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Sample records for understanding virulence mechanisms

  1. Pathogenic Leptospira: Advances in understanding the molecular pathogenesis and virulence

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    Ciamak Ghazaei

    2018-01-01

    Full Text Available Leptospirosis is a common zoonotic disease has emerged as a major public health problem, with developing countries bearing disproportionate burdens. Although the diverse range of clinical manifestations of the leptospirosis in humans is widely documented, the mechanisms through which the pathogen causes disease remain undetermined. In addition, leptospirosis is a much-neglected life-threatening disease although it is one of the most important zoonoses occurring in a diverse range of epidemiological distribution. Recent advances in molecular profiling of pathogenic species of the genus Leptospira have improved our understanding of the evolutionary factors that determine virulence and mechanisms that the bacteria employ to survive. However, a major impediment to the formulation of intervention strategies has been the limited understanding of the disease determinants. Consequently, the association of the biological mechanisms to the pathogenesis of Leptospira, as well as the functions of numerous essential virulence factors still remain implicit. This review examines recent advances in genetic screening technologies, the underlying microbiological processes, the virulence factors and associated molecular mechanisms driving pathogenesis of Leptospira species.

  2. Pathogenic Leptospira: Advances in understanding the molecular pathogenesis and virulence

    Science.gov (United States)

    Ghazaei, Ciamak

    2018-01-01

    Leptospirosis is a common zoonotic disease has emerged as a major public health problem, with developing countries bearing disproportionate burdens. Although the diverse range of clinical manifestations of the leptospirosis in humans is widely documented, the mechanisms through which the pathogen causes disease remain undetermined. In addition, leptospirosis is a much-neglected life-threatening disease although it is one of the most important zoonoses occurring in a diverse range of epidemiological distribution. Recent advances in molecular profiling of pathogenic species of the genus Leptospira have improved our understanding of the evolutionary factors that determine virulence and mechanisms that the bacteria employ to survive. However, a major impediment to the formulation of intervention strategies has been the limited understanding of the disease determinants. Consequently, the association of the biological mechanisms to the pathogenesis of Leptospira, as well as the functions of numerous essential virulence factors still remain implicit. This review examines recent advances in genetic screening technologies, the underlying microbiological processes, the virulence factors and associated molecular mechanisms driving pathogenesis of Leptospira species. PMID:29445617

  3. Investigating the ?Trojan Horse? Mechanism of Yersinia pestis Virulence

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    McCutchen-Maloney, S L; Fitch, J P

    2005-02-08

    Yersinia pestis, the etiological agent of plague, is a Gram-negative, highly communicable, enteric bacterium that has been responsible for three historic plague pandemics. Currently, several thousand cases of plague are reported worldwide annually, and Y. pestis remains a considerable threat from a biodefense perspective. Y. pestis infection can manifest in three forms: bubonic, septicemic, and pneumonic plague. Of these three forms, pneumonic plague has the highest fatality rate ({approx}100% if left untreated), the shortest intervention time ({approx}24 hours), and is highly contagious. Currently, there are no rapid, widely available vaccines for plague and though plague may be treated with antibiotics, the emergence of both naturally occurring and potentially engineered antibiotic resistant strains makes the search for more effective therapies and vaccines for plague of pressing concern. The virulence mechanism of this deadly bacterium involves induction of a Type III secretion system, a syringe-like apparatus that facilitates the injection of virulence factors, termed Yersinia outer membrane proteins (Yops), into the host cell. These virulence factors inhibit phagocytosis and cytokine secretion, and trigger apoptosis of the host cell. Y. pestis virulence factors and the Type III secretion system are induced thermally, when the bacterium enters the mammalian host from the flea vector, and through host cell contact (or conditions of low Ca{sup 2+} in vitro). Apart from the temperature increase from 26 C to 37 C and host cell contact (or low Ca{sup 2+} conditions), other molecular mechanisms that influence virulence induction in Y. pestis are largely uncharacterized. This project focused on characterizing two novel mechanisms that regulate virulence factor induction in Y. pestis, immunoglobulin G (IgG) binding and quorum sensing, using a real-time reporter system to monitor induction of virulence. Incorporating a better understanding of the mechanisms of virulence

  4. [Virulence mechanisms of enteropathogenic Escherichia coli].

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    Farfán-García, Ana Elvira; Ariza-Rojas, Sandra Catherine; Vargas-Cárdenas, Fabiola Andrea; Vargas-Remolina, Lizeth Viviana

    2016-08-01

    Acute diarrheal disease (ADD) is a global public health problem, especially in developing countries and is one of the causes of mortality in children under five. ADD etiologic agents include viruses, bacteria and parasites in that order. Escherichia coli bacteria it is classified as a major diarrheagenic agent and transmitted by consuming contaminated water or undercooked foods. This review compiled updates on information virulence factors and pathogenic mechanisms involved in adhesion and colonization of seven pathotypes of E. coli called enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), shigatoxigenic E. coli (STEC), enteroaggregative E. coli (EAEC) and diffusely-adherent E. coli (DAEC). A final pathotype, adherent-invasive E. coli (AIEC) associated with Crohn's disease was also reviewed. The diarrheagenic pathotypes of E. coli affect different population groups and knowledge of the molecular mechanisms involved in the interaction with the human is important to guide research towards the development of vaccines and new tools for diagnosis and control.

  5. Mechanisms Controlling Virulence Thresholds of Mixed Viral Populations ▿

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    Lancaster, Karen Z.; Pfeiffer, Julie K.

    2011-01-01

    The propensity of RNA viruses to revert attenuating mutations contributes to disease and complicates vaccine development. Despite the presence of virulent revertant viruses in some live-attenuated vaccines, disease from vaccination is rare. This suggests that in mixed viral populations, attenuated viruses may limit the pathogenesis of virulent viruses, thus establishing a virulence threshold. Here we examined virulence thresholds using mixtures of virulent and attenuated viruses in a transgenic mouse model of poliovirus infection. We determined that a 1,000-fold excess of the attenuated Sabin strain of poliovirus was protective against disease induced by the virulent Mahoney strain. Protection was induced locally, and inactivated virus conferred protection. Treatment with a poliovirus receptor-blocking antibody phenocopied the protective effect of inactivated viruses in vitro and in vivo, suggesting that one mechanism controlling virulence thresholds may be competition for a viral receptor. Additionally, the type I interferon response reduces poliovirus pathogenesis; therefore, we examined virulence thresholds in mice lacking the alpha/beta interferon receptor. We found that the attenuated virus was virulent in immunodeficient mice due to the enhanced replication and reversion of attenuating mutations. Therefore, while the type I interferon response limits the virulence of the attenuated strain by reducing replication, protection from disease conferred by the attenuated strain in immunocompetent mice can occur independently of replication. Our results identified mechanisms controlling the virulence of mixed viral populations and indicate that live-attenuated vaccines containing virulent virus may be safe, as long as virulent viruses are present at levels below a critical threshold. PMID:21795346

  6. Understanding Defense Mechanisms.

    Science.gov (United States)

    Cramer, Phebe

    2015-12-01

    Understanding defense mechanisms is an important part of psychotherapy. In this article, we trace the history of the concept of defense, from its origin with Freud to current views. The issue of defense as an unconscious mechanism is examined. The question of whether defenses are pathological, as well as their relation to pathology, is discussed. The effect of psychotherapy on the use of defenses, and their relation to a therapeutic alliance is explored. A series of empirical research studies that demonstrate the functioning of defense mechanisms and that support the theory is presented. Research also shows that as part of normal development, different defenses emerge at different developmental periods, and that gender differences in defense use occur.

  7. New insights into virulence mechanisms of rice pathogen Acidovorax avenae subsp. avenae strain RS-1 following exposure to ?-lactam antibiotics

    OpenAIRE

    Li, Bin; Ge, Mengyu; Zhang, Yang; Wang, Li; Ibrahim, Muhammad; Wang, Yanli; Sun, Guochang; Chen, Gongyou

    2016-01-01

    Recent research has shown that pathogen virulence can be altered by exposure to antibiotics, even when the growth rate is unaffected. Investigating this phenomenon provides new insights into understanding the virulence mechanisms of bacterial pathogens. This study investigates the phenotypic and transcriptomic responses of the rice pathogenic bacterium Acidovorax avenae subsp. avenae (Aaa) strain RS-1 to ?-lactam antibiotics especially Ampicillin (Amp). Our results indicate that exposure to A...

  8. Understanding mechanical ventilators.

    Science.gov (United States)

    Chatburn, Robert L

    2010-12-01

    The respiratory care academic community has not yet adopted a standardized system for classifying and describing modes of ventilation. As a result, there is enough confusion that patient care, clinician education and even ventilator sales are all put at risk. This article summarizes a ventilator mode taxonomy that has been extensively published over the last 15 years. Specifically, the classification system has three components: a description of the control variables within breath; a description of the sequence of mandatory and spontaneous breaths; and a specification for the targeting scheme. This three-level specification provides scalability of detail to make the mode description appropriate for the particular need. At the bedside, we need only refer to a mode briefly using the first or perhaps first and second components. To distinguish between similar modes and brand names, we would need to include all components. This taxonomy uses the equation of motion for the respiratory system as the underlying theoretical framework. All terms relevant to describing modes of mechanical ventilation are defined in an extensive appendix.

  9. Impact of AmpC Derepression on Fitness and Virulence: the Mechanism or the Pathway?

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    Marcelo Pérez-Gallego

    2016-10-01

    Full Text Available Understanding the interplay between antibiotic resistance and bacterial fitness and virulence is essential to guide individual treatments and improve global antibiotic policies. A paradigmatic example of a resistance mechanism is the intrinsic inducible chromosomal β-lactamase AmpC from multiple Gram-negative bacteria, including Pseudomonas aeruginosa, a major nosocomial pathogen. The regulation of ampC expression is intimately linked to peptidoglycan recycling, and AmpC-mediated β-lactam resistance is frequently mediated by inactivating mutations in ampD, encoding an N-acetyl-anhydromuramyl-l-alanine amidase, affecting the levels of ampC-activating muropeptides. Here we dissect the impact of the multiple pathways causing AmpC hyperproduction on P. aeruginosa fitness and virulence. Through a detailed analysis, we demonstrate that the lack of all three P. aeruginosa AmpD amidases causes a dramatic effect in fitness and pathogenicity, severely compromising growth rates, motility, and cytotoxicity; the latter effect is likely achieved by repressing key virulence factors, such as protease LasA, phospholipase C, or type III secretion system components. We also show that ampC overexpression is required but not sufficient to confer the growth-motility-cytotoxicity impaired phenotype and that alternative pathways leading to similar levels of ampC hyperexpression and resistance, such as those involving PBP4, had no fitness-virulence cost. Further analysis indicated that fitness-virulence impairment is caused by overexpressing ampC in the absence of cell wall recycling, as reproduced by expressing ampC from a plasmid in an AmpG (muropeptide permease-deficient background. Thus, our findings represent a major step in the understanding of β-lactam resistance biology and its interplay with fitness and pathogenesis.

  10. Caenorhabditis elegans reveals novel Pseudomonas aeruginosa virulence mechanism

    NARCIS (Netherlands)

    Utari, Putri Dwi; Quax, Wim J.

    The susceptibility of Caenorhabditis elegans to different virulent phenotypes of Pseudomonas aeruginosa makes the worms an excellent model for studying host-pathogen interactions. Including the recently described liquid killing, five different killing assays are now available offering superb

  11. Understanding Virulence in the Brucellae and Francisellae: Towards Efficacious Treatments for Two Potential Biothreat Agents

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    Rasley, A; Parsons, D A; El-Etr, S; Roux, C; Tsolis, R

    2009-12-30

    Francisella tularensis, Yersinia pestis and Brucellae species are highly infectious pathogens classified as select agents by the Centers for Disease Control and Prevention (CDC) with the potential for use in bioterrorism attacks. These organisms are known to be facultative intracellular pathogens that preferentially infect human monocytes. As such, understanding how the host responds to infection with these organisms is paramount in detecting and combating human disease. We have compared the ability of fully virulent strains of each pathogen and their non-pathogenic near neighbors to enter and survive inside the human monocytic cell line THP-1 and have quantified the cellular response to infection with the goal of identifying both unique and common host response patterns. We expanded the scope of these studies to include experiments with pathogenic and non-pathogenic strains of Y. pestis, the causative agent of plague. Nonpathogenic strains of each organism were impaired in their ability to survive intracellularly compared with their pathogenic counterparts. Furthermore, infection of THP-1 cells with pathogenic strains of Y. pestis and F. tularensis resulted in marked increases in the secretion of the inflammatory chemokines IL-8, RANTES, and MIP-1{beta}. In contrast, B. melitensis infection failed to elicit any significant increases in a panel of cytokines tested. These differences may underscore distinct strategies in pathogenic mechanisms employed by these pathogens.

  12. Understanding the mechanisms of lung mechanical stress

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    C.S.N.B. Garcia

    2006-06-01

    Full Text Available Physical forces affect both the function and phenotype of cells in the lung. Bronchial, alveolar, and other parenchymal cells, as well as fibroblasts and macrophages, are normally subjected to a variety of passive and active mechanical forces associated with lung inflation and vascular perfusion as a result of the dynamic nature of lung function. These forces include changes in stress (force per unit area or strain (any forced change in length in relation to the initial length and shear stress (the stress component parallel to a given surface. The responses of cells to mechanical forces are the result of the cell's ability to sense and transduce these stimuli into intracellular signaling pathways able to communicate the information to its interior. This review will focus on the modulation of intracellular pathways by lung mechanical forces and the intercellular signaling. A better understanding of the mechanisms by which lung cells transduce physical forces into biochemical and biological signals is of key importance for identifying targets for the treatment and prevention of physical force-related disorders.

  13. Understanding Bohmian mechanics: A dialogue

    OpenAIRE

    Tumulka, Roderich

    2004-01-01

    This paper is an introduction to the ideas of Bohmian mechanics, an interpretation of quantum mechanics in which the observer plays no fundamental role. Bohmian mechanics describes, instead of probabilities of measurement results, objective microscopic events. In recent years, Bohmian mechanics has attracted increasing attention by researchers. The form of a dialogue allows me to address questions about the Bohmian view that often arise.

  14. Molecular Mechanism of Quorum-Sensing in Enterococcus faecalis: Its Role in Virulence and Therapeutic Approaches.

    Science.gov (United States)

    Ali, Liaqat; Goraya, Mohsan Ullah; Arafat, Yasir; Ajmal, Muhammad; Chen, Ji-Long; Yu, Daojin

    2017-05-03

    Quorum-sensing systems control major virulence determinants in Enterococcus faecalis , which causes nosocomial infections. The E . faecalis quorum-sensing systems include several virulence factors that are regulated by the cytolysin operon, which encodes the cytolysin toxin. In addition, the E . faecalis Fsr regulator system controls the expression of gelatinase, serine protease, and enterocin O16. The cytolysin and Fsr virulence factor systems are linked to enterococcal diseases that affect the health of humans and other host models. Therefore, there is substantial interest in understanding and targeting these regulatory pathways to develop novel therapies for enterococcal infection control. Quorum-sensing inhibitors could be potential therapeutic agents for attenuating the pathogenic effects of E . faecalis . Here, we discuss the regulation of cytolysin, the LuxS system, and the Fsr system, their role in E . faecalis -mediated infections, and possible therapeutic approaches to prevent E . faecalis infection.

  15. Insights on the virulence mechanisms of European Edwardsiella tarda strains isolated from turbot

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    Nuria Castro Iglesias

    2014-06-01

    Full Text Available Edwardsiella tarda is a common inhabitant of diverse ecological niches as well as a common guest of a high variety of animals including fish, reptiles, amphibians, chickens and other warm-blooded animals as humans. With regard to the aquatic environments, E. tarda has been described as the causative agent of infections in more than 20 fish species including some important fish species in aquaculture industry. Several potential pathogenic properties have been suggested to contribute to the infection process of E. tarda, which include adhesins, Type III and Type VI secretion system, and ability to survive and replicate in phagocytes, among others. Identification of these virulence-related genes is essential for understanding the pathogenesis of the species. Since E. tarda causes great losses in the Chinese aquaculture, great efforts have been recently devoted to study the pathogenicity mechanism of E. tarda in Asian countries. However, all these studies were conducted employing Asian isolates. Being E. tarda a pathogen of great economical concern in European turbot aquaculture and since the high intraspecific variability of E. tarda is well known, it becomes evident that additional pathogenicity studies conducted with non-Asiatic strains are needed. Enzymes such as chondroitinase are believed to play an important role in the pathogenicity of bacteria that cause infections (Tam et al., 1982. Chondroitinase activity was proposed to be one virulence contributor in Edwardsiella spp. and mediates the cartilage degradation in the chronic “hole-in-the-head” lesion. In Gram-negative bacteria, the most intensively studied quorum sensing systems rely on the use of N-acylhomoserine lactones (AHLs, which production is common among marine and fish pathogenic Proteobacteria, controlling the expression of key virulence factors. In the case of E. tarda, strain NUF251 from diseased flounder had the ability to produce two kinds of AHL molecules. It is likely

  16. Understanding Mechanical Design with Respect to Manufacturability

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    Mondell, Skyler

    2010-01-01

    At the NASA Prototype Development Laboratory in Kennedy Space Center, Fl, several projects concerning different areas of mechanical design were undertaken in order to better understand the relationship between mechanical design and manufacturabiIity. The assigned projects pertained specifically to the NASA Space Shuttle, Constellation, and Expendable Launch Vehicle programs. During the work term, mechanical design practices relating to manufacturing processes were learned and utilized in order to obtain an understanding of mechanical design with respect to manufacturability.

  17. Understanding Mechanisms of Radiological Contamination

    Energy Technology Data Exchange (ETDEWEB)

    Rick Demmer; John Drake; Ryan James, PhD

    2014-03-01

    Over the last 50 years, the study of radiological contamination and decontamination has expanded significantly. This paper addresses the mechanisms of radiological contamination that have been reported and then discusses which methods have recently been used during performance testing of several different decontamination technologies. About twenty years ago the Idaho Nuclear Technology Engineering Center (INTEC) at the INL began a search for decontamination processes which could minimize secondary waste. In order to test the effectiveness of these decontamination technologies, a new simulated contamination, termed SIMCON, was developed. SIMCON was designed to replicate the types of contamination found on stainless steel, spent fuel processing equipment. Ten years later, the INL began research into methods for simulating urban contamination resulting from a radiological dispersal device (RDD). This work was sponsored by the Defense Advanced Research Projects Agency (DARPA) and included the initial development an aqueous application of contaminant to substrate. Since 2007, research sponsored by the US Environmental Protection Agency (EPA) has advanced that effort and led to the development of a contamination method that simulates particulate fallout from an Improvised Nuclear Device (IND). The IND method diverges from previous efforts to create tenacious contamination by simulating a reproducible “loose” contamination. Examining these different types of contamination (and subsequent decontamination processes), which have included several different radionuclides and substrates, sheds light on contamination processes that occur throughout the nuclear industry and in the urban environment.

  18. New insights into virulence mechanisms of rice pathogen Acidovorax avenae subsp. avenae strain RS-1 following exposure to ß-lactam antibiotics.

    Science.gov (United States)

    Li, Bin; Ge, Mengyu; Zhang, Yang; Wang, Li; Ibrahim, Muhammad; Wang, Yanli; Sun, Guochang; Chen, Gongyou

    2016-02-26

    Recent research has shown that pathogen virulence can be altered by exposure to antibiotics, even when the growth rate is unaffected. Investigating this phenomenon provides new insights into understanding the virulence mechanisms of bacterial pathogens. This study investigates the phenotypic and transcriptomic responses of the rice pathogenic bacterium Acidovorax avenae subsp. avenae (Aaa) strain RS-1 to ß-lactam antibiotics especially Ampicillin (Amp). Our results indicate that exposure to Amp does not influence bacterial growth and biofilm formation, but alters the virulence, colonization capacity, composition of extracellular polymeric substances and secretion of Type VI secretion system (T6SS) effector Hcp. This attenuation in virulence is linked to unique or differential expression of known virulence-associated genes based on genome-wide transcriptomic analysis. The reliability of expression data generated by RNA-Seq was verified with quantitative real-time PCR of 21 selected T6SS genes, where significant down-regulation in expression of hcp gene, corresponding to the reduction in secretion of Hcp, was observed under exposure to Amp. Hcp is highlighted as a potential target for Amp, with similar changes observed in virulence-associated phenotypes between exposure to Amp and mutation of hcp gene. In addition, Hcp secretion is reduced in knockout mutants of 4 differentially expressed T6SS genes.

  19. Understanding biochar mechanisms for practical implementation

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    Glaser, Bruno [Halle-Wittenberg Univ. (Germany). Inst. fuer Agrar- und Ernaehrungeswissenschaften Bodenbiogeochemie; Kammann, Claudia [Arbeitskreis zur Nutzung von Sekundaerrohstoffen und fuer Klimaschutz (ANS) e.V., Braunschweig (Germany). Fachausschuss Biokohle; Hochschule Geisenheim Univ. (Germany). Klimafolgenforschung-Klimawandel in Spezialkulturen; Loewen, Achim (ed.) [Arbeitskreis zur Nutzung von Sekundaerrohstoffen und fuer Klimaschutz (ANS) e.V., Braunschweig (Germany); HAWK Hochschule fuer Angewandte Wissenschaft und Kunst Hildesheim, Holzminden, Goettingen (Germany). Fachgebiet Nachhaltige Energie- und Umwelttechnik NEUtec

    2015-07-01

    The conference on ''understanding biochar mechanisms for practical implementation'' 2015 at the Geisenheim University aims at understanding biochar mechanism, that are crucial for beneficial and safety biochar technology implementation. Further issues are ecotoxicology, biochar in agriculture, horticulture, and animal husbandry. Practical issues concern analysis and characterization of technological processes, sustainable uses and certification, regulation and marketing aspects. The Conference is structured in 10 sessions.

  20. A population genetics-based and phylogenetic approach to understanding the evolution of virulence in the genus Listeria.

    Science.gov (United States)

    den Bakker, Henk C; Bundrant, Brittany N; Fortes, Esther D; Orsi, Renato H; Wiedmann, Martin

    2010-09-01

    The genus Listeria includes (i) the opportunistic pathogens L. monocytogenes and L. ivanovii, (ii) the saprotrophs L. innocua, L. marthii, and L. welshimeri, and (iii) L. seeligeri, an apparent saprotroph that nevertheless typically contains the prfA virulence gene cluster. A novel 10-loci multilocus sequence typing scheme was developed and used to characterize 67 isolates representing six Listeria spp. (excluding L. grayi) in order to (i) provide an improved understanding of the phylogeny and evolution of the genus Listeria and (ii) use Listeria as a model to study the evolution of pathogenicity in opportunistic environmental pathogens. Phylogenetic analyses identified six well-supported Listeria species that group into two main subdivisions, with each subdivision containing strains with and without the prfA virulence gene cluster. Stochastic character mapping and phylogenetic analysis of hly, a gene in the prfA cluster, suggest that the common ancestor of the genus Listeria contained the prfA virulence gene cluster and that this cluster was lost at least five times during the evolution of Listeria, yielding multiple distinct saprotrophic clades. L. welshimeri, which appears to represent the most ancient clade that arose from an ancestor with a prfA cluster deletion, shows a considerably lower average sequence divergence than other Listeria species, suggesting a population bottleneck and a putatively different ecology than other saprotrophic Listeria species. Overall, our data suggest that, for some pathogens, loss of virulence genes may represent a selective advantage, possibly by facilitating adaptation to a specific ecological niche.

  1. A Population Genetics-Based and Phylogenetic Approach to Understanding the Evolution of Virulence in the Genus Listeria▿ †

    Science.gov (United States)

    den Bakker, Henk C.; Bundrant, Brittany N.; Fortes, Esther D.; Orsi, Renato H.; Wiedmann, Martin

    2010-01-01

    The genus Listeria includes (i) the opportunistic pathogens L. monocytogenes and L. ivanovii, (ii) the saprotrophs L. innocua, L. marthii, and L. welshimeri, and (iii) L. seeligeri, an apparent saprotroph that nevertheless typically contains the prfA virulence gene cluster. A novel 10-loci multilocus sequence typing scheme was developed and used to characterize 67 isolates representing six Listeria spp. (excluding L. grayi) in order to (i) provide an improved understanding of the phylogeny and evolution of the genus Listeria and (ii) use Listeria as a model to study the evolution of pathogenicity in opportunistic environmental pathogens. Phylogenetic analyses identified six well-supported Listeria species that group into two main subdivisions, with each subdivision containing strains with and without the prfA virulence gene cluster. Stochastic character mapping and phylogenetic analysis of hly, a gene in the prfA cluster, suggest that the common ancestor of the genus Listeria contained the prfA virulence gene cluster and that this cluster was lost at least five times during the evolution of Listeria, yielding multiple distinct saprotrophic clades. L. welshimeri, which appears to represent the most ancient clade that arose from an ancestor with a prfA cluster deletion, shows a considerably lower average sequence divergence than other Listeria species, suggesting a population bottleneck and a putatively different ecology than other saprotrophic Listeria species. Overall, our data suggest that, for some pathogens, loss of virulence genes may represent a selective advantage, possibly by facilitating adaptation to a specific ecological niche. PMID:20656873

  2. A Population Genetics-Based and Phylogenetic Approach to Understanding the Evolution of Virulence in the Genus Listeria▿ †

    OpenAIRE

    den Bakker, Henk C.; Bundrant, Brittany N.; Fortes, Esther D.; Orsi, Renato H.; Wiedmann, Martin

    2010-01-01

    The genus Listeria includes (i) the opportunistic pathogens L. monocytogenes and L. ivanovii, (ii) the saprotrophs L. innocua, L. marthii, and L. welshimeri, and (iii) L. seeligeri, an apparent saprotroph that nevertheless typically contains the prfA virulence gene cluster. A novel 10-loci multilocus sequence typing scheme was developed and used to characterize 67 isolates representing six Listeria spp. (excluding L. grayi) in order to (i) provide an improved understanding of the phylogeny an...

  3. Talaromyces marneffei Genomic, Transcriptomic, Proteomic and Metabolomic Studies Reveal Mechanisms for Environmental Adaptations and Virulence

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    Susanna K. P. Lau

    2017-06-01

    Full Text Available Talaromyces marneffei is a thermally dimorphic fungus causing systemic infections in patients positive for HIV or other immunocompromised statuses. Analysis of its ~28.9 Mb draft genome and additional transcriptomic, proteomic and metabolomic studies revealed mechanisms for environmental adaptations and virulence. Meiotic genes and genes for pheromone receptors, enzymes which process pheromones, and proteins involved in pheromone response pathway are present, indicating its possibility as a heterothallic fungus. Among the 14 Mp1p homologs, only Mp1p is a virulence factor binding a variety of host proteins, fatty acids and lipids. There are 23 polyketide synthase genes, one for melanin and two for mitorubrinic acid/mitorubrinol biosynthesis, which are virulence factors. Another polyketide synthase is for biogenesis of the diffusible red pigment, which consists of amino acid conjugates of monascorubin and rubropunctatin. Novel microRNA-like RNAs (milRNAs and processing proteins are present. The dicer protein, dcl-2, is required for biogenesis of two milRNAs, PM-milR-M1 and PM-milR-M2, which are more highly expressed in hyphal cells. Comparative transcriptomics showed that tandem repeat-containing genes were overexpressed in yeast phase, generating protein polymorphism among cells, evading host’s immunity. Comparative proteomics between yeast and hyphal cells revealed that glyceraldehyde-3-phosphate dehydrogenase, up-regulated in hyphal cells, is an adhesion factor for conidial attachment.

  4. Mechanisms relevant to the enhanced virulence of a dihydroxynaphthalene-melanin metabolically engineered entomopathogen.

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    Min-Nan Tseng

    Full Text Available The entomopathogenic fungus Metarhizium anisopliae MA05-169 is a transformant strain that has been metabolically engineered to express dihydroxynaphthalene-melanin biosynthesis genes. In contrast to the wild type strain, the transformant displays a greater resistance to environmental stress and a higher virulence toward target insect host. However, the underlying mechanisms for these characteristics remain unclear; hence experiments were initiated to explore the possible mechanism(s through physiological and molecular approaches. Although both transformant and wild type strains could infect and share the same insect host range, the former germinated faster and produced more appressoria than the latter, both in vivo and in vitro. The transformant showed a significantly shorter median lethal time (LT50 when infecting the diamondback moth (Plutella xylostella and the striped flea beetle (Phyllotreta striolata, than the wild type. Additionally, the transformant was more tolerant to reactive oxygen species (ROS, produced 40-fold more orthosporin and notably overexpressed the transcripts of the pathogenicity-relevant hydrolytic enzymes (chitinase, protease, and phospholipase genes in vivo. In contrast, appressorium turgor pressure and destruxin A content were slightly decreased compared to the wild type. The transformant's high anti-stress tolerance, its high virulence against five important insect pests (cowpea aphid Aphis craccivora, diamondback moth Pl. xylostella, striped flea beetle Ph. striolata, and silverleaf whitefly Bemisia argentifolii and its capacity to colonize the root system are key properties for its potential bio-control field application.

  5. The Mechanisms of Virulence Regulation by Small Noncoding RNAs in Low GC Gram-Positive Pathogens

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    Stephanie Pitman

    2015-12-01

    Full Text Available The discovery of small noncoding regulatory RNAs (sRNAs in bacteria has grown tremendously recently, giving new insights into gene regulation. The implementation of computational analysis and RNA sequencing has provided new tools to discover and analyze potential sRNAs. Small regulatory RNAs that act by base-pairing to target mRNAs have been found to be ubiquitous and are the most abundant class of post-transcriptional regulators in bacteria. The majority of sRNA studies has been limited to E. coli and other gram-negative bacteria. However, examples of sRNAs in gram-positive bacteria are still plentiful although the detailed gene regulation mechanisms behind them are not as well understood. Strict virulence control is critical for a pathogen’s survival and many sRNAs have been found to be involved in that process. This review outlines the targets and currently known mechanisms of trans-acting sRNAs involved in virulence regulation in various gram-positive pathogens. In addition, their shared characteristics such as CU interaction motifs, the role of Hfq, and involvement in two-component regulators, riboswitches, quorum sensing, or toxin/antitoxin systems are described.

  6. Improving students' understanding of quantum mechanics

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    Singh, Chandralekha

    2011-03-01

    Learning quantum mechanics is especially challenging, in part due to the abstract nature of the subject. We have been conducting investigations of the difficulties that students have in learning quantum mechanics. To help improve student understanding of quantum concepts, we are developing quantum interactive learning tutorials (QuILTs) as well as tools for peer-instruction. The goal of QuILTs and peer-instruction tools is to actively engage students in the learning process and to help them build links between the formalism and the conceptual aspects of quantum physics without compromising the technical content. They focus on helping students integrate qualitative and quantitative understanding, confront and resolve their misconceptions and difficulties, and discriminate between concepts that are often confused. In this talk, I will give examples from my research in physics education of how students' prior knowledge relevant for quantum mechanics can be assessed, and how learning tools can be designed to help students develop a robust knowledge structure and critical thinking skills. Supported by the National Science Foundation.

  7. Human Hemorrhagic Fever Causing Arenaviruses: Molecular Mechanisms Contributing to Virus Virulence and Disease Pathogenesis

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    Junjie Shao

    2015-05-01

    Full Text Available Arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (LCMV to highly virulent hemorrhagic fever (HF causing viruses such as Lassa (LASV, Junin (JUNV, Machupo (MACV, Lujo (LUJV, Sabia (SABV, Guanarito (GTOV, and Chapare (CHPV, for which there are limited preventative and therapeutic measures. Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma. Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases. This review summarizes current knowledge of the roles of each of the four viral proteins and some known cellular factors in the pathogenesis of arenaviral HF as well as of some human primary cell-culture and animal models that lend themselves to studying arenavirus-induced HF disease pathogenesis. Knowledge gained from these studies can be applied towards the development of novel therapeutics and vaccines against these deadly human pathogens.

  8. Antibiotic resistance and virulence: Understanding the link and its consequences for prophylaxis and therapy.

    Science.gov (United States)

    Guillard, Thomas; Pons, Stéphanie; Roux, Damien; Pier, Gerald B; Skurnik, David

    2016-07-01

    "Antibiotic resistance is usually associated with a fitness cost" is frequently accepted as common knowledge in the field of infectious diseases. However, with the advances in high-throughput DNA sequencing that allows for a comprehensive analysis of bacterial pathogenesis at the genome scale, including antibiotic resistance genes, it appears that this paradigm might not be as solid as previously thought. Recent studies indicate that antibiotic resistance is able to enhance bacterial fitness in vivo with a concomitant increase in virulence during infections. As a consequence, strategies to minimize antibiotic resistance turn out to be not as simple as initially believed. Indeed, decreased antibiotic use may not be sufficient to let susceptible strains outcompete the resistant ones. Here, we put in perspective these findings and review alternative approaches, such as preventive and therapeutic anti-bacterial immunotherapies that have the potential to by-pass the classic antibiotics. © 2016 WILEY Periodicals, Inc.

  9. Understanding the molecular mechanisms of reprogramming

    Energy Technology Data Exchange (ETDEWEB)

    Krause, Marie N. [Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA (United States); University Hospital of Würzburg, Department of Pediatrics, 2 Josef-Schneiderstrasse, 97080 Würzburg (Germany); Sancho-Martinez, Ignacio [Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA (United States); Centre for Stem Cells and Regenerative Medicine, King' s College London, 28th Floor, Tower Wing, Guy' s Hospital, Great Maze Pond, London (United Kingdom); Izpisua Belmonte, Juan Carlos, E-mail: belmonte@salk.edu [Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA (United States)

    2016-05-06

    Despite the profound and rapid advancements in reprogramming technologies since the generation of the first induced pluripotent stem cells (iPSCs) in 2006[1], the molecular basics of the process and its implications are still not fully understood. Recent work has suggested that a subset of TFs, so called “Pioneer TFs”, play an important role during the stochastic phase of iPSC reprogramming [2–6]. Pioneer TFs activities differ from conventional transcription factors in their mechanism of action. They bind directly to condensed chromatin and elicit a series of chromatin remodeling events that lead to opening of the chromatin. Chromatin decondensation by pioneer factors progressively occurs during cell division and in turn exposes specific gene promoters in the DNA to which TFs can now directly bind to promoters that are readily accessible[2, 6]. Here, we will summarize recent advancements on our understanding of the molecular mechanisms underlying reprogramming to iPSC as well as the implications that pioneer Transcription Factor activities might play during different lineage conversion processes. - Highlights: • Pioneer transcription factor activity underlies the initial steps of iPSC generation. • Reprogramming can occur by cis- and/or trans- reprogramming events. • Cis-reprogramming implies remodeling of the chromatin for enabling TF accessibility. • Trans-reprogramming encompasses direct binding of Tfs to their target gene promoters.

  10. Virulence factors and mechanisms of antimicrobial resistance in Shigella strains from periurban areas of Lima (Peru).

    Science.gov (United States)

    Lluque, Angela; Mosquito, Susan; Gomes, Cláudia; Riveros, Maribel; Durand, David; Tilley, Drake H; Bernal, María; Prada, Ana; Ochoa, Theresa J; Ruiz, Joaquim

    2015-01-01

    The study was aimed to describe the serotype, mechanisms of antimicrobial resistance, and virulence determinants in Shigella spp. isolated from Peruvian children. Eighty three Shigella spp. were serogrouped and serotyped being established the antibiotic susceptibility. The presence of 12 virulence factors (VF) and integrase 1 and 2, along with commonly found antibiotic resistance genes was established by PCR. S. flexneri was the most relevant serogroup (55 isolates, 66%), with serotype 2a most frequently detected (27 of 55, 49%), followed by S. boydii and S. sonnei at 12 isolates each (14%) and S. dysenteriae (four isolates, 5%). Fifty isolates (60%) were multi-drug resistant (MDR) including 100% of S. sonnei and 64% of S. flexneri. Resistance levels were high to trimethoprim-sulfamethoxazole (86%), tetracycline (74%), ampicillin (67%), and chloramphenicol (65%). Six isolates showed decreased azithromycin susceptibility. No isolate was resistant to nalidixic acid, ciprofloxacin, nitrofurantoin, or ceftriaxone. The most frequent resistance genes were sul2 (95%), tet(B) (92%), cat (80%), dfrA1 (47%), blaOXA-1like (40%), with intl1 and intl2 detected in 51 and 52% of the isolates, respectively. Thirty-one different VF profiles were observed, being the ipaH (100%), sen (77%), virA and icsA (75%) genes the most frequently found. Differences in the prevalence of VF were observed between species with S. flexneri isolates, particularly serotype 2a, possessing high numbers of VF. In conclusion, this study highlights the high heterogeneity of Shigella VF and resistance genes, and prevalence of MDR organisms within this geographic region. Copyright © 2015 Elsevier GmbH. All rights reserved.

  11. Rice-Infecting Pseudomonas Genomes Are Highly Accessorized and Harbor Multiple Putative Virulence Mechanisms to Cause Sheath Brown Rot

    Science.gov (United States)

    Quibod, Ian Lorenzo; Grande, Genelou; Oreiro, Eula Gems; Borja, Frances Nikki; Dossa, Gerbert Sylvestre; Mauleon, Ramil; Cruz, Casiana Vera; Oliva, Ricardo

    2015-01-01

    Sheath rot complex and seed discoloration in rice involve a number of pathogenic bacteria that cannot be associated with distinctive symptoms. These pathogens can easily travel on asymptomatic seeds and therefore represent a threat to rice cropping systems. Among the rice-infecting Pseudomonas, P. fuscovaginae has been associated with sheath brown rot disease in several rice growing areas around the world. The appearance of a similar Pseudomonas population, which here we named P. fuscovaginae-like, represents a perfect opportunity to understand common genomic features that can explain the infection mechanism in rice. We showed that the novel population is indeed closely related to P. fuscovaginae. A comparative genomics approach on eight rice-infecting Pseudomonas revealed heterogeneous genomes and a high number of strain-specific genes. The genomes of P. fuscovaginae-like harbor four secretion systems (Type I, II, III, and VI) and other important pathogenicity machinery that could probably facilitate rice colonization. We identified 123 core secreted proteins, most of which have strong signatures of positive selection suggesting functional adaptation. Transcript accumulation of putative pathogenicity-related genes during rice colonization revealed a concerted virulence mechanism. The study suggests that rice-infecting Pseudomonas causing sheath brown rot are intrinsically diverse and maintain a variable set of metabolic capabilities as a potential strategy to occupy a range of environments. PMID:26422147

  12. Rice-Infecting Pseudomonas Genomes Are Highly Accessorized and Harbor Multiple Putative Virulence Mechanisms to Cause Sheath Brown Rot.

    Directory of Open Access Journals (Sweden)

    Ian Lorenzo Quibod

    Full Text Available Sheath rot complex and seed discoloration in rice involve a number of pathogenic bacteria that cannot be associated with distinctive symptoms. These pathogens can easily travel on asymptomatic seeds and therefore represent a threat to rice cropping systems. Among the rice-infecting Pseudomonas, P. fuscovaginae has been associated with sheath brown rot disease in several rice growing areas around the world. The appearance of a similar Pseudomonas population, which here we named P. fuscovaginae-like, represents a perfect opportunity to understand common genomic features that can explain the infection mechanism in rice. We showed that the novel population is indeed closely related to P. fuscovaginae. A comparative genomics approach on eight rice-infecting Pseudomonas revealed heterogeneous genomes and a high number of strain-specific genes. The genomes of P. fuscovaginae-like harbor four secretion systems (Type I, II, III, and VI and other important pathogenicity machinery that could probably facilitate rice colonization. We identified 123 core secreted proteins, most of which have strong signatures of positive selection suggesting functional adaptation. Transcript accumulation of putative pathogenicity-related genes during rice colonization revealed a concerted virulence mechanism. The study suggests that rice-infecting Pseudomonas causing sheath brown rot are intrinsically diverse and maintain a variable set of metabolic capabilities as a potential strategy to occupy a range of environments.

  13. Mechanisms of pathogen virulence and host susceptibility in virulent Aeromonas hydrophila infections of channel catfish (Ictalurus punctatus)

    Science.gov (United States)

    An emerging pathotype of Aeromonas hydrophila (vAh) has been responsible for widespread farm losses in the US catfish industry over the last decade. While our genetic and biochemical understanding of vAh has been greatly enhanced in this time frame, our ability to reliably induce the disease in the...

