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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. 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

  3. The molecular pathways underlying host resistance and tolerance to pathogens

    PubMed Central

    Glass, Elizabeth J.

    2012-01-01

    Breeding livestock that are better able to withstand the onslaught of endemic- and exotic pathogens is high on the wish list of breeders and farmers world-wide. However, the defense systems in both pathogens and their hosts are complex and the degree of genetic variation in resistance and tolerance will depend on the trade-offs that they impose on host fitness as well as their life-histories. The genes and pathways underpinning resistance and tolerance traits may be distinct or intertwined as the outcome of any infection is a result of a balance between collateral damage of host tissues and control of the invading pathogen. Genes and molecular pathways associated with resistance are mainly expressed in the mucosal tract and the innate immune system and control the very early events following pathogen invasion. Resistance genes encode receptors involved in uptake of pathogens, as well as pattern recognition receptors (PRR) such as the toll-like receptor family as well as molecules involved in strong and rapid inflammatory responses which lead to rapid pathogen clearance, yet do not lead to immunopathology. In contrast tolerance genes and pathways play a role in reducing immunopathology or enhancing the host's ability to protect against pathogen associated toxins. Candidate tolerance genes may include cytosolic PRRs and unidentified sensors of pathogen growth, perturbation of host metabolism and intrinsic danger or damage associated molecules. In addition, genes controlling regulatory pathways, tissue repair and resolution are also tolerance candidates. The identities of distinct genetic loci for resistance and tolerance to infectious pathogens in livestock species remain to be determined. A better understanding of the mechanisms involved and phenotypes associated with resistance and tolerance should ultimately help to improve livestock health and welfare. PMID:23403960

  4. The molecular pathways underlying host resistance and tolerance to pathogens.

    PubMed

    Glass, Elizabeth J

    2012-01-01

    Breeding livestock that are better able to withstand the onslaught of endemic- and exotic pathogens is high on the wish list of breeders and farmers world-wide. However, the defense systems in both pathogens and their hosts are complex and the degree of genetic variation in resistance and tolerance will depend on the trade-offs that they impose on host fitness as well as their life-histories. The genes and pathways underpinning resistance and tolerance traits may be distinct or intertwined as the outcome of any infection is a result of a balance between collateral damage of host tissues and control of the invading pathogen. Genes and molecular pathways associated with resistance are mainly expressed in the mucosal tract and the innate immune system and control the very early events following pathogen invasion. Resistance genes encode receptors involved in uptake of pathogens, as well as pattern recognition receptors (PRR) such as the toll-like receptor family as well as molecules involved in strong and rapid inflammatory responses which lead to rapid pathogen clearance, yet do not lead to immunopathology. In contrast tolerance genes and pathways play a role in reducing immunopathology or enhancing the host's ability to protect against pathogen associated toxins. Candidate tolerance genes may include cytosolic PRRs and unidentified sensors of pathogen growth, perturbation of host metabolism and intrinsic danger or damage associated molecules. In addition, genes controlling regulatory pathways, tissue repair and resolution are also tolerance candidates. The identities of distinct genetic loci for resistance and tolerance to infectious pathogens in livestock species remain to be determined. A better understanding of the mechanisms involved and phenotypes associated with resistance and tolerance should ultimately help to improve livestock health and welfare. PMID:23403960

  5. Subversion of membrane transport pathways by vacuolar pathogens

    PubMed Central

    Alix, Eric; Mukherjee, Shaeri

    2011-01-01

    Mammalian phagocytes control bacterial infections effectively through phagocytosis, the process by which particles engulfed at the cell surface are transported to lysosomes for destruction. However, intracellular pathogens have evolved mechanisms to avoid this fate. Many bacterial pathogens use specialized secretion systems to deliver proteins into host cells that subvert signaling pathways controlling membrane transport. These bacterial effectors modulate the function of proteins that regulate membrane transport and alter the phospholipid content of membranes. Elucidating the biochemical function of these effectors has provided a greater understanding of how bacteria control membrane transport to create a replicative niche within the host and provided insight into the regulation of membrane transport in eukaryotic cells. PMID:22123831

  6. 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

  7. Stress signaling pathways for the pathogenicity of Cryptococcus.

    PubMed

    Bahn, Yong-Sun; Jung, Kwang-Woo

    2013-12-01

    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

    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

    2015-05-14

    Mitogen-activated protein kinase (MAPK) cascades play central roles in innate immune signalling networks in plants and animals. In plants, however, the molecular mechanisms of how signal perception is transduced to MAPK activation remain elusive. Here we report that pathogen-secreted proteases activate a previously unknown signalling pathway in Arabidopsis thaliana involving the Gα, Gβ, and Gγ subunits of heterotrimeric G-protein complexes, which function upstream of an 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 signalling to downstream activation of an MAPK cascade. The protease-G-protein-RACK1-MAPK cascade modules identified in these studies are distinct from previously described plant immune signalling pathways such as that elicited by bacterial flagellin, in which G proteins function downstream of or in parallel to an MAPK cascade without the involvement of the RACK1 scaffolding protein. The discovery of the new protease-mediated immune signalling 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 immunoregulatory strategies that account for its niche adaptation to diverse host tissues and immune systems. PMID:25731164

  9. 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; Djonovi?, 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 G?, G? and G? 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 G? 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

  10. 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 ?2-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-? production, likely through NF-?B 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

  11. The spore differentiation pathway in the enteric pathogen Clostridium difficile.

    PubMed

    Pereira, Fátima C; Saujet, Laure; Tomé, Ana R; Serrano, Mónica; Monot, Marc; Couture-Tosi, Evelyne; Martin-Verstraete, Isabelle; Dupuy, Bruno; Henriques, Adriano O

    2013-01-01

    Endosporulation is an ancient bacterial developmental program that culminates with the differentiation of a highly resistant endospore. In the model organism Bacillus subtilis, gene expression in the forespore and in the mother cell, the two cells that participate in endospore development, is governed by cell type-specific RNA polymerase sigma subunits. σ(F) in the forespore, and σ(E) in the mother cell control early stages of development and are replaced, at later stages, by σ(G) and σ(K), respectively. Starting with σ(F), the activation of the sigma factors is sequential, requires the preceding factor, and involves cell-cell signaling pathways that operate at key morphological stages. Here, we have studied the function and regulation of the sporulation sigma factors in the intestinal pathogen Clostridium difficile, an obligate anaerobe in which the endospores are central to the infectious cycle. The morphological characterization of mutants for the sporulation sigma factors, in parallel with use of a fluorescence reporter for single cell analysis of gene expression, unraveled important deviations from the B. subtilis paradigm. While the main periods of activity of the sigma factors are conserved, we show that the activity of σ(E) is partially independent of σ(F), that σ(G) activity is not dependent on σ(E), and that the activity of σ(K) does not require σ(G). We also show that σ(K) is not strictly required for heat resistant spore formation. In all, our results indicate reduced temporal segregation between the activities of the early and late sigma factors, and reduced requirement for the σ(F)-to-σ(E), σ(E)-to-σ(G), and σ(G)-to-σ(K) cell-cell signaling pathways. Nevertheless, our results support the view that the top level of the endosporulation network is conserved in evolution, with the sigma factors acting as the key regulators of the pathway, established some 2.5 billion years ago upon its emergence at the base of the Firmicutes Phylum. PMID:24098139

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

    PubMed

    Knig, 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. PMID:23649940

  13. 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

  14. Convergent pathogenic pathways in Alzheimer’s and Huntington disease: Shared targets for drug development

    PubMed Central

    Ehrnhoefer, Dagmar E.; Wong, Bibiana K.Y.; Hayden, Michael R.

    2011-01-01

    Neurodegenerative diseases exemplified by Alzheimer’s and Huntington disease are characterized by the progressive neuropsychiatric dysfunction and loss of specific neuronal subtypes. Even though there are differences in the exact sites of pathology and clinical profiles only partially overlap, considerable similarities in disease mechanisms and pathogenic pathways can be observed. These shared mechanisms raise the possibility of common therapeutic targets for drug development. Huntington disease with a monogenic cause and the possibility to accurately identify pre-manifest mutation carriers could be exploited as a ‘model’ for Alzheimer’s disease to test the efficacy of therapeutic interventions targeting shared pathogenic pathways. PMID:22015920

  15. Co-evolution and exploitation of host cell signaling pathways by bacterial pathogens.

    PubMed

    Shames, Stephanie R; Auweter, Sigrid D; Finlay, B Brett

    2009-02-01

    Bacterial pathogens have evolved by combinations of gene acquisition, deletion, and modification, which increases their fitness. Additionally, bacteria are able to evolve in "quantum leaps" via the ability to promiscuously acquire new genes. Many bacterial pathogens - especially Gram-negative enteric pathogens - have evolved mechanisms by which to subvert signal transduction pathways of eukaryotic cells by expressing genes that mimic or regulate host protein factors involved in a variety of signaling cascades. This results in the ability to cause diseases ranging from tumor formation in plants to gastroenteritis and bubonic plague. Here, we present recent advances on mechanisms of bacterial pathogen evolution, including specific signaling cascades targeted by their virulence genes with an emphasis on the ubiquitin modification system, Rho GTPase regulators, cytoskeletal modulators, and host innate immunity. We also comment briefly on evolution of host defense mechanisms in place that limit disease caused by bacterial pathogens. PMID:18775503

  16. 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. PMID:25745806

  17. Analysis and construction of pathogenicity island regulatory pathways in Salmonella enterica serovar Typhi.

    PubMed

    Ong, Su Yean; Ng, Fui Ling; Badai, Siti Suriawati; Yuryev, Anton; Alam, Maqsudul

    2010-01-01

    Signal transduction through protein-protein interactions and protein modifications are the main mechanisms controlling many biological processes. Here we described the implementation of MedScan information extraction technology and Pathway Studio software (Ariadne Genomics Inc.) to create a Salmonella specific molecular interaction database. Using the database, we have constructed several signal transduction pathways in Salmonella enterica serovar Typhi which causes Typhoid Fever, a major health threat especially in developing countries. S. Typhi has several pathogenicity islands that control rapid switching between different phenotypes including adhesion and colonization, invasion, intracellular survival, proliferation, and biofilm formation in response to environmental changes. Understanding of the detailed mechanism for S. Typhi survival in host cells is necessary for development of efficient detection and treatment of this pathogen. The constructed pathways were validated using publically available gene expression microarray data for Salmonella. PMID:20861532

  18. 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

  19. 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

  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. PMID:26867180

  1. The Renaissance of Bacillosamine and Its Derivatives: Pathway Characterization and Implications in Pathogenicity

    PubMed Central

    2015-01-01

    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. PMID:24383882

  2. Transcriptome of Aphanomyces euteiches: new oomycete putative pathogenicity factors and metabolic pathways.

    PubMed

    Gaulin, Elodie; Madoui, Mohammed-Amine; Bottin, Arnaud; Jacquet, Christophe; Math, Catherine; Couloux, Arnaud; Wincker, Patrick; Dumas, Bernard

    2008-01-01

    Aphanomyces euteiches is an oomycete pathogen that causes seedling blight and root rot of legumes, such as alfalfa and pea. The genus Aphanomyces is phylogenically distinct from well-studied oomycetes such as Phytophthora sp., and contains species pathogenic on plants and aquatic animals. To provide the first foray into gene diversity of A. euteiches, two cDNA libraries were constructed using mRNA extracted from mycelium grown in an artificial liquid medium or in contact to plant roots. A unigene set of 7,977 sequences was obtained from 18,864 high-quality expressed sequenced tags (ESTs) and characterized for potential functions. Comparisons with oomycete proteomes revealed major differences between the gene content of A. euteiches and those of Phytophthora species, leading to the identification of biosynthetic pathways absent in Phytophthora, of new putative pathogenicity genes and of expansion of gene families encoding extracellular proteins, notably different classes of proteases. Among the genes specific of A. euteiches are members of a new family of extracellular proteins putatively involved in adhesion, containing up to four protein domains similar to fungal cellulose binding domains. Comparison of A. euteiches sequences with proteomes of fully sequenced eukaryotic pathogens, including fungi, apicomplexa and trypanosomatids, allowed the identification of A. euteiches genes with close orthologs in these microorganisms but absent in other oomycetes sequenced so far, notably transporters and non-ribosomal peptide synthetases, and suggests the presence of a defense mechanism against oxidative stress which was initially characterized in the pathogenic trypanosomatids. PMID:18320043

  3. Population history and pathways of spread of the plant pathogen Phytophthora plurivora.

    PubMed

    Schoebel, Corine N; Stewart, Jane; Grnwald, Niklaus J; 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

  4. IntPath--an integrated pathway gene relationship database for model organisms and important pathogens

    PubMed Central

    2012-01-01

    Background Pathway data are important for understanding the relationship between genes, proteins and many other molecules in living organisms. Pathway gene relationships are crucial information for guidance, prediction, reference and assessment in biochemistry, computational biology, and medicine. Many well-established databases--e.g., KEGG, WikiPathways, and BioCyc--are dedicated to collecting pathway data for public access. However, the effectiveness of these databases is hindered by issues such as incompatible data formats, inconsistent molecular representations, inconsistent molecular relationship representations, inconsistent referrals to pathway names, and incomprehensive data from different databases. Results In this paper, we overcome these issues through extraction, normalization and integration of pathway data from several major public databases (KEGG, WikiPathways, BioCyc, etc). We build a database that not only hosts our integrated pathway gene relationship data for public access but also maintains the necessary updates in the long run. This public repository is named IntPath (Integrated Pathway gene relationship database for model organisms and important pathogens). Four organisms--S. cerevisiae, M. tuberculosis H37Rv, H. Sapiens and M. musculus--are included in this version (V2.0) of IntPath. IntPath uses the "full unification" approach to ensure no deletion and no introduced noise in this process. Therefore, IntPath contains much richer pathway-gene and pathway-gene pair relationships and much larger number of non-redundant genes and gene pairs than any of the single-source databases. The gene relationships of each gene (measured by average node degree) per pathway are significantly richer. The gene relationships in each pathway (measured by average number of gene pairs per pathway) are also considerably richer in the integrated pathways. Moderate manual curation are involved to get rid of errors and noises from source data (e.g., the gene ID errors in WikiPathways and relationship errors in KEGG). We turn complicated and incompatible xml data formats and inconsistent gene and gene relationship representations from different source databases into normalized and unified pathway-gene and pathway-gene pair relationships neatly recorded in simple tab-delimited text format and MySQL tables, which facilitates convenient automatic computation and large-scale referencing in many related studies. IntPath data can be downloaded in text format or MySQL dump. IntPath data can also be retrieved and analyzed conveniently through web service by local programs or through web interface by mouse clicks. Several useful analysis tools are also provided in IntPath. Conclusions We have overcome in IntPath the issues of compatibility, consistency, and comprehensiveness that often hamper effective use of pathway databases. We have included four organisms in the current release of IntPath. Our methodology and programs described in this work can be easily applied to other organisms; and we will include more model organisms and important pathogens in future releases of IntPath. IntPath maintains regular updates and is freely available at http://compbio.ddns.comp.nus.edu.sg:8080/IntPath. PMID:23282057

  5. Niche-specific regulation of central metabolic pathways in a fungal pathogen.

    PubMed

    Barelle, Caroline J; Priest, Claire L; Maccallum, Donna M; Gow, Neil A R; Odds, Frank C; Brown, Alistair J P

    2006-06-01

    To establish an infection, the pathogen Candida albicans must assimilate carbon and grow in its mammalian host. This fungus assimilates six-carbon compounds via the glycolytic pathway, and two-carbon compounds via the glyoxylate cycle and gluconeogenesis. We address a paradox regarding the roles of these central metabolic pathways in C. albicans pathogenesis: the glyoxylate cycle is apparently required for virulence although glyoxylate cycle genes are repressed by glucose at concentrations present in the bloodstream. Using GFP fusions, we confirm that glyoxylate cycle and gluconeogenic genes in C. albicans are repressed by physiologically relevant concentrations of glucose, and show that these genes are inactive in the majority of fungal cells infecting the mouse kidney. However, these pathways are induced following phagocytosis by macrophages or neutrophils. In contrast, glycolytic genes are not induced following phagocytosis and are expressed in infected kidney. Mutations in all three pathways attenuate the virulence of this fungus, highlighting the importance of central carbon metabolism for the establishment of C. albicans infections. We conclude that C. albicans displays a metabolic program whereby the glyoxylate cycle and gluconeogenesis are activated early, when the pathogen is phagocytosed by host cells, while the subsequent progression of systemic disease is dependent upon glycolysis. PMID:16681837

  6. PTS1 Peroxisomal Import Pathway Plays Shared and Distinct Roles to PTS2 Pathway in Development and Pathogenicity of Magnaporthe oryzae

    PubMed Central

    Wang, Jiaoyu; Zhang, Zhen; Wang, Yanli; Li, Ling; Chai, Rongyao; Mao, Xueqin; Jiang, Hua; Qiu, Haiping; Du, Xinfa; Lin, Fucheng; Sun, Guochang

    2013-01-01

    Peroxisomes participate in various important metabolisms and are required in pathogenicity of fungal plant pathogens. Peroxisomal matrix proteins are imported from cytoplasm into peroxisomes through peroxisomal targeting signal 1 (PTS1) or peroxisomal targeting signal 2 (PTS2) import pathway. PEX5 and PEX7 genes participate in the two pathways respectively. The involvement of PEX7 mediated PTS2 import pathway in fungal pathogenicity has been documented, while that of PTS1 remains unclear. Through null mutant analysis of MoPEX5, the PEX5 homolog in Magnaporthe oryzae, we report the crucial roles of PTS1 pathway in the development and host infection in the rice blast fungus, and compared with those of PTS2. We found that MoPEX5 disruption specifically blocked the PTS1 pathway. Δmopex5 was unable to use lipids as sole carbon source and lost pathogenicity completely. Similar as Δmopex7, Δmopex5 exhibited significant reduction in lipid utilization and mobilization, appressorial turgor genesis and H2O2 resistance. Additionally, Δmopex5 presented some distinct defects which were undetected in Δmopex7 in vegetative growth, conidial morphogenesis, appressorial morphogenesis and melanization. The results indicated that the PTS1 peroxisomal import pathway, in addition to PTS2, is required for fungal development and pathogenicity of the rice blast fungus, and also, as a main peroxisomal import pathway, played a more predominant role than PTS2. PMID:23405169

  7. A sophisticated network of signaling pathways regulates stomatal defenses to bacterial pathogens.

    PubMed

    Arnaud, Dominique; Hwang, Ildoo

    2015-04-01

    Guard cells are specialized cells forming stomatal pores at the leaf surface for gas exchanges between the plant and the atmosphere. Stomata have been shown to play an important role in plant defense as a part of the innate immune response. Plants actively close their stomata upon contact with microbes, thereby preventing pathogen entry into the leaves and the subsequent colonization of host tissues. In this review, we present current knowledge of molecular mechanisms and signaling pathways implicated in stomatal defenses, with particular emphasis on plant-bacteria interactions. Stomatal defense responses begin from the perception of pathogen-associated molecular patterns (PAMPs) and activate a signaling cascade involving the production of secondary messengers such as reactive oxygen species, nitric oxide, and calcium for the regulation of plasma membrane ion channels. The analyses on downstream molecular mechanisms implicated in PAMP-triggered stomatal closure have revealed extensive interplays among the components regulating hormonal signaling pathways. We also discuss the strategies deployed by pathogenic bacteria to counteract stomatal immunity through the example of the phytotoxin coronatine. PMID:25661059

  8. Peroxisomal and Mitochondrial ?-Oxidation Pathways Influence the Virulence of the Pathogenic Fungus Cryptococcus neoformans

    PubMed Central

    Kretschmer, Matthias; Wang, Joyce

    2012-01-01

    An understanding of the connections between metabolism and elaboration of virulence factors during host colonization by the human-pathogenic fungus Cryptococcus neoformans is important for developing antifungal therapies. Lipids are abundant in host tissues, and fungal pathogens in the phylum basidiomycota possess both peroxisomal and mitochondrial ?-oxidation pathways to utilize this potential carbon source. In addition, lipids are important signaling molecules in both fungi and mammals. In this report, we demonstrate that defects in the peroxisomal and mitochondrial ?-oxidation pathways influence the growth of C. neoformans on fatty acids as well as the virulence of the fungus in a mouse inhalation model of cryptococcosis. Disease attenuation may be due to the cumulative influence of altered carbon source acquisition or processing, interference with secretion, changes in cell wall integrity, and an observed defect in capsule production for the peroxisomal mutant. Altered capsule elaboration in the context of a ?-oxidation defect was unexpected but is particularly important because this trait is a major virulence factor for C. neoformans. Additionally, analysis of mutants in the peroxisomal pathway revealed a growth-promoting activity for C. neoformans, and subsequent work identified oleic acid and biotin as candidates for such factors. Overall, this study reveals that ?-oxidation influences virulence in C. neoformans by multiple mechanisms that likely include contributions to carbon source acquisition and virulence factor elaboration. PMID:22707485

  9. The STING pathway and regulation of innate immune signaling in response to DNA pathogens.

    PubMed

    Ishikawa, Hiroki; Barber, Glen N

    2011-04-01

    The innate immune system has evolved a variety of sensing mechanisms to detect and counter microbial invasion. These include the Toll-like receptor (TLR), cytoplasmic, nucleotide binding oligomerization domain (NOD)-like receptor and RIG-I-like helicase (RLH) pathways. However, how the cell detects pathogen-associated DNA to trigger host defense, including the production of interferon, remains to be fully clarified. Understanding these processes could have profound implications into how we understand and treat a variety of microbial-related disease, including viral-associated cancers, as well as autoimmune disorders. Recently, an endoplasmic reticulum-associated molecule referred to as STING (for stimulator of interferon genes) was isolated and shown to be critical for regulating the production of IFN in response to cytoplasmic DNA. Here, we review recent discoveries relating to the detection of foreign DNA, including the importance of the STING and inflammasome pathways and the triggering of innate signaling processes. PMID:21161320

  10. 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

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

    PubMed

    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

  12. 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

  13. Metabolic pathways of Pseudomonas aeruginosa involved in competition with respiratory bacterial pathogens

    PubMed Central

    Beaume, Marie; Khler, Thilo; Fontana, Thierry; Tognon, Mikael; Renzoni, Adriana; van Delden, Christian

    2015-01-01

    Background: Chronic airway infection by Pseudomonas aeruginosa considerably contributes to lung tissue destruction and impairment of pulmonary function in cystic-fibrosis (CF) patients. Complex interplays between P. aeruginosa and other co-colonizing pathogens including Staphylococcus aureus, Burkholderia sp., and Klebsiella pneumoniae may be crucial for pathogenesis and disease progression. Methods: We generated a library of PA14 transposon insertion mutants to identify P. aeruginosa genes required for exploitative and direct competitions with S. aureus, Burkholderia cenocepacia, and K. pneumoniae. Results: Whereas wild-type PA14 inhibited S. aureus growth, two transposon insertions located in pqsC and carB, resulted in reduced growth inhibition. PqsC is involved in the synthesis of 4-hydroxy-2-alkylquinolines (HAQs), a family of molecules having antibacterial properties, while carB is a key gene in pyrimidine biosynthesis. The carB mutant was also unable to grow in the presence of B. cepacia and K. pneumoniae but not Escherichia coli and S. epidermidis. We further identified a transposon insertion in purF, encoding a key enzyme of purine metabolism. This mutant displayed a severe growth deficiency in the presence of Gram-negative but not of Gram-positive bacteria. We identified a beneficial interaction in a bioA transposon mutant, unable to grow on rich medium. This growth defect could be restored either by addition of biotin or by co-culturing the mutant in the presence of K. pneumoniae or E. coli. Conclusion: Complex interactions take place between the various bacterial species colonizing CF-lungs. This work identified both detrimental and beneficial interactions occurring between P. aeruginosa and three other respiratory pathogens involving several major metabolic pathways. Manipulating these pathways could be used to interfere with bacterial interactions and influence the colonization by respiratory pathogens. PMID:25954256

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

    PubMed

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

    2015-09-01

    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

  15. 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

  16. Cyclic di-GMP-dependent signaling pathways in the pathogenic Firmicute Listeria monocytogenes.

    PubMed

    Chen, Li-Hong; Kseo?lu, Volkan K; Gvener, Zehra T; Myers-Morales, Tanya; Reed, Joseph M; D'Orazio, Sarah E F; Miller, Kurt W; Gomelsky, Mark

    2014-08-01

    We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all phosphodiesterase genes (?pdeB/C/D) or expression of a heterologous diguanylate cyclase stimulated production of a previously unknown exopolysaccharide. The synthesis of this exopolysaccharide was attributed to the pssA-E (lmo0527-0531) gene cluster. The last gene of the cluster encodes the fourth listerial GGDEF domain protein, PssE, that functions as an I-site c-di-GMP receptor essential for exopolysaccharide synthesis. The c-di-GMP-inducible exopolysaccharide causes cell aggregation in minimal medium and impairs bacterial migration in semi-solid agar, however, it does not promote biofilm formation on abiotic surfaces. The exopolysaccharide also greatly enhances bacterial tolerance to commonly used disinfectants as well as desiccation, which may contribute to survival of L. monocytogenes on contaminated food products and in food-processing facilities. The exopolysaccharide and another, as yet unknown c-di-GMP-dependent target, drastically decrease listerial invasiveness in enterocytes in vitro, and lower pathogen load in the liver and gallbladder of mice infected via an oral route, which suggests that elevated c-di-GMP levels play an overall negative role in listerial virulence. PMID:25101646

  17. Cyclic di-GMP-dependent Signaling Pathways in the Pathogenic Firmicute Listeria monocytogenes

    PubMed Central

    Chen, Li-Hong; Köseoğlu, Volkan K.; Güvener, Zehra T.; Myers-Morales, Tanya; Reed, Joseph M.; D'Orazio, Sarah E. F.; Miller, Kurt W.; Gomelsky, Mark

    2014-01-01

    We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all phosphodiesterase genes (ΔpdeB/C/D) or expression of a heterologous diguanylate cyclase stimulated production of a previously unknown exopolysaccharide. The synthesis of this exopolysaccharide was attributed to the pssA-E (lmo0527-0531) gene cluster. The last gene of the cluster encodes the fourth listerial GGDEF domain protein, PssE, that functions as an I-site c-di-GMP receptor essential for exopolysaccharide synthesis. The c-di-GMP-inducible exopolysaccharide causes cell aggregation in minimal medium and impairs bacterial migration in semi-solid agar, however, it does not promote biofilm formation on abiotic surfaces. The exopolysaccharide also greatly enhances bacterial tolerance to commonly used disinfectants as well as desiccation, which may contribute to survival of L. monocytogenes on contaminated food products and in food-processing facilities. The exopolysaccharide and another, as yet unknown c-di-GMP-dependent target, drastically decrease listerial invasiveness in enterocytes in vitro, and lower pathogen load in the liver and gallbladder of mice infected via an oral route, which suggests that elevated c-di-GMP levels play an overall negative role in listerial virulence. PMID:25101646

  18. The human pathogen Pseudomonas aeruginosa utilizes conserved virulence pathways to infect the social amoeba Dictyostelium discoideum

    PubMed Central

    Pukatzki, Stefan; Kessin, Richard H.; Mekalanos, John J.

    2002-01-01

    Genetically accessible host models are useful for studying microbial pathogenesis because they offer the means to identify novel strategies that pathogens use to evade immune mechanisms, cause cellular injury, and induce disease. We have developed conditions under which the human pathogen Pseudomonas aeruginosa infects Dictyostelium discoideum, a genetically tractable eukaryotic organism. When D. discoideum is plated on nutrient agar plates with different P. aeruginosa strains, the bacteria form lawns on these plates with amoebae embedded in them. Virulent P. aeruginosa strains kill these amoebae and leave an intact bacterial lawn. A number of P. aeruginosa mutants have been identified that are avirulent in this assay. Amoebae feed on these bacteria and form plaques in their bacterial lawns. One avirulent mutant strain carries an insertional mutation in the lasR gene. LasR is a transcription factor that controls a number of virulence genes in a density-dependent fashion. Another class of avirulent P. aeruginosa mutants is defective in type III secretion. One mutant lacks the PscJ protein, a structural component of the secretion apparatus, suggesting that cytotoxins are injected into the D. discoideum cell. One of these cytotoxins is ExoU, and exoU mutants are avirulent toward D. discoideum. Complementation of the lasR and exoU mutations restores virulence. Therefore, P. aeruginosa uses conserved virulence pathways to kill D. discoideum. PMID:11867744

  19. Inhibitors of the sulfur assimilation pathway in bacterial pathogens as enhancers of antibiotic therapy.

    PubMed

    Campanini, Barbara; Pieroni, Marco; Raboni, Samanta; Bettati, Stefano; Benoni, Roberto; Pecchini, Chiara; Costantino, Gabriele; Mozzarelli, Andrea

    2015-01-01

    The rising emergence of antibiotic resistance urges the search for new strategies to defeat microorganisms that lead to persistent infections of the host. Tolerant to antibiotics, slowly replicating bacteria often cause latent and persistent infections that are the most challenging for pharmacological treatment. Persistence inside the host requires an extensive re-programming of the pathogen metabolic functions, due to the extremely hostile environment they face. Therefore, targeting key metabolic functions could result in better antibiotic treatments, shortened latency periods, and increased susceptibility to traditional antibiotics. Bacteria, differently from mammals, assimilate inorganic sulfur into cysteine, the precursor of a number of key metabolites including reducing agents, cofactors and membrane components. Inhibition of cysteine biosynthesis was proven to interfere heavily with the ability of pathogens to fight oxidative stress, to infect the host and to establish long-term infections. This review has the purpose of i) briefly summarizing the key structural and functional properties of transporters and enzymes involved in sulfur assimilation, ii) presenting biological evidence that supports the exploitation of this pathway for the identification of potential targets and, iii) highlighting intense efforts and advancements in the search of promising candidates for the development of novel compounds that enhance antibiotics therapy. PMID:25388010

  20. 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

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

    PubMed

    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

    2015-07-01

    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

  2. Interference with nuclear factor kappaB signaling pathway by pathogen-encoded proteases: global and selective inhibition.

    PubMed

    Hodgson, Andrea; Wan, Fengyi

    2016-02-01

    Pathogens have evolved a myriad of ways to abrogate and manipulate the host response to infections. Of the various mechanisms involved, pathogen-encoded and sometimes host-encoded proteases are an important category of virulence factors that cause robust changes on the host response by targeting key proteins along signaling cascades. The nuclear factor kappaB (NF-?B) signaling pathway is a crucial regulatory mechanism for the cell, controlling the expression of survival, immune and proliferation genes. Proteases from pathogens of almost all types have been demonstrated to target and cleave members of the NF-?B signaling pathway at nearly every level. This review provides discussion of proteases targeting the most abundant NF-?B subunit, p65, and the impact of protease-mediated p65 cleavage on the immune responses and survival of the infected host cell. After examining various examples of protease interference, it becomes evident that the cleavage fragments produced by pathogen-driven proteolytic processing should be further characterized to determine whether they have novel and unique functions within the cell. The selective targeting of p65 and its effect on gene transcription reveals unique mechanisms by which pathogens acutely alter their microenvironment, and further research may open new opportunities for novel therapeutics to combat pathogens. PMID:26449378

  3. 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...

