor)

    2003-01-01

    A directionally solidified nickel-base superalloy article has a defect therein extending parallel to the solidification direction. The article is repaired by removing any foreign matter present in the defect, and then heating the article to a repair temperature of from about 60 to about 98 percent of the solidus temperature of the base material in a chamber containing a protective gas that inhibits oxidation of the base material. The defect is filled with a filler metal while maintaining the article at the repair temperature. The filling is accomplished by providing a source of the filler metal of substantially the same composition as the base material of the directionally solidified article, and melting the filler metal into the defect progressively while moving the source of the filler metal relative to the article in a direction parallel to the solidification direction. Optionally, additional artificial heat extraction is accomplished in a heat-flow direction that is within about 45 degrees of the solidification direction, as the filler metal solidifies within the defect. The article may thereafter be heat treated.

  16. Weld repair of directionally solidified articles

    NASA Technical Reports Server (NTRS)

    Smashey, Russell W. (Inventor); Snyder, John H. (Inventor); Borne, Bruce L. (Inventor)

    2002-01-01

    A directionally solidified nickel-base superalloy article has a defect therein extending parallel to the solidification direction. The article is repaired by removing any foreign matter present in the defect, and then heating the article to a repair temperature of from about 60 to about 98 percent of the solidus temperature of the base material in a chamber containing a protective gas that inhibits oxidation of the base material. The defect is filled with a filler metal while maintaining the article at the repair temperature. The filling is accomplished by providing a source of the filler metal of substantially the same composition as the base material of the directionally solidified article, and melting the filler metal into the defect progressively while moving the source of the filler metal relative to the article in a direction parallel to the solidification direction. Optionally, additional artificial heat extraction is accomplished in a heat-flow direction that is within about 45 degrees of the solidification direction, as the filler metal solidifies within the defect. The article may thereafter be heat treated.

  17. Infectious pathogens and bronchiolitis outcomes.

    PubMed

    Hasegawa, Kohei; Mansbach, Jonathan M; Camargo, Carlos A

    2014-07-01

    Bronchiolitis is a common early childhood illness and an important cause of morbidity, it is the number one cause of hospitalization among US infants. Bronchiolitis is also an active area of research, and recent studies have advanced our understanding of this illness. Although it has long been the conventional wisdom that the infectious etiology of bronchiolitis does not affect outcomes, a growing number of studies have linked specific pathogens of bronchiolitis (e.g., rhinovirus) to short- and long-term outcomes, such as future risk of developing asthma. The authors review the advent of molecular diagnostic techniques that have demonstrated diverse pathogens in bronchiolitis, and they review recent studies on the complex link between infectious pathogens of bronchiolitis and the development of childhood asthma.

  18. The Main Aeromonas Pathogenic Factors

    PubMed Central

    Tomás, J. M.

    2012-01-01

    The members of the Aeromonas genus are ubiquitous, water-borne bacteria. They have been isolated from marine waters, rivers, lakes, swamps, sediments, chlorine water, water distribution systems, drinking water and residual waters; different types of food, such as meat, fish, seafood, vegetables, and processed foods. Aeromonas strains are predominantly pathogenic to poikilothermic animals, and the mesophilic strains are emerging as important pathogens in humans, causing a variety of extraintestinal and systemic infections as well as gastrointestinal infections. The most commonly described disease caused by Aeromonas is the gastroenteritis; however, no adequate animal model is available to reproduce this illness caused by Aeromonas. The main pathogenic factors associated with Aeromonas are: surface polysaccharides (capsule, lipopolysaccharide, and glucan), S-layers, iron-binding systems, exotoxins and extracellular enzymes, secretion systems, fimbriae and other nonfilamentous adhesins, motility and flagella. PMID:23724321

  19. Proteomics of Plant Pathogenic Fungi

    PubMed Central

    González-Fernández, Raquel; Prats, Elena; Jorrín-Novo, Jesús V.

    2010-01-01

    Plant pathogenic fungi cause important yield losses in crops. In order to develop efficient and environmental friendly crop protection strategies, molecular studies of the fungal biological cycle, virulence factors, and interaction with its host are necessary. For that reason, several approaches have been performed using both classical genetic, cell biology, and biochemistry and the modern, holistic, and high-throughput, omic techniques. This work briefly overviews the tools available for studying Plant Pathogenic Fungi and is amply focused on MS-based Proteomics analysis, based on original papers published up to December 2009. At a methodological level, different steps in a proteomic workflow experiment are discussed. Separate sections are devoted to fungal descriptive (intracellular, subcellular, extracellular) and differential expression proteomics and interactomics. From the work published we can conclude that Proteomics, in combination with other techniques, constitutes a powerful tool for providing important information about pathogenicity and virulence factors, thus opening up new possibilities for crop disease diagnosis and crop protection. PMID:20589070

  20. Xylella Genomics and Bacterial Pathogenicity to Plants

    PubMed Central

    Dow, J. M.

    2000-01-01

    Xylella fastidiosa, a pathogen of citrus, is the first plant pathogenic bacterium for which the complete genome sequence has been published. Inspection of the sequence reveals high relatedness to many genes of other pathogens, notably Xanthomonas campestris. Based on this, we suggest that Xylella possesses certain easily testable properties that contribute to pathogenicity. We also present some general considerations for deriving information on pathogenicity from bacterial genomics. PMID:11119303

  1. Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus

    PubMed Central

    Leonardi, William; Zilbermintz, Leeor; Cheng, Luisa W.; Zozaya, Josue; Tran, Sharon H.; Elliott, Jeffrey H.; Polukhina, Kseniya; Manasherob, Robert; Li, Amy; Chi, Xiaoli; Gharaibeh, Dima; Kenny, Tara; Zamani, Rouzbeh; Soloveva, Veronica; Haddow, Andrew D.; Nasar, Farooq; Bavari, Sina; Bassik, Michael C.; Cohen, Stanley N.; Levitin, Anastasia; Martchenko, Mikhail

    2016-01-01

    Diverse pathogenic agents often utilize overlapping host networks, and hub proteins within these networks represent attractive targets for broad-spectrum drugs. Using bacterial toxins, we describe a new approach for discovering broad-spectrum therapies capable of inhibiting host proteins that mediate multiple pathogenic pathways. This approach can be widely used, as it combines genetic-based target identification with cell survival-based and protein function-based multiplex drug screens, and concurrently discovers therapeutic compounds and their protein targets. Using B-lymphoblastoid cells derived from the HapMap Project cohort of persons of African, European, and Asian ancestry we identified host caspases as hub proteins that mediate the lethality of multiple pathogenic agents. We discovered that an approved drug, Bithionol, inhibits host caspases and also reduces the detrimental effects of anthrax lethal toxin, diphtheria toxin, cholera toxin, Pseudomonas aeruginosa exotoxin A, Botulinum neurotoxin, ricin, and Zika virus. Our study reveals the practicality of identifying host proteins that mediate multiple disease pathways and discovering broad-spectrum therapies that target these hub proteins. PMID:27686742

  2. Plants, plant pathogens, and microgravity--a deadly trio

    NASA Technical Reports Server (NTRS)

    Leach, J. E.; Ryba-White, M.; Sun, Q.; Wu, C. J.; Hilaire, E.; Gartner, C.; Nedukha, O.; Kordyum, E.; Keck, M.; Leung, H.; Guikema, J. A.