  14. Comparative analysis of the pathogenic mechanisms of street rabies virus strains with different virulence levels.

    Science.gov (United States)

    Yin, Jing Feng; Ding, Yu Lin; Huang, Ying; Tao, Xiao Yan; Li, Hao; Yu, Peng Cheng; Shen, Xin Xin; Jiao, Wen Tao; Liang, Guo Dong; Tang, Qing; Wang, Feng Long

    2014-10-01

    To characterize two strains of street rabies virus (RABV) isolated from the brain tissue of cattle from Inner Mongolia. Differences in the histopathological and ultrastructural changes in the brain tissue of infected mice were determined to reveal variation in the pathogenesis of infection between street rabies virus strains. Ten-day-old mice were intracranially inoculated with one of three virus strains and brain tissue harvested when the mice were moribund. Various histopathological and ultrastructural markers of disease were then compared between the groups. Infection with the street virus strain CNM1101C resulted in severe neuronal dendrites damage, but only mild cell apoptosis, T lymphocyte infiltration and microglial activation. Infection with the other street virus strain, CNM1103C, was characterized by cell apoptosis, T lymphocyte infiltration and microglial activation as well as dendrites damage. However, in comparison, infection with the attenuated virus strain CTN caused severe T lymphocyte infiltration, microglial activation and cell apoptosis, but left the neuronal dendrites intact. The two street rabies virus strains isolated from cattle from Inner Mongolia had different levels of virulence and caused distinct pathological changes in infected mice. Therefore, we concluded that different pathogenic mechanisms exist between different RABV strains. Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  15. Fusarium verticillioides: Advancements in Understanding the Toxicity, Virulence, and Niche Adaptations of a Model Mycotoxigenic Pathogen of Maize.

    Science.gov (United States)

    Blacutt, Alex A; Gold, Scott E; Voss, Kenneth A; Gao, Minglu; Glenn, Anthony E

    2018-03-01

    The importance of understanding the biology of the mycotoxigenic fungus Fusarium verticillioides and its various microbial and plant host interactions is critical given its threat to maize, one of the world's most valuable food crops. Disease outbreaks and mycotoxin contamination of grain threaten economic returns and have grave implications for human and animal health and food security. Furthermore, F. verticillioides is a member of a genus of significant phytopathogens and, thus, data regarding its host association, biosynthesis of secondary metabolites, and other metabolic (degradative) capabilities are consequential to both basic and applied research efforts across multiple pathosystems. Notorious among its secondary metabolites are the fumonisin mycotoxins, which cause severe animal diseases and are implicated in human disease. Additionally, studies of these mycotoxins have led to new understandings of F. verticillioides plant pathogenicity and provide tools for research into cellular processes and host-pathogen interaction strategies. This review presents current knowledge regarding several significant lines of F. verticillioides research, including facets of toxin production, virulence, and novel fitness strategies exhibited by this fungus across rhizosphere and plant environments.

  16. Understanding molecular structure from molecular mechanics.

    Science.gov (United States)

    Allinger, Norman L

    2011-04-01

    Molecular mechanics gives us a well known model of molecular structure. It is less widely recognized that valence bond theory gives us structures which offer a direct interpretation of molecular mechanics formulations and parameters. The electronic effects well-known in physical organic chemistry can be directly interpreted in terms of valence bond structures, and hence quantitatively calculated and understood. The basic theory is outlined in this paper, and examples of the effects, and their interpretation in illustrative examples is presented.

  17. Understanding Kinetic Energy paradox in Quantum Mechanics

    OpenAIRE

    Kornyushin, Yuri

    2008-01-01

    A concept of Kinetic Energy in Quantum Mechanics is analyzed. Kinetic Energy is not zero in many cases where there are no motion and flux. This paradox can be understood, using expansion of the wave function in Fourier integral, that is on the basis of virtual plane waves.

  18. Evolutionary mechanisms involved in the virulence of infectious salmon anaemia virus (ISAV), a piscine orthomyxovirus

    International Nuclear Information System (INIS)

    Markussen, Turhan; Jonassen, Christine Monceyron; Numanovic, Sanela; Braaen, Stine; Hjortaas, Monika; Nilsen, Hanne; Mjaaland, Siri

    2008-01-01

    Infectious salmon anaemia virus (ISAV) is an orthomyxovirus causing a multisystemic, emerging disease in Atlantic salmon. Here we present, for the first time, detailed sequence analyses of the full-genome sequence of a presumed avirulent isolate displaying a full-length hemagglutinin-esterase (HE) gene (HPR0), and compare this with full-genome sequences of 11 Norwegian ISAV isolates from clinically diseased fish. These analyses revealed the presence of a virulence marker right upstream of the putative cleavage site R 267 in the fusion (F) protein, suggesting a Q 266 → L 266 substitution to be a prerequisite for virulence. To gain virulence in isolates lacking this substitution, a sequence insertion near the cleavage site seems to be required. This strongly suggests the involvement of a protease recognition pattern at the cleavage site of the fusion protein as a determinant of virulence, as seen in highly pathogenic influenza A virus H5 or H7 and the paramyxovirus Newcastle disease virus

  19. Novel Regulatory Mechanisms of Pathogenicity and Virulence to Combat MDR in Candida albicans

    Directory of Open Access Journals (Sweden)

    Saif Hameed

    2013-01-01

    Full Text Available Continuous deployment of antifungals in treating infections caused by dimorphic opportunistic pathogen Candida albicans has led to the emergence of drug resistance resulting in cross-resistance to many unrelated drugs, a phenomenon termed multidrug resistance (MDR. Despite the current understanding of major factors which contribute to MDR mechanisms, there are many lines of evidence suggesting that it is a complex interplay of multiple factors which may be contributed by still unknown mechanisms. Coincidentally with the increased usage of antifungal drugs, the number of reports for antifungal drug resistance has also increased which further highlights the need for understanding novel molecular mechanisms which can be explored to combat MDR, namely, ROS, iron, hypoxia, lipids, morphogenesis, and transcriptional and signaling networks. Considering the worrying evolution of MDR and significance of C. albicans being the most prevalent human fungal pathogen, this review summarizes these new regulatory mechanisms which could be exploited to prevent MDR development in C. albicans as established from recent studies.

  20. Virulence Factors IN Fungi OF Systemic Mycoses

    Directory of Open Access Journals (Sweden)

    KUROKAWA Cilmery Suemi

    1998-01-01

    Full Text Available Pathogenic fungi that cause systemic mycoses retain several factors which allow their growth in adverse conditions provided by the host, leading to the establishment of the parasitic relationship and contributing to disease development. These factors are known as virulence factors which favor the infection process and the pathogenesis of the mycoses. The present study evaluates the virulence factors of pathogenic fungi such as Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum and Paracoccidioides brasiliensis in terms of thermotolerance, dimorphism, capsule or cell wall components as well as enzyme production. Virulence factors favor fungal adhesion, colonization, dissemination and the ability to survive in hostile environments and elude the immune response mechanisms of the host. Both the virulence factors presented by different fungi and the defense mechanisms provided by the host require action and interaction of complex processes whose knowledge allows a better understanding of the pathogenesis of systemic mycoses.

  1. Genome-Wide Transposon Mutagenesis Indicates that Mycobacterium marinum Customizes Its Virulence Mechanisms for Survival and Replication in Different Hosts

    KAUST Repository

    Weerdenburg, Eveline M.

    2015-02-17

    The interaction of environmental bacteria with unicellular eukaryotes is generally considered a major driving force for the evolution of intracellular pathogens, allowing them to survive and replicate in phagocytic cells of vertebrate hosts. To test this hypothesis on a genome-wide level, we determined for the intracellular pathogen Mycobacterium marinum whether it uses conserved strategies to exploit host cells from both protozoan and vertebrate origin. Using transposon-directed insertion site sequencing (TraDIS), we determined differences in genetic requirements for survival and replication in phagocytic cells of organisms from different kingdoms. In line with the general hypothesis, we identified a number of general virulence mechanisms, including the type VII protein secretion system ESX-1, biosynthesis of polyketide lipids, and utilization of sterols. However, we were also able to show that M. marinum contains an even larger set of host-specific virulence determinants, including proteins involved in the modification of surface glycolipids and, surprisingly, the auxiliary proteins of the ESX-1 system. Several of these factors were in fact counterproductive in other hosts. Therefore, M. marinum contains different sets of virulence factors that are tailored for specific hosts. Our data imply that although amoebae could function as a training ground for intracellular pathogens, they do not fully prepare pathogens for crossing species barriers.

  2. Crossing the line: selection and evolution of virulence traits.

    Directory of Open Access Journals (Sweden)

    2006-05-01

    Full Text Available The evolution of pathogens presents a paradox. Pathogenic species are often absolutely dependent on their host species for their propagation through evolutionary time, yet the pathogenic lifestyle requires that the host be damaged during this dependence. It is clear that pathogenic strategies are successful in evolutionary terms because a diverse array of pathogens exists in nature. Pathogens also evolve using a broad range of molecular mechanisms to acquire and modulate existing virulence traits in order to achieve this success. Detailing the benefit of enhanced selection derived through virulence and understanding the mechanisms through which virulence evolves are important to understanding the natural world and both have implications for human health.

  3. The Complete Genome Sequence of the Fish Pathogen Tenacibaculum maritimum Provides Insights into Virulence Mechanisms

    Directory of Open Access Journals (Sweden)

    David Pérez-Pascual

    2017-08-01

    Full Text Available Tenacibaculum maritimum is a devastating bacterial pathogen of wild and farmed marine fish with a broad host range and a worldwide distribution. We report here the complete genome sequence of the T. maritimum type strain NCIMB 2154T. The genome consists of a 3,435,971-base pair circular chromosome with 2,866 predicted protein-coding genes. Genes encoding the biosynthesis of exopolysaccharides, the type IX secretion system, iron uptake systems, adhesins, hemolysins, proteases, and glycoside hydrolases were identified. They are likely involved in the virulence process including immune escape, invasion, colonization, destruction of host tissues, and nutrient scavenging. Among the predicted virulence factors, type IX secretion-mediated and cell-surface exposed proteins were identified including an atypical sialidase, a sphingomyelinase and a chondroitin AC lyase which activities were demonstrated in vitro.

  4. Using Quantitative Spectrometry to Understand the Influence of Genetics and Nutritional Perturbations On the Virulence Potential ofStaphylococcus aureus.

    Science.gov (United States)

    Chapman, Jessica R; Balasubramanian, Divya; Tam, Kayan; Askenazi, Manor; Copin, Richard; Shopsin, Bo; Torres, Victor J; Ueberheide, Beatrix M

    2017-04-01

    Staphylococcus aureus ( Sa ) is the leading cause of a variety of bacterial infections ranging from superficial skin infections to invasive and life threatening diseases such as septic bacteremia, necrotizing pneumonia, and endocarditis. The success of Sa as a human pathogen is contributed to its ability to adapt to different environments by changing expression, production, or secretion of virulence factors. Although Sa immune evasion is well-studied, the regulation of virulence factors under different nutrient and growth conditions is still not well understood. Here, we used label-free quantitative mass spectrometry to quantify and compare the Sa exoproteins ( i.e. exoproteomes) of master regulator mutants or established reference strains. Different environmental conditions were addressed by growing the bacteria in rich or minimal media at different phases of growth. We observed clear differences in the composition of the exoproteomes depending on the genetic background or growth conditions. The relative abundance of cytotoxins determined in our study correlated well with differences in cytotoxicity measured by lysis of human neutrophils. Our findings demonstrate that label-free quantitative mass spectrometry is a versatile tool for predicting the virulence of bacterial strains and highlights the importance of the experimental design for in vitro studies. Furthermore, the results indicate that label-free proteomics can be used to cluster isolates into groups with similar virulence properties, highlighting the power of label-free quantitative mass spectrometry to distinguish Sa strains. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Edwardsiella comparative phylogenomics reveal the new intra/inter-species taxonomic relationships, virulence evolution and niche adaptation mechanisms.

    Directory of Open Access Journals (Sweden)

    Minjun Yang

    Full Text Available Edwardsiella bacteria are leading fish pathogens causing huge losses to aquaculture industries worldwide. E. tarda is a broad-host range pathogen that infects more than 20 species of fish and other animals including humans while E. ictaluri is host-adapted to channel catfish causing enteric septicemia of catfish (ESC. Thus, these two species consist of a useful comparative system for studying the intricacies of pathogen evolution. Here we present for the first time the phylogenomic comparisons of 8 genomes of E. tarda and E. ictaluri isolates. Genome-based phylogenetic analysis revealed that E. tarda could be separate into two kinds of genotypes (genotype I, EdwGI and genotype II, EdwGII based on the sequence similarity. E. tarda strains of EdwGI were clustered together with the E. ictaluri lineage and showed low sequence conservation to E. tarda strains of EdwGII. Multilocus sequence analysis (MLSA of 48 distinct Edwardsiella strains also supports the new taxonomic relationship of the lineages. We identified the type III and VI secretion systems (T3SS and T6SS as well as iron scavenging related genes that fulfilled the criteria of a key evolutionary factor likely facilitating the virulence evolution and adaptation to a broad range of hosts in EdwGI E. tarda. The surface structure-related genes may underlie the adaptive evolution of E. ictaluri in the host specification processes. Virulence and competition assays of the null mutants of the representative genes experimentally confirmed their contributive roles in the evolution/niche adaptive processes. We also reconstructed the hypothetical evolutionary pathway to highlight the virulence evolution and niche adaptation mechanisms of Edwardsiella. This study may facilitate the development of diagnostics, vaccines, and therapeutics for this under-studied pathogen.

  6. Crystal Structure of the LasA Virulence Factor from Pseudomonas aeruginosa: Substrate Specificity and Mechanism of M23 Metallopeptidases

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, James; Murphy, Loretta M.; Conners, Rebecca; Sessions, Richard B.; Gamblin, Steven J. (Wales); (Bristol Med Sci); (NIMR)

    2010-09-21

    Pseudomonas aeruginosa is an opportunist Gram-negative bacterial pathogen responsible for a wide range of infections in immunocompromized individuals and is a leading cause of mortality in cystic fibrosis patients. A number of secreted virulence factors, including various proteolytic enzymes, contribute to the establishment and maintenance of Pseudomonas infection. One such is LasA, an M23 metallopeptidase related to autolytic glycylglycine endopeptidases such as Staphylococcus aureus lysostaphin and LytM, and to DD-endopeptidases involved in entry of bacteriophage to host bacteria. LasA is implicated in a range of processes related to Pseudomonas virulence, including stimulating ectodomain shedding of the cell surface heparan sulphate proteoglycan syndecan-1 and elastin degradation in connective tissue. Here we present crystal structures of active LasA as a complex with tartrate and in the uncomplexed form. While the overall fold resembles that of the other M23 family members, the LasA active site is less constricted and utilizes a different set of metal ligands. The active site of uncomplexed LasA contains a five-coordinate zinc ion with trigonal bipyramidal geometry and two metal-bound water molecules. Using these structures as a starting point, we propose a model for substrate binding by LasA that explains its activity against a wider range of substrates than those used by related lytic enzymes, and offer a catalytic mechanism for M23 metallopeptidases consistent with available structural and mutagenesis data. Our results highlight how LasA is a structurally distinct member of this endopeptidase family, consistent with its activity against a wider range of substrates and with its multiple roles in Pseudomonas virulence.

  7. Insights into a multidrug resistant Escherichia coli pathogen of the globally disseminated ST131 lineage: genome analysis and virulence mechanisms.

    Science.gov (United States)

    Totsika, Makrina; Beatson, Scott A; Sarkar, Sohinee; Phan, Minh-Duy; Petty, Nicola K; Bachmann, Nathan; Szubert, Marek; Sidjabat, Hanna E; Paterson, David L; Upton, Mathew; Schembri, Mark A

    2011-01-01

    Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum β-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI.

  8. Molecular mechanisms for the subversion of MyD88 signaling by TcpC from virulent uropathogenic Escherichia coli.

    Science.gov (United States)

    Snyder, Greg A; Cirl, Christine; Jiang, Jiansheng; Chen, Kang; Waldhuber, Anna; Smith, Patrick; Römmler, Franziska; Snyder, Nathaniel; Fresquez, Theresa; Dürr, Susanne; Tjandra, Nico; Miethke, Thomas; Xiao, Tsan Sam

    2013-04-23

    The Toll/IL-1 receptor (TIR) domains are crucial signaling modules during innate immune responses involving the Toll-like receptors (TLRs) and IL-1 receptor (IL-1R). Myeloid differential factor 88 (MyD88) is a central TIR domain-containing adapter molecule responsible for nearly all TLR-mediated signaling and is targeted by a TIR domain-containing protein C (TcpC) from virulent uropathogenic Escherichia coli, a common human pathogen. The mechanism of such molecular antagonism has remained elusive. We present the crystal structure of the MyD88 TIR domain with distinct loop conformations that underscore the functional specialization of the adapter, receptor, and microbial TIR domains. Our structural analyses shed light on the genetic mutations at these loops as well as the Poc site. We demonstrate that TcpC directly associates with MyD88 and TLR4 through its predicted DD and BB loops to impair the TLR-induced cytokine induction. Furthermore, NMR titration experiments identify the unique CD, DE, and EE loops from MyD88 at the TcpC-interacting surface, suggesting that TcpC specifically engages these MyD88 structural elements for immune suppression. These findings thus provide a molecular basis for the subversion of TLR signaling by the uropathogenic E. coli virulence factor TcpC and furnish a framework for the design of novel therapeutic agents that modulate immune activation.

  9. Regulation of Virulence in Staphylococcus aureus: Molecular Mechanisms and Remaining Puzzles.

    Science.gov (United States)

    Wang, Boyuan; Muir, Tom W

    2016-02-18

    The agr locus encodes a quorum-sensing (QS) circuit required for the virulence of a spectrum of Gram-positive pathogens and is, therefore, regarded as an important target for the development of chemotherapeutics. In recent years, many of the biochemical events in the Staphylococcus aureus agr circuit have been reconstituted and subject to quantitative analysis in vitro. This work, in conjunction with structural studies on several key players in the signaling circuit, has furnished mechanistic insights into the regulation and evolution of the agr QS system. Here, we review this progress and discuss the remaining open questions in the area. We also highlight advances in the discovery of small-molecule agr modulators and how the newly available biochemical and structural information might be leveraged for the design of next-generation therapeutics targeting the agr system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Acute virulent infection with feline immunodeficiency virus (FIV) results in lymphomagenesis via an indirect mechanism.

    Science.gov (United States)

    Magden, Elizabeth; Miller, Craig; MacMillan, Martha; Bielefeldt-Ohmann, Helle; Avery, Anne; Quackenbush, Sandra L; Vandewoude, Sue

    2013-02-20

    Four cats (24%) experimentally infected with FIV unexpectedly developed neoplastic changes within four months of inoculation. While FIV has previously been associated with neoplasia, the rapidity and high attack rate seen here is highly unusual. PCR for antigen receptor rearrangements (PARR) detected clonally rearranged T cells in two animals diagnosed with B cell follicular lymphoma by classical means. All cats were negative for feline leukemia virus; gamma-herpesvirus DNA was not amplified using degenerate primers. FIV proviral load in neoplastic tissue was two orders of magnitude lower than in the periphery, lower in neoplastic vs non-neoplastic lymph node, and clonal integration was not detected. We hypothesize that neoplasia was secondary to FIV immune dysregulation, and show that PARR can augment our capacity to phenotype these tumors and distinguish follicular hyperplasia from lymphoma. Age of exposure and relative virulence of the inoculum likely contributed to this unusual presentation of FIV infection. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Bacteriophage Resistance Mechanisms in the Fish Pathogen Flavobacterium psychrophilum: Linking Genomic Mutations to Changes in Bacterial Virulence Factors

    DEFF Research Database (Denmark)

    Castillo, Daniel; Christiansen, Rói Hammershaimb; Dalsgaard, Inger

    2015-01-01

    requires overcoming the selection for phage resistance in the bacterial populations. Here, we analyzed resistance mechanisms in F. psychrophilum after phage exposure using whole-genome sequencing of the ancestral phage-sensitive strain 950106-1/1 and six phage-resistant isolates. The phage-resistant...... resistance and the genetic modifications were supported by direct measurements of bacteriophage adsorption rates, biofilm formation, and secretion of extracellular enzymes, which were all impaired in the resistant strains, probably due to superficial structural changes. The clustered regularly interspaced...... were associated with a number of derived effects on the physiological properties of the pathogen, including reduced virulence under in vitro conditions. Consequently, phage-driven physiological changes associated with resistance may have implications for the impact of the pathogen in aquaculture...

  12. The Effects of Low-Shear Mechanical Stress on Yersinia pestis Virulence

    Science.gov (United States)

    Lawal, Abidat; Jejelowo, Olufisayo A.; Rosenzweig, Jason A.

    2010-11-01

    Manned space exploration has created a need to evaluate the effects of spacelike stress on pathogenic and opportunistic microbes astronauts could carry with them to the International Space Station and beyond. Yersinia pestis (YP) causes bubonic, septicemic, and pneumonic plague and is capable of killing infected patients within 3-7 days. In this study, low-shear modeled microgravity (LSMMG), a spacelike stress, was used to physically stress YP; and its effects on proliferation, cold growth, and type III secretion system (T3SS) function were evaluated. YP was grown to saturation in either LSMMG or normal gravity (NG) conditions prior to being used for RAW 246.7 cell infections, HeLa cell infections, and Yop secretion assays. A mutant strain of YP (ΔyopB) that lacks the ability to inject Yersinia outer membrane proteins (Yops) into the host cell was used as a negative control in cell infection experiments. Our experimental results indicate that YP cultivated under LSMMG resulted in reduced YopM production and secretion compared to its NG-grown counterpart. Similarly, NG-grown YP induced more cell rounding in HeLa cells than did the LSMMG-grown YP, which suggests that LSMMG somehow impairs T3SS optimum function. Also, LSMMG-grown YP used to infect cultured RAW 246.7 cells showed a similar pattern of dysfunction in that it proliferated less than did its NG-grown counterpart during an 8-hour infection period. This study suggests that LSMMG can attenuate bacterial virulence contrary to previously published data that have demonstrated LSMMG-induced hypervirulence of other Gram-negative enterics.

  13. Structural and Molecular Mechanism of CdpR Involved in Quorum-Sensing and Bacterial Virulence in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Jingru Zhao

    2016-04-01

    Full Text Available Although quorum-sensing (QS systems are important regulators of virulence gene expression in the opportunistic human pathogen Pseudomonas aeruginosa, their detailed regulatory mechanisms have not been fully characterized. Here, we show that deletion of PA2588 resulted in increased production of pyocyanin and biofilm, as well as enhanced pathogenicity in a mouse model. To gain insights into the function of PA2588, we performed a ChIP-seq assay and identified 28 targets of PA2588, including the intergenic region between PA2588 and pqsH, which encodes the key synthase of Pseudomonas quinolone signal (PQS. Though the C-terminal domain was similar to DNA-binding regions of other AraC family members, structural studies revealed that PA2588 has a novel fold at the N-terminal region (NTR, and its C-terminal HTH (helix-turn-helix domain is also unique in DNA recognition. We also demonstrated that the adaptor protein ClpS, an essential regulator of ATP-dependent protease ClpAP, directly interacted with PA2588 before delivering CdpR to ClpAP for degradation. We named PA2588 as CdpR (ClpAP-degradation and pathogenicity Regulator. Moreover, deletion of clpP or clpS/clpA promotes bacterial survival in a mouse model of acute pneumonia infection. Taken together, this study uncovered that CdpR is an important QS regulator, which can interact with the ClpAS-P system to regulate the expression of virulence factors and pathogenicity.

  14. Understanding Mechanism of Photocatalytic Microbial Decontamination of Environmental Wastewater

    Directory of Open Access Journals (Sweden)

    Chhabilal Regmi

    2018-02-01

    Full Text Available Several photocatalytic nanoparticles are synthesized and studied for potential application for the degradation of organic and biological wastes. Although these materials degrade organic compounds by advance oxidation process, the exact mechanisms of microbial decontamination remains partially known. Understanding the real mechanisms of these materials for microbial cell death and growth inhibition helps to fabricate more efficient semiconductor photocatalyst for large-scale decontamination of environmental wastewater or industries and hospitals/biomedical labs generating highly pathogenic bacteria and toxic molecules containing liquid waste by designing a reactor. Recent studies on microbial decontamination by photocatalytic nanoparticles and their possible mechanisms of action is highlighted with examples in this mini review.

  15. AUTOMOTIVE DIESEL MAINTENANCE 2. UNIT I, UNDERSTANDING MECHANICAL CLUTCHES.

    Science.gov (United States)

    Minnesota State Dept. of Education, St. Paul. Div. of Vocational and Technical Education.

    ONE OF A 25-MODULE COURSE DESIGNED TO UPGRADE THE JOB SKILLS AND TECHNICAL KNOWLEDGE OF DIESEL MAINENANCE MECHANICS THIS MATERIAL WAS DEVELOPED BY INDUSTRIAL TRAINING AND SUBJECT-MATTER SPECIALISTS AND TESTED IN INDUSTRIAL TRAINING SITUATIONS. THE PURPOSE OF THIS FIRST UNIT IS TO DEVELOP AN UNDERSTANDING OF COMPONENTS, OPERATION, AND ADJUSTMENTS…

  16. Student Understanding of Time Dependence in Quantum Mechanics

    Science.gov (United States)

    Emigh, Paul J.; Passante, Gina; Shaffer, Peter S.

    2015-01-01

    The time evolution of quantum states is arguably one of the more difficult ideas in quantum mechanics. In this article, we report on results from an investigation of student understanding of this topic after lecture instruction. We demonstrate specific problems that students have in applying time dependence to quantum systems and in recognizing…

  17. Advanced waterflooding in chalk reservoirs: Understanding of underlying mechanisms

    DEFF Research Database (Denmark)

    Zahid, Adeel; Sandersen, Sara Bülow; Stenby, Erling Halfdan

    2011-01-01

    Over the last decade, a number of studies have shown SO42−, Ca2+ and Mg2+ to be potential determining ions, which may be added to the injected brine for improving oil recovery during waterflooding in chalk reservoirs. However the understanding of the mechanism leading to an increase in oil recove...... of a microemulsion phase could be the possible reasons for the observed increase in oil recovery with sulfate ions at high temperature in chalk reservoirs besides the mechanism of the rock wettability alteration, which has been reported in most previous studies.......Over the last decade, a number of studies have shown SO42−, Ca2+ and Mg2+ to be potential determining ions, which may be added to the injected brine for improving oil recovery during waterflooding in chalk reservoirs. However the understanding of the mechanism leading to an increase in oil recovery...

  18. Global Regulator of Virulence A (GrvA) Coordinates Expression of Discrete Pathogenic Mechanisms in Enterohemorrhagic Escherichia coli through Interactions with GadW-GadE.

    Science.gov (United States)

    Morgan, Jason K; Carroll, Ronan K; Harro, Carly M; Vendura, Khoury W; Shaw, Lindsey N; Riordan, James T

    2016-02-01

    Global regulator of virulence A (GrvA) is a ToxR-family transcriptional regulator that activates locus of enterocyte effacement (LEE)-dependent adherence in enterohemorrhagic Escherichia coli (EHEC). LEE activation by GrvA requires the Rcs phosphorelay response regulator RcsB and is sensitive to physiologically relevant concentrations of bicarbonate, a known stimulant of virulence systems in intestinal pathogens. This study determines the genomic scale of GrvA-dependent regulation and uncovers details of the molecular mechanism underlying GrvA-dependent regulation of pathogenic mechanisms in EHEC. In a grvA-null background of EHEC strain TW14359, RNA sequencing analysis revealed the altered expression of over 700 genes, including the downregulation of LEE- and non-LEE-encoded effectors and the upregulation of genes for glutamate-dependent acid resistance (GDAR). Upregulation of GDAR genes corresponded with a marked increase in acid resistance. GrvA-dependent regulation of GDAR and the LEE required gadE, the central activator of GDAR genes and a direct repressor of the LEE. Control of gadE by GrvA was further determined to occur through downregulation of the gadE activator GadW. This interaction of GrvA with GadW-GadE represses the acid resistance phenotype, while it concomitantly activates the LEE-dependent adherence and secretion of immune subversion effectors. The results of this study significantly broaden the scope of GrvA-dependent regulation and its role in EHEC pathogenesis. Enterohemorrhagic Escherichia coli (EHEC) is an intestinal human pathogen causing acute hemorrhagic colitis and life-threatening hemolytic-uremic syndrome. For successful transmission and gut colonization, EHEC relies on the glutamate-dependent acid resistance (GDAR) system and a type III secretion apparatus, encoded on the LEE pathogenicity island. This study investigates the mechanism whereby the DNA-binding regulator GrvA coordinates activation of the LEE with repression of GDAR

  19. Association between antimicrobial resistance and virulence in Escherichia coli.

    Science.gov (United States)

    Da Silva, Gabriela Jorge; Mendonça, Nuno

    2012-01-01

    Escherichia coli represents a major cause of morbidity and mortality worldwide. The treatment of E. coli infections is now threatened by the emergence of antimicrobial resistance. The dissemination of resistance is associated with genetic mobile elements, such as plasmids, that may also carry virulence determinants. A proficient pathogen should be virulent, resistant to antibiotics, and epidemic. However, the interplay between resistance and virulence is poorly understood. This review aims to critically discuss the association and linked transmission of both resistance and virulence traits in strains from extraintestinal infections in E. coli, and intestinal pathotypes. Despite the numerous controversies on this topic, findings from research published to date indicate that there is a link between resistance and virulence, as illustrated by the successful E. coli ST131 epidemic clone. Perhaps the most commonly accepted view is that resistance to quinolones is linked to a loss of virulence factors. However, the low virulent phylogenetic groups might be more prone to acquire resistance to quinolones. Specific characteristics of the E. coli genome that have yet to be identified may contribute to such genetic linkages. Research based on bacterial populations is sorely needed to help understand the molecular mechanisms underlying the association between resistance and virulence, that, in turn, may help manage the future disseminations of infectious diseases in their entirety.

  20. Advances in the understanding of crystal growth mechanisms

    CERN Document Server

    Nishinaga, T; Harada, J; Sasaki, A; Takei, H

    1997-01-01

    This book contains the results of a research project entitled Crystal Growth Mechanisms on an Atomic Scale, which was carried out for 3 years by some 72 reseachers. Until recently in Japan, only the technological aspects of crystal growth have been emphasized and attention was paid only to its importance in industry. However the scientific aspects also need to be considered so that the technology of crystal growth can be developed even further. This project therefore aimed at understanding crystal growth and the emphasis was on finding growth mechanisms on an atomic scale.

  1. Macrolide resistance mechanisms and virulence factors in erythromycin-resistant Campylobacter species isolated from chicken and swine feces and carcasses.

    Science.gov (United States)

    Lim, Suk-Kyung; Moon, Dong-Chan; Chae, Myung Hwa; Kim, Hae Ji; Nam, Hyang-Mi; Kim, Su-Ran; Jang, Gum-Chan; Lee, Kichan; Jung, Suk-Chan; Lee, Hee-Soo

    2017-01-10

    Resistance to antimicrobials was measured in 73 isolates of Campylobacter jejuni (C. jejuni) and 121 isolates of Campylobacter coli (C. coli) from chicken and swine feces and carcasses in Korea. Both bacterial species showed the highest resistance to (fluoro) quinolones (ciprofloxacin and nalidixic acid) out of the nine antimicrobials tested. Erythromycin resistance was much higher in C. coli (19.0%, 23/121) than in C. jejuni (6.8%, 5/73). The mutation in the 23S rRNA gene was primarily responsible for macrolide resistance in Campylobacter isolates. Several amino acid substitutions in the L4 and L22 ribosomal proteins may play a role in the mechanism of resistance, but the role requires further evaluation. A total of eight virulence genes were detected in 28 erythromycin-resistant Campylobacter isolates. All C. jejuni isolates carried more than four such genes, while C. coli isolates carried fewer than three such genes. The high rate of resistance highlights the need to employ more prudent use of critically important antimicrobials, such as fluoroquinolones and macrolides, in swine and poultry production, and to more carefully monitor antimicrobial resistance in Campylobacter isolates in food animals.

  2. Understanding and imitating unfamiliar actions: distinct underlying mechanisms.

    Directory of Open Access Journals (Sweden)

    Joana C Carmo

    Full Text Available The human "mirror neuron system" has been proposed to be the neural substrate that underlies understanding and, possibly, imitating actions. However, since the brain activity with mirror properties seems insufficient to provide a good description for imitation of actions outside one's own repertoire, the existence of supplementary processes has been proposed. Moreover, it is unclear whether action observation requires the same neural mechanisms as the explicit access to their meaning. The aim of this study was two-fold as we investigated whether action observation requires different processes depending on 1 whether the ultimate goal is to imitate or understand the presented actions and 2 whether the to-be-imitated actions are familiar or unfamiliar to the subject. Participants were presented with both meaningful familiar actions and meaningless unfamiliar actions that they had to either imitate or discriminate later. Event-related Potentials were used as differences in brain activity could have been masked by the use of other techniques with lower temporal resolution. In the imitation task, a sustained left frontal negativity was more pronounced for meaningless actions than for meaningful ones, starting from an early time-window. Conversely, observing unfamiliar versus familiar actions with the intention of discriminating them led to marked differences over right centro-posterior scalp regions, in both middle and latest time-windows. These findings suggest that action imitation and action understanding may be sustained by dissociable mechanisms: while imitation of unfamiliar actions activates left frontal processes, that are likely to be related to learning mechanisms, action understanding involves dedicated operations which probably require right posterior regions, consistent with their involvement in social interactions.

  3. Understanding mechanisms of toxicity: Insights from drug discovery research

    International Nuclear Information System (INIS)

    Houck, Keith A.; Kavlock, Robert J.

    2008-01-01

    Toxicology continues to rely heavily on use of animal testing for prediction of potential for toxicity in humans. Where mechanisms of toxicity have been elucidated, for example endocrine disruption by xenoestrogens binding to the estrogen receptor, in vitro assays have been developed as surrogate assays for toxicity prediction. This mechanistic information can be combined with other data such as exposure levels to inform a risk assessment for the chemical. However, there remains a paucity of such mechanistic assays due at least in part to lack of methods to determine specific mechanisms of toxicity for many toxicants. A means to address this deficiency lies in utilization of a vast repertoire of tools developed by the drug discovery industry for interrogating the bioactivity of chemicals. This review describes the application of high-throughput screening assays as experimental tools for profiling chemicals for potential for toxicity and understanding underlying mechanisms. The accessibility of broad panels of assays covering an array of protein families permits evaluation of chemicals for their ability to directly modulate many potential targets of toxicity. In addition, advances in cell-based screening have yielded tools capable of reporting the effects of chemicals on numerous critical cell signaling pathways and cell health parameters. Novel, more complex cellular systems are being used to model mammalian tissues and the consequences of compound treatment. Finally, high-throughput technology is being applied to model organism screens to understand mechanisms of toxicity. However, a number of formidable challenges to these methods remain to be overcome before they are widely applicable. Integration of successful approaches will contribute towards building a systems approach to toxicology that will provide mechanistic understanding of the effects of chemicals on biological systems and aid in rationale risk assessments

  4. Structure, Adsorption to Host, and Infection Mechanism of Virulent Lactococcal Phage p2

    Science.gov (United States)

    Bebeacua, Cecilia; Tremblay, Denise; Farenc, Carine; Chapot-Chartier, Marie-Pierre; Sadovskaya, Irina; van Heel, Marin; Veesler, David

    2013-01-01

    Lactococcal siphophages from the 936 and P335 groups infect the Gram-positive bacterium Lactococcus lactis using receptor binding proteins (RBPs) attached to their baseplate, a large multiprotein complex at the distal part of the tail. We have previously reported the crystal and electron microscopy (EM) structures of the baseplates of phages p2 (936 group) and TP901-1 (P335 group) as well as the full EM structure of the TP901-1 virion. Here, we report the complete EM structure of siphophage p2, including its capsid, connector complex, tail, and baseplate. Furthermore, we show that the p2 tail is characterized by the presence of protruding decorations, which are related to adhesins and are likely contributed by the major tail protein C-terminal domains. This feature is reminiscent of the tail of Escherichia coli phage λ and Bacillus subtilis phage SPP1 and might point to a common mechanism for establishing initial interactions with their bacterial hosts. Comparative analyses showed that the architecture of the phage p2 baseplate differs largely from that of lactococcal phage TP901-1. We quantified the interaction of its RBP with the saccharidic receptor and determined that specificity is due to lower koff values of the RBP/saccharidic dissociation. Taken together, these results suggest that the infection of L. lactis strains by phage p2 is a multistep process that involves reversible attachment, followed by baseplate activation, specific attachment of the RBPs to the saccharidic receptor, and DNA ejection. PMID:24027307

  5. Understanding the mechanism of nanoparticle formation in wire explosion process

    International Nuclear Information System (INIS)

    Bora, B.; Wong, C.S.; Bhuyan, H.; Lee, Y.S.; Yap, S.L.; Favre, M.

    2013-01-01

    The mechanism of nanoparticle formation by wire explosion process has been investigated by optical emission spectroscopy in Antony et al. 2010 [2] [J Quant Spectrosc Radiat Transfer 2010; 111:2509]. It was reported that the size of the nanoparticles formed in Ar ambience increases with increasing pressure, while an opposite trend was observed for the nanoparticles produced in N 2 and He ambiences. However, the physics behind this opposite trend seems unclear. In this work, we have investigated the probable mechanism behind the opposite trend in particle size with pressure of different gases and understand the mechanism of nanoparticle formation in wire explosion process. The experiment was carried out to investigate the effect of ambient gas species (Ar and N 2 ) and pressure on arc plasma formation and its corresponding effects on the characteristics of the produced nanoparticles in wire explosion process. Our results show that the arc plasma formation is probably the mechanism that may account for the opposite trend of particle size with pressure of different gases. -- Highlights: ► Cu nanoparticles have been synthesized by wire explosion technique. ► Investigate the effect of the ambient gas species and pressure. ► Arc plasma formation in wire explosion process is investigated. ► Arc plasma formation plays a crucial role in characteristic of the nanoparticles

  6. Understanding the thermal, mechanical and electrical properties of epoxy nanocomposites

    International Nuclear Information System (INIS)

    Sarathi, R.; Sahu, R.K.; Rajeshkumar, P.

    2007-01-01

    In the present work, the electrical, mechanical and thermal properties of epoxy nanocomposite materials were studied. The electrical insulation characteristics were analyzed through short time breakdown voltage test, accelerated electrical ageing test, and by tracking test. The breakdown voltage increases with increase in nano-clay content up to 5 wt%, under AC and DC voltages. The volume resistivity, permittivity and tan(δ) of the epoxy nanocomposites were measured. The Weibull studies indicate that addition of nanoclay upto 5 wt% enhances the characteristic life of epoxy nanocomposite insulation material. The tracking test results indicate that the tracking time is high with epoxy nanocomposites as compared to pure epoxy. Ageing studies were carried out to understand the surface characteristic variation through contact angle measurement. The hydrophobicity of the insulating material was analysed through contact angle measurement. The diffusion coefficients of the material with different percentage of clay in epoxy nanocomposites were calculated. The exfoliation characteristics in epoxy nanocomposites were analyzed through wide angle X-ray diffraction (WAXD) studies. The thermal behaviour of the epoxy nanocomposites was analyzed by carrying out thermo gravimetric-differential thermal analysis (TG-DTA) studies. Heat deflection temperature of the material was measured to understand the stability of the material for intermittent temperature variation. The dynamic mechanical analysis (DMA) results indicated that storage modulus of the material increases with small amount of clay in epoxy resin. The activation energy of the material was calculated from the DMA results

  7. The pathogenic mechanism of the Mycobacterium ulcerans virulence factor, mycolactone, depends on blockade of protein translocation into the ER.

    Directory of Open Access Journals (Sweden)

    Belinda S Hall

    2014-04-01

    Full Text Available Infection with Mycobacterium ulcerans is characterised by tissue necrosis and immunosuppression due to mycolactone, the necessary and sufficient virulence factor for Buruli ulcer disease pathology. Many of its effects are known to involve down-regulation of specific proteins implicated in important cellular processes, such as immune responses and cell adhesion. We have previously shown mycolactone completely blocks the production of LPS-dependent proinflammatory mediators post-transcriptionally. Using polysome profiling we now demonstrate conclusively that mycolactone does not prevent translation of TNF, IL-6 and Cox-2 mRNAs in macrophages. Instead, it inhibits the production of these, along with nearly all other (induced and constitutive proteins that transit through the ER. This is due to a blockade of protein translocation and subsequent degradation of aberrantly located protein. Several lines of evidence support this transformative explanation of mycolactone function. First, cellular TNF and Cox-2 can be once more detected if the action of the 26S proteasome is inhibited concurrently. Second, restored protein is found in the cytosol, indicating an inability to translocate. Third, in vitro translation assays show mycolactone prevents the translocation of TNF and other proteins into the ER. This is specific as the insertion of tail-anchored proteins into the ER is unaffected showing that the ER remains structurally intact. Fourth, metabolic labelling reveals a near-complete loss of glycosylated and secreted proteins from treated cells, whereas cytosolic proteins are unaffected. Notably, the profound lack of glycosylated and secreted protein production is apparent in a range of different disease-relevant cell types. These studies provide a new mechanism underlying mycolactone's observed pathological activities both in vitro and in vivo. Mycolactone-dependent inhibition of protein translocation into the ER not only explains the deficit of innate

  8. Understanding Neurological Disease Mechanisms in the Era of Epigenetics

    Science.gov (United States)

    Qureshi, Irfan A.; Mehler, Mark F.

    2015-01-01

    The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type–specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues. PMID:23571666

  9. Differential compartmentalization of Streptococcus pyogenes virulence factors and host protein binding properties as a mechanism for host adaptation.