  4. Two Functional Type VI Secretion Systems in Avian Pathogenic Escherichia coli Are Involved in Different Pathogenic Pathways

    PubMed Central

    Ma, Jiale; Bao, Yinli; Sun, Min; Dong, Wenyang; Pan, Zihao; Zhang, Wei; Lu, Chengping

    2014-01-01

    Type VI secretion systems (T6SSs) are involved in the pathogenicity of several Gram-negative bacteria. The VgrG protein, a core component and effector of T6SS, has been demonstrated to perform diverse functions. The N-terminal domain of VgrG protein is a homologue of tail fiber protein gp27 of phage T4, which performs a receptor binding function and determines the host specificity. Based on sequence analysis, we found that two putative T6SS loci exist in the genome of the avian pathogenic Escherichia coli (APEC) strain TW-XM. To assess the contribution of these two T6SSs to TW-XM pathogenesis, the crucial clpV clusters of these two T6SS loci and their vgrG genes were deleted to generate a series of mutants. Consequently, T6SS1-associated mutants presented diminished adherence to and invasion of several host cell lines cultured in vitro, decreased pathogenicity in duck and mouse infection models in vivo, and decreased biofilm formation and bacterial competitive advantage. In contrast, T6SS2-associated mutants presented a significant decrease only in the adherence to and invasion of mouse brain microvascular endothelial cell (BMEC) line bEnd.3 and brain tissue of the duck infection model. These results suggested that T6SS1 was involved in the proliferation of APEC in systemic infection, whereas VgrG-T6SS2 was responsible only for cerebral infection. Further study demonstrated that VgrG-T6SS2 was able to bind to the surface of bEnd.3 cells, whereas it did not bind to DF-1 (chicken embryo fibroblast) cells, which further proved the interaction of VgrG-T6SS2 with the surface of BMECs. PMID:24980972

  5. Differential involvement of indole-3-acetic acid biosynthetic pathways in pathogenicity and epiphytic fitness of Erwinia herbicola pv. gypsophilae.

    PubMed

    Manulis, S; Haviv-Chesner, A; Brandl, M T; Lindow, S E; Barash, I

    1998-07-01

    Erwinia herbicola pv. gypsophilae (Ehg), which induces galls on Gypsophila paniculata, harbors two major pathways for indole-3-acetic acid (IAA) synthesis, the indole-3-acetamide (IAM) and indole-3-pyruvate (IPyA) routes, as well as cytokinin biosynthetic genes. Mutants were generated in which the various biosynthetic routes were disrupted separately or jointly in order to assess the contribution of IAA of various origins and cytokinins to pathogenicity and epiphytic fitness. Inactivation of the IAM pathway or cytokinin biosynthesis caused the largest reduction in gall size. Inactivation of the IPyA pathway caused a minor, nonsignificant decrease in pathogenicity. No further reduction in gall size was observed by the simultaneous inactivation of both IAA pathways only or in combination with that of cytokinin production. However, inactivation of the IPyA pathway caused a 14-fold reduction in the population of Ehg on bean plants. Inactivation of the IAM pathway or cytokinin production did not affect epiphytic fitness. While the apparent transcriptional activity of iaaM-inaZ fusion increased slightly in cells of Ehg on bean and gypsophila leaves, compared with that in culture, very high levels of induction were observed in cells injected into gypsophila stems. In contrast, moderate levels of induction of ipdC-inaZ in Ehg were observed on leaves of these plants and in gypsophila stems, when compared with that in culture. These results suggest that the IAM pathway is involved primarily in gall formation and support the main contribution of the IpyA pathway to the epiphytic fitness of this bacterial species. PMID:9650296

  6. 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

  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

    Grecov, Gabriela; Neboh?ov, Martina; Zeman, Igor; Pryszcz, Leszek P; Tomka, ?ubomr; Gabaldn, 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. Crosstalk between the Unfolded Protein Response and Pathways That Regulate Pathogenic Development in Ustilago maydis[C][W

    PubMed Central

    Heimel, Kai; Freitag, Johannes; Hampel, Martin; Ast, Julia; Blker, Michael; Kmper, Jrg

    2013-01-01

    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. PMID:24179126

  10. A Resealed-Cell System for Analyzing Pathogenic Intracellular Events: Perturbation of Endocytic Pathways under Diabetic Conditions

    PubMed Central

    Kano, Fumi; Nakatsu, Daiki; Noguchi, Yoshiyuki; Yamamoto, Akitsugu; Murata, Masayuki

    2012-01-01

    Cell-based assay systems that can serve as cellular models of aberrant function in pathogenic organs would be novel and useful tools for screening drugs and clarifying the molecular mechanisms of various diseases. We constructed model cells that replicated the conditions in diabetic hepatocytes by using the cell resealing technique, which enables the exchange of cytosol. The plasma membrane of HeLa cells was permeabilized with the streptococcal toxin streptolysin O, and cytosol that had been prepared from wild-type or db/db diabetic mice was introduced into the resulting semi-intact cells. By resealing the plasma membrane by exposure to Ca2+, we created WT or Db model cells, in which the cytosolic conditions replicated those of healthy or diabetic liver. Interestingly, phosphorylation of p38 MAPK was promoted, whereas the level of endosomal phosphatidylinositol-3-phosphate was decreased, in Db cells. We investigated several endocytic pathways in WT and Db cells, and found that retrograde endosome-to-Golgi transport was delayed in a p38 MAPK-dependent manner in Db cells. Furthermore, the degradation pathway of the EGF receptor from endosomes to lysosomes was enhanced in Db cells, and this did not depend on the activation of p38 MAPK. The disease model cell system should become a powerful tool for the detection of aberrant processes in cells under pathogenic conditions and for therapeutic applications. PMID:22952896

  11. 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. PMID:26726767

  12. 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

  13. Anti-inflammatory pathways as a host evasion mechanism for pathogens.

    PubMed

    Aliberti, Julio; Bafica, Andre

    2005-01-01

    Lipoxins play a key role in controlling potent pro-inflammatory responses triggered by infection with pathogens, such as Toxoplasma gondii and Mycobacterium tuberculosis. In order to contain microbial dissemination, infected hosts must mount a powerful immune response to prevent mortality. The onset of the chronic phase of infection is characterized by continuous cell-mediated immunity. Such potent responses are kept under tight control by a class of anti-inflammatory eicosanoids, the lipoxins. Here, we review such immune-containment strategies from the host's perspective, to keep pro-inflammatory responses under control during chronic disease, as well as from the perspective of the pathogen, which pirates the host's lipoxygenase machinery to its own advantage as a probable immune-escape mechanism. PMID:15982863

  14. Plasticity of the malleobactin pathway and its impact on siderophore action in human pathogenic bacteria.

    PubMed

    Franke, Jakob; Ishida, Keishi; Hertweck, Christian

    2015-05-26

    The human pathogenic bacteria Burkholderia mallei, Burkholderia pseudomallei, and Burkholderia thailandensis harbor a highly conserved gene cluster coding for the biosynthesis of the long sought-after malleobactins. Four new, unexpected congeners of the malleobactin family that were isolated and fully characterized in this study feature unusual deviations from the parent, ornibactin-like architecture. Thus, the malleobactin non-ribosomal peptide synthetase (NRPS) has a rare flexibility that yields diverse peptide backbones, of which one candidate confers pronounced siderophore activity (EC50: 8.4 μM, CAS assay). These findings not only unveil a highly diverse assembly line but also are an important addition to the knowledgebase of the pathogens' metabolomes. PMID:25873483

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

    PubMed Central

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

    2010-01-01

    The signaling network of innate immunity in Drosophila is constructed by multiple evolutionarily conserved pathways, including the Toll- or Imd-regulated NF-?B 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. PMID:21076039

  16. 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. PMID:21076039

  17. Bacterial Pathogens Activate a Common Inflammatory Pathway through IFN? Regulation of PDCD4

    PubMed Central

    Cohen, Taylor S.; Prince, Alice S.

    2013-01-01

    The type III interferon (IFN?) receptor IL-28R is abundantly expressed in the respiratory tract and has been shown essential for host defense against some viral pathogens, however no data are available concerning its role in the innate immune response to bacterial pathogens. Staphylococcus aureus and Pseudomonas aeruginosa induced significant production of IFN? in the lung, and clearance of these bacteria from the lung was significantly increased in IL-28R null mice compared to controls. Improved bacterial clearance correlated with reduced lung pathology and a reduced ratio of pro- vs anti-inflammatory cytokines in the airway. In human epithelial cells IFN? inhibited miR-21 via STAT3 resulting in upregulation of PDCD4, a protein known to promote inflammatory signaling. In vivo 18 hours following infection with either pathogen, miR-21 was significantly reduced and PDCD4 increased in the lungs of wild type compared to IL-28R null mice. Infection of PDCD4 null mice with USA300 resulted in improved clearance, reduced pathology, and reduced inflammatory cytokine production. These data suggest that during bacterial pneumonia IFN? promotes inflammation by inhibiting miR-21 regulation of PDCD4. PMID:24098127

  18. IDENTIFYING DISEASE RESISTANCE GENES AND PATHWAYS THROUGH HOST-PATHOGEN PROTEIN INTERACTIONS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major objective of both animal and plant genomics research is to identify disease resistance genes and pathways. Popular approaches to achieve this goal include candidate gene testing, genome-wide QTL screens, and DNA microarrays. We argue that the two-hybrid assay, which detects protein-protein...

  19. Silicon induces resistance to the brown spot fungus Cochliobolus miyabeanus by preventing the pathogen from hijacking the rice ethylene pathway.

    PubMed

    Van Bockhaven, Jonas; Spchal, Luk; Novk, Ond?ej; Strnad, Miroslav; Asano, Takayuki; Kikuchi, Shoshi; Hfte, Monica; De Vleesschauwer, David

    2015-04-01

    Although numerous studies have shown the ability of silicon (Si) to mitigate a wide variety of abiotic and biotic stresses, relatively little is known about the underlying mechanism(s). Here, we have investigated the role of hormone defense pathways in Si-induced resistance to the rice brown spot fungus Cochliobolus miyabeanus. To delineate the involvement of multiple hormone pathways, a multidisciplinary approach was pursued, combining exogenous hormone applications, pharmacological inhibitor experiments, time-resolved hormone measurements, and bioassays with hormone-deficient and/or -insensitive mutant lines. Contrary to other types of induced resistance, we found Si-induced brown spot resistance to function independently of the classic immune hormones salicylic acid and jasmonic acid. Our data also rule out a major role of the abscisic acid (ABA) and cytokinin pathways, but suggest that Si mounts resistance to C.miyabeanus by preventing the fungus from hijacking the rice ethylene (ET) machinery. Interestingly, rather than suppressing rice ET signaling per se, Si probably interferes with the production and/or action of fungal ET. Together our findings favor a scenario whereby Si induces brown spot resistance by disarming fungal ET and argue that impairment of pathogen virulence factors is a core resistance mechanism underpinning Si-induced plant immunity. PMID:25625327

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

    PubMed

    Thywien, 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. PMID:21747802

  1. Highly pathogenic H5N1 avian influenza: entry pathways into North America via bird migration.

    PubMed

    Peterson, A Townsend; Benz, Brett W; Papeş, Monica

    2007-01-01

    Given the possibility of highly pathogenic H5N1 avian influenza arriving in North America and monitoring programs that have been established to detect and track it, we review intercontinental movements of birds. We divided 157 bird species showing regular intercontinental movements into four groups based on patterns of movement-one of these groups (breed Holarctic, winter Eurasia) fits well with the design of the monitoring programs (i.e., western Alaska), but the other groups have quite different movement patterns, which would suggest the importance of H5N1 monitoring along the Pacific, Atlantic, and Gulf coasts of North America. PMID:17330144

  2. The pilin O-glycosylation pathway of pathogenic Neisseria is a general system that glycosylates AniA, an outer membrane nitrite reductase.

    PubMed

    Ku, S C; Schulz, B L; Power, P M; Jennings, M P

    2009-01-01

    O-Glycosylation is emerging as a common posttranslational modification of surface exposed proteins in bacterial mucosal pathogens. In pathogenic Neisseria an O-glycosylation pathway modifies a single abundant protein, pilin, the subunit protein that forms pili. Here, we identify an additional outer membrane glycoprotein in pathogenic Neisseria, the nitrite reductase AniA, that is glycosylated in its C-terminal repeat region by the pilin glycosylation pathway. To our knowledge, this is the first report of a general O-glycosylation pathway in a prokaryote. We also show that AniA displays polymorphisms in residues that map to the surface of the protein. A frame-shift mutation abolishes AniA expression in 34% of Neisseria meningitidis strains surveyed, however, all Neisseria gonorrhoeae strains examined are predicted to express AniA, implying a crucial role for AniA in gonococcal biology. PMID:19013435

  3. Unraveling Unique Structure and Biosynthesis Pathway of N-Linked Glycans in Human Fungal Pathogen Cryptococcus neoformans by Glycomics Analysis*

    PubMed Central

    Park, Jeong-Nam; Lee, Dong-Jik; Kwon, Ohsuk; Oh, Doo-Byoung; Bahn, Yong-Sun; Kang, Hyun Ah

    2012-01-01

    The encapsulated fungal pathogen Cryptococcus neoformans causes cryptococcosis in immunocompromised individuals. Although cell surface mannoproteins have been implicated in C. neoformans pathogenicity, the structure of N-linked glycans assembled on mannoproteins has not yet been elucidated. By analyzing oligosaccharide profiles combined with exoglycosidase treatment, we report here that C. neoformans has serotype-specific high mannose-type N-glycans with or without a β1,2-xylose residue, which is attached to the trimannosyl core of N-glycans. Interestingly, the neutral N-glycans of serotypes A and D were shown to contain a xylose residue, whereas those of serotype B appeared to be much shorter and devoid of a xylose residue. Moreover, analysis of the C. neoformans uxs1Δ mutant demonstrated that UDP-xylose is utilized as a donor sugar in N-glycan biosynthesis. We also constructed and analyzed a set of C. neoformans mutant strains lacking genes putatively assigned to the reconstructed N-glycan biosynthesis pathway. It was shown that the outer chain of N-glycan is initiated by CnOch1p with addition of an α1,6-mannose residue and then subsequently extended by CnMnn2p with multiple additions of α1,2-mannose residues. Finally, comparative analysis of acidic N-glycans from wild-type, Cnoch1Δ, Cnmnn2Δ, and Cnuxs1Δ strains strongly indicated the presence of xylose phosphate attached to mannose residues in the core and outer region of N-glycans. Our data present the first report on the unique structure and biosynthesis pathway of N-glycans in C. neoformans. PMID:22500028

  4. The opportunistic pathogen Pseudomonas aeruginosa activates the DNA double-strand break signaling and repair pathway in infected cells.

    PubMed

    Elsen, Sylvie; Collin-Faure, Vronique; Gidrol, Xavier; Lemercier, Claudie

    2013-11-01

    Highly hazardous DNA double-strand breaks can be induced in eukaryotic cells by a number of agents including pathogenic bacterial strains. We have investigated the genotoxic potential of Pseudomonas aeruginosa, an opportunistic pathogen causing devastating nosocomial infections in cystic fibrosis or immunocompromised patients. Our data revealed that infection of immune or epithelial cells by P. aeruginosa triggered DNA strand breaks and phosphorylation of histone H2AX (?H2AX), a marker of DNA double-strand breaks. Moreover, it induced formation of discrete nuclear repair foci similar to gamma-irradiation-induced foci, and containing ?H2AX and 53BP1, an adaptor protein mediating the DNA-damage response pathway. Gene deletion, mutagenesis, and complementation in P. aeruginosa identified ExoS bacterial toxin as the major factor involved in ?H2AX induction. Chemical inhibition of several kinases known to phosphorylate H2AX demonstrated that Ataxia Telangiectasia Mutated (ATM) was the principal kinase in P. aeruginosa-induced H2AX phosphorylation. Finally, infection led to ATM kinase activation by an auto-phosphorylation mechanism. Together, these data show for the first time that infection by P. aeruginosa activates the DNA double-strand break repair machinery of the host cells. This novel information sheds new light on the consequences of P. aeruginosa infection in mammalian cells. As pathogenic Escherichia coli or carcinogenic Helicobacter pylori can alter genome integrity through DNA double-strand breaks, leading to chromosomal instability and eventually cancer, our findings highlight possible new routes for further investigations of P. aeruginosa in cancer biology and they identify ATM as a potential target molecule for drug design. PMID:23760206

  5. Novel Pathways Revealed in Bursa of Fabricius Transcriptome in Response to Extraintestinal Pathogenic Escherichia coli (ExPEC) Infection

    PubMed Central

    Sun, Hongyan; Liu, Peng; Nolan, Lisa K.; Lamont, Susan J.

    2015-01-01

    Extraintestinal pathogenic Escherichia coli (ExPEC) has major negative impacts on human and animal health. Recent research suggests food-borne links between human and animal ExPEC diseases with particular concern for poultry contaminated with avian pathogenic E. coli (APEC), the avian ExPEC. APEC is also a very important animal pathogen, causing colibacillosis, one of the world’s most widespread bacterial diseases of poultry. Previous studies showed marked atrophy and lymphocytes depletion in the bursa during APEC infection. Thus, a more comprehensive understanding of the avian bursa response to APEC infection will facilitate genetic selection for disease resistance. Four-week-old commercial male broiler chickens were infected with APEC O1 or given saline as a control. Bursas were collected at 1 and 5 days post-infection (dpi). Based on lesion scores of liver, pericardium and air sacs, infected birds were classified as having mild or severe pathology, representing resistant and susceptible phenotypes, respectively. Twenty-two individual bursa RNA libraries were sequenced, each yielding an average of 27 million single-end, 100-bp reads. There were 2469 novel genes in the total of 16,603 detected. Large numbers of significantly differentially expressed (DE) genes were detected when comparing susceptible and resistant birds at 5 dpi, susceptible and non-infected birds at 5 dpi, and susceptible birds at 5 dpi and 1 dpi. The DE genes were associated with signal transduction, the immune response, cell growth and cell death pathways. These data provide considerable insight into potential mechanisms of resistance to ExPEC infection, thus paving the way to develop strategies for ExPEC prevention and treatment, as well as enhancing innate resistance by genetic selection in animals. PMID:26556806

  6. A nitrogen response pathway regulates virulence in plant pathogenic fungi: role of TOR and the bZIP protein MeaB.

    PubMed

    López-Berges, Manuel S; Rispail, Nicolas; Prados-Rosales, Rafael C; Di Pietro, Antonio

    2010-12-01

    Virulence in plant pathogenic fungi is controlled through a variety of cellular pathways in response to the host environment. Nitrogen limitation has been proposed to act as a key signal to trigger the in planta expression of virulence genes. Moreover, a conserved Pathogenicity mitogen activated protein kinase (MAPK) cascade is strictly required for plant infection in a wide range of pathogens. We investigated the relationship between nitrogen signaling and the Pathogenicity MAPK cascade in controlling infectious growth of the vascular wilt fungus Fusarium oxysporum. Several MAPK-activated virulence functions such as invasive growth, vegetative hyphal fusion and host adhesion were strongly repressed in the presence of the preferred nitrogen source ammonium. Repression of these functions by ammonium was abolished by L-Methionine sulfoximine (MSX) or rapamycin, two specific inhibitors of Gln synthetase and the protein kinase TOR (Target Of Rapamycin), respectively, and was dependent on the bZIP protein MeaB. Supplying tomato plants with ammonium rather than nitrate resulted in a significant delay of vascular wilt symptoms caused by the F. oxysporum wild type strain, but not by the ΔmeaB mutant. Ammonium also repressed invasive growth in two other pathogens, the rice blast fungus Magnaporthe oryzae and the wheat head blight pathogen Fusarium graminearum. Our results suggest the presence of a conserved nitrogen-responsive pathway that operates via TOR and MeaB to control infectious growth in plant pathogenic fungi. PMID:21139428

  7. Leukocyte transcriptome from chickens infected with avian pathogenic Escherichia coli identifies pathways associated with resistance

    PubMed Central

    Sandford, Erin E.; Orr, Megan; Shelby, Mandy; Li, Xianyao; Zhou, Huaijun; Johnson, Timothy J.; Kariyawasam, Subhashinie; Liu, Peng; Nolan, Lisa K.; Lamont, Susan J.

    2012-01-01

    Avian pathogenic Escherichia coli (APEC) causes colibacillosis, which is responsible for morbidity and mortality in chickens. Gene expression patterns have previously been demonstrated to differ between chicken populations that are resistant vs. susceptible to bacterial infection, but little is currently known about gene expression response to APEC. Increased understanding of gene expression patterns associated with resistance will facilitate genetic selection to increase resistance to APEC. Male broiler chicks were vaccinated at 2 weeks of age and challenged with APEC at 4 weeks of age. Peripheral blood leukocytes were collected at 1 and 5 day post-infection. Lesions on the liver, pericardium, and air sacs were used to assign a mild or severe pathology status to non-vaccinated, challenged chicks. Ten treatment groups were therefore generated with a priori factors of vaccination, challenge, day post-infection, and the a posteriori factor of pathology status. Global transcriptomic response was evaluated using the Agilent 44K chicken microarray. APEC infection resulted in more up-regulation than down-regulation of differentially expressed genes. Immune response and metabolic processes were enriched with differentially expressed genes. Although vaccination significantly reduced lesions in challenged bird, there was no detectable effect of vaccination on gene expression. This study investigated the transcriptomic differences in host responses associated with mild vs. severe pathology, in addition to the effects of vaccination and challenge, thus revealing genes and networks associated with response to APEC and providing a foundation for future studies on, and genetic selection for, genetic resistance to APEC. PMID:24371566

  8. What’s the Damage? The Impact of Pathogens on Pathways that Maintain Host Genome Integrity

    PubMed Central

    Weitzman, Matthew D.; Weitzman, Jonathan B.

    2014-01-01

    Maintaining genome integrity and transmission of intact genomes is critical for cellular, organismal, and species survival. Cells can detect damaged DNA, activate checkpoints, and either enable DNA repair or trigger apoptosis to eliminate the damaged cell. Aberrations in these mechanisms lead to somatic mutations and genetic instability, which are hallmarks of cancer. Considering the long history of host-microbe coevolution, an impact of microbial infection on host genome integrity is not unexpected, and emerging links between microbial infections and oncogenesis further reinforce this idea. In this review, we compare strategies employed by viruses, bacteria, and parasites to alter, subvert, or otherwise manipulate host DNA damage and repair pathways. We highlight how microbes contribute to tumorigenesis by directly inducing DNA damage, inactivating checkpoint controls, or manipulating repair processes. We also discuss indirect effects resulting from inflammatory responses, changes in cellular metabolism, nuclear architecture, and epigenome integrity, and the associated evolutionary tradeoffs. PMID:24629335

  9. The protozoan pathogen Toxoplasma gondii targets the paracellular pathway to invade the intestinal epithelium.

    PubMed

    Weight, Caroline M; Carding, Simon R

    2012-07-01

    Abstract? Toxoplasma gondii is a ubiquitous parasite found within all mammals and birds worldwide that can cause fatal infections in immunocompromised persons and fetuses. The parasite causes chronic infections by residing in long-living tissues of the muscle and brain. T. gondii infects the host through contaminated meat and water consumption with the gastrointestinal tract (GI tract) being the first point of contact with the host. The mechanisms by which the parasite invades the host through the GI tract are unknown, although it has been suggested that the paracellular pathway is important for parasite dissemination. Studies indicate that epithelial tight junction-associated proteins are affected by T. gondii, although which junctional proteins are affected and the nature of host protein-parasite interactions have not been established. We have uncovered evidence that T. gondii influences the cellular distribution of occludin to transmigrate the intestinal epithelium and suggest how candidate binding partners can be identified. PMID:22731726

  10. Evolution of a Pathogen: A Comparative Genomics Analysis Identifies a Genetic Pathway to Pathogenesis in Acinetobacter

    PubMed Central

    Sahl, Jason W.; Gillece, John D.; Schupp, James M.; Waddell, Victor G.; Driebe, Elizabeth M.; Engelthaler, David M.; Keim, Paul

    2013-01-01

    Acinetobacter baumannii is an emergent and global nosocomial pathogen. In addition to A. baumannii, other Acinetobacter species, especially those in the Acinetobacter calcoaceticus-baumannii (Acb) complex, have also been associated with serious human infection. Although mechanisms of attachment, persistence on abiotic surfaces, and pathogenesis in A. baumannii have been identified, the genetic mechanisms that explain the emergence of A. baumannii as the most widespread and virulent Acinetobacter species are not fully understood. Recent whole genome sequencing has provided insight into the phylogenetic structure of the genus Acinetobacter. However, a global comparison of genomic features between Acinetobacter spp. has not been described in the literature. In this study, 136 Acinetobacter genomes, including 67 sequenced in this study, were compared to identify the acquisition and loss of genes in the expansion of the Acinetobacter genus. A whole genome phylogeny confirmed that A. baumannii is a monophyletic clade and that the larger Acb complex is also a well-supported monophyletic group. The whole genome phylogeny provided the framework for a global genomic comparison based on a blast score ratio (BSR) analysis. The BSR analysis demonstrated that specific genes have been both lost and acquired in the evolution of A. baumannii. In addition, several genes associated with A. baumannii pathogenesis were found to be more conserved in the Acb complex, and especially in A. baumannii, than in other Acinetobacter genomes; until recently, a global analysis of the distribution and conservation of virulence factors across the genus was not possible. The results demonstrate that the acquisition of specific virulence factors has likely contributed to the widespread persistence and virulence of A. baumannii. The identification of novel features associated with transcriptional regulation and acquired by clades in the Acb complex presents targets for better understanding the evolution of pathogenesis and virulence in the expansion of the genus. PMID:23365658

  11. 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

  12. In Planta Biocontrol of Pectobacterium atrosepticum by Rhodococcus erythropolis Involves Silencing of Pathogen Communication by the Rhodococcal Gamma-Lactone Catabolic Pathway

    PubMed Central

    Barbey, Corinne; Crpin, Alexandre; Bergeau, Dorian; Ouchiha, Asma; Mijouin, Lily; Taupin, Laure; Orange, Nicole; Feuilloley, Marc; Dufour, Alain; Burini, Jean-Franois; Latour, Xavier

    2013-01-01

    The virulence of numerous Gram-negative bacteria is under the control of a quorum sensing process based on synthesis and perception of N-acyl homoserine lactones. Rhodococcus erythropolis, a Gram-positive bacterium, has recently been proposed as a biocontrol agent for plant protection against soft-rot bacteria, including Pectobacterium. Here, we show that the ?-lactone catabolic pathway of R. erythropolis disrupts Pectobacterium communication and prevents plant soft-rot. We report the first characterization and demonstration of N-acyl homoserine lactone quenching in planta. In particular, we describe the transcription of the R. erythropolis lactonase gene, encoding the key enzyme of this pathway, and the subsequent lactone breakdown. The role of this catabolic pathway in biocontrol activity was confirmed by deletion of the lactonase gene from R. erythropolis and also its heterologous expression in Escherichia coli. The ?-lactone catabolic pathway is induced by pathogen communication rather than by pathogen invasion. This is thus a novel and unusual biocontrol pathway, differing from those previously described as protecting plants from phytopathogens. These findings also suggest the existence of an additional pathway contributing to plant protection. PMID:23805254

  13. Pathogenic Vibrio harveyi, in contrast to non-pathogenic strains, intervenes with the p38 MAPK pathway to avoid an abalone haemocyte immune response.

    PubMed

    Travers, Marie-Agnès; Le Bouffant, Ronan; Friedman, Carolyn S; Buzin, Florence; Cougard, Bertrand; Huchette, Sylvain; Koken, Marcel; Paillard, Christine

    2009-01-01

    Vibrio harveyi is a marine bacterial pathogen responsible for episodic abalone epidemics associated with massive mortalities in France, Japan, and Australia. The aim of this study was the understanding of a possible role of the p38 MAPK in abalone haemocyte responses towards this bacterium. First, the pathogenicity of different V. harveyi strains was compared in both immersion and injection trials, and clear differences were detected. The three strains, ORM4, 04/092, and 05/053, all isolated from moribund abalone, induced up to 80% mortalities in immersion or injection challenges (LD(50) (ORM4) = 2.5 x 10(2) CFU animal(-1)). The two strains, LMG 4044T and LMG 7890 were non-pathogenic towards abalone in immersion trials, and needed very high numbers for killing by intramuscular injections (LD(50) = 8.9 x 10(4) and 1.6 x 10(5) CFU animal(-1), respectively). To start unraveling the mechanism explaining these differences, the p38-MAPK, a keyplayer in antimicrobial immune response, was studied. The non-pathogenic strain, LMG 7890 can be eliminated by abalone haemocytes and induces haemocyte phagocytosis and high ROS production. With different concentrations of a p38-specific inhibitor, SB203580, p38 implication was shown. This inhibitor reduced phagocytosis and ROS induction leading to LMG 7890 proliferation. In the case of the pathogenic ORM4 which can not be eliminated by abalone haemocytes, no phagocytosis and ROS production was induced, and a retarded p38 activation was observed. Taken together, our results suggest that p38 MAPK modulation may be one of the ways of virulent V. harveyi to attack its host and escape abalone immune response. PMID:19058134

  14. Pathogen signatures activate a ubiquitinylation pathway that modulates function of the metabolic checkpoint kinase mTOR

    PubMed Central

    Ivanov, Stanimir S.; Roy, Craig R.

    2013-01-01

    The mammalian immune system has the ability to discriminate between pathogenic and non-pathogenic microbes to control inflammation. Here we investigated ubiquitinylation profiles of host proteins after infection of macrophages with a virulent strain of the intracellular bacterium Legionella pneumophila and a non-pathogenic mutant. Only infection with pathogenic Legionella resulted in ubiquitinylation of positive regulators of the metabolic checkpoint kinase mTOR leading to diminished mTOR activity. Detection of pathogen signatures resulted in translational biasing to proinflammatory cytokines through mTOR-mediated regulation of cap-dependent translation. Thus, there is a pathogen detection program in macrophages that stimulates protein ubiquitinylation and degradation of mTOR regulators, which suppresses mTOR function and directs a proinflammatory cytokine program. PMID:24121838

  15. Pathogen-pathogen interaction

    PubMed Central

    2010-01-01

    There is growing awareness of the health implications of the fact that infectious agents often do not act independently; rather their disease potential is mediated in diverse and significant ways by their relationships with other pathogens. Pathogen-pathogen interaction (PPI), for example, impacts various virulence factors in human infection. Although still in its infancy, the study of PPI, a form of epidemiological synergism, is emerging as an important arena of new research and new understanding in health and clinical care. The aims of this paper are to: (1) draw attention to the role of PPI in human disease patterns; (2) present the syndemics model as a biosocial approach for examining the nature, pathways, contexts, and health implications of PPI and (3) suggest the utility of this approach to PPI. Toward these ends, this paper (a) reviews three case examples of alternative PPIs, (b) describes the development and key concepts and components of the syndemics model with specific reference to interacting infectious agents, (c) contextualizes this discussion with a brief review of broader syndemics disease processes (not necessarily involving infections disease) and (d) comments on the research, treatment and prevention implications of syndemic interaction among pathogens. PMID:21178409

  16. 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 ?M 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

  17. 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. PMID:25714412

  18. 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

  19. 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

    2016-01-01

    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

  20. 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

  1. Coenzyme Q regulates the expression of essential genes of the pathogen- and xenobiotic-associated defense pathway in C. elegans.