    2001-01-01

    Plants grown in spaceflight conditions are more susceptible to colonization by plant pathogens. The underlying causes for this enhanced susceptibility are not known. Possibly the formation of structural barriers and the activation of plant defense response components are impaired in spaceflight conditions. Either condition would result from altered gene expression of the plant. Because of the tools available, past studies focused on a few physiological responses or biochemical pathways. With recent advances in genomics research, new tools, including microarray technologies, are available to examine the global impact of growth in the spacecraft on the plant's gene expression profile. In ground-based studies, we have developed cDNA subtraction libraries of rice that are enriched for genes induced during pathogen infection and the defense response. Arrays of these genes are being used to dissect plant defense response pathways in a model system involving wild-type rice plants and lesion mimic mutants. The lesion mimic mutants are ideal experimental tools because they erratically develop defense response-like lesions in the absence of pathogens. The gene expression profiles from these ground-based studies will provide the molecular basis for understanding the biochemical and physiological impacts of spaceflight on plant growth, development and disease defense responses. This, in turn, will allow the development of strategies to manage plant disease for life in the space environment.

  3. Production of super-smooth articles

    SciTech Connect

    Duchane, D.V.

    1981-05-29

    Super-smooth rounded or formed articles made of thermoplastic materials including various poly(methyl methacrylate) or acrylonitrile-butadiene-styrene copolymers are produced by immersing the articles into a bath, the composition of which is slowly changed with time. The starting composition of the bath is made up of at least one solvent for the polymer and a diluent made up of at least one nonsolvent for the polymer and optional materials which are soluble in the bath. The resulting extremely smooth articles are useful as mandrels for laser fusion and should be useful for a wide variety of other purposes, for example lenses.

  4. Production of super-smooth articles

    DOEpatents

    Duchane, David V.

    1983-01-01

    Super-smooth rounded or formed articles made of thermoplastic materials including various poly(methyl methacrylate) or acrylonitrile-butadiene-styrene copolymers are produced by immersing the articles into a bath, the composition of which is slowly changed with time. The starting composition of the bath is made up of at least one solvent for the polymer and a diluent made up of at least one nonsolvent for the polymer and optional materials which are soluble in the bath. The resulting extremely smooth articles are useful as mandrels for laser fusion and should be useful for a wide variety of other purposes, for example lenses.

  5. Torsional texturing of superconducting oxide composite articles

    DOEpatents

    Christopherson, Craig John; Riley, Jr., Gilbert N.; Scudiere, John

    2002-01-01

    A method of texturing a multifilamentary article having filaments comprising a desired oxide superconductor or its precursors by torsionally deforming the article is provided. The texturing is induced by applying a torsional strain which is at least about 0.3 and preferably at least about 0.6 at the surface of the article, but less than the strain which would cause failure of the composite. High performance multifilamentary superconducting composite articles having a plurality of low aspect ratio, twisted filaments with substantially uniform twist pitches in the range of about 1.00 inch to 0.01 inch (25 to 0.25 mm), each comprising a textured desired superconducting oxide material, may be obtained using this texturing method. If tighter twist pitches are desired, the article may be heat treated or annealed and the strain repeated as many times as necessary to obtain the desired twist pitch. It is preferred that the total strain applied per step should be sufficient to provide a twist pitch tighter than 5 times the diameter of the article, and twist pitches in the range of 1 to 5 times the diameter of the article are most preferred. The process may be used to make a high performance multifilamentary superconducting article, having a plurality of twisted filaments, wherein the degree of texturing varies substantially in proportion to the radial distance from the center of the article cross-section, and is substantially radially homogeneous at any given cross-section of the article. Round wires and other low aspect ratio multifilamentary articles are preferred forms. The invention is not dependent on the melting characteristics of the desired superconducting oxide. Desired oxide superconductors or precursors with micaceous or semi-micaceous structures are preferred. When used in connection with desired superconducting oxides which melt irreversibly, it provides multifilamentary articles that exhibit high DC performance characteristics and AC performance markedly

  6. Coated article and method of making

    NASA Technical Reports Server (NTRS)

    Wang, Hongyu (Inventor); Lee, Kang Neung (Inventor)

    2002-01-01

    An article includes a silicon-containing substrate and a modified mullite coating. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating. The article can further comprise a thermal barrier coating applied to the modified mullite coating. The modified mullite coating functions as a bond coating between the external environmental/thermal barrier coating and the silicon-containing substrate. In a method of forming an article, a silicon-containing substrate is formed and a modified mullite coating is applied. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating.

  7. Coated article and method of making

    NASA Technical Reports Server (NTRS)

    Wang, Hongyu (Inventor); Lee, Kang Neung (Inventor)

    2003-01-01

    An article includes a silicon-containing substrate and a modified mullite coating. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating. The article can further comprise a thermal barrier coating applied to the modified mullite coating. The modified mullite coating functions as a bond coating between the external environmental/thermal barrier coating and the silicon-containing substrate. In a method of forming an article, a silicon-containing substrate is formed and a modified mullite coating is applied. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating.

  8. From multiple pathogenicity islands to a unique organized pathogenicity archipelago

    PubMed Central

    Bouyioukos, Costas; Reverchon, Sylvie; Képès, François

    2016-01-01

    Pathogenicity islands are sets of successive genes in a genome that determine the virulence of a bacterium. In a growing number of studies, bacterial virulence appears to be determined by multiple islands scattered along the genome. This is the case in a family of seven plant pathogens and a human pathogen that, under KdgR regulation, massively secrete enzymes such as pectinases that degrade plant cell wall. Here we show that their multiple pathogenicity islands form together a coherently organized, single “archipelago” at the genome scale. Furthermore, in half of the species, most genes encoding secreted pectinases are expressed from the same DNA strand (transcriptional co-orientation). This genome architecture favors DNA conformations that are conducive to genes spatial co-localization, sometimes complemented by co-orientation. As proteins tend to be synthetized close to their encoding genes in bacteria, we propose that this architecture would favor the efficient funneling of pectinases at convergent points within the cell. The underlying functional hypothesis is that this convergent funneling of the full blend of pectinases constitutes a crucial strategy for successful degradation of the plant cell wall. Altogether, our work provides a new approach to describe and predict, at the genome scale, the full virulence complement. PMID:27302835

  9. INTERNATIONAL CHILDHOOD CANCER COHORT CONSORTIUM (Journal Article)

    EPA Science Inventory

    Childhood cancers are rare conditions whose etiology is poorly understood. There is evidence that for some, the causal pathway may commence in utero or during peri-conception. One traditional epidemiologic approach to the study of rare diseases is the use of a retrospective cas...