    Science.gov (United States)

    Kilsgård, Ola; Karlsson, Christofer; Malmström, Erik; Malmström, Johan

    2016-11-01

    Streptococcus pyogenes is an important human pathogen responsible for substantial morbidity and mortality worldwide. Although S. pyogenes is a strictly human pathogen with no other known animal reservoir, several murine infection models exist to explore different aspects of the bacterial pathogenesis. Inoculating mice with wild-type S. pyogenes strains can result in the generation of new bacterial phenotypes that are hypervirulent compared to the original inoculum. In this study, we used a serial mass spectrometry based proteomics strategy to investigate if these hypervirulent strains have an altered distribution of virulence proteins across the intracellular, surface associated and secreted bacterial compartments and if any change in compartmentalization can alter the protein-protein interaction network between bacteria and host proteins. Quantitative analysis of the S. pyogenes surface and secreted proteomes revealed that animal passaged strains are associated with significantly higher amount of virulence factors on the bacterial surface and in the media. This altered virulence factor compartmentalization results in increased binding of several mouse plasma proteins to the bacterial surface, a trend that was consistent for mouse plasma from several different mouse strains. In general, both the wild-type strain and animal passaged strain were capable of binding high amounts of human plasma proteins. However, compared to the non-passaged strains, the animal passaged strains displayed an increased ability to bind mouse plasma proteins, in particular for M protein binders, indicating that the increased affinity for mouse blood plasma proteins is a consequence of host adaptation of this pathogen to a new host. In conclusion, plotting the total amount of virulence factors against the total amount of plasma proteins associated to the bacterial surface could clearly separate out animal passaged strains from wild type strains indicating a virulence model that could

  10. When green and red mycology meet: Impressions from an interdisciplinary forum on virulence mechanisms of phyto- and human-pathogenic fungi.

    Science.gov (United States)

    Yu, Yidong; Hube, Bernhard; Kämper, Jörg; Meyer, Vera; Krappmann, Sven

    2017-10-03

    Fungal infections pose a constant threat to plants and humans, but detailed knowledge about pathogenesis, immunity, or virulence is rather scarce. Due to the fact that a certain overlap in the armoury of infection exists between plant- and human-pathogenic fungi, an interdisciplinary forum was held in October 2016 at the Institute for Clinical Microbiology, Immunology and Hygiene in Erlangen under the organisational umbrella from two special interest groups of German microbial societies. Scientific exchange and intense discussion of this timely topic was fostered by bringing together renowned experts in their respective fields to present their thoughts and recent findings in the course of a plenary lecture and six themed sessions, accompanied by oral and poster contributions of young researchers. By targeting the topic of fungal virulence mechanisms from various angles and in the context of plant and human hosts, some common grounds and exciting perspectives could be deduced during this vibrant scientific event.

  11. Understanding Liver Regeneration: From Mechanisms to Regenerative Medicine.

    Science.gov (United States)

    Gilgenkrantz, Hélène; Collin de l'Hortet, Alexandra

    2018-04-16

    Liver regeneration is a complex and unique process. When two-thirds of a mouse liver is removed, the remaining liver recovers its initial weight in approximately 10 days. The understanding of the mechanisms responsible for liver regeneration may help patients needing large liver resections or transplantation and may be applied to the field of regenerative medicine. All differentiated hepatocytes are capable of self-renewal, but different subpopulations of hepatocytes seem to have distinct proliferative abilities. In the setting of chronic liver diseases, a ductular reaction ensues in which liver progenitor cells (LPCs) proliferate in the periportal region. Although these LPCs have the capacity to differentiate into hepatocytes and biliary cells in vitro, their ability to participate in liver regeneration is far from clear. Their expansion has even been associated with increased fibrosis and poorer prognosis in chronic liver diseases. Controversies also remain on their origin: lineage studies in experimental mouse models of chronic injury have recently suggested that these LPCs originate from hepatocyte dedifferentiation, whereas in other situations, they seem to come from cholangiocytes. This review summarizes data published in the past 5 years in the liver regeneration field, discusses the mechanisms leading to regeneration disruption in chronic liver disorders, and addresses the potential use of novel approaches for regenerative medicine. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  12. Cryptosporidium Pathogenicity and Virulence

    Science.gov (United States)

    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

  13. Bronchopulmonary dysplasia: understanding of the underlying pathological mechanisms

    Directory of Open Access Journals (Sweden)

    Daniela Fanni

    2014-06-01

    Full Text Available Bronchopulmonary dysplasia (BPD is a chronic lung disease occurring in preterm infants, typically before 28 weeks of gestational age, characterized by a prolonged need for supplemental oxygen or positive pressure ventilation. The normal stages of lung development and their relation to the timing of preterm birth is strategic in order to understand the pathogenesis of BPD. In embryonic and pseudoglandular stages the lungs arise from the anterior foregut as a bud where the branching morphogenesis generate a tree-like network of airways. The canalicular stage is characterized by increasing proliferation of distal lung epithelial cells and rapid expansion of the intra-acinar capillaries. The complexity of the airways increases, secondary crests begin to form and full maturation of the alveolus occurs during the saccular and the alveolar stages. Mesechyme components, expecially elastin and myofibroblast, display a major role in normal lung development. BPD is thought to result after an acute insult to the neonatal lung following therapy with oxygen supplementation and mechanical ventilation. Chorioamnionitis, infections and genetic susceptibly are hypothesized to contribute to the injury that affect the normal human lung development. Abnormalities in the mesenchyme were consistently seen in association with inhibition of alveolarization. The pathological features that characterize BPD are complex and differ according with the disease progression. Alveolar simplification, interstitial fibrosis, septal thickness, large airways, smooth muscle hypertrophy, fetal artery persistance and decrease in the arterial number can be histologically observed. In conclusion, in order to reach a complete clinical-pathological diagnosis, the correlation of the pathological features with the fundamental steps of lung morphogenesis and a strict dialogue between the neonatologist and the perinatal pathologist are required. Given these conditions, in our experience, a

  14. Infectious haematopoietic necrosis virus genogroup-specific virulence mechanisms in sockeye salmon, Oncorhynchus nerka (Walbaum), from Redfish Lake, Idaho

    Science.gov (United States)

    Purcell, M.K.; Garver, K.A.; Conway, C.; Elliott, D.G.; Kurath, G.

    2009-01-01

    Characterization of infectious haematopoietic necrosis virus (IHNV) field isolates from North America has established three main genogroups (U, M and L) that differ in host-specific virulence. In sockeye salmon, Oncorhynchus nerka, the U genogroup is highly virulent, whereas the M genogroup is nearly non-pathogenic. In this study, we sought to characterize the virus-host dynamics that contribute to genogroup-specific virulence in a captive stock of sockeye salmon from Redfish Lake in Idaho. Juvenile sockeye salmon were challenged by immersion and injection with either a representative U or M viral strain and sampled periodically until 14 days post-infection (p.i.). Fish challenged with each strain had positive viral titre by day 3, regardless of challenge route, but the fish exposed to the M genogroup virus had significantly lower virus titres than fish exposed to the U genogroup virus. Gene expression analysis by quantitative reverse transcriptase PCR was used to simultaneously assess viral load and host interferon (IFN) response in the anterior kidney. Viral load was significantly higher in the U-challenged fish relative to M-challenged fish. Both viruses induced expression of the IFN-stimulated genes (ISGs), but expression was usually significantly lower in the M-challenged group, particularly at later time points (7 and 14 days p.i.). However, ISG expression was comparable with 3 days post-immersion challenge despite a significant difference in viral load. Our data indicated that the M genogroup virus entered the host, replicated and spread in the sockeye salmon tissues, but to a lesser extent than the U genogroup. Both virus types induced a host IFN response, but the high virulence strain (U) continued to replicate in the presence of this response, whereas the low virulence strain (M) was cleared below detectable levels. We hypothesize that high virulence is associated with early in vivo replication allowing the virus to achieve a threshold level, which the

  15. Understanding the mechanisms behind coking pressure: Relationship to pore structure

    Energy Technology Data Exchange (ETDEWEB)

    John J. Duffy; M. Castro Diaz; Colin E. Snape; Karen M. Steel; Merrick R. Mahoney [University of Nottingham, Nottingham (United Kingdom). Nottingham Fuel and Energy Centre, School of Chemical, Environmental and Mining Engineering

    2007-09-15

    Three low volatile coals A, B and C with oven wall pressures of 100 kPa, 60 kPa and 20 kPa respectively were investigated using high-temperature rheometry, {sup 1}H NMR, thermogravimetric analysis and SEM, with the primary aim to better understand the mechanisms behind the coking pressure phenomenon. Rheometer plate displacement measurements ({Delta}L) have shown differences in the expansion and contraction behaviour of the three coals, which seem to correlate with changes in rheological properties; while SEM images have shown that the expansion process coincides with development of pore structure. It is considered that the point of maximum plate height ({Delta}L{sub max}) prior to contraction may be indicative of a cell opening or pore network forming process, based on analogies with other foam systems. Such a process may be considered important for coking pressure since it provides a potential mechanism for volatile escape, relieving internal gas pressure and inducing charge contraction. For coal C, which has the highest fluidity {delta}L{sub max} occurs quite early in the softening process and consequently a large degree of contraction is observed; while for the lower fluidity coal B, the process is delayed since pore development and consequently wall thinning progress at a slower rate. When {Delta}L{sub max} is attained, a lower degree of contraction is observed because the event occurs closer to resolidification where the increasing viscosity/elasticity can stabilise the expanded pore structure. For coal A which is relatively high fluidity, but also high coking pressure, a greater degree of swelling is observed prior to cell rupture, which may be due to greater fluid elasticity during the expansion process. This excessive expansion is considered to be a potential reason for its high coking pressure. 58 refs., 15 figs., 1 tab.

  16. Understanding sleep-wake mechanisms and drug discovery.

    Science.gov (United States)

    Equihua-Benítez, Ana Clementina; Guzmán-Vásquez, Khalil; Drucker-Colín, René

    2017-07-01

    Although not discernible at first glance, sleep is a highly active and regulated brain state. Although we spend practically one third of our lifetimes in this stage, its importance is often taken for granted. Sleep loss can lead to disease, error and economic loss. Our understanding of how sleep is achieved has greatly advanced in recent years, and with that, the management of sleep disorders has improved. There is still room for improvement and recently many new compounds have reached clinical trials with a few being approved for commercial use. Areas covered: In this review, the authors make the case of sleep disorders as a matter of public health. The mechanisms of sleep transition are discussed emphasizing the wake and sleep promoting interaction of different brain regions. Finally, advances in pharmacotherapy are examined in the context of chronic insomnia and narcolepsy. Expert opinion: The orexinergic system is an example of a breakthrough in sleep medicine that has catalyzed drug development. Nevertheless, sleep is a topic still with many unanswered questions. That being said, the melanin-concentrating hormone system is becoming increasingly relevant and we speculate it will be the next target of sleep medication.

  17. Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes

    Energy Technology Data Exchange (ETDEWEB)

    Lowden, Michael J.; Skorupski, Karen; Pellegrini, Maria; Chiorazzo, Michael G.; Taylor, Ronald K.; Kull, F. Jon (Dartmouth)

    2010-03-04

    Cholera is an acute intestinal infection caused by the bacterium Vibrio cholerae. In order for V. cholerae to cause disease, it must produce two virulence factors, the toxin-coregulated pilus (TCP) and cholera toxin (CT), whose expression is controlled by a transcriptional cascade culminating with the expression of the AraC-family regulator, ToxT. We have solved the 1.9 {angstrom} resolution crystal structure of ToxT, which reveals folds in the N- and C-terminal domains that share a number of features in common with AraC, MarA, and Rob as well as the unexpected presence of a buried 16-carbon fatty acid, cis-palmitoleate. The finding that cis-palmitoleic acid reduces TCP and CT expression in V. cholerae and prevents ToxT from binding to DNA in vitro provides a direct link between the host environment of V. cholerae and regulation of virulence gene expression.

  18. Differential virulence mechanisms of infectious hematopoietic necrosis virus in rainbow trout (Oncorhynchus mykiss) include host entry and virus replication kinetics

    Science.gov (United States)

    Penaranda, M.M.D.; Purcell, M.K.; Kurath, G.

    2009-01-01

    Host specificity is a phenomenon exhibited by all viruses. For the fish rhabdovirus infectious hematopoietic necrosis virus (IHNV), differential specificity of virus strains from the U and M genogroups has been established both in the field and in experimental challenges. In rainbow trout (Oncorhynchus mykiss), M IHNV strains are consistently more prevalent and more virulent than U IHNV. The basis of the differential ability of these two IHNV genogroups to cause disease in rainbow trout was investigated in live infection challenges with representative U and M IHNV strains. When IHNV was delivered by intraperitoneal injection, the mortality caused by U IHNV increased, indicating that the low virulence of U IHNV is partly due to inefficiency in entering the trout host. Analyses of in vivo replication showed that U IHNV consistently had lower prevalence and lower viral load than M IHNV during the course of infection. In analyses of the host immune response, M IHNV-infected fish consistently had higher and longer expression of innate immune-related genes such as Mx-1. This suggests that the higher virulence of M IHNV is not due to suppression of the immune response in rainbow trout. Taken together, the results support a kinetics hypothesis wherein faster replication enables M IHNV to rapidly achieve a threshold level of virus necessary to override the strong host innate immune response. ?? 2009 SGM.

  19. Changing the Game: Using Integrative Genomics to Probe Virulence Mechanisms of the Stem Rust Pathogen Puccinia graminis f. sp. tritici.

    Science.gov (United States)

    Figueroa, Melania; Upadhyaya, Narayana M; Sperschneider, Jana; Park, Robert F; Szabo, Les J; Steffenson, Brian; Ellis, Jeff G; Dodds, Peter N

    2016-01-01

    The recent resurgence of wheat stem rust caused by new virulent races of Puccinia graminis f. sp. tritici (Pgt) poses a threat to food security. These concerns have catalyzed an extensive global effort toward controlling this disease. Substantial research and breeding programs target the identification and introduction of new stem rust resistance (Sr) genes in cultivars for genetic protection against the disease. Such resistance genes typically encode immune receptor proteins that recognize specific components of the pathogen, known as avirulence (Avr) proteins. A significant drawback to deploying cultivars with single Sr genes is that they are often overcome by evolution of the pathogen to escape recognition through alterations in Avr genes. Thus, a key element in achieving durable rust control is the deployment of multiple effective Sr genes in combination, either through conventional breeding or transgenic approaches, to minimize the risk of resistance breakdown. In this situation, evolution of pathogen virulence would require changes in multiple Avr genes in order to bypass recognition. However, choosing the optimal Sr gene combinations to deploy is a challenge that requires detailed knowledge of the pathogen Avr genes with which they interact and the virulence phenotypes of Pgt existing in nature. Identifying specific Avr genes from Pgt will provide screening tools to enhance pathogen virulence monitoring, assess heterozygosity and propensity for mutation in pathogen populations, and confirm individual Sr gene functions in crop varieties carrying multiple effective resistance genes. Toward this goal, much progress has been made in assembling a high quality reference genome sequence for Pgt, as well as a Pan-genome encompassing variation between multiple field isolates with diverse virulence spectra. In turn this has allowed prediction of Pgt effector gene candidates based on known features of Avr genes in other plant pathogens, including the related flax rust

  20. Changing the game: using integrative genomics to probe virulence mechanisms of the stem rust pathogen Puccinia graminis f. sp. tritici

    Directory of Open Access Journals (Sweden)

    Melania eFigueroa

    2016-02-01

    Full Text Available The recent resurgence of wheat stem rust caused by new virulent races of Puccinia graminis f. sp. tritici (Pgt poses a threat to food security. These concerns have catalyzed an extensive global effort towards controlling this disease. Substantial research and breeding programs target the identification and introduction of new stem rust resistance (Sr genes in cultivars for genetic protection against the disease. Such resistance genes typically encode immune receptor proteins that recognize specific components of the pathogen, known as avirulence (Avr proteins. A significant drawback to deploying cultivars with single Sr genes is that they are often overcome by evolution of the pathogen to escape recognition through alterations in Avr genes. Thus, a key element in achieving durable rust control is the deployment of multiple effective Sr genes in combination, either through conventional breeding or transgenic approaches, to minimize the risk of resistance breakdown. In this situation, evolution of pathogen virulence would require simultaneous changes in multiple Avr genes in order to bypass recognition. However, choosing the optimal Sr gene combinations to deploy is a challenge that requires detailed knowledge of the pathogen Avr genes with which they interact and the virulence phenotypes of Pgt existing in nature. Identifying specific Avr genes from Pgt will provide screening tools to enhance pathogen virulence monitoring, assess heterozygosity and propensity for mutation in pathogen populations, and confirm individual Sr gene functions in crop varieties carrying multiple effective resistance genes. Towards this goal, much progress has been made in assembling a high quality reference genome sequence for Pgt, as well as a Pan-genome encompassing variation between multiple field isolates with diverse virulence spectra. In turn this has allowed prediction of Pgt effector gene candidates based on known features of Avr genes in other plant pathogens

  1. Understanding the mechanism of base development of hydrogen silsesquioxane

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jihoon; Chao, Weilun; Liang, Xiaogan; Griedel, Brian D.; Olynick, Deirdre L

    2009-01-09

    There have been numerous studies of electron beam exposed hydrogen silsesquioxane (HSQ) development conditions in order to improve the developer contrast. For TMAH based development, improvements were made by going to higher TMAH normalities and heating the developer. Yang and Berggren showed development of electron beam exposed (HSQ) by NaOH with added Na salts (various anions) significantly improves the contrast. Here, we study the contrast and etching rates of 100 keV exposed HSQ in NaOH in the presence of LiCl, NaCl, and KCl salts and use this as a segway to understand the mechanisms governing contrast during development HSQ development. The basic mechanism of development of HSQ can be understood by comparing to etching of quartz in basic solutions. Hydroxide ions act as nucleophiles which attack silicon. When a silicon-oxygen bond of the Si-O-Si matrix is broken, Si-O{sup -} and Si-OH are formed which can reversibly react to form the original structure. When a Si-H bond is broken via reaction with hydroxide, Si-O{sup -} and H{sub 2} gas are formed. Salts can change the etching rates as a function of dose in a non-linear fashion to increase etch contrast. Figs. 1, 2, and 3 show contrast curves for HSQ developed in 0.25 N sodium hydroxide and with the addition of NaCl, LiCl and KCl salts at several concentrations. NaCl addition resulted in the highest contrast. Contrast improves with additional salt concentration while sensitivity decreases. Interestingly enough, addition of salt decreases the removal of material of NaOH alone at higher doses while increasing the rate at lower concentrations. Addition of LiCl salts improves contrast over NaOH alone. Furthermore, the sensitivity at all doses increases as the LiCl concentration increases, a salting out effect. Similar to NaCl salt behavior, the addition of KCl salts, improves contrast at the expense of sensitivity. However, unlike NaCl, even at very high doses, KCl addition increases removal rate of HSQ. We

  2. Host cell interactions of outer membrane vesicle-associated virulence factors of enterohemorrhagic Escherichia coli O157: Intracellular delivery, trafficking and mechanisms of cell injury

    Science.gov (United States)

    Greune, Lilo; Jarosch, Kevin-André; Steil, Daniel; Zhang, Wenlan; He, Xiaohua; Lloubes, Roland; Fruth, Angelika; Kim, Kwang Sik; Schmidt, M. Alexander; Dobrindt, Ulrich; Mellmann, Alexander; Karch, Helge

    2017-01-01

    Outer membrane vesicles (OMVs) are important tools in bacterial virulence but their role in the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC) O157, the leading cause of life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, electron and confocal laser scanning microscopy, immunoblotting, and bioassays, we investigated OMVs secreted by EHEC O157 clinical isolates for virulence factors cargoes, interactions with pathogenetically relevant human cells, and mechanisms of cell injury. We demonstrate that O157 OMVs carry a cocktail of key virulence factors of EHEC O157 including Shiga toxin 2a (Stx2a), cytolethal distending toxin V (CdtV), EHEC hemolysin, and flagellin. The toxins are internalized by cells via dynamin-dependent endocytosis of OMVs and differentially separate from vesicles during intracellular trafficking. Stx2a and CdtV-B, the DNase-like CdtV subunit, separate from OMVs in early endosomes. Stx2a is trafficked, in association with its receptor globotriaosylceramide within detergent-resistant membranes, to the Golgi complex and the endoplasmic reticulum from where the catalytic Stx2a A1 fragment is translocated to the cytosol. CdtV-B is, after its retrograde transport to the endoplasmic reticulum, translocated to the nucleus to reach DNA. CdtV-A and CdtV-C subunits remain OMV-associated and are sorted with OMVs to lysosomes. EHEC hemolysin separates from OMVs in lysosomes and targets mitochondria. The OMV-delivered CdtV-B causes cellular DNA damage, which activates DNA damage responses leading to G2 cell cycle arrest. The arrested cells ultimately die of apoptosis induced by Stx2a and CdtV via caspase-9 activation. By demonstrating that naturally secreted EHEC O157 OMVs carry and deliver into cells a cocktail of biologically active virulence factors, thereby causing cell death, and by performing first comprehensive analysis of intracellular trafficking of OMVs and OMV-delivered virulence factors

  3. Host cell interactions of outer membrane vesicle-associated virulence factors of enterohemorrhagic Escherichia coli O157: Intracellular delivery, trafficking and mechanisms of cell injury.

    Directory of Open Access Journals (Sweden)

    Martina Bielaszewska

    2017-02-01

    Full Text Available Outer membrane vesicles (OMVs are important tools in bacterial virulence but their role in the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC O157, the leading cause of life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, electron and confocal laser scanning microscopy, immunoblotting, and bioassays, we investigated OMVs secreted by EHEC O157 clinical isolates for virulence factors cargoes, interactions with pathogenetically relevant human cells, and mechanisms of cell injury. We demonstrate that O157 OMVs carry a cocktail of key virulence factors of EHEC O157 including Shiga toxin 2a (Stx2a, cytolethal distending toxin V (CdtV, EHEC hemolysin, and flagellin. The toxins are internalized by cells via dynamin-dependent endocytosis of OMVs and differentially separate from vesicles during intracellular trafficking. Stx2a and CdtV-B, the DNase-like CdtV subunit, separate from OMVs in early endosomes. Stx2a is trafficked, in association with its receptor globotriaosylceramide within detergent-resistant membranes, to the Golgi complex and the endoplasmic reticulum from where the catalytic Stx2a A1 fragment is translocated to the cytosol. CdtV-B is, after its retrograde transport to the endoplasmic reticulum, translocated to the nucleus to reach DNA. CdtV-A and CdtV-C subunits remain OMV-associated and are sorted with OMVs to lysosomes. EHEC hemolysin separates from OMVs in lysosomes and targets mitochondria. The OMV-delivered CdtV-B causes cellular DNA damage, which activates DNA damage responses leading to G2 cell cycle arrest. The arrested cells ultimately die of apoptosis induced by Stx2a and CdtV via caspase-9 activation. By demonstrating that naturally secreted EHEC O157 OMVs carry and deliver into cells a cocktail of biologically active virulence factors, thereby causing cell death, and by performing first comprehensive analysis of intracellular trafficking of OMVs and OMV

  4. Metals in fungal virulence.

    Science.gov (United States)

    Gerwien, Franziska; Skrahina, Volha; Kasper, Lydia; Hube, Bernhard; Brunke, Sascha

    2018-01-01

    Metals are essential for life, and they play a central role in the struggle between infecting microbes and their hosts. In fact, an important aspect of microbial pathogenesis is the 'nutritional immunity', in which metals are actively restricted (or, in an extended definition of the term, locally enriched) by the host to hinder microbial growth and virulence. Consequently, fungi have evolved often complex regulatory networks, uptake and detoxification systems for essential metals such as iron, zinc, copper, nickel and manganese. These systems often differ fundamentally from their bacterial counterparts, but even within the fungal pathogens we can find common and unique solutions to maintain metal homeostasis. Thus, we here compare the common and species-specific mechanisms used for different metals among different fungal species-focusing on important human pathogens such as Candida albicans, Aspergillus fumigatus or Cryptococcus neoformans, but also looking at model fungi such as Saccharomyces cerevisiae or A. nidulans as well-studied examples for the underlying principles. These direct comparisons of our current knowledge reveal that we have a good understanding how model fungal pathogens take up iron or zinc, but that much is still to learn about other metals and specific adaptations of individual species-not the least to exploit this knowledge for new antifungal strategies. © FEMS 2017.

  5. Understanding human action: integrating meanings, mechanisms, causes, and contexts

    NARCIS (Netherlands)

    Keestra, M.; Repko, A.F.; Newell, W.H.; Szostak, R.

    2012-01-01

    Humans are capable of understanding an incredible variety of actions performed by other humans. Even though these range from primary biological actions like eating and fleeing, to acts in parliament or in poetry, humans generally can make sense of each other’s actions. Understanding other people’s

  6. Virulence of the zoonotic agent of leptospirosis: still terra incognita?

    Science.gov (United States)

    Picardeau, Mathieu

    2017-05-01

    Pathogenic leptospires are the bacterial agents of leptospirosis, which is an emerging zoonotic disease that affects animals and humans worldwide. The success of leptospires as pathogens is explained by their spiral shape and endoflagellar motility (which enable these spirochetes to rapidly cross connective tissues and barriers), as well as by their ability to escape or hijack the host immune system. However, the basic biology and virulence factors of leptospires remain poorly characterized. In this Review, we discuss the recent advances in our understanding of the epidemiology, taxonomy, genomics and the molecular basis of virulence in leptospires, and how these properties contribute to the mechanism of pathogenesis of leptospirosis.

  7. Understanding the mechanism of base development of HSQ

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jihoon; Chao, Weilun; Griedel, Brian; Liang, Xiaogan; Lewis, Mark; Hilken, Dawn; Olynick, Deirdre

    2009-06-16

    We study the dissolution mechanism of HSQ (hydrogen silsesquioxane) in base solutions with the addition of chloride salts to elucidate the development mechanism. Reaction mechanisms are proposed based on the dissolution mechanism of quartz. Development kinetics points to two dose-dependent development mechanisms. Considering ion sizes, both hydrated and non-hydrated, and ion exchange, we propose that a combination of a surface dominated reaction at higher doses and a matrix dominated reaction at lower doses accounts for the high development contrast with a NaOH base/NaCl salt mixture. The interplay between the hydrated and non-hydrated ion size leads to higher contrast developers, such as tetramethyl ammonium hydroxide (TMAH) with NaCl.

  8. The Nobel Prize for understanding autophagy, a cellular mechanism ...

    Indian Academy of Sciences (India)

    The Nobel Prize in Physiology or Medicine, 2016, was awarded to Prof Yoshinori Ohsumi from TokyoInstitute of Technology, Yokohoma, Japan, for his work that helped in understanding the molecularmechanisms of autophagy, a process used by most eukaryotic cells to degrade a portion of cytoplasmincluding damaged ...

  9. Understanding "Understanding" Flow for Network-Centric Warfare: Military Knowledge-Flow Mechanics

    National Research Council Canada - National Science Library

    Nissen, Mark

    2002-01-01

    Network-centric warfare (NCW) emphasizes information superiority for battlespace efficacy, but it is clear that the mechanics of how knowledge flows are just as important as those pertaining to the networks and communication...

  10. Understanding the Role and Mechanism of Metformin in Obesity ...

    African Journals Online (AJOL)

    Metformin, a biguanide, is a widely used drug for the treatment of type 2 diabetes mellitus. The drug also found to be beneficial in other class of diseases like obesity but its role and mechanism of action in obesity is still not well established. A literature survey was done in order to evaluate the evidence supporting metformin ...

  11. Understanding the Mechanism behind Maternal Imprisonment and Adolescent School Dropout

    Science.gov (United States)

    Cho, Rosa M.

    2011-01-01

    This study empirically tested 3 mechanisms commonly suggested to disadvantage youths whose mothers are incarcerated in prison. An event history analysis of school dropout was conducted on a sample of 6,008 adolescents in a large city created by merging several Illinois state administrative data. Findings revealed that adolescents are indeed at…

  12. Understanding the biological mechanisms of Zika virus disease ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    This project will use advanced biomolecular, genomics and proteomics techniques to explain the molecular mechanisms by which the Zika virus infects and persists in the human body, how it affects the human reproductive and central nervous system, and how the risk of fetal abnormalities can be better predicted in infected ...

  13. How Electroconvulsive Therapy Works?: Understanding the Neurobiological Mechanisms

    Science.gov (United States)

    Singh, Amit; Kar, Sujita Kumar

    2017-01-01

    Electroconvulsive therapy (ECT) is a time tested treatment modality for the management of various psychiatric disorders. There have been a lot of modifications in the techniques of delivering ECT over decades. Despite lots of criticisms encountered, ECT has still been used commonly in clinical practice due to its safety and efficacy. Research evidences found multiple neuro-biological mechanisms for the therapeutic effect of ECT. ECT brings about various neuro-physiological as well as neuro-chemical changes in the macro- and micro-environment of the brain. Diverse changes involving expression of genes, functional connectivity, neurochemicals, permeability of blood-brain-barrier, alteration in immune system has been suggested to be responsible for the therapeutic effects of ECT. This article reviews different neurobiological mechanisms responsible for the therapeutic efficacy of ECT. PMID:28783929

  14. Omics approaches to understand the nature of virulence in Puccinia striiformis f.sp. tritici

    DEFF Research Database (Denmark)

    Walter, Stephanie; Kemen, Eric; Brown, James K. M.

    2009-01-01

    New genomic and transcriptomic methods greatly facilitate the study of the biology and evolution of fungal plant pathogens. The obligate biotrophic and asexually reproducing rust fungus Puccinia striiformis f.sp. tritici (Pst) forms haustoria during plant infection and delivers proteins and other...... effector molecules into the plant cell. Rust effectors take a key function in the rust-host interaction: on the one hand they are target of the plant resistance protein system and on the other hand they mediate virulence as subjects of diversifying selection. The virulence of Pst also depends...... on the presence and rapid evolution of such effectors. Pst causes yellow rust on wheat, one of the also depends on the presence and rapid evolution of such effectors. causes yellow rust on wheat, one of the most devastating diseases worldwide, and poses an imminent danger to previously resistant wheat varieties...

  15. Advances in understanding Giardia: determinants and mechanisms of chronic sequelae

    Science.gov (United States)

    Sartor, R. Balfour

    2015-01-01

    Giardia lamblia is a flagellated protozoan that is the most common cause of intestinal parasitic infection in children living in resource-limited settings. The pathogenicity of Giardia has been debated since the parasite was first identified, and clinical outcomes vary across studies. Among recent perplexing findings are diametrically opposed associations between Giardia and acute versus persistent diarrhea and a poorly understood potential for long-term sequelae, including impaired child growth and cognitive development. The mechanisms driving these protean clinical outcomes remain elusive, but recent advances suggest that variability in Giardia strains, host nutritional status, the composition of microbiota, co-infecting enteropathogens, host genetically determined mucosal immune responses, and immune modulation by Giardia are all relevant factors influencing disease manifestations after Giardia infection. PMID:26097735

  16. Understanding mechanisms of autoimmunity through translational research in vitiligo

    Science.gov (United States)

    Strassner, James P; Harris, John E

    2016-01-01

    Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells. Once the autoimmune T cell response is established, the IFN-γ-STAT1-CXCL10 signaling axis becomes the primary inflammatory pathway driving both progression and maintenance of vitiligo. This pathway is a tempting target for both existing and developing pharmaceuticals, but further detailing how melanocytes signal their own demise may also lead to new therapeutic targets. Research in vitiligo may be the future key to understand the pathogenesis of organ-specific autoimmunity, as vitiligo is common, reversible, progresses over the life of the individual, has been relatively well-defined, and is quite easy to study using translational and clinical approaches. What is revealed in these studies can lead to innovative treatments and also help elucidate the principles that underlie similar organ-specific autoimmune diseases, especially in cases where the target organ is less accessible. PMID:27764715

  17. Understanding the kinetic mechanism of RNA single base pair formation.

    Science.gov (United States)

    Xu, Xiaojun; Yu, Tao; Chen, Shi-Jie

    2016-01-05

    RNA functions are intrinsically tied to folding kinetics. The most elementary step in RNA folding is the closing and opening of a base pair. Understanding this elementary rate process is the basis for RNA folding kinetics studies. Previous studies mostly focused on the unfolding of base pairs. Here, based on a hybrid approach, we investigate the folding process at level of single base pairing/stacking. The study, which integrates molecular dynamics simulation, kinetic Monte Carlo simulation, and master equation methods, uncovers two alternative dominant pathways: Starting from the unfolded state, the nucleotide backbone first folds to the native conformation, followed by subsequent adjustment of the base conformation. During the base conformational rearrangement, the backbone either retains the native conformation or switches to nonnative conformations in order to lower the kinetic barrier for base rearrangement. The method enables quantification of kinetic partitioning among the different pathways. Moreover, the simulation reveals several intriguing ion binding/dissociation signatures for the conformational changes. Our approach may be useful for developing a base pair opening/closing rate model.

  18. Understanding the mechanisms of glutamine action in critically ill patients

    Directory of Open Access Journals (Sweden)

    Gisele P. Oliveira

    2010-06-01

    Full Text Available Glutamine (Gln is an important energy source and has been used as a supplementary energy substrate. Furthermore, Gln is an essential component for numerous metabolic functions, including acid-base homeostasis, gluconeogenesis, nitrogen transport and synthesis of proteins and nucleic acids. Therefore, glutamine plays a significant role in cell homeostasis and organ metabolism. This article aims to review the mechanisms of glutamine action during severe illnesses. In critically ill patients, the increase in mortality was associated with a decreased plasma Gln concentration. During catabolic stress, Gln consumption rate exceeds the supply, and both plasma and skeletal muscle pools of free Gln are severely reduced. The dose and route of Gln administration clearly influence its effectiveness: high-dose parenteral appears to be more beneficial than low-dose enteral administration. Experimental studies reported that Gln may protect cells, tissues, and whole organisms from stress and injury through the following mechanisms: attenuation of NF (nuclear factor-kB activation, a balance between pro- and anti-inflammatory cytokines, reduction in neutrophil accumulation, improvement in intestinal integrity and immune cell function, and enhanced of heat shock protein expression. In conclusion, high-doses of parenteral Gln (>0.50 g/kg/day demonstrate a greater potential to benefit in critically ill patients, although Gln pathophysiological mechanisms requires elucidation.A glutamina (Gln é uma importante fonte de energia e tem sido usada como substrato energético suplementar. Além disso, a Gln é um componente essencial para numerosas funções metabólicas tais como: homeostase ácido-base, gliconeogênese, transporte de nitrogênio e síntese de proteínas e ácidos nucléicos. Portanto, a glutamina desempenha um papel importante na homeostase celular e no metabolismo dos órgãos. Esse artigo objetiva rever os mecanismos de ação da glutamina na doen

  19. Bacterial Prostatitis: Bacterial Virulence, Clinical Outcomes, and New Directions.

    Science.gov (United States)

    Krieger, John N; Thumbikat, Praveen

    2016-02-01

    Four prostatitis syndromes are recognized clinically: acute bacterial prostatitis, chronic bacterial prostatitis, chronic prostatitis/chronic pelvic pain syndrome, and asymptomatic prostatitis. Because Escherichia coli represents the most common cause of bacterial prostatitis, we investigated the importance of bacterial virulence factors and antimicrobial resistance in E. coli strains causing prostatitis and the potential association of these characteristics with clinical outcomes. A structured literature review revealed that we have limited understanding of the virulence-associated characteristics of E. coli causing acute prostatitis. Therefore, we completed a comprehensive microbiological and molecular investigation of a unique strain collection isolated from healthy young men. We also considered new data from an animal model system suggesting certain E. coli might prove important in the etiology of chronic prostatitis/chronic pelvic pain syndrome. Our human data suggest that E. coli needs multiple pathogenicity-associated traits to overcome anatomic and immune responses in healthy young men without urological risk factors. The phylogenetic background and accumulation of an exceptional repertoire of extraintestinal pathogenic virulence-associated genes indicate that these E. coli strains belong to a highly virulent subset of uropathogenic variants. In contrast, antibiotic resistance confers little added advantage to E. coli strains in these healthy outpatients. Our animal model data also suggest that certain pathogenic E. coli may be important in the etiology of chronic prostatitis/chronic pelvic pain syndrome through mechanisms that are dependent on the host genetic background and the virulence of the bacterial strain.

  20. Structural and mutational analyses of the Leptospira interrogans virulence-related heme oxygenase provide insights into its catalytic mechanism.

    Directory of Open Access Journals (Sweden)

    Anabel Soldano

    Full Text Available Heme oxygenase from Leptospira interrogans is an important virulence factor. During catalysis, redox equivalents are provided to this enzyme by the plastidic-type ferredoxin-NADP+ reductase also found in L. interrogans. This process may have evolved to aid this bacterial pathogen to obtain heme-iron from their host and enable successful colonization. Herein we report the crystal structure of the heme oxygenase-heme complex at 1.73 Å resolution. The structure reveals several distinctive features related to its function. A hydrogen bonded network of structural water molecules that extends from the catalytic site to the protein surface was cleared observed. A depression on the surface appears to be the H+ network entrance from the aqueous environment to the catalytic site for O2 activation, a key step in the heme oxygenase reaction. We have performed a mutational analysis of the F157, located at the above-mentioned depression. The mutant enzymes were unable to carry out the complete degradation of heme to biliverdin since the reaction was arrested at the verdoheme stage. We also observed that the stability of the oxyferrous complex, the efficiency of heme hydroxylation and the subsequent conversion to verdoheme was adversely affected. These findings underscore a long-range communication between the outer fringes of the hydrogen-bonded network of structural waters and the heme active site during catalysis. Finally, by analyzing the crystal structures of ferredoxin-NADP+ reductase and heme oxygenase, we propose a model for the productive association of these proteins.

  1. The Fatty Acid Regulator FadR Influences the Expression of the Virulence Cascade in the El Tor Biotype of Vibrio cholerae by Modulating the Levels of ToxT via Two Different Mechanisms.

    Science.gov (United States)

    Kovacikova, Gabriela; Lin, Wei; Taylor, Ronald K; Skorupski, Karen

    2017-04-01

    FadR is a master regulator of fatty acid (FA) metabolism that coordinates the pathways of FA degradation and biosynthesis in enteric bacteria. We show here that a Δ fadR mutation in the El Tor biotype of Vibrio cholerae prevents the expression of the virulence cascade by influencing both the transcription and the posttranslational regulation of the master virulence regulator ToxT. FadR is a transcriptional regulator that represses the expression of genes involved in FA degradation, activates the expression of genes involved in unsaturated FA (UFA) biosynthesis, and also activates the expression of two operons involved in saturated FA (SFA) biosynthesis. Since FadR does not bind directly to the toxT promoter, we determined whether the regulation of any of its target genes indirectly influenced ToxT. This was accomplished by individually inserting a double point mutation into the FadR-binding site in the promoter of each target gene, thereby preventing their activation or repression. Although preventing FadR-mediated activation of fabA , which encodes the enzyme that carries out the first step in UFA biosynthesis, did not significantly influence either the transcription or the translation of ToxT, it reduced its levels and prevented virulence gene expression. In the mutant strain unable to carry out FadR-mediated activation of fabA , expressing fabA ectopically restored the levels of ToxT and virulence gene expression. Taken together, the results presented here indicate that V. cholerae FadR influences the virulence cascade in the El Tor biotype by modulating the levels of ToxT via two different mechanisms. IMPORTANCE Fatty acids (FAs) play important roles in membrane lipid homeostasis and energy metabolism in all organisms. In Vibrio cholerae , the causative agent of the acute intestinal disease cholera, they also influence virulence by binding into an N-terminal pocket of the master virulence regulator, ToxT, and modulating its activity. FadR is a transcription

  2. Understanding cracking failures of coatings: A fracture mechanics approach

    Science.gov (United States)

    Kim, Sung-Ryong

    A fracture mechanics analysis of coating (paint) cracking was developed. A strain energy release rate (G(sub c)) expression due to the formation of a new crack in a coating was derived for bending and tension loadings in terms of the moduli, thicknesses, Poisson's ratios, load, residual strain, etc. Four-point bending and instrumented impact tests were used to determine the in-situ fracture toughness of coatings as functions of increasing baking (drying) time. The system used was a thin coating layer on a thick substrate layer. The substrates included steel, aluminum, polycarbonate, acrylonitrile-butadiene-styrene (ABS), and Noryl. The coatings included newly developed automotive paints. The four-point bending configuration promoted nice transversed multiple coating cracks on both steel and polymeric substrates. The crosslinked type automotive coatings on steel substrates showed big cracks without microcracks. When theoretical predictions for energy release rate were compared to experimental data for coating/steel substrate samples with multiple cracking, the agreement was good. Crosslinked type coatings on polymeric substrates showed more cracks than theory predicted and the G(sub c)'s were high. Solvent evaporation type coatings on polymeric substrates showed clean multiple cracking and the G(sub c)'s were higher than those obtained by tension analysis of tension experiments with the same substrates. All the polymeric samples showed surface embrittlement after long baking times using four-point bending tests. The most apparent surface embrittlement was observed in the acrylonitrile-butadiene-styrene (ABS) substrate system. The impact properties of coatings as a function of baking time were also investigated. These experiments were performed using an instrumented impact tester. There was a rapid decrease in G(sub c) at short baking times and convergence to a constant value at long baking times. The surface embrittlement conditions and an embrittlement toughness

  3. Understanding ozone mechanisms to alleviate ceramic membrane fouling

    Science.gov (United States)

    Chu, Irma Giovanna Llamosas

    Ceramic membranes are a strong prospect as an advanced treatment in the drinking water domain. But their high capital cost and the lack of specific research on their performance still discourage their application in this field. Thus, knowing that fouling is the main drawback experienced in filtration processes, this bench-scale study was aimed to assess the impact of an ozonation pre-treatment on the alleviation of the fouling of UF ceramic membranes. Preozonation and filtration steps were performed under two different pH and ozone doses. Chosen pH values were at the limits of natural surface waters range (6.5 and 8.5) to keep practicability. Raw water from the Thousand Isle's river at Quebec-Canada was used for the tests. The filtration setup involved an unstirred dead-end filtration cell operated at constant flux. Results showed that pre-oxidation by ozone indeed reduced the fouling degree of the membranes according to the dose applied (up to 60 and 85% for membranes 8 and 50 kDa, respectively). Direct NOM oxidation was found responsible for this effect as the presence of molecular ozone was not essential to achieve these results. In the context of this experiment, however, pH showed to be more effective than the ozonation pre-treatment to keep fouling at low levels: 70% lower at pH 6.5 than at pH 8.5 for un-ozonated waters, which was contrary to most of the literature found on the topic (Changwon, 2013; De Angelis & Fidalgo, 2013; Karnik et al., 2005; S. Lee & Kim, 2014). This behaviour results mainly from the operation mode used in the experiment, the electrical repulsions between MON molecules at basic pH that led to the accumulation of material on the feed side of the membranes (concentration polarisation) and ulterior cake formation. In addition, solution pH showed an influence in the definition of fouling mechanisms. At solution pH 6.5, which was precisely the isoelectric point of the membranes (+/-6.5), the blocking fouling mode was frequently detected

  4. Sixth-Grade Students' Progress in Understanding the Mechanisms of Global Climate Change

    Science.gov (United States)

    Visintainer, Tammie; Linn, Marcia

    2015-01-01

    Developing solutions for complex issues such as global climate change requires an understanding of the mechanisms involved. This study reports on the impact of a technology-enhanced unit designed to improve understanding of global climate change, its mechanisms, and their relationship to everyday energy use. Global Climate Change, implemented in…

  5. Mucoid conversion of Pseudomonas aeruginosa by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung

    DEFF Research Database (Denmark)

    Mathee, K; Ciofu, O; Sternberg, C

    1999-01-01

    Da protein associated with alginate overproducing strains was identified as AlgE (Alg76) by N-terminal sequence analysis. Thus, the common phenotype of the mucoid variants, which included a genetically engineered mucA22 mutant, suggested that the only mutation incurred as a result of H2O2 treatment....... These findings indicate that gene activation in bacteria by toxic oxygen radicals, similar to that found in plants and mammalian cells, may serve as a defence mechanism for the bacteria. This suggests that mucoid conversion is a response to oxygen radical exposure and that this response is a mechanism of defence...