    PubMed

    Fischer, Alexandra; Niklowitz, Petra; Menke, Thomas; Dring, Frank

    2015-11-01

    Coenzyme Q (CoQ) is necessary for mitochondrial energy production and modulates the expression of genes that are important for inflammatory processes, growth and detoxification reactions. A cellular surveillance-activated detoxification and defenses (cSADDs) pathway has been recently identified in C. elegans. The down-regulation of the components of the cSADDs pathway initiates an aversion behavior of the nematode. Here we hypothesized that CoQ regulates genes of the cSADDs pathway. To verify this we generated CoQ-deficient worms ("CoQ-free") and performed whole-genome expression profiling. We found about 30% (120 genes) of the cSADDs pathway genes were differentially regulated under CoQ-deficient condition. Remarkably, 83% of these genes were down-regulated. The majority of the CoQ-sensitive cSADDs pathway genes encode for proteins involved in larval development (enrichment score (ES)=38.0, p=5.0E(-37)), aminoacyl-tRNA biosynthesis, proteasome function (ES 8.2, p=5.9E(-31)) and mitochondria function (ES 3.4, p=1.7E(-5)). 67% (80 genes) of these genes are categorized as lethal. Thus it is shown for the first time that CoQ regulates a substantial number of essential genes that function in the evolutionary conserved cellular surveillance-activated detoxification and defenses pathway in C. elegans. PMID:26566301

  2. Coenzyme Q regulates the expression of essential genes of the pathogen- and xenobiotic-associated defense pathway in C. elegans

    PubMed Central

    Fischer, Alexandra; Niklowitz, Petra; Menke, Thomas; Dring, Frank

    2015-01-01

    Coenzyme Q (CoQ) is necessary for mitochondrial energy production and modulates the expression of genes that are important for inflammatory processes, growth and detoxification reactions. A cellular surveillance-activated detoxification and defenses (cSADDs) pathway has been recently identified in C. elegans. The down-regulation of the components of the cSADDs pathway initiates an aversion behavior of the nematode. Here we hypothesized that CoQ regulates genes of the cSADDs pathway. To verify this we generated CoQ-deficient worms (CoQ-free) and performed whole-genome expression profiling. We found about 30% (120 genes) of the cSADDs pathway genes were differentially regulated under CoQ-deficient condition. Remarkably, 83% of these genes were down-regulated. The majority of the CoQ-sensitive cSADDs pathway genes encode for proteins involved in larval development (enrichment score (ES)=38.0, p=5.0E?37), aminoacyl-tRNA biosynthesis, proteasome function (ES 8.2, p=5.9E?31) and mitochondria function (ES 3.4, p=1.7E?5). 67% (80 genes) of these genes are categorized as lethal. Thus it is shown for the first time that CoQ regulates a substantial number of essential genes that function in the evolutionary conserved cellular surveillance-activated detoxification and defenses pathway in C. elegans. PMID:26566301

  3. 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

  4. 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. PMID:26055366

  5. 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

  6. 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

  7. 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

  8. A large, mobile pathogenicity island confers plant pathogenicity on Streptomyces species.

    PubMed

    Kers, Johan A; Cameron, Kimberly D; Joshi, Madhumita V; Bukhalid, Raghida A; Morello, Joanne E; Wach, Michael J; Gibson, Donna M; Loria, Rosemary

    2005-02-01

    Potato scab is a globally important disease caused by polyphyletic plant pathogenic Streptomyces species. Streptomyces acidiscabies, Streptomyces scabies and Streptomyces turgidiscabies possess a conserved biosynthetic pathway for the nitrated dipeptide phytotoxin thaxtomin. These pathogens also possess the nec1 gene which encodes a necrogenic protein that is an independent virulence factor. In this article we describe a large (325-660 kb) pathogenicity island (PAI) conserved among these three plant pathogenic Streptomyces species. A partial DNA sequence of this PAI revealed the thaxtomin biosynthetic pathway, nec1, a putative tomatinase gene, and many mobile genetic elements. In addition, the PAI from S. turgidiscabies contains a plant fasciation (fas) operon homologous to and colinear with the fas operon in the plant pathogen Rhodococcus fascians. The PAI was mobilized during mating from S. turgidiscabies to the non-pathogens Streptomyces coelicolor and Streptomyces diastatochromogenes on a 660 kb DNA element and integrated site-specifically into a putative integral membrane lipid kinase. Acquisition of the PAI conferred a pathogenic phenotype on S. diastatochromogenes but not on S. coelicolor. This PAI is the first to be described in a Gram-positive plant pathogenic bacterium and is responsible for the emergence of new plant pathogenic Streptomyces species in agricultural systems. PMID:15686551

  9. 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. PMID:25234642

  10. Role of ficolin-A and lectin complement pathway in the innate defense against pathogenic Aspergillus species.

    PubMed

    Bidula, Stefan; Kenawy, Hany; Ali, Youssif M; Sexton, Darren; Schwaeble, Wilhelm J; Schelenz, Silke

    2013-05-01

    Aspergillus species are saprophytic molds causing life-threatening invasive fungal infections in the immunocompromised host. Innate immune recognition, in particular, the mechanisms of opsonization and complement activation, has been reported to be an integral part of the defense against fungi. We have shown that the complement component ficolin-A significantly binds to Aspergillus conidia and hyphae in a concentration-dependent manner and was inhibited by N-acetylglucosamine and N-acetylgalactosamine. Calcium-independent binding to Aspergillus fumigatus and A. terreus was observed, but binding to A. flavus and A. niger was calcium dependent. Ficolin-A binding to conidia was increased under low-pH conditions, and opsonization led to enhanced binding of conidia to A549 airway epithelial cells. In investigations of the lectin pathway of complement activation, ficolin-A-opsonized conidia did not lead to lectin pathway-specific C4 deposition. In contrast, the collectin mannose binding lectin C (MBL-C) but not MBL-A led to efficient lectin pathway activation on A. fumigatus in the absence of ficolin-A. In addition, ficolin-A opsonization led to a modulation of the proinflammatory cytokine interleukin-8. We conclude that ficolin-A may play an important role in the innate defense against Aspergillus by opsonizing conidia, immobilizing this fungus through enhanced adherence to epithelial cells and modulation of inflammation. However, it appears that other immune pattern recognition molecules, i.e., those of the collectin MBL-C, are involved in the Aspergillus-lectin complement pathway activation rather than ficolin-A. PMID:23478320

  11. Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species

    PubMed Central

    Bidula, Stefan; Kenawy, Hany; Ali, Youssif M.; Sexton, Darren; Schwaeble, Wilhelm J.

    2013-01-01

    Aspergillus species are saprophytic molds causing life-threatening invasive fungal infections in the immunocompromised host. Innate immune recognition, in particular, the mechanisms of opsonization and complement activation, has been reported to be an integral part of the defense against fungi. We have shown that the complement component ficolin-A significantly binds to Aspergillus conidia and hyphae in a concentration-dependent manner and was inhibited by N-acetylglucosamine and N-acetylgalactosamine. Calcium-independent binding to Aspergillus fumigatus and A. terreus was observed, but binding to A. flavus and A. niger was calcium dependent. Ficolin-A binding to conidia was increased under low-pH conditions, and opsonization led to enhanced binding of conidia to A549 airway epithelial cells. In investigations of the lectin pathway of complement activation, ficolin-A-opsonized conidia did not lead to lectin pathway-specific C4 deposition. In contrast, the collectin mannose binding lectin C (MBL-C) but not MBL-A led to efficient lectin pathway activation on A. fumigatus in the absence of ficolin-A. In addition, ficolin-A opsonization led to a modulation of the proinflammatory cytokine interleukin-8. We conclude that ficolin-A may play an important role in the innate defense against Aspergillus by opsonizing conidia, immobilizing this fungus through enhanced adherence to epithelial cells and modulation of inflammation. However, it appears that other immune pattern recognition molecules, i.e., those of the collectin MBL-C, are involved in the Aspergillus-lectin complement pathway activation rather than ficolin-A. PMID:23478320

  12. 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

  13. The Arabidopsis Rho of plants GTPase AtROP6 functions in developmental and pathogen response pathways.

    PubMed

    Poraty-Gavra, Limor; Zimmermann, Philip; Haigis, Sabine; Bednarek, Pawel; Hazak, Ora; Stelmakh, Oksana Rogovoy; Sadot, Einat; Schulze-Lefert, Paul; Gruissem, Wilhelm; Yalovsky, Shaul

    2013-03-01

    How plants coordinate developmental processes and environmental stress responses is a pressing question. Here, we show that Arabidopsis (Arabidopsis thaliana) Rho of Plants6 (AtROP6) integrates developmental and pathogen response signaling. AtROP6 expression is induced by auxin and detected in the root meristem, lateral root initials, and leaf hydathodes. Plants expressing a dominant negative AtROP6 (rop6(DN)) under the regulation of its endogenous promoter are small and have multiple inflorescence stems, twisted leaves, deformed leaf epidermis pavement cells, and differentially organized cytoskeleton. Microarray analyses of rop6(DN) plants revealed that major changes in gene expression are associated with constitutive salicylic acid (SA)-mediated defense responses. In agreement, their free and total SA levels resembled those of wild-type plants inoculated with a virulent powdery mildew pathogen. The constitutive SA-associated response in rop6(DN) was suppressed in mutant backgrounds defective in SA signaling (nonexpresser of PR genes1 [npr1]) or biosynthesis (salicylic acid induction deficient2 [sid2]). However, the rop6(DN) npr1 and rop6(DN) sid2 double mutants retained the aberrant developmental phenotypes, indicating that the constitutive SA response can be uncoupled from ROP function(s) in development. rop6(DN) plants exhibited enhanced preinvasive defense responses to a host-adapted virulent powdery mildew fungus but were impaired in preinvasive defenses upon inoculation with a nonadapted powdery mildew. The host-adapted powdery mildew had a reduced reproductive fitness on rop6(DN) plants, which was retained in mutant backgrounds defective in SA biosynthesis or signaling. Our findings indicate that both the morphological aberrations and altered sensitivity to powdery mildews of rop6(DN) plants result from perturbations that are independent from the SA-associated response. These perturbations uncouple SA-dependent defense signaling from disease resistance execution. PMID:23319551

  14. 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

  15. Wnt5a attenuates the pathogenic effects of the Wnt/?-catenin pathway in human retinal pigment epithelial cells via down-regulating ?-catenin and Snail

    PubMed Central

    Kim, Joo-Hyun; Park, Seoyoung; Chung, Hyewon; Oh, Sangtaek

    2015-01-01

    Activation of the Wnt/?-catenin pathway plays a pathogenic role in age-related macular degeneration (AMD) and is thus a potential target for the development of therapeutics for this disease. Here, we demonstrated that Wnt5a antagonized ?-catenin response transcription (CRT) induced with Wnt3a by promoting ?-catenin phosphorylation at Ser33/Ser37/Thr41 and its subsequent degradation in human retinal pigment epithelial (RPE) cells. Wnt5a decreased the levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-?(TNF-?), and nuclear factor-?B (NF-?B), which was up-regulated by Wnt3a. Furthermore, Wnt5a increased E-cadherin expression and decreased cell migration by down-regulating Snail expression, thereby abrogating the Wnt3a-induced epithelial-mesenchymal transition (EMT) in human RPE cells. Our findings suggest that Wnt5a suppresses the pathogenic effects of canonical Wnt signaling in human RPE cells by promoting ?-catenin phosphorylation and degradation. Therefore, Wnt5a has significant therapeutic potential for the treatment of AMD. [BMB Reports 2015; 48(9): 525-530] PMID:26246285

  16. Inhibition of multiple pathogenic pathways by histone deacetylase inhibitor SAHA in a corneal alkali-burn injury model

    PubMed Central

    Li, Xinyu; Zhou, Qinbo; Hanus, Jakub; Anderson, Chastain; Zhang, Hongmei; Dellinger, Michael; Brekken, Rolf; Wang, Shusheng

    2013-01-01

    Neovascularization (NV) in the cornea is a major cause of vision impairment and corneal blindness. Hemangiogenesis and lymphangiogenesis induced by inflammation underlie the pathogenesis of corneal NV. The current mainstay treatment, corticosteroid, treats the inflammation associated with corneal NV, but is not satisfactory due to such side effects as cataract and the increase in intraocular pressure. It is imperative to develop a novel therapy that specifically targets the hemangiogenesis, lymphangiogenesis and inflammation pathways underlying corneal NV. Histone deacetylase inhibitors (HDACi) have been in clinical trials for cancer and other diseases. In particular, HDACi suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza) has been approved by the FDA for the treatment of cutaneous T-cell lymphoma. The functional mechanism of SAHA in cancer and especially in corneal NV remains unclear. Here, we show that topical application of SAHA inhibits neovascularization in an alkali-burn corneal injury model. Mechanistically, SAHA inhibits corneal NV by repressing hemangiogenesis, inflammation pathways and previously overlooked lymphangiogenesis. Topical SAHA is well tolerated on the ocular surface. In addition, the potency of SAHA in corneal NV appears to be comparable to the current steroid therapy. SAHA may possess promising therapeutic potential in alkali-burn corneal injury and other inflammatory neovascularization disorders. PMID:23186311

  17. Sequential Activation of Two Pathogen-Sensing Pathways Required for Type I Interferon Expression and Resistance to an Acute DNA Virus Infection.

    PubMed

    Xu, Ren-Huan; Wong, Eric B; Rubio, Daniel; Roscoe, Felicia; Ma, Xueying; Nair, Savita; Remakus, Sanda; Schwendener, Reto; John, Shinu; Shlomchik, Mark; Sigal, Luis J

    2015-12-15

    Toll-like receptor 9 (TLR9), its adaptor MyD88, the downstream transcription factor interferon regulatory factor 7 (IRF7), and type I interferons (IFN-I) are all required for resistance to infection with ectromelia virus (ECTV). However, it is not known how or in which cells these effectors function to promote survival. Here, we showed that after infection with ECTV, theTLR9-MyD88-IRF7 pathway was necessary in CD11c(+) cells for the expression of proinflammatory cytokines and the recruitment of inflammatory monocytes (iMos) to the draining lymph node (dLN). In the dLN, the major producers of IFN-I were infected iMos, which used the DNA sensor-adaptor STING to activate IRF7 and nuclear factor ?B (NF-?B) signaling to induce the expression of IFN-? and IFN-?, respectively. Thus, invivo, two pathways of DNA pathogen sensing act sequentially in two distinct cell types to orchestrate resistance to a viral disease. PMID:26682986

  18. The High-Osmolarity Glycerol Response Pathway in the Human Fungal Pathogen Candida glabrata Strain ATCC 2001 Lacks a Signaling Branch That Operates in Baker's Yeast▿

    PubMed Central

    Gregori, Christa; Schüller, Christoph; Roetzer, Andreas; Schwarzmüller, Tobias; Ammerer, Gustav; Kuchler, Karl

    2007-01-01

    The high-osmolarity glycerol (HOG) mitogen-activated protein (MAP) kinase pathway mediates adaptation to high-osmolarity stress in the yeast Saccharomyces cerevisiae. Here we investigate the function of HOG in the human opportunistic fungal pathogen Candida glabrata. C. glabrata sho1Δ (Cgsho1Δ) deletion strains from the sequenced ATCC 2001 strain display severe growth defects under hyperosmotic conditions, a phenotype not observed for yeast sho1Δ mutants. However, deletion of CgSHO1 in other genetic backgrounds fails to cause osmostress hypersensitivity, whereas cells lacking the downstream MAP kinase Pbs2 remain osmosensitive. Notably, ATCC 2001 Cgsho1Δ cells also display methylglyoxal hypersensitivity, implying the inactivity of the Sln1 branch in ATCC 2001. Genomic sequencing of CgSSK2 in different C. glabrata backgrounds demonstrates that ATCC 2001 harbors a truncated and mutated Cgssk2-1 allele, the only orthologue of yeast SSK2/SSK22 genes. Thus, the osmophenotype of ATCC 2001 is caused by a point mutation in Cgssk2-1, which debilitates the second HOG pathway branch. Functional complementation experiments unequivocally demonstrate that HOG signaling in yeast and C. glabrata share similar functions in osmostress adaptation. In contrast to yeast, however, Cgsho1Δ mutants display hypersensitivity to weak organic acids such as sorbate and benzoate. Hence, CgSho1 is also implicated in modulating weak acid tolerance, suggesting that HOG signaling in C. glabrata mediates the response to multiple stress conditions. PMID:17616630

  19. WATERBORNE PATHOGENS IN URBAN WATERSHEDS

    EPA Science Inventory

    Pathogens are microorganisms that can cause sickness or even death. 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, combi...

  20. Synovial fibroblasts directly induce Th17 pathogenicity via the cyclooxygenase/prostaglandin E2 pathway, independent of IL-23.

    PubMed

    Paulissen, Sandra M J; van Hamburg, Jan Piet; Davelaar, Nadine; Asmawidjaja, Patrick S; Hazes, Johanna M W; Lubberts, Erik

    2013-08-01

    Th17 cells are critically involved in autoimmune disease induction and severity. Recently, we showed that Th17 cells from patients with rheumatoid arthritis (RA) directly induced a proinflammatory loop upon interaction with RA synovial fibroblasts (RASF), including increased autocrine IL-17A production. To unravel the mechanism driving this IL-17A production, we obtained primary CD4(+)CD45RO(+)CCR6(+) (Th17) cells and CD4(+)CD45RO(+)CCR6(-) (CCR6(-)) T cells from RA patients or healthy individuals and cocultured these with RASF. IL-1?, IL-6, IL-23p19, and cyclooxygenase (COX)-2 expression and PGE2 production in Th17-RASF cultures were higher than in CCR6(-) T cell-RASF cultures. Cytokine neutralization showed that IL-1? and IL-6, but not IL-23, contributed to autocrine IL-17A induction. Importantly, treatment with celecoxib, a COX-2 inhibitor, resulted in significantly lower PGE2 and IL-17A, but not IFN-?, production. Combined celecoxib and TNF-? blockade more effectively suppressed the proinflammatory loop than did single treatment, as shown by lower IL-6, IL-8, matrix metalloproteinase-1 and matrix metalloproteinase-3 production. These findings show a critical role for the COX-2/PGE2 pathway in driving Th17-mediated synovial inflammation in an IL-23- and monocyte-independent manner. Therefore, it would be important to control PGE2 in chronic inflammation in RA and potentially other Th17-mediated autoimmune disorders. PMID:23817417

  1. 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. PMID:26486420

  2. 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

  3. 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

  4. Effects of a Defective Endoplasmic Reticulum-Associated Degradation Pathway on the Stress Response, Virulence, and Antifungal Drug Susceptibility of the Mold Pathogen Aspergillus fumigatus

    PubMed Central

    Krishnan, Karthik; Feng, Xizhi; Powers-Fletcher, Margaret V.; Bick, Gregory; Richie, Daryl L.; Woollett, Laura A.

    2013-01-01

    Proteins that are destined for release outside the eukaryotic cell, insertion into the plasma membrane, or delivery to intracellular organelles are processed and folded in the endoplasmic reticulum (ER). An imbalance between the level of nascent proteins entering the ER and the organelle's ability to manage that load results in the accumulation of unfolded proteins. Terminally unfolded proteins are disposed of by ER-associated degradation (ERAD), a pathway that transports the aberrant proteins across the ER membrane into the cytosol for proteasomal degradation. The ERAD pathway was targeted in the mold pathogen Aspergillus fumigatus by deleting the hrdA gene, encoding the A. fumigatus ortholog of Hrd1, the E3 ubiquitin ligase previously shown to contribute to ERAD in other species. Loss of HrdA was associated with impaired degradation of a folding-defective ERAD substrate, CPY*, as well as activation of the unfolded-protein response (UPR). The ΔhrdA mutant showed resistance to voriconazole and reduced thermotolerance but was otherwise unaffected by a variety of environmental stressors. A double-deletion mutant deficient in both HrdA and another component of the same ERAD complex, DerA, was defective in secretion and showed hypersensitivity to ER, thermal, and cell wall stress. However, the ΔhrdA ΔderA mutant remained virulent in mouse and insect infection models. These data demonstrate that HrdA and DerA support complementary ERAD functions that promote survival under conditions of ER stress but are dispensable for virulence in the host environment. PMID:23355008

  5. Transformation of Eutypa dieback and esca disease pathogen toxins by antagonistic fungal strains reveals a second detoxification pathway not present in Vitis vinifera.

    PubMed

    Christen, Danilo; Tharin, Manuel; Perrin-Cherioux, Sandrine; Abou-Mansour, Eliane; Tabacchi, Raphal; Dfago, Genevive

    2005-09-01

    Eutypine, 4-hydroxybenzaldehyde, and 3-phenyllactic acid are some of the phytotoxins produced by the pathogens causing Eutypa dieback and esca disease, two trunk diseases of grapevine (Vitis vinifera). Known biocontrol agents such as Fusarium lateritium and Trichoderma sp. were screened for their ability to consume these toxins. Transformation time courses were performed, and an high-performance liquid chromatography-based method was developed to analyze toxin metabolism and to identify and quantify the converted products. The results show that the aldehyde function of eutypine was reduced to eutypinol, as by V. vinifera cv. Merlot, the cultivar tolerant to Eutypa dieback. We revealed a supplementary detoxification pathway, not known in Merlot, where the aldehyde function was oxidized to eutypinic acid. Moreover, some strains tested could further metabolize the transformation products. Every strain tested could transform 4-hydroxybenzaldehyde to the corresponding alcohol and acid, and these intermediates disappeared totally at the end of the time courses. When biological assays on cells of V. vinifera cv. Chasselas were carried out, the transformation products exhibited a lower toxicity than the toxins. The possibility of selecting new biocontrol agents against trunk diseases of grapevine based on microbial detoxification is discussed. PMID:16131109

  6. Siderophore-based iron acquisition and pathogen control.

    PubMed

    Miethke, Marcus; Marahiel, Mohamed A

    2007-09-01

    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

  7. 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

  8. 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.

  9. New World Clade B Arenaviruses Can Use Transferrin Receptor 1 (TfR1)-Dependent and -Independent Entry Pathways, and Glycoproteins from Human Pathogenic Strains Are Associated with the Use of TfR1▿

    PubMed Central

    Flanagan, Meg L.; Oldenburg, Jill; Reignier, Therese; Holt, Nathalia; Hamilton, Genevieve A.; Martin, Vanessa K.; Cannon, Paula M.

    2008-01-01

    Arenaviruses are rodent-borne viruses, with five members of the family capable of causing severe hemorrhagic fevers if transmitted to humans. To date, two distinct cellular receptors have been identified that are used by different pathogenic viruses, α-dystroglycan by Lassa fever virus and transferrin receptor 1 (TfR1) by certain New World clade B viruses. Our previous studies have suggested that other, as-yet-unknown receptors are involved in arenavirus entry. In the present study, we examined the use of TfR1 by the glycoproteins (GPs) from a panel of New World clade B arenaviruses comprising three pathogenic and two nonpathogenic strains. Interestingly, we found that TfR1 was only used by the GPs from the pathogenic viruses, with entry of the nonpathogenic strains being TfR1 independent. The pathogenic GPs could also direct entry into cells by TfR1-independent pathways, albeit less efficiently. A comparison of the abilities of TfR1 orthologs from different species to support arenavirus entry found that the human and feline receptors were able to enhance entry of the pathogenic strains, but that neither the murine or canine forms were functional. Since the ability to use TfR1 is a characteristic feature of the human pathogens, this interaction may represent an important target in the treatment of New World hemorrhagic fevers. In addition, the ability to use TfR1 may be a useful tool to predict the likelihood that any existing or newly discovered viruses in this family could infect humans. PMID:18003730

  10. 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. PMID:24934960

  11. Pathogen Phytosensing: Plants to Report Plant Pathogens

    PubMed Central

    Mazarei, Mitra; Teplova, Irina; Hajimorad, M. Reza; Stewart, C. Neal

    2008-01-01

    Real-time systems that provide evidence of pathogen contamination in crops can be an important new line of early defense in agricultural centers. Plants possess defense mechanisms to protect against pathogen attack. Inducible plant defense is controlled by signal transduction pathways, inducible promoters and cis-regulatory elements corresponding to key genes involved in defense, and pathogen-specific responses. Identified inducible promoters and cis-acting elements could be utilized in plant sentinels, or phytosensors, by fusing these to reporter genes to produce plants with altered phenotypes in response to the presence of pathogens. Here, we have employed cis-acting elements from promoter regions of pathogen inducible genes as well as those responsive to the plant defense signal molecules salicylic acid, jasmonic acid, and ethylene. Synthetic promoters were constructed by combining various regulatory elements supplemented with the enhancer elements from the Cauliflower mosaic virus (CaMV) 35S promoter to increase basal level of the GUS expression. The inducibility of each synthetic promoter was first assessed in transient expression assays using Arabidopsis thaliana protoplasts and then examined for efficacy in stably transgenic Arabidopsis and tobacco plants. Histochemical and fluorometric GUS expression analyses showed that both transgenic Arabidopsis and tobacco plants responded to elicitor and phytohormone treatments with increased GUS expression when compared to untreated plants. Pathogen-inducible phytosensor studies were initiated by analyzing the sensitivity of the synthetic promoters against virus infection. Transgenic tobacco plants infected with Alfalfa mosaic virus showed an increase in GUS expression when compared to mock-inoculated control plants, whereas Tobacco mosaic virus infection caused no changes in GUS expression. Further research, using these transgenic plants against a range of different pathogens with the regulation of detectable reporter gene could provide biological evidence to define the functional differences between pathogens, and provide new technology and applications for transgenic plants as phytosensors.

  12. Transcriptional responses to pathogens in Caenorhabditis elegans

    PubMed Central

    Shivers, Robert P.; Youngman, Matthew J.; Kim, Dennis H.

    2008-01-01

    Summary Evolutionarily conserved signaling pathways, such as the p38 and ERK MAPK pathways, the TGF-? pathway, and the insulin signaling pathway are required for resistance to pathogens in C. elegans. Recent microarray expression profiling studies have identified both candidate immune effector genes which may recognize and eliminate microbial pathogens as well as uncharacterized gene classes that are broadly induced in response to pathogen. Comparative analysis of these microarray studies is suggestive of basal versus induced components of the ancient innate immune response in C. elegans. In particular, whereas the PMK-1 p38 MAPK pathway regulates genes that are induced by pathogen, the Forkhead family transcription factor DAF-16 confers pathogen resistance through the regulation of genes that are non-overlapping with pathogen-induced genes. PMID:18567532

  13. Interactions with microbial pathogens.

    PubMed Central

    Darby, Creg

    2005-01-01

    A wide variety of bacterial pathogens, as well as several fungi, kill C. elegans or produce non-lethal disease symptoms. This allows the nematode to be used as a simple, tractable model host for infectious disease. Human pathogens that affect C. elegans include gram-negative bacteria of genera Burkholderia, Pseudomonas, Salmonella, Serratia and Yersinia; gram-positive bacteria Enterococcus, Staphylococcus and Streptococcus; and the fungus Cryptococcus neoformans. Microbes that are not pathogenic to mammals, such as the insect pathogen Bacillus thuringiensis and the nematode-specific Microbacterium nematophilum, are also studied with C. elegans. Many of the pathogens investigated colonize the C. elegans intestine, and pathology is usually quantified as decreased lifespan of the nematode. A few microbes adhere to the nematode cuticle, while others produce toxins that kill C. elegans without a requirement for whole, live pathogen cells to contact the worm. The rapid growth and short generation time of C. elegans permit extensive screens for mutant pathogens with diminished killing, and some of the factors identified in these screens have been shown to play roles in mammalian infections. Genetic screens for toxin-resistant C. elegans mutants have identified host pathways exploited by bacterial toxins. PMID:18050390

  14. Conservation and divergence of the cyclic adenosine monophosphateprotein kinase A (cAMPPKA) 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...

  15. Pathogen-responsive expression of a putative ATP-binding cassette transporter gene conferring resistance to the diterpenoid sclareol is regulated by multiple defense signaling pathways in Arabidopsis.

    PubMed

    Campbell, Emma J; Schenk, Peer M; Kazan, Kemal; Penninckx, Iris A M A; Anderson, Jonathan P; Maclean, Don J; Cammue, Bruno P A; Ebert, Paul R; Manners, John M

    2003-11-01

    The ATP-binding cassette (ABC) transporters are encoded by large gene families in plants. Although these proteins are potentially involved in a number of diverse plant processes, currently, very little is known about their actual functions. In this paper, through a cDNA microarray screening of anonymous cDNA clones from a subtractive library, we identified an Arabidopsis gene (AtPDR12) putatively encoding a member of the pleiotropic drug resistance (PDR) subfamily of ABC transporters. AtPDR12 displayed distinct induction profiles after inoculation of plants with compatible and incompatible fungal pathogens and treatments with salicylic acid, ethylene, or methyl jasmonate. Analysis of AtPDR12 expression in a number of Arabidopsis defense signaling mutants further revealed that salicylic acid accumulation, NPR1 function, and sensitivity to jasmonates and ethylene were all required for pathogen-responsive expression of AtPDR12. Germination assays using seeds from an AtPDR12 insertion line in the presence of sclareol resulted in lower germination rates and much stronger inhibition of root elongation in the AtPDR12 insertion line than in wild-type plants. These results suggest that AtPDR12 may be functionally related to the previously identified ABC transporters SpTUR2 and NpABC1, which transport sclareol. Our data also point to a potential role for terpenoids in the Arabidopsis defensive armory. PMID:14526118

  16. Conserved glycolipid termini in capsular polysaccharides synthesized by ATP-binding cassette transporter-dependent pathways in Gram-negative pathogens

    PubMed Central

    Willis, Lisa M.; Stupak, Jacek; Richards, Michele R.; Lowary, Todd L.; Li, Jianjun; Whitfield, Chris

    2013-01-01

    Bacterial capsules are surface layers made of long-chain polysaccharides. They are anchored to the outer membrane of many Gram-negative bacteria, including pathogens such as Escherichia coli, Neisseria meningitidis, Haemophilus influenzae, and Pasteurella multocida. Capsules protect pathogens from host defenses including complement-mediated killing and phagocytosis and therefore represent a major virulence factor. Capsular polysaccharides are synthesized by enzymes located in the inner (cytoplasmic) membrane and are then translocated to the cell surface. Whereas the enzymes that synthesize the polysaccharides have been studied in detail, the structure and biosynthesis of the anchoring elements have not been definitively resolved. Here we determine the structure of the glycolipid attached to the reducing terminus of the polysialic acid capsular polysaccharides from E. coli K1 and N. meningitidis group B and the heparosan-like capsular polysaccharide from E. coli K5. All possess the same unique glycolipid terminus consisting of a lyso-phosphatidylglycerol moiety with a ?-linked poly-(3-deoxy-d-manno-oct-2-ulosonic acid) (poly-Kdo) linker attached to the reducing terminus of the capsular polysaccharide. PMID:23610430

  17. Antibiotic targeting of the bacterial secretory pathway.

    PubMed

    Rao C V, Smitha; De Waelheyns, Evelien; Economou, Anastassios; Anné, Jozef

    2014-08-01

    Finding new, effective antibiotics is a challenging research area driven by novel approaches required to tackle unconventional targets. In this review we focus on the bacterial protein secretion pathway as a target for eliminating or disarming pathogens. We discuss the latest developments in targeting the Sec-pathway for novel antibiotics focusing on two key components: SecA, the ATP-driven motor protein responsible for driving preproteins across the cytoplasmic membrane and the Type I signal peptidase that is responsible for the removal of the signal peptide allowing the release of the mature protein from the membrane. We take a bird's-eye view of other potential targets in the Sec-pathway as well as other Sec-dependent or Sec-independent protein secretion pathways as targets for the development of novel antibiotics. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. PMID:24534745

  18. 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

  19. The CRE1 Cytokinin Pathway Is Differentially Recruited Depending on Medicago truncatula Root Environments and Negatively Regulates Resistance to a Pathogen

    PubMed Central

    Laffont, Carole; Rey, Thomas; André, Olivier; Novero, Mara; Kazmierczak, Théophile; Debellé, Frédéric; Bonfante, Paola; Jacquet, Christophe; Frugier, Florian

    2015-01-01

    Cytokinins are phytohormones that regulate many developmental and environmental responses. The Medicago truncatula cytokinin receptor MtCRE1 (Cytokinin Response 1) is required for the nitrogen-fixing symbiosis with rhizobia. As several cytokinin signaling genes are modulated in roots depending on different biotic and abiotic conditions, we assessed potential involvement of this pathway in various root environmental responses. Phenotyping of cre1 mutant roots infected by the Gigaspora margarita arbuscular mycorrhizal (AM) symbiotic fungus, the Aphanomyces euteiches root oomycete, or subjected to an abiotic stress (salt), were carried out. Detailed histological analysis and quantification of cre1 mycorrhized roots did not reveal any detrimental phenotype, suggesting that MtCRE1 does not belong to the ancestral common symbiotic pathway shared by rhizobial and AM symbioses. cre1 mutants formed an increased number of emerged lateral roots compared to wild-type plants, a phenotype which was also observed under non-stressed conditions. In response to A. euteiches, cre1 mutants showed reduced disease symptoms and an increased plant survival rate, correlated to an enhanced formation of lateral roots, a feature previously linked to Aphanomyces resistance. Overall, we showed that the cytokinin CRE1 pathway is not only required for symbiotic nodule organogenesis but also affects both root development and resistance to abiotic and biotic environmental stresses. PMID:25562779

  20. The CRE1 cytokinin pathway is differentially recruited depending on Medicago truncatula root environments and negatively regulates resistance to a pathogen.