  10. New trends in emerging pathogens.

    PubMed

    Skovgaard, Niels

    2007-12-15

    The emergence of pathogens is the result of a number of impact in all parts of the food chain. The emerging technologies in food production explain how new pathogens can establish themselves in the food chain and compromise food safety. The impact of the food technology is analysed for several bacteria, such as Yersinia, Campylobacter, Arcobacter, Helicobacter pullorum, Enterobacter sakazakii, Mycobacterium avium spp. paratuberculosis, prions related to vCJD and others. The importance of the ability of many microbes to form VBNC forms is elaborated on. Research on culture independent methods may address this outstanding issue to the better understanding of emerging pathogens. The "demerging" of pathogens also occur, and examples of this are explained. The reaction of bacteria to stresses and sublethal treatments, and how exposure to one stress factor can confer resistance to other stresses, literally speaking causing contagious resistance, are explained. The implication of this e.g. in modern approaches of food preservation, such as Minimally processed Foods, is considerable. Intestinal colonization of EHEC may be regulated by Quorum sensing, and this ability of microbes plays an important role in the colonization of microbes in food and on food processing equipment, an important factor in the emergence of pathogens. The emergence of Saccharomyces cerevisiae, as an opportunistic human pathogen, used for centuries for food and production of alcoholic beverages, calls for research in molecular tools to distinguish between probiotic and clinical strains. Cyclospora cayetanensis and Norovirus outbreaks can no longer be designated as emerging pathogens, they share however one characteristic in the epidemiology of emerging nature, the importance of the hygiene in the primary production stage, including supply of potable water, and the application of GMP and the HACCP principles in the beginning of the food chain. Hepatitis E virus is a potential emerging food borne

  11. New trends in emerging pathogens.

    PubMed

    Skovgaard, Niels

    2007-12-15

    The emergence of pathogens is the result of a number of impact in all parts of the food chain. The emerging technologies in food production explain how new pathogens can establish themselves in the food chain and compromise food safety. The impact of the food technology is analysed for several bacteria, such as Yersinia, Campylobacter, Arcobacter, Helicobacter pullorum, Enterobacter sakazakii, Mycobacterium avium spp. paratuberculosis, prions related to vCJD and others. The importance of the ability of many microbes to form VBNC forms is elaborated on. Research on culture independent methods may address this outstanding issue to the better understanding of emerging pathogens. The "demerging" of pathogens also occur, and examples of this are explained. The reaction of bacteria to stresses and sublethal treatments, and how exposure to one stress factor can confer resistance to other stresses, literally speaking causing contagious resistance, are explained. The implication of this e.g. in modern approaches of food preservation, such as Minimally processed Foods, is considerable. Intestinal colonization of EHEC may be regulated by Quorum sensing, and this ability of microbes plays an important role in the colonization of microbes in food and on food processing equipment, an important factor in the emergence of pathogens. The emergence of Saccharomyces cerevisiae, as an opportunistic human pathogen, used for centuries for food and production of alcoholic beverages, calls for research in molecular tools to distinguish between probiotic and clinical strains. Cyclospora cayetanensis and Norovirus outbreaks can no longer be designated as emerging pathogens, they share however one characteristic in the epidemiology of emerging nature, the importance of the hygiene in the primary production stage, including supply of potable water, and the application of GMP and the HACCP principles in the beginning of the food chain. Hepatitis E virus is a potential emerging food borne

  12. Pathogenic rickettsiae as bioterrorism agents.

    PubMed

    Azad, Abdu F

    2007-07-15

    Because of their unique biological characteristics, such as environmental stability, small size, aerosol transmission, persistence in infected hosts, low infectious dose, and high associated morbidity and mortality, Rickettsia prowazekii and Coxiella burnetii have been weaponized. These biological attributes would make the pathogenic rickettsiae desirable bioterrorism agents. However, production of highly purified, virulent, weapon-quality rickettsiae is a daunting task that requires expertise and elaborate, state-of-the art laboratory procedures to retain rickettsial survival and virulence. Another drawback to developing rickettsial pathogens as biological weapons is their lack of direct transmission from host to host and the availability of very effective therapeutic countermeasures against these obligate intracellular bacteria.

  13. An algorithm for efficient identification of branched metabolic pathways.

    PubMed

    Heath, Allison P; Bennett, George N; Kavraki, Lydia E

    2011-11-01

    This article presents a new graph-based algorithm for identifying branched metabolic pathways in multi-genome scale metabolic data. The term branched is used to refer to metabolic pathways between compounds that consist of multiple pathways that interact biochemically. A branched pathway may produce a target compound through a combination of linear pathways that split compounds into smaller ones, work in parallel with many compounds, and join compounds into larger ones. While branched metabolic pathways predominate in metabolic networks, most previous work has focused on identifying linear metabolic pathways. The ability to automatically identify branched pathways is important in applications that require a deeper understanding of metabolism, such as metabolic engineering and drug target identification. The algorithm presented in this article utilizes explicit atom tracking to identify linear metabolic pathways and then merges them together into branched metabolic pathways. We provide results on several well-characterized metabolic pathways that demonstrate that the new merging approach can efficiently find biologically relevant branched metabolic pathways.

  14. Planning for Secondary Expansion in Sub-Saharan Africa--Pathways towards Sustainable Financing. Research Article

    ERIC Educational Resources Information Center

    Lewin, Keith

    2006-01-01

    Investment in secondary schooling in sub-Saharan Africa has been neglected over the last two decades. Emphasis on universalising primary schooling has shaped national policy and flows of international assistance to favour rapid expansion at the first level of schooling. Though there are many good reasons for this emphasis, this has resulted in…

  15. Adverse Outcome Pathways and Ecological Risk Assessment: Bridging to Population Level Effects, Journal Article

    EPA Science Inventory

    The viability of populations of plants and animals is a key focus for environmental regulation. Population-level responses integrate the cumulative effects of chemical stressors on individuals as those individuals interact with and are affected by their con-specifics, competitor...

  16. 48 CFR 25.104 - Nonavailable articles.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... articles have been determined to be nonavailable in accordance with 25.103(b)(1)(i): Acetylene, black. Agar.... Chalk, English. Chestnuts. Chicle. Chrome ore or chromite. Cinchona bark. Cobalt, in cathodes,...

  17. 48 CFR 25.104 - Nonavailable articles.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... articles have been determined to be nonavailable in accordance with 25.103(b)(1)(i): Acetylene, black. Agar.... Chalk, English. Chestnuts. Chicle. Chrome ore or chromite. Cinchona bark. Cobalt, in cathodes,...

  18. 48 CFR 25.104 - Nonavailable articles.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... articles have been determined to be nonavailable in accordance with 25.103(b)(1)(i): Acetylene, black. Agar.... Chalk, English. Chestnuts. Chicle. Chrome ore or chromite. Cinchona bark. Cobalt, in cathodes,...