  6. Virulence and Fitness Determinants of Uropathogenic Escherichia coli

    Science.gov (United States)

    Subashchandrabose, Sargurunathan; Mobley, Harry L T.

    2015-01-01

    Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is a major global public health concern. Increasing antibiotic resistance found in clinical UPEC isolates underscores the immediate need for development of novel therapeutics against this pathogen. Better understanding of the fitness and virulence mechanisms that are integral to the pathogenesis of UTI will facilitate identification of novel strategies to prevent and treat infection with UPEC. Working towards that goal, the global UPEC research community has made great strides at unraveling various virulence and fitness genes. Here, we summarize major findings on virulence and fitness determinants that enable UPEC to successfully survive and colonize the urinary tract of mammalian hosts. Major sections of this chapter are devoted to the role of iron acquisition systems, metabolic pathways, fimbriae, flagella, toxins, biofilm formation, capsule, and strain-specific genes in the initiation and progression of UTIs. Transcriptomes of UPEC during experimental UTI in a murine model and naturally occurring UTI in women are compared to elucidate virulence mechanisms specifically involved in human UTI. Capitalizing on the advances in molecular pathogenesis research by translating these findings will help develop better clinical strategies for prevention and management of UTIs. PMID:26350328

  7. A dynamic and intricate regulatory network determines Pseudomonas aeruginosa virulence

    Science.gov (United States)

    Balasubramanian, Deepak; Schneper, Lisa; Kumari, Hansi; Mathee, Kalai

    2013-01-01

    Pseudomonas aeruginosa is a metabolically versatile bacterium that is found in a wide range of biotic and abiotic habitats. It is a major human opportunistic pathogen causing numerous acute and chronic infections. The critical traits contributing to the pathogenic potential of P. aeruginosa are the production of a myriad of virulence factors, formation of biofilms and antibiotic resistance. Expression of these traits is under stringent regulation, and it responds to largely unidentified environmental signals. This review is focused on providing a global picture of virulence gene regulation in P. aeruginosa. In addition to key regulatory pathways that control the transition from acute to chronic infection phenotypes, some regulators have been identified that modulate multiple virulence mechanisms. Despite of a propensity for chaotic behaviour, no chaotic motifs were readily observed in the P. aeruginosa virulence regulatory network. Having a ‘birds-eye’ view of the regulatory cascades provides the forum opportunities to pose questions, formulate hypotheses and evaluate theories in elucidating P. aeruginosa pathogenesis. Understanding the mechanisms involved in making P. aeruginosa a successful pathogen is essential in helping devise control strategies. PMID:23143271

  8. Virulence and Fitness Determinants of Uropathogenic Escherichia coli.

    Science.gov (United States)

    Subashchandrabose, Sargurunathan; Mobley, Harry L T

    2015-08-01

    Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is a major global public health concern. Increasing antibiotic resistance found in clinical UPEC isolates underscores the immediate need for development of novel therapeutics against this pathogen. Better understanding of the fitness and virulence mechanisms that are integral to the pathogenesis of UTI will facilitate identification of novel strategies to prevent and treat infection with UPEC. Working towards that goal, the global UPEC research community has made great strides at unraveling various virulence and fitness genes. Here, we summarize major findings on virulence and fitness determinants that enable UPEC to successfully survive and colonize the urinary tract of mammalian hosts. Major sections of this chapter are devoted to the role of iron acquisition systems, metabolic pathways, fimbriae, flagella, toxins, biofilm formation, capsule, and strain-specific genes in the initiation and progression of UTIs. Transcriptomes of UPEC during experimental UTI in a murine model and naturally occurring UTI in women are compared to elucidate virulence mechanisms specifically involved in human UTI. Capitalizing on the advances in molecular pathogenesis research by translating these findings will help develop better clinical strategies for prevention and management of UTIs.

  9. ECOLOGICAL HOMEORHESIS IN THE MECHANISMS OF VIRULENCE EVOLUTION AND PENETRATION OF AGENTS OF FERAL HERD INFETIONS INTO HUMANS

    OpenAIRE

    A. V. Dubov

    2014-01-01

    We defined the characteristics of formation of ecological homeorhesis in feral herd infections (as exemplified by tick-borne encephalitis). By ecological homeorhesis we understand the process of harmonization between ecological factors and homeostasis systems on population, species and especially interspecies levels. We marked the evolution of epidemiology and clinical features of feral herd infections under anthropogenic influence upon natural hot spots. We also found in the circulation in e...

  10. [Virulence factors of Candida albicans].

    Science.gov (United States)

    Staniszewska, Monika; Bondaryk, Małgorzata; Piłat, Joanna; Siennicka, Katarzyna; Magda, Urszula; Kurzatkowski, Wiesław

    2012-01-01

    Candida albicans is the most common etiological factor of opportunistic human fungal infections. In this review, we focus on the major virulence factors that mediate the pathogenesis of C. albicans. Among these virulence factors, secreted aspartyl proteases, adherence, pleomorphism are the most important features of C. albicans infections. Ability to exist as different pleomorphic forms is defined as pleomorphism. A number of quorum sensing (QS) molecules have been described which affect morphogenesis process in C. albicans. Furthermore, the morphological transition of C. albicans in response to changing environmental conditions represent a means by which the strain adapts to different biological niches. Furthermore, every morphotype has own virulence profile and each pleomorphic form provide critical functions required for pathogenesis. Candida albicans is a producer of extracellular hydrolytic enzymes. Among them lipases, phospholipases and secreted aspartyl proteinases (Sap) are most significant in virulence. Sap proteins contribute to pathogenesis by digestion of host cell membranes and molecules of the host immune system to avoid antimicrobial attack by the host. One of the key features in the development of candidiasis is adhesion ofC. albicans to buccal and vaginal epithelial cells. The adhesion to host cells represents the first step in the internalization process which involves adhesins. Knowledge of the role of the various C. albicans' virulence factors during in vivo infections is still incomplete, therefore further studies including quantification of genes expression and histopathological examination of tissues damage are required to fully understand pathogenesis of this opportunistic pathogen.

  11. Virulence Markers of Dengue Viruses

    Science.gov (United States)

    1990-02-20

    pathogenetic mechanism from dengue-2 and dengue-4 viruses . Additional detailed epidemiological, virological and clinical evaluation on dengue-1 and...Soawy Ca saoouj Virulence Markers of Dengue Viruses (U) 12. PCIRSONAL AUTHORS) James L. Hardy, Ph.D. and Srisakul C. Kliks, Ph.D. 13a. TYPE Of REPORT...17. COSATI COOLS I& S UBiJECT TERMS0,G ’-mPJ!’ iwin.. - fl OV nu0a mef) FIELD I GROUP SUS-GROUIP Dengue viruses , dengue hemorrhagic fever, virulence

  12. ECOLOGICAL HOMEORHESIS IN THE MECHANISMS OF VIRULENCE EVOLUTION AND PENETRATION OF AGENTS OF FERAL HERD INFETIONS INTO HUMANS

    Directory of Open Access Journals (Sweden)

    A. V. Dubov

    2014-01-01

    Full Text Available We defined the characteristics of formation of ecological homeorhesis in feral herd infections (as exemplified by tick-borne encephalitis. By ecological homeorhesis we understand the process of harmonization between ecological factors and homeostasis systems on population, species and especially interspecies levels. We marked the evolution of epidemiology and clinical features of feral herd infections under anthropogenic influence upon natural hot spots. We also found in the circulation in endotherms and Lyme ticks the participation of such agents, which are unusual for these hot spots. 

  13. Understanding mechanisms of raveling to extend open graded friction course (OGFC) service life.

    Science.gov (United States)

    2016-03-01

    To understand the mechanisms of raveling in open graded friction course (OGFC) mixtures, this project was divided into experimental measurements and finite element (FE) modeling. For the experimental part, mixtures with good and poor field performanc...

  14. Global Regulator of Virulence A (GrvA) Coordinates Expression of Discrete Pathogenic Mechanisms in Enterohemorrhagic Escherichia coli through Interactions with GadW-GadE

    OpenAIRE

    Morgan, Jason K.; Carroll, Ronan K.; Harro, Carly M.; Vendura, Khoury W.; Shaw, Lindsey N.; Riordan, James T.

    2016-01-01

    Global regulator of virulence A (GrvA) is a ToxR-family transcriptional regulator that activates locus of enterocyte effacement (LEE)-dependent adherence in enterohemorrhagic Escherichia coli (EHEC). LEE activation by GrvA requires the Rcs phosphorelay response regulator RcsB and is sensitive to physiologically relevant concentrations of bicarbonate, a known stimulant of virulence systems in intestinal pathogens. This study determines the genomic scale of GrvA-dependent regulation and uncover...

  15. Understanding the mechanism(s) of mosaic trisomy 21 by using DNA polymorphism analysis

    Energy Technology Data Exchange (ETDEWEB)

    Pangalos, C.; Abazis, D.; Avramopoulos, D.; Blouin, J.L.; Antonaraksi, S.E. (Univ. of Patras Medical School (Greece)); Raoul, O.; deBlois, M.C.; Prieur, M. (Cytogenetics Laboratory, Paris (France)); Schinzel, A.A.

    1994-03-01

    In order to investigate the mechanism(s) underlying mosaicism for trisomy 21, the authors genotyped 17 families with mosaic trisomy 21 probands, using 28 PCR-detectable DNA polymorphic markers that map in the pericentromeric region and long arm of chromosome 21. The percentage of cells with trisomy 21 in the probands' blood lymphocytes was 6%-94%. There were two classes of autoradiographic results: In class I, a third allele' of lower intensity was detected in the proband's DNA for at least two chromosome 21 markers. The interpretation of this result was that the proband had inherited three chromosomes 21 after meiotic nondisjunction (NDJ) (trisomy 21 zygote) and subsequently lost one because of mitotic (somatic) error, the lost chromosome 21 being that with the lowest-intensity polymorphic allele. The parental origin and the meiotic stage of NDJ could also be determined. In class II, a third allele' was never detected. In these cases, the mosaicism probably occurred either by a postzygotic, mitotic error in anormal zygote that followed a normal meiosis (class IIA mechanism); by premeiotic, mitotic NDJ yielding an aneusomic zygote after meiosis, and subsequent mitotic loss (class IIB mechanism); or by a meiosis II error with lack of crossover in the preceding meiosis I, followed by mitotic loss after fertilization (class IIC mechanism). Among class II mechanisms, the most likely is mechanism IIA, while IIC is the least likely. There were 10 cases of class I and 7 cases of class II results. Within class I, there were nine cases with maternal meitoic errors (six meiosis I and three meiosis II errors, on the basis of pericentromeric markers) and one with paternal meiosis I error. The postzygotic loss of chromosome 21 was determined in eight maternal class I cases, and it was maternally derived in five cases and paternally derived in three; this suggests that the postzygotic loss of chromosome 21 is probably random. 28 refs., 1 fig., 2 tabs.

  16. Antifungal activity of phlorotannins against dermatophytes and yeasts: approaches to the mechanism of action and influence on Candida albicans virulence factor.

    Directory of Open Access Journals (Sweden)

    Graciliana Lopes

    Full Text Available In the last few decades, fungal infections, particularly nosocomial, increased all around the world. This increment stimulated the search for new antifungal agents, especially those derived from nature. Among natural products, those from marine sources have gained prominence in the last years. Purified phlorotannins extracts from three brown seaweeds (Cystoseira nodicaulis (Withering M. Roberts, Cystoseira usneoides (Linnaeus M. Roberts and Fucus spiralis Linnaeus were screened for their antifungal activity against human pathogenic yeast and filamentous fungi. The purified phlorotannins extracts from the studied seaweeds displayed fungistatic and fungicidal activity against yeast and dermatophytes, respectively, pointing to their interest as anti-dermatophyte agent. C. albicans ATCC 10231 was the most susceptible among yeast, while Epidermophyton floccosum and Trichophyton rubrum were the most susceptible among dermatophytes. Since the antifungal mechanism constitutes an important strategy for limiting the emergence of resistance to the commercially available agents, the mechanism of action of purified phlorotannins extracts was approached. C. nodicaulis and C. usneoides seem to act by affecting the ergosterol composition of the cell membrane of yeast and dermatophyte, respectively. F. spiralis influenced the dermatophyte cell wall composition by reducing the levels of chitin. Phlorotannins also seem to affect the respiratory chain function, as all of the studied species significantly increased the activity of mitochondrial dehydrogenases and increased the incorporation of rhodamine 123 by yeast cells. Phlorotannins from F. spiralis inhibited the dimorphic transition of Candida albicans, leading to the formation of pseudohyphae with diminished capacity to adhere to epithelial cells. This finding is associated with a decrease of C. albicans virulence and capacity to invade host cells and can be potentially interesting for combined antifungal

  17. Antifungal activity of phlorotannins against dermatophytes and yeasts: approaches to the mechanism of action and influence on Candida albicans virulence factor.

    Science.gov (United States)

    Lopes, Graciliana; Pinto, Eugénia; Andrade, Paula B; Valentão, Patrícia

    2013-01-01

    In the last few decades, fungal infections, particularly nosocomial, increased all around the world. This increment stimulated the search for new antifungal agents, especially those derived from nature. Among natural products, those from marine sources have gained prominence in the last years. Purified phlorotannins extracts from three brown seaweeds (Cystoseira nodicaulis (Withering) M. Roberts, Cystoseira usneoides (Linnaeus) M. Roberts and Fucus spiralis Linnaeus) were screened for their antifungal activity against human pathogenic yeast and filamentous fungi. The purified phlorotannins extracts from the studied seaweeds displayed fungistatic and fungicidal activity against yeast and dermatophytes, respectively, pointing to their interest as anti-dermatophyte agent. C. albicans ATCC 10231 was the most susceptible among yeast, while Epidermophyton floccosum and Trichophyton rubrum were the most susceptible among dermatophytes. Since the antifungal mechanism constitutes an important strategy for limiting the emergence of resistance to the commercially available agents, the mechanism of action of purified phlorotannins extracts was approached. C. nodicaulis and C. usneoides seem to act by affecting the ergosterol composition of the cell membrane of yeast and dermatophyte, respectively. F. spiralis influenced the dermatophyte cell wall composition by reducing the levels of chitin. Phlorotannins also seem to affect the respiratory chain function, as all of the studied species significantly increased the activity of mitochondrial dehydrogenases and increased the incorporation of rhodamine 123 by yeast cells. Phlorotannins from F. spiralis inhibited the dimorphic transition of Candida albicans, leading to the formation of pseudohyphae with diminished capacity to adhere to epithelial cells. This finding is associated with a decrease of C. albicans virulence and capacity to invade host cells and can be potentially interesting for combined antifungal therapy, namely for

  18. Framework for Understanding the Patterns of Student Difficulties in Quantum Mechanics

    Science.gov (United States)

    Marshman, Emily; Singh, Chandralekha

    2015-01-01

    Compared with introductory physics, relatively little is known about the development of expertise in advanced physics courses, especially in the case of quantum mechanics. Here, we describe a framework for understanding the patterns of student reasoning difficulties and how students develop expertise in quantum mechanics. The framework posits that…

  19. Insight into bacterial virulence mechanisms against host immune response via the Yersinia pestis-human protein-protein interaction network.

    Science.gov (United States)

    Yang, Huiying; Ke, Yuehua; Wang, Jian; Tan, Yafang; Myeni, Sebenzile K; Li, Dong; Shi, Qinghai; Yan, Yanfeng; Chen, Hui; Guo, Zhaobiao; Yuan, Yanzhi; Yang, Xiaoming; Yang, Ruifu; Du, Zongmin

    2011-11-01

    A Yersinia pestis-human protein interaction network is reported here to improve our understanding of its pathogenesis. Up to 204 interactions between 66 Y. pestis bait proteins and 109 human proteins were identified by yeast two-hybrid assay and then combined with 23 previously published interactions to construct a protein-protein interaction network. Topological analysis of the interaction network revealed that human proteins targeted by Y. pestis were significantly enriched in the proteins that are central in the human protein-protein interaction network. Analysis of this network showed that signaling pathways important for host immune responses were preferentially targeted by Y. pestis, including the pathways involved in focal adhesion, regulation of cytoskeleton, leukocyte transendoepithelial migration, and Toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling. Cellular pathways targeted by Y. pestis are highly relevant to its pathogenesis. Interactions with host proteins involved in focal adhesion and cytoskeketon regulation pathways could account for resistance of Y. pestis to phagocytosis. Interference with TLR and MAPK signaling pathways by Y. pestis reflects common characteristics of pathogen-host interaction that bacterial pathogens have evolved to evade host innate immune response by interacting with proteins in those signaling pathways. Interestingly, a large portion of human proteins interacting with Y. pestis (16/109) also interacted with viral proteins (Epstein-Barr virus [EBV] and hepatitis C virus [HCV]), suggesting that viral and bacterial pathogens attack common cellular functions to facilitate infections. In addition, we identified vasodilator-stimulated phosphoprotein (VASP) as a novel interaction partner of YpkA and showed that YpkA could inhibit in vitro actin assembly mediated by VASP.

  20. Microbial communication and virulence: lessons from evolutionary theory.

    Science.gov (United States)

    Diggle, Stephen P

    2010-12-01

    At the heart of tackling the huge challenge posed by infectious micro-organisms is the overwhelming need to understand their nature. A major question is, why do some species of bacteria rapidly kill their host whilst others are relatively benign? For example, Yersinia pestis, the causative organism of plague, is a highly virulent human pathogen whilst the closely related Yersinia pseudotuberculosis causes a much less severe disease. Using molecular techniques such as mutating certain genes, microbiologists have made significant advances over recent decades in elucidating the mechanisms that govern the production of virulence factors involved in causing disease in many bacterial species. There are also evolutionary and ecological factors which will influence virulence. Many of these ideas have arisen through the development of evolutionary theory and yet there is strikingly little empirical evidence testing them. By applying both mechanistic and adaptive approaches to microbial behaviours we can begin to address questions such as, what factors influence cooperation and the evolution of virulence in microbes and can we exploit these factors to develop new antimicrobial strategies?

  1. Economic Game Theory to Model the Attenuation of Virulence of an Obligate Intracellular Bacterium.

    Science.gov (United States)

    Tago, Damian; Meyer, Damien F

    2016-01-01

    Diseases induced by obligate intracellular pathogens have a large burden on global human and animal health. Understanding the factors involved in the virulence and fitness of these pathogens contributes to the development of control strategies against these diseases. Based on biological observations, a theoretical model using game theory is proposed to explain how obligate intracellular bacteria interact with their host. The equilibrium in such a game shows that the virulence and fitness of the bacterium is host-triggered and by changing the host's defense system to which the bacterium is confronted, an evolutionary process leads to an attenuated strain. Although, the attenuation procedure has already been conducted in practice in order to develop an attenuated vaccine (e.g., with Ehrlichia ruminantium), there was a lack of understanding of the theoretical basis behind this process. Our work provides a model to better comprehend the existence of different phenotypes and some underlying evolutionary mechanisms for the virulence of obligate intracellular bacteria.

  2. Cross-kingdom gene transfer facilitates the evolution of virulence in fungal pathogens.

    Science.gov (United States)

    Gardiner, Donald M; Kazan, Kemal; Manners, John M

    2013-09-01

    The constant interaction between plants and their pathogens has resulted in the evolution of a diverse array of microbial infection strategies. It is increasingly evident that horizontal acquisition of new virulence functions in fungi is one of the evolutionary processes that maintain pathogens' competitive edge over host plants. Genome analyses of fungi are pointing towards this phenomenon being particularly prevalent in the subphylum Pezizomycota. While the extent of cross-kingdom gene transfer can be determined with existing genomic tools and databases, so far very few horizontally transmitted genes have been functionally characterised, and an understanding of their physiological roles in virulence has been determined for even fewer genes. Understanding the evolutionary selection pressures that drive the retention of acquired genes in particular fungal lineages is important, as it will undoubtedly reveal new insights into both fungal virulence mechanisms and corresponding plant defence processes in the future. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Assessing the diversity of the virulence potential of Escherichia coli isolated from bacteremia in São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    A.C.M. Santos

    2013-11-01

    Full Text Available Most of the knowledge of the virulence determinants of extraintestinal pathogenic Escherichia coli (ExPEC comes from studies with human strains causing urinary tract infections and neonatal meningitis and animal strains causing avian colibacillosis. In this research, we analyzed the phylogenetic background, the presence of 20 ExPEC virulence factors, and the intrinsic virulence potential of 74 E. coli strains isolated in São Paulo, Brazil, from 74 hospitalized patients (43 males and 31 females with unknown-source bacteremia. Unlike other places in the world, the bacteremic strains originated equally from phylogroups B2 (35% and D (30%. A great variability in the profiles of virulence factors was noted in this survey. Nevertheless, 61% of the strains were classified as ExPEC, meaning that they possessed intrinsic virulent potential. Accordingly, these strains presented high virulence factor scores (average of 8.7, and were positively associated with 12 of 17 virulence factors detected. On the contrary, the non-ExPEC strains, isolated from 39% of the patients, presented a generally low virulence capacity (medium virulence factor score of 3.1, and were positively associated with only the colicin cvaC gene. These results show the importance of discriminating E. coli isolates that possess characteristics of true pathogens from those that may be merely opportunistic in order to better understand the virulence mechanisms involved in extraintestinal E. coli infections. Such knowledge is essential for epidemiological purposes as well as for development of control measures aimed to minimize the incidence of these life-threatening and costly infections.

  4. Analysis of Sporothrix schenckii sensu stricto and Sporothrix brasiliensis virulence in Galleria mellonella.

    Science.gov (United States)

    Clavijo-Giraldo, Diana M; Matínez-Alvarez, José A; Lopes-Bezerra, Leila M; Ponce-Noyola, Patricia; Franco, Bernardo; Almeida, Ricardo S; Mora-Montes, Héctor M

    2016-03-01

    The study of the host-pathogen interaction is essential to understand the mechanisms underlying adhesion, colonization and tissue damage by pathogens. This is usually achieved by performing in vivo studies using small mammals, such as rats, mice and guinea pigs. Nowadays, the mouse models of systemic or subcutaneous infection are the gold standard assays to analyze the virulence of members of the Sporothrix schenckii complex. There are, however, invertebrates that have been recently used as alternative hosts to assess the virulence of both bacteria and fungi, and among them, larvae of Galleria mellonella are popular because they are easy to breed, and require non-specialized facilities to maintain the colony. Here, we assessed the use of G. mellonella larvae to test the virulence of S. schenckii sensu stricto and Sporothrix brasiliensis strains, and found that infection with yeast-like cells, but not with conidia or germlings, reproduces the virulence data generated in the mouse model of infection. Furthermore, with this insect model we could classify the virulence of some strains as low, intermediate or high, in line with the observations in the mammalian model. Therefore, G. mellonella is suitable, and a new alternative, to test virulence of both S. schenckii sensu stricto and S. brasiliensis. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Use of Metarhizium anisopliae Chitinase Genes for Genotyping and Virulence Characterization

    Directory of Open Access Journals (Sweden)

    Saliou Niassy

    2013-01-01

    Full Text Available Virulence is the primary factor used for selection of entomopathogenic fungi (EPF for development as biopesticides. To understand the genetic mechanisms underlying differences in virulence of fungal isolates on various arthropod pests, we compared the chitinase genes, chi2 and chi4, of 8 isolates of Metarhizium anisopliae. The clustering of the isolates showed various groups depending on their virulence. However, the analysis of their chitinase DNA sequences chi2 and chi4 did not reveal major divergences. Although their protein translates have been implicated in fungal virulence, the predicted protein structure of chi2 was identical for all isolates. Despite the critical role of chitin digestion in fungal infection, we conclude that chi2 and chi4 genes cannot serve as molecular markers to characterize observed variations in virulence among M. anisopliae isolates as previously suggested. Nevertheless, processes controlling the efficient upregulation of chitinase expression might be responsible for different virulence characteristics. Further studies using comparative “in vitro” chitin digestion techniques would be more appropriate to compare the quality and the quantity of chitinase production between fungal isolates.

  6. Plasmid-mediated resistance and virulence mechanisms in the private health sector in KwaZulu-Natal, South Africa: An investigation of methicillin resistant Staphylococcus aureus (MRSA) clinical isolates collected during a three month period.

    Science.gov (United States)

    Amoako, Daniel G; Bester, Linda A; Somboro, Anou M; Baijnath, Sooraj; Govind, Chetna N; Essack, Sabiha Y

    2016-05-01

    Due to the lack of information on the plasmid content of MRSA strains in South Africa (SA), this study investigated the resistance and virulence mechanisms of 27 clinical isolates from the private health care sector over a period of 3 months. Plasmids were extracted and the presence of MRSA confirmed by the presence of mecA. The isolates were subjected to antimicrobial susceptibility testing and molecular characterization of common resistance encoding genes and frequently encountered virulence factors by PCR using plasmid DNA as the template. The genetic relatedness between the isolates was determined by pulsed field gel electrophoresis (PFGE). All isolates were plasmid positive, and displayed ampillicin, ciprofloxacin, gentamicin, rifampicin, tetracycline, erythromycin, and clindamycin resistance. They were all fully susceptible to daptomycin, linezolid, vancomycin, tigecycline and fusidic acid. Multidrug resistance (MDR) was found in 74.1% (20/27) of the MRSA isolates. The frequency of the resistance and virulence genes ranged from 100% to 0%. PFGE analysis revealed 10 pulsotypes, designated A-J, which showed correlation with resistance profile of the isolates in each group. Of note, 85.2% (23/27) of the isolates clustered into six major PFGE types giving an indication of similar circulating MRSA clones. This study highlights the genetic diversity and resistance mechanisms in MRSA strains from the private health sector in SA hence the need for implementing effective infection control programs. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. New Drugs for Anemia Treatment Based on a New Understanding of the Mechanisms of Stress Erythropoiesis

    Science.gov (United States)

    2015-11-01

    Award Number: W81XWH-12-1-0449 TITLE: New Drugs for Anemia Treatment Based on a New Understanding of the Mechanisms of Stress Erythropoiesis...COVERED 1Sep2012 - 31Aug2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER New Drugs for Anemia Treatment Based on a New Understanding of the...cell formation in "Nan" (neonatal anemia ) mice, raising the level of red cells to almost normal. It also causes an increase in the numbers of splenic

  8. Stress Response Protein BolA Influences Fitness and Promotes Salmonella enterica Serovar Typhimurium Virulence.

    Science.gov (United States)

    Mil-Homens, Dalila; Barahona, Susana; Moreira, Ricardo N; Silva, Inês J; Pinto, Sandra N; Fialho, Arsénio M; Arraiano, Cecília M

    2018-04-15

    The intracellular pathogen Salmonella enterica serovar Typhimurium has emerged as a major cause of foodborne illness, representing a severe clinical and economic concern worldwide. The capacity of this pathogen to efficiently infect and survive inside the host depends on its ability to synchronize a complex network of virulence mechanisms. Therefore, the identification of new virulence determinants has become of paramount importance in the search of new targets for drug development. BolA-like proteins are widely conserved in all kingdoms of life. In Escherichia coli , this transcription factor has a critical regulatory role in several mechanisms that are tightly related to bacterial virulence. Therefore, in the present work we used the well-established infection model Galleria mellonella to evaluate the role of BolA protein in S Typhimurium virulence. We have shown that BolA is an important player in S Typhimurium pathogenesis. Specifically, the absence of BolA leads to a defective virulence capacity that is most likely related to the remarkable effect of this protein on S Typhimurium evasion of the cellular response. Furthermore, it was demonstrated that BolA has a critical role in bacterial survival under harsh conditions since BolA conferred protection against acidic and oxidative stress. Hence, we provide evidence that BolA is a determining factor in the ability of Salmonella to survive and overcome host defense mechanisms, and this is an important step in progress to an understanding of the pathways underlying bacterial virulence. IMPORTANCE BolA has been described as an important protein for survival in the late stages of bacterial growth and under harsh environmental conditions. High levels of BolA in stationary phase and under stresses have been connected with a plethora of phenotypes, strongly suggesting its important role as a master regulator. Here, we show that BolA is a determining factor in the ability of Salmonella to survive and overcome host

  9. Understanding Creep Mechanisms in Graphite with Experiments, Multiscale Simulations, and Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Eapen, Jacob [North Carolina State Univ., Raleigh, NC (United States); Murty, Korukonda [North Carolina State Univ., Raleigh, NC (United States); Burchell, Timothy [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-06-02

    Disordering mechanisms in graphite have a long history with conflicting viewpoints. Using Raman and x-ray photon spectroscopy, electron microscopy, x-ray diffraction experiments and atomistic modeling and simulations, the current project has developed a fundamental understanding of early-to-late state radiation damage mechanisms in nuclear reactor grade graphite (NBG-18 and PCEA). We show that the topological defects in graphite play an important role under neutron and ion irradiation.

  10. Virulence determinants of equine infectious anemia virus.

    Science.gov (United States)

    Payne, Susan L; Fuller, Frederick J

    2010-01-01

    Equine infectious anemia virus (EIAV) is a macrophage-tropic lentivirus that rapidly Induces disease in experimentally infected horses. Because EIAV infection and replication is centered on the monocyte/macrophage and has a pronounced acute disease stage, it is a useful model system for understanding the contribution of monocyte/macrophages to other lentivirus-induced diseases. Genetic mapping studies utilizing chimeric proviruses in which parental viruses are acutely virulent or avirulent have allowed the identification of important regions that influence acute virulence. U3 regions in the viral LTR, surface envelope (SU) protein and the accessory S2 gene strongly influence acute disease expression. While the chimeric proviruses provide insight into genes or genome regions that affect viral pathogenesis, it is then necessary to further dissect those regions to focus on specific virus-host mechanisms that lead to disease expression. The V6 region of the viral env protein is an example of one identified region that may interact with the ELR-1 receptor in an important way and we are currently identifying S2 protein motifs required for disease expression.

  11. Host cell interactions of outer membrane vesicle-associated virulence factors of Enterohemorrhagic Escherichia coli O157: intracellular delivery, trafficking and mechanisms of cell injury

    Science.gov (United States)

    Outer membrane vesicles (OMVs) are important tools in bacterial virulence but their role in the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC) O157, the leading cause of life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, confocal laser...

  12. Sixth-Grade Students' Progress in Understanding the Mechanisms of Global Climate Change

    Science.gov (United States)

    Visintainer, Tammie; Linn, Marcia

    2015-04-01

    Developing solutions for complex issues such as global climate change requires an understanding of the mechanisms involved. This study reports on the impact of a technology-enhanced unit designed to improve understanding of global climate change, its mechanisms, and their relationship to everyday energy use. Global Climate Change, implemented in the Web-based Inquiry Science Environment (WISE), engages sixth-grade students in conducting virtual investigations using NetLogo models to foster an understanding of core mechanisms including the greenhouse effect. Students then test how the greenhouse effect is enhanced by everyday energy use. This study draws on three data sources: (1) pre- and post-unit interviews, (2) analysis of embedded assessments following virtual investigations, and (3) contrasting cases of two students (normative vs. non-normative understanding of the greenhouse effect). Results show the value of using virtual investigations for teaching the mechanisms associated with global climate change. Interviews document that students hold a wide range of ideas about the mechanisms driving global climate change. Investigations with models help students use evidence-based reasoning to distinguish their ideas. Results show that understanding the greenhouse effect offers a foundation for building connections between everyday energy use and increases in global temperature. An impediment to establishing coherent understanding was the persistence of an alternative conception about ozone as an explanation for climate change. These findings illustrate the need for regular revision of curriculum based on classroom trials. We discuss key design features of models and instructional revisions that can transform the teaching and learning of global climate change.

  13. Effects of Representation Sequences and Spatial Ability on Students' Scientific Understandings about the Mechanism of Breathing

    Science.gov (United States)

    Wu, Hsin-Kai; Lin, Yu-Fen; Hsu, Ying-Shao

    2013-01-01

    The purpose of this study was to investigate the effects of representation sequences and spatial ability on students' scientific understandings about the mechanism of breathing in human beings. 130 seventh graders were assigned to two groups with different sequential combinations of static and dynamic representations: SD group (i.e., viewing…

  14. Enhanced understanding of the relationship between chemical modification and mechanical properties of wood

    Science.gov (United States)

    Charles R. Frihart; Daniel J. Yelle; John Ralph; Robert J. Moon; Donald S. Stone; Joseph E. Jakes

    2008-01-01

    Chemical additions to wood often change its bulk properties, which can be determined using conventional macroscopic mechanical tests. However, the controlling interactions between chemicals and wood take place at and below the scale of individual cells and cell walls. To better understand the effects of chemical additions to wood, we have adapted and extended two...

  15. The DSF Family of Cell-Cell Signals: An Expanding Class of Bacterial Virulence Regulators.

    Directory of Open Access Journals (Sweden)

    Robert P Ryan

    2015-07-01

    Full Text Available Many pathogenic bacteria use cell-cell signaling systems involving the synthesis and perception of diffusible signal molecules to control virulence as a response to cell density or confinement to niches. Bacteria produce signals of diverse structural classes. Signal molecules of the diffusible signal factor (DSF family are cis-2-unsaturated fatty acids. The paradigm is cis-11-methyl-2-dodecenoic acid from Xanthomonas campestris pv. campestris (Xcc, which controls virulence in this plant pathogen. Although DSF synthesis was thought to be restricted to the xanthomonads, it is now known that structurally related molecules are produced by the unrelated bacteria Burkholderia cenocepacia and Pseudomonas aeruginosa. Furthermore, signaling involving these DSF family members contributes to bacterial virulence, formation of biofilms and antibiotic tolerance in these important human pathogens. Here we review the recent advances in understanding DSF signaling and its regulatory role in different bacteria. These advances include the description of the pathway/mechanism of DSF biosynthesis, identification of novel DSF synthases and new members of the DSF family, the demonstration of a diversity of DSF sensors to include proteins with a Per-Arnt-Sim (PAS domain and the description of some of the signal transduction mechanisms that impinge on virulence factor expression. In addition, we address the role of DSF family signals in interspecies signaling that modulates the behavior of other microorganisms. Finally, we consider a number of recently reported approaches for the control of bacterial virulence through the modulation of DSF signaling.

  16. A direct link between carbohydrate utilization and virulence in the major human pathogen group A Streptococcus.

    Science.gov (United States)

    Shelburne, Samuel A; Keith, David; Horstmann, Nicola; Sumby, Paul; Davenport, Michael T; Graviss, Edward A; Brennan, Richard G; Musser, James M

    2008-02-05

    Although central to pathogenesis, the molecular mechanisms used by microbes to regulate virulence factor production in specific environments during host-pathogen interaction are poorly defined. Several recent ex vivo and in vivo studies have found that the level of group A Streptococcus (GAS) virulence factor gene transcripts is temporally related to altered expression of genes encoding carbohydrate utilization proteins. These findings stimulated us to analyze the role in pathogenesis of catabolite control protein A (CcpA), a GAS ortholog of a key global regulator of carbohydrate metabolism in Bacillus subtilis. Inasmuch as the genomewide effects of CcpA in a human pathogen are unknown, we analyzed the transcriptome of a DeltaccpA isogenic mutant strain grown in nutrient-rich medium. CcpA influences the transcript levels of many carbohydrate utilization genes and several well characterized GAS virulence factors, including the potent cytolysin streptolysin S. Compared with the wild-type parental strain, the DeltaccpA isogenic mutant strain was significantly less virulent in a mouse model of invasive infection. Moreover, the isogenic mutant strain was significantly impaired in ability to colonize the mouse oropharynx. When grown in human saliva, a nutrient-limited environment, CcpA influenced production of several key virulence factors not influenced during growth in nutrient-rich medium. Purified recombinant CcpA bound to the promoter region of the gene encoding streptolysin S. Our discovery that GAS virulence and complex carbohydrate utilization are directly linked through CcpA provides enhanced understanding of a mechanism used by a Gram-positive pathogen to modulate virulence factor production in specific environments.

  17. Virulence on the fly: Drosophila melanogaster as a model genetic organism to decipher host-pathogen interactions.

    NARCIS (Netherlands)

    Limmer, S.; Quintin, J.; Hetru, C.; Ferrandon, D.

    2011-01-01

    To gain an in-depth grasp of infectious processes one has to know the specific interactions between the virulence factors of the pathogen and the host defense mechanisms. A thorough understanding is crucial for identifying potential new drug targets and designing drugs against which the pathogens

  18. Campylobacter virulence and survival factors.

    Science.gov (United States)

    Bolton, Declan J

    2015-06-01

    Despite over 30 years of research, campylobacteriosis is the most prevalent foodborne bacterial infection in many countries including in the European Union and the United States of America. However, relatively little is known about the virulence factors in Campylobacter or how an apparently fragile organism can survive in the food chain, often with enhanced pathogenicity. This review collates information on the virulence and survival determinants including motility, chemotaxis, adhesion, invasion, multidrug resistance, bile resistance and stress response factors. It discusses their function in transition through the food processing environment and human infection. In doing so it provides a fundamental understanding of Campylobacter, critical for improved diagnosis, surveillance and control. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Unit Mechanisms of Fission Gas Release: Current Understanding and Future Needs

    Energy Technology Data Exchange (ETDEWEB)

    Tonks, Michael; Andersson , David; Devanathan, Ram; Dubourg, Roland; El-Azab, Anter A.; Freyss, Michel; Iglesias, Fernando; Kulacsy, Katalin; Pastore, Giovanni; Phillpot, Simon R.; Welland, Michael

    2018-03-16

    Gaseous fission product transport and release has a large impact on fuel performance, degrading fuel properties and, once the gas is released into the gap between the fuel and cladding, lowering gap thermal conductivity and increasing gap pressure. While gaseous fission product behavior has been investigated with bulk reactor experiments and simplified analytical models, recent improvements in experimental and modeling approaches at the atomistic and mesoscales are being applied to provide unprecedented understanding of the unit mechanisms that define the fission product behavior. In this article, existing research on the basic mechanisms behind the various stages of fission gas release during normal reactor operation are summarized and critical areas where experimental and simulation work is needed are identified. This basic understanding of the fission gas behavior mechanisms has the potential to revolutionize our ability to predict fission product behavior during reactor operation and to design fuels that have improved fission product retention. In addition, this work can serve as a model on how a coupled experimental and modeling approach can be applied to understand the unit mechanisms behind other critical behaviors in reactor materials.