    PubMed

    Laffont, Carole; Rey, Thomas; André, Olivier; Novero, Mara; Kazmierczak, Théophile; Debellé, Frédéric; Bonfante, Paola; Jacquet, Christophe; Frugier, Florian

    2015-01-01

    Cytokinins are phytohormones that regulate many developmental and environmental responses. The Medicago truncatula cytokinin receptor MtCRE1 (Cytokinin Response 1) is required for the nitrogen-fixing symbiosis with rhizobia. As several cytokinin signaling genes are modulated in roots depending on different biotic and abiotic conditions, we assessed potential involvement of this pathway in various root environmental responses. Phenotyping of cre1 mutant roots infected by the Gigaspora margarita arbuscular mycorrhizal (AM) symbiotic fungus, the Aphanomyces euteiches root oomycete, or subjected to an abiotic stress (salt), were carried out. Detailed histological analysis and quantification of cre1 mycorrhized roots did not reveal any detrimental phenotype, suggesting that MtCRE1 does not belong to the ancestral common symbiotic pathway shared by rhizobial and AM symbioses. cre1 mutants formed an increased number of emerged lateral roots compared to wild-type plants, a phenotype which was also observed under non-stressed conditions. In response to A. euteiches, cre1 mutants showed reduced disease symptoms and an increased plant survival rate, correlated to an enhanced formation of lateral roots, a feature previously linked to Aphanomyces resistance. Overall, we showed that the cytokinin CRE1 pathway is not only required for symbiotic nodule organogenesis but also affects both root development and resistance to abiotic and biotic environmental stresses. PMID:25562779

  1. Evasion of inflammasome activation by microbial pathogens

    PubMed Central

    Ulland, Tyler K.; Ferguson, Polly J.; Sutterwala, Fayyaz S.

    2015-01-01

    Activation of the inflammasome occurs in response to infection with a wide array of pathogenic microbes. The inflammasome serves as a platform to activate caspase-1, which results in the subsequent processing and secretion of the proinflammatory cytokines IL-1? and IL-18 and the initiation of an inflammatory cell death pathway termed pyroptosis. Effective inflammasome activation is essential in controlling pathogen replication as well as initiating adaptive immune responses against the offending pathogens. However, a number of pathogens have developed strategies to evade inflammasome activation. In this Review, we discuss these pathogen evasion strategies as well as the potential infectious complications of therapeutic blockade of IL-1 pathways. PMID:25642707

  2. Immune response of non-pathogenic gram(+) and gram(-) bacteria in inductive sites of the intestinal mucosa study of the pathway of signaling involved.

    PubMed

    Dogi, C A; Weill, F; Perdigón, G

    2010-01-01

    The gut associated lymphoid tissue (GALT) is anatomical and functionally divided in inductive and effectors sites. In previous works we demonstrated that non-pathogenic bacteria with probiotic characteristics can improve the gut mucosal immune system, with an increase in the number of IgA and cytokines producing cells in the effector site of the intestine. In the present work we studied the effect of non-pathogenic Gram(+), Gram(-) bacteria and a Gram(+) probiotic strain on the inductor site (PP) after the oral administration to BALB/c mice. We also studied some signals induced by the assayed strain in the effectors site, such as the enzyme calcineurin and TLR-9 as a way to understand the mechanisms induced in such bacterial stimulation. The implicance of the lipoteichoic acid (LTA) in the immunostimulation was analyzed. All strains increased the number of IFN-gamma and TNF-alpha(+) cells, but not of IL-10(+) cells in the total population of PP. The release of IFN-gamma and TNF-alpha was only induced by LPS stimulation. All assayed strains increased the number of calcineurin(+) cells, while only Gram(+) strains increased the number of TLR-9(+) cells. The immunostimulatory properties of the purified LTA from Gram(+) strains was evaluated on a monocyte-macrophage U937 cell line. These cells showed capacity to release TNF-alpha and IL-10 in response to all LTA assayed in a dose-dependent way. Gram(+) strains induced signals through the calcineurin enzyme able to activate the transcriptional factor NFAT and through TLR-9. The LTA molecule from Gram(+) strains would not be the only structure involved in the immunostimulatory properties observed, specially for the probiotic strain. PMID:19250703

  3. Unraveling the novel structure and biosynthetic pathway of O-linked glycans in the Golgi apparatus of the human pathogenic yeast Cryptococcus neoformans.

    PubMed

    Lee, Dong-Jik; Bahn, Yong-Sun; Kim, Hong-Jin; Chung, Seung-Yeon; Kang, Hyun Ah

    2015-01-16

    Cryptococcus neoformans is an encapsulated basidiomycete causing cryptococcosis in immunocompromised humans. The cell surface mannoproteins of C. neoformans were reported to stimulate the host T-cell response and to be involved in fungal pathogenicity; however, their O-glycan structure is uncharacterized. In this study, we performed a detailed structural analysis of the O-glycans attached to cryptococcal mannoproteins using HPLC combined with exoglycosidase treatment and showed that the major C. neoformans O-glycans were short manno-oligosaccharides that were connected mostly by ?1,2-linkages but connected by an ?1,6-linkage at the third mannose residue. Comparison of the O-glycan profiles from wild-type and uxs1? mutant strains strongly supports the presence of minor O-glycans carrying a xylose residue. Further analyses of C. neoformans mutant strains identified three mannosyltransferase genes involved in O-glycan extensions in the Golgi. C. neoformans KTR3, the only homolog of the Saccharomyces cerevisiae KRE2/MNT1 family genes, was shown to encode an ?1,2-mannosyltransferase responsible for the addition of the second mannose residue via an ?1,2-linkage to the major O-glycans. C. neoformans HOC1 and HOC3, homologs of the Saccharomyces cerevisiae OCH1 family genes, were shown to encode ?1,6-mannosyltransferases that can transfer the third mannose residue, via an ?1,6-linkage, to minor O-glycans containing xylose and to major O-glycans without xylose, respectively. Moreover, the C. neoformans ktr3? mutant strain, which displayed increased sensitivity to SDS, high salt, and high temperature, showed attenuated virulence in a mouse model of cryptococcosis, suggesting that the extended structure of O-glycans is required for cell integrity and full pathogenicity of C. neoformans. PMID:25477510

  4. The Arabidopsis Rho of Plants GTPase AtROP6 Functions in Developmental and Pathogen Response Pathways1[C][W][OA

    PubMed Central

    Poraty-Gavra, Limor; Zimmermann, Philip; Haigis, Sabine; Bednarek, Paweł; Hazak, Ora; Stelmakh, Oksana Rogovoy; Sadot, Einat; Schulze-Lefert, Paul; Gruissem, Wilhelm; Yalovsky, Shaul

    2013-01-01

    How plants coordinate developmental processes and environmental stress responses is a pressing question. Here, we show that Arabidopsis (Arabidopsis thaliana) Rho of Plants6 (AtROP6) integrates developmental and pathogen response signaling. AtROP6 expression is induced by auxin and detected in the root meristem, lateral root initials, and leaf hydathodes. Plants expressing a dominant negative AtROP6 (rop6DN) under the regulation of its endogenous promoter are small and have multiple inflorescence stems, twisted leaves, deformed leaf epidermis pavement cells, and differentially organized cytoskeleton. Microarray analyses of rop6DN plants revealed that major changes in gene expression are associated with constitutive salicylic acid (SA)-mediated defense responses. In agreement, their free and total SA levels resembled those of wild-type plants inoculated with a virulent powdery mildew pathogen. The constitutive SA-associated response in rop6DN was suppressed in mutant backgrounds defective in SA signaling (nonexpresser of PR genes1 [npr1]) or biosynthesis (salicylic acid induction deficient2 [sid2]). However, the rop6DN npr1 and rop6DN sid2 double mutants retained the aberrant developmental phenotypes, indicating that the constitutive SA response can be uncoupled from ROP function(s) in development. rop6DN plants exhibited enhanced preinvasive defense responses to a host-adapted virulent powdery mildew fungus but were impaired in preinvasive defenses upon inoculation with a nonadapted powdery mildew. The host-adapted powdery mildew had a reduced reproductive fitness on rop6DN plants, which was retained in mutant backgrounds defective in SA biosynthesis or signaling. Our findings indicate that both the morphological aberrations and altered sensitivity to powdery mildews of rop6DN plants result from perturbations that are independent from the SA-associated response. These perturbations uncouple SA-dependent defense signaling from disease resistance execution. PMID:23319551

  5. Unraveling the Novel Structure and Biosynthetic Pathway of O-Linked Glycans in the Golgi Apparatus of the Human Pathogenic Yeast Cryptococcus neoformans*

    PubMed Central

    Lee, Dong-Jik; Bahn, Yong-Sun; Kim, Hong-Jin; Chung, Seung-Yeon; Kang, Hyun Ah

    2015-01-01

    Cryptococcus neoformans is an encapsulated basidiomycete causing cryptococcosis in immunocompromised humans. The cell surface mannoproteins of C. neoformans were reported to stimulate the host T-cell response and to be involved in fungal pathogenicity; however, their O-glycan structure is uncharacterized. In this study, we performed a detailed structural analysis of the O-glycans attached to cryptococcal mannoproteins using HPLC combined with exoglycosidase treatment and showed that the major C. neoformans O-glycans were short manno-oligosaccharides that were connected mostly by α1,2-linkages but connected by an α1,6-linkage at the third mannose residue. Comparison of the O-glycan profiles from wild-type and uxs1Δ mutant strains strongly supports the presence of minor O-glycans carrying a xylose residue. Further analyses of C. neoformans mutant strains identified three mannosyltransferase genes involved in O-glycan extensions in the Golgi. C. neoformans KTR3, the only homolog of the Saccharomyces cerevisiae KRE2/MNT1 family genes, was shown to encode an α1,2-mannosyltransferase responsible for the addition of the second mannose residue via an α1,2-linkage to the major O-glycans. C. neoformans HOC1 and HOC3, homologs of the Saccharomyces cerevisiae OCH1 family genes, were shown to encode α1,6-mannosyltransferases that can transfer the third mannose residue, via an α1,6-linkage, to minor O-glycans containing xylose and to major O-glycans without xylose, respectively. Moreover, the C. neoformans ktr3Δ mutant strain, which displayed increased sensitivity to SDS, high salt, and high temperature, showed attenuated virulence in a mouse model of cryptococcosis, suggesting that the extended structure of O-glycans is required for cell integrity and full pathogenicity of C. neoformans. PMID:25477510

  6. Environmental transmission of low pathogenicity avian influenza viruses and its implications for pathogen invasion

    PubMed Central

    Rohani, Pejman; Breban, Romulus; Stallknecht, David E.; Drake, John M.

    2009-01-01

    Understanding the transmission dynamics and persistence of avian influenza viruses (AIVs) in the wild is an important scientific and public health challenge because this system represents both a reservoir for recombination and a source of novel, potentially human-pathogenic strains. The current paradigm locates all important transmission events on the nearly direct fecal/oral bird-to-bird pathway. In this article, on the basis of overlooked evidence, we propose that an environmental virus reservoir gives rise to indirect transmission. This transmission mode could play an important epidemiological role. Using a stochastic model, we demonstrate how neglecting environmentally generated transmission chains could underestimate the explosiveness and duration of AIV epidemics. We show the important pathogen invasion implications of this phenomenon: the nonnegligible probability of outbreak even when direct transmission is absent, the long-term infectivity of locations of prior outbreaks, and the role of environmental heterogeneity in risk. PMID:19497868

  7. 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 Acid1[C][W][OA

    PubMed Central

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

    2012-01-01

    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

  8. 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

  9. Proteome Analysis of Coinfection of Epithelial Cells with Filifactor alocis and Porphyromonas gingivalis Shows Modulation of Pathogen and Host Regulatory Pathways

    PubMed Central

    Aruni, A. Wilson; Zhang, Kangling; Dou, Yuetan

    2014-01-01

    Changes in periodontal status are associated with shifts in the composition of the bacterial community in the periodontal pocket. The relative abundances of several newly recognized microbial species, including Filifactor alocis, as-yet-unculturable organisms, and other fastidious organisms have raised questions on their impact on disease development. We have previously reported that the virulence attributes of F. alocis are enhanced in coculture with Porphyromonas gingivalis. We have evaluated the proteome of host cells and F. alocis during a polymicrobial infection. Coinfection of epithelial cells with F. alocis and P. gingivalis strains showed approximately 20% to 30% more proteins than a monoinfection. Unlike F. alocis ATCC 35896, the D-62D strain expressed more proteins during coculture with P. gingivalis W83 than with P. gingivalis 33277. Proteins designated microbial surface component-recognizing adhesion matrix molecules (MSCRAMMs) and cell wall anchor proteins were highly upregulated during the polymicrobial infection. Ultrastructural analysis of the epithelial cells showed formation of membrane microdomains only during coinfection. The proteome profile of epithelial cells showed proteins related to cytoskeletal organization and gene expression and epigenetic modification to be in high abundance. Modulation of proteins involved in apoptotic and cell signaling pathways was noted during coinfection. The enhanced virulence potential of F. alocis may be related to the differential expression levels of several putative virulence factors and their effects on specific host cell pathways. PMID:24866790

  10. Broken-Symmetry DFT Computations for the Reaction Pathway of IspH, an Iron-Sulfur Enzyme in Pathogenic Bacteria.

    PubMed

    Blachly, Patrick G; Sandala, Gregory M; Giammona, Debra Ann; Bashford, Donald; McCammon, J Andrew; Noodleman, Louis

    2015-07-01

    The recently discovered methylerythritol phosphate (MEP) pathway provides new targets for the development of antibacterial and antimalarial drugs. In the final step of the MEP pathway, the [4Fe-4S] IspH protein catalyzes the 2e(-)/2H(+) reductive dehydroxylation of (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) to afford the isoprenoid precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). Recent experiments have attempted to elucidate the IspH catalytic mechanism to drive inhibitor development. Two competing mechanisms have recently emerged, differentiated by their proposed HMBPP binding modes upon 1e(-) reduction of the [4Fe-4S] cluster: (1) a Birch reduction mechanism, in which HMBPP remains bound to the [4Fe-4S] cluster through its terminal C4-OH group (ROH-bound) until the -OH is cleaved as water; and (2) an organometallic mechanism, in which the C4-OH group rotates away from the [4Fe-4S] cluster, allowing the HMBPP olefin group to form a metallacycle complex with the apical iron (η(2)-bound). We perform broken-symmetry density functional theory computations to assess the energies and reduction potentials associated with the ROH- and η(2)-bound states implicated by these competing mechanisms. Reduction potentials obtained for ROH-bound states are more negative (-1.4 to -1.0 V) than what is typically expected of [4Fe-4S] ferredoxin proteins. Instead, we find that η(2)-bound states are lower in energy than ROH-bound states when the [4Fe-4S] cluster is 1e(-) reduced. Furthermore, η(2)-bound states can already be generated in the oxidized state, yielding reduction potentials of ca. -700 mV when electron addition occurs after rotation of the HMBPP C4-OH group. We demonstrate that such η(2)-bound states are kinetically accessible both when the IspH [4Fe-4S] cluster is oxidized and 1e(-) reduced. The energetically preferred pathway gives 1e(-) reduction of the cluster after substrate conformational change, generating the 1e(-) reduced intermediate proposed in the organometallic mechanism. PMID:26098647

  11. A Luman/CREB3ADP-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 CREB3ARF4 signaling cascade that may be part of a Golgi stress response set in motion by stimuli compromising Golgi capacity. PMID:24185178

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

    PubMed Central

    Neres, Joo; 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

  13. 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

  14. Including pathogen risk in life cycle assessment of wastewater management. 1. Estimating the burden of disease associated with pathogens.

    PubMed

    Harder, Robin; Heimersson, Sara; Svanstrm, Magdalena; Peters, Gregory M

    2014-08-19

    The environmental performance of wastewater and sewage sludge management is commonly assessed using life cycle assessment (LCA), whereas pathogen risk is evaluated with quantitative microbial risk assessment (QMRA). This study explored the application of QMRA methodology with intent to include pathogen risk in LCA and facilitate a comparison with other potential impacts on human health considered in LCA. Pathogen risk was estimated for a model wastewater treatment system (WWTS) located in an industrialized country and consisting of primary, secondary, and tertiary wastewater treatment, anaerobic sludge digestion, and land application of sewage sludge. The estimation was based on eight previous QMRA studies as well as parameter values taken from the literature. A total pathogen risk (expressed as burden of disease) on the order of 0.2-9 disability-adjusted life years (DALY) per year of operation was estimated for the model WWTS serving 28,600 persons and for the pathogens and exposure pathways included in this study. The comparison of pathogen risk with other potential impacts on human health considered in LCA is detailed in part 2 of this article series. PMID:25058492

  15. Nonstarch Polysaccharides Modulate Bacterial Microbiota, Pathways for Butyrate Production, and Abundance of Pathogenic Escherichia coli in the Pig Gastrointestinal Tract▿ †

    PubMed Central

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

    2010-01-01

    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 β-glucan (LG), and with high-viscosity, high-fermentability oat β-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. PMID:20382813

  16. 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-? 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-? to the COX-1 promoter by luciferase reporter and chromatin immunoprecipitation assays. In addition, silencing of C/EBP-? 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-? 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

  17. 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

    Background Following Helicobacter pylori eradication in idiopathic parkinsonism (IP), hypokinesia improved but flexor-rigidity increased. Small intestinal bacterial-overgrowth (SIBO) is a candidate driver of the rigidity: hydrogen-breath-test-positivity is common in IP and case histories suggest that Helicobacter keeps SIBO at bay. Methods In a surveillance study, we explore relationships of IP-facets to peripheral immune/inflammatory-activation, in light of presence/absence of Helicobacter infection (urea-breath- and/or stool-antigen-test: positivity confirmed by gastric-biopsy) and hydrogen-breath-test status for SIBO (positivity: >20 ppm increment, 2 consecutive 15-min readings, within 2h of 25G lactulose). We question whether any relationships found between facets and blood leukocyte subset counts stand in patients free from anti-parkinsonian drugs, and are robust enough to defy fluctuations in performance consequent on short t therapy. Results Of 51 IP-probands, 36 had current or past Helicobacter infection on entry, 25 having undergone successful eradication (median 3.4 years before). Thirty-four were hydrogen-breath-test-positive initially, 42 at sometime (343 tests) during surveillance (2.8 years). Hydrogen-breath-test-positivity was associated inversely with Helicobacter-positivity (OR 0.20 (95% CI 0.04, 0.99), p<0.05). In 38 patients (untreated (17) or on stable long-t IP-medication), the higher the natural-killer count, the shorter stride, slower gait and greater flexor-rigidity (by mean 49 (14, 85) mm, 54 (3, 104) mm.s-1, 89 (2, 177) Nm.10-3, per 100 cells.?l-1 increment, p=0.007, 0.04 & 0.04 respectively, adjusted for patient characteristics). T-helper count was inversely associated with flexor-rigidity before (p=0.01) and after adjustment for natural-killer count (-36(-63, -10) Nm.10-3 per 100 cells.?l-1, p=0.007). Neutrophil count was inversely associated with tremor (visual analogue scale, p=0.01). Effect-sizes were independent of IP-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

  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. 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.

  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. 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…

  2. 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

  3. Metagenomic identification of viral pathogens.

    PubMed

    Bibby, Kyle

    2013-05-01

    The target-independent identification of viral pathogens using 'shotgun' metagenomic sequencing is an emerging approach with potentially wide applications in clinical diagnostics, public health monitoring, and viral discovery. In this approach, all viral nucleic acids present in a sample are sequenced in a random, shotgun manner. Pathogens are then identified without the prerequisite of searching for a specific viral pathogen. In this opinion article, I discuss the current state and future research directions for this emerging and disruptive technology. With further technical developments, viral metagenomics has the potential to be deployed as a powerful and widely adopted tool, transforming the way that viral disease is researched, monitored, and treated. PMID:23415279

  4. [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. PMID:26058770

  5. SEWAGE SLUDGE PATHOGEN TRANSPORT MODEL PROJECT

    EPA Science Inventory

    The sewage sludge pathogen transport model predicts the number of Salmonella, Ascaris, and polioviruses which might be expected to occur at various points in the environment along 13 defined pathways. These pathways describe the use of dried or liquid, raw or anaerobically digest...

  6. Article Watch: September 2013

    PubMed Central

    Slaughter, Clive A.

    2013-01-01

    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; 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.

  7. 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.

  8. 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.

  9. 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…

  10. [Animal pathogens as biological weapons].

    PubMed

    Chomiczewski, Krzysztof

    2003-01-01

    In this article, the most important animal pathogens, which, according to CDC classification, can be used as biological agents, are presented. The means of dissemination and the ways of infection's propagation are reviewed. Typical and the most dangerous signs and symptoms are described, as well as the consequences of these infections. PMID:12910606

  11. Ammonium chloride, an inhibitor of phagosome-lysosome fusion in macrophages, concurrently induces phagosome-endosome fusion, and opens a novel pathway: studies of a pathogenic mycobacterium and a nonpathogenic yeast.

    PubMed

    Hart, P D; Young, M R

    1991-10-01

    The weak base ammonium chloride has been previously reported to inhibit lysosomal movements and phagosome-lysosome (Ph-L) fusion in cultured mouse macrophages (M phi), thus reducing delivery, to an intraphagosomal infection, of endocytosed solutes that have concentrated in secondary lysosomes. We have now addressed the question, whether NH4Cl might affect any direct interaction (if it exists) between such infection phagosomes and earlier, nonlysosomal compartments of the endocytic pathway, i.e., solute-containing endosomes. The phagosomes studied were formed after ingestion of the mouse pathogen Mycobacterium microti and the nonpathogenic yeast Saccharomyces cerevisiae; and the endosomes were formed after nonreceptor-mediated endocytosis of electronopaque and fluorescent soluble markers. By electron microscopy, survey of the cell profiles of M phi that had been treated with 10 mM NH4Cl so that Ph-L fusion was prevented, and that displayed many ferritin-labeled endosomes, revealed numerous examples of the fusion of electronlucent endosomes, revealed numerous examples of the fusion of electronlucent vesicles with phagosomes, whether containing M. microti bacilli or S. cerevisiae yeasts. Fusion was recognized by transfer of label and by morphological evidence of fusion in progress. The fusing vesicles were classed as endosomes, not NH4Cl-lysosomes, by their appearance and provenance, and because lysosome participation was excluded by the concurrent, NH4Cl-caused block of Ph-L fusion and associated lysosomal stasis. No evidence of such phagosome-endosome (Ph-E) fusion was observed in profiles from M phi treated with chloroquine, nor in those from normal, untreated M phi. NH4Cl-treated living M phi that had ingested yeasts at 37 degrees C, followed by endocytosis of lucifer yellow at 17 degrees C (to accumulate labeled endosomes and postpone label passing to lysosomes), were then restored to 37 degrees C. Fluorescence microscopy showed that as many as half of the yeast phagosomes (previously unlabeled) rapidly became colored. We inferred that this transfer was from endosomes (by Ph-E fusion) because Ph-L passage was blocked (by the NH4Cl). We conclude that NH4Cl induces Ph-E fusion at the same time as it suppressed Ph-L fusion. We discuss the mechanisms of these concurrent effects and suggest that they are independent; and we consider the implications of NH4Cl opening a direct route for endocytosed molecules to reach an intraphagosomal infection without involving lysosomes. PMID:1919441

  12. 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 infection through modulation of both inflammatory and anti-inflammatory pathways. PMID:25993608

  13. 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.

  14. 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.

  15. 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.

  16. Article Watch: September 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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...

  2. Bacterial itaconate degradation promotes pathogenicity.

    PubMed

    Sasikaran, Jahminy; Ziemski, Micha?; Zadora, Piotr K; Fleig, Angela; Berg, Ivan A

    2014-05-01

    Itaconate (methylenesuccinate) was recently identified as a mammalian metabolite whose production is substantially induced during macrophage activation. This compound is a potent inhibitor of isocitrate lyase, a key enzyme of the glyoxylate cycle, which is a pathway required for the survival of many pathogens inside the eukaryotic host. Here we show that numerous bacteria, notably many pathogens such as Yersinia pestis and Pseudomonas aeruginosa, have three genes for itaconate degradation. They encode itaconate coenzyme A (CoA) transferase, itaconyl-CoA hydratase and (S)-citramalyl-CoA lyase, formerly referred to as CitE-like protein. These genes are known to be crucial for survival of some pathogens in macrophages. The corresponding enzymes convert itaconate into the cellular building blocks pyruvate and acetyl-CoA, thus enabling the bacteria to metabolize itaconate and survive in macrophages. The itaconate degradation and detoxification pathways of Yersinia and Pseudomonas are the result of convergent evolution. This work revealed a common persistence factor operating in many pathogenic bacteria. PMID:24657929

  3. Pathways to Teaching.

    ERIC Educational Resources Information Center

    Future Teacher, 1997

    1997-01-01

    Articles in this theme issue explore pathways into teaching, focusing on programs that recruit future teachers, and specifically on programs that target minority future teachers. "Pathways to Teaching: Building Quality and Diversity in America's Schools" by Segun Eubanks introduces a number of programs that are drawing from populations

  4. 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.

  5. 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

  6. Heme uptake in bacterial pathogens

    PubMed Central

    Contreras, Heidi; Chim, Nicholas; Credali, Alfredo; Goulding, Celia W.

    2014-01-01

    Iron is an essential nutrient for the survival of organisms. Bacterial pathogens possess specialized pathways to acquire heme from their human hosts. In this review, we present recent structural and biochemical data that provide mechanistic insights into several bacterial heme uptake pathways, encompassing the sequestration of heme from human hemoproteins to secreted or membrane-associated bacterial proteins, the transport of heme across bacterial membranes, and the degradation of heme within the bacterial cytosol to liberate iron. The pathways for heme transport into the bacterial cytosol are divergent, harboring non-homologous protein sequences, novel structures, varying numbers of proteins, and different mechanisms. Congruously, the breakdown of heme within the bacterial cytosol by sequence-divergent proteins releases iron and distinct degradation products. PMID:24780277

  7. 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.

  8. Pathogens Hijack the Epigenome

    PubMed Central

    Silmon de Monerri, Natalie C.; Kim, Kami

    2015-01-01

    Pathogens have evolved strategies to promote their survival by dramatically modifying the transcriptional profile and protein content of the host cells they infect. Modifications of the host transcriptome and proteome are mediated by pathogen-encoded effector molecules that modulate host cells through a variety of different mechanisms. Recent studies highlight the importance of the host chromatin and other epigenetic regulators as targets of pathogens. Host gene regulatory mechanisms may be targeted through cytoplasmic signaling, directly by pathogen effector proteins, and possibly by pathogen RNA. Although many of these changes are short-lived and persist only during the course of infection, several studies indicate that pathogens are able to induce long-term, heritable changes that are essential to pathogenesis of infectious diseases and persistence of pathogens within their hosts. In this review, we discuss how pathogens modulate the epigenome of host cells, a new and flourishing avenue of host-pathogen interaction studies. PMID:24525150

  9. 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

  10. 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

  11. PATHOGENS: VIEWS OF EPA'S PATHOGEN EQUIVALENCY COMMITTEE

    EPA Science Inventory

    This presentation reviews the pathogenic microorganisms that may be found in municipal sewage sludge and the commonly employed Class A and B processes for controlling pathogens. It notes how extensively they are used and discusses issues and concerns with their application. Pre...

  12. 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.