  19. 48 CFR 25.104 - Nonavailable articles.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... articles have been determined to be nonavailable in accordance with 25.103(b)(1)(i): Acetylene, black. Agar.... Chalk, English. Chestnuts. Chicle. Chrome ore or chromite. Cinchona bark. Cobalt, in cathodes,...

  20. Biaxially textured articles formed by powder metallurgy

    DOEpatents

    Goyal, Amit; Williams, Robert K.; Kroeger, Donald M.

    2003-10-21

    A strengthened, biaxially textured alloy article having a magnetism less than pure Ni includes a rolled and annealed, compacted and sintered powder-metallurgy preform article, the preform article having been formed from a powder mixture selected from the group of mixtures consisting of: Ni, Ag, Ag--Cu, Ag--Pd, Ni--Cu, Ni--V, Ni--Mo, Ni--Al, Ni--Cr--Al, Ni--W--Al, Ni--V--Al, Ni--Mo--Al, Ni--Cu--Al; and at least one fine metal oxide powder; the article having a grain size which is fine and homogeneous; and having a dominant cube oriented {100}<100> orientation texture; and further having a Curie temperature less than that of pure Ni.

  1. Pathway modulators and inhibitors.

    PubMed

    Smith, John A

    2009-07-01

    Inhibitors of specific cellular pathways are useful for investigating the roles of proteins of unknown function, and for selectively inhibiting a protein in complex pathways to uncover its relationships to other proteins in this and other interacting pathways. This appendix provides links to Web sites that describe cellular processes and pathways along with the various classes of inhibitors, numerous references, downloadable diagrams, and technical tips.

  2. Satellite RNA pathogens of plants: impacts and origins-an RNA silencing perspective.

    PubMed

    Wang, Ming-Bo; Smith, Neil A

    2016-01-01

    Viral satellite RNAs (satRNAs) are among the smallest RNA pathogens in plants. They have little or no protein-coding capacity but can have a major impact on the host plants through trilateral interactions with helper viruses and host plants. Studies around the 1980s revealed much of what we know about satRNAs: they can affect helper virus accumulation, modulate helper virus-induced disease symptoms, and induce their own symptoms with the assistance of helper viruses which depend on specific nucleotide sequences of their genome and host species. The molecular basis of these satRNA-caused impacts and the origin of satRNAs have yet to be fully understood and revealed, but recent understanding of the antiviral RNA silencing pathways and advancement in RNA and DNA sequencing technologies have provided new avenues and opportunities to examine these unanswered questions. These RNA silencing-based studies have revealed the existence of cross silencing between some satRNAs and helper viruses, the downregulation of helper virus-encoded suppressor (VSR) of RNA silencing or inhibition/enhancement of VSR activity by satRNAs, the silencing of host-encoded genes by satRNA-derived small interfering RNA (siRNAs), and the presence of satRNA-like small RNAs in uninfected host plants. These findings have provided alternative RNA silencing-based models to explain the pathogenicity and origin of satRNAs. WIREs RNA 2016, 7:5-16. doi: 10.1002/wrna.1311 For further resources related to this article, please visit the WIREs website.

  3. Biaxially textured articles formed by plastic deformation

    DOEpatents

    Goyal, Amit

    2001-01-01

    A method of preparing a biaxially textured article comprises the steps of providing a metal preform, coating or laminating the preform with a metal layer, deforming the layer to a sufficient degree, and rapidly recrystallizing the layer to produce a biaxial texture. A superconducting epitaxial layer may then be deposited on the biaxial texture. In some embodiments the article further comprises buffer layers, electromagnetic devices or electro-optical devices.

  4. Method of producing microchannel and nanochannel articles

    DOEpatents

    D'Urso, Brian R.

    2010-05-04

    A method of making an article having channels therethrough includes the steps of: providing a ductile structure defining at least one macro-channel, the macro-channel containing a salt; drawing the ductile structure in the axial direction of the at least one macro-channel to reduce diameter of the macro-channel; and contacting the salt with a solvent to dissolve the salt to produce an article having at least one microchannel.

  5. Pharmacology of intracellular signalling pathways

    PubMed Central

    Nahorski, Stefan R

    2006-01-01

    This article provides a brief and somewhat personalized review of the dramatic developments that have occurred over the last 45 years in our understanding of intracellular signalling pathways associated with G-protein-coupled receptor activation. Signalling via cyclic AMP, the phosphoinositides and Ca2+ is emphasized and these systems have already been revealed as new pharmacological targets. The therapeutic benefits of most of such targets are, however, yet to be realized, but it is certain that the discipline of pharmacology needs to widen its boundaries to meet these challenges in the future. PMID:16402119

  6. Database citation in full text biomedical articles.

    PubMed

    Kafkas, Şenay; Kim, Jee-Hyub; McEntyre, Johanna R

    2013-01-01

    Molecular biology and literature databases represent essential infrastructure for life science research. Effective integration of these data resources requires that there are structured cross-references at the level of individual articles and biological records. Here, we describe the current patterns of how database entries are cited in research articles, based on analysis of the full text Open Access articles available from Europe PMC. Focusing on citation of entries in the European Nucleotide Archive (ENA), UniProt and Protein Data Bank, Europe (PDBe), we demonstrate that text mining doubles the number of structured annotations of database record citations supplied in journal articles by publishers. Many thousands of new literature-database relationships are found by text mining, since these relationships are also not present in the set of articles cited by database records. We recommend that structured annotation of database records in articles is extended to other databases, such as ArrayExpress and Pfam, entries from which are also cited widely in the literature. The very high precision and high-throughput of this text-mining pipeline makes this activity possible both accurately and at low cost, which will allow the development of new integrated data services.

  7. Tracking Multiple Topics for Finding Interesting Articles

    SciTech Connect

    Pon, R K; Cardenas, A F; Buttler, D J; Critchlow, T J

    2007-02-15

    We introduce multiple topic tracking (MTT) for iScore to better recommend news articles for users with multiple interests and to address changes in user interests over time. As an extension of the basic Rocchio algorithm, traditional topic detection and tracking, and single-pass clustering, MTT maintains multiple interest profiles to identify interesting articles for a specific user given user-feedback. Focusing on only interesting topics enables iScore to discard useless profiles to address changes in user interests and to achieve a balance between resource consumption and classification accuracy. Also by relating a topic's interestingness to an article's interestingness, iScore is able to achieve higher quality results than traditional methods such as the Rocchio algorithm. We identify several operating parameters that work well for MTT. Using the same parameters, we show that MTT alone yields high quality results for recommending interesting articles from several corpora. The inclusion of MTT improves iScore's performance by 9% to 14% in recommending news articles from the Yahoo! News RSS feeds and the TREC11 adaptive filter article collection. And through a small user study, we show that iScore can still perform well when only provided with little user feedback.