  20. How LeuT shapes our understanding of the mechanisms of sodium-coupled neurotransmitter transporters.

    Science.gov (United States)

    Penmatsa, Aravind; Gouaux, Eric

    2014-03-01

    Neurotransmitter transporters are ion-coupled symporters that drive the uptake of neurotransmitters from neural synapses. In the past decade, the structure of a bacterial amino acid transporter, leucine transporter (LeuT), has given valuable insights into the understanding of architecture and mechanism of mammalian neurotransmitter transporters. Different conformations of LeuT, including a substrate-free state, inward-open state, and competitive and non-competitive inhibitor-bound states, have revealed a mechanistic framework for the transport and transport inhibition of neurotransmitters. The current review integrates our understanding of the mechanistic and pharmacological properties of eukaryotic neurotransmitter transporters obtained through structural snapshots of LeuT.

  1. Understanding the growth mechanism of carbon nanotubes via the ``cluster volume to surface area" model

    Science.gov (United States)

    Mandati, Sreekanth; Kunstmann, Jens; Boerrnert, Felix; Schoenfelder, Ronny; Ruemmeli, Mark; Kar, Kamal K.; Cuniberti, Gianaurelio

    2010-03-01

    The influence of mixed catalysts for the high yield production of carbon nanotubes (CNTs) has been studied systematically. Based on extensive experimental data a ``Catalyst Volume to Surface Area'' (CVSA) model was developed to understand the influence of the process parameters on the yield and CNT diameter distribution [1]. In our study, we present a refined version of the CVSA model developed by combining experiments and simulations. We discuss our current understanding of the growth mechanism and how the model might be used to increase CNT yields by using mixed catalysts.[4pt] [1] S. Tetali et al., ACS Nano (2009), DOI: 10.1021/nn9012548.

  2. Proteomic approaches to understanding the role of the cytoskeleton in host-defense mechanisms

    Science.gov (United States)

    Radulovic, Marko; Godovac-Zimmermann, Jasminka

    2014-01-01

    The cytoskeleton is a cellular scaffolding system whose functions include maintenance of cellular shape, enabling cellular migration, division, intracellular transport, signaling and membrane organization. In addition, in immune cells, the cytoskeleton is essential for phagocytosis. Following the advances in proteomics technology over the past two decades, cytoskeleton proteome analysis in resting and activated immune cells has emerged as a possible powerful approach to expand our understanding of cytoskeletal composition and function. However, so far there have only been a handful of studies of the cytoskeleton proteome in immune cells. This article considers promising proteomics strategies that could augment our understanding of the role of the cytoskeleton in host-defense mechanisms. PMID:21329431

  3. Understanding the Mechanisms of Radiation Belt Dropouts Observed by Van Allen Probes

    Science.gov (United States)

    Xiang, Zheng; Tu, Weichao; Li, Xinlin; Ni, Binbin; Morley, S. K.; Baker, D. N.

    2017-10-01

    To achieve a better understanding of the dominant loss mechanisms for the rapid dropouts of radiation belt electrons, three distinct radiation belt dropout events observed by Van Allen Probes are comprehensively investigated. For each event, observations of the pitch angle distribution of electron fluxes and electromagnetic ion cyclotron (EMIC) waves are analyzed to determine the effects of atmospheric precipitation loss due to pitch angle scattering induced by EMIC waves. Last closed drift shells (LCDS) and magnetopause standoff position are obtained to evaluate the effects of magnetopause shadowing loss. Evolution of electron phase space density (PSD) versus L* profiles and the μ and K (first and second adiabatic invariants) dependence of the electron PSD drops are calculated to further analyze the dominant loss mechanisms at different L*. Our findings suggest that these radiation belt dropouts can be classified into distinct classes in terms of dominant loss mechanisms: magnetopause shadowing dominant, EMIC wave scattering dominant, and combination of both mechanisms. Different from previous understanding, our results show that magnetopause shadowing can deplete electrons at L* 4. Compared to the magnetopause standoff position, it is more reliable to use LCDS to evaluate the impact of magnetopause shadowing. The evolution of electron PSD versus L* profile and the μ, K dependence of electron PSD drops can provide critical and credible clues regarding the mechanisms responsible for electron losses at different L* over the outer radiation belt.

  4. Unified understanding of folding and binding mechanisms of globular and intrinsically disordered proteins.

    Science.gov (United States)

    Arai, Munehito

    2018-01-06

    Extensive experimental and theoretical studies have advanced our understanding of the mechanisms of folding and binding of globular proteins, and coupled folding and binding of intrinsically disordered proteins (IDPs). The forces responsible for conformational changes and binding are common in both proteins; however, these mechanisms have been separately discussed. Here, we attempt to integrate the mechanisms of coupled folding and binding of IDPs, folding of small and multi-subdomain proteins, folding of multimeric proteins, and ligand binding of globular proteins in terms of conformational selection and induced-fit mechanisms as well as the nucleation-condensation mechanism that is intermediate between them. Accumulating evidence has shown that both the rate of conformational change and apparent rate of binding between interacting elements can determine reaction mechanisms. Coupled folding and binding of IDPs occurs mainly by induced-fit because of the slow folding in the free form, while ligand binding of globular proteins occurs mainly by conformational selection because of rapid conformational change. Protein folding can be regarded as the binding of intramolecular segments accompanied by secondary structure formation. Multi-subdomain proteins fold mainly by the induced-fit (hydrophobic collapse) mechanism, as the connection of interacting segments enhances the binding (compaction) rate. Fewer hydrophobic residues in small proteins reduce the intramolecular binding rate, resulting in the nucleation-condensation mechanism. Thus, the folding and binding of globular proteins and IDPs obey the same general principle, suggesting that the coarse-grained, statistical mechanical model of protein folding is promising for a unified theoretical description of all mechanisms.

  5. Material properties of biofilms – key methods for understanding permeability and mechanics

    Science.gov (United States)

    Billings, Nicole; Birjiniuk, Alona; Samad, Tahoura S.; Doyle, Patrick S.; Ribbeck, Katharina

    2015-01-01

    Microorganisms can form biofilms, which are multicellular communities surrounded by a hydrated extracellular matrix of polymers. Central properties of the biofilm are governed by this extracellular matrix, which provides mechanical stability to the three-dimensional biofilm structure, regulates the ability of the biofilm to adhere to surfaces, and determines the ability of the biofilm to adsorb gasses, solutes, and foreign cells. Despite their critical relevance for understanding and eliminating of biofilms, the materials properties of the extracellular matrix are understudied. Here, we offer the reader a guide to current technologies that can be utilized to specifically assess the permeability and mechanical properties of the biofilm matrix and its interacting components. In particular, we highlight technological advances in instrumentation and interactions between multiple disciplines that have broadened the spectrum of methods available to conduct these studies. We review pioneering work that furthers our understanding of the material properties of biofilms. PMID:25719969

  6. Understanding the mechanism of catalytic fast pyrolysis by unveiling reactive intermediates in heterogeneous catalysis

    Science.gov (United States)

    Hemberger, Patrick; Custodis, Victoria B. F.; Bodi, Andras; Gerber, Thomas; van Bokhoven, Jeroen A.

    2017-06-01

    Catalytic fast pyrolysis is a promising way to convert lignin into fine chemicals and fuels, but current approaches lack selectivity and yield unsatisfactory conversion. Understanding the pyrolysis reaction mechanism at the molecular level may help to make this sustainable process more economic. Reactive intermediates are responsible for product branching and hold the key to unveiling these mechanisms, but are notoriously difficult to detect isomer-selectively. Here, we investigate the catalytic pyrolysis of guaiacol, a lignin model compound, using photoelectron photoion coincidence spectroscopy with synchrotron radiation, which allows for isomer-selective detection of reactive intermediates. In combination with ambient pressure pyrolysis, we identify fulvenone as the central reactive intermediate, generated by catalytic demethylation to catechol and subsequent dehydration. The fulvenone ketene is responsible for the phenol formation. This technique may open unique opportunities for isomer-resolved probing in catalysis, and holds the potential for achieving a mechanistic understanding of complex, real-life catalytic processes.

  7. Understanding the mechanism of catalytic fast pyrolysis by unveiling reactive intermediates in heterogeneous catalysis

    Science.gov (United States)

    Hemberger, Patrick; Custodis, Victoria B. F.; Bodi, Andras; Gerber, Thomas; van Bokhoven, Jeroen A.

    2017-01-01

    Catalytic fast pyrolysis is a promising way to convert lignin into fine chemicals and fuels, but current approaches lack selectivity and yield unsatisfactory conversion. Understanding the pyrolysis reaction mechanism at the molecular level may help to make this sustainable process more economic. Reactive intermediates are responsible for product branching and hold the key to unveiling these mechanisms, but are notoriously difficult to detect isomer-selectively. Here, we investigate the catalytic pyrolysis of guaiacol, a lignin model compound, using photoelectron photoion coincidence spectroscopy with synchrotron radiation, which allows for isomer-selective detection of reactive intermediates. In combination with ambient pressure pyrolysis, we identify fulvenone as the central reactive intermediate, generated by catalytic demethylation to catechol and subsequent dehydration. The fulvenone ketene is responsible for the phenol formation. This technique may open unique opportunities for isomer-resolved probing in catalysis, and holds the potential for achieving a mechanistic understanding of complex, real-life catalytic processes. PMID:28660882

  8. Improving student understanding of addition of angular momentum in quantum mechanics

    Directory of Open Access Journals (Sweden)

    Guangtian Zhu

    2013-01-01

    Full Text Available We describe the difficulties advanced undergraduate and graduate students have with concepts related to addition of angular momentum in quantum mechanics. We also describe the development and implementation of a research-based learning tool, Quantum Interactive Learning Tutorial (QuILT, to reduce these difficulties. The preliminary evaluation shows that the QuILT related to the basics of the addition of angular momentum is helpful in improving students’ understanding of these concepts.

  9. Understanding treatment effect mechanisms of the CAMBRA randomized trial in reducing caries increment

    OpenAIRE

    Cheng, J; Chaffee, BW; Cheng, NF; Gansky, SA; Featherstone, JDB

    2015-01-01

    © International & American Associations for Dental Research 2014. The Caries Management By Risk Assessment (CAMBRA) randomized controlled trial showed that an intervention featuring combined antibacterial and fluoride therapy significantly reduced bacterial load and suggested reduced caries increment in adults with 1 to 7 baseline cavitated teeth. While trial results speak to the overall effectiveness of an intervention, insight can be gained from understanding the mechanism by which an int...

  10. Heteropathogenic virulence and phylogeny reveal phased pathogenic metamorphosis in Escherichia coli O2:H6.

    Science.gov (United States)

    Bielaszewska, Martina; Schiller, Roswitha; Lammers, Lydia; Bauwens, Andreas; Fruth, Angelika; Middendorf, Barbara; Schmidt, M Alexander; Tarr, Phillip I; Dobrindt, Ulrich; Karch, Helge; Mellmann, Alexander

    2014-03-01

    Extraintestinal pathogenic and intestinal pathogenic (diarrheagenic) Escherichia coli differ phylogenetically and by virulence profiles. Classic theory teaches simple linear descent in this species, where non-pathogens acquire virulence traits and emerge as pathogens. However, diarrheagenic Shiga toxin-producing E. coli (STEC) O2:H6 not only possess and express virulence factors associated with diarrheagenic and uropathogenic E. coli but also cause diarrhea and urinary tract infections. These organisms are phylogenetically positioned between members of an intestinal pathogenic group (STEC) and extraintestinal pathogenic E. coli. STEC O2:H6 is, therefore, a 'heteropathogen,' and the first such hybrid virulent E. coli identified. The phylogeny of these E. coli and the repertoire of virulence traits they possess compel consideration of an alternate view of pathogen emergence, whereby one pathogroup of E. coli undergoes phased metamorphosis into another. By understanding the evolutionary mechanisms of bacterial pathogens, rational strategies for counteracting their detrimental effects on humans can be developed.

  11. Salmonella-secreted Virulence Factors

    Energy Technology Data Exchange (ETDEWEB)

    Heffron, Fred; Niemann, George; Yoon, Hyunjin; Kidwai, Afshan S.; Brown, Roslyn N.; McDermott, Jason E.; Smith, Richard D.; Adkins, Joshua N.

    2011-05-01

    In this short review we discuss secreted virulence factors of Salmonella, which directly affect Salmonella interaction with its host. Salmonella secretes protein to subvert host defenses but also, as discussed, to reduce virulence thereby permitting the bacteria to persist longer and more successfully disperse. The type III secretion system (TTSS) is the best known and well studied of the mechanisms that enable secretion from the bacterial cytoplasm to the host cell cytoplasm. Other secretion systems include outer membrane vesicles, which are present in all Gram-negative bacteria examined to date, two-partner secretion, and type VI secretion will also be addressed. Excellent reviews of Salmonella secreted effectors have focused on themes such as actin rearrangements, vesicular trafficking, ubiquitination, and the activities of the virulence factors themselves. This short review is based on S. Typhimurium infection of mice because it is a model of typhoid like disease in humans. We have organized effectors in terms of events that happen during the infection cycle and how secreted effectors may be involved.

  12. Integrating Classical with Emerging Concepts for Better Understanding of Salinity Stress Tolerance Mechanisms in Rice

    Directory of Open Access Journals (Sweden)

    Navdeep Kaur

    2017-07-01

    Full Text Available Rice is an important cereal crop responsible for world's food security. The sensitivity of rice plants toward a range of abiotic stresses is a prime challenge for its overall growth and productivity. Among these, salinity is a major stress which results in a significant loss of global rice yield annually. For finding straightforward and strict future solutions in order to assure the food security to growing world population, understanding of the various mechanisms responsible for salt stress tolerance in rice is of paramount importance. In classical studies, identification of salt tolerant cultivars and the genetic markers linked to salt tolerance and breeding approaches have been given emphasis. It further affirmed on the identification of various pathways regulating the complex process of salt stress adaptation. However, only limited success has been achieved in these approaches as salt tolerance is a complex process and is governed by multiple factors. Hence, for better understanding of salt tolerance mechanisms, a comprehensive approach involving physiological, biochemical and molecular studies is much warranted. Modern experimental and genetic resources have provided a momentum in this direction and have provided molecular insights into different salt stress responsive pathways at the signaling and regulatory level. The integrative knowledge of classical and modern research of the understanding of salt stress adaptive pathways can help the researchers for designing effective strategies to fight against salt stress. Hence, the present review is focused on the understanding of the salt stress tolerance mechanisms in rice through the consolidative knowledge of classical and modern concepts. It further highlights the emerging new trends of salt stress adaptive pathways in rice.

  13. Understanding cellular responses to toxic agents: a model for mechanism-choice in bacterial metal resistance.

    Science.gov (United States)

    Rouch, D A; Lee, B T; Morby, A P

    1995-02-01

    Bacterial resistances to metals are heterogeneous in both their genetic and biochemical bases. Metal resistance may be chromosomally-, plasmid- or transposon-encoded, and one or more genes may be involved: at the biochemical level at least six different mechanisms are responsible for resistance. Various types of resistance mechanisms can occur singly or in combination and for a particular metal different mechanisms of resistance can occur in the same species. To understand better the diverse responses of bacteria to metal ion challenge we have constructed a qualitative model for the selection of metal resistance in bacteria. How a bacterium becomes resistant to a particular metal depends on the number and location of cellular components sensitive to the specific metal ion. Other important selective factors include the nature of the uptake systems for the metal, the role and interactions of the metal in the normal metabolism of the cell and the availability of plasmid (or transposon) encoded resistance mechanisms. The selection model presented is based on the interaction of these factors and allows predictions to be made about the evolution of metal resistance in bacterial populations. It also allows prediction of the genetic basis and of mechanisms of resistance which are in substantial agreement with those in well-documented populations. The interaction of, and selection for resistance to, toxic substances in addition to metals, such as antibiotics and toxic analogues, involve similar principles to those concerning metals. Potentially, models for selection of resistance to any substance can be derived using this approach.

  14. Mutations induced by ultraviolet radiation affecting virulence in Puccinia striiformis

    International Nuclear Information System (INIS)

    Shang Hongsheng; Jing Jinxue; Li Zhenqi

    1994-01-01

    Uredospores of parent culture, cy 29-1, were treated by ultraviolet radiation and mutations to virulent were tested on resistant wheat cultivars inoculated with treated spores. 7 mutant cultures virulent to the test cultivars were developed with estimated mutation rate 10~6~10~4. The virulence of mutant cultures was different from the all known races of stripe rust. Resistance segregation to mutant cultures was detected in two test cultivars. The results suggested that mutation was important mechanism of virulence variation operative in asexual population of rust fungi

  15. Exploring virulence and immunogenicity in the emerging pathogen Sporothrix brasiliensis.

    Science.gov (United States)

    Della Terra, Paula Portella; Rodrigues, Anderson Messias; Fernandes, Geisa Ferreira; Nishikaku, Angela Satie; Burger, Eva; de Camargo, Zoilo Pires

    2017-08-01

    Sporotrichosis is a polymorphic chronic infection of humans and animals classically acquired after traumatic inoculation with soil and plant material contaminated with Sporothrix spp. propagules. An alternative and successful route of transmission is bites and scratches from diseased cats, through which Sporothrix yeasts are inoculated into mammalian tissue. The development of a murine model of subcutaneous sporotrichosis mimicking the alternative route of transmission is essential to understanding disease pathogenesis and the development of novel therapeutic strategies. To explore the impact of horizontal transmission in animals (e.g., cat-cat) and zoonotic transmission on Sporothrix fitness, the left hind footpads of BALB/c mice were inoculated with 5×106 yeasts (n = 11 S. brasiliensis, n = 2 S. schenckii, or n = 1 S. globosa). Twenty days post-infection, our model reproduced both the pathophysiology and symptomology of sporotrichosis with suppurating subcutaneous nodules that progressed proximally along lymphatic channels. Across the main pathogenic members of the S. schenckii clade, S. brasiliensis was usually more virulent than S. schenckii and S. globosa. However, the virulence in S. brasiliensis was strain-dependent, and we demonstrated that highly virulent isolates disseminate from the left hind footpad to the liver, spleen, kidneys, lungs, heart, and brain of infected animals, inducing significant and chronic weight loss (losing up to 15% of their body weight). The weight loss correlated with host death between 2 and 16 weeks post-infection. Histopathological features included necrosis, suppurative inflammation, and polymorphonuclear and mononuclear inflammatory infiltrates. Immunoblot using specific antisera and homologous exoantigen investigated the humoral response. Antigenic profiles were isolate-specific, supporting the hypothesis that different Sporothrix species can elicit a heterogeneous humoral response over time, but cross reaction was observed

  16. Geographic variation and trade-offs in parasitoid virulence.

    Science.gov (United States)

    Fors, Lisa; Markus, Robert; Theopold, Ulrich; Ericson, Lars; Hambäck, Peter A

    2016-11-01

    Host-parasitoid systems are characterized by a continuous development of new defence strategies in hosts and counter-defence mechanisms in parasitoids. This co-evolutionary arms race makes host-parasitoid systems excellent for understanding trade-offs in host use caused by evolutionary changes in host immune responses and parasitoid virulence. However, knowledge obtained from natural host-parasitoid systems on such trade-offs is still limited. In this study, the aim was to examine trade-offs in parasitoid virulence in Asecodes parviclava (Hymenoptera: Eulophidae) when attacking three closely related beetles: Galerucella pusilla, Galerucella calmariensis and Galerucella tenella (Coleoptera: Chrysomelidae). A second aim was to examine whether geographic variation in parasitoid infectivity or host immune response could explain differences in parasitism rate between northern and southern sites. More specifically, we wanted to examine whether the capacity to infect host larvae differed depending on the previous host species of the parasitoids and if such differences were connected to differences in the induction of host immune systems. This was achieved by combining controlled parasitism experiments with cytological studies of infected larvae. Our results reveal that parasitism success in A. parviclava differs both depending on previous and current host species, with a higher virulence when attacking larvae of the same species as the previous host. Virulence was in general high for parasitoids from G. pusilla and low for parasitoids from G. calmariensis. At the same time, G. pusilla larvae had the strongest immune response and G. calmariensis the weakest. These observations were linked to changes in the larval hemocyte composition, showing changes in cell types important for the encapsulation process in individuals infected by more or less virulent parasitoids. These findings suggest ongoing evolution in parasitoid virulence and host immune response, making the

  17. It's Rather like Learning a Language: Development of talk and conceptual understanding in mechanics lessons

    Science.gov (United States)

    Rincke, Karsten

    2011-01-01

    Although a broad literature exists concerning the development of conceptual understanding of force and other topics within mechanics, little is known about the role and development of students' talk about the subject. The paper presents an in-depth investigation of students' talk whilst being introduced to the concept of force. The main research goal was to investigate and understand how students develop an understanding of the concept of force and how they use and understand the term 'force'. Therefore, we make relation to the research field of students' preconceptions and the field of second language learning. Two classes of students (N = 47) were videotaped during a time period of nine lessons, each transcribed and analysed using a category system. Additional data were obtained via written tasks, logs kept by the students, and tests. The detailed analysis of the talk and the results of the tests indicate that students face difficulties in using the term 'force' scientifically similar to those in a foreign language instruction. Vygotsky already recognised a relationship between learning in science and learning a language. In this paper, important aspects of this relationship are discussed based upon empirical data. We conclude that in some respects it might be useful to make reference to the research related to language learning when thinking about improving science education. In particular, according to Selinker's concept of interlanguage describing language-learning processes within language instruction, the language used by the students during physics lessons can be viewed as a 'scientific interlanguage'.

  18. IscR Is Essential for Yersinia pseudotuberculosis Type III Secretion and Virulence

    OpenAIRE

    Miller, Halie K.; Kwuan, Laura; Schwiesow, Leah; Bernick, David L.; Mettert, Erin; Ramirez, Hector A.; Ragle, James M.; Chan, Patricia P.; Kiley, Patricia J.; Lowe, Todd M.; Auerbuch, Victoria

    2014-01-01

    Type III secretion systems (T3SS) are essential for virulence in dozens of pathogens, but are not required for growth outside the host. Therefore, the T3SS of many bacterial species are under tight regulatory control. To increase our understanding of the molecular mechanisms behind T3SS regulation, we performed a transposon screen to identify genes important for T3SS function in the food-borne pathogen Yersinia pseudotuberculosis. We identified two unique transposon insertions in YPTB2860, a ...

  19. Understanding dental CAD/CAM for restorations--the digital workflow from a mechanical engineering viewpoint.

    Science.gov (United States)

    Tapie, L; Lebon, N; Mawussi, B; Fron Chabouis, H; Duret, F; Attal, J-P

    2015-01-01

    As digital technology infiltrates every area of daily life, including the field of medicine, so it is increasingly being introduced into dental practice. Apart from chairside practice, computer-aided design/computer-aided manufacturing (CAD/CAM) solutions are available for creating inlays, crowns, fixed partial dentures (FPDs), implant abutments, and other dental prostheses. CAD/CAM dental solutions can be considered a chain of digital devices and software for the almost automatic design and creation of dental restorations. However, dentists who want to use the technology often do not have the time or knowledge to understand it. A basic knowledge of the CAD/CAM digital workflow for dental restorations can help dentists to grasp the technology and purchase a CAM/CAM system that meets the needs of their office. This article provides a computer-science and mechanical-engineering approach to the CAD/CAM digital workflow to help dentists understand the technology.

  20. Cognitive neuroepigenetics: the next evolution in our understanding of the molecular mechanisms underlying learning and memory?

    Science.gov (United States)

    Marshall, Paul; Bredy, Timothy W.

    2016-07-01

    A complete understanding of the fundamental mechanisms of learning and memory continues to elude neuroscientists. Although many important discoveries have been made, the question of how memories are encoded and maintained at the molecular level remains. So far, this issue has been framed within the context of one of the most dominant concepts in molecular biology, the central dogma, and the result has been a protein-centric view of memory. Here, we discuss the evidence supporting a role for neuroepigenetic mechanisms, which constitute dynamic and reversible, state-dependent modifications at all levels of control over cellular function, and their role in learning and memory. This neuroepigenetic view suggests that DNA, RNA and protein each influence one another to produce a holistic cellular state that contributes to the formation and maintenance of memory, and predicts a parallel and distributed system for the consolidation, storage and retrieval of the engram.

  1. Utilizing toxicogenomic data to understand chemical mechanism of action in risk assessment

    International Nuclear Information System (INIS)

    Wilson, Vickie S.; Keshava, Nagalakshmi; Hester, Susan; Segal, Deborah; Chiu, Weihsueh; Thompson, Chad M.; Euling, Susan Y.

    2013-01-01

    The predominant role of toxicogenomic data in risk assessment, thus far, has been one of augmentation of more traditional in vitro and in vivo toxicology data. This article focuses on the current available examples of instances where toxicogenomic data has been evaluated in human health risk assessment (e.g., acetochlor and arsenicals) which have been limited to the application of toxicogenomic data to inform mechanism of action. This article reviews the regulatory policy backdrop and highlights important efforts to ultimately achieve regulatory acceptance. A number of research efforts on specific chemicals that were designed for risk assessment purposes have employed mechanism or mode of action hypothesis testing and generating strategies. The strides made by large scale efforts to utilize toxicogenomic data in screening, testing, and risk assessment are also discussed. These efforts include both the refinement of methodologies for performing toxicogenomics studies and analysis of the resultant data sets. The current issues limiting the application of toxicogenomics to define mode or mechanism of action in risk assessment are discussed together with interrelated research needs. In summary, as chemical risk assessment moves away from a single mechanism of action approach toward a toxicity pathway-based paradigm, we envision that toxicogenomic data from multiple technologies (e.g., proteomics, metabolomics, transcriptomics, supportive RT-PCR studies) can be used in conjunction with one another to understand the complexities of multiple, and possibly interacting, pathways affected by chemicals which will impact human health risk assessment

  2. Twenty-five years of progress in understanding pollination mechanisms in palms (Arecaceae)

    Science.gov (United States)

    Barfod, Anders S.; Hagen, Melanie; Borchsenius, Finn

    2011-01-01

    Background With more than 90 published studies of pollination mechanisms, the palm family is one of the better studied tropical families of angiosperms. Understanding palm–pollinator interactions has implications for tropical silviculture, agroforestry and horticulture, as well as for our understanding of palm evolution and diversification. We review the rich literature on pollination mechanisms in palms that has appeared since the last review of palm pollination studies was published 25 years ago. Scope and Conclusions Visitors to palm inflorescences are attracted by rewards such as food, shelter and oviposition sites. The interaction between the palm and its visiting fauna represents a trade-off between the services provided by the potential pollinators and the antagonistic activities of other insect visitors. Evidence suggests that beetles constitute the most important group of pollinators in palms, followed by bees and flies. Occasional pollinators include mammals (e.g. bats and marsupials) and even crabs. Comparative studies of palm–pollinator interactions in closely related palm species document transitions in floral morphology, phenology and anatomy correlated with shifts in pollination vectors. Synecological studies show that asynchronous flowering and partitioning of pollinator guilds may be important regulators of gene flow between closely related sympatric taxa and potential drivers of speciation processes. Studies of larger plant–pollinator networks point out the importance of competition for pollinators between palms and other flowering plants and document how the insect communities in tropical forest canopies probably influence the reproductive success of palms. However, published studies have a strong geographical bias towards the South American region and a taxonomic bias towards the tribe Cocoseae. Future studies should try to correct this imbalance to provide a more representative picture of pollination mechanisms and their evolutionary

  3. Progress in Understanding Degradation Mechanisms and Improving Stability in Organic Photovoltaics

    KAUST Repository

    Mateker, William R.

    2016-12-23

    Understanding the degradation mechanisms of organic photovoltaics is particularly important, as they tend to degrade faster than their inorganic counterparts, such as silicon and cadmium telluride. An overview is provided here of the main degradation mechanisms that researchers have identified so far that cause extrinsic degradation from oxygen and water, intrinsic degradation in the dark, and photo-induced burn-in. In addition, it provides methods for researchers to identify these mechanisms in new materials and device structures to screen them more quickly for promising long-term performance. These general strategies will likely be helpful in other photovoltaic technologies that suffer from insufficient stability, such as perovskite solar cells. Finally, the most promising lifetime results are highlighted and recommendations to improve long-term performance are made. To prevent degradation from oxygen and water for sufficiently long time periods, OPVs will likely need to be encapsulated by barrier materials with lower permeation rates of oxygen and water than typical flexible substrate materials. To improve stability at operating temperatures, materials will likely require glass transition temperatures above 100 °C. Methods to prevent photo-induced burn-in are least understood, but recent research indicates that using pure materials with dense and ordered film morphologies can reduce the burn-in effect.

  4. Progress in Understanding Degradation Mechanisms and Improving Stability in Organic Photovoltaics.

    Science.gov (United States)

    Mateker, William R; McGehee, Michael D

    2017-03-01

    Understanding the degradation mechanisms of organic photovoltaics is particularly important, as they tend to degrade faster than their inorganic counterparts, such as silicon and cadmium telluride. An overview is provided here of the main degradation mechanisms that researchers have identified so far that cause extrinsic degradation from oxygen and water, intrinsic degradation in the dark, and photo-induced burn-in. In addition, it provides methods for researchers to identify these mechanisms in new materials and device structures to screen them more quickly for promising long-term performance. These general strategies will likely be helpful in other photovoltaic technologies that suffer from insufficient stability, such as perovskite solar cells. Finally, the most promising lifetime results are highlighted and recommendations to improve long-term performance are made. To prevent degradation from oxygen and water for sufficiently long time periods, OPVs will likely need to be encapsulated by barrier materials with lower permeation rates of oxygen and water than typical flexible substrate materials. To improve stability at operating temperatures, materials will likely require glass transition temperatures above 100 °C. Methods to prevent photo-induced burn-in are least understood, but recent research indicates that using pure materials with dense and ordered film morphologies can reduce the burn-in effect. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Understanding comorbidity among internalizing problems: Integrating latent structural models of psychopathology and risk mechanisms

    Science.gov (United States)

    Hankin, Benjamin L.; Snyder, Hannah R.; Gulley, Lauren D.; Schweizer, Tina H.; Bijttebier, Patricia; Nelis, Sabine; Toh, Gim; Vasey, Michael W.

    2016-01-01

    It is well known that comorbidity is the rule, not the exception, for categorically defined psychiatric disorders, and this is also the case for internalizing disorders of depression and anxiety. This theoretical review paper addresses the ubiquity of comorbidity among internalizing disorders. Our central thesis is that progress in understanding this co-occurrence can be made by employing latent dimensional structural models that organize both psychopathology as well as vulnerabilities and risk mechanisms and by connecting the multiple levels of risk and psychopathology outcomes together. Different vulnerabilities and risk mechanisms are hypothesized to predict different levels of the structural model of psychopathology. We review the present state of knowledge based on concurrent and developmental sequential comorbidity patterns among common discrete psychiatric disorders in youth, and then we advocate for the use of more recent bifactor dimensional models of psychopathology (e.g., p factor, Caspi et al., 2014) that can help to explain the co-occurrence among internalizing symptoms. In support of this relatively novel conceptual perspective, we review six exemplar vulnerabilities and risk mechanisms, including executive function, information processing biases, cognitive vulnerabilities, positive and negative affectivity aspects of temperament, and autonomic dysregulation, along with the developmental occurrence of stressors in different domains, to show how these vulnerabilities can predict the general latent psychopathology factor, a unique latent internalizing dimension, as well as specific symptom syndrome manifestations. PMID:27739389

  6. Features of Knowledge Building in Biology: Understanding Undergraduate Students’ Ideas about Molecular Mechanisms

    Science.gov (United States)

    Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S.

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning. PMID:26931398

  7. Understanding the Impact of Root Morphology on Overturning Mechanisms: A Modelling Approach

    Science.gov (United States)

    Fourcaud, Thierry; Ji, Jin-Nan; Zhang, Zhi-Qiang; Stokes, Alexia

    2008-01-01

    Background and Aims The Finite Element Method (FEM) has been used in recent years to simulate overturning processes in trees. This study aimed at using FEM to determine the role of individual roots in tree anchorage with regard to different rooting patterns, and to estimate stress distribution in the soil and roots during overturning. Methods The FEM was used to carry out 2-D simulations of tree uprooting in saturated soft clay and loamy sand-like soil. The anchorage model consisted of a root system embedded in a soil block. Two root patterns were used and individual roots removed to determine their contribution to anchorage. Key Results In clay-like soil the size of the root–soil plate formed during overturning was defined by the longest roots. Consequently, all other roots localized within this plate had no influence on anchorage strength. In sand-like soil, removing individual root elements altered anchorage resistance. This result was due to a modification of the shape and size of the root–soil plate, as well as the location of the rotation axis. The tap root and deeper roots had more influence on overturning resistance in sand-like soil compared with clay-like soil. Mechanical stresses were higher in the most superficial roots and also in leeward roots in sand-like soil. The relative difference in stresses between the upper and lower sides of lateral roots was sensitive to root insertion angle. Assuming that root eccentricity is a response to mechanical stresses, these results explain why eccentricity differs depending on root architecture. Conclusions A simple 2-D Finite Element model was developed to better understand the mechanisms involved during tree overturning. It has been shown how root system morphology and soil mechanical properties can modify the shape of the root plate slip surface as well as the position of the rotation axis, which are major components of tree anchorage. PMID:17942593

  8. Using the glacial geomorphology of palaeo-ice streams to understand mechanisms of ice sheet collapse

    Science.gov (United States)

    Stokes, Chris R.; Margold, Martin; Clark, Chris; Tarasov, Lev

    2017-04-01

    Processes which bring about ice sheet deglaciation are critical to our understanding of glacial-interglacial cycles and ice sheet sensitivity to climate change. The precise mechanisms of deglaciation are also relevant to our understanding of modern-day ice sheet stability and concerns over global sea level rise. Mass loss from ice sheets can be broadly partitioned between melting and a 'dynamic' component whereby rapidly-flowing ice streams/outlet glaciers transfer ice from the interior to the oceans. Surface and basal melting (e.g. of ice shelves) are closely linked to atmospheric and oceanic conditions, but the mechanisms that drive dynamic changes in ice stream discharge are more complex, which generates much larger uncertainties about their future contribution to ice sheet mass loss and sea level rise. A major problem is that observations of modern-day ice streams typically span just a few decades and, at the ice-sheet scale, it is unclear how the entire drainage network of ice streams evolves during deglaciation. A key question is whether ice streams might increase and sustain rates of mass loss over centuries or millennia, beyond those expected for a given ocean-climate forcing. To address this issue, numerous workers have sought to understand ice stream dynamics over longer time-scales using their glacial geomorphology in the palaeo-record. Indeed, our understanding of their geomorphology has grown rapidly in the last three decades, from almost complete ignorance to a detailed knowledge of their geomorphological products. Building on this body of work, this paper uses the glacial geomorphology of 117 ice streams in the North American Laurentide Ice Sheet to reconstruct their activity during its deglaciation ( 22,000 to 7,000 years ago). Ice stream activity was characterised by high variability in both time and space, with ice streams switching on and off in different locations. During deglaciation, we find that their overall number decreased, they occupied a

  9. Gender differences in conceptual understanding of Newtonian mechanics: a UK cross-institution comparison

    International Nuclear Information System (INIS)

    Bates, Simon; Donnelly, Robyn; MacPhee, Cait; Sands, David; Birch, Marion; Walet, Niels R

    2013-01-01

    We present the results of a combined study from three UK universities where we investigate the existence and persistence of a performance gender gap in conceptual understanding of Newtonian mechanics. Using the Force Concept Inventory, we find that students at all three universities exhibit a statistically significant gender gap, with males outperforming females. This gap is narrowed but not eliminated after instruction, using a variety of instructional approaches. Furthermore, we find that before instruction the quartile with the lowest performance on the diagnostic instrument comprises a disproportionately high fraction (∼50%) of the total female cohort. The majority of these students remain in the lowest-performing quartile post-instruction. Analysis of responses to individual items shows that male students outperform female students on practically all items on the instrument. Comparing the performance of the same group of students on end-of-course examinations, we find no statistically significant gender gaps. (paper)

  10. Emerging understanding of the mechanism of action of Bronchial Thermoplasty in asthma.

    Science.gov (United States)

    d'Hooghe, J N S; Ten Hacken, N H T; Weersink, E J M; Sterk, P J; Annema, J T; Bonta, P I

    2018-01-01

    Bronchial Thermoplasty (BT) is an endoscopic treatment for moderate-to-severe asthma patients who are uncontrolled despite optimal medical therapy. Effectiveness of BT has been demonstrated in several randomized clinical trials. However, the asthma phenotype that benefits most of this treatment is unclear, partly because the mechanism of action is incompletely understood. BT was designed to reduce the amount of airway smooth muscle (ASM), but additional direct and indirect effects on airway pathophysiology are expected. This review will provide an overview of the different components of airway pathophysiology including remodeling, with the ASM as the key player. Current concepts in the understanding of BT clinical effectiveness with a focus on its impact on airway remodeling will be reviewed. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. The contributions of cognitive neuroscience and neuroimaging to understanding mechanisms of behavior change in addiction.

    Science.gov (United States)

    Morgenstern, Jon; Naqvi, Nasir H; Debellis, Robert; Breiter, Hans C

    2013-06-01

    In the last decade, there has been an upsurge of interest in understanding the mechanisms of behavior change (MOBC) and effective behavioral interventions as a strategy to improve addiction-treatment efficacy. However, there remains considerable uncertainty about how treatment research should proceed to address the MOBC issue. In this article, we argue that limitations in the underlying models of addiction that inform behavioral treatment pose an obstacle to elucidating MOBC. We consider how advances in the cognitive neuroscience of addiction offer an alternative conceptual and methodological approach to studying the psychological processes that characterize addiction, and how such advances could inform treatment process research. In addition, we review neuroimaging studies that have tested aspects of neurocognitive theories as a strategy to inform addiction therapies and discuss future directions for transdisciplinary collaborations across cognitive neuroscience and MOBC research. 2013 APA, all rights reserved

  12. From screen to target: insights and approaches into the development of anti-virulence compounds

    Directory of Open Access Journals (Sweden)

    Katherine SH Beckham

    2014-09-01

    Full Text Available The detailed understanding of host-pathogen interactions provides exciting opportunities to interfere with the infection process. Anti-virulence compounds aim to modulate or pacify pathogenesis by reducing expression of critical virulence determinants. In particular, prevention of attachment by inhibiting adhesion mechanisms has been the subject of intense research. Whilst it has proven relatively straightforward to develop robust screens for potential antivirulence compounds, understanding their precise mode of action has proven much more challenging. In this review we illustrate this challenge from our own experiences working with the salicylidene acylhydrazide group of compounds. We aim to provide a useful perspective to guide researchers interested in this field and to avoid some of the obvious pitfalls.

  13. Stress Biology and Aging Mechanisms: Toward Understanding the Deep Connection Between Adaptation to Stress and Longevity

    Science.gov (United States)

    2014-01-01

    The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress (“hormetic stress”). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses (“toxic stress”) and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e.g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease. PMID:24833580

  14. Stress biology and aging mechanisms: toward understanding the deep connection between adaptation to stress and longevity.

    Science.gov (United States)

    Epel, Elissa S; Lithgow, Gordon J

    2014-06-01

    The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress ("hormetic stress"). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses ("toxic stress") and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e.g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Smartphone users: Understanding how security mechanisms are perceived and new persuasive methods

    Science.gov (United States)

    Alsaleh, Mansour; Alomar, Noura; Alarifi, Abdulrahman

    2017-01-01

    Protecting smartphones against security threats is a multidimensional problem involving human and technological factors. This study investigates how smartphone users’ security- and privacy-related decisions are influenced by their attitudes, perceptions, and understanding of various security threats. In this work, we seek to provide quantified insights into smartphone users’ behavior toward multiple key security features including locking mechanisms, application repositories, mobile instant messaging, and smartphone location services. To the best of our knowledge, this is the first study that reveals often unforeseen correlations and dependencies between various privacy- and security-related behaviors. Our work also provides evidence that making correct security decisions might not necessarily correlate with individuals’ awareness of the consequences of security threats. By comparing participants’ behavior and their motives for adopting or ignoring certain security practices, we suggest implementing additional persuasive approaches that focus on addressing social and technological aspects of the problem. On the basis of our findings and the results presented in the literature, we identify the factors that might influence smartphone users’ security behaviors. We then use our understanding of what might drive and influence significant behavioral changes to propose several platform design modifications that we believe could improve the security levels of smartphones. PMID:28297719

  16. Smartphone users: Understanding how security mechanisms are perceived and new persuasive methods.

    Science.gov (United States)

    Alsaleh, Mansour; Alomar, Noura; Alarifi, Abdulrahman

    2017-01-01

    Protecting smartphones against security threats is a multidimensional problem involving human and technological factors. This study investigates how smartphone users' security- and privacy-related decisions are influenced by their attitudes, perceptions, and understanding of various security threats. In this work, we seek to provide quantified insights into smartphone users' behavior toward multiple key security features including locking mechanisms, application repositories, mobile instant messaging, and smartphone location services. To the best of our knowledge, this is the first study that reveals often unforeseen correlations and dependencies between various privacy- and security-related behaviors. Our work also provides evidence that making correct security decisions might not necessarily correlate with individuals' awareness of the consequences of security threats. By comparing participants' behavior and their motives for adopting or ignoring certain security practices, we suggest implementing additional persuasive approaches that focus on addressing social and technological aspects of the problem. On the basis of our findings and the results presented in the literature, we identify the factors that might influence smartphone users' security behaviors. We then use our understanding of what might drive and influence significant behavioral changes to propose several platform design modifications that we believe could improve the security levels of smartphones.