  13. 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

  14. 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

  15. Phosphoinositides and host-pathogen interactions.

    PubMed

    Pizarro-Cerdá, Javier; Kühbacher, Andreas; Cossart, Pascale

    2015-06-01

    Phosphoinositides control key cellular processes including vesicular trafficking and actin polymerization. Intracellular bacterial pathogens manipulate phosphoinositide metabolism in order to promote their uptake by target cells and to direct in some cases the biogenesis of their replication compartments. In this chapter, we review the molecular strategies that major pathogens including Listeria, Mycobacterium, Shigella, Salmonella, Legionella and Yersinia use to hijack phosphoinositides during infection. This article is part of a Special Issue entitled Phosphoinositides. PMID:25241942

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

    PubMed

    Guo, Li; Breakspear, Andrew; Zhao, Guoyi; Gao, Lixin; Kistler, H Corby; Xu, Jin-Rong; Ma, Li-Jun

    2016-02-01

    The cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway is a central signalling cascade that transmits extracellular stimuli and governs cell responses through the second messenger cAMP. The importance of cAMP signalling in fungal biology has been well documented and the key conserved components, adenylate cyclase (AC) and the catalytic subunit of PKA (CPKA), have been functionally characterized. However, other genes involved in this signalling pathway and their regulation are not well understood in filamentous fungi. Here, we performed a comparative transcriptomics analysis of AC and CPKA mutants in two closely related fungi: Fusarium graminearum (Fg) and F.?verticillioides (Fv). Combining available Fg transcriptomics and phenomics data, we reconstructed the Fg cAMP signalling pathway. We developed a computational program that combines sequence conservation and patterns of orthologous gene expression to facilitate global transcriptomics comparisons between different organisms. We observed highly correlated expression patterns for most orthologues (80%) between Fg and Fv. We also identified a subset of 482 (6%) diverged orthologues, whose expression under all conditions was at least 50% higher in one genome than in the other. This enabled us to dissect the conserved and unique portions of the cAMP-PKA pathway. Although the conserved portions controlled essential functions, such as metabolism, the cell cycle, chromatin remodelling and the oxidative stress response, the diverged portions had species-specific roles, such as the production and detoxification of secondary metabolites unique to each species. The evolution of the cAMP-PKA signalling pathway seems to have contributed directly to fungal divergence and niche adaptation. PMID:25907134

  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

    PubMed Central

    Guo, Li; Breakspear, Andrew; Zhao, Guoyi; Gao, Lixin; Kistler, H. Corby; Xu, Jin‐Rong

    2015-01-01

    Summary The cyclic adenosine monophosphate–protein kinase A (cAMP–PKA) pathway is a central signalling cascade that transmits extracellular stimuli and governs cell responses through the second messenger cAMP. The importance of cAMP signalling in fungal biology has been well documented and the key conserved components, adenylate cyclase (AC) and the catalytic subunit of PKA (CPKA), have been functionally characterized. However, other genes involved in this signalling pathway and their regulation are not well understood in filamentous fungi. Here, we performed a comparative transcriptomics analysis of AC and CPKA mutants in two closely related fungi: Fusarium graminearum (Fg) and F. verticillioides (Fv). Combining available Fg transcriptomics and phenomics data, we reconstructed the Fg cAMP signalling pathway. We developed a computational program that combines sequence conservation and patterns of orthologous gene expression to facilitate global transcriptomics comparisons between different organisms. We observed highly correlated expression patterns for most orthologues (80%) between Fg and Fv. We also identified a subset of 482 (6%) diverged orthologues, whose expression under all conditions was at least 50% higher in one genome than in the other. This enabled us to dissect the conserved and unique portions of the cAMP–PKA pathway. Although the conserved portions controlled essential functions, such as metabolism, the cell cycle, chromatin remodelling and the oxidative stress response, the diverged portions had species‐specific roles, such as the production and detoxification of secondary metabolites unique to each species. The evolution of the cAMP–PKA signalling pathway seems to have contributed directly to fungal divergence and niche adaptation. PMID:25907134

  18. 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

  19. Transcript profiling in host-pathogen interactions.

    PubMed

    Wise, Roger P; Moscou, Matthew J; Bogdanove, Adam J; Whitham, Steven A

    2007-01-01

    Using genomic technologies, it is now possible to address research hypotheses in the context of entire developmental or biochemical pathways, gene networks, and chromosomal location of relevant genes and their inferred evolutionary history. Through a range of platforms, researchers can survey an entire transcriptome under a variety of experimental and field conditions. Interpretation of such data has led to new insights and revealed previously undescribed phenomena. In the area of plant-pathogen interactions, transcript profiling has provided unparalleled perception into the mechanisms underlying gene-for-gene resistance and basal defense, host vs nonhost resistance, biotrophy vs necrotrophy, and pathogenicity of vascular vs nonvascular pathogens, among many others. In this way, genomic technologies have facilitated a system-wide approach to unifying themes and unique features in the interactions of hosts and pathogens. PMID:17480183

  20. Autophagy and checkpoints for intracellular pathogen defense

    PubMed Central

    Paulus, Geraldine L.C.; Xavier, Ramnik J.

    2015-01-01

    Purpose of review Autophagy plays a crucial role in intracellular defense against various pathogens. Xenophagy is a form of selective autophagy that targets intracellular pathogens for degradation. In addition, several related yet distinct intracellular defense responses depend on autophagy-related (ATG) genes. This review gives an overview of these processes, pathogen strategies to subvert them, and their crosstalk with various cell death programs. Recent findings The recruitment of ATG proteins plays a key role in multiple intracellular defense programs, specifically xenophagy, LC3-associated phagocytosis (LAP), and the IFN?-mediated elimination of pathogens such as Toxoplasma gondii and murine norovirus. Recent progress has revealed methods employed by pathogens to resist these intracellular defense mechanisms and/or persist in spite of them. The intracellular pathogen load can tip the balance between cell survival and cell death. Further, it was recently observed that LAP is indispensable for the efficient clearance of dying cells. Summary Autophagy-dependent and ATG gene-dependent pathways are essential in intracellular defense against a broad range of pathogens. PMID:25394238

  1. 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

  2. Modulation of NF-κB signalling by microbial pathogens

    PubMed Central

    Rahman, Masmudur M.; McFadden, Grant

    2013-01-01

    The nuclear factor-κB (NF-κB) family of transcription factors plays a central part in the host response to infection by microbial pathogens, by orchestrating the innate and acquired host immune responses. The NF-κB proteins are activated by diverse signalling pathways that originate from many different cellular receptors and sensors. Many successful pathogens have acquired sophisticated mechanisms to regulate the NF-κB signalling pathways by deploying subversive proteins or hijacking the host signalling molecules. Here, we describe the mechanisms by which viruses and bacteria micromanage the host NF-κB signalling circuitry to favour the continued survival of the pathogen. PMID:21383764

  3. RNA-mediated pathogenic mechanisms in polyglutamine diseases and amyotrophic lateral sclerosis

    PubMed Central

    Chan, Ho Yin Edwin

    2014-01-01

    Gene transcription produces a wide variety of ribonucleic acid (RNA) species in eukaryotes. Individual types of RNA, such as messenger, structural and regulatory RNA, are known to play distinct roles in the cell. Recently, researchers have identified a large number of RNA-mediated toxicity pathways that play significant pathogenic roles in numerous human disorders. In this article, we describe various common RNA toxicity pathways, namely epigenetic gene silencing, nucleolar stress, nucleocytoplasmic transport, bi-directional gene transcription, repeat-associated non-ATG translation, RNA foci formation and cellular protein sequestration. We emphasize RNA toxicity mechanisms that involve nucleotide repeat expansion, such as those related to polyglutamine (polyQ) disorders and frontotemporal lobar degeneration-amyotrophic lateral sclerosis. PMID:25565965

  4. 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

  5. Metagenomes of Microbial Communities in Arsenic- and Pathogen-Contaminated Well and Surface Water from Bangladesh

    PubMed Central

    Layton, Alice C.; Chauhan, Archana; Williams, Daniel E.; Mailloux, Brian; Knappett, Peter S. K.; Ferguson, Andrew S.; McKay, Larry D.; Alam, M. Jahangir; Matin Ahmed, Kazi; van Geen, Alexander

    2014-01-01

    The contamination of drinking water from both arsenic and microbial pathogens occurs in Bangladesh. A general metagenomic survey of well water and surface water provided information on the types of pathogens present and may help elucidate arsenic metabolic pathways and potential assay targets for monitoring surface-to-ground water pathogen transport. PMID:25414497

  6. Resistant pathogens, fungi, and viruses.

    PubMed

    Guidry, Christopher A; Mansfield, Sara A; Sawyer, Robert G; Cook, Charles H

    2014-12-01

    Although originally described in Staphylococcus aureus, resistance among bacteria has now become a race to determine which classes of bacteria will become more resistant. Availability of antibacterial agents has allowed the development of entirely new diseases caused by nonbacterial pathogens, related largely to fungi that are inherently resistant to antibacterials. This article presents the growing body of knowledge of the herpes family of viruses, and their occurrence and consequences in patients with concomitant surgical disease or critical illness. The focus is on previously immunocompetent patients, as the impact of herpes viruses in immunosuppressed patients has received thorough coverage elsewhere. PMID:25440119

  7. Src-family and Syk Kinases in Activating and Inhibitory Pathways in Innate Immune Cells: Signaling Cross Talk

    PubMed Central

    Lowell, Clifford A.

    2011-01-01

    The response of innate immune cells to growth factors, immune complexes, extracellular matrix proteins, cytokines, pathogens, cellular damage, and many other stimuli is regulated by a complex net of intracellular signal transduction pathways. The majority of these pathways are either initiated or modulated by Src-family or Syk tyrosine kinases present in innate cells. The Src-family kinases modulate the broadest range of signaling responses, including regulating immunoreceptors, C-type lectins, integrins, G-protein-coupled receptors, and many others. Src-family kinases also modulate the activity of other kinases, including the Tec-family members as well as FAK and Pyk2. Syk kinase is required for initiation of signaling involving receptors that utilize immunoreceptor tyrosine activation (ITAM) domains. This article reviews the major activating and inhibitory signaling pathways regulated by these cytoplasmic tyrosine kinases, illuminating the many examples of signaling cross talk between pathways. PMID:21068150

  8. Microwave sintering of multiple articles

    DOEpatents

    Blake, Rodger D. (Santa Fe, NM); Katz, Joel D. (Los Alamos, NM)

    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.

  9. 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…

  10. 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

  11. Emerging foodborne pathogens.

    PubMed

    Tauxe, Robert V

    2002-09-15

    The broad spectrum of foodborne infections has changed dramatically over time, as well-established pathogens have been controlled or eliminated, and new ones have emerged. The burden of foodborne disease remains substantial: one in four Americans is estimated to have a significant foodborne illness each year. The majority of these illnesses are not accounted for by known pathogens, so more must remain to be discovered. Among the known foodborne pathogens, those more recently identified predominate, suggesting that as more and more is learned about pathogens, they come under control. In addition to the emergence or recognition of new pathogens, other trends include global pandemics of some foodborne pathogens, the emergence of antimicrobial resistance, the identification of pathogens that are highly opportunistic, affecting only the most high-risk subpopulations, and the increasing identification of large and dispersed outbreaks. New pathogens can emerge because of changing ecology or changing technology that connects a potential pathogen with the food chain. They also can emerge de novo by transfer of mobile virulence factors, often through bacteriophage. Though this is rarely observed, it can be reconstructed. Better understanding of the ecology and dynamics of phage transmission among bacteria will help us to understand the appearance of new pathogens in the future. One may look for emerging foodborne pathogens among the silent zoonoses, and among the severe infections affecting the immunocompromised humans. We should expect the unexpected. In the past, separating human sewage and animal manure from human food and water supplies was critical to improving public health. Now, our health depends increasingly on the safety of the feed and water supplies for the animals themselves. The successes of the 20th century and the new challenges we face mean that public health vigilance, careful investigation of new problems, responsible attention to food safety from farm to table, and partnerships to bring about new foodborne disease control measures will be needed for the foreseeable future. PMID:12222636

  12. The Arabidopsis Cyclic Nucleotide-Gated Ion Channels AtCNGC2 and AtCNGC4 Work in the Same Signaling Pathway to Regulate Pathogen Defense and Floral Transition1[C][W][OPEN

    PubMed Central

    Chin, Kimberley; DeFalco, Thomas A.; Moeder, Wolfgang; Yoshioka, Keiko

    2013-01-01

    Arabidopsis (Arabidopsis thaliana) cyclic nucleotide-gated ion channels (CNGCs) form a large family consisting of 20 members and have been implicated in Ca2+ signaling related to various physiological processes, such as pathogen defense, development, and thermotolerance. The null mutant of AtCNGC2, defense, no death (dnd1), exhibits autoimmune phenotypes, while it is impaired in mounting the hypersensitive response, which is a hallmark of effector-triggered (i.e. RESISTANCE-gene mediated) resistance. It has been suggested that AtCNGC2 is involved in defense responses and likely other aspects of physiology through its role as a Ca2+-conducting channel. However, the downstream signaling components and its relation with AtCNGC4, which is the closest paralog of AtCNGC2, remain elusive. Despite the fact that cngc4 mutants display almost identical phenotypes to those seen in cngc2 mutants, not much is known about their relationship. Here, we report the identification and characterization of the Arabidopsis mutant repressor of defense no death1 (rdd1), obtained from a suppressor screen of a transfer DNA insertion knockout mutant of AtCNGC2 in order to identify downstream components of dnd1-mediated signal transduction. rdd1 suppressed the majority of dnd1-mediated phenotypes except Ca2+ hypersensitivity. In addition, rdd1 also suppressed the dnd1-mediated late-flowering phenotype that was discovered in this study. Our genetic analysis conducted to elucidate the relationship between AtCNGC2 and AtCNGC4 indicates that RDD1 is also involved in AtCNGC4-mediated signal transduction. Lastly, bimolecular fluorescence complementation analysis suggests that AtCNGC2 and AtCNGC4 are likely part of the same channel complex. PMID:24027242

  13. The lipoxygenase pathway.

    PubMed

    Feussner, Ivo; Wasternack, Claus

    2002-01-01

    Lipid peroxidation is common to all biological systems, both appearing in developmentally and environmentally regulated processes of plants. The hydroperoxy polyunsaturated fatty acids, synthesized by the action of various highly specialized forms of lipoxygenases, are substrates of at least seven different enzyme families. Signaling compounds such as jasmonates, antimicrobial and antifungal compounds such as leaf aldehydes or divinyl ethers, and a plant-specific blend of volatiles including leaf alcohols are among the numerous products. Cloning of many lipoxygenases and other key enzymes within the lipoxygenase pathway, as well as analyses by reverse genetic and metabolic profiling, revealed new reactions and the first hints of enzyme mechanisms, multiple functions, and regulation. These aspects are reviewed with respect to activation of this pathway as an initial step in the interaction of plants with pathogens, insects, or abiotic stress and at distinct stages of development. PMID:12221977

  14. 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.

  15. 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.

  16. Parallel independent evolution of pathogenicity within the genus Yersinia.

    PubMed

    Reuter, Sandra; Connor, Thomas R; Barquist, Lars; Walker, Danielle; Feltwell, Theresa; Harris, Simon R; Fookes, Maria; Hall, Miquette E; Petty, Nicola K; Fuchs, Thilo M; Corander, Jukka; Dufour, Muriel; Ringwood, Tamara; Savin, Cyril; Bouchier, Christiane; Martin, Liliane; Miettinen, Minna; Shubin, Mikhail; Riehm, Julia M; Laukkanen-Ninios, Riikka; Sihvonen, Leila M; Siitonen, Anja; Skurnik, Mikael; Falco, Juliana Pfrimer; Fukushima, Hiroshi; Scholz, Holger C; Prentice, Michael B; Wren, Brendan W; Parkhill, Julian; Carniel, Elisabeth; Achtman, Mark; McNally, Alan; Thomson, Nicholas R

    2014-05-01

    The genus Yersinia has been used as a model system to study pathogen evolution. Using whole-genome sequencing of all Yersinia species, we delineate the gene complement of the whole genus and define patterns of virulence evolution. Multiple distinct ecological specializations appear to have split pathogenic strains from environmental, nonpathogenic lineages. This split demonstrates that contrary to hypotheses that all pathogenic Yersinia species share a recent common pathogenic ancestor, they have evolved independently but followed parallel evolutionary paths in acquiring the same virulence determinants as well as becoming progressively more limited metabolically. Shared virulence determinants are limited to the virulence plasmid pYV and the attachment invasion locus ail. These acquisitions, together with genomic variations in metabolic pathways, have resulted in the parallel emergence of related pathogens displaying an increasingly specialized lifestyle with a spectrum of virulence potential, an emerging theme in the evolution of other important human pathogens. PMID:24753568

  17. Parallel independent evolution of pathogenicity within the genus Yersinia

    PubMed Central

    Reuter, Sandra; Connor, Thomas R.; Barquist, Lars; Walker, Danielle; Feltwell, Theresa; Harris, Simon R.; Fookes, Maria; Hall, Miquette E.; Petty, Nicola K.; Fuchs, Thilo M.; Corander, Jukka; Dufour, Muriel; Ringwood, Tamara; Savin, Cyril; Bouchier, Christiane; Martin, Liliane; Miettinen, Minna; Shubin, Mikhail; Riehm, Julia M.; Laukkanen-Ninios, Riikka; Sihvonen, Leila M.; Siitonen, Anja; Skurnik, Mikael; Falcão, Juliana Pfrimer; Fukushima, Hiroshi; Scholz, Holger C.; Prentice, Michael B.; Wren, Brendan W.; Parkhill, Julian; Carniel, Elisabeth; Achtman, Mark; McNally, Alan; Thomson, Nicholas R.

    2014-01-01

    The genus Yersinia has been used as a model system to study pathogen evolution. Using whole-genome sequencing of all Yersinia species, we delineate the gene complement of the whole genus and define patterns of virulence evolution. Multiple distinct ecological specializations appear to have split pathogenic strains from environmental, nonpathogenic lineages. This split demonstrates that contrary to hypotheses that all pathogenic Yersinia species share a recent common pathogenic ancestor, they have evolved independently but followed parallel evolutionary paths in acquiring the same virulence determinants as well as becoming progressively more limited metabolically. Shared virulence determinants are limited to the virulence plasmid pYV and the attachment invasion locus ail. These acquisitions, together with genomic variations in metabolic pathways, have resulted in the parallel emergence of related pathogens displaying an increasingly specialized lifestyle with a spectrum of virulence potential, an emerging theme in the evolution of other important human pathogens. PMID:24753568

  18. 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...

  19. 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.

  20. 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...

  1. 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.

  2. 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 activated in flax in response to infection by pathogenic and non-pathogenic Fusarium strains. PMID:25972886

  3. Protein glycosylation in bacterial mucosal pathogens.

    PubMed

    Szymanski, Christine M; Wren, Brendan W

    2005-03-01

    In eukaryotes, glycosylated proteins are ubiquitous components of extracellular matrices and cellular surfaces. Their oligosaccharide moieties are implicated in a wide range of cell-cell and cell-matrix recognition events that are required for biological processes ranging from immune recognition to cancer development. Glycosylation was previously considered to be restricted to eukaryotes; however, through advances in analytical methods and genome sequencing, there have been increasing reports of both O-linked and N-linked protein glycosylation pathways in bacteria, particularly amongst mucosal-associated pathogens. Studying glycosylation in relatively less-complicated bacterial systems provides the opportunity to elucidate and exploit glycoprotein biosynthetic pathways. We will review the genetic organization, glycan structures and function of glycosylation systems in mucosal bacterial pathogens, and speculate on how this knowledge may help us to understand glycosylation processes in more complex eukaryotic systems and how it can be used for glycoengineering. PMID:15738950

  4. Mobile DNA in the pathogenic Neisseria

    PubMed Central

    Obergfell, Kyle P.; Seifert, H. Steven

    2015-01-01

    The genus Neisseria contains two pathogenic species of notable 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 programed 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. PMID:25866700

  5. Selected Fencing Articles. Sports Articles Reprint Series. First Edition.

    ERIC Educational Resources Information Center

    Herndon, Myrtis, Ed.

    This collection of articles on fencing is "The Division for Girls and Women's Sports (DGWS) Guides" 1946-1971 and the Second National Institute on Girls Sports. It is the latest in the American Association for Health, Physical Education, and Recreation's Sports Articles Reprint Series, a special project of the Publications Area, DGWS. This is the

  6. Flexible, microporous rubber base articles

    SciTech Connect

    Goldberg, B.S.; Shah, M.

    1980-10-07

    As an article of manufacture, a microporous flexible shape or sheet of a sulfur-free, cured polymeric material of a curable rubber, an ethylene-propylene copolymer or mixtures of the curable rubber and ethylene-propylene copolymer is described. The article possesses an average pore size of less than 2 microns, a predetermined flexibility, and improved toughness, when compared to prior art sulfur cured articles.

  7. 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

  8. Microbial pathogenicity: a new approach to drug development.

    PubMed

    Chakrabarty, Ananda M

    2014-01-01

    Pathogenic microorganisms, particularly pathogenic bacteria that cause debilitating diseases, are considered a threat for human health and well-being. Infectious diseases are rampant, particularly in developing countries. However, there are many other deadly diseases, such as cancer, diabetes, cardiac malfunction, etc., that account for significant loss of life and trauma in our society. In this article, I try to describe the role certain bacterial pathogens with long term residence in the human body can play in providing us with our next generation anticancer and other drugs, demonstrating that a certain amount of good can come out of such bacterial pathogens as well. PMID:24595609

  9. Space Shuttle inflatable training articles

    NASA Technical Reports Server (NTRS)

    West, M. L.

    1984-01-01

    The design, development, construction, and testing of the Long Duration Exposure Facility inflatable and the space telescope training articles are discussed. While these articles are of similar nature, materials, and construction, they vary in size and present different problems with regards to size, shape, gross/net lift, and balance.

  10. Do TEFL Articles Solve Problems?

    ERIC Educational Resources Information Center

    Edge, Julian

    1985-01-01

    Discusses the problem which English-as-a-foreign-language (EFL) teacher trainees who are nonnative English speakers have in reading articles about EFL teaching methods. As a solution to this problem, the author produced a worksheet for the students to fill in while reading the articles which followed Hoey's…

  11. Evolution of plant pathogenicity in Streptomyces.

    PubMed

    Loria, Rosemary; Kers, Johan; Joshi, Madhumita

    2006-01-01

    Among the multitude of soil-inhabiting, saprophytic Streptomyces species are a growing number of plant pathogens that cause economically important diseases, including potato scab. Streptomyces scabies is the dominant pathogenic species worldwide, but is only one of many that cause very similar disease symptoms on plants. Molecular genetic analysis is beginning to identify the mechanisms used by plant pathogenic species to manipulate their hosts. The nitrated dipeptide phytotoxin, thaxtomin, inhibits cellulose biosynthesis in expanding plant tissues, stimulates Ca2+ spiking, and causes cell death. A secreted necrogenic protein, Nec1, contributes to virulence on diverse plant species. The thaxtomin biosynthetic genes and nec1 lie on a large mobilizable PAI, along with other putative virulence genes including a cytokinin biosynthetic pathway and a saponinase homolog. The PAI is mobilized during conjugation and site-specifically inserts in the linear chromosome of recipient species, accounting for the emergence of new pathogens in agricultural systems. The recently available genome sequence of S. scabies will accelerate research on host-pathogen interactions. PMID:16719719

  12. Inflammasome/IL-1β Responses to Streptococcal Pathogens

    PubMed Central

    LaRock, Christopher N.; Nizet, Victor

    2015-01-01

    Inflammation mediated by the inflammasome and the cytokine IL-1β are some of the earliest and most important alarms to infection. These pathways are responsive to the virulence factors that pathogens use to subvert immune processes, and thus are typically activated only by microbes with potential to cause severe disease. Among the most serious human infections are those caused by the pathogenic streptococci, in part because these species numerous strategies for immune evasion. Since the virulence factor armament of each pathogen is unique, the role of IL-1β and the pathways leading to its activation varies for each infection. This review summarizes the role of IL-1β during infections caused by streptococcal pathogens, with emphasis on emergent mechanisms and concepts countering paradigms determined for other organisms. PMID:26500655

  13. 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 pathogenicity of those candidate genes uncovered from these studies will be further ascertained by direct knock outs (gene inactivation) and by in vivo studies using an animal model. Discovery of new virulence factors in Y. pestis will directly impact the development of new signatures for detection and geo-location since it will help us to understand and identify those genes that are essential in making the organism pathogenic. These are genes that cannot be altered or removed from the pathogen and as such constitute the best type of signature that we can utilize in their detection and identification. Applications such as this will also enable the utilization of similar technologies to study other pathogens such as Francisella and Brucella, for which we know substantially less in terms of their modality of virulence.

  14. Herpesvirus Exploitation of Host Immune Inhibitory Pathways

    PubMed Central

    Stack, Gabrielle; Stacey, Maria A.; Humphreys, Ian R.

    2012-01-01

    Herpesviruses employ a plethora of mechanisms to circumvent clearance by host immune responses. A key feature of mammalian immune systems is the employment of regulatory pathways that limit immune responsiveness. The primary functions of these mechanisms are to control autoimmunity and limit exuberant responses to harmless antigen in mucosal surfaces. However, such pathways can be exploited by viral pathogens to enable acute infection, persistence and dissemination. Herein, we outline the current understanding of inhibitory pathways in modulating antiviral immunity during herpesvirus infections in vivo and discuss strategies employed by herpesviruses to exploit these pathways to limit host antiviral immunity. PMID:23012619

  15. Professional Communication through Journal Articles.

    ERIC Educational Resources Information Center

    Rochester, Maxine K.

    1996-01-01

    Reviews studies of journal articles as a means of professional communication in the field of library and information science. The focus has been on content analysis and bibliometrics, which includes author, topic, and citation analysis. (LAM)

  16. Outbreaks where food workers have been implicated in the spread of foodborne disease. Part 6. Transmission and survival of pathogens in the food processing and preparation environment.

    PubMed

    Todd, Ewen C D; Greig, Judy D; Bartleson, Charles A; Michaels, Barry S

    2009-01-01

    This article, the sixth in a series reviewing the role of food workers in foodborne outbreaks, describes the source and means of pathogen transfer. The transmission and survival of enteric pathogens in the food processing and preparation environment through human and raw food sources is reviewed, with the main objective of providing information critical to the reduction of illness due to foodborne outbreaks. Pathogens in the food preparation area can originate from infected food workers, raw foods, or other environmental sources. These pathogens can then spread within food preparation or processing facilities through sometimes complex pathways and may infect one or more workers or the consumer of foods processed or prepared by these infected workers. The most frequent means of worker contamination is the fecal-oral route, and study results have indicated that toilet paper may not stop transmission of pathogens to hands. However, contact with raw foods of animal origin, worker aerosols (from sneezes), vomitus, and exposed hand lesions also have been associated with outbreaks. Transfer of pathogens has been documented through contaminated fabrics and carpets, rings, currency, skin surfaces, dust, and aerosols and though person-to-person transmission. Results of experiments on pathogen survival have indicated that transmission depends on the species, the inoculum delivery route, the contact surface type, the duration and temperature of exposure, and the relative humidity. Generally, viruses and encysted parasites are more resistant than enteric bacteria to adverse environmental conditions, but all pathogens can survive long enough for transfer from a contaminated worker to food, food contact surfaces, or fellow workers. PMID:19205488

  17. Metabolic crosstalk between host and pathogen: sensing, adapting and competing.

    PubMed

    Olive, Andrew J; Sassetti, Christopher M

    2016-04-01

    Our understanding of bacterial pathogenesis is dominated by the cell biology of the host-pathogen interaction. However, the majority of metabolites that are used in prokaryotic and eukaryotic physiology and signalling are chemically similar or identical. Therefore, the metabolic crosstalk between pathogens and host cells may be as important as the interactions between bacterial effector proteins and their host targets. In this Review we focus on host-pathogen interactions at the metabolic level: chemical signalling events that enable pathogens to sense anatomical location and the local physiology of the host; microbial metabolic pathways that are dedicated to circumvent host immune mechanisms; and a few metabolites as central points of competition between the host and bacterial pathogens. PMID:26949049

  18. RAB11-mediated trafficking in host-pathogen interactions.

    PubMed

    Guichard, Annabel; Nizet, Victor; Bier, Ethan

    2014-09-01

    Many bacterial and viral pathogens block or subvert host cellular processes to promote successful infection. One host protein that is targeted by invading pathogens is the small GTPase RAB11, which functions in vesicular trafficking. RAB11 functions in conjunction with a protein complex known as the exocyst to mediate terminal steps in cargo transport via the recycling endosome to cell-cell junctions, phagosomes and cellular protrusions. These processes contribute to host innate immunity by promoting epithelial and endothelial barrier integrity, sensing and immobilizing pathogens and repairing pathogen-induced cellular damage. In this Review, we discuss the various mechanisms that pathogens have evolved to disrupt or subvert RAB11-dependent pathways as part of their infection strategy. PMID:25118884

  19. 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.

  20. An evolutionary perspective on zinc uptake by human fungal pathogens

    PubMed Central

    Wilson, Duncan

    2015-01-01

    The mammalian immune system has evolved sophisticated mechanisms to withhold essential micronutrients from invading pathogens. These processes, collectively known as nutritional immunity serve to limit microbial proliferation and bolster killing of the invader. Successful pathogens, therefore, have developed strategies to counteract nutritional immunity and acquire essential micronutrients in the restrictive environment of the infected host. Here I take advantage of the now large number of sequenced fungal genomes to explore the zinc acquisition strategies of human fungal pathogens and reflect on the evolutionary context of these uptake pathways. PMID:25652414

  1. Pathogens and polymers: Microbehost 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. 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.

  3. 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

  4. A comprehensive Prunus pathogen array

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A comprehensive pathogen array was developed for the detection of pathogens of many major crops in the Prunus genus. The APS disease lists for peach, plum, apricot and cherry were combined into a single Prunus pathogen list, containing 102 pathogens (75 fungi, 18 viruses, 6 bacteria and 3 phytoplasm...

  5. 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

  6. A Network Approach to Predict Pathogenic Genes for Fusarium graminearum

    PubMed Central

    Liu, Xiaoping; Tang, Wei-Hua; Zhao, Xing-Ming; Chen, Luonan

    2010-01-01

    Fusarium graminearum is the pathogenic agent of Fusarium head blight (FHB), which is a destructive disease on wheat and barley, thereby causing huge economic loss and health problems to human by contaminating foods. Identifying pathogenic genes can shed light on pathogenesis underlying the interaction between F. graminearum and its plant host. However, it is difficult to detect pathogenic genes for this destructive pathogen by time-consuming and expensive molecular biological experiments in lab. On the other hand, computational methods provide an alternative way to solve this problem. Since pathogenesis is a complicated procedure that involves complex regulations and interactions, the molecular interaction network of F. graminearum can give clues to potential pathogenic genes. Furthermore, the gene expression data of F. graminearum before and after its invasion into plant host can also provide useful information. In this paper, a novel systems biology approach is presented to predict pathogenic genes of F. graminearum based on molecular interaction network and gene expression data. With a small number of known pathogenic genes as seed genes, a subnetwork that consists of potential pathogenic genes is identified from the protein-protein interaction network (PPIN) of F. graminearum, where the genes in the subnetwork are further required to be differentially expressed before and after the invasion of the pathogenic fungus. Therefore, the candidate genes in the subnetwork are expected to be involved in the same biological processes as seed genes, which imply that they are potential pathogenic genes. The prediction results show that most of the pathogenic genes of F. graminearum are enriched in two important signal transduction pathways, including G protein coupled receptor pathway and MAPK signaling pathway, which are known related to pathogenesis in other fungi. In addition, several pathogenic genes predicted by our method are verified in other pathogenic fungi, which demonstrate the effectiveness of the proposed method. The results presented in this paper not only can provide guidelines for future experimental verification, but also shed light on the pathogenesis of the destructive fungus F. graminearum. PMID:20957229

  7. Parachlamydiaceae: Potential Emerging Pathogens

    PubMed Central

    Greub, Gilbert

    2002-01-01

    Parachlamydiaceae, which naturally infect amoebae, form a sister taxon to the Chlamydiaceae on the basis of the Chlamydia-like cycle of replication and 80% to 90% homology of ribosomal RNA genes. Because intra-amoebal growth could increase the virulence of some intracellular bacteria, Parachlamydiaceae may be pathogenic. Arguments supporting a pathogenic role are that Chlamydia pneumoniae, a well-recognized agent of pneumonia, was shown to infect free-living amoebae and that another member of the Chlamydiales, Simkania negevensis, which has 88% homology with Parachlamydia acanthamoebae, has caused pneumonia in adults and acute bronchiolitis in infants. The recent identification of a 16S rRNA gene sequence of a Parachlamydiaceae from bronchoalveolar lavage is additional evidence supporting potential for pathogenicity. PMID:12023921

  8. Candida albicans pathogenicity mechanisms.

    PubMed

    Mayer, Franois L; Wilson, Duncan; Hube, Bernhard

    2013-02-15

    The polymorphic fungus Candida albicans is a member of the normal human microbiome. In most individuals, C. albicans resides as a lifelong, harmless commensal. Under certain circumstances, however, C. albicans can cause infections that range from superficial infections of the skin to life-threatening systemic infections. Several factors and activities have been identified which contribute to the pathogenic potential of this fungus. Among them are molecules which mediate adhesion to and invasion into host cells, the secretion of hydrolases, the yeast-to-hypha transition, contact sensing and thigmotropism, biofilm formation, phenotypic switching and a range of fitness attributes. Our understanding of when and how these mechanisms and factors contribute to infection has significantly increased during the last years. In addition, novel virulence mechanisms have recently been discovered. In this review we present an update on our current understanding of the pathogenicity mechanisms of this important human pathogen. PMID:23302789

  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. 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.