  8. Retrieval and classification of dental research articles.

    PubMed

    Bartling, W C; Schleyer, T K; Visweswaran, S

    2003-12-01

    Successful retrieval of a corpus of literature on a broad topic can be difficult. This study demonstrates a method to retrieve the dental and craniofacial research literature. We explored MeSH manually for dental or craniofacial indexing terms. MEDLINE was searched using these terms, and a random sample of references was extracted from the resulting set. Sixteen dental research experts categorized these articles, reading only the title and abstract, as either: (1) dental research, (2) dental non-research, (3) non-dental, or (4) not sure. Identify Patient Sets (IPS), a probabilistic text classifier, created models, based on the presence or absence of words or UMLS phrases, that distinguished dental research articles from all others. These models were applied to a test set with different inputs for each article: (1) title and abstract only, (2) MeSH terms only, or (3) both. By title and abstract only, IPS correctly classified 64% of all dental research articles present in the test set. The percentage of correctly classified dental research articles in this retrieved set was 71%. MeSH term inclusion decreased performance. Computer programs that use text input to categorize articles may aid in retrieval of a broad corpus of literature better than indexing terms or key words alone.

  9. Thermally Dimorphic Human Fungal Pathogens--Polyphyletic Pathogens with a Convergent Pathogenicity Trait.

    PubMed

    Sil, Anita; Andrianopoulos, Alex

    2015-08-01

    Fungi are adept at changing their cell shape and developmental program in response to signals in their surroundings. Here we focus on a group of evolutionarily related fungal pathogens of humans known as the thermally dimorphic fungi. These organisms grow in a hyphal form in the environment but shift their morphology drastically within a mammalian host. Temperature is one of the main host signals that initiates their conversion to the "host" form and is sufficient in the laboratory to trigger establishment of this host-adapted developmental program. Here we discuss the major human pathogens in this group, which are Blastomyces dermatiditis, Coccidioides immitis/posadasii, Histoplasma capsulatum, Paracoccidioides brasiliensis/lutzii, Sporothrix schenckii, and Talaromyces marneffei (formerly known as Penicillium marneffei). The majority of these organisms are primary pathogens, with the ability to cause disease in healthy humans who encounter them in endemic areas. PMID:25384771

  10. Masquerading microbial pathogens: Capsular polysaccharides mimic host-tissue molecules

    PubMed Central

    Cress, Brady F.; Englaender, Jacob A.; He, Wenqin; Kasper, Dennis; Linhardt, Robert J.; Koffas, Mattheos A. G.

    2014-01-01

    Summary Bacterial pathogens bearing capsular polysaccharides identical to mammalian glycans benefit from an additional level of protection from host immune response. The increasing prevalence of antibiotic resistant bacteria portends an impending post-antibiotic age, characterized by diminishing efficacy of common antibiotics and routine application of multifaceted, complementary therapeutic approaches to treat bacterial infections, particularly multidrug-resistant organisms. The first line of defense for most bacterial pathogens consists of a physical and immunological barrier known as the capsule, commonly composed of a viscous layer of carbohydrates that are covalently bound to the cell wall in Gram-positive bacteria or often to lipids of the outer membrane in many Gram-negative bacteria. Bacterial capsular polysaccharides are a diverse class of high molecular weight polysaccharides contributing to virulence of many human pathogens in the gut, respiratory tree, urinary tract, and other host tissues, by hiding cell-surface components that might otherwise elicit host immune response. This review highlights capsular polysaccharides that are structurally identical or similar to polysaccharides found in mammalian tissues, including polysialic acid and glycosaminoglycan capsules hyaluronan, heparosan, and chondroitin. Such non-immunogenic coatings render pathogens insensitive to certain immune responses, effectively increasing residence time in host tissues and enabling pathologically relevant population densities to be reached. Biosynthetic pathways and capsular involvement in immune system evasion are described providing a basis for potential therapies aimed at supplementing or replacing antibiotic treatment. PMID:24372337

  11. Signaling events in pathogen-induced macrophage foam cell formation.

    PubMed

    Shaik-Dasthagirisaheb, Yazdani B; Mekasha, Samrawit; He, Xianbao; Gibson, Frank C; Ingalls, Robin R

    2016-08-01

    Macrophage foam cell formation is a key event in atherosclerosis. Several triggers induce low-density lipoprotein (LDL) uptake by macrophages to create foam cells, including infections with Porphyromonas gingivalis and Chlamydia pneumoniae, two pathogens that have been linked to atherosclerosis. While gene regulation during foam cell formation has been examined, comparative investigations to identify shared and specific pathogen-elicited molecular events relevant to foam cell formation are not well documented. We infected mouse bone marrow-derived macrophages with P. gingivalis or C. pneumoniae in the presence of LDL to induce foam cell formation, and examined gene expression using an atherosclerosis pathway targeted plate array. We found over 30 genes were significantly induced in response to both pathogens, including PPAR family members that are broadly important in atherosclerosis and matrix remodeling genes that may play a role in plaque development and stability. Six genes mainly involved in lipid transport were significantly downregulated. The response overall was remarkably similar and few genes were regulated in a pathogen-specific manner. Despite very divergent lifestyles, P. gingivalis and C. pneumoniae activate similar gene expression profiles during foam cell formation that may ultimately serve as targets for modulating infection-elicited foam cell burden, and progression of atherosclerosis.

  12. Arabidopsis WRKY33 transcription factor is required for resistance to necrotrophic fungal pathogens.

    PubMed

    Zheng, Zuyu; Qamar, Synan Abu; Chen, Zhixiang; Mengiste, Tesfaye

    2006-11-01

    Plant WRKY transcription factors are key regulatory components of plant responses to microbial infection. In addition to regulating the expression of defense-related genes, WRKY transcription factors have also been shown to regulate cross-talk between jasmonate- and salicylate-regulated disease response pathways. The two pathways mediate resistance against different types of microbial pathogens, and there are numerous reports of antagonistic interactions between them. Here we show that mutations of the Arabidopsis WRKY33 gene encoding a WRKY transcription factor cause enhanced susceptibility to the necrotrophic fungal pathogens Botrytis cinerea and Alternaria brassicicola concomitant with reduced expression of the jasmonate-regulated plant defensin PDF1.2 gene. Ectopic over-expression of WRKY33, on the other hand, increases resistance to the two necrotrophic fungal pathogens. The wrky33 mutants do not show altered responses to a virulent strain of the bacterial pathogen Pseudomonas syringae, although the ectopic expression of WRKY33 results in enhanced susceptibility to this pathogen. The susceptibility of WRKY33-over-expressing plants to P. syringae is associated with reduced expression of the salicylate-regulated PR-1 gene. The WRKY33 transcript is induced in response to pathogen infection, or treatment with salicylate or the paraquat herbicide that generates activated oxygen species in exposed cells. WRKY33 is localized to the nucleus of plant cells and recognizes DNA molecules containing the TTGACC W-box sequence. Together, these results indicate that pathogen-induced WRKY33 is an important transcription factor that regulates the antagonistic relationship between defense pathways mediating responses to P. syringae and necrotrophic pathogens.