  17. Understanding dental CAD/CAM for restorations--accuracy from a mechanical engineering viewpoint.

    Science.gov (United States)

    Tapie, Laurent; Lebon, Nicolas; Mawussi, Bernardin; Fron-Chabouis, Hélène; Duret, Francois; Attal, Jean-Pierre

    2015-01-01

    As is the case in the field of medicine, as well as in most areas of daily life, digital technology is increasingly being introduced into dental practice. Computer-aided design/ computer-aided manufacturing (CAD/CAM) solutions are available not only for chairside practice but also for creating inlays, crowns, fixed partial dentures (FPDs), implant abutments, and other dental prostheses. CAD/CAM dental practice can be considered as the handling of devices and software processing for the almost automatic design and creation of dental restorations. However, dentists who want to use dental CAD/CAM systems often do not have enough information to understand the variations offered by such technology practice. Knowledge of the random and systematic errors in accuracy with CAD/CAM systems can help to achieve successful restorations with this technology, and help with the purchasing of a CAD/CAM system that meets the clinical needs of restoration. This article provides a mechanical engineering viewpoint of the accuracy of CAD/ CAM systems, to help dentists understand the impact of this technology on restoration accuracy.

  18. Investigating and improving student understanding of the expectation values of observables in quantum mechanics

    Science.gov (United States)

    Marshman, Emily; Singh, Chandralekha

    2017-07-01

    The expectation value of an observable is an important concept in quantum mechanics since measurement outcomes are, in general, probabilistic and we only have information about the probability distribution of measurement outcomes in a given quantum state of a system. However, we find that upper-level undergraduate and PhD students in physics have both conceptual and procedural difficulties when determining the expectation value of a physical observable in a given quantum state in terms of the eigenstates and eigenvalues of the corresponding operator, especially when using Dirac notation. Here we first describe the difficulties that these students have with determining the expectation value of an observable in Dirac notation. We then discuss how the difficulties found via student responses to written surveys and individual interviews were used as a guide in the development of a quantum interactive learning tutorial (QuILT) to help students develop a good grasp of the expectation value. The QuILT strives to help students integrate conceptual understanding and procedural skills to develop a coherent understanding of the expectation value. We discuss the effectiveness of the QuILT in helping students learn this concept from in-class evaluations.

  19. Smartphone users: Understanding how security mechanisms are perceived and new persuasive methods.

    Directory of Open Access Journals (Sweden)

    Mansour Alsaleh

    Full Text Available Protecting smartphones against security threats is a multidimensional problem involving human and technological factors. This study investigates how smartphone users' security- and privacy-related decisions are influenced by their attitudes, perceptions, and understanding of various security threats. In this work, we seek to provide quantified insights into smartphone users' behavior toward multiple key security features including locking mechanisms, application repositories, mobile instant messaging, and smartphone location services. To the best of our knowledge, this is the first study that reveals often unforeseen correlations and dependencies between various privacy- and security-related behaviors. Our work also provides evidence that making correct security decisions might not necessarily correlate with individuals' awareness of the consequences of security threats. By comparing participants' behavior and their motives for adopting or ignoring certain security practices, we suggest implementing additional persuasive approaches that focus on addressing social and technological aspects of the problem. On the basis of our findings and the results presented in the literature, we identify the factors that might influence smartphone users' security behaviors. We then use our understanding of what might drive and influence significant behavioral changes to propose several platform design modifications that we believe could improve the security levels of smartphones.

  20. Towards understanding the mechanisms and the kinetics of nanoparticle penetration through protective gloves

    International Nuclear Information System (INIS)

    Vinches, L; Boutrigue, N; Zemzem, M; Hallé, S; Peyrot, C; Lemarchand, L; Wilkinson, K J; Tufenkji, N

    2015-01-01

    Parallel to the increased use of engineered nanoparticles (ENP) in the formulation of commercial products or in medicine, numerous health and safety agencies have recommended the application of the precautionary principle to handle ENP; namely, the recommendation to use protective gloves against chemicals. However, recent studies reveal the penetration of titanium dioxide nanoparticles through nitrile rubber protective gloves in conditions simulating occupational use. This project is designed to understand the links between the penetration of gold nanoparticles (nAu) through nitrile rubber protective gloves and the mechanical and physical behaviour of the elastomer material subjected to conditions simulating occupational use (i.e., mechanical deformations (MD) and sweat). Preliminary analyses show that nAu suspensions penetrate selected glove materials after exposure to prolonged (3 hours) dynamic deformations. Significant morphological changes are observed on the outer surface of the glove sample; namely, the number and the surface of the micropores on the surface increase. Moreover, nitrile rubber protective gloves are also shown to be sensitive to the action of nAu suspension and to the action of the saline solution used to simulate sweat (swelling). (paper)

  1. Understanding the mechanisms of familiar voice-identity recognition in the human brain.

    Science.gov (United States)

    Maguinness, Corrina; Roswandowitz, Claudia; Von Kriegstein, Katharina

    2018-03-31

    Humans have a remarkable skill for voice-identity recognition: most of us can remember many voices that surround us as 'unique'. In this review, we explore the computational and neural mechanisms which may support our ability to represent and recognise a unique voice-identity. We examine the functional architecture of voice-sensitive regions in the superior temporal gyrus/sulcus, and bring together findings on how these regions may interact with each other, and additional face-sensitive regions, to support voice-identity processing. We also contrast findings from studies on neurotypicals and clinical populations which have examined the processing of familiar and unfamiliar voices. Taken together, the findings suggest that representations of familiar and unfamiliar voices might dissociate in the human brain. Such an observation does not fit well with current models for voice-identity processing, which by-and-large assume a common sequential analysis of the incoming voice signal, regardless of voice familiarity. We provide a revised audio-visual integrative model of voice-identity processing which brings together traditional and prototype models of identity processing. This revised model includes a mechanism of how voice-identity representations are established and provides a novel framework for understanding and examining the potential differences in familiar and unfamiliar voice processing in the human brain. Copyright © 2018. Published by Elsevier Ltd.

  2. The use of micro-/milli-fluidics to better understand the mechanisms behind deep venous thrombosis

    Science.gov (United States)

    Schofield, Zoe; Alexiadis, Alessio; Brill, Alexander; Nash, Gerard; Vigolo, Daniele

    2016-11-01

    Deep venous thrombosis (DVT) is a dangerous and painful condition in which blood clots form in deep veins (e.g., femoral vein). If these clots become unstable and detach from the thrombus they can be delivered to the lungs resulting in a life threatening complication called pulmonary embolism (PE). Mechanisms of clot development in veins remain unclear but researchers suspect that the specific flow patterns in veins, especially around the valve flaps, play a fundamental role. Here we show how it is now possible to mimic the current murine model by developing micro-/milli-fluidic experiments. We exploited a novel detection technique, ghost particle velocimetry (GPV), to analyse the velocity profiles for various geometries. These vary from regular microfluidics with a rectangular cross section with a range of geometries (mimicking the presence of side and back branches in veins, closed side branch and flexible valves) to a more accurate venous representation with a 3D cylindrical geometry obtained by 3D printing. In addition to the GPV experiments, we analysed the flow field developing in these geometries by using computational fluid dynamic simulations to develop a better understanding of the mechanisms behind DVT. ZS gratefully acknowledges financial support from the EPSRC through a studentship from the Sci-Phy-4-Health Centre for Doctoral Training (EP/L016346/1).

  3. Understanding the molecular mechanisms of human microtia via a pig model of HOXA1 syndrome

    Directory of Open Access Journals (Sweden)

    Ruimin Qiao

    2015-06-01

    Full Text Available Microtia is a congenital malformation of the outer ears. Although both genetic and environmental components have been implicated in microtia, the genetic causes of this innate disorder are poorly understood. Pigs have naturally occurring diseases comparable to those in humans, providing exceptional opportunity to dissect the molecular mechanism of human inherited diseases. Here we first demonstrated that a truncating mutation in HOXA1 causes a monogenic disorder of microtia in pigs. We further performed RNA sequencing (RNA-Seq analysis on affected and healthy pig embryos (day 14.25. We identified a list of 337 differentially expressed genes (DEGs between the normal and mutant samples, shedding light on the transcriptional network involving HOXA1. The DEGs are enriched in biological processes related to cardiovascular system and embryonic development, and neurological, renal and urological diseases. Aberrant expressions of many DEGs have been implicated in human innate deformities corresponding to microtia-associated syndromes. After applying three prioritizing algorithms, we highlighted appealing candidate genes for human microtia from the 337 DEGs. We searched for coding variants of functional significance within six candidate genes in 147 microtia-affected individuals. Of note, we identified one EVC2 non-synonymous mutation (p.Asp1174Asn as a potential disease-implicating variant for a human microtia-associated syndrome. The findings advance our understanding of the molecular mechanisms underlying human microtia, and provide an interesting example of the characterization of human disease-predisposing variants using pig models.

  4. Next Steps Toward Understanding Human Habitation of Space: Environmental Impacts and Mechanisms

    Science.gov (United States)

    Globus, Ruth

    2016-01-01

    factor alone implying at least some shared underlying mechanisms. Thus, both ground based and spaceflight research utilizing model organisms provide the opportunity to better understand environmental factors and biological mechanisms that contribute to human health and survival in space.

  5. Raman analysis of DLC coated engine components with complex shape: Understanding wear mechanisms

    International Nuclear Information System (INIS)

    Jaoul, C.; Jarry, O.; Tristant, P.; Merle-Mejean, T.; Colas, M.; Dublanche-Tixier, C.; Jacquet, J.-M.

    2009-01-01

    Hydrogenated amorphous carbon (a-C:H) films were deposited on flat samples and engine components using an industrial scale reactor. Characterization of the coating allowed validating its application on engine parts due to high hardness (32 GPa) and high level of adhesion achieved using sublayers. The original approach of this work concerned the use of Raman analysis not only on flat samples after tribometer tests but also directly on coated engine parts with complex shape (like cam/follower system), in order to understand wear mechanisms occurring in motorsport engines. As wear could lead to a coating thickness decrease, a particular attention was paid on the Raman signal of the sublayers. Among the different values extracted from Raman spectrum to characterize structural organization, the value of G peak intensity appeared as a criterion of validity of analyses because it is directly linked to the remaining thickness of the a-C:H layer. For flat samples tested on ball-on-disc tribometer, structure of a-C:H film observed by Raman spectroscopy in the wear track remained stable in depth. Then, a-C:H coated engine components were studied before and after working in real conditions. Two different wear mechanisms were identified. The first one did not show any structural modification of the bulk a-C:H layer. In the second one, the high initial roughness of samples (R t = 1.15 μm) lead to coating delaminations after sliding. Massive graphitization which decreases drastically mechanical properties of the coatings was observed by Raman analyses on the contact area. The increase of the temperature on rough edges of the scratches could explain this graphitization.

  6. Features of Knowledge Building in Biology: Understanding Undergraduate Students' Ideas about Molecular Mechanisms.

    Science.gov (United States)

    Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning. © 2016 K. Southard et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  7. Poxvirus targeting of E3 ligase β-TrCP by molecular mimicry: a mechanism to inhibit NF-κB activation and promote immune evasion and virulence.

    Directory of Open Access Journals (Sweden)

    Daniel S Mansur

    2013-02-01

    Full Text Available The transcription factor NF-κB is essential for immune responses against pathogens and its activation requires the phosphorylation, ubiquitination and proteasomal degradation of IκBα. Here we describe an inhibitor of NF-κB from vaccinia virus that has a closely related counterpart in variola virus, the cause of smallpox, and mechanistic similarity with the HIV protein Vpu. Protein A49 blocks NF-κB activation by molecular mimicry and contains a motif conserved in IκBα which, in IκBα, is phosphorylated by IKKβ causing ubiquitination and degradation. Like IκBα, A49 binds the E3 ligase β-TrCP, thereby preventing ubiquitination and degradation of IκBα. Consequently, A49 stabilised phosphorylated IκBα (p-IκBα and its interaction with p65, so preventing p65 nuclear translocation. Serine-to-alanine mutagenesis within the IκBα-like motif of A49 abolished β-TrCP binding, stabilisation of p-IκBα and inhibition of NF-κB activation. Remarkably, despite encoding nine other inhibitors of NF-κB, a VACV lacking A49 showed reduced virulence in vivo.

  8. Poxvirus targeting of E3 ligase β-TrCP by molecular mimicry: a mechanism to inhibit NF-κB activation and promote immune evasion and virulence.

    Science.gov (United States)

    Mansur, Daniel S; Maluquer de Motes, Carlos; Unterholzner, Leonie; Sumner, Rebecca P; Ferguson, Brian J; Ren, Hongwei; Strnadova, Pavla; Bowie, Andrew G; Smith, Geoffrey L

    2013-02-01

    The transcription factor NF-κB is essential for immune responses against pathogens and its activation requires the phosphorylation, ubiquitination and proteasomal degradation of IκBα. Here we describe an inhibitor of NF-κB from vaccinia virus that has a closely related counterpart in variola virus, the cause of smallpox, and mechanistic similarity with the HIV protein Vpu. Protein A49 blocks NF-κB activation by molecular mimicry and contains a motif conserved in IκBα which, in IκBα, is phosphorylated by IKKβ causing ubiquitination and degradation. Like IκBα, A49 binds the E3 ligase β-TrCP, thereby preventing ubiquitination and degradation of IκBα. Consequently, A49 stabilised phosphorylated IκBα (p-IκBα) and its interaction with p65, so preventing p65 nuclear translocation. Serine-to-alanine mutagenesis within the IκBα-like motif of A49 abolished β-TrCP binding, stabilisation of p-IκBα and inhibition of NF-κB activation. Remarkably, despite encoding nine other inhibitors of NF-κB, a VACV lacking A49 showed reduced virulence in vivo.

  9. Understanding the hydrolysis mechanism of ethyl acetate catalyzed by an aqueous molybdocene: a computational chemistry investigation.

    Science.gov (United States)

    Tílvez, Elkin; Cárdenas-Jirón, Gloria I; Menéndez, María I; López, Ramón

    2015-02-16

    , in general, the information reported here could be of interest in designing new catalysts and understanding the reaction mechanism of these and other metal-catalyzed hydrolysis reactions.

  10. BarA-UvrY two-component system regulates virulence of uropathogenic E. coli CFT073.

    Science.gov (United States)

    Palaniyandi, Senthilkumar; Mitra, Arindam; Herren, Christopher D; Lockatell, C Virginia; Johnson, David E; Zhu, Xiaoping; Mukhopadhyay, Suman

    2012-01-01

    Uropathogenic Escherichia coli (UPEC), a member of extraintestinal pathogenic E. coli, cause ∼80% of community-acquired urinary tract infections (UTI) in humans. UPEC initiates its colonization in epithelial cells lining the urinary tract with a complicated life cycle, replicating and persisting in intracellular and extracellular niches. Consequently, UPEC causes cystitis and more severe form of pyelonephritis. To further understand the virulence characteristics of UPEC, we investigated the roles of BarA-UvrY two-component system (TCS) in regulating UPEC virulence. Our results showed that mutation of BarA-UvrY TCS significantly decreased the virulence of UPEC CFT073, as assessed by mouse urinary tract infection, chicken embryo killing assay, and cytotoxicity assay on human kidney and uroepithelial cell lines. Furthermore, mutation of either barA or uvrY gene reduced the production of hemolysin, lipopolysaccharide (LPS), proinflammatory cytokines (TNF-α and IL-6) and chemokine (IL-8). The virulence phenotype was restored similar to that of wild-type by complementation of either barA or uvrY gene in trans. In addition, we discussed a possible link between the BarA-UvrY TCS and CsrA in positively and negatively controlling virulence in UPEC. Overall, this study provides the evidences for BarA-UvrY TCS regulates the virulence of UPEC CFT073 and may point to mechanisms by which virulence regulations are observed in different ways may control the long-term survival of UPEC in the urinary tract.

  11. Disruption of tetR type regulator adeN by mobile genetic element confers elevated virulence in Acinetobacter baumannii.

    Science.gov (United States)

    Saranathan, Rajagopalan; Pagal, Sudhakar; Sawant, Ajit R; Tomar, Archana; Madhangi, M; Sah, Suresh; Satti, Annapurna; Arunkumar, K P; Prashanth, K

    2017-10-03

    Acinetobacter baumannii is an important human pathogen and considered as a major threat due to its extreme drug resistance. In this study, the genome of a hyper-virulent MDR strain PKAB07 of A. baumannii isolated from an Indian patient was sequenced and analyzed to understand its mechanisms of virulence, resistance and evolution. Comparative genome analysis of PKAB07 revealed virulence and resistance related genes scattered throughout the genome, instead of being organized as an island, indicating the highly mosaic nature of the genome. Many intermittent horizontal gene transfer events, insertion sequence (IS) element insertions identified were augmenting resistance machinery and elevating the SNP densities in A. baumannii eventually aiding in their swift evolution. ISAba1, the most widely distributed insertion sequence in A. baumannii was found in multiple sites in PKAB07. Out of many ISAba1 insertions, we identified novel insertions in 9 different genes wherein insertional inactivation of adeN (tetR type regulator) was significant. To assess the significance of this disruption in A. baumannii, adeN mutant and complement strains were constructed in A. baumannii ATCC 17978 strain and studied. Biofilm levels were abrogated in the adeN knockout when compared with the wild type and complemented strain of adeN knockout. Virulence of the adeN knockout mutant strain was observed to be high, which was validated by in vitro experiments and Galleria mellonella infection model. The overexpression of adeJ, a major component of AdeIJK efflux pump observed in adeN knockout strain could be the possible reason for the elevated virulence in adeN mutant and PKB07 strain. Knocking out of adeN in ATCC strain led to increased resistance and virulence at par with the PKAB07. Disruption of tetR type regulator adeN by ISAba1 consequently has led to elevated virulence in this pathogen.

  12. BarA-UvrY two-component system regulates virulence of uropathogenic E. coli CFT073.

    Directory of Open Access Journals (Sweden)

    Senthilkumar Palaniyandi

    Full Text Available Uropathogenic Escherichia coli (UPEC, a member of extraintestinal pathogenic E. coli, cause ∼80% of community-acquired urinary tract infections (UTI in humans. UPEC initiates its colonization in epithelial cells lining the urinary tract with a complicated life cycle, replicating and persisting in intracellular and extracellular niches. Consequently, UPEC causes cystitis and more severe form of pyelonephritis. To further understand the virulence characteristics of UPEC, we investigated the roles of BarA-UvrY two-component system (TCS in regulating UPEC virulence. Our results showed that mutation of BarA-UvrY TCS significantly decreased the virulence of UPEC CFT073, as assessed by mouse urinary tract infection, chicken embryo killing assay, and cytotoxicity assay on human kidney and uroepithelial cell lines. Furthermore, mutation of either barA or uvrY gene reduced the production of hemolysin, lipopolysaccharide (LPS, proinflammatory cytokines (TNF-α and IL-6 and chemokine (IL-8. The virulence phenotype was restored similar to that of wild-type by complementation of either barA or uvrY gene in trans. In addition, we discussed a possible link between the BarA-UvrY TCS and CsrA in positively and negatively controlling virulence in UPEC. Overall, this study provides the evidences for BarA-UvrY TCS regulates the virulence of UPEC CFT073 and may point to mechanisms by which virulence regulations are observed in different ways may control the long-term survival of UPEC in the urinary tract.

  13. Temporal Profile of Biofilm Formation, Gene Expression and Virulence Analysis in Candida albicans Strains.

    Science.gov (United States)

    de Barros, Patrícia Pimentel; Rossoni, Rodnei Dennis; De Camargo Ribeiro, Felipe; Junqueira, Juliana Campos; Jorge, Antonio Olavo Cardoso

    2017-04-01

    The characterization of Candida albicans strains with different degrees of virulence became very useful to understand the mechanisms of fungal virulence. Then, the objective of this study was to assess and compare the temporal profiles of biofilms formation, gene expression of ALS1, ALS3, HWP1, BCR1, EFG1, TEC1, SAP5, PLB2 and LIP9 and virulence in Galleria mellonella of C. albicans ATCC18804 and a clinical sample isolated from an HIV-positive patient (CA60). Although the CFU/mL counting was higher in biofilms formed in vitro by ATCC strain, the temporal profile of the analysis of the transcripts of the C. albicans strains was elevated to Ca60 compared to strain ATCC, especially in the genes HWP1, ALS3, SAP5, PLB2 and LIP9 (up regulation). Ca60 was more pathogenic for G. mellonella in the survival assay (p = 0.0394) and hemocytes density (p = 0.0349), agreeing with upregulated genes that encode the expression of hyphae and hydrolase genes of Ca60. In conclusion, the C. albicans strains used in this study differ in the amount of biofilm formation, virulence in vivo and transcriptional profiles of genes analyzed that can change factors associated with colonization, proliferation and survival of C. albicans at different niches. SAP5 and HWP1 were the genes more expressed in the formation of biofilm in vitro.

  14. Understanding the molecular mechanism of pulse current charging for stable lithium-metal batteries.

    Science.gov (United States)

    Li, Qi; Tan, Shen; Li, Linlin; Lu, Yingying; He, Yi

    2017-07-01

    High energy and safe electrochemical storage are critical components in multiple emerging fields of technologies. Rechargeable lithium-metal batteries are considered to be promising alternatives for current lithium-ion batteries, leading to as much as a 10-fold improvement in anode storage capacity (from 372 to 3860 mAh g -1 ). One of the major challenges for commercializing lithium-metal batteries is the reliability and safety issue, which is often associated with uneven lithium electrodeposition (lithium dendrites) during the charging stage of the battery cycling process. We report that stable lithium-metal batteries can be achieved by simply charging cells with square-wave pulse current. We investigated the effects of charging period and frequency as well as the mechanisms that govern this process at the molecular level. Molecular simulations were performed to study the diffusion and the solvation structure of lithium cations (Li + ) in bulk electrolyte. The model predicts that loose association between cations and anions can enhance the transport of Li + and eventually stabilize the lithium electrodeposition. We also performed galvanostatic measurements to evaluate the cycling behavior and cell lifetime under pulsed electric field and found that the cell lifetime can be more than doubled using certain pulse current waveforms. Both experimental and simulation results demonstrate that the effectiveness of pulse current charging on dendrite suppression can be optimized by choosing proper time- and frequency-dependent pulses. This work provides a molecular basis for understanding the mechanisms of pulse current charging to mitigating lithium dendrites and designing pulse current waveforms for stable lithium-metal batteries.

  15. Glucose starvation boosts Entamoeba histolytica virulence.

    Directory of Open Access Journals (Sweden)

    Ayala Tovy

    2011-08-01

    Full Text Available The unicellular parasite, Entamoeba histolytica, is exposed to numerous adverse conditions, such as nutrient deprivation, during its life cycle stages in the human host. In the present study, we examined whether the parasite virulence could be influenced by glucose starvation (GS. The migratory behaviour of the parasite and its capability to kill mammalian cells and to lyse erythrocytes is strongly enhanced following GS. In order to gain insights into the mechanism underlying the GS boosting effects on virulence, we analyzed differences in protein expression levels in control and glucose-starved trophozoites, by quantitative proteomic analysis. We observed that upstream regulatory element 3-binding protein (URE3-BP, a transcription factor that modulates E.histolytica virulence, and the lysine-rich protein 1 (KRiP1 which is induced during liver abscess development, are upregulated by GS. We also analyzed E. histolytica membrane fractions and noticed that the Gal/GalNAc lectin light subunit LgL1 is up-regulated by GS. Surprisingly, amoebapore A (Ap-A and cysteine proteinase A5 (CP-A5, two important E. histolytica virulence factors, were strongly down-regulated by GS. While the boosting effect of GS on E. histolytica virulence was conserved in strains silenced for Ap-A and CP-A5, it was lost in LgL1 and in KRiP1 down-regulated strains. These data emphasize the unexpected role of GS in the modulation of E.histolytica virulence and the involvement of KRiP1 and Lgl1 in this phenomenon.

  16. Understanding creep in sandstone reservoirs - theoretical deformation mechanism maps for pressure solution in granular materials

    Science.gov (United States)

    Hangx, Suzanne; Spiers, Christopher

    2014-05-01

    Subsurface exploitation of the Earth's natural resources removes the natural system from its chemical and physical equilibrium. As such, groundwater extraction and hydrocarbon production from subsurface reservoirs frequently causes surface subsidence and induces (micro)seismicity. These effects are not only a problem in onshore (e.g. Groningen, the Netherlands) and offshore hydrocarbon fields (e.g. Ekofisk, Norway), but also in urban areas with extensive groundwater pumping (e.g. Venice, Italy). It is known that fluid extraction inevitably leads to (poro)elastic compaction of reservoirs, hence subsidence and occasional fault reactivation, and causes significant technical, economic and ecological impact. However, such effects often exceed what is expected from purely elastic reservoir behaviour and may continue long after exploitation has ceased. This is most likely due to time-dependent compaction, or 'creep deformation', of such reservoirs, driven by the reduction in pore fluid pressure compared with the rock overburden. Given the societal and ecological impact of surface subsidence, as well as the current interest in developing geothermal energy and unconventional gas resources in densely populated areas, there is much need for obtaining better quantitative understanding of creep in sediments to improve the predictability of the impact of geo-energy and groundwater production. The key problem in developing a reliable, quantitative description of the creep behaviour of sediments, such as sands and sandstones, is that the operative deformation mechanisms are poorly known and poorly quantified. While grain-scale brittle fracturing plus intergranular sliding play an important role in the early stages of compaction, these time-independent, brittle-frictional processes give way to compaction creep on longer time-scales. Thermally-activated mass transfer processes, like pressure solution, can cause creep via dissolution of material at stressed grain contacts, grain

  17. Towards Understanding the Catalytic Mechanism of Human Paraoxonase 1: Experimental and In Silico Mutagenesis Studies.

    Science.gov (United States)

    Tripathy, Rajan K; Aggarwal, Geetika; Bajaj, Priyanka; Kathuria, Deepika; Bharatam, Prasad V; Pande, Abhay H

    2017-08-01

    Human paraoxonase 1 (h-PON1) is a ~45-kDa serum enzyme that can hydrolyze a variety of substrates, including organophosphate (OP) compounds. It is a potential candidate for the development of antidote against OP poisoning in humans. However, insufficient OP-hydrolyzing activity of native enzyme affirms the urgent need to develop improved variant(s) having enhanced OP-hydrolyzing activity. The crystal structure of h-PON1 remains unsolved, and the molecular details of how the enzyme catalyses hydrolysis of different types of substrates are also not clear. Understanding the molecular details of the catalytic mechanism of h-PON1 is essential to engineer better variant(s) of enzyme. In this study, we have used a random mutagenesis approach to increase the OP-hydrolyzing activity of recombinant h-PON1. The mutants not only showed a 10-340-fold increased OP-hydrolyzing activity against different OP substrates but also exhibited differential lactonase and arylesterase activities. In order to investigate the mechanistic details of the effect of observed mutations on the hydrolytic activities of enzyme, molecular docking studies were performed with selected mutants. The results suggested that the observed mutations permit differential binding of substrate/inhibitor into the enzyme's active site. This may explain differential hydrolytic activities of the enzyme towards different substrates.

  18. Understanding the mechanisms of secondary nucleation for protein aggregation: an analytical approach

    Science.gov (United States)

    Michaels, Thomas; Knowles, Tuomas P. J.

    2013-03-01

    Filamentous protein self-assembly is a general type of behaviour accessible to a wide range of different polypeptide sequences. This phenomenon underlies key molecular events both in normal and aberrant biology, but a general theory of the crucial nucleation steps that govern this process has remained elusive. In this talk we discuss our attempts to provide a general description of secondary nucleation in filamentous protein assembly based on the Becker-Döring kinetic scheme to describe cluster-catalytic effects. This systematic procedure allows extracting low-dimensional systems of equations out of the full kinetic model, in a master equation formalism typically consisting of infinitely many coupled non-linear equations. Using this procedure, we propose and discuss various mechanisms that can underlie the secondary nucleation process. Using data curve-fitting and analysis we show that the addition of a monomer to heterogeneous nuclei is effectively irreversible and discuss the implications of our framework for the more general understanding of the physics of multi-step nucleation phenomena in nature.

  19. Understanding the mechanisms of sickle cell disease by simulations with a discrete particle model

    Science.gov (United States)

    Hui, Katrina; Lin, Guang; Pan, Wenxiao

    2013-01-01

    Sickle cell disease (SCD) is an inherited blood disorder characterized by rigid, sickle-shaped red blood cells (RBCs). Because of their rigidity and shape, sickle cells can get stuck in smaller blood vessels, causing blockages and depriving oxygen to tissues. This study develops and applies mathematical models to better understand the mechanism of SCD. Two-dimensional models of RBCs and blood vessels have been constructed by representing them as discrete particles interacting with different forces. The nonlinear, elastic property of healthy RBCs could be adequately reproduced using a cosine angle bending force and a worm-like chain spring force. With the ability to deform, RBCs can squeeze through narrow blood vessels. In modeling sickle cells as rigid bodies and applying repelling and friction forces from the blood vessel, this study shows that geometrical factors (dimensions of the sickle cell and blood vessels) as well as rigidity and adhesiveness of the sickle cell all play an important role in determining how, and if, sickle cells become trapped within narrow blood capillaries. With lack of data to validate the model, this study primarily provides a sensitivity analysis of factors influencing sickle cell occlusion and identified critical data to support future modeling.

  20. Regulatory principles governing Salmonella and Yersinia virulence

    Science.gov (United States)

    Erhardt, Marc; Dersch, Petra

    2015-01-01

    Enteric pathogens such as Salmonella and Yersinia evolved numerous strategies to survive and proliferate in different environmental reservoirs and mammalian hosts. Deciphering common and pathogen-specific principles for how these bacteria adjust and coordinate spatiotemporal expression of virulence determinants, stress adaptation, and metabolic functions is fundamental to understand microbial pathogenesis. In order to manage sudden environmental changes, attacks by the host immune systems and microbial competition, the pathogens employ a plethora of transcriptional and post-transcriptional control elements, including transcription factors, sensory and regulatory RNAs, RNAses, and proteases, to fine-tune and control complex gene regulatory networks. Many of the contributing global regulators and the molecular mechanisms of regulation are frequently conserved between Yersinia and Salmonella. However, the interplay, arrangement, and composition of the control elements vary between these closely related enteric pathogens, which generate phenotypic differences leading to distinct pathogenic properties. In this overview we present common and different regulatory networks used by Salmonella and Yersinia to coordinate the expression of crucial motility, cell adhesion and invasion determinants, immune defense strategies, and metabolic adaptation processes. We highlight evolutionary changes of the gene regulatory circuits that result in different properties of the regulatory elements and how this influences the overall outcome of the infection process. PMID:26441883

  1. Bacterial proteases and virulence

    DEFF Research Database (Denmark)

    Frees, Dorte; Brøndsted, Lone; Ingmer, Hanne

    2013-01-01

    with the proteases either encoded within the same polypeptide or on separate subunits. In contrast, substrate recognition by extracellular proteases is less selective and therefore these enzymes are generally expressed as zymogens to prevent premature proteolytic activity that would be detrimental to the cell......Bacterial pathogens rely on proteolysis for variety of purposes during the infection process. In the cytosol, the main proteolytic players are the conserved Clp and Lon proteases that directly contribute to virulence through the timely degradation of virulence regulators and indirectly by providing...... signalling to short-circuit host cell processes. Common to both intra- and extracellular proteases is the tight control of their proteolytic activities. In general, substrate recognition by the intracellular proteases is highly selective which is, in part, attributed to the chaperone activity associated...

  2. Regulation of Yersina pestis Virulence by AI-2 Mediated Quorum Sensing

    Energy Technology Data Exchange (ETDEWEB)

    Segelke, B; Hok, S; Lao, V; Corzett, M; Garcia, E

    2010-03-29

    The proposed research was motivated by an interest in understanding Y. pestis virulence mechanisms and bacteria cell-cell communication. It is expected that a greater understanding of virulence mechanisms will ultimately lead to biothreat countermeasures and novel therapeutics. Y. pestis is the etiological agent of plague, the most devastating disease in human history. Y. pestis infection has a high mortality rate and a short incubation before mortality. There is no widely available and effective vaccine for Y. pestis and multi-drug resistant strains are emerging. Y. pestis is a recognized biothreat agent based on the wide distribution of the bacteria in research laboratories around the world and on the knowledge that methods exist to produce and aerosolize large amounts of bacteria. We hypothesized that cell-cell communication via signaling molecules, or quorum sensing, by Y. pestis is important for the regulation of virulence factor gene expression during host invasion, though a causative link had never been established. Quorum sensing is a mode of intercellular communication which enables orchestration of gene expression for many bacteria as a function of population density and available evidence suggests there may be a link between quorum sensing and regulation of Y. pesits virulence. Several pathogenic bacteria have been shown to regulate expression of virulence factor genes, including genes encoding type III secretion, via quorum sensing. The Y. pestis genome encodes several cell-cell signaling pathways and the interaction of at least three of these are thought to be involved in one or more modes of host invasion. Furthermore, Y. pestis gene expression array studies carried out at LLNL have established a correlation between expression of known virulence factors and genes involved in processing of the AI-2 quorum sensing signal. This was a basic research project that was intended to provide new insights into bacterial intercellular communication and how it is

  3. Development of Quorum-Based Anti-Virulence Therapeutics Targeting Gram-Negative Bacterial Pathogens

    Directory of Open Access Journals (Sweden)

    Wen Shan Yew

    2013-08-01

    Full Text Available Quorum sensing is a cell density-dependent signaling phenomenon used by bacteria for coordination of population-wide phenotypes, such as expression of virulence genes, antibiotic resistance and biofilm formation. Lately, disruption of bacterial communication has emerged as an anti-virulence strategy with enormous therapeutic potential given the increasing incidences of drug resistance in pathogenic bacteria. The quorum quenching therapeutic approach promises a lower risk of resistance development, since interference with virulence generally does not affect the growth and fitness of the bacteria and, hence, does not exert an associated selection pressure for drug-resistant strains. With better understanding of bacterial communication networks and mechanisms, many quorum quenching methods have been developed against various clinically significant bacterial pathogens. In particular, Gram-negative bacteria are an important group of pathogens, because, collectively, they are responsible for the majority of hospital-acquired infections. Here, we discuss the current understanding of existing quorum sensing mechanisms and present important inhibitory strategies that have been developed against this group of pathogenic bacteria.

  4. Two Major Inositol Transporters and Their Role in Cryptococcal Virulence ▿ †

    Science.gov (United States)

    Wang, Yina; Liu, Tong-bao; Delmas, Guillaume; Park, Steven; Perlin, David; Xue, Chaoyang

    2011-01-01

    Cryptococcus neoformans is an AIDS-associated human fungal pathogen and the most common cause of fungal meningitis, with a mortality rate over 40% in AIDS patients. Significant advances have been achieved in understanding its disease mechanisms. Yet the underlying mechanism of a high frequency of cryptococcal meningitis remains unclear. The existence of high inositol concentrations in brain and our earlier discovery of a large inositol transporter (ITR) gene family in C. neoformans led us to investigate the potential role of inositol in Cryptococcus-host interactions. In this study, we focus on functional analyses of two major ITR genes to understand their role in virulence of C. neoformans. Our results show that ITR1A and ITR3C are the only two ITR genes among 10 candidates that can complement the growth defect of a Saccharomyces cerevisiae strain lacking inositol transporters. Both S. cerevisiae strains heterologously expressing ITR1A or ITR3C showed high inositol uptake activity, an indication that they are major inositol transporters. Significantly, itr1a itr3c double mutants showed significant virulence attenuation in murine infection models. Mutating both ITR1A and ITR3C in an ino1 mutant background activates the expression of several remaining ITR candidates and does not show more severe virulence attenuation, suggesting that both inositol uptake and biosynthetic pathways are important for inositol acquisition. Overall, our study provides evidence that host inositol and fungal inositol transporters are important for Cryptococcus pathogenicity. PMID:21398509

  5. Current understanding of the driving mechanisms for spatiotemporal variations of atmospheric speciated mercury: a review

    Directory of Open Access Journals (Sweden)

    H. Mao

    2016-10-01

    Full Text Available Atmospheric mercury (Hg is a global pollutant and thought to be the main source of mercury in oceanic and remote terrestrial systems, where it becomes methylated and bioavailable; hence, atmospheric mercury pollution has global consequences for both human and ecosystem health. Understanding of spatial and temporal variations of atmospheric speciated mercury can advance our knowledge of mercury cycling in various environments. This review summarized spatiotemporal variations of total gaseous mercury or gaseous elemental mercury (TGM/GEM, gaseous oxidized mercury (GOM, and particulate-bound mercury (PBM in various environments including oceans, continents, high elevation, the free troposphere, and low to high latitudes. In the marine boundary layer (MBL, the oxidation of GEM was generally thought to drive the diurnal and seasonal variations of TGM/GEM and GOM in most oceanic regions, leading to lower GEM and higher GOM from noon to afternoon and higher GEM during winter and higher GOM during spring–summer. At continental sites, the driving mechanisms of TGM/GEM diurnal patterns included surface and local emissions, boundary layer dynamics, GEM oxidation, and for high-elevation sites mountain–valley winds, while oxidation of GEM and entrainment of free tropospheric air appeared to control the diurnal patterns of GOM. No pronounced diurnal variation was found for Tekran measured PBM at MBL and continental sites. Seasonal variations in TGM/GEM at continental sites were attributed to increased winter combustion and summertime surface emissions, and monsoons in Asia, while those in GOM were controlled by GEM oxidation, free tropospheric transport, anthropogenic emissions, and wet deposition. Increased PBM at continental sites during winter was primarily due to local/regional coal and wood combustion emissions. Long-term TGM measurements from the MBL and continental sites indicated an overall declining trend. Limited measurements suggested TGM

  6. Understanding treatment effect mechanisms of the CAMBRA randomized trial in reducing caries increment.

    Science.gov (United States)

    Cheng, J; Chaffee, B W; Cheng, N F; Gansky, S A; Featherstone, J D B

    2015-01-01

    The Caries Management By Risk Assessment (CAMBRA) randomized controlled trial showed that an intervention featuring combined antibacterial and fluoride therapy significantly reduced bacterial load and suggested reduced caries increment in adults with 1 to 7 baseline cavitated teeth. While trial results speak to the overall effectiveness of an intervention, insight can be gained from understanding the mechanism by which an intervention acts on putative intermediate variables (mediators) to affect outcomes. This study conducted mediation analyses on 109 participants who completed the trial to understand whether the intervention reduced caries increment through its action on potential mediators (oral bacterial load, fluoride levels, and overall caries risk based on the composite of bacterial challenge and salivary fluoride) between the intervention and dental outcomes. The primary outcome was the increment from baseline in decayed, missing, and filled permanent surfaces (ΔDMFS) 24 mo after completing restorations for baseline cavitated lesions. Analyses adjusted for baseline overall risk, bacterial challenge, and fluoride values under a potential outcome framework using generalized linear models. Overall, the CAMBRA intervention was suggestive in reducing the 24-mo DMFS increment (reduction in ΔDMFS: -0.96; 95% confidence interval [CI]: -2.01 to 0.08; P = 0.07); the intervention significantly reduced the 12-mo overall risk (reduction in overall risk: -19%; 95% CI, -7 to -41%;], P = 0.005). Individual mediators, salivary log10 mutans streptococci, log10 lactobacilli, and fluoride level, did not represent statistically significant pathways alone through which the intervention effect was transmitted. However, 36% of the intervention effect on 24-mo DMFS increment was through a mediation effect on 12-mo overall risk (P = 0.03). These findings suggest a greater intervention effect carried through the combined action on multiple aspects of the caries process rather than

  7. Understanding and Exploration of the Biomineralization Mechanisms for the Controllable Synthesis of Nanomaterials

    Science.gov (United States)

    Xiao, Junwu

    This thesis is mainly concerned with understanding the biomineralization mechanisms, and further extrapolating them for the controllable synthesis of transition metal compound nanomaterials on graphene sheets for energy storage applications in electrochemical capacitors and lithium ion batteries (LIB). Firstly, we have studied the mimetic biomineralization process of CaCO 3 on a stearic acid or 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) Langmuir monolayer at the air-water interface by in-situ Brewster angle microscopy (BAM) and ex-situ electron microscopy. Amorphous calcium carbonate (ACC) precursors are directly nucleated from solvated ions prior to the crystal nuclei on a Langmuir monolayer. On a DPPC monolayer, numerous fresh ACC nanoparticles heterogeneously and continuously nucleated at the air-water interface are transformed into the metastable vaterite nanocrystals. Driven by the trend to decrease surface energy, the vaterite nanocrystals self-aggregate and grow into the loose-packed hollow ellipsoidal vaterite polycrystals. These nanocrystals in vaterite polycrystals are then gradually orientated in the same direction to evolve into tight-packed ellipsoidal mesocrystals. As the crystallization time is further increased, the metastable vaterite mesocrystals are eventually transformed into the most thermodynamically stable calcite crystals. Secondly, organic and inorganic additives control over the shapes, sizes and phases of inorganic nanocrystals and arrange them into ordered structures from amorphous precursors in the organisms. This interesting phenomenon has galvanized many attempts to mimic the biomineralization process for synthesizing novel materials. We have studied the crystallization processes from small citrate molecules stabilized ACC precursors under cetyltrimethyl ammonium bromide (CTAB) micellar structures. Amorphous precursors, with a hydrated and disordered structure, are easily transformed and molded into CaCO 3 crystals with

  8. The Success of Acinetobacter Species; Genetic, Metabolic and Virulence Attributes

    Science.gov (United States)

    Peleg, Anton Y.; de Breij, Anna; Adams, Mark D.; Cerqueira, Gustavo M.; Mocali, Stefano; Galardini, Marco; Nibbering, Peter H.; Earl, Ashlee M.; Ward, Doyle V.; Paterson, David L.; Seifert, Harald; Dijkshoorn, Lenie

    2012-01-01

    An understanding of why certain Acinetobacter species are more successful in causing nosocomial infections, transmission and epidemic spread in healthcare institutions compared with other species is lacking. We used genomic, phenotypic and virulence studies to identify differences between Acinetobacter species. Fourteen strains representing nine species were examined. Genomic analysis of six strains showed that the A. baumannii core genome contains many genes important for diverse metabolism and survival in the host. Most of the A. baumannii core genes were also present in one or more of the less clinically successful species. In contrast, when the accessory genome of an individual A. baumannii strain was compared to a strain of a less successful species (A. calcoaceticus RUH2202), many operons with putative virulence function were found to be present only in the A. baumannii strain, including the csu operon, the acinetobactin chromosomal cluster, and bacterial defence mechanisms. Phenotype microarray analysis showed that compared to A. calcoaceticus (RUH2202), A. baumannii ATCC 19606T was able to utilise nitrogen sources more effectively and was more tolerant to pH, osmotic and antimicrobial stress. Virulence differences were also observed, with A. baumannii ATCC 19606T, A. pittii SH024, and A. nosocomialis RUH2624 persisting and forming larger biofilms on human skin than A. calcoaceticus. A. baumannii ATCC 19606T and A. pittii SH024 were also able to survive in a murine thigh infection model, whereas the other two species were eradicated. The current study provides important insights into the elucidation of differences in clinical relevance among Acinetobacter species. PMID:23144699

  9. The success of acinetobacter species; genetic, metabolic and virulence attributes.

    Directory of Open Access Journals (Sweden)

    Anton Y Peleg

    Full Text Available An understanding of why certain Acinetobacter species are more successful in causing nosocomial infections, transmission and epidemic spread in healthcare institutions compared with other species is lacking. We used genomic, phenotypic and virulence studies to identify differences between Acinetobacter species. Fourteen strains representing nine species were examined. Genomic analysis of six strains showed that the A. baumannii core genome contains many genes important for diverse metabolism and survival in the host. Most of the A. baumannii core genes were also present in one or more of the less clinically successful species. In contrast, when the accessory genome of an individual A. baumannii strain was compared to a strain of a less successful species (A. calcoaceticus RUH2202, many operons with putative virulence function were found to be present only in the A. baumannii strain, including the csu operon, the acinetobactin chromosomal cluster, and bacterial defence mechanisms. Phenotype microarray analysis showed that compared to A. calcoaceticus (RUH2202, A. baumannii ATCC 19606(T was able to utilise nitrogen sources more effectively and was more tolerant to pH, osmotic and antimicrobial stress. Virulence differences were also observed, with A. baumannii ATCC 19606(T, A. pittii SH024, and A. nosocomialis RUH2624 persisting and forming larger biofilms on human skin than A. calcoaceticus. A. baumannii ATCC 19606(T and A. pittii SH024 were also able to survive in a murine thigh infection model, whereas the other two species were eradicated. The current study provides important insights into the elucidation of differences in clinical relevance among Acinetobacter species.