  11. 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. PMID:22491118

  12. 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

  13. 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

  14. Isolation of pathogen-containing vacuoles.

    PubMed

    Shevchuk, Olga; Steinert, Michael

    2013-01-01

    Dictyostelium discoideum cells are "professional phagocytes," as they ingest a large variety of bacteria, yeast, and inert particles. Several bacterial pathogens are able to survive intracellularly within specialized vacuoles of D. discoideum by interfering with host signaling pathways. To better understand the molecular mechanisms underlying these evolutionary conserved processes we have established a method for the isolation of pathogen-containing vacuoles (PCVs). The isolation protocol describes the infection of D. discoideum cells with the intracellular pathogen Legionella pneumophila, loading of the lysosomal compartment with colloidal iron, mechanical lysis of host cells, iodophenylnitrophenyltetrazolium (INT) heavy labeling of mitochondria, removal of nucleic acid by Benzonase treatment, separation of nuclei by low-speed centrifugation, and the magnetic removal of lysosomes. The subcellular fractionation in a discontinuous sucrose density OptiPrep gradient allows the separation of mitochondria and to prepare PCVs with high purity. The proteins isolated from PCVs have been successfully subjected to mass spectrometry and allowed to analyze pathogen-directed maturation processes of vacuoles. The method can also be applied for subsequent protein modification analyses and lipidome comparisons. PMID:23494321

  15. 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

  16. A More Flexible Lipoprotein Sorting Pathway

    PubMed Central

    Chahales, Peter

    2015-01-01

    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

  17. "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

  18. GEOGRAPHIC INDEX OF ENVIRONMENTAL ARTICLES

    EPA Science Inventory

    This index was produced in accordance with the "Environmental Research Geographic Location Act," Public Law 101-617, enacted by the U.S. Congress on Nov. 16, 1990. ompiled by EPA, it is a quick reference for finding published articles about environmental issues for geographic loc...

  19. 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

  20. 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...

  1. 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

  2. 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...

  3. 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...

  4. Pathogenicity and virulence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many pathogenic microorganisms are host-specific in that they parasitize only one or a few animal species. For example, the cause of equine strangles, Streptococcus equi subspecies equi, is essentially limited to infection of horses. Otherscertain Salmonella serotypes, for examplehave a broad host...

  5. Stress adaptation in a pathogenic fungus.

    PubMed

    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

  6. 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 fungushost interactions during disease progression, are mediated by multiple mechanisms that include signalling and chemical crosstalk, stress pathway interference and a biological transistor. PMID:24353214

  7. 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.

  8. Fabrication of Molded Magnetic Article

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

    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.

  9. 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)

  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. PMID:26235082

  11. The secretory pathway kinases.

    PubMed

    Sreelatha, Anju; Kinch, Lisa N; Tagliabracci, Vincent S

    2015-10-01

    Protein phosphorylation is a nearly universal post-translation modification involved in a plethora of cellular events. Even though phosphorylation of extracellular proteins had been observed, the identity of the kinases that phosphorylate secreted proteins remained a mystery until only recently. Advances in genome sequencing and genetic studies have paved the way for the discovery of a new class of kinases that localize within the endoplasmic reticulum, Golgi apparatus and the extracellular space. These novel kinases phosphorylate proteins and proteoglycans in the secretory pathway and appear to regulate various extracellular processes. Mutations in these kinases cause human disease, thus underscoring the biological importance of phosphorylation within the secretory pathway. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases. PMID:25862977

  12. Five Reasons to Consider Phytophthora infestans a Reemerging Pathogen.

    PubMed

    Fry, W E; Birch, P R J; Judelson, H S; Grünwald, N J; Danies, G; Everts, K L; Gevens, A J; Gugino, B K; Johnson, D A; Johnson, S B; McGrath, M T; Myers, K L; Ristaino, J B; Roberts, P D; Secor, G; Smart, C D

    2015-07-01

    Phytophthora infestans has been a named pathogen for well over 150 years and yet it continues to "emerge", with thousands of articles published each year on it and the late blight disease that it causes. This review explores five attributes of this oomycete pathogen that maintain this constant attention. First, the historical tragedy associated with this disease (Irish potato famine) causes many people to be fascinated with the pathogen. Current technology now enables investigators to answer some questions of historical significance. Second, the devastation caused by the pathogen continues to appear in surprising new locations or with surprising new intensity. Third, populations of P. infestans worldwide are in flux, with changes that have major implications to disease management. Fourth, the genomics revolution has enabled investigators to make tremendous progress in terms of understanding the molecular biology (especially the pathogenicity) of P. infestans. Fifth, there remain many compelling unanswered questions. PMID:25760519

  13. 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.

  14. Chitosan against cutaneous pathogens

    PubMed Central

    2013-01-01

    Propionibacterium acnes and Staphylococcus aureus are cutaneous pathogens that have become increasingly resistant to antibiotics. We sought to determine if chitosan, a polymer of deacetylated chitin, could be used as a potential treatment against these bacteria. We found that higher molecular weight chitosan had superior antimicrobial properties compared to lower molecular weights, and that this activity occurred in a pH dependent manner. Electron and fluorescence microscopy revealed that chitosan forms aggregates and binds to the surface of bacteria, causing shrinkage of the bacterial membrane from the cell wall. Of special relevance, clinical isolates of P. acnes were vulnerable to chitosan, which could be combined with benzoyl peroxide for additive antibacterial effect. Chitosan also demonstrated significantly less cytotoxicity to monocytes than benzoyl peroxide. Overall, chitosan demonstrates many promising qualities for treatment of cutaneous pathogens. PMID:23829873

  15. Newspaper articles and physics teaching

    NASA Astrophysics Data System (ADS)

    Mazurova, Jaroslava; Slabeycius, Juraj

    1995-09-01

    We describe here a physics teaching method which can motivate students and stimulate their creative thinking. Many sources of information from everyday life (for instance newspaper articles) contain facts which can be evaluated from a physical point of view, and the analysis of this information can be used to teach physics. It is a spontaneous and interesting way to show students that physics is not only a theoretical abstraction (a set of formal relations), but that it is primarily a useful tool, making critical evaluation possible of often passively accepted news from everyday life.

  16. 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.

  17. 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.

  18. PATHOGENIC ESCHERICHIA COLI IN FOODS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pathogenic Escherichia coli are defined as those E. coli strains that are capable of causing diarrhoeal disease in humans. Subdivision of the pathogenic forms is made on the basis of the mechanism underlying the illness. Presently, four types of pathogenic E. coli have been implicated in foodborne...

  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-Durn, 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. PMID:25584723

  1. Exploring NAD(+) metabolism in host-pathogen interactions.

    PubMed

    Mesquita, Inês; Varela, Patrícia; Belinha, Ana; Gaifem, Joana; Laforge, Mireille; Vergnes, Baptiste; Estaquier, Jérôme; Silvestre, Ricardo

    2016-03-01

    Nicotinamide adenine dinucleotide (NAD(+)) is a vital molecule found in all living cells. NAD(+) intracellular levels are dictated by its synthesis, using the de novo and/or salvage pathway, and through its catabolic use as co-enzyme or co-substrate. The regulation of NAD(+) metabolism has proven to be an adequate drug target for several diseases, including cancer, neurodegenerative or inflammatory diseases. Increasing interest has been given to NAD(+) metabolism during innate and adaptive immune responses suggesting that its modulation could also be relevant during host-pathogen interactions. While the maintenance of NAD(+) homeostatic levels assures an adequate environment for host cell survival and proliferation, fluctuations in NAD(+) or biosynthetic precursors bioavailability have been described during host-pathogen interactions, which will interfere with pathogen persistence or clearance. Here, we review the double-edged sword of NAD(+) metabolism during host-pathogen interactions emphasizing its potential for treatment of infectious diseases. PMID:26718485

  2. Microbiota-mediated colonization resistance against intestinal pathogens

    PubMed Central

    Buffie, Charlie G.; Pamer, Eric G.

    2014-01-01

    Commensal bacteria inhabit mucosal and epidermal surfaces in mice and humans, and have effects on metabolic and immune pathways in their hosts. Recent studies indicate that the commensal microbiota can be manipulated to prevent and even to cure infections that are caused by pathogenic bacteria, particularly pathogens that are broadly resistant to antibiotics, such as vancomycin-resistant Enterococcus faecium, Gram-negative Enterobacteriaceae and Clostridium difficile. In this Review, we discuss how immune- mediated colonization resistance against antibiotic-resistant intestinal pathogens is influenced by the composition of the commensal microbiota. We also review recent advances characterizing the ability of different commensal bacterial families, genera and species to restore colonization resistance to intestinal pathogens in antibiotic-treated hosts. PMID:24096337

  3. Do plant and human pathogens have a common pathogenicity strategy?

    PubMed

    Kempf, Volkhard A J; Hitziger, Niclas; Riess, Tanja; Autenrieth, Ingo B

    2002-06-01

    Recently, a novel 'two-step' model of pathogenicity has been described that suggests host-cell-derived vasculoproliferative factors play a crucial role in the pathogenesis of bacillary angiomatosis, a disease caused by the human pathogenic bacterium Bartonella henselae. The resulting proliferation of endothelial cells could be interpreted as bacterial pathogens triggering the promotion of their own habitat: the host cell. Similar disease mechanisms are well known in the plant pathogen Agrobacterium tumefaciens, which causes crown gall disease. There are notable similarities between the pathogenicity of A. tumefaciens leading to tumourous disease in plants and to the B. henselae-triggered proliferation of endothelial cells in humans. Here, we hypothesize that this pathogenicity strategy might be common to several bacterial species in different hosts owing to shared pathogenicity factors. PMID:12088662

  4. Microbial Pathogens in the Fungal Kingdom.

    PubMed

    Heitman, Joseph

    2011-03-01

    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 derived fungal lineages that are retained in basal fungi, and shared and divergent virulence strategies of successful human pathogens, including dimorphic and trimorphic transitions in form. The overarching conclusion is that fungal pathogens of animals have arisen repeatedly and independently throughout the fungal tree of life, and while they share general properties, there are also unique features to the virulence strategies of each successful microbial pathogen. PMID:21528015

  5. 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 derived fungal lineages that are retained in basal fungi, and shared and divergent virulence strategies of successful human pathogens, including dimorphic and trimorphic transitions in form. The overarching conclusion is that fungal pathogens of animals have arisen repeatedly and independently throughout the fungal tree of life, and while they share general properties, there are also unique features to the virulence strategies of each successful microbial pathogen. PMID:21528015

  6. 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, Drte; 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

  7. 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

  8. Preferential Amplification of Pathogenic Sequences

    PubMed Central

    Ge, Fang; Parker, Jayme; Chul Choi, Sang; Layer, Mark; Ross, Katherine; Jilly, Bernard; Chen, Jack

    2015-01-01

    The application of next generation sequencing (NGS) technology in the diagnosis of human pathogens is hindered by the fact that pathogenic sequences, especially viral, are often scarce in human clinical specimens. This known disproportion leads to the requirement of subsequent deep sequencing and extensive bioinformatics analysis. Here we report a method we called Preferential Amplification of Pathogenic Sequences (PATHseq) that can be used to greatly enrich pathogenic sequences. Using a computer program, we developed 8-, 9-, and 10-mer oligonucleotides called non-human primers that do not match the most abundant human transcripts, but instead selectively match transcripts of human pathogens. Instead of using random primers in the construction of cDNA libraries, the PATHseq method recruits these short non-human primers, which in turn, preferentially amplifies non-human, presumably pathogenic sequences. Using this method, we were able to enrich pathogenic sequences up to 200-fold in the final sequencing library. This method does not require prior knowledge of the pathogen or assumption of the infection; therefore, it provides a fast and sequence-independent approach for detection and identification of human viruses and other pathogens. The PATHseq method, coupled with NGS technology, can be broadly used in identification of known human pathogens and discovery of new pathogens. PMID:26067233

  9. PIPS: Pathogenicity Island Prediction Software

    PubMed Central

    Soares, Siomar C.; Abreu, Vincius A. C.; Ramos, Rommel T. J.; Cerdeira, Louise; Silva, Artur; Baumbach, Jan; Trost, Eva; Tauch, Andreas; Hirata, Raphael; Mattos-Guaraldi, Ana L.; Miyoshi, Anderson; Azevedo, Vasco

    2012-01-01

    The adaptability of pathogenic bacteria to hosts is influenced by the genomic plasticity of the bacteria, which can be increased by such mechanisms as horizontal gene transfer. Pathogenicity islands play a major role in this type of gene transfer because they are large, horizontally acquired regions that harbor clusters of virulence genes that mediate the adhesion, colonization, invasion, immune system evasion, and toxigenic properties of the acceptor organism. Currently, pathogenicity islands are mainly identified in silico based on various characteristic features: (1) deviations in codon usage, G+C content or dinucleotide frequency and (2) insertion sequences and/or tRNA genetic flanking regions together with transposase coding genes. Several computational techniques for identifying pathogenicity islands exist. However, most of these techniques are only directed at the detection of horizontally transferred genes and/or the absence of certain genomic regions of the pathogenic bacterium in closely related non-pathogenic species. Here, we present a novel software suite designed for the prediction of pathogenicity islands (pathogenicity island prediction software, or PIPS). In contrast to other existing tools, our approach is capable of utilizing multiple features for pathogenicity island detection in an integrative manner. We show that PIPS provides better accuracy than other available software packages. As an example, we used PIPS to study the veterinary pathogen Corynebacterium pseudotuberculosis, in which we identified seven putative pathogenicity islands. PMID:22355329

  10. Bacterial pathogen evolution: breaking news.

    PubMed

    Jackson, Robert W; Johnson, Louise J; Clarke, Simon R; Arnold, Dawn L

    2011-01-01

    The immense social and economic impact of bacterial pathogens, from drug-resistant infections in hospitals to the devastation of agricultural resources, has resulted in major investment to understand the causes and consequences of pathogen evolution. Recent genome sequencing projects have provided insight into the evolution of bacterial genome structures; revealing the impact of mobile DNA on genome restructuring and pathogenicity. Sequencing of multiple genomes of related strains has enabled the delineation of pathogen evolution and facilitated the tracking of bacterial pathogens globally. Other recent theoretical and empirical studies have shown that pathogen evolution is significantly influenced by ecological factors, such as the distribution of hosts within the environment and the effects of co-infection. We suggest that the time is ripe for experimentalists to use genomics in conjunction with evolutionary ecology experiments to further understanding of how bacterial pathogens evolve. PMID:21047697

  11. Immunogenicity of infectious pathogens and vaccine antigens.

    PubMed

    Mahanty, Siddhartha; Prigent, Antoine; Garraud, Olivier

    2015-01-01

    The concept of the immunogenicity of an antigen is frequently encountered in the context of vaccine development, an area of intense interest currently due to the emergence or re-emergence of infectious pathogens with the potential for worldwide spread. However, the theoretical notion of immunogenicity as discussed in older textbooks of immunology needs reconsideration due to advances in our understanding of immunologic responses. Immunogenicity is a property that can either be a desirable attribute, for example in the generation of an effective protective immunity against infectious pathogens or an undesirable trait, for example when it relates to novel therapeutic compounds and drugs, where an immune response needs to be prevented or inhibited. In this Forum Article, we aimed to revisit the issue of immunogenicity to discuss a series of simple questions relevant to the concept that are frequently rephrased but incompletely resolved in the immunologic literature. PMID:26021448

  12. Killing them softly: managing pathogen polymorphism and virulence in spatially variable environments

    PubMed Central

    Vale, Pedro F.

    2013-01-01

    Understanding why pathogen populations are genetically variable is vital because genetic variation fuels evolution, which often hampers disease control efforts. Here I argue that classical models of evolution in spatially variable environments specifically, models of hard and soft selection provide a useful framework to understand the maintenance of pathogen polymorphism and the evolution of virulence. First, the similarities between models of hard and soft selection and pathogen life cycles are described, highlighting how the type and timing of pathogen control measures impose density regulation that may affect both the level of pathogen polymorphism and virulence. The article concludes with an outline of potential lines of future theoretical and experimental work. PMID:23928098

  13. Green Light to Plant Responses to Pathogens: The Role of Chloroplast Light-Dependent Signaling in Biotic Stress.

    PubMed

    Delprato, Mara Laura; Krapp, Adriana R; Carrillo, Nstor

    2015-01-01

    Light has a key impact on the outcome of biotic stress responses in plants by providing most of the energy and many signals for the deployment of defensive barriers. Within this context, chloroplasts are not only the major source of energy in the light; they also host biosynthetic pathways for the production of stress hormones and secondary metabolites, as well as reactive oxygen species and other signals which modulate nuclear gene expression and plant resistance to pathogens. Environmental, and in particular, light-dependent regulation of immune responses may allow plants to anticipate and react more effectively to pathogen threats. As more information is gathered, increasingly complex models are developed to explain how light and reactive oxygen species signaling could interact with endogenous defense pathways to elicit efficient protective responses against invading microorganisms. The emerging picture places chloroplasts in a key position of an intricate regulatory network which involves several other cellular compartments. This article reviews current knowledge on the extent and the main features of chloroplast contribution to plant defensive strategies against biotic stress. PMID:25989185

  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. Portable pathogen detection system

    DOEpatents

    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.

  16. Subolesin expression in response to pathogen infection in ticks

    PubMed Central

    2010-01-01

    Background Ticks (Acari: Ixodidae) are vectors of pathogens worldwide that cause diseases in humans and animals. Ticks and pathogens have co-evolved molecular mechanisms that contribute to their mutual development and survival. Subolesin was discovered as a tick protective antigen and was subsequently shown to be similar in structure and function to akirins, an evolutionarily conserved group of proteins in insects and vertebrates that controls NF-kB-dependent and independent expression of innate immune response genes. The objective of this study was to investigate subolesin expression in several tick species infected with a variety of pathogens and to determine the effect of subolesin gene knockdown on pathogen infection. In the first experiment, subolesin expression was characterized in ticks experimentally infected with the cattle pathogen, Anaplasma marginale. Subolesin expression was then characterized in questing or feeding adult ticks confirmed to be infected with Anaplasma, Ehrlichia, Rickettsia, Babesia or Theileria spp. Finally, the effect of subolesin knockdown by RNA interference (RNAi) on tick infection was analyzed in Dermacentor variabilis males exposed to various pathogens by capillary feeding (CF). Results Subolesin expression increased with pathogen infection in the salivary glands but not in the guts of tick vector species infected with A. marginale. When analyzed in whole ticks, subolesin expression varied between tick species and in response to different pathogens. As reported previously, subolesin knockdown in D. variabilis infected with A. marginale and other tick-borne pathogens resulted in lower infection levels, while infection with Francisella tularensis increased in ticks after RNAi. When non-tick-borne pathogens were fed to ticks by CF, subolesin RNAi did not affect or resulted in lower infection levels in ticks. However, subolesin expression was upregulated in D. variabilis exposed to Escherichia coli, suggesting that although this pathogen may induce subolesin expression in ticks, silencing of this molecule reduced bacterial multiplication by a presently unknown mechanism. Conclusions Subolesin expression in infected ticks suggested that subolesin may be functionally important for tick innate immunity to pathogens, as has been reported for the akirins. However, subolesin expression and consequently subolesin-mediated innate immunity varied with the pathogen and tick tissue. Subolesin may plays a role in tick innate immunity in the salivary glands by limiting pathogen infection levels, but activates innate immunity only for some pathogen in the guts and other tissues. In addition, these results provided additional support for the role of subolesin in other molecular pathways including those required for tissue development and function and for pathogen infection and multiplication in ticks. Consequently, RNAi experiments demonstrated that subolesin knockdown in ticks may affect pathogen infection directly by reducing tick innate immunity that results in higher infection levels and indirectly by affecting tissue structure and function and the expression of genes that interfere with pathogen infection and multiplication. The impact of the direct or indirect effects of subolesin knockdown on pathogen infection may depend on several factors including specific tick-pathogen molecular interactions, pathogen life cycle in the tick and unknown mechanisms affected by subolesin function in the control of global gene expression in ticks. PMID:20170494

  17. Stress Response and Pathogenicity of the Necrotrophic Fungal Pathogen Alternaria alternata

    PubMed Central

    Chung, Kuang-Ren

    2012-01-01

    The production of host-selective toxins by the necrotrophic fungus Alternaria alternata is essential for the pathogenesis. A. alternata infection in citrus leaves induces rapid lipid peroxidation, accumulation of hydrogen peroxide (H2O2), and cell death. The mechanisms by which A. alternata avoids killing by reactive oxygen species (ROS) after invasion have begun to be elucidated. The ability to coordinate of signaling pathways is essential for the detoxification of cellular stresses induced by ROS and for pathogenicity in A. alternata. A low level of H2O2, produced by the NADPH oxidase (NOX) complex, modulates ROS resistance and triggers conidiation partially via regulating the redox-responsive regulators (YAP1 and SKN7) and the mitogen-activated protein (MAP) kinase (HOG1) mediated pathways, which subsequently regulate the genes required for the biosynthesis of siderophore, an iron-chelating compound. Siderophore-mediated iron acquisition plays a key role in ROS detoxification because of the requirement of iron for the activities of antioxidants (e.g., catalase and SOD). Fungal strains impaired for the ROS-detoxifying system severely reduce the virulence on susceptible citrus cultivars. This paper summarizes the current state of knowledge of signaling pathways associated with cellular responses to multidrugs, oxidative and osmotic stress, and fungicides, as well as the pathogenicity/virulence in the tangerine pathotype of A. alternata. PMID:24278721

  18. Axonal transport and neuronal transcytosis of trophic factors, tracers, and pathogens.

    PubMed

    von Bartheld, Christopher S

    2004-02-01

    Neurons can specifically internalize macromolecules, such as trophic factors, lectins, toxins, and other pathogens. Upon internalization in terminals, proteins can move retrogradely along axons, or, upon internalization at somatodendritic domains, they can move into an anterograde axonal transport pathway. Release of internalized proteins from neurons after either retrograde or anterograde axonal transport results in transcytosis and trafficking of proteins across multiple synapses. Recent studies of binding properties of several such proteins suggest that pathogens and lectins may utilize existing transport machineries designed for trafficking of trophic factors. Specific pathways may protect trophic factors, pathogens, and toxins from degradation after internalization and may target the trophic or pathogenic cargo for transcytosis after either retrograde or anterograde transport along axons. Elucidating the molecular mechanisms of sorting steps and transport pathways will further our understanding of trophic signaling and could be relevant for an understanding and possible treatment of neurological diseases such as rabies, Alzheimer's disease, and prion encephalopathies. At present, our knowledge is remarkably sparse about the types of receptors used by pathogens for trafficking, the signals that sort trophins or pathogens into recycling or degradation pathways, and the mechanisms that regulate their release from somatodendritic domains or axon terminals. This review intends to draw attention to potential convergences and parallels in trafficking of trophic and pathogenic proteins. It discusses axonal transport/trafficking mechanisms that may help to understand and eventually treat neurological diseases by targeted drug delivery. PMID:14704960

  19. 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

  20. 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.

  1. New pathogens and old resistance genes.

    PubMed

    Davies, J

    1994-01-01

    In the past fifty years the treatment and ecology of infectious diseases has evolved greatly. The major changes have come as the development of "new" pathogens which are usually "old" pathogens in new guises. The chief environmental factor responsible for this change is the use of antimicrobial agents. It is estimated that more than 10(9) kg of antibiotic have been produced and used since the early 1959's. In spite of this threat, bacterial pathogens have not only survived, but even flourished. It is now too late to reverse this trend, since the treatment of infectious diseases relies heavily on antibiotics and there is a well-established pool of antibiotic resistance genes in nature. Hospital are unique, varied ecological niches for microbial diversity, and we know little about where resistance genes come from or the pathways by which these genes are passed around the bacterial population. Since less than 10% of the bacterial species on earth can be identified, we are ignorant of a large component of the factors responsible for health, disease and antibiotic resistance. What can we look forward to? There has been much talk of reemerging pathogens such as Mycobacterium tuberculosis, Listeria monocytogenes, enterococci and various fungi. These organisms have surfaced because of their ability to survive in hostile environments (antibiotics, antiseptics). We should anticipate the reappearance of other such organisms, and clinicians and the pharmaceutical industry should be prepared for this. Now it is the time to get profit from the lessons of the past, which, together with better knowledge of microbial biochemistry and ecology, must be applied to the problems of infectious diseases. PMID:7946130

  2. 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

  3. 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. PMID:25449751

  4. The role of ubiquitylation in immune defence and pathogen evasion

    PubMed Central

    Jiang, Xiaomo; Chen, Zhijian J.

    2013-01-01

    Ubiquitylation is a widely used post-translational protein modification that regulates many biological processes, including immune responses. The role of ubiquitin in immune regulation was originally uncovered through studies of antigen presentation and the nuclear factor-κB family of transcription factors, which orchestrate host defence against microorganisms. Recent studies have revealed crucial roles of ubiquitylation in many aspects of the immune system, including innate and adaptive immunity and antimicrobial autophagy. In addition, mounting evidence indicates that microbial pathogens exploit the ubiquitin pathway to evade the host immune system. Here, we review recent advances on the role of ubiquitylation in host defence and pathogen evasion. PMID:22158412

  5. A new cyanogenic metabolite in Arabidopsis required for inducible pathogen defence.

    PubMed

    Rajniak, Jakub; Barco, Brenden; Clay, Nicole K; Sattely, Elizabeth S

    2015-09-17

    Thousands of putative biosynthetic genes in Arabidopsis thaliana have no known function, which suggests that there are numerous molecules contributing to plant fitness that have not yet been discovered. Prime among these uncharacterized genes are cytochromes P450 upregulated in response to pathogens. Here we start with a single pathogen-induced P450 (ref. 5), CYP82C2, and use a combination of untargeted metabolomics and coexpression analysis to uncover the complete biosynthetic pathway to 4-hydroxyindole-3-carbonyl nitrile (4-OH-ICN), a previously unknown Arabidopsis metabolite. This metabolite harbours cyanogenic functionality that is unprecedented in plants and exceedingly rare in nature; furthermore, the aryl cyanohydrin intermediate in the 4-OH-ICN pathway reveals a latent capacity for cyanogenic glucoside biosynthesis in Arabidopsis. By expressing 4-OH-ICN biosynthetic enzymes in Saccharomyces cerevisiae and Nicotiana benthamiana, we reconstitute the complete pathway in vitro and in vivo and validate the functions of its enzymes. Arabidopsis 4-OH-ICN pathway mutants show increased susceptibility to the bacterial pathogen Pseudomonas syringae, consistent with a role in inducible pathogen defence. Arabidopsis has been the pre-eminent model system for studying the role of small molecules in plant innate immunity; our results uncover a new branch of indole metabolism distinct from the canonical camalexin pathway, and support a role for this pathway in the Arabidopsis defence response. These results establish a more complete framework for understanding how the model plant Arabidopsis uses small molecules in pathogen defence. PMID:26352477

  6. 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. PMID:25576662

  7. Bloodborne pathogens exposure from occupational fingernail scratches.

    PubMed Central

    Lohiya, Ghan-Shyam; Tan-Figueroa, Lilia; Lohiya, Sonia

    2007-01-01

    Following occupational fingernail scratches (OFSs) in a developmental center, the source resident and the injured employee were tested for bloodborne pathogens (BPs). The pros and cons of this practice were scrutinized since fingernails usually contain no blood. Available records revealed no OFS-related BP transmission in 14 years. PubMed displayed no article linking OFS with BP. The facility's practice was discontinued as it was deemed unnecessary, wasteful, an impediment to the event's expeditious closure, an ineffective workers' compensation safeguard, and a potential source of venipuncture-related complications and false-positive laboratory results. Even long-standing practices require periodic scientific review. PMID:18020103

  8. The Oxylipin Pathway in Arabidopsis

    PubMed Central

    Creelman, Robert A.; Mulpuri, Rao

    2002-01-01

    Oxylipins are acyclic or cyclic oxidation products derived from the catabolism of fatty acids which regulate many defense and developmental pathways in plants. The dramatic increase in the volume of publications and reviews on these compounds since 1997 documents the increasing interest in this compound and its role in plants. Research on this topic has solidified our understanding of the chemistry and biosynthetic pathways for oxylipin production. However, more information is still needed on how free fatty acids are produced and the role of beta-oxidation in the biosynthetic pathway for oxylipins. It is also becoming apparent that oxylipin content and composition changes during growth and development and during pathogen or insect attack. Oxylipins such as jasmonic acid (JA) or 12-oxo-phytodienoic acid modulate the expression of numerous genes and influence specific aspects of plant growth, development and responses to abiotic and biotic stresses. Although oxylipins are believed to act alone, several examples were presented to illustrate that JA-induced responses are modulated by the type and the nature of crosstalk with other signaling molecules such as ethylene and salicylic acid. How oxylipins cause changes in gene expression and instigate a physiological response is becoming understood with the isolation of mutations in both positive and negative regulators in the jasmonate signaling pathway and the use of cDNA microarrays. PMID:22303193

  9. The oxylipin pathway in Arabidopsis.

    PubMed

    Creelman, Robert A; Mulpuri, Rao

    2002-01-01

    Oxylipins are acyclic or cyclic oxidation products derived from the catabolism of fatty acids which regulate many defense and developmental pathways in plants. The dramatic increase in the volume of publications and reviews on these compounds since 1997 documents the increasing interest in this compound and its role in plants. Research on this topic has solidified our understanding of the chemistry and biosynthetic pathways for oxylipin production. However, more information is still needed on how free fatty acids are produced and the role of beta-oxidation in the biosynthetic pathway for oxylipins. It is also becoming apparent that oxylipin content and composition changes during growth and development and during pathogen or insect attack. Oxylipins such as jasmonic acid (JA) or 12-oxo-phytodienoic acid modulate the expression of numerous genes and influence specific aspects of plant growth, development and responses to abiotic and biotic stresses. Although oxylipins are believed to act alone, several examples were presented to illustrate that JA-induced responses are modulated by the type and the nature of crosstalk with other signaling molecules such as ethylene and salicylic acid. How oxylipins cause changes in gene expression and instigate a physiological response is becoming understood with the isolation of mutations in both positive and negative regulators in the jasmonate signaling pathway and the use of cDNA microarrays. PMID:22303193

  10. Bacterial pathogens: from natural ecosystems to human hosts.

    PubMed

    Martínez, José L

    2013-02-01

    The analysis of the genomes of bacterial pathogens indicates that they have acquired their pathogenic capability by incorporating different genetic elements through horizontal gene transfer. The ancestors of virulent bacteria, as well as the origin of virulence determinants, lay most likely in the environmental microbiota. Studying the role that these determinants may have in non-clinical ecosystems is thus of value for understanding in detail the evolution and the ecology of bacterial pathogens. In this article, I propose that classical virulence determinants might be relevant for basic metabolic processes (for instance iron-uptake systems) or in modulating prey/predator relationships (toxins) in natural, non-infective ecosystems. The different role that horizontal gene transfer and mutation may have in the evolution of bacterial pathogens either for their speciation or in short-sighted evolution processes is also discussed. PMID:22857004

  11. Reactive oxygen species and plant resistance to fungal pathogens.

    PubMed

    Lehmann, Silke; Serrano, Mario; L'Haridon, Floriane; Tjamos, Sotirios E; Metraux, Jean-Pierre

    2015-04-01

    Reactive oxygen species (ROS) have been studied for their role in plant development as well as in plant immunity. ROS were consistently observed to accumulate in the plant after the perception of pathogens and microbes and over the years, ROS were postulated to be an integral part of the defence response of the plant. In this article we will focus on recent findings about ROS involved in the interaction of plants with pathogenic fungi. We will describe the ways to detect ROS, their modes of action and their importance in relation to resistance to fungal pathogens. In addition we include some results from works focussing on the fungal interactor and from studies investigating roots during pathogen attack. PMID:25264341

  12. Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens.