  13. Pathogen pollution and the emergence of a deadly amphibian pathogen.

    PubMed

    McKenzie, Valerie J; Peterson, Anna C

    2012-11-01

    Imagine a single pathogen that is responsible for mass mortality of over a third of an entire vertebrate class. For example, if a single pathogen were causing the death, decline and extinction of 30% of mammal species (including humans), the entire world would be paying attention. This is what has been happening to the world's amphibians - the frogs, toads and salamanders that are affected by the chytrid fungal pathogen, Batrachochytrium dendrobatidis (referred to as Bd), which are consequently declining at an alarming rate. It has aptly been described as the worst pathogen in history in terms of its effects on biodiversity (Kilpatrick et al. 2010). The pathogen was only formally described about 13 years ago (Longcore et al. 1999), and scientists are still in the process of determining where it came from and investigating the question: why now? Healthy debate has ensued as to whether Bd is a globally endemic organism that only recently started causing high mortality due to shifting host responses and/or environmental change (e.g. Pounds et al. 2006) or whether a virulent strain of the pathogen has rapidly disseminated around the world in recent decades, affecting new regions with a vengeance (e.g. Morehouse et al. 2003; Weldon et al. 2004; Lips et al. 2008). We are finally beginning to shed more light on this question, due to significant discoveries that have emerged as a result of intensive DNA-sequencing methods comparing Bd isolates from different amphibian species across the globe. Evidence is mounting that there is indeed a global panzootic lineage of Bd (BdGPL) in addition to what appear to be more localized endemic strains (Fisher et al. 2009; James et al. 2009; Farrer et al. 2011). Additionally, BdGPL appears to be a hypervirulent strain that has resulted from the hybridization of different Bd strains that came into contact in recent decades, and is now potentially replacing the less-virulent endemic strains of the pathogen (Farrer et al. 2011

  14. Pathogen pollution and the emergence of a deadly amphibian pathogen.

    PubMed

    McKenzie, Valerie J; Peterson, Anna C

    2012-11-01

    Imagine a single pathogen that is responsible for mass mortality of over a third of an entire vertebrate class. For example, if a single pathogen were causing the death, decline and extinction of 30% of mammal species (including humans), the entire world would be paying attention. This is what has been happening to the world's amphibians - the frogs, toads and salamanders that are affected by the chytrid fungal pathogen, Batrachochytrium dendrobatidis (referred to as Bd), which are consequently declining at an alarming rate. It has aptly been described as the worst pathogen in history in terms of its effects on biodiversity (Kilpatrick et al. 2010). The pathogen was only formally described about 13 years ago (Longcore et al. 1999), and scientists are still in the process of determining where it came from and investigating the question: why now? Healthy debate has ensued as to whether Bd is a globally endemic organism that only recently started causing high mortality due to shifting host responses and/or environmental change (e.g. Pounds et al. 2006) or whether a virulent strain of the pathogen has rapidly disseminated around the world in recent decades, affecting new regions with a vengeance (e.g. Morehouse et al. 2003; Weldon et al. 2004; Lips et al. 2008). We are finally beginning to shed more light on this question, due to significant discoveries that have emerged as a result of intensive DNA-sequencing methods comparing Bd isolates from different amphibian species across the globe. Evidence is mounting that there is indeed a global panzootic lineage of Bd (BdGPL) in addition to what appear to be more localized endemic strains (Fisher et al. 2009; James et al. 2009; Farrer et al. 2011). Additionally, BdGPL appears to be a hypervirulent strain that has resulted from the hybridization of different Bd strains that came into contact in recent decades, and is now potentially replacing the less-virulent endemic strains of the pathogen (Farrer et al. 2011

  15. Bloodborne Pathogens Exposure Control Plan.

    ERIC Educational Resources Information Center

    National Child Care Association, Atlanta, GA.

    This sample exposure control plan is a guide to assist child care providers in complying with the blood-borne pathogens standard issued by the Occupational Safety and Health Administration (OSHA). The standard requires employers to establish a written exposure control plan by May 5, 1992 (for exposure to microorganisms in human blood that cause…

  16. Asian citrus psyllid viral pathogen

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A newly discovered viral pathogen of Asian citrus psyllid, AsCP, Diaphorina citri, Kuwayama (Psyllidae: Hemiptera) was classified as a Reoviridae. This virus may serve as a biological control agent for AsCP. The AsCP is an efficient vector of the plant-infecting bacterium (Candidatus Liberibacter as...

  17. Biosignatures of Pathogen and Host

    SciTech Connect

    Fitch, J P; Chromy, B A; Forde, C E; Garcia, E; Gardner, S N; Gu, P P; Kuczmarksi, T A; Melius, C F; McCutchen-Maloney, S L; Milanovich, F P; Motin, V L; Ott, L L; Quong, A A; Quong, J N; Rocco, J M; Slezak, T R; Sokhansanj, B A; Vitalis, E A; Zemla, A T; McCready, P M

    2002-08-27

    In information theory, a signature is characterized by the information content as well as noise statistics of the communication channel. Biosignatures have analogous properties. A biosignature can be associated with a particular attribute of a pathogen or a host. However, the signature may be lost in backgrounds of similar or even identical signals from other sources. In this paper, we highlight statistical and signal processing challenges associated with identifying good biosignatures for pathogens in host and other environments. In some cases it may be possible to identify useful signatures of pathogens through indirect but amplified signals from the host. Discovery of these signatures requires new approaches to modeling and data interpretation. For environmental biosignal collections, it is possible to use signal processing techniques from other applications (e.g., synthetic aperture radar) to track the natural progression of microbes over large areas. We also present a computer-assisted approach to identify unique nucleic-acid based microbial signatures. Finally, an understanding of host-pathogen interactions will result in better detectors as well as opportunities in vaccines and therapeutics.

  18. Microbial Forensics and Plant Pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    New awareness of the vulnerability of a nation's agricultural infrastructure to the intentional introduction of pathogens or pests has led to the enhancement of programs for prevention and preparedness. A necessary component of a balanced bio-security plan is the capability to determine whether an ...

  19. USEPA PERSPECTIVE ON CONTROLLING PATHOGENS

    EPA Science Inventory

    EPA minimizes the risk of infectious diseases from the beneficial use of sludge by requiring its treatment to reduce pathogen levels below the detection limit. How new treatment processes can be shown equivalent to ones specified in 40CFR503 will be discussed together with ways t...

  20. The Evolution of Foodborne Pathogens

    NASA Astrophysics Data System (ADS)

    Abu-Ali, Galeb S.; Manning, Shannon D.