  10. The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in IBS.

    Science.gov (United States)

    Staudacher, Heidi M; Whelan, Kevin

    2017-08-01

    There is an intensifying interest in the interaction between diet and the functional GI symptoms experienced in IBS. Recent studies have used MRI to demonstrate that short-chain fermentable carbohydrates increase small intestinal water volume and colonic gas production that, in those with visceral hypersensitivity, induces functional GI symptoms. Dietary restriction of short-chain fermentable carbohydrates (the low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet) is now increasingly used in the clinical setting. Initial research evaluating the efficacy of the low FODMAP diet was limited by retrospective study design and lack of comparator groups, but more recently well-designed clinical trials have been published. There are currently at least 10 randomised controlled trials or randomised comparative trials showing the low FODMAP diet leads to clinical response in 50%-80% of patients with IBS, in particular with improvements in bloating, flatulence, diarrhoea and global symptoms. However, in conjunction with the beneficial clinical impact, recent studies have also demonstrated that the low FODMAP diet leads to profound changes in the microbiota and metabolome, the duration and clinical relevance of which are as yet unknown. This review aims to present recent advances in the understanding of the mechanisms by which the low FODMAP diet impacts on symptoms in IBS, recent evidence for its efficacy, current findings regarding the consequences of the diet on the microbiome and recommendations for areas for future research. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Characterization of the Contribution to Virulence of Three Large Plasmids of Avian Pathogenic Escherichia coli χ7122 (O78:K80:H9) ▿ †

    Science.gov (United States)

    Mellata, Melha; Ameiss, Keith; Mo, Hua; Curtiss, Roy

    2010-01-01

    Despite the fact that the presence of multiple large plasmids is a defining feature of extraintestinal pathogenic Escherichia coli (ExPEC), such as avian pathogenic E. coli (APEC), and despite the fact that these bacteria pose a considerable threat to both human and animal health, characterization of these plasmids is still limited. In this study, after successfully curing APEC of its plasmids, we were able to investigate, for the first time, the contribution to virulence of three plasmids, pAPEC-1 (103 kb), pAPEC-2 (90 kb), and pAPEC-3 (60 kb), from APEC strain χ7122 individually as well as in all combinations in the wild-type background. Characterization of the different strains revealed unique features of APEC virulence. In vivo assays showed that curing the three plasmids resulted in severe attenuation of virulence. The presence of different plasmids and combinations of plasmids resulted in strains with different pathotypes and levels of virulence, reflecting the diversity of APEC strains associated with colibacillosis in chickens. Unexpectedly, our results associated the decrease in growth of some strains in some media with the virulence of APEC, and the mechanism was associated with some combinations of plasmids that included pAPEC-1. This study provided new insights into the roles of large plasmids in the virulence, growth, and evolution of APEC by showing for the first time that both the nature of plasmids and combinations of plasmids have an effect on these phenomena. It also provided a plausible explanation for some of the conflicting results related to the virulence of ExPEC strains. This study should help us understand the virulence of other ExPEC strains and design more efficient infection control strategies. PMID:20086082

  12. Understanding the mechanisms that change the conductivity of damaged ITO-coated polymeric films: A micro-mechanical investigation

    KAUST Repository

    Nasr Saleh, Mohamed

    2014-11-01

    Degradation from mechanical loading of transparent electrodes made of indium tin oxide (ITO) endangers the integrity of any material based on these electrodes, including flexible organic solar cells. However, how different schemes of degradation change the conductivity of ITO devices remains unclear. We propose a systematic micro-mechanics-based approach to clarify the relationship between degradation and changes in electrical resistance. By comparing experimentally measured channel crack densities to changes in electrical resistance returned by the different micro-mechanical schemes, we highlight the key role played by the residual conductivity in the interface between the ITO electrode and its substrate after delamination. We demonstrate that channel cracking alone does not explain the experimental observations. Our results indicate that delamination has to take place between the ITO electrode and the substrate layers and that the residual conductivity of this delaminated interface plays a major role in changes in electrical resistance of the degraded device. © 2014 Elsevier B.V.

  13. Regulation of Three Virulence Strategies of Mycobacterium tuberculosis: A Success Story

    Science.gov (United States)

    van Dam, Jesse C. J.; Martins dos Santos, Vitor A. P.

    2018-01-01

    Tuberculosis remains one of the deadliest diseases. Emergence of drug-resistant and multidrug-resistant M. tuberculosis strains makes treating tuberculosis increasingly challenging. In order to develop novel intervention strategies, detailed understanding of the molecular mechanisms behind the success of this pathogen is required. Here, we review recent literature to provide a systems level overview of the molecular and cellular components involved in divalent metal homeostasis and their role in regulating the three main virulence strategies of M. tuberculosis: immune modulation, dormancy and phagosomal rupture. We provide a visual and modular overview of these components and their regulation. Our analysis identified a single regulatory cascade for these three virulence strategies that respond to limited availability of divalent metals in the phagosome. PMID:29364195

  14. Interplay between Colistin Resistance, Virulence and Fitness in Acinetobacter baumannii

    Directory of Open Access Journals (Sweden)

    Gabriela Jorge Da Silva

    2017-11-01

    Full Text Available Acinetobacter baumannii is an important opportunistic nosocomial pathogen often resistant to multiple antibiotics classes. Colistin, an “old” antibiotic, is now considered a last-line treatment option for extremely resistant isolates. In the meantime, resistance to colistin has been reported in clinical A. baumannii strains. Colistin is a cationic peptide that disrupts the outer membrane (OM of Gram-negative bacteria. Colistin resistance is primarily due to post-translational modification or loss of the lipopolysaccharide (LPS molecules inserted into the outer leaflet of the OM. LPS modification prevents the binding of polymyxin to the bacterial surface and may lead to alterations in bacterial virulence. Antimicrobial pressure drives the evolution of antimicrobial resistance and resistance is often associated with a reduced bacterial fitness. Therefore, the alterations in LPS may induce changes in the fitness of A. baumannii. However, compensatory mutations in clinical A. baumannii may ameliorate the cost of resistance and may play an important role in the dissemination of colistin-resistant A. baumannii isolates. The focus of this review is to summarize the colistin resistance mechanisms, and understand their impact on the fitness and virulence of bacteria and on the dissemination of colistin-resistant A. baumannii strains.

  15. Chemical Inhibition of Kynureninase Reduces Pseudomonas aeruginosa Quorum Sensing and Virulence Factor Expression.

    Science.gov (United States)

    Kasper, Stephen H; Bonocora, Richard P; Wade, Joseph T; Musah, Rabi Ann; Cady, Nathaniel C

    2016-04-15

    The opportunistic pathogen Pseudomonas aeruginosa utilizes multiple quorum sensing (QS) pathways to coordinate an arsenal of virulence factors. We previously identified several cysteine-based compounds inspired by natural products from the plant Petiveria alliacea which are capable of antagonizing multiple QS circuits as well as reducing P. aeruginosa biofilm formation. To understand the global effects of such compounds on virulence factor production and elucidate their mechanism of action, RNA-seq transcriptomic analysis was performed on P. aeruginosa PAO1 exposed to S-phenyl-l-cysteine sulfoxide, the most potent inhibitor from the prior study. Exposure to this inhibitor down-regulated expression of several QS-regulated virulence operons (e.g., phenazine biosynthesis, type VI secretion systems). Interestingly, many genes that were differentially regulated pertain to the related metabolic pathways that yield precursors of pyochelin, tricarboxylic acid cycle intermediates, phenazines, and Pseudomonas quinolone signal (PQS). Activation of the MexT-regulon was also indicated, including the multidrug efflux pump encoded by mexEF-oprN, which has previously been shown to inhibit QS and pathogenicity. Deeper investigation of the metabolites involved in these systems revealed that S-phenyl-l-cysteine sulfoxide has structural similarity to kynurenine, a precursor of anthranilate, which is critical for P. aeruginosa virulence. By supplementing exogenous anthranilate, the QS-inhibitory effect was reversed. Finally, it was shown that S-phenyl-l-cysteine sulfoxide competitively inhibits P. aeruginosa kynureninase (KynU) activity in vitro and reduces PQS production in vivo. The kynurenine pathway has been implicated in P. aeruginosa QS and virulence factor expression; however, this is the first study to show that targeted inhibition of KynU affects P. aeruginosa gene expression and QS, suggesting a potential antivirulence strategy.

  16. Laboratory experiments for understanding mechanical properties of fractured granite under supercritical conditions

    Science.gov (United States)

    Kitamura, M.; Takahashi, M.; Takagi, K.; Hirano, N.; Tsuchiya, N.

    2017-12-01

    To extract geothermal energy effectively and safely from magma and/or adjacent hot rock, we need to tackle many issues which require new technology development, such as a technique to control a risk from induced-earthquakes. On a development of induced-earthquake mitigation technology, it is required to understand roles of factors on occurrences of the induced-earthquake (e.g., strength, crack density, and fluid-rock reaction) and their intercorrelations (e.g., Asanuma et al., 2012). Our purpose of this series of experiments is to clarify a relationship between the rock strength and the crack density under supercritical conditions. We conducted triaxial deformation test on intact granite rock strength under high-temperature (250 - 750°C), high-pressure (104 MPa) condition at a constant load velocity (0.1 μm/sec) using a gas-rig at AIST. We used Oshima granite, which has initially stress drop became smaller at higher temperature. Young's modulus increased with decreasing the temperature from 32.3 GPa at 750°C to 57.4 GPa at 250°C. At 400 °C, the stress drop accelerated the deformation with 98 times faster velocity than that at load-point. In contrast, at 650°C and 750°C, the velocity during stress drop kept the same order of the load-point velocity. Therefore, the deformation mechanism may start to be changed from brittle to ductile when the temperature exceeds 650°C. Highly dense cracked granite specimens were formed by a rapid decompression test (RDT) using an autoclave settled at Tohoku University (Hirano et al., 2016JpGU), caused by a reduction of fluid pressure within 1-2 sec from vapor/supercritical state (10 - 48 MPa, 550 °C) to ambient pressure. The specimens after RDT show numerous microcracks on X-ray CT images. The RDT imposed the porosity increasing towards 3.75 % and Vp and Vs decreasing towards 1.37±0.52 km/s and 0.97±0.25 km/s. The Poisson's ratio shows the negative values in dry and 0.5 in wet. In the meeting, we will present results of

  17. Toward Understanding Mechanisms Controlling Urea Delivery in a Coastal Plain Watershed

    Science.gov (United States)

    Tzilkowski, S. S.; Buda, A. R.; Boyer, E. W.; Bryant, R. B.; May, E. B.

    2012-12-01

    Improved understanding of nutrient mobilization and delivery to surface waters is critical to protecting water quality in agricultural watersheds. Urea, a form of organic nitrogen, is a common nutrient found in fertilizers, manures, and human waste, and is gaining recognition as an important driver of coastal eutrophication, particularly through the development of harmful algal blooms. While several studies have documented elevated urea concentrations in tributaries draining to the Chesapeake Bay, little is known about the potential sources and flow pathways responsible for urea delivery from the landscape to surface waters, as well as how these sources and pathways might vary with changing seasons, antecedent conditions, and storm types. In this study, we investigated hydrologic controls on urea delivery in the Manokin River watershed through the analysis of urea concentration dynamics and hysteresis patterns during seven storm events that occurred in 2010 and 2011. The Manokin River is a Coastal Plain watershed (11.1 km2) on the Delmarva Peninsula that drains directly to the Chesapeake Bay and is characterized by extensive rural development coupled with intensive agriculture, particularly poultry production. Sampling was conducted through monthly grab sampling at baseflow conditions and by time-weighted, automated (Sigma) samplers during stormflow events. Monitored storms were chosen to represent a spectrum of antecedent conditions based on precipitation and groundwater levels in the area. Flushing from the landscape during events was found to be the predominant urea delivery mechanism, as urea concentrations increased 3-9 times above baseflow concentrations during storms. The timing and number of flushes, as well as the degree of increased concentrations were dependent on antecedent conditions and the characteristics of the storm event. For instance, during an intense (13.7 mm hr-1), short-duration (4 hrs) storm in August of 2010 when antecedent conditions were

  18. Virulence evolution at the front line of spreading epidemics.

    Science.gov (United States)

    Griette, Quentin; Raoul, Gaël; Gandon, Sylvain

    2015-11-01

    Understanding and predicting the spatial spread of emerging pathogens is a major challenge for the public health management of infectious diseases. Theoretical epidemiology shows that the speed of an epidemic is governed by the life-history characteristics of the pathogen and its ability to disperse. Rapid evolution of these traits during the invasion may thus affect the speed of epidemics. Here we study the influence of virulence evolution on the spatial spread of an epidemic. At the edge of the invasion front, we show that more virulent and transmissible genotypes are expected to win the competition with other pathogens. Behind the front line, however, more prudent exploitation strategies outcompete virulent pathogens. Crucially, even when the presence of the virulent mutant is limited to the edge of the front, the invasion speed can be dramatically altered by pathogen evolution. We support our analysis with individual-based simulations and we discuss the additional effects of demographic stochasticity taking place at the front line on virulence evolution. We confirm that an increase of virulence can occur at the front, but only if the carrying capacity of the invading pathogen is large enough. These results are discussed in the light of recent empirical studies examining virulence evolution at the edge of spreading epidemics. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  19. Candida albicans secreted aspartyl proteinases in virulence and pathogenesis.

    Science.gov (United States)

    Naglik, Julian R; Challacombe, Stephen J; Hube, Bernhard

    2003-09-01

    Candida albicans is the most common fungal pathogen of humans and has developed an extensive repertoire of putative virulence mechanisms that allows successful colonization and infection of the host under suitable predisposing conditions. Extracellular proteolytic activity plays a central role in Candida pathogenicity and is produced by a family of 10 secreted aspartyl proteinases (Sap proteins). Although the consequences of proteinase secretion during human infections is not precisely known, in vitro, animal, and human studies have implicated the proteinases in C. albicans virulence in one of the following seven ways: (i) correlation between Sap production in vitro and Candida virulence, (ii) degradation of human proteins and structural analysis in determining Sap substrate specificity, (iii) association of Sap production with other virulence processes of C. albicans, (iv) Sap protein production and Sap immune responses in animal and human infections, (v) SAP gene expression during Candida infections, (vi) modulation of C. albicans virulence by aspartyl proteinase inhibitors, and (vii) the use of SAP-disrupted mutants to analyze C. albicans virulence. Sap proteins fulfill a number of specialized functions during the infective process, which include the simple role of digesting molecules for nutrient acquisition, digesting or distorting host cell membranes to facilitate adhesion and tissue invasion, and digesting cells and molecules of the host immune system to avoid or resist antimicrobial attack by the host. We have critically discussed the data relevant to each of these seven criteria, with specific emphasis on how this proteinase family could contribute to Candida virulence and pathogenesis.

  20. Brucella, nitrogen and virulence.

    Science.gov (United States)

    Ronneau, Severin; Moussa, Simon; Barbier, Thibault; Conde-Álvarez, Raquel; Zuniga-Ripa, Amaia; Moriyon, Ignacio; Letesson, Jean-Jacques

    2016-08-01

    The brucellae are α-Proteobacteria causing brucellosis, an important zoonosis. Although multiplying in endoplasmic reticulum-derived vacuoles, they cause no cell death, suggesting subtle but efficient use of host resources. Brucellae are amino-acid prototrophs able to grow with ammonium or use glutamate as the sole carbon-nitrogen source in vitro. They contain more than twice amino acid/peptide/polyamine uptake genes than the amino-acid auxotroph Legionella pneumophila, which multiplies in a similar vacuole, suggesting a different nutritional strategy. During these two last decades, many mutants of key actors in nitrogen metabolism (transporters, enzymes, regulators, etc.) have been described to be essential for full virulence of brucellae. Here, we review the genomic and experimental data on Brucella nitrogen metabolism and its connection with virulence. An analysis of various aspects of this metabolism (transport, assimilation, biosynthesis, catabolism, respiration and regulation) has highlighted differences and similarities in nitrogen metabolism with other α-Proteobacteria. Together, these data suggest that, during their intracellular life cycle, the brucellae use various nitrogen sources for biosynthesis, catabolism and respiration following a strategy that requires prototrophy and a tight regulation of nitrogen use.

  1. Towards a neurobiological understanding of pain in chronic pancreatitis: mechanisms and implications for treatment

    Directory of Open Access Journals (Sweden)

    Søren S. Olesen

    2017-12-01

    Conclusion:. Chronic pancreatitis is associated with abnormal processing of pain at the peripheral and central level of the pain system. This neurobiological understanding of pain has important clinical implications for treatment and prevention of pain chronification.

  2. Advances in understanding of soil biogeochemical cycles: the mechanism of HS entry into the root interior

    Science.gov (United States)

    Aleksandrova, Olga

    2017-04-01

    Humic substances represent the major reservoir of carbon (C) in ecosystems, and their turnover is crucial for understanding the global C cycle. As shown by some investigators [1-2], the phenomenon of the uptake of the whole humic particles by plant roots is a significant step of biogeochemical cycle of carbon in soils. The mechanism of HS entry the root interior remained unknown for a long time. However recently, the last one was discovered [3]. An advanced model [3] includes two hypotheses. These hypotheses are as follows: (1) each nano-size particle possesses a quantum image that can be revealed as a packet of electromagnetic waves; (2) the interaction of nano-size particle with the membrane (plasma membrane) of living cells, on which it is adsorbed, occurs via the development of the Rayleigh-Taylor (RT) instability on the membrane surface. An advanced model allows us to look insight some into some phenomena that were observed by experiments but remained not understood [2]. The authors [2] applied tritium autoradiography to wheat seedlings cultivated with tritium-labeled HS to consider the uptake of humic particles by plant roots. They found a significant increase in the content of some polar (monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), sulfoquinovosyl diacylglycerol (SQDG) and phosphatidylcholine (PC)) and neutral (free fatty acids, FFA) lipids which were detected in the wheat seedlings treated with humic particles. Authors [2] pointed that lipids MGDG, DGDG, SQDG are crucial for functional and structural integrity of the photosystem complex. Therefore, a stimulating action of adsorbed humic particles evoked phenomena like photosynthesis in root cells that can be interpreted using an advanced model: humic particles being nano-size particles become adsorbed on the plant roots in soils, and influence their micro environment, where they are located, with the specific electromagnetic exposure. Another finding of authors consisted in the

  3. Oxide nanoparticle EUV resists: toward understanding the mechanism of positive and negative tone patterning

    KAUST Repository

    Chakrabarty, Souvik

    2013-04-01

    DUV, EUV and e-beam patterning of hybrid nanoparticle photoresists have been reported previously by Ober and coworkers. The present work explores the underlying mechanism that is responsible for the dual tone patterning capability of these photoresist materials. Spectroscopic results correlated with mass loss and dissolution studies suggest a ligand exchange mechanism responsible for altering the solubility between the exposed and unexposed regions. © 2013 SPIE.

  4. Using realist synthesis to understand the mechanisms of interprofessional teamwork in health and social care.

    Science.gov (United States)

    Hewitt, Gillian; Sims, Sarah; Harris, Ruth

    2014-11-01

    Realist synthesis offers a novel and innovative way to interrogate the large literature on interprofessional teamwork in health and social care teams. This article introduces realist synthesis and its approach to identifying and testing the underpinning processes (or "mechanisms") that make an intervention work, the contexts that trigger those mechanisms and their subsequent outcomes. A realist synthesis of the evidence on interprofessional teamwork is described. Thirteen mechanisms were identified in the synthesis and findings for one mechanism, called "Support and value" are presented in this paper. The evidence for the other twelve mechanisms ("collaboration and coordination", "pooling of resources", "individual learning", "role blurring", "efficient, open and equitable communication", "tactical communication", "shared responsibility and influence", "team behavioural norms", "shared responsibility and influence", "critically reviewing performance and decisions", "generating and implementing new ideas" and "leadership") are reported in a further three papers in this series. The "support and value" mechanism referred to the ways in which team members supported one another, respected other's skills and abilities and valued each other's contributions. "Support and value" was present in some, but far from all, teams and a number of contexts that explained this variation were identified. The article concludes with a discussion of the challenges and benefits of undertaking this realist synthesis.

  5. Understanding User Preferences and Awareness: Privacy Mechanisms in Location-Based Services

    Science.gov (United States)

    Burghardt, Thorben; Buchmann, Erik; Müller, Jens; Böhm, Klemens

    Location based services (LBS) let people retrieve and share information related to their current position. Examples are Google Latitude or Panoramio. Since LBS share user-related content, location information etc., they put user privacy at risk. Literature has proposed various privacy mechanisms for LBS. However, it is unclear which mechanisms humans really find useful, and how they make use of them. We present a user study that addresses these issues. To obtain realistic results, we have implemented a geotagging application on the web and on GPS cellphones, and our study participants use this application in their daily lives. We test five privacy mechanisms that differ in the awareness, mental effort and degree of informedness required from the users. Among other findings, we have observed that in situations where a single simple mechanism does not meet all privacy needs, people want to use simple and sophisticated mechanisms in combination. Further, individuals are concerned about the privacy of others, even when they do not value privacy for themselves.

  6. Combating mutations in genetic disease and drug resistance: understanding molecular mechanisms to guide drug design.

    Science.gov (United States)

    Albanaz, Amanda T S; Rodrigues, Carlos H M; Pires, Douglas E V; Ascher, David B

    2017-06-01

    Mutations introduce diversity into genomes, leading to selective changes and driving evolution. These changes have contributed to the emergence of many of the current major health concerns of the 21st century, from the development of genetic diseases and cancers to the rise and spread of drug resistance. The experimental systematic testing of all mutations in a system of interest is impractical and not cost-effective, which has created interest in the development of computational tools to understand the molecular consequences of mutations to aid and guide rational experimentation. Areas covered: Here, the authors discuss the recent development of computational methods to understand the effects of coding mutations to protein function and interactions, particularly in the context of the 3D structure of the protein. Expert opinion: While significant progress has been made in terms of innovative tools to understand and quantify the different range of effects in which a mutation or a set of mutations can give rise to a phenotype, a great gap still exists when integrating these predictions and drawing causality conclusions linking variants. This often requires a detailed understanding of the system being perturbed. However, as part of the drug development process it can be used preemptively in a similar fashion to pharmacokinetics predictions, to guide development of therapeutics to help guide the design and analysis of clinical trials, patient treatment and public health policy strategies.

  7. Laboratory Activities to Support Student Understanding of the Molecular Mechanisms of Mutation & Natural Selection

    Science.gov (United States)

    Hubler, Tina; Adams, Patti; Scammell, Jonathan

    2015-01-01

    The molecular basis of evolution is an important and challenging concept for students to understand. In a previous article, we provided some of the scientific background necessary to teach this topic. This article features a series of laboratory activities demonstrating that molecular events can alter the genomes of organisms. These activities are…

  8. Differential interactions of virulent and non-virulent H. parasuis strains with naïve or swine influenza virus pre-infected dendritic cells

    Directory of Open Access Journals (Sweden)

    Mussá Tufária

    2012-11-01

    Full Text Available Abstract Pigs possess a microbiota in the upper respiratory tract that includes Haemophilus parasuis. Pigs are also considered the reservoir of influenza viruses and infection with this virus commonly results in increased impact of bacterial infections, including those by H. parasuis. However, the mechanisms involved in host innate responses towards H. parasuis and their implications in a co-infection with influenza virus are unknown. Therefore, the ability of a non-virulent H. parasuis serovar 3 (SW114 and a virulent serovar 5 (Nagasaki strains to interact with porcine bone marrow dendritic cells (poBMDC and their modulation in a co-infection with swine influenza virus (SwIV H3N2 was examined. At 1 hour post infection (hpi, SW114 interaction with poBMDC was higher than that of Nagasaki, while at 8 hpi both strains showed similar levels of interaction. The co-infection with H3N2 SwIV and either SW114 or Nagasaki induced higher levels of IL-1β, TNF-α, IL-6, IL-12 and IL-10 compared to mock or H3N2 SwIV infection alone. Moreover, IL-12 and IFN-α secretion differentially increased in cells co-infected with H3N2 SwIV and Nagasaki. These results pave the way for understanding the differences in the interaction of non-virulent and virulent strains of H. parasuis with the swine immune system and their modulation in a viral co-infection.

  9. Towards an understanding of hot carrier cooling mechanisms in multiple quantum wells

    Science.gov (United States)

    Conibeer, Gavin; Zhang, Yi; Bremner, Stephen P.; Shrestha, Santosh

    2017-09-01

    Multiple quantum wells have been shown significantly reduced hot carrier cooling rates compared to bulk material and are thus a promising candidate for hot carrier solar cell absorbers. However, the mechanism(s) by which hot carrier cooling is restricted is not clear. A systematic study of carrier cooling rates in GaAs/AlAs multiple quantum wells (MQWs) with either varying barrier thickness or varying well thickness is presented in this paper. These allow an investigation as to whether the mechanisms of either a modification in hot carrier diffusion or a localisation of phonons emitted by hot carriers are primarily responsible for reduced carrier cooling rates. With the conclusion that for the structures investigated the situation is rather more complex with both carrier mobility to modify hot carrier diffusion, different diffusion rates for electrons and holes and reflection and localisation of phonons to enhance phonon bottleneck all playing their parts in modulating phonon reabsorption and hot carrier behaviour.

  10. The contribution of experimental in vivo models to understanding the mechanisms of adaptation to mechanical loading in bone

    Directory of Open Access Journals (Sweden)

    Lee B Meakin

    2014-10-01

    Full Text Available Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading.Jiri Heřt introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gauges to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced.Experiments combining strain gauge instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats and mice has yielded significant insight into the control of strain-related adaptive (remodeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice which is now the model of choice for many studies. Together such studies have demonstrated that; over the physiological strain range, bone’s mechanically-adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles and that these are most effective when interrupted by short periods of

  11. The Contribution of Experimental in vivo Models to Understanding the Mechanisms of Adaptation to Mechanical Loading in Bone

    Science.gov (United States)

    Meakin, Lee B.; Price, Joanna S.; Lanyon, Lance E.

    2014-01-01

    Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading. Jiri Hert introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gages to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced. Experiments combining strain gage instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats, and mice has yielded significant insight into the control of strain-related adaptive (re)modeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice, which is now the model of choice for many studies. Together such studies have demonstrated that over the physiological strain range, bone’s mechanically adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles, and that these are most effective when interrupted by short periods of rest between them

  12. Understanding the mechanism of nanotube synthesis for controlled production of specific (n,m) structures

    Energy Technology Data Exchange (ETDEWEB)

    Resasco, Daniel E.

    2010-02-11

    This report shows the extensive research on the mechanism responsible for the formation of single walled carbon nanotubes in order to get control over their structural parameters (diameter and chirality). Catalyst formulations, pre-treatment conditions, and reaction conditions are described in detail as well as mechanisms to produce nanotubes structures of specific arrays (vertical forest, nanotube pillars). Applications of SWNT in different fields are also described in this report. In relation to this project five students have graduated (3 PhD and 2 MS) and 35 papers have been published.

  13. Are Dispersal Mechanisms Changing the Host-Parasite Relationship and Increasing the Virulence of Varroa destructor (Mesostigmata: Varroidae) in Managed Honey Bee (Hymenoptera: Apidae) Colonies?

    Science.gov (United States)

    DeGrandi-Hoffman, Gloria; Ahumada, Fabiana; Graham, Henry

    2017-08-01

    Varroa (Varroa destructor Anderson and Trueman) are a serious pest of European honey bees (Apis mellifera L.), and difficult to control in managed colonies. In our 11-mo longitudinal study, we applied multiple miticide treatments, yet mite numbers remained high and colony losses exceeded 55%. High mortality from varroa in managed apiaries is a departure from the effects of the mite in feral colonies where bees and varroa can coexist. Differences in mite survival strategies and dispersal mechanisms may be contributing factors. In feral colonies, mites can disperse through swarming. In managed apiaries, where swarming is reduced, mites disperse on foragers robbing or drifting from infested hives. Using a honey bee-varroa population model, we show that yearly swarming curtails varroa population growth, enabling colony survival for >5 yr. Without swarming, colonies collapsed by the third year. To disperse, varroa must attach to foragers that then enter other hives. We hypothesize that stress from parasitism and virus infection combined with effects that viruses have on cognitive function may contribute to forager drift and mite and virus dispersal. We also hypothesize that drifting foragers with mites can measurably increase mite populations. Simulations initialized with field data indicate that low levels of drifting foragers with mites can create sharp increases in mite populations in the fall and heavily infested colonies in the spring. We suggest new research directions to investigate factors leading to mite dispersal on foragers, and mite management strategies with consideration of varroa as a migratory pest. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.

  14. A mathematical model towards understanding the mechanism of neuronal regulation of wake-NREMS-REMS states.

    Directory of Open Access Journals (Sweden)

    Rupesh Kumar

    Full Text Available In this study we have constructed a mathematical model of a recently proposed functional model known to be responsible for inducing waking, NREMS and REMS. Simulation studies using this model reproduced sleep-wake patterns as reported in normal animals. The model helps to explain neural mechanism(s that underlie the transitions between wake, NREMS and REMS as well as how both the homeostatic sleep-drive and the circadian rhythm shape the duration of each of these episodes. In particular, this mathematical model demonstrates and confirms that an underlying mechanism for REMS generation is pre-synaptic inhibition from substantia nigra onto the REM-off terminals that project on REM-on neurons, as has been recently proposed. The importance of orexinergic neurons in stabilizing the wake-sleep cycle is demonstrated by showing how even small changes in inputs to or from those neurons can have a large impact on the ensuing dynamics. The results from this model allow us to make predictions of the neural mechanisms of regulation and patho-physiology of REMS.

  15. The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

    Science.gov (United States)

    Cheng, Ying; Shao, Can; Lathrop, Quinn N.

    2016-01-01

    Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable…

  16. Understanding the antimicrobial mechanism of TiO2-based nanocomposite films in a pathogenic bacterium

    NARCIS (Netherlands)

    Kubacka, A.; Suarez Diez, M.; Rojo, D.; Bargiela, R.; Ciordia, S.; Zapico, I.; Albar, J.P.; Barbas, C.; Martins Dos Santos, V.A.P.; Fernández-García, M.; Ferrer, M.

    2014-01-01

    Titania (TiO2)-based nanocomposites subjected to light excitation are remarkably effective in eliciting microbial death. However, the mechanism by which these materials induce microbial death and the effects that they have on microbes are poorly understood. Here, we assess the low dose

  17. Understanding the mechanism of action of triazine-phosphonate derivatives as flame retardants for cotton fabrics

    Science.gov (United States)

    Countless hours of research and studies on triazine, phosphonate and their combination have provided insightful information into their flame retardant properties on polymeric systems. However, only limited number of studies shed light on the mechanism of flame retardant cotton fabrics. The purpose...

  18. Investigating and improving student understanding of quantum mechanics in the context of single photon interference

    Science.gov (United States)

    Marshman, Emily; Singh, Chandralekha

    2017-06-01

    Single photon experiments involving a Mach-Zehnder interferometer can illustrate the fundamental principles of quantum mechanics, e.g., the wave-particle duality of a single photon, single photon interference, and the probabilistic nature of quantum measurement involving single photons. These experiments explicitly make the connection between the abstract quantum theory and concrete laboratory settings and have the potential to help students develop a solid grasp of the foundational issues in quantum mechanics. Here we describe students' conceptual difficulties with these topics in the context of Mach-Zehnder interferometer experiments with single photons and how the difficulties found in written surveys and individual interviews were used as a guide in the development of a Quantum Interactive Learning Tutorial (QuILT). The QuILT uses an inquiry-based approach to learning and takes into account the conceptual difficulties found via research to help upper-level undergraduate and graduate students learn about foundational quantum mechanics concepts using the concrete quantum optics context. It strives to help students learn the basics of quantum mechanics in the context of single photon experiment, develop the ability to apply fundamental quantum principles to experimental situations in quantum optics, and explore the differences between classical and quantum ideas in a concrete context. We discuss the findings from in-class evaluations suggesting that the QuILT was effective in helping students learn these abstract concepts.

  19. Improving Student Understanding of Addition of Angular Momentum in Quantum Mechanics

    Science.gov (United States)

    Zhu, Guangtian; Singh, Chandralekha

    2013-01-01

    We describe the difficulties advanced undergraduate and graduate students have with concepts related to addition of angular momentum in quantum mechanics. We also describe the development and implementation of a research-based learning tool, Quantum Interactive Learning Tutorial (QuILT), to reduce these difficulties. The preliminary evaluation…

  20. A Changing Landscape of Advanced Prostate Cancer: Understanding Mechanisms of Resistance to Potent Hormonal Therapies

    Science.gov (United States)

    2016-10-01

    mechanisms of NEPC progression using deep sequencing techniques of metastatic tumor biopsies and non-invasively using liquid biopsies including...from each site. (b) AR signaling (right) based on abundance of mRNA transcripts included in the AR signaling signature described in ref 19. Violin

  1. Recent advances in understanding the reinforcing ability and mechanism of carbon nanotubes in ceramic matrix composites

    International Nuclear Information System (INIS)

    Estili, Mehdi; Sakka, Yoshio

    2014-01-01

    Since the discovery of carbon nanotubes (CNTs), commonly referred to as ultimate reinforcement, the main purpose for fabricating CNT–ceramic matrix composites has been mainly to improve the fracture toughness and strength of the ceramic matrix materials. However, there have been many studies reporting marginal improvements or even the degradation of mechanical properties. On the other hand, those studies claiming noticeable toughening measured using indentation, which is an indirect/unreliable characterization method, have not demonstrated the responsible mechanisms applicable to the nanoscale, flexible CNTs; instead, those studies proposed those classical methods applicable to microscale fiber/whisker reinforced ceramics without showing any convincing evidence of load transfer to the CNTs. Therefore, the ability of CNTs to directly improve the macroscopic mechanical properties of structural ceramics has been strongly questioned and debated in the last ten years. In order to properly discuss the reinforcing ability (and possible mechanisms) of CNTs in a ceramic host material, there are three fundamental questions to our knowledge at both the nanoscale and macroscale levels that need to be addressed: (1) does the intrinsic load-bearing ability of CNTs change when embedded in a ceramic host matrix?; (2) when there is an intimate atomic-level interface without any chemical reaction with the matrix, could one expect any load transfer to the CNTs along with effective load bearing by them during crack propagation?; and (3) considering their nanometer-scale dimensions, flexibility and radial softness, are the CNTs able to improve the mechanical properties of the host ceramic matrix at the macroscale when individually, intimately and uniformly dispersed? If so, how? Also, what is the effect of CNT concentration in such a defect-free composite system? Here, we briefly review the recent studies addressing the above fundamental questions. In particular, we discuss the new

  2. Understanding NOx SCR Mechanism and Activity on Cu/Chabazite Structures throughout the Catalyst Life Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Fabio; Delgass, Nick; Gounder, Rajmani; Schneider, William F.; Miller, Jeff; Yezerets, Aleksey; McEwen, Jean-Sabin; Peden, Charles HF; Howden, Ken

    2014-12-09

    Oxides of nitrogen (NOx) compounds contribute to acid rain and photochemical smog and have been linked to respiratory ailments. NOx emissions regulations continue to tighten, driving the need for high performance, robust control strategies. The goal of this project is to develop a deep, molecular level understanding of the function of Cu-SSZ-13 and Cu-SAPO-34 materials that catalyze the SCR of NOx with NH3.

  3. Progress in understanding the mechanical behavior of pressure-vessel materials at elevated temperatures

    International Nuclear Information System (INIS)

    Swindeman, R.W.; Brinkman, C.R.

    1981-01-01

    Progress during the 1970's on the production of high-temperature mechanical properties data for pressure vessel materials was reviewed. The direction of the research was toward satisfying new data requirements to implement advances in high-temperature inelastic design methods. To meet these needs, servo-controlled testing machines and high-resolution extensometry were developed to gain more information on the essential behavioral features of high-temperature alloys. The similarities and differences in the mechanical response of various pressure vessel materials were identified. High-temperature pressure vessel materials that have received the most attention included Type 304 stainless steel, Type 316 stainless steel, 2 1/4 Cr-1 Mo steel, alloy 800H, and Hastelloy X

  4. Understanding reaction mechanisms in organic chemistry from catastrophe theory applied to the electron localization function topology.

    Science.gov (United States)

    Polo, Victor; Andres, Juan; Berski, Slawomir; Domingo, Luis R; Silvi, Bernard

    2008-08-07

    Thom's catastrophe theory applied to the evolution of the topology of the electron localization function (ELF) gradient field constitutes a way to rationalize the reorganization of electron pairing and a powerful tool for the unambiguous determination of the molecular mechanisms of a given chemical reaction. The identification of the turning points connecting the ELF structural stability domains along the reaction pathway allows a rigorous characterization of the sequence of electron pair rearrangements taking place during a chemical transformation, such as multiple bond forming/breaking processes, ring closure processes, creation/annihilation of lone pairs, transformations of C-C multiple bonds into single ones. The reaction mechanism of some relevant organic reactions: Diels-Alder, 1,3-dipolar cycloaddition and Cope rearrangement are reviewed to illustrate the potential of the present approach.

  5. Understanding the Acute Skin Injury Mechanism Caused by Player-Surface Contact During Soccer

    Science.gov (United States)

    van den Eijnde, Wilbert A.J.; Peppelman, Malou; Lamers, Edwin A.D.; van de Kerkhof, Peter C.M.; van Erp, Piet E.J.