    PubMed

    LaRock, Christopher N; Nizet, Victor

    2015-11-01

    Cationic antimicrobial peptides (CAMPs) are critical front line contributors to host defense against invasive bacterial infection. These immune factors have direct killing activity toward microbes, but many pathogens are able to resist their effects. Group A Streptococcus, group B Streptococcus and Streptococcus pneumoniae are among the most common pathogens of humans and display a variety of phenotypic adaptations to resist CAMPs. Common themes of CAMP resistance mechanisms among the pathogenic streptococci are repulsion, sequestration, export, and destruction. Each pathogen has a different array of CAMP-resistant mechanisms, with invasive disease potential reflecting the utilization of several mechanisms that may act in synergy. Here we discuss recent progress in identifying the sources of CAMP resistance in the medically important Streptococcus genus. Further study of these mechanisms can contribute to our understanding of streptococcal pathogenesis, and may provide new therapeutic targets for therapy and disease prevention. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides. PMID:25701232

  13. Advances in rapid detection methods for foodborne pathogens.

    PubMed

    Zhao, Xihong; Lin, Chii-Wann; Wang, Jun; Oh, Deog Hwan

    2014-03-28

    Food safety is increasingly becoming an important public health issue, as foodborne diseases present a widespread and growing public health problem in both developed and developing countries. The rapid and precise monitoring and detection of foodborne pathogens are some of the most effective ways to control and prevent human foodborne infections. Traditional microbiological detection and identification methods for foodborne pathogens are well known to be time consuming and laborious as they are increasingly being perceived as insufficient to meet the demands of rapid food testing. Recently, various kinds of rapid detection, identification, and monitoring methods have been developed for foodborne pathogens, including nucleic-acid-based methods, immunological methods, and biosensor-based methods, etc. This article reviews the principles, characteristics, and applications of recent rapid detection methods for foodborne pathogens. PMID:24375418

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

    PubMed Central

    Merino, Octavio; Alberdi, Pilar; Prez de la Lastra, Jos M.; de la Fuente, Jos

    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

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

    PubMed

    Merino, Octavio; Alberdi, Pilar; Prez de la Lastra, Jos M; de la Fuente, Jos

    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

  16. 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

  17. 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.

  18. [Streptococcus pyogenes pathogenic factors].

    PubMed

    Bidet, Ph; Bonacorsi, S

    2014-11-01

    The pathogenicity of -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

  19. Lipoproteins of bacterial pathogens.

    PubMed

    Kovacs-Simon, A; Titball, R W; Michell, S L

    2011-02-01

    Bacterial lipoproteins are a set of membrane proteins with many different functions. Due to this broad-ranging functionality, these proteins have a considerable significance in many phenomena, from cellular physiology through cell division and virulence. Here we give a general overview of lipoprotein biogenesis and highlight examples of the roles of lipoproteins in bacterial disease caused by a selection of medically relevant Gram-negative and Gram-positive pathogens: Mycobacterium tuberculosis, Streptococcus pneumoniae, Borrelia burgdorferi, and Neisseria meningitidis. Lipoproteins have been shown to play key roles in adhesion to host cells, modulation of inflammatory processes, and translocation of virulence factors into host cells. As such, a number of lipoproteins have been shown to be potential vaccines. This review provides a summary of some of the reported roles of lipoproteins and of how this knowledge has been exploited in some cases for the generation of novel countermeasures to bacterial diseases. PMID:20974828

  20. Lipoproteins of Bacterial Pathogens?

    PubMed Central

    Kovacs-Simon, A.; Titball, R. W.; Michell, S. L.

    2011-01-01

    Bacterial lipoproteins are a set of membrane proteins with many different functions. Due to this broad-ranging functionality, these proteins have a considerable significance in many phenomena, from cellular physiology through cell division and virulence. Here we give a general overview of lipoprotein biogenesis and highlight examples of the roles of lipoproteins in bacterial disease caused by a selection of medically relevant Gram-negative and Gram-positive pathogens: Mycobacterium tuberculosis, Streptococcus pneumoniae, Borrelia burgdorferi, and Neisseria meningitidis. Lipoproteins have been shown to play key roles in adhesion to host cells, modulation of inflammatory processes, and translocation of virulence factors into host cells. As such, a number of lipoproteins have been shown to be potential vaccines. This review provides a summary of some of the reported roles of lipoproteins and of how this knowledge has been exploited in some cases for the generation of novel countermeasures to bacterial diseases. PMID:20974828

  1. 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-? 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). PMID:22403475

  2. 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 and the Perlin lab in sample preparation and testing in animal models.

  3. Protein disulfide isomerase and host-pathogen interaction.

    PubMed

    Stolf, Beatriz S; Smyrnias, Ioannis; Lopes, Lucia R; Vendramin, Alcione; Goto, Hiro; Laurindo, Francisco R M; Shah, Ajay M; Santos, Celio X C

    2011-01-01

    Reactive oxygen species (ROS) production by immunological cells is known to cause damage to pathogens. Increasing evidence accumulated in the last decade has shown, however, that ROS (and redox signals) functionally regulate different cellular pathways in the host-pathogen interaction. These especially affect (i) pathogen entry through protein redox switches and redox modification (i.e., intra- and interdisulfide and cysteine oxidation) and (ii) phagocytic ROS production via Nox family NADPH oxidase enzyme and the control of phagolysosome function with key implications for antigen processing. The protein disulfide isomerase (PDI) family of redox chaperones is closely involved in both processes and is also implicated in protein unfolding and trafficking across the endoplasmic reticulum (ER) and towards the cytosol, a thiol-based redox locus for antigen processing. Here, we summarise examples of the cellular association of host PDI with different pathogens and explore the possible roles of pathogen PDIs in infection. A better understanding of these complex regulatory steps will provide insightful information on the redox role and coevolutional biological process, and assist the development of more specific therapeutic strategies in pathogen-mediated infections. PMID:22125433

  4. [Critical pathway for community-acquired pneumonia].

    PubMed

    Garin, N; Harbarth, S; Nendaz, M; Rochat, T; Rutschmann, O

    2011-04-27

    A clinical pathway is a methodological tool for standardizing medical practice, improving the quality and efficiency of care delivery, and enhancing the diffusion of evidence-based medicine. Despite the fact that a majority of trials have shown that the use of clinical pathways improves certain specific outcomes such as length of stay or complications, the overall impact of these pathways in the clinical setting has yet to be documented. In the setting of community-acquired pneumonia, a few observational and one large randomized trial have shown positive effects on various outcomes. We describe in this article the clinical pathway for community-acquired pneumonia developed at our institution. PMID:21674896

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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…

  10. 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...

  11. 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

  12. 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 PECs membership on emerging pathogens, analytical methods, disinfection techniques, risk analysis, preparat...

  13. Pathogens of Whiteflies (Hemiptera: Aleyrodidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Whiteflies belong to the order Homoptera, and the family Aleyrodidae. They are tropical and subtropical in origin, and can be serious pests in field crops of the southern areas of the world and in glasshouses. Whiteflies have many pathogens, but nearly all known pathogens are fungi, which can infect...

  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. 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

  16. Characterization of plant fungal interactions involving necrotrophic effector-producing plant pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, great strides have been made in the area of host-pathogen interactions involving necrotrophic fungi. In this article we describe a method to identify, produce, and characterize effectors that are important in host necrotrophic fungal pathogen interactions, and to genetically characterize...

  17. Molecular pathogenicity of Streptococcus anginosus.

    PubMed

    Asam, D; Spellerberg, B

    2014-08-01

    Streptococcus anginosus and the closely related species Streptococcus constellatus and Streptococcus intermedius, are primarily commensals of the mucosa. The true pathogenic potential of this group has been under-recognized for a long time because of difficulties in correct species identification as well as the commensal nature of these species. In recent years, streptococci of the S. anginosus group have been increasingly found as relevant microbial pathogens in abscesses and blood cultures and they play a pathogenic role in cystic fibrosis. Several international studies have shown a surprisingly high frequency of infections caused by the S. anginosus group. Recent studies and a genome-wide comparative analysis suggested the presence of multiple putative virulence factors that are well-known from other streptococcal species. However, very little is known about the molecular basis of pathogenicity in these bacteria. This review summarizes our current knowledge of pathogenicity factors and their regulation in S. anginosus. PMID:24848553

  18. Population biology of multihost pathogens.

    PubMed

    Woolhouse, M E; Taylor, L H; Haydon, D T

    2001-05-11

    The majority of pathogens, including many of medical and veterinary importance, can infect more than one species of host. Population biology has yet to explain why perceived evolutionary advantages of pathogen specialization are, in practice, outweighed by those of generalization. Factors that predispose pathogens to generalism include high levels of genetic diversity and abundant opportunities for cross-species transmission, and the taxonomic distributions of generalists and specialists appear to reflect these factors. Generalism also has consequences for the evolution of virulence and for pathogen epidemiology, making both much less predictable. The evolutionary advantages and disadvantages of generalism are so finely balanced that even closely related pathogens can have very different host range sizes. PMID:11352066

  19. 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

  20. Red card for pathogens: phytoalexins in sorghum and maize.

    PubMed

    Poloni, Alana; Schirawski, Jan

    2014-01-01

    Cereal crop plants such as maize and sorghum are constantly being attacked by a great variety of pathogens that cause large economic losses. Plants protect themselves against pathogens by synthesizing antimicrobial compounds, which include phytoalexins. In this review we summarize the current knowledge on phytoalexins produced by sorghum (luteolinidin, apigeninidin) and maize (zealexin, kauralexin, DIMBOA and HDMBOA). For these molecules, we highlight biosynthetic pathways, known intermediates, proposed enzymes, and mechanisms of elicitation. Finally, we discuss the involvement of phytoalexins in plant resistance and their possible application in technology, medicine and agriculture. For those whose world is round we tried to set the scene in the context of a hypothetical football game in which pathogens fight with phytoalexins on the different playing fields provided by maize and sorghum. PMID:24983861

  1. Metabolite profiles of Populus in response to pathogen stress.

    PubMed

    Wu, Qiuming; Chen, Min; Zhou, Hailong; Zhou, Xianqing; Wang, Yanwei

    2015-09-25

    Populus canker is a widespread disease that seriously affects the growth and productivity of trees, and may even cause tree death. To assess the metabolic changes in Populus in response to pathogen stress, Populus stems infected or not with Dothiorella gregaria were analyzed by GC-MS. A total of 4, 051 features were detected and 44 metabolites were identified to be changed significantly in Populus upon infection. The identified responsive metabolites include saccharides, alcohols, organic acids, and amino acids and some secondary metabolites and most of the metabolites were detected at increased levels. Responsive metabolites were investigated about their metabolism pathway and the corresponding metabolic networks were further constructed. To our knowledge, this is the first study to identify the metabolite profiles of Populus in response to pathogen stress. The results extend our understanding of the mechanisms involved in the defense of Populus against pathogens and provide a basis for further research on plant defenses. PMID:26291267

  2. Pathogen specific, IRF3-dependent signaling and innate resistance to human kidney infection.

    PubMed

    Fischer, Hans; Lutay, Nataliya; Ragnarsdttir, Brynds; Yadav, Manisha; Jnsson, Klas; Urbano, Alexander; Al Hadad, Ahmed; Rmisch, Sebastian; Storm, Petter; Dobrindt, Ulrich; Salvador, Ellaine; Karpman, Diana; Jodal, Ulf; Svanborg, Catharina

    2010-01-01

    The mucosal immune system identifies and fights invading pathogens, while allowing non-pathogenic organisms to persist. Mechanisms of pathogen/non-pathogen discrimination are poorly understood, as is the contribution of human genetic variation in disease susceptibility. We describe here a new, IRF3-dependent signaling pathway that is critical for distinguishing pathogens from normal flora at the mucosal barrier. Following uropathogenic E. coli infection, Irf3(-/-) mice showed a pathogen-specific increase in acute mortality, bacterial burden, abscess formation and renal damage compared to wild type mice. TLR4 signaling was initiated after ceramide release from glycosphingolipid receptors, through TRAM, CREB, Fos and Jun phosphorylation and p38 MAPK-dependent mechanisms, resulting in nuclear translocation of IRF3 and activation of IRF3/IFN?-dependent antibacterial effector mechanisms. This TLR4/IRF3 pathway of pathogen discrimination was activated by ceramide and by P-fimbriated E. coli, which use ceramide-anchored glycosphingolipid receptors. Relevance of this pathway for human disease was supported by polymorphic IRF3 promoter sequences, differing between children with severe, symptomatic kidney infection and children who were asymptomatic bacterial carriers. IRF3 promoter activity was reduced by the disease-associated genotype, consistent with the pathology in Irf3(-/-) mice. Host susceptibility to common infections like UTI may thus be strongly influenced by single gene modifications affecting the innate immune response. PMID:20886096

  3. 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 ?-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 ?-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 ?-arabinosidase activity. Galactose, when used as the carbon source, stimulates ?-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 ?-arabinosidase are secreted first, followed by ?-xylosidase and cellulase, then ?-glucosidase, and, finally, ?-galactosidase. PMID:16657562

  4. Intricate Roles of Mammalian Sirtuins in Defense against Viral Pathogens.

    PubMed

    Budayeva, Hanna G; Rowland, Elizabeth A; Cristea, Ileana M

    2015-01-01

    For a number of years, sirtuin enzymes have been appreciated as effective "sensors" of the cellular environment to rapidly transmit information to diverse cellular pathways. Much effort was placed into exploring their roles in human cancers and aging. However, a growing body of literature brings these enzymes to the spotlight in the field of virology. Here, we discuss sirtuin functions in the context of viral infection, which provide regulatory points for therapeutic intervention against pathogens. PMID:26491165

  5. 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 patterns. PMID:21187901

  6. Algodystrophy: recent insight into the pathogenic framework.

    PubMed

    Varenna, Massimo; Zucchi, Francesca

    2015-01-01

    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

  7. Bacterial pathogen manipulation of host membrane trafficking.

    PubMed

    Asrat, Seblewongel; de Jesús, Dennise A; Hempstead, Andrew D; Ramabhadran, Vinay; Isberg, Ralph R

    2014-01-01

    Pathogens use a vast number of strategies to alter host membrane dynamics. Targeting the host membrane machinery is important for the survival and pathogenesis of several extracellular, vacuolar, and cytosolic bacteria. Membrane manipulation promotes bacterial replication while suppressing host responses, allowing the bacterium to thrive in a hostile environment. This review provides a comprehensive summary of various strategies used by both extracellular and intracellular bacteria to hijack host membrane trafficking machinery. We start with mechanisms used by bacteria to alter the plasma membrane, delve into the hijacking of various vesicle trafficking pathways, and conclude by summarizing bacterial adaptation to host immune responses. Understanding bacterial manipulation of host membrane trafficking provides insights into bacterial pathogenesis and uncovers the molecular mechanisms behind various processes within a eukaryotic cell. PMID:25103867

  8. 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

  9. Interaction between pathogenic proteins in neurodegenerative disorders.

    PubMed

    Jellinger, Kurt A

    2012-06-01

    The misfolding and progressive aggregation of specific proteins in selective regions of the nervous system is a seminal occurrence in many neurodegenerative disorders, and the interaction between pathological/toxic proteins to cause neurodegeneration is a hot topic of current neuroscience research. Despite clinical, genetic and experimental differences, increasing evidence indicates considerable overlap between synucleinopathies, tauopathies and other protein-misfolding diseases. Inclusions, often characteristic hallmarks of these disorders, suggest interactions of pathological proteins enganging common downstream pathways. Novel findings that have shifted our understanding in the role of pathologic proteins in the pathogenesis of Alzheimer, Parkinson, Huntington and prion diseases, have confirmed correlations/overlaps between these and other neurodegenerative disorders. Emerging evidence, in addition to synergistic effects of tau protein, amyloid-β, α-synuclein and other pathologic proteins, suggests that prion-like induction and spreading, involving secreted proteins, are major pathogenic mechanisms in various neurodegenerative diseases, depending on genetic backgrounds and environmental factors. The elucidation of the basic molecular mechanisms underlying the interaction and spreading of pathogenic proteins, suggesting a dualism or triad of neurodegeneration in protein-misfolding disorders, is a major challenge for modern neuroscience, to provide a deeper insight into their pathogenesis as a basis of effective diagnosis and treatment. PMID:22176890

  10. Transient virulence of emerging pathogens

    PubMed Central

    Bolker, Benjamin M.; Nanda, Arjun; Shah, Dharmini

    2010-01-01

    Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence evolution based on a tradeoff between high transmission rates and long infectious periods imply that epidemic growth conditions will select for higher virulence, possibly leading to a transient peak in virulence near the beginning of an epidemic. This transient selection could lead to high virulence in emerging pathogens. Using a simple model of the epidemiological and evolutionary dynamics of emerging pathogens, along with rough estimates of parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we estimated the potential magnitude and timing of such transient virulence peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase selection could contribute significantly to the virulence of emerging pathogens. In order to further assess the potential significance of this mechanism, we bring together data from the literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia) and the level of genetic variation for virulence for one (myxomatosis). We discuss the need for better data on tradeoff curves and genetic variance in order to evaluate the plausibility of various scenarios of virulence evolution. PMID:19864267

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

    PubMed

    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

  12. 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

  13. 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.

  14. 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.

  15. Host Pathogen Relations: Exploring Animal Models for Fungal Pathogens

    PubMed Central

    Harwood, Catherine G.; Rao, Reeta P.

    2014-01-01

    Pathogenic fungi cause superficial infections but pose a significant public health risk when infections spread to deeper tissues, such as the lung. Within the last three decades, fungi have been identified as the leading cause of nosocomial infections making them the focus of research. This review outlines the model systems such as the mouse, zebrafish larvae, flies, and nematodes, as well as ex vivo and in vitro systems available to study common fungal pathogens. PMID:25438011

  16. 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

  17. 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…

  18. 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

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 48 CFR 25.104 - Nonavailable articles.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Nonavailable articles. 25... PROGRAMS FOREIGN ACQUISITION Buy American Act-Supplies 25.104 Nonavailable articles. (a) The following articles have been determined to be nonavailable in accordance with 25.103(b)(1)(i): Acetylene, black....

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 48 CFR 25.104 - Nonavailable articles.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Nonavailable articles. 25... PROGRAMS FOREIGN ACQUISITION Buy American Act-Supplies 25.104 Nonavailable articles. (a) The following articles have been determined to be nonavailable in accordance with 25.103(b)(1)(i): Acetylene, black....

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 48 CFR 25.104 - Nonavailable articles.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Nonavailable articles. 25... PROGRAMS FOREIGN ACQUISITION Buy American Act-Supplies 25.104 Nonavailable articles. (a) The following articles have been determined to be nonavailable in accordance with 25.103(b)(1)(i): Acetylene, black....

  3. 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...

  4. 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.

  5. 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...

  6. 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…

  7. 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.

  8. 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...

  9. dbDiarrhea: the database of pathogen proteins and vaccine antigens from diarrheal pathogens.

    PubMed

    Ramana, Jayashree; Tamanna

    2012-12-01

    Diarrhea occurs world-wide and is most commonly caused by gastrointestinal infections which kill around 2.2 million people globally each year, mostly children in developing countries. We describe here dbDiarrhea, which is currently the most comprehensive catalog of proteins implicated in the pathogenesis of diarrhea caused by major bacterial, viral and parasitic species. The current release of the database houses 820 proteins gleaned through an extensive and critical survey of research articles from PubMed. The major contributors to this compendium of proteins are Escherichia coli and Salmonella enterica. These proteins are classified into different categories such as Type III secretion system effectors, Type III secretion system components, and Pathogen proteins. There is another complementary module called 'Host proteins'. dbDiarrhea also serves as a repository of the research articles describing (1) trials of subunit and whole organism vaccines (2) high-throughput screening of Type III secretion system inhibitors and (3) diagnostic assays, for various diarrheal pathogens. The database is web accessible through an intuitive user interface that allows querying proteins and research articles for different organism, keywords and accession number. Besides providing the search facility through browsing, the database supports sequence similarity search with the BLAST tool. With the rapidly burgeoning global burden of the diarrhea, we anticipate that this database would serve as a source of useful information for furthering research on diarrhea. The database can be freely accessed at http://www.juit.ac.in/attachments/dbdiarrhea/diarrhea_home.html. PMID:22917656

  10. 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. PMID:26004652

  11. p47 GTPases: regulators of immunity to intracellular pathogens.

    PubMed

    Taylor, Gregory A; Feng, Carl G; Sher, Alan

    2004-02-01

    Activation of the innate immune system by interferon-gamma (IFN-gamma is crucial for host resistance to infection. IFN-gamma induces the expression of a wide range of mediators that undermine the ability of pathogens to survive in host cells, including a newly discovered family of 47-kDa GTPases. Elimination of different p47 GTPases in mice by gene targeting severely cripples IFN-gamma-regulated defence against Toxoplasma gondii, Listeria monocytogenes, Mycobacterium spp. and other pathogens. In this article, we review our understanding of the role of p47 GTPases in resistance to intracellular infection and discuss the present evidence concerning their mode of action. PMID:15040583

  12. 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

  13. In vitro pathogenicity assay for the ergot fungus Claviceps purpurea.

    PubMed

    Scheffer, Jan; Tudzynski, Paul

    2006-04-01

    The pathogenic development of the biotrophic ergot fungus Claviceps purpurea is strictly limited to the ovary of grasses. Early colonization stages occur within a defined spatio-temporal course of events, including the directed growth to the vascular tissue for nutrient supply. To characterize mutant strains with putative defects in pathogenicity, the close observation of the infection pathway is therefore indispensable. Here, we describe the establishment of a new pathogenicity assay, based on the in vitro cultivation of isolated rye ovaries. The pathogenic development of a wild-type strain of C. purpurea was compared with the infection of mature rye flowers on whole plants. Up to the sixth day post inoculation, the route of infection within the isolated ovaries was maintained and temporally equal to that seen in mature flowers. Therefore, the in vitro pathogenicity assay is an effective alternative to the whole-plant infection tests, and suitable for detailed infection studies and screening high numbers of mutants for defects in early pathogenesis. PMID:16483754

  14. The Road Less Traveled: HIV's Use of Alternative Routes through Cellular Pathways

    PubMed Central

    Marx, Ailie

    2015-01-01

    Pathogens such as HIV-1, with their minimalist genomes, must navigate cellular networks and rely on hijacking and manipulating the host machinery for successful replication. Limited overlap of host factors identified as vital for pathogen replication may be explained by considering that pathogens target, rather than specific cellular factors, crucial cellular pathways by targeting different, functionally equivalent, protein-protein interactions within that pathway. The ability to utilize alternative routes through cellular pathways may be essential for pathogen survival when restricted and provide flexibility depending on the viral replication stage and the environment in the infected host. In this minireview, we evaluate evidence supporting this notion, discuss specific HIV-1 examples, and consider the molecular mechanisms which allow pathogens to flexibly exploit different routes. PMID:25762730

  15. 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

  16. 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.

  17. Firefox Extension Framework for News Article Tagging

    Energy Science and Technology Software Center (ESTSC)

    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

  18. Firefox Extension Framework for News Article Tagging

    SciTech Connect

    Pon, Raymond K.; Buttler, David J.

    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 for predicting how interesting future news article may be for the user.

  19. 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.

  20. 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

  1. Rhamnolipids in perspective: gene regulatory pathways, metabolic engineering, production and technological forecasting.

    PubMed

    Dobler, Leticia; Vilela, Leonardo F; Almeida, Rodrigo V; Neves, Bianca C

    2016-01-25

    Rhamnolipids have emerged as a very promising class of biosurfactants in the last decades, exhibiting properties of great interest in several industrial applications, and have represented a suitable alternative to chemically-synthesized surfactants. This class of biosurfactants has been extensively studied in recent years, aiming at their large-scale production based on renewable resources, which still require high financial costs. Development of non-pathogenic, high-producing strains has been the focus of a number of studies involving heterologous microbial hosts as platforms. However, the intricate gene regulation network controlling rhamnolipid biosynthesis represents a challenge to metabolic engineering and remains to be further understood and explored. This article provides an overview of the biosynthetic pathways and the main gene regulatory factors involved in rhamnolipid production within Pseudomonas aeruginosa, the prototypal producing species. In addition, we provide a perspective view into the main strategies applied to metabolic engineering and biotechnological production. PMID:26409933

  2. Ameobal Pathogen Mimivirus Infects Macrophages through Phagocytosis

    PubMed Central

    Ghigo, Eric; Kartenbeck, Jrgen; Lien, Pham; Pelkmans, Lucas; Capo, Christian; Mege, Jean-Louis; Raoult, Didier

    2008-01-01

    Mimivirus, or Acanthamoeba polyphaga mimivirus (APMV), a giant double-stranded DNA virus that grows in amoeba, was identified for the first time in 2003. Entry by phagocytosis within amoeba has been suggested but not demonstrated. We demonstrate here that APMV was internalized by macrophages but not by non-phagocytic cells, leading to productive APMV replication. Clathrin- and caveolin-mediated endocytosis pathways, as well as degradative endosome-mediated endocytosis, were not used by APMV to invade macrophages. Ultrastructural analysis showed that protrusions were formed around the entering virus, suggesting that macropinocytosis or phagocytosis was involved in APMV entry. Reorganization of the actin cytoskeleton and activation of phosphatidylinositol 3-kinases were required for APMV entry. Blocking macropinocytosis and the lack of APMV colocalization with rabankyrin-5 showed that macropinocytosis was not involved in viral entry. Overexpression of a dominant-negative form of dynamin-II, a regulator of phagocytosis, inhibited APMV entry. Altogether, our data demonstrated that APMV enters macrophages through phagocytosis, a new pathway for virus entry in cells. This reinforces the paradigm that intra-amoebal pathogens have the potential to infect macrophages. PMID:18551172

  3. Ameobal pathogen mimivirus infects macrophages through phagocytosis.

    PubMed

    Ghigo, Eric; Kartenbeck, Jrgen; Lien, Pham; Pelkmans, Lucas; Capo, Christian; Mege, Jean-Louis; Raoult, Didier

    2008-06-01

    Mimivirus, or Acanthamoeba polyphaga mimivirus (APMV), a giant double-stranded DNA virus that grows in amoeba, was identified for the first time in 2003. Entry by phagocytosis within amoeba has been suggested but not demonstrated. We demonstrate here that APMV was internalized by macrophages but not by non-phagocytic cells, leading to productive APMV replication. Clathrin- and caveolin-mediated endocytosis pathways, as well as degradative endosome-mediated endocytosis, were not used by APMV to invade macrophages. Ultrastructural analysis showed that protrusions were formed around the entering virus, suggesting that macropinocytosis or phagocytosis was involved in APMV entry. Reorganization of the actin cytoskeleton and activation of phosphatidylinositol 3-kinases were required for APMV entry. Blocking macropinocytosis and the lack of APMV colocalization with rabankyrin-5 showed that macropinocytosis was not involved in viral entry. Overexpression of a dominant-negative form of dynamin-II, a regulator of phagocytosis, inhibited APMV entry. Altogether, our data demonstrated that APMV enters macrophages through phagocytosis, a new pathway for virus entry in cells. This reinforces the paradigm that intra-amoebal pathogens have the potential to infect macrophages. PMID:18551172

  4. Co-transcriptomic Analysis by RNA Sequencing to Simultaneously Measure Regulated Gene Expression in Host and Bacterial Pathogen.

    PubMed

    Ravasi, Timothy; Mavromatis, Charalampos Harris; Bokil, Nilesh J; Schembri, Mark A; Sweet, Matthew J

    2016-01-01

    Intramacrophage pathogens subvert antimicrobial defence pathways using various mechanisms, including the targeting of host TLR-mediated transcriptional responses. Conversely, TLR-inducible host defence mechanisms subject intramacrophage pathogens to stress, thus altering pathogen gene expression programs. Important biological insights can thus be gained through the analysis of gene expression changes in both the host and the pathogen during an infection. Traditionally, research methods have involved the use of qPCR, microarrays and/or RNA sequencing to identify transcriptional changes in either the host or the pathogen. Here we describe the application of RNA sequencing using samples obtained from in vitro infection assays to simultaneously quantify both host and bacterial pathogen gene expression changes, as well as general approaches that can be undertaken to interpret the RNA sequencing data that is generated. These methods can be used to provide insights into host TLR-regulated transcriptional responses to microbial challenge, as well as pathogen subversion mechanisms against such responses. PMID:26803628

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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. PMID:24788265

  11. Waterborne protozoan pathogens.

    PubMed Central

    Marshall, M M; Naumovitz, D; Ortega, Y; Sterling, C R

    1997-01-01

    Protozoan parasites were the most frequently identified etiologic agents in waterborne disease outbreak from 1991 to 1994. The waterborne parasites Giardia lamblia, Naegleria fowleri, Acanthamoeba spp., Entamoeba histolytica, Cryptosporidium parvum, Cyclospora cayetanesis, Isospora belli, and the microsporidia are reviewed. For each parasite, the review includes history, life cycle, incidence, symptoms, and therapy. Clinical detection methods are compared, and emerging technologies are discussed. Information on the association of these parasites with waterborne outbreaks is reviewed. Current information on protozoan parasites identified as etiological agents in waterborne outbreaks is discussed. Water industry issues related to recent disease outbreaks are examined in the context of water quality testing regulations for G. lamblia and those proposed for C. parvum. The review identifies the limitations of the American Society of Testing and Materials water-testing method for these parasites. An overview of federal regulations affecting the water industry and laboratories that test for water quality is also provided. The article highlights the importance of the clinical laboratory as a frontline defense for the detection of infectious organisms. The review points to the need for clinical laboratories, physicians, and public health personnel to cooperatively plan and assess the challenge of meeting this potential public health threat. PMID:8993859

  12. Antimicrobial aptamers for detection and inhibition of microbial pathogen growth.

    PubMed

    Özalp, Veli Cengiz; Bilecen, Kivanc; Kavruk, Murat; Öktem, Hüseyin Avni

    2013-03-01

    Discovery of alternative sources of antimicrobial agents are essential in the ongoing battle against microbial pathogens. Legislative and scientific challenges considerably hinder the discovery and use of new antimicrobial drugs, and new approaches are in urgent demand. On the other hand, rapid, specific and sensitive detection of airborne pathogens is becoming increasingly critical for public health. In this respect affinity oligonucleotides, aptamers, provide unique opportunities for the development of nanotechnological solutions for such medical applications. In recent years, aptamers specifically recognizing microbial cells and viruses showed great potential in a range of analytical and therapeutic applications. This article describes the significant advances in the development of aptamers targeting specific pathogens. Therapeutic application of aptamers as neutralizing agents demonstrates great potential as a future source of antimicrobial agent. PMID:23464374

  13. 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:23675295

  14. Method of producing silicon carbide articles

    DOEpatents

    Milewski, John V. (Los Alamos, NM)

    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.

  15. 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.