    Despite continuous advances in food safety and disease surveillance, control, and prevention, foodborne bacterial infections remain a major public health concern. Because foodborne pathogens are commonly exposed to multiple environmental stressors, such as low pH and antibiotics, most have evolved specific mechanisms to facilitate survival in adverse environments.

  1. MANAGING URBAN WATERSHED PATHOGEN CONTAMINATION

    EPA Science Inventory

    This presentation is a summary of the EPA National Risk Management Research Laboratory (NRMRL) publication entitled Managing Urban Watershed Pathogen Contamination, EPA/600/R-03/111 (September 2003). It is available on the internet at http://www.epa.gov/ednnrmrl/repository/water...

  2. Proteomics of foodborne bacterial pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter focuses on recent research on foodborne bacterial pathogens that use mass spectrometry-based proteomic techniques as well as protein microarrays. Mass spectrometry ionization techniques (e.g. electrospray ionization and matrix-assisted laser desorption/ionization), analyzers (e.g. ion ...

  3. EXTRAINTESTINAL PATHOGENIC ESCHERICHIA COLI (EXPEC)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Extraintestinal pathogenic Escherichia coli (ExPEC) possess virulence traits that allow them to invade, colonize, and induce disease in bodily sites outside of the gastrointestinal tract. Human diseases caused by ExPEC include urinary tract infections, neonatal meningitis, sepsis, pneumonia, surgic...

  4. Developmental pathways to antisocial behavior: the delayed-onset pathway in girls.

    PubMed

    Silverthorn, P; Frick, P J

    1999-01-01

    Recent research has suggested that there are two distinct trajectories for the development of antisocial behavior in boys: a childhood-onset pathway and an adolescent-onset pathway. After reviewing the limited available research on antisocial girls, we propose that this influential method of conceptualizing the development of severe antisocial behavior may not apply to girls without some important modifications. Antisocial girls appear to show many of the correlates that have been associated with the childhood-onset pathway in boys, and they tend to show impaired adult adjustment, which is also similar to boys in the childhood-onset pathway. However, antisocial girls typically show an adolescent-onset to their antisocial behavior. We have proposed that these girls show a third developmental pathway which we have labeled the "delayed-onset" pathway. This model rests on the assumption that many of the putative pathogenic mechanisms that contribute to the development of antisocial behavior in girls, such as cognitive and neuropsychological deficits, a dysfunctional family environment, and/or the presence of a callous and unemotional interpersonal style, may be present in childhood, but they do not lead to severe and overt antisocial behavior until adolescence. Therefore, we propose that the delayed-onset pathway for girls is analogous to the childhood-onset pathway in boys and that there is no analogous pathway in girls to the adolescent-onset pathway in boys. Although this model clearly needs to be tested in future research, it highlights the need to test the applicability of current theoretical models for explaining the development of antisocial behavior in girls.

  5. Pathways to Childlessness: A Life Course Perspective

    ERIC Educational Resources Information Center

    Hagestad, Gunhild O.; Call, Vaughn R. A.

    2007-01-01

    In this article life history data from the U.S. National Survey of Families and Households (NSFH), and the Dutch survey on Older Adults' Living Arrangements and Social Networks (NESTOR-LSN) are used to shed light on the various pathways leading to and associated with childlessness, and the proportions of men and women who have followed a…

  6. Instructional Partnerships: A Pathway to Leadership

    ERIC Educational Resources Information Center

    Moreillon, Judi, Ed.; Ballard, Susan, Ed.

    2013-01-01

    In this Best of "Knowledge Quest" monograph, the editors have collected seminal articles to support pre-service and in-service school librarians in developing and strengthening the instructional partner role. "Instructional Partnerships: A Pathway to Leadership" provides readers with background knowledge, research-based…

  7. Response Ability Pathways: A Curriculum for Connecting

    ERIC Educational Resources Information Center

    Koehler, Nancy; Seger, Vikki

    2005-01-01

    This article describes a new training curriculum for educators, youth workers, and mentors which draws from research and best practices in positive youth development and positive behavior support. Response Ability Pathways or RAP focuses on three practical interventions: connect to others for support, clarify challenging problems, and restore…

  8. Career pathways in research: clinical research.

    PubMed

    Kenkre, J E; Foxcroft, D R

    This article, the second in a series on career pathways, informs readers of the knowledge they require to conduct clinical therapeutic trials to recognised standards. Many nurses start their careers in research as clinical research nurses. The skills and knowledge they develop through conducting multi-centre studies gives them an excellent grounding in the discipline, organisation and management of research.

  9. Perspective: Adhesion Mediated Signal Transduction in Bacterial Pathogens.

    PubMed

    Moorthy, Sudha; Keklak, Julia; Klein, Eric A

    2016-01-01

    During the infection process, pathogenic bacteria undergo large-scale transcriptional changes to promote virulence and increase intrahost survival. While much of this reprogramming occurs in response to changes in chemical environment, such as nutrient availability and pH, there is increasing evidence that adhesion to host-tissue can also trigger signal transduction pathways resulting in differential gene expression. Determining the molecular mechanisms of adhesion-mediated signaling requires disentangling the contributions of chemical and mechanical stimuli. Here we highlight recent work demonstrating that surface attachment drives a transcriptional response in bacterial pathogens, including uropathogenic Escherichia coli (E. coli), and discuss the complexity of experimental design when dissecting the specific role of adhesion-mediated signaling during infection.

  10. Infection Strategies of Intestinal Parasite Pathogens and Host Cell Responses.

    PubMed

    Di Genova, Bruno M; Tonelli, Renata R

    2016-01-01

    Giardia lamblia, Cryptosporidium sp., and Entamoeba histolytica are important pathogenic intestinal parasites and are amongst the leading causes worldwide of diarrheal illness in humans. Diseases caused by these organisms, giardiasis, cryptosporidiosis, and amoebiasis, respectively, are characterized by self-limited diarrhea but can evolve to long-term complications. The cellular and molecular mechanisms underlying the pathogenesis of diarrhea associated with these three pathogens are being unraveled, with knowledge of both the strategies explored by the parasites to establish infection and the methods evolved by hosts to avoid it. Special attention is being given to molecules participating in parasite-host interaction and in the mechanisms implicated in the diseases' pathophysiologic processes. This review focuses on cell mechanisms that are modulated during infection, including gene transcription, cytoskeleton rearrangements, signal transduction pathways, and cell death. PMID:26973630

  11. Infection Strategies of Intestinal Parasite Pathogens and Host Cell Responses

    PubMed Central

    Di Genova, Bruno M.; Tonelli, Renata R.