  16. Leading a sheltered life: Intracellular pathogens and maintenance of vacuolar compartments

    PubMed Central

    Kumar, Yadunanda

    2009-01-01

    A large number of intracellular pathogens survive in vacuolar niches composed of host-derived membranes modified extensively by pathogen proteins and lipids. Although intracellular lifestyles offer protection from humoral immune responses, vacuole-bound pathogens nevertheless face powerful intracellular innate immune surveillance pathways that can trigger fusion with lysosomes, autophagy and host cell death. While many of the strategies used by vacuole-bound pathogens to invade and establish a replicative vacuole are well described, how the integrity and stability of these parasitic vacuoles are maintained is poorly understood. Here we identify potential mechanisms of pathogenic vacuole maintenance and the consequences of vacuole disruption by highlighting a select subset of bacterial and protozoan parasites. PMID:19527886

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. [How to write a scientific article].

    PubMed

    Misak, Aleksandra

    2006-01-01

    Scientific articles published in science journals are the main means of communicating scientific information today. A scientific article as a type of publication is characterized by a specific design and content. It is defined as a special type of publication intended to convey scientific information. There are different types of scientific articles: original scientific article, review article, systematic review and meta-analysis, case report, etc. Original scientific article and how to write it is the main topic of this article. It is considered a primary scientific publication that brings research results that have not been published before and contains enough data for other researchers to assess the presented evidence, repeat the study, and critically assess the conclusions. Original scientific article usually follows the IMRaD structure, i.e., it consists of four main sections as follows: introduction, methods, results, and discussion. Each section has a different purpose and brings different part of information on the study that was conducted. Furthermore, other elements of a scientific article are presented and explained, such as a title, abstract, key words, and reference format. Hopefully useful suggestions are offered about the use of scientific language and style. PMID:16526311

  6. 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.

  7. 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.

  8. 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.

  9. Suppression of fungal and nematode plant pathogens through arbuscular mycorrhizal fungi

    PubMed Central

    Veresoglou, Stavros D.; Rillig, Matthias C.

    2012-01-01

    Arbuscular mycorrhizal (AM) fungi represent ubiquitous mutualists of terrestrial plants. Through the symbiosis, plant hosts, among other benefits, receive protection from pathogens. A meta-analysis was conducted on 106 articles to determine whether, following pathogen infection of AM-colonized plants, the identity of the organisms involved (pathogens, AM fungi and host plants) had implications for the extent of the AM-induced pathogen suppression. Data on fungal and nematode pathogens were analysed separately. Although we found no differences in AM effectiveness with respect to the identity of the plant pathogen, the identity of the AM isolate had a dramatic effect on the level of pathogen protection. AM efficiency differences with respect to nematode pathogens were mainly limited to the number of AM isolates present; by contrast, modification of the ability to suppress fungal pathogens could occur even through changing the identity of the Glomeraceae isolate applied. N-fixing plants received more protection from fungal pathogens than non-N-fixing dicotyledons; this was attributed to the more intense AM colonization in N-fixing plants. Results have implications for understanding mycorrhizal ecology and agronomic applications. PMID:22012951

  10. Finding the sweet spot: how human fungal pathogens acquire and turn the sugar inositol against their hosts.

    PubMed

    Xue, Chaoyang

    2015-01-01

    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. PMID:25736882

  11. Fusobacterium nucleatum: a commensal-turned pathogen

    PubMed Central

    Han, Yiping W.

    2015-01-01

    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 syndrom and Alzheimer’s disease. The virulence mechanisms involved in the diseases are discussed, with a particular 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. PMID:25576662

  12. 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 area of host-pathogen interactions as well as policy makers from federal agencies. The main objectives of the workshop are: (1) to assess the current national needs, capabilities, near-term technologies, and future challenges in applying various diagnostics tools to public health and bio-defense; (2) to evaluate the utility and feasibility of host-response and pathogen biomarker profiling in the diagnosis and management of infectious diseases; and (3) to create a comprehensive developmental strategy from proof-of-concept, through validation, to deployment of appropriate advanced technology for the clinical/public health and bio-defense environments.

  13. 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 susceptibleinfectedrecovered (SIR) model. However, there is growing evidence that the complexity of many hostpathogen 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

  14. 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.

  15. 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

  16. Qualitative Research Articles: Guidelines, Suggestions and Needs

    ERIC Educational Resources Information Center

    Crescentini, Alberto; Mainardi, Giuditta

    2009-01-01

    Purpose: The purpose of this paper is to give ideas and suggestions to avoid some typical problems of qualitative articles. The aim is not to debate quality in qualitative research but to indicate some practical solutions. Design/methodology/approach: The paper discusses the design of qualitative research and the structure of a qualitative article

  17. 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...

  18. 19 CFR 4.69 - Shipping articles.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....S.C. chapter 103, in the form provided for in 46 CFR 14.05-1. ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Shipping articles. 4.69 Section 4.69 Customs... VESSELS IN FOREIGN AND DOMESTIC TRADES Foreign Clearances § 4.69 Shipping articles. No vessel of the...

  19. 48 CFR 25.104 - Nonavailable articles.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Nonavailable articles. 25.104 Section 25.104 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Buy American-Supplies 25.104 Nonavailable articles. (a) The following...

  20. 19 CFR 4.69 - Shipping articles.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....S.C. chapter 103, in the form provided for in 46 CFR 14.05-1. ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Shipping articles. 4.69 Section 4.69 Customs... VESSELS IN FOREIGN AND DOMESTIC TRADES Foreign Clearances § 4.69 Shipping articles. No vessel of the...

  1. 19 CFR 4.69 - Shipping articles.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....S.C. chapter 103, in the form provided for in 46 CFR 14.05-1. ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Shipping articles. 4.69 Section 4.69 Customs... VESSELS IN FOREIGN AND DOMESTIC TRADES Foreign Clearances § 4.69 Shipping articles. No vessel of the...

  2. 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...

  3. 19 CFR 4.69 - Shipping articles.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ....S.C. chapter 103, in the form provided for in 46 CFR 14.05-1. ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Shipping articles. 4.69 Section 4.69 Customs... VESSELS IN FOREIGN AND DOMESTIC TRADES Foreign Clearances § 4.69 Shipping articles. No vessel of the...

  4. 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...

  5. 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...

  6. 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...

  7. 19 CFR 4.69 - Shipping articles.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....S.C. chapter 103, in the form provided for in 46 CFR 14.05-1. ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Shipping articles. 4.69 Section 4.69 Customs... VESSELS IN FOREIGN AND DOMESTIC TRADES Foreign Clearances § 4.69 Shipping articles. No vessel of the...

  8. How Teachers and Researchers Read Academic Articles

    ERIC Educational Resources Information Center

    Bartels, Nat

    2003-01-01

    This study looks at language teachers' and language researchers' expectations and evaluations of two kinds of journal articles, either researcher-oriented or teacher-oriented. The results show that teachers and academics use different ways of validating information in journal articles and use the information contained in them in distinctly

  9. 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. PMID:23975542

  10. [Work on a scientific medical article].

    PubMed

    Kazarian, A M; Evdokomova, Iu A

    2002-01-01

    Motivations to writing scientific medical articles are outlined as well as types of medical publications and requirements to a good article. Market of medical papers is analysed and algorithm of search for a journal for sending publication is presented. Correlations between medical practice and science, training of personnel and co-authorship are considered. PMID:12181816

  11. 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…

  12. 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)

  13. 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…

  14. 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. ...

  15. 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 Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT Disposition of Articles Produced by Patients § 35.35 Unsalable...

  16. 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 Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT Disposition of Articles Produced by Patients § 35.35 Unsalable...

  17. 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 Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT Disposition of Articles Produced by Patients § 35.35 Unsalable...

  18. 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 Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT Disposition of Articles Produced by Patients § 35.35 Unsalable...

  19. 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 Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT Disposition of Articles Produced by Patients § 35.35 Unsalable...

  20. 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.

  1. 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

  2. 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

  3. 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…

  4. Reverse protein arrays applied to host-pathogen interaction studies.

    PubMed

    Cid, Vctor J; Kauffmann, Ekkehard; Molina, Mara

    2011-01-01

    Infection of cells and tissues by pathogenic microorganisms often involves severe reprogramming of host cell signaling. Typically, invasive microorganisms manipulate host cellular pathways seeking advantage for replication and survival within the host, or to evade the immune response. Understanding such subversion of the host cell by intracellular pathogens at a molecular level is the key to possible preventive and therapeutic interventions on infectious diseases. Reverse Protein Arrays (RPAs) have been exploited in other fields, especially in molecular oncology. However, this technology has not been applied yet to the study of infectious diseases. Coupling classic in vitro infection techniques used by cellular microbiologists to proteomic approaches such as RPA analysis should provide a wealth of information about how host cell pathways are manipulated by pathogens. The increasing availability of antibodies specific for phosphorylated epitopes in signaling proteins allows monitoring global changes in phosphorylation through the infection process by utilizing RPA analyses. In our lab, we have shown the potential of RPA technology in this field by devising a microarray consisting of lysates from cell cultures infected by Salmonella typhimurium. The protocols used are described here. PMID:21370058

  5. 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.

  6. Food Microbial Pathogen Detection and Analysis Using DNA Microarray Technologies

    PubMed Central

    Herold, Keith E.

    2008-01-01

    Abstract Culture-based methods used for microbial detection and identification are simple to use, relatively inexpensive, and sensitive. However, culture-based methods are too time-consuming for high-throughput testing and too tedious for analysis of samples with multiple organisms and provide little clinical information regarding the pathogen (e.g., antibiotic resistance genes, virulence factors, or strain subtype). DNA-based methods, such as polymerase chain reaction (PCR), overcome some these limitations since they are generally faster and can provide more information than culture-based methods. One limitation of traditional PCR-based methods is that they are normally limited to the analysis of a single pathogen, a small group of related pathogens, or a small number of relevant genes. Microarray technology enables a significant expansion of the capability of DNA-based methods in terms of the number of DNA sequences that can be analyzed simultaneously, enabling molecular identification and characterization of multiple pathogens and many genes in a single array assay. Microarray analysis of microbial pathogens has potential uses in research, food safety, medical, agricultural, regulatory, public health, and industrial settings. In this article, we describe the main technical elements of microarray technology and the application and potential use of DNA microarrays for food microbial analysis. PMID:18673074

  7. 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.

  8. 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.

  9. Antigenic Variation in Bacterial Pathogens.

    PubMed

    Palmer, Guy H; Bankhead, Troy; Seifert, H Steven

    2016-02-01

    Antigenic variation is a strategy used by a broad diversity of microbial pathogens to persist within the mammalian host. Whereas viruses make use of a minimal proofreading capacity combined with large amounts of progeny to use random mutation for variant generation, antigenically variant bacteria have evolved mechanisms which use a stable genome, which aids in protecting the fitness of the progeny. Here, three well-characterized and highly antigenically variant bacterial pathogens are discussed: Anaplasma, Borrelia, and Neisseria. These three pathogens display a variety of mechanisms used to create the structural and antigenic variation needed for immune escape and long-term persistence. Intrahost antigenic variation is the focus; however, the role of these immune escape mechanisms at the population level is also presented. PMID:26999387

  10. 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

  11. 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

  12. 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 pathogen and swine may serve as a source of infection in human, a most challenging issue in greater part of the world raising pigs. Tick-borne encephalitis virus infection, either thick borne or caused by consumption of raw milk, is an increasing trend in the industrialized part of the world. Consumer awareness, ethics of food, sustainability in food production, and trust in foods, are of growing importance to the consumer. The reaction of the consumer to new technology, such as nanotechnology, is unpredictable. Many efforts should be devoted to communication of non-biased information to both the food producers as well as the consumer. PMID:17976849

  13. 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. PMID:26481458

  14. Comparative Metabolic Systems Analysis of Pathogenic Burkholderia

    PubMed Central

    Bartell, Jennifer A.; Yen, Phillip; Varga, John J.; Goldberg, Joanna B.

    2014-01-01

    Burkholderia cenocepacia and Burkholderia multivorans are opportunistic drug-resistant pathogens that account for the majority of Burkholderia cepacia complex infections in cystic fibrosis patients and also infect other immunocompromised individuals. While they share similar genetic compositions, B. cenocepacia and B. multivorans exhibit important differences in pathogenesis. We have developed reconciled genome-scale metabolic network reconstructions of B. cenocepacia J2315 and B. multivorans ATCC 17616 in parallel (designated iPY1537 and iJB1411, respectively) to compare metabolic abilities and contextualize genetic differences between species. The reconstructions capture the metabolic functions of the two species and give insight into similarities and differences in their virulence and growth capabilities. The two reconstructions have 1,437 reactions in common, and iPY1537 and iJB1411 have 67 and 36 metabolic reactions unique to each, respectively. After curating the extensive reservoir of metabolic genes in Burkholderia, we identified 6 genes essential to growth that are unique to iPY1513 and 13 genes uniquely essential to iJB1411. The reconstructions were refined and validated by comparing in silico growth predictions to in vitro growth capabilities of B. cenocepacia J2315, B. cenocepacia K56-2, and B. multivorans ATCC 17616 on 104 carbon sources. Overall, we identified functional pathways that indicate B. cenocepacia can produce a wider array of virulence factors compared to B. multivorans, which supports the clinical observation that B. cenocepacia is more virulent than B. multivorans. The reconciled reconstructions provide a framework for generating and testing hypotheses on the metabolic and virulence capabilities of these two related emerging pathogens. PMID:24163337

  15. Reconciling West Nile virus with the autophagic pathway.

    PubMed

    Martn-Acebes, Miguel A; Blzquez, Ana-Beln; Saiz, Juan-Carlos

    2015-01-01

    West Nile virus (WNV) is a neurotropic mosquito-borne flavivirus responsible for recurrent outbreaks of meningitis and encephalitis. Several studies analyzing the interactions of this pathogen with the autophagic pathway have reported opposite results with evidence for and against the upregulation of autophagy in infected cells. In this regard, we have recently reported that minimal genetic changes (single amino acid substitutions) in nonstructural proteins of WNV can modify the ability of the virus to induce autophagic features such as LC3 modification and aggregation in infected cells. We think that these results could help explain some of the previously reported discrepancies. These findings could also aid in deciphering the interactions of this pathogen with the autophagic pathway at the molecular level aimed to develop feasible antiviral strategies to combat this pathogen, and other related flaviviruses. PMID:25946067

  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. 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.

  18. 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

  19. Energetics of pathogenic bacteria and opportunities for drug development.

    PubMed

    Cook, Gregory M; Greening, Chris; Hards, Kiel; Berney, Michael

    2014-01-01

    The emergence and spread of drug-resistant pathogens and our inability to develop new antimicrobials to overcome resistance has inspired scientists to consider new targets for drug development. Cellular bioenergetics is an area showing promise for the development of new antimicrobials, particularly in the discovery of new anti-tuberculosis drugs where several new compounds have entered clinical trials. In this review, we have examined the bioenergetics of various bacterial pathogens, highlighting the versatility of electron donor and acceptor utilisation and the modularity of electron transport chain components in bacteria. In addition to re-examining classical concepts, we explore new literature that reveals the intricacies of pathogen energetics, for example, how Salmonella enterica and Campylobacter jejuni exploit host and microbiota to derive powerful electron donors and sinks; the strategies Mycobacterium tuberculosis and Pseudomonas aeruginosa use to persist in lung tissues; and the importance of sodium energetics and electron bifurcation in the chemiosmotic anaerobe Fusobacterium nucleatum. A combination of physiological, biochemical, and pharmacological data suggests that, in addition to the clinically-approved target F1Fo-ATP synthase, NADH dehydrogenase type II, succinate dehydrogenase, hydrogenase, cytochrome bd oxidase, and menaquinone biosynthesis pathways are particularly promising next-generation drug targets. The realisation of cellular energetics as a rich target space for the development of new antimicrobials will be dependent upon gaining increased understanding of the energetic processes utilised by pathogens in host environments and the ability to design bacterial-specific inhibitors of these processes. PMID:25476763

  20. Inflammasomes bridge signalling between pathogen identification and the immune response

    PubMed Central

    Abdul-Sater, Ali A.; Sad-Sadier, Najwane; Ojcius, David M.; Yilmaz, zlem; Kelly, Kathy A.

    2010-01-01

    Microbial organisms express pathogen-associated molecular patterns (PAMPs) that can stimulate expression of pro-inflammatory mediators following ligation of pathogen recognition receptors. However, both commensal organisms and pathogens can express PAMPs. The immune system can distinguish between commensals and pathogens in part through secretion of the key inflammatory cytokines IL-1? and IL-18. A PAMP such as lipopolysaccharide can induce production of intracellular pro-IL-1? and pro-IL-18, but not their secretion. A second danger signal, derived from host-cell molecules that are released from stressed or infected cells, or detected as a PAMP that is present in the cytosol, can stimulate assembly of an inflammasome that activates the protease caspase-1. Caspase-1, in turn, is responsible for processing and secretion of the mature IL-1? and IL-18. Many diverse ligands leading to inflammasome activation have been identified, but the cell signaling pathways initiated by the ligands tend to converge on a small set of common mechanisms. PMID:20011701

  1. Host Response to Respiratory Bacterial Pathogens as Identified by Integrated Analysis of Human Gene Expression Data

    PubMed Central

    Smith, Steven B.; Magid-Slav, Michal; Brown, James R.

    2013-01-01

    Respiratory bacterial pathogens are one of the leading causes of infectious death in the world and a major health concern complicated by the rise of multi-antibiotic resistant strains. Therapeutics that modulate host genes essential for pathogen infectivity could potentially avoid multi-drug resistance and provide a wider scope of treatment options. Here, we perform an integrative analysis of published human gene expression data generated under challenges from the gram-negative and Gram-positive bacteria pathogens, Pseudomonas aeruginosa and Streptococcus pneumoniae, respectively. We applied a previously described differential gene and pathway enrichment analysis pipeline to publicly available host mRNA GEO datasets resulting from exposure to bacterial infection. We found 72 canonical human pathways common between four GEO datasets, representing P. aeruginosa and S. pneumoniae. Although the majority of these pathways are known to be involved with immune response, we found several interesting new interactions such as the SUMO1 pathway that might have a role in bacterial infections. Furthermore, 36 host-bacterial pathways were also shared with our previous results for respiratory virus host gene expression. Based on our pathway analysis we propose several drug-repurposing opportunities supported by the literature. PMID:24086587

  2. 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...

  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. 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.

  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 superior to any currently available for these materials. In a preferred embodiment, the desired superconducting oxide material is BSCCO 2223.

  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. Sex-Dependent Resistance to the Pathogenic Fungus Cryptococcus neoformans

    PubMed Central

    van den Berg, Maaike C. W.; Woerlee, Jessica Z.; Ma, Hansong; May, Robin C.

    2006-01-01

    Sex differences occur in most species and affect a variety of biological traits including morphology, behavior, and life history. The nematode Caenorhabditis elegans exists as a population of self-fertile hermaphrodites with occasional males, which differ anatomically and behaviorally from hermaphrodites. Here we show that male C. elegans also differ from hermaphrodites in their susceptibility to a fungal pathogen, Cryptococcus neoformans. Wild-type males show greater resistance than hermaphrodite animals to killing by this pathogen and this resistance can be induced in hermaphrodite animals by inappropriate activation of the male sex-determination pathway. Resistance is molecularly determined, rather than resulting from behavioral changes or reproductive differences, and requires the activity of the stress-response transcription factor DAF-16. Finally, we demonstrate that resistance to C. neoformans correlates broadly with longevity within the Caenorhabditis genus. Our results hint at an overlap between the pathways controlling immunity and longevity and raise the possibility that differential regulation of these pathways may contribute to sex-dependent and species-dependent variation. PMID:16582430

  8. 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

  9. 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...

  10. 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

  11. A new cyanogenic metabolite in Arabidopsis required for inducible pathogen defense

    PubMed Central

    Rajniak, Jakub; Barco, Brenden; Clay, Nicole K.; Sattely, Elizabeth S.

    2015-01-01

    SUMMARY Thousands of putative biosynthetic genes in Arabidopsis thaliana have no known function, suggesting that there are numerous molecules contributing to plant fitness that have not yet been discovered1,2. Prime among these uncharacterized genes are cytochromes P450 upregulated in response to pathogens3,4. Starting with a single pathogen-induced P4505, CYP82C2, we used a combination of untargeted metabolomics and co-expression analysis to uncover the complete biosynthetic pathway to a previously unknown Arabidopsis metabolite, 4-hydroxyindole-3-carbonyl nitrile (4-OH-ICN), which harbors cyanogenic functionality that is unprecedented in plants and exceedingly rare in nature6,7. The aryl cyanohydrin intermediate in the 4-OH-ICN pathway reveals a latent capacity for cyanogenic glucoside biosynthesis8,9 in Arabidopsis. By expressing 4-OH-ICN biosynthetic enzymes in Saccharomyces cerevisiae and Nicotiana benthamiana, we reconstitute the complete pathway in vitro and in vivo and validate the functions of its enzymes. 4-OH-ICN pathway mutants show increased susceptibility to the bacterial pathogen Pseudomonas syringae, consistent with a role in inducible pathogen defense. Arabidopsis has been the preeminent model system10,11 for studying the role of small molecules in plant innate immunity12; our results uncover a new branch of indole metabolism distinct from the canonical camalexin pathway, and support a role for this pathway in the Arabidopsis defense response.13 These results establish a more complete framework for understanding how the model plant Arabidopsis uses small molecules in pathogen defense. PMID:26352477

  12. 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...

  13. Biosensors for Monitoring Airborne Pathogens.

    PubMed

    Fronczek, Christopher F; Yoon, Jeong-Yeol

    2015-08-01

    Airborne pathogens affect both humans and animals and are often highly and rapidly transmittable. Many problematic airborne pathogens, both viral (influenza A/H1N1, Rubella, and avian influenza/H5N1) and bacterial (Mycobacterium tuberculosis, Streptococcus pneumoniae, and Bacillus anthracis), have huge impacts on health care and agricultural applications, and can potentially be used as bioterrorism agents. Many different laboratory-based methods have been introduced and are currently being used. However, such detection is generally limited by sample collection, including nasal swabs and blood analysis. Direct identification from air (specifically, aerosol samples) would be ideal, but such detection has not been very successful due to the difficulty in sample collection and the extremely low pathogen concentration found in aerosol samples. In this review, we will discuss the portable biosensors and/or micro total analysis systems (TAS) that can be used for monitoring such airborne pathogens, similar to smoke detectors. Current laboratory-based methods will be reviewed, and possible solutions to convert these lab-based methods into TAS biosensors will be discussed. PMID:25862683

  14. 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

  15. MANAGING URBAN WATERSHED PATHOGEN CONTAMINATION

    EPA Science Inventory

    This document is written as a resource for state and local watershed managers who have the responsibility of managing pathogen contamination in urban watersheds. In addition it can be an information source for members of the public interested in watershed mitigation efforts aime...

  16. 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...

  17. 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...

  18. 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...

  19. PATHOGENIC 'NAEGLERIA': DISTRIBUTION IN NATURE

    EPA Science Inventory

    Infection in man with pathogenic Naegleria, a free-living soil amoeba, results in a usually fatal disease entity known as primary amoebic meningoencephalitis. Epidemiological data usually included exposure to freshwater lakes or streams within the week prior to onset. However, no...

  20. Pathogenicity of Aseptic Bursaphelenchus xylophilus

    PubMed Central

    Zhu, Li-hua; Ye, Jianren; Negi, Sapna; Xu, Xu-ling; Wang, Zhang-li; Ji, Jin-yi

    2012-01-01

    Pine wilt is a disease of pine (Pinus spp.) caused by the pine wood nematode (PWN), Bursaphelenchus xylophilus. However, the pathogenic mechanism of pine wilt disease (PWD) remains unclear. Although the PWN was thought to be the only pathogenic agent associated with this disease, a potential role for bacterial symbionts in the disease process was recently proposed. Studies have indicated that aseptic PWNs do not cause PWD in aseptic pine trees, while PWNs associated with bacteria cause wilting symptoms. To investigate the pathogenicity of the PWN and its associated bacteria, 3-month-old microcuttings derived from certain clones of Pinus densiflora Siebold & Zucc. produced in vitro were inoculated under aseptic conditions with aseptic PWNs, non-aseptic PWNs and bacteria isolated from the nematodes. Six-month-old aseptic P. densiflora microcuttings and 7-month-old P. massoniana seedlings were also inoculated under aseptic conditions with aseptic PWNs and non-aseptic PWNs. The results showed that the aseptic microcuttings and seedlings inoculated with aseptic PWNs or non-aseptic PWNs wilted, while those inoculated with bacterial isolates did not wilt. Nematodes were recovered from wilted microcuttings and seedlings inoculated with aseptic PWNs and non-aseptic PWNs, and the asepsis of nematodes recovered from aseptic PWN-inoculated microcuttings and seedlings was reconfirmed by culturing them in NB liquid medium at 30C for more than 7 days. Taken together, the results indicate that the asepsis of PWN did not cause the loss of pathogenicity. PMID:22662271

  1. 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 ...

  2. 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…

  3. Pathogenicity of aseptic Bursaphelenchus xylophilus.

    PubMed

    Zhu, Li-hua; Ye, Jianren; Negi, Sapna; Xu, Xu-ling; Wang, Zhang-li; Ji, Jin-yi

    2012-01-01

    Pine wilt is a disease of pine (Pinus spp.) caused by the pine wood nematode (PWN), Bursaphelenchus xylophilus. However, the pathogenic mechanism of pine wilt disease (PWD) remains unclear. Although the PWN was thought to be the only pathogenic agent associated with this disease, a potential role for bacterial symbionts in the disease process was recently proposed. Studies have indicated that aseptic PWNs do not cause PWD in aseptic pine trees, while PWNs associated with bacteria cause wilting symptoms. To investigate the pathogenicity of the PWN and its associated bacteria, 3-month-old microcuttings derived from certain clones of Pinus densiflora Siebold & Zucc. produced in vitro were inoculated under aseptic conditions with aseptic PWNs, non-aseptic PWNs and bacteria isolated from the nematodes. Six-month-old aseptic P. densiflora microcuttings and 7-month-old P. massoniana seedlings were also inoculated under aseptic conditions with aseptic PWNs and non-aseptic PWNs. The results showed that the aseptic microcuttings and seedlings inoculated with aseptic PWNs or non-aseptic PWNs wilted, while those inoculated with bacterial isolates did not wilt. Nematodes were recovered from wilted microcuttings and seedlings inoculated with aseptic PWNs and non-aseptic PWNs, and the asepsis of nematodes recovered from aseptic PWN-inoculated microcuttings and seedlings was reconfirmed by culturing them in NB liquid medium at 30C for more than 7 days. Taken together, the results indicate that the asepsis of PWN did not cause the loss of pathogenicity. PMID:22662271

  4. 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 ...

  5. Overview of Pathogen Groups: Fungi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Fungi comprise a diverse array of taxa that exhibit a great diversity of properties and requirements. These microorganisms collectively occupy virtually every niche in which arthropods are also found, and, consequently, there has been great interest in the use of these pathogens as microbial bi...

  6. 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 etal. 2010). The pathogen was only formally described about 13years ago (Longcore etal. 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 etal. 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 etal. 2003; Weldon etal. 2004; Lips etal. 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 etal. 2009; James etal. 2009; Farrer etal. 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 etal. 2011). In a new study published in this issue of Molecular Ecology, Schloegel etal. (2012) identify an additional unique Bd lineage that is endemic to the Atlantic Brazilian rainforests (Bd-Brazil) and provide striking evidence that the Bd-Brazil lineage has sexually recombined with the BdGPL lineage in an area where the two lineages likely came into contact as a result of classic anthropogenically mediated 'pathogen pollution'(see below). Fungal pathogens, including Bd, have the propensity to form recombinant lineages when allopatric populations that have not yet formed genetic reproductive barriers are provided with opportunities to intermingle, and virulent strains may be selected for because they tend to be highly transmissible (Fisher etal. 2012). As Schloegel etal. (2012) point out, the demonstrated ability for Bd to undergo meiosis may also mean that it has the capacity to form a resistant spore stage (as yet undiscovered), based on extrapolation from other sexually reproducing chytrids that all have spore stages. PMID:23075064

  7. 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

  8. 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. PMID:26901228

  9. Evolution of pathogenicity and sexual reproduction in eight Candida genomes

    PubMed Central

    Butler, Geraldine; Rasmussen, Matthew D.; Lin, Michael F.; Santos, Manuel A.S.; Sakthikumar, Sharadha; Munro, Carol A.; Rheinbay, Esther; Grabherr, Manfred; Forche, Anja; Reedy, Jennifer L.; Agrafioti, Ino; Arnaud, Martha B.; Bates, Steven; Brown, Alistair J.P.; Brunke, Sascha; Costanzo, Maria C.; Fitzpatrick, David A.; de Groot, Piet W. J.; Harris, David; Hoyer, Lois L.; Hube, Bernhard; Klis, Frans M.; Kodira, Chinnappa; Lennard, Nicola; Logue, Mary E.; Martin, Ronny; Neiman, Aaron M.; Nikolaou, Elissavet; Quail, Michael A.; Quinn, Janet; Santos, Maria C.; Schmitzberger, Florian F.; Sherlock, Gavin; Shah, Prachi; Silverstein, Kevin; Skrzypek, Marek S.; Soll, David; Staggs, Rodney; Stansfield, Ian; Stumpf, Michael P H; Sudbery, Peter E.; Thyagarajan, Srikantha; Zeng, Qiandong; Berman, Judith; Berriman, Matthew; Heitman, Joseph; Gow, Neil A. R.; Lorenz, Michael C.; Birren, Bruce W.; Kellis, Manolis; Cuomo, Christina A.

    2009-01-01

    Candida species are the most common cause of opportunistic fungal infection worldwide. We report the genome sequences of six Candida species and compare these and related pathogens and nonpathogens. There are significant expansions of cell wall, secreted, and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the Mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/alpha2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine to serine genetic code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the C. albicans gene catalog, identifying many new genes. PMID:19465905

  10. 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

  11. 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.

  12. Network-assisted genetic dissection of pathogenicity and drug resistance in the opportunistic human pathogenic fungus Cryptococcus neoformans

    PubMed Central

    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. PMID:25739925

  13. 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…

  14. Pathways to Aggression in Children and Adolescents

    ERIC Educational Resources Information Center

    Watson, Malcolm W.; Fischer, Kurt W.; Andreas, Jasmina Burdzovic; Smith, Kevin W.

    2004-01-01

    In this article, Malcolm Watson, Kurt Fischer, Jasmina Burdzovic Andreas, and Kevin Smith describe and compare two approaches to assessing risk factors that lead to aggression in children. The first, the severe risks approach, focuses on how risk factors form a pathway that leads to aggressive behavior. Within this approach, an inhibited

  15. Alternative Certification Pathways: Filling a Gap?

    ERIC Educational Resources Information Center

    Ludlow, Carlyn

    2013-01-01

    The purpose of this article is to examine the proliferation of alternative certification pathways through an analysis of the role and history of teacher certification and supply followed by a synthesis of national, regional, and state research studies on alternative routes to certification programs and a review of studies conducted on well-known

  16. 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

  17. 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

  18. 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…

  19. Immunotherapy and Oncogenic Pathways: The PTEN Connection.

    PubMed

    Rizvi, Naiyer A; Chan, Timothy A

    2016-02-01

    Peng and colleagues describe the effects of PTEN inactivation on antitumor immunity and response to immune checkpoint blockade in melanoma. These results shed light on the intricate interplay between oncogenic pathways and antitumor immune response. Cancer Discov; 6(2); 128-9. 2016 AACR.See related article by Peng et al., p. 202. PMID:26851183

  20. 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