    2016-01-01

    Giardia lamblia, Cryptosporidium sp., and Entamoeba histolytica are important pathogenic intestinal parasites and are amongst the leading causes worldwide of diarrheal illness in humans. Diseases caused by these organisms, giardiasis, cryptosporidiosis, and amoebiasis, respectively, are characterized by self-limited diarrhea but can evolve to long-term complications. The cellular and molecular mechanisms underlying the pathogenesis of diarrhea associated with these three pathogens are being unraveled, with knowledge of both the strategies explored by the parasites to establish infection and the methods evolved by hosts to avoid it. Special attention is being given to molecules participating in parasite–host interaction and in the mechanisms implicated in the diseases’ pathophysiologic processes. This review focuses on cell mechanisms that are modulated during infection, including gene transcription, cytoskeleton rearrangements, signal transduction pathways, and cell death. PMID:26973630

  12. Perspective: Adhesion Mediated Signal Transduction in Bacterial Pathogens

    PubMed Central

    Moorthy, Sudha; Keklak, Julia; Klein, Eric A.

    2016-01-01

    During the infection process, pathogenic bacteria undergo large-scale transcriptional changes to promote virulence and increase intrahost survival. While much of this reprogramming occurs in response to changes in chemical environment, such as nutrient availability and pH, there is increasing evidence that adhesion to host-tissue can also trigger signal transduction pathways resulting in differential gene expression. Determining the molecular mechanisms of adhesion-mediated signaling requires disentangling the contributions of chemical and mechanical stimuli. Here we highlight recent work demonstrating that surface attachment drives a transcriptional response in bacterial pathogens, including uropathogenic Escherichia coli (E. coli), and discuss the complexity of experimental design when dissecting the specific role of adhesion-mediated signaling during infection. PMID:26901228

  13. Human pathogenic bacteria, fungi, and viruses in Drosophila

    PubMed Central

    Panayidou, Stavria; Ioannidou, Eleni; Apidianakis, Yiorgos

    2014-01-01

    Drosophila has been the invertebrate model organism of choice for the study of innate immune responses during the past few decades. Many Drosophila–microbe interaction studies have helped to define innate immunity pathways, and significant effort has been made lately to decipher mechanisms of microbial pathogenesis. Here we catalog 68 bacterial, fungal, and viral species studied in flies, 43 of which are relevant to human health. We discuss studies of human pathogens in flies revealing not only the elicitation and avoidance of immune response but also mechanisms of tolerance, host tissue homeostasis, regeneration, and predisposition to cancer. Prominent among those is the emerging pattern of intestinal regeneration as a defense response induced by pathogenic and innocuous bacteria. Immunopathology mechanisms and many microbial virulence factors have been elucidated, but their relevance to human health conventionally necessitates validation in mammalian models of infection. PMID:24398387

  14. Infection Strategies of Intestinal Parasite Pathogens and Host Cell Responses.

    PubMed

    Di Genova, Bruno M; Tonelli, Renata R

    2016-01-01

    Giardia lamblia, Cryptosporidium sp., and Entamoeba histolytica are important pathogenic intestinal parasites and are amongst the leading causes worldwide of diarrheal illness in humans. Diseases caused by these organisms, giardiasis, cryptosporidiosis, and amoebiasis, respectively, are characterized by self-limited diarrhea but can evolve to long-term complications. The cellular and molecular mechanisms underlying the pathogenesis of diarrhea associated with these three pathogens are being unraveled, with knowledge of both the strategies explored by the parasites to establish infection and the methods evolved by hosts to avoid it. Special attention is being given to molecules participating in parasite-host interaction and in the mechanisms implicated in the diseases' pathophysiologic processes. This review focuses on cell mechanisms that are modulated during infection, including gene transcription, cytoskeleton rearrangements, signal transduction pathways, and cell death.

  15. Network-assisted genetic dissection of pathogenicity and drug resistance in the opportunistic human pathogenic fungus Cryptococcus neoformans.

    PubMed

    Kim, Hanhae; Jung, Kwang-Woo; Maeng, Shinae; Chen, Ying-Lien; Shin, Junha; Shim, Jung Eun; Hwang, Sohyun; Janbon, Guilhem; Kim, Taeyup; Heitman, Joseph; Bahn, Yong-Sun; Lee, Insuk

    2015-01-01

    Cryptococcus neoformans is an opportunistic human pathogenic fungus that causes meningoencephalitis. Due to the increasing global risk of cryptococcosis and the emergence of drug-resistant strains, the development of predictive genetics platforms for the rapid identification of novel genes governing pathogenicity and drug resistance of C. neoformans is imperative. The analysis of functional genomics data and genome-scale mutant libraries may facilitate the genetic dissection of such complex phenotypes but with limited efficiency. Here, we present a genome-scale co-functional network for C. neoformans, CryptoNet, which covers ~81% of the coding genome and provides an efficient intermediary between functional genomics data and reverse-genetics resources for the genetic dissection of C. neoformans phenotypes. CryptoNet is the first genome-scale co-functional network for any fungal pathogen. CryptoNet effectively identified novel genes for pathogenicity and drug resistance using guilt-by-association and context-associated hub algorithms. CryptoNet is also the first genome-scale co-functional network for fungi in the basidiomycota phylum, as Saccharomyces cerevisiae belongs to the ascomycota phylum. CryptoNet may therefore provide insights into pathway evolution between two distinct phyla of the fungal kingdom. The CryptoNet web server (www.inetbio.org/cryptonet) is a public resource that provides an interactive environment of network-assisted predictive genetics for C. neoformans.

  16. 7 CFR 301.45-7 - Assembly and inspection of regulated articles and outdoor household articles.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Assembly and inspection of regulated articles and outdoor household articles. 301.45-7 Section 301.45-7 Agriculture Regulations of the Department of... QUARANTINE NOTICES Gypsy Moth § 301.45-7 Assembly and inspection of regulated articles and outdoor...

  17. 7 CFR 301.45-7 - Assembly and inspection of regulated articles and outdoor household articles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Assembly and inspection of regulated articles and outdoor household articles. 301.45-7 Section 301.45-7 Agriculture Regulations of the Department of... QUARANTINE NOTICES Gypsy Moth § 301.45-7 Assembly and inspection of regulated articles and outdoor...

  18. 7 CFR 301.45-7 - Assembly and inspection of regulated articles and outdoor household articles.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Assembly and inspection of regulated articles and outdoor household articles. 301.45-7 Section 301.45-7 Agriculture Regulations of the Department of... QUARANTINE NOTICES Gypsy Moth § 301.45-7 Assembly and inspection of regulated articles and outdoor...

  19. 7 CFR 301.45-7 - Assembly and inspection of regulated articles and outdoor household articles.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Assembly and inspection of regulated articles and outdoor household articles. 301.45-7 Section 301.45-7 Agriculture Regulations of the Department of... QUARANTINE NOTICES Gypsy Moth § 301.45-7 Assembly and inspection of regulated articles and outdoor...

  20. 7 CFR 319.75 - Restrictions on importation of restricted articles; disposal of articles refused importation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...; disposal of articles refused importation. 319.75 Section 319.75 Agriculture Regulations of the Department...; disposal of articles refused importation. (a) The Secretary has determined that in order to prevent the... subpart. (b) Any article refused importation for noncompliance with the requirements of this subpart...