    2014-01-01

    Background: Superficial skin injuries are considered minor, and their incidence is probably underestimated. Insight into the incidence and mechanism of acute skin injury can be helpful in developing suitable preventive measures and safer playing surfaces for soccer and other field sports. Purpose: To gain insight into the incidence and severity of skin injuries related to soccer and to describe the skin injury mechanism due to player-surface contact. Study Design: Systematic review; Level of evidence, 4. Methods: The prevention model by van Mechelen et al (1992) combined with the injury causation model of Bahr and Krosshaug (2005) were used as a framework for the survey to describe the skin injury incidence and mechanism caused by player-surface contact. Results: The reviewed literature showed that common injury reporting methods are mainly based on time lost from participation or the need for medical attention. Because skin abrasions seldom lead to absence or medical attention, they are often not reported. When reported, the incidence of abrasion/laceration injuries varies from 0.8 to 6.1 injuries per 1000 player-hours. Wound assessment techniques such as the Skin Damage Area and Severity Index can be a valuable tool to obtain a more accurate estimation of the incidence and severity of acute skin injuries. Conclusion: The use of protective equipment, a skin lubricant, or wet surface conditions has a positive effect on preventing abrasion-type injuries from artificial turf surfaces. The literature also shows that essential biomechanical information of the sliding event is lacking, such as how energy is transferred to the area of contact. From a clinical and histological perspective, there are strong indications that a sliding-induced skin lesion is caused by mechanical rather than thermal injury to the skin. PMID:26535330

  6. Understanding the Personality and Behavioral Mechanisms Defining Hypersexuality in Men Who Have Sex With Men.

    Science.gov (United States)

    Miner, Michael H; Romine, Rebecca Swinburne; Raymond, Nancy; Janssen, Erick; MacDonald, Angus; Coleman, Eli

    2016-09-01

    Hypersexuality has been conceptualized as sexual addiction, compulsivity, and impulsivity, among others, in the absence of strong empirical data in support of any specific conceptualization. To investigate personality factors and behavioral mechanisms that are relevant to hypersexuality in men who have sex with men. A sample of 242 men who have sex with men was recruited from various sites in a moderate-size mid-western city. Participants were assigned to a hypersexuality group or a control group using an interview similar to the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition. Self-report inventories were administered that measured the broad personality constructs of positive emotionality, negative emotionality, and constraint and more narrow constructs related to sexual behavioral control, behavioral activation, behavioral inhibition, sexual excitation, sexual inhibition, impulsivity, attention-deficit/hyperactivity disorder, and sexual behavior. Hierarchical logistic regression was used to determine the relation between these personality and behavioral variables and group membership. A hierarchical logistic regression controlling for age showed a significant positive relation between hypersexuality and negative emotionality and a negative relation with constraint. None of the behavioral mechanism variables entered this equation. However, a hierarchical multiple regression analysis predicting sexual behavioral control indicated that lack of such control was positively related to sexual excitation and sexual inhibition owing to the threat of performance failure and negatively related to sexual inhibition owing to the threat of performance consequences and general behavioral inhibition Hypersexuality was found to be related to two broad personality factors that are characterized by emotional reactivity, risk taking, and impulsivity. The associated lack of sexual behavior control is influenced by sexual

  7. The effects of bariatric surgery – will understanding its mechanism render the knife unnecessary?

    OpenAIRE

    Browning, Kirsteen N; Hajnal, Andras

    2013-01-01

    The incidence of obesity is increasing worldwide at a dramatic rate, accompanied by an associated increase in comorbid conditions. Bariatric surgery is the most effective treatment for severe obesity with, until recently, Roux-en-Y gastric bypass (RYGB) being the most commonly performed procedures, yet the underlying mechanisms by which it induces a wide-array of beneficial effects remains obscure. From both basic science as well as clinical standpoints, there are several areas of current int...

  8. Understanding Freshness Perception from the Cognitive Mechanisms of Flavor: The Case of Beverages

    Science.gov (United States)

    Roque, Jérémy; Auvray, Malika; Lafraire, Jérémie

    2018-01-01

    Freshness perception has received recent consideration in the field of consumer science mainly because of its hedonic dimension, which is assumed to influence consumers’ preference and behavior. However, most studies have considered freshness as a multisensory attribute of food and beverage products without investigating the cognitive mechanisms at hand. In the present review, we endorse a slightly different perspective on freshness. We focus on (i) the multisensory integration processes that underpin freshness perception, and (ii) the top–down factors that influence the explicit attribution of freshness to a product by consumers. To do so, we exploit the recent literature on the cognitive underpinnings of flavor perception as a heuristic to better characterize the mechanisms of freshness perception in the particular case of beverages. We argue that the lack of consideration of particular instances of flavor, such as freshness, has resulted in a lack of consensus about the content and structure of different types of flavor representations. We then enrich these theoretical analyses, with a review of the cognitive mechanisms of flavor perception: from multisensory integration processes to the influence of top–down factors (e.g., attentional and semantic). We conclude that similarly to flavor, freshness perception is characterized by hybrid content, both perceptual and semantic, but that freshness has a higher-degree of specificity than flavor. In particular, contrary to flavor, freshness is characterized by specific functions (e.g., alleviation of oropharyngeal symptoms) and likely differs from flavor with respect to the weighting of each sensory contributor, as well as to its subjective location. Finally, we provide a comprehensive model of the cognitive mechanisms that underlie freshness perception. This model paves the way for further empirical research on particular instances of flavor, and will enable advances in the field of food and beverage cognition

  9. Investigating and improving student understanding of quantum mechanical observables and their corresponding operators in Dirac notation

    Science.gov (United States)

    Marshman, Emily; Singh, Chandralekha

    2018-01-01

    In quantum mechanics, for every physical observable, there is a corresponding Hermitian operator. According to the most common interpretation of quantum mechanics, measurement of an observable collapses the quantum state into one of the possible eigenstates of the operator and the corresponding eigenvalue is measured. Since Dirac notation is an elegant notation that is commonly used in upper-level quantum mechanics, it is important that students learn to express quantum operators corresponding to observables in Dirac notation in order to apply the quantum formalism effectively in diverse situations. Here we focus on an investigation that suggests that, even though Dirac notation is used extensively, many advanced undergraduate and PhD students in physics have difficulty expressing the identity operator and other Hermitian operators corresponding to physical observables in Dirac notation. We first describe the difficulties students have with expressing the identity operator and a generic Hermitian operator corresponding to an observable in Dirac notation. We then discuss how the difficulties found via written surveys and individual interviews were used as a guide in the development of a quantum interactive learning tutorial (QuILT) to help students develop a good grasp of these concepts. The QuILT strives to help students become proficient in expressing the identity operator and a generic Hermitian operator corresponding to an observable in Dirac notation. We also discuss the effectiveness of the QuILT based on in-class evaluations.

  10. Marine phospholipids: The current understanding of their oxidation mechanisms and potential uses for food fortification

    DEFF Research Database (Denmark)

    Lu, Henna Fung Sieng; Nielsen, Nina Skall; Baron, Caroline P.

    2017-01-01

    and storage of marine PL. For example, nonenzymatic browning reactions may occur between lipid oxidation products and primary amine group from phosphatidylethanolamine or amino acid residues that are present inmarine PL. Therefore, marine PL contain products from nonenzymatic browning and lipid oxidation...... reactions, namely, Strecker aldehydes, pyrroles, oxypolymers, and other impurities that may positively or negatively affect the oxidative stability and quality of marine PL. This review was undertaken to provide the industry and academia with an overview of the current understanding of the quality changes...... taking place in PL during their production and their storage as well as with regards to their utilization for food fortification....

  11. Understanding the Atomic Scale Mechanisms that Control the Attainment of Ultralow Friction and Wear in Carbon-Based Materials

    Science.gov (United States)

    2016-01-16

    2015. 15. Invited. New Insights into Friction and Wear through In-Situ Nanotribology. Joint Symposium of the Surface Science Society of Japan and...and Carpick, R.W. Influence of Surface Passivation on the Friction and Wear Behavior of Ultrananocrystalline Diamond and Tetrahedral Amorphous Carbon...AFRL-AFOSR-JP-TR-2016-0053 Understanding the Atomic Scale Mechanism that controls the attainment of ultralow friction and wear in carbon based

  12. The effects of students' reasoning abilities on conceptual understandings and problem-solving skills in introductory mechanics

    International Nuclear Information System (INIS)

    Ates, S; Cataloglu, E

    2007-01-01

    The purpose of this study was to determine if there are relationships among freshmen/first year students' reasoning abilities, conceptual understandings and problem-solving skills in introductory mechanics. The sample consisted of 165 freshmen science education prospective teachers (female = 86, male = 79; age range 17-21) who were enrolled in an introductory physics course. Data collection was done during the fall semesters in two successive years. At the beginning of each semester, the force concept inventory (FCI) and the classroom test of scientific reasoning (CTSR) were administered to assess students' initial understanding of basic concepts in mechanics and reasoning levels. After completing the course, the FCI and the mechanics baseline test (MBT) were administered. The results indicated that there was a significant difference in problem-solving skill test mean scores, as measured by the MBT, among concrete, formal and postformal reasoners. There were no significant differences in conceptual understanding levels of pre- and post-test mean scores, as measured by FCI, among the groups. The Benferroni post hoc comparison test revealed which set of reasoning levels showed significant difference for the MBT scores. No statistical difference between formal and postformal reasoners' mean scores was observed, while the mean scores between concrete and formal reasoners and concrete and postformal reasoners were statistically significantly different

  13. Understanding of bonding and mechanical characteristics of cementitious mineral tobermorite from first principles.

    Science.gov (United States)

    Tunega, Daniel; Zaoui, Ali

    2011-01-30

    This paper reports density functional theory study of the structural and mechanical properties of tobermorite mineral (9 Å phase) as one of the main component of cementitious materials in a concrete chemistry. Calculated bulk modulus and elastic constants reflect a relatively high resistance of the tobermorite structure with respect to external isostatic compression. Moreover, the elastic constants proved the anisotropic character of the tobermorite structure. The directions parallel to the axb plane are more resistant to the compression than the perpendicular direction. The largest contribution to this resistance comes from the "dreierketten" silicate chains. The bonding analysis linked macroscopic mechanical properties and the atomic structure of the tobermorite. It was found that polar covalent Si-O bonds are stiffer than iono-covalent Ca-O bonds. The SiO(4) tetrahedra are resistant with respect to the compression and the effect of external pressure is reflected by the large mutual tilting of these tetrahedra as it is shown by changes of the Si-O-Si bridging angles. Polyhedra with the seven-fold coordinated Ca(2+) cations undergo large structural changes. Especially, axial Ca-O bonds perpendicular to the axb plane are significantly shortened. Besides, it was shown that structural parameters, more or less in parallel orientation to the axb plane, are mainly responsible for the high resistance of the tobermorite structure to external pressure. The main mechanism of a dissipation of energy entered to the structure through the compression is proceeded by the tilting of the tetrahedra of the silicate chains and by large shortening of the axial Ca-O distances. Copyright © 2010 Wiley Periodicals, Inc.

  14. Understanding flocculation mechanism of graphene oxide for organic dyes from water: Experimental and molecular dynamics simulation

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2015-11-01

    Full Text Available Flocculation treatment processes play an important role in water and wastewater pretreatment. Here we investigate experimentally and theoretically the possibility of using graphene oxide (GO as a flocculant to remove methylene blue (MB from water. Experimental results show that GO can remove almost all MB from aqueous solutions at its optimal dosages and molecular dynamics simulations indicate that MB cations quickly congregate around GO in water. Furthermore, PIXEL energy contribution analysis reveals that most of the strong interactions between GO and MB are of a van der Waals (London dispersion character. These results offer new insights for shedding light on the molecular mechanism of interaction between GO and organic pollutants.

  15. Understanding organometallic reaction mechanisms and catalysis experimental and computational tools computational and experimental tools

    CERN Document Server

    Ananikov, Valentin P

    2014-01-01

    Exploring and highlighting the new horizons in the studies of reaction mechanisms that open joint application of experimental studies and theoretical calculations is the goal of this book. The latest insights and developments in the mechanistic studies of organometallic reactions and catalytic processes are presented and reviewed. The book adopts a unique approach, exemplifying how to use experiments, spectroscopy measurements, and computational methods to reveal reaction pathways and molecular structures of catalysts, rather than concentrating solely on one discipline. The result is a deeper

  16. Zingerone silences quorum sensing and attenuates virulence of Pseudomonas aeruginosa.

    Science.gov (United States)

    Kumar, Lokender; Chhibber, Sanjay; Kumar, Rajnish; Kumar, Manoj; Harjai, Kusum

    2015-04-01

    Quorum sensing in Pseudomonas aeruginosa plays an imperative role in virulence factor, biofilm formation and antimicrobial resistance. Blocking quorum sensing pathways are viewed as viable anti-virulent therapy in association with traditional antimicrobial therapy. Anti-quorum sensing dietary phytochemicals with may prove to be a safe and viable choice as anti-virulent drug candidates. Previously, our lab proved zingerone as potent anti-biofilm agent hence; further its anti-virulent and anti-quorum activities were evaluated. Zingerone, besides decreasing swimming, swarming and twitching phenotypes of P. aeruginosa PAO1, reduced biofilm forming capacity and production of virulence factors including rhamnolipid, elastase, protease, pyocyanin, cell free and cell bound hemolysin (pquorum sensing signal molecules by clinical isolates of P. aeruginosa but also showed significant interference with the activation of QS reporter strains. To study the mechanism of blocking quorum sensing cascade, in silico analysis was carried out. Anti-QS activity was attributed to interference with the ligand receptor interaction of zingerone with QS receptors (TraR, LasR, RhlR and PqsR). Zingerone showed a good comparative docking score to respective autoinducer molecules which was even higher than that of vanillin, a proven anti-quorum sensing phytochemical. The results of the present study revealed the anti-quorum sensing activity of zingerone targeting ligand-receptor interaction, hence proposing zingerone as a suitable anti-virulent drug candidate against P. aeruginosa infections. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis

    Directory of Open Access Journals (Sweden)

    Cheng-Yen Kao

    2016-02-01

    Full Text Available Helicobacter pylori pathogenesis and disease outcomes are mediated by a complex interplay between bacterial virulence factors, host, and environmental factors. After H. pylori enters the host stomach, four steps are critical for bacteria to establish successful colonization, persistent infection, and disease pathogenesis: (1 Survival in the acidic stomach; (2 movement toward epithelium cells by flagella-mediated motility; (3 attachment to host cells by adhesins/receptors interaction; (4 causing tissue damage by toxin release. Over the past 20 years, the understanding of H. pylori pathogenesis has been improved by studies focusing on the host and bacterial factors through epidemiology researches and molecular mechanism investigations. These include studies identifying the roles of novel virulence factors and their association with different disease outcomes, especially the bacterial adhesins, cag pathogenicity island, and vacuolating cytotoxin. Recently, the development of large-scale screening methods, including proteomic, and transcriptomic tools, has been used to determine the complex gene regulatory networks in H. pylori. In addition, a more available complete genomic database of H. pylori strains isolated from patients with different gastrointestinal diseases worldwide is helpful to characterize this bacterium. This review highlights the key findings of H. pylori virulence factors reported over the past 20 years.

  18. A Multiscale Understanding of the Thermodynamic and Kinetic Mechanisms of Laser Additive Manufacturing

    Directory of Open Access Journals (Sweden)

    Dongdong Gu

    2017-10-01

    Full Text Available Selective laser melting (SLM additive manufacturing (AM technology has become an important option for the precise manufacturing of complex-shaped metallic parts with high performance. The SLM AM process involves complicated physicochemical phenomena, thermodynamic behavior, and phase transformation as a high-energy laser beam melts loose powder particles. This paper provides multiscale modeling and coordinated control for the SLM of metallic materials including an aluminum (Al-based alloy (AlSi10Mg, a nickel (Ni-based super-alloy (Inconel 718, and ceramic particle-reinforced Al-based and Ni-based composites. The migration and distribution mechanisms of aluminium nitride (AlN particles in SLM-processed Al-based nanocomposites and the in situ formation of a gradient interface between the reinforcement and the matrix in SLM-processed tungsten carbide (WC/Inconel 718 composites were studied in the microscale. The laser absorption and melting/densification behaviors of AlSi10Mg and Inconel 718 alloy powder were disclosed in the mesoscale. Finally, the stress development during line-by-line localized laser scanning and the parameter-dependent control methods for the deformation of SLM-processed composites were proposed in the macroscale. Multiscale numerical simulation and experimental verification methods are beneficial in monitoring the complicated powder-laser interaction, heat and mass transfer behavior, and microstructural and mechanical properties development during the SLM AM process.

  19. Understanding the differing governance of EU emissions trading and renewable: feedback mechanisms and policy entrepreneurs

    Energy Technology Data Exchange (ETDEWEB)

    Boasson, Elin Lerum; Wettestad, Joergen

    2010-04-15

    This paper presents a comparative study of two central EU climate policies: the revised Emissions Trading System (ETS), and the revised Renewable Energy Directive (RES). Both were originally developed in the early 2000s and revised policies were adopted in December 2008. While the ETS from 2013 on will have a quite centralized and market-streamlined design, the revised RES stands forward as a more decentralized and technology-focused policy. Differing institutional feed-back mechanisms and related roles of policy entrepreneurs can shed considerable light on these policy differences. Due to member states' cautiousness and contrary to the preferences of the Commission, the initial ETS was designed as a rather decentralized and 'politicized' market system, creating a malfunctioning institutional dynamic. In the revision process, the Commission skillfully highlighted this ineffective dynamic to win support for a much more centralized and market-streamlined approach. In the case of RES, national technology-specific support schemes and the strong links between the renewable industry and member states promoted the converse outcome: decentralization and technology development. Members of the European Parliament utilized these mechanisms through policy networking, while the Commission successfully used developments within the global climate regime to induce some degree of centralization. (Author)

  20. Understanding the Mechanisms of Gold Shell Growth onto Polymer Microcapsules to Control Shell Thickness.

    Science.gov (United States)

    Tasker, Alison L; Hitchcock, James; Baxter, Elaine A; Cayre, Dr Olivier J; Biggs, Simon

    2017-07-04

    Polymer microcapsules have been used commercially for decades, however they have an inherent flaw which renders them impractical as a carrier of small, volatile molecules. The porous nature of the polymer shell allows for diffusion of the encapsulated molecules into the bulk. The use of metal shells is an innovative way to prevent undesired loss of small molecules from the core of microcapsules, however it is important, particularly when using expensive metals to ensure that the resulting shell is as thin as possible. Here we investigate the fundamental mechanisms controlling the gold shell thickness when a fragrance oil is encapsulated in a poly(methyl methacrylate) shell. We consider the distribution of the nanoparticles on the capsule surface, and from quantification of the adsorbed nanoparticle (NP) density and resulting shell thickness, we propose mechanisms to describe the gold shell growth for systems with high and low NP surface coverage. We suggest from our observations that the gold grows to fill in the gaps between NPs. At low NP concentrations, thicker metal shells form. We postulate that this is due to the low NP density on the surface, forcing the gold clusters to grow larger before they meet the adjacent ones. Thus, to grow the thinnest possible shells a densely packed monolayer of platinum nanoparticles is required on the capsule surface. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Understanding of carbon-based supercapacitors ageing mechanisms by electrochemical and analytical methods

    Science.gov (United States)

    Liu, Yinghui; Soucaze-Guillous, Benoît; Taberna, Pierre-Louis; Simon, Patrice

    2017-10-01

    In order to shed light on ageing mechanisms of Electrochemical Double Layer Capacitor (EDLC), two kinds of activated carbons are studied in tetraethyl ammonium tetrafluoroborate (Et4NBF4) in acetonitrile. In floating mode, it turns out that two different ageing mechanisms are observed, depending on the activated carbon electrode materials used. On one hand, carbon A exhibits a continuous capacitance and series resistance fall-off; on the other hand, for carbon B, only the series resistance degrades after ageing while the capacitance keeps unchanged. Additional electrochemical characterizations (Electrochemical Impedance Spectroscopy - EIS - and diffusion coefficient calculations) were carried out showing that carbon A's ageing behavior is suspected to be primarily related to the carbon degradation while for carbon B a passivation occurs leading to the formation of a Solid Electrolyte Interphase-Like (SEI-L) film. These hypotheses are supported by TG-IR and Raman spectroscopy analysis. The outcome forms the latter is an increase of carbon defects on carbon A on positive electrode.

  2. Atmospheric Compensation of Variations in Tropical Ocean Heat Transport: Understanding Mechanisms and Implications on Tectonic Timescales

    Science.gov (United States)

    Rencurrel, M. C.; Rose, B. E. J.

    2015-12-01

    The poleward transport of energy is a key aspect of the climate system, with surface ocean currents presently dominating the transport out of deep tropics. A classic study by Stone (1978) proposed that the total heat transport is determined by astronomical parameters and is highly insensitive to the detailed atmosphere-ocean dynamics. On the other hand, previous modeling work has shown that past continental configurations could have produced substantially different tropical ocean heat transport (OHT). How thoroughly does the atmosphere compensate for changes in ocean transport in terms of the top-of-atmosphere (TOA) radiative budget, what are the relevant mechanisms, and what are the consequences for surface temperature and climate on tectonic timescales? We examine these issues in a suite of aquaplanet GCM simulations subject to large prescribed variations in OHT. We find substantial but incomplete compensation, in which adjustment of the atmospheric Hadley circulation plays a key role. We then separate out the dynamical and thermodynamical components of the adjustment mechanism. Increased OHT tends to warm the mid- to high latitudes without cooling the tropics due asymmetries in radiative feedback processes. The warming is accompanied by hydrological cycle changes that are completely different from those driven by greenhouse gases, suggesting that drivers of past global change might be detectable from combinations of hydroclimate and temperature proxies.

  3. Psychosomatic medicine in the 21st century: understanding mechanisms and barriers to utilization.

    Science.gov (United States)

    Wise, Thomas N; Balon, Richard

    2015-01-01

    The psychosomatic approach arose in antiquity as mankind looked for explanations for illness and death. With the rise of modern medicine, the links between emotions and medical conditions, such as cardiac disease and diabetes, were described by astute clinical observers, but the mechanisms for these conditions were based on correlation from observations rather than on experimental design. Psychoanalytic theory was often utilized to explain many common diseases. For example, peptic ulcer disease was blamed upon anger and stress, but scientific methodology discovered Helicobacter pylori to be the significant causal factor of this disease and resulted in the development of more effective treatments. Nevertheless emotional factors are still linked to disease states and morbidity; for example, depression is a risk factor for mortality following myocardial infarction. Advances in neuroscience demonstrate that the reduction of telomere length by anxiety and stress leads to more rapid aging and potential disease vulnerability. Thus, neuroscientific probes may allow for the elucidation of psychosomatic mechanisms. Sadly, clinical barriers, in terms of time pressure upon physicians and the current separation of mental health services from primary care settings, continue the dualistic treatment of many conditions where psychological factors are important. It is not clear whether a mandate for the integration of behavioral health into primary care will remedy this partition and finally maximize a psychosomatic approach to medical care. © 2015 S. Karger AG, Basel.

  4. A New Alkali-Stable Phosphonium Cation Based on Fundamental Understanding of Degradation Mechanisms.

    Science.gov (United States)

    Zhang, Bingzi; Kaspar, Robert B; Gu, Shuang; Wang, Junhua; Zhuang, Zhongbin; Yan, Yushan

    2016-09-08

    Highly alkali-stable cationic groups are a critical component of hydroxide exchange membranes (HEMs). To search for such cations, we studied the degradation kinetics and mechanisms of a series of quaternary phosphonium (QP) cations. Benzyl tris(2,4,6-trimethoxyphenyl)phosphonium [BTPP-(2,4,6-MeO)] was determined to have higher alkaline stability than the benchmark cation, benzyl trimethylammonium (BTMA). A multi-step methoxy-triggered degradation mechanism for BTPP-(2,4,6-MeO) was proposed and verified. By replacing methoxy substituents with methyl groups, a superior QP cation, methyl tris(2,4,6-trimethylphenyl)phosphonium [MTPP-(2,4,6-Me)] was developed. MTPP-(2,4,6-Me) is one of the most stable cations reported to date, with <20 % degradation after 5000 h at 80 °C in a 1 m KOD in CD3 OD/D2 O (5:1 v/v) solution. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Understanding the evolution of the windlass mechanism of the human foot from comparative anatomy: Insights, obstacles, and future directions.

    Science.gov (United States)

    Griffin, Nicole L; Miller, Charlotte E; Schmitt, Daniel; D'Août, Kristiaan

    2015-01-01

    Humans stand alone from other primates in that we propel our bodies forward on a relatively stiff and arched foot and do so by employing an anatomical arrangement of bones and ligaments in the foot that can operate like a "windlass." This is a significant evolutionary innovation, but it is currently unknown when during hominin evolution this mechanism developed and within what genera or species it originated. The presence of recently discovered fossils along with novel research in the past two decades have improved our understanding of foot mechanics in humans and other apes, making it possible to consider this question more fully. Here we review the main elements thought to be involved in the production of an effective, modern human-like windlass mechanism. These elements are the triceps surae, plantar aponeurosis, medial longitudinal arch, and metatarsophalangeal joints. We discuss what is presently known about the evolution of these features and the challenges associated with identifying each of these specific components and/or their function in living and extinct primates for the purpose of predicting the presence of the windlass mechanism in our ancestors. In some cases we recommend alternative pathways for inferring foot mechanics and for testing the hypothesis that the windlass mechanism evolved to increase the speed and energetic efficiency of bipedal gait in hominins. © 2014 Wiley Periodicals, Inc.

  6. Understanding the mechanisms of thermal disintegrating treatment in the reduction of sludge production.

    Science.gov (United States)

    Camacho, P; Ginestet, P; Audic, J-M

    2005-01-01

    Among the technologies aimed at reducing sludge production, the combination of thermal treatment at 95 degrees C of sludge and the activated sludge process is a promising route. The feasibility of such a combined process is demonstrated (up to 60% sludge reduction) and the impacts of operating conditions on its efficiency are presented. Major emphasis was put on understanding the complex phenomena occurring within the thermal treatment: release and biodegradability of sludge organic matter, impact on the biological activity (decay, maintenance requirements, etc.). These effects were taken into account for the development of an ASM1-based model. Comparison between the modeling approach and experimental data (continuous and batch) showed that thermal treatment had three major issues partly explaining the reduction of sludge production: (i) a low release of organics; (ii) an immediate and reversible biological inactivation associated with additional maintenance energy requirements; and (iii) a potential inert production.

  7. Understanding mechanisms of solid-state phase transformations by probing nuclear materials

    Science.gov (United States)

    Banerjee, Srikumar; Donthula, Harish

    2018-04-01

    In this review a few examples will be cited to illustrate that a study on a specific nuclear material sometimes lead to a better understanding of scientific phenomena of broader interests. Zirconium alloys offer some unique opportunities in addressing fundamental issues such as (i) distinctive features between displacive and diffusional transformations, (ii) characteristics of shuffle and shear dominated displacive transformations and (iii) nature of mixed-mode transformations. Whether a transformation is of first or higher order?" is often raised while classifying it. There are rare examples, such as Ni-Mo alloys, in which during early stages of ordering the system experiences tendencies for both first order and second order transitions. Studies on the order-disorder transitions under a radiation environment have established the pathway for the evolution of ordering. These studies have also identified the temperature range over which the chemically ordered state remains stable in steady state under radiation.

  8. Understanding the desensitizing mechanism of olefin in explosives: shear slide of mixed HMX-olefin systems.

    Science.gov (United States)

    Zhang, Chaoyang; Cao, Xia; Xiang, Bin

    2012-04-01

    We simulated the shear slide behavior of typical mixed HMX-olefin systems and the effect of thickness of olefin layers (4-22 Å) on the behavior at a molecular level by considering two cases: bulk shear and interfacial shear. The results show that: (1) the addition of olefin into HMX can reduce greatly the shear sliding barriers relative to the pure HMX in the two cases, suggesting that the desensitizing mechanism of olefin is controlled dominantly by its good lubricating property; (2) the change of interaction energy in both systoles of shear slide is strongly dominated by van der Waals interaction; and (3) the thickness of olefin layers in the mixed explosives can influence its desensitizing efficiency. That is, the excessive thinness of olefin layers in the mixed explosive systems, for example, several angstroms, can lead to very high sliding barriers.

  9. Heat and mass transfer models to understand the drying mechanisms of a porous substrate.

    Science.gov (United States)

    Songok, Joel; Bousfield, Douglas W; Gane, Patrick A C; Toivakka, Martti

    2016-02-01

    While drying of paper and paper coatings is expensive, with significant energy requirements, the rate controlling mechanisms are not currently fully understood. Two two-dimensional models are used as a first approximation to predict the heat transfer during hot air drying and to evaluate the role of various parameters on the drying rates of porous coatings. The models help determine the structural limiting factors during the drying process, while applying for the first time the recently known values of coating thermal diffusivity. The results indicate that the thermal conductivity of the coating structure is not the controlling factor, but the drying rate is rather determined by the thermal transfer process at the structure surface. This underlines the need for ensuring an efficient thermal transfer from hot air to coating surface during drying, before considering further measures to increase the thermal conductivity of porous coatings.

  10. Understanding the neural mechanisms involved in sensory control of voice production.

    Science.gov (United States)

    Parkinson, Amy L; Flagmeier, Sabina G; Manes, Jordan L; Larson, Charles R; Rogers, Bill; Robin, Donald A

    2012-05-15

    Auditory feedback is important for the control of voice fundamental frequency (F0). In the present study we used neuroimaging to identify regions of the brain responsible for sensory control of the voice. We used a pitch-shift paradigm where subjects respond to an alteration, or shift, of voice pitch auditory feedback with a reflexive change in F0. To determine the neural substrates involved in these audio-vocal responses, subjects underwent fMRI scanning while vocalizing with or without pitch-shifted feedback. The comparison of shifted and unshifted vocalization revealed activation bilaterally in the superior temporal gyrus (STG) in response to the pitch shifted feedback. We hypothesize that the STG activity is related to error detection by auditory error cells located in the superior temporal cortex and efference copy mechanisms whereby this region is responsible for the coding of a mismatch between actual and predicted voice F0. Published by Elsevier Inc.

  11. The effects of bariatric surgery: will understanding its mechanism render the knife unnecessary?

    Science.gov (United States)

    Browning, Kirsteen N; Hajnal, Andras

    2014-01-01

    The incidence of obesity is increasing worldwide at a dramatic rate, accompanied by an associated increase in comorbid conditions. Bariatric surgery is the most effective treatment for morbid obesity with Roux-en-Y gastric bypass being the most commonly performed procedure, yet the underlying mechanisms by which it induces a wide-array of beneficial effects remains obscure. From basic science as well as clinical standpoints, there are several areas of current interest that warrant continued investigation. Several major focus areas have also emerged in current research that may guide future efforts in this field, particularly with regards to using novel, non-surgical approaches to mimic the success of bariatric surgery while minimizing its adverse side effects.

  12. Metal Oxide Nanomaterial QNAR Models: Available Structural Descriptors and Understanding of Toxicity Mechanisms

    Directory of Open Access Journals (Sweden)

    Jiali Ying

    2015-10-01

    Full Text Available Metal oxide nanomaterials are widely used in various areas; however, the divergent published toxicology data makes it difficult to determine whether there is a risk associated with exposure to metal oxide nanomaterials. The application of quantitative structure activity relationship (QSAR modeling in metal oxide nanomaterials toxicity studies can reduce the need for time-consuming and resource-intensive nanotoxicity tests. The nanostructure and inorganic composition of metal oxide nanomaterials makes this approach different from classical QSAR study; this review lists and classifies some structural descriptors, such as size, cation charge, and band gap energy, in recent metal oxide nanomaterials quantitative nanostructure activity relationship (QNAR studies and discusses the mechanism of metal oxide nanomaterials toxicity based on these descriptors and traditional nanotoxicity tests.

  13. Oxide Nanoparticle EUV (ONE) Photoresists: Current Understanding of the Unusual Patterning Mechanism

    KAUST Repository

    Jiang, Jing

    2015-01-01

    © 2015 SPST. In the past few years, industry has made significant progress to deliver a stable high power EUV scanner and a 100 W light source is now being tested on the manufacuring scale. The success of a high power EUV source demands a fast and high resolution EUV resist. However, chemcially amplied resists encounter unprecedented challenges beyond the 22 nm node due to resolution, roughness and sensitivity tradeoffs. Unless novel solutions for EUV resists are proposed and further optimzed, breakthroughs can hardly be achieved. Oxide nanoparticle EUV (ONE) resists stablized by organic ligands were originally proposed by Ober et al. Recently this work attracts more and more attention due to its extraordinanry EUV sensitivity. This new class of photoresist utilizes ligand cleavage with a ligand exchange mechanism to switch its solubilty for dual-tone patterning. Therefore, ligand selection of the nanoparticles is extremely important to its EUV performance.

  14. Towards a better understanding of the therapeutic applications and corresponding mechanisms of action of honey.

    Science.gov (United States)

    Khan, Rifat Ullah; Naz, Shabana; Abudabos, Alaeldein M

    2017-12-01

    Honey is a bee-derived supersaturated solution composed of complex contents mainly glucose, fructose, amino acids, vitamins, and minerals. Composition of honey may vary due to the difference in nectar, season, geography, and storage condition. Honey has been used since times immemorial in folk medicine and has recently been rediscovered as an excellent therapeutic agent. In the past, honey was used for a variety of ailments without knowing the scientific background and active ingredients of honey. Today, honey has been scientifically proven for its antioxidant, regulation of glycemic response, antitumor, antimicrobial, anti-inflammatory, and cardiovascular potentiating agent. It can be used as a wound dressing and healing substance. Honey is different in color, flavor, sensory perception, and medical response. Apart from highlighting the nutritional facts of honey, we collected the finding of the published literature to know the mechanism of action of honey in different diseases. This review covers the composition, physiochemical characteristics, and some medical uses.

  15. Understanding Central Mechanisms of Acupuncture Analgesia Using Dynamic Quantitative Sensory Testing: A Review

    Directory of Open Access Journals (Sweden)

    Jiang-Ti Kong

    2013-01-01

    Full Text Available We discuss the emerging translational tools for the study of acupuncture analgesia with a focus on psychophysical methods. The gap between animal mechanistic studies and human clinical trials of acupuncture analgesia calls for effective translational tools that bridge neurophysiological data with meaningful clinical outcomes. Temporal summation (TS and conditioned pain modulation (CPM are two promising tools yet to be widely utilized. These psychophysical measures capture the state of the ascending facilitation and the descending inhibition of nociceptive transmission, respectively. We review the basic concepts and current methodologies underlying these measures in clinical pain research, and illustrate their application to research on acupuncture analgesia. Finally, we highlight the strengths and limitations of these research methods and make recommendations on future directions. The appropriate addition of TS and CPM to our current research armamentarium will facilitate our efforts to elucidate the central analgesic mechanisms of acupuncture in clinical populations.

  16. Understanding the Broad Substrate Repertoire of Nitroreductase Based on Its Kinetic Mechanism*

    Science.gov (United States)

    Pitsawong, Warintra; Hoben, John P.; Miller, Anne-Frances

    2014-01-01

    The oxygen-insensitive nitroreductase from Enterobacter cloacae (NR) catalyzes two-electron reduction of nitroaromatics to the corresponding nitroso compounds and, subsequently, to hydroxylamine products. NR has an unusually broad substrate repertoire, which may be related to protein dynamics (flexibility) and/or a simple non-selective kinetic mechanism. To investigate the possible role of mechanism in the broad substrate repertoire of NR, the kinetics of oxidation of NR by para-nitrobenzoic acid (p-NBA) were investigated using stopped-flow techniques at 4 °C. The results revealed a hyperbolic dependence on the p-NBA concentration with a limiting rate of 1.90 ± 0.09 s−1, indicating one-step binding before the flavin oxidation step. There is no evidence for a distinct binding step in which specificity might be enforced. The reduction of p-NBA is rate-limiting in steady-state turnover (1.7 ± 0.3 s−1). The pre-steady-state reduction kinetics of NR by NADH indicate that NADH reduces the enzyme with a rate constant of 700 ± 20 s−1 and a dissociation constant of 0.51 ± 0.04 mm. Thus, we demonstrate simple transient kinetics in both the reductive and oxidative half-reactions that help to explain the broad substrate repertoire of NR. Finally, we tested the ability of NR to reduce para-hydroxylaminobenzoic acid, demonstrating that the corresponding amine does not accumulate to significant levels even under anaerobic conditions. Thus E. cloacae NR is not a good candidate for enzymatic production of aromatic amines. PMID:24706760

  17. Mechanisms of Bunyavirus Virulence: A Genetic Approach.

    Science.gov (United States)

    1984-12-01

    coefficient porcine blood, elastase, and thermolysin with the Bio-Rad method. were obtained from Sigma. Chymotrypsin For preparing radiolabeled virus...70% gradient was frequently stopped with bovine or soybean trypsin run prior to final pelleting of labeled LAC. inhibitor (final concentration 200 ag...min at room temperature the reaction was stopped by the addition of 200 pg/ml soybean trypein inhibitor and boiled for 2 min in Laemmli’s sample

  18. Mechanisms of Bunyavirus Virulence. A Genetic Approach.

    Science.gov (United States)

    1983-12-01

    iunoprecipitation of viral proteins. These antibodies have been shown to be useful tools for the classification of new viral isolates and for the...Phenotyping of reassortant viruses with monoclones 14 (h) Clasification of California serogroup viruses with monoclones 17 (i) Variant viruses against...acute viral encephalitis. Among these factors are virus determinants (neuroinvasiveness and neurovirulence) and host determinants (recovery from

  19. Epigenetic mechanisms and the evolution of virulence

    Science.gov (United States)

    The interaction between pathogenic organisms and their hosts presents numerous opportunities to observe and test basic biological concepts such as adaptation, fitness, selection, and coevolution. The host-pathogen interaction is an inherently unstable relationship that makes hard evolutionary demand...

  20. Omics strategies for revealing Yersinia pestis virulence

    Science.gov (United States)

    Yang, Ruifu; Du, Zongmin; Han, Yanping; Zhou, Lei; Song, Yajun; Zhou, Dongsheng; Cui, Yujun

    2012-01-01

    Omics has remarkably changed the way we investigate and understand life. Omics differs from traditional hypothesis-driven research because it is a discovery-driven approach. Mass datasets produced from omics-based studies require experts from different fields to reveal the salient features behind these data. In this review, we summarize omics-driven studies to reveal the virulence features of Yersinia pestis through genomics, trascriptomics, proteomics, interactomics, etc. These studies serve as foundations for further hypothesis-driven research and help us gain insight into Y. pestis pathogenesis. PMID:23248778

  1. CRISPR interference can prevent natural transformation and virulence acquisition during in vivo bacterial infection.

    Science.gov (United States)

    Bikard, David; Hatoum-Aslan, Asma; Mucida, Daniel; Marraffini, Luciano A

    2012-08-16

    Pathogenic bacterial strains emerge largely due to transfer of virulence and antimicrobial resistance genes between bacteria, a process known as horizontal gene transfer (HGT). Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci of bacteria and archaea encode a sequence-specific defense mechanism against bacteriophages and constitute a programmable barrier to HGT. However, the impact of CRISPRs on the emergence of virulence is unknown. We programmed the human pathogen Streptococcus pneumoniae with CRISPR sequences that target capsule genes, an essential pneumococcal virulence factor, and show that CRISPR interference can prevent transformation of nonencapsulated, avirulent pneumococci into capsulated, virulent strains during infection in mice. Further, at low frequencies bacteria can lose CRISPR function, acquire capsule genes, and mount a successful infection. These results demonstrate that CRISPR interference can prevent the emergence of virulence in vivo and that strong selective pressure for virulence or antibiotic resistance can lead to CRISPR loss in bacterial pathogens. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Contribution of transcranial magnetic stimulation to the understanding of cortical mechanisms involved in motor control.

    Science.gov (United States)

    Reis, Janine; Swayne, Orlando B; Vandermeeren, Yves; Camus, Mickael; Dimyan, Michael A; Harris-Love, Michelle; Perez, Monica A; Ragert, Patrick; Rothwell, John C; Cohen, Leonardo G

    2008-01-15

    Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corticospinal tract in humans non-invasively. Since these early studies, the development of paired-pulse and repetitive TMS protocols allowed investigators to explore inhibitory and excitatory interactions of various motor and non-motor cortical regions within and across cerebral hemispheres. These applications have provided insight into the intracortical physiological processes underlying the functional role of different brain regions in various cognitive processes, motor control in health and disease and neuroplastic changes during recovery of function after brain lesions. Used in combination with neuroimaging tools, TMS provides valuable information on functional connectivity between different brain regions, and on the relationship between physiological processes and the anatomical configuration of specific brain areas and connected pathways. More recently, there has been increasing interest in the extent to which these physiological processes are modulated depending on the behavioural setting. The purpose of this paper is (a) to present an up-to-date review of the available electrophysiological data and the impact on our understanding of human motor behaviour and (b) to discuss some of the gaps in our present knowledge as well as future directions of research in a format accessible to new students and/or investigators. Finally, areas of uncertainty and limitations in the interpretation of TMS studies are discussed in some detail.

  3. Accelerating Our Understanding of Supernova Explosion Mechanism via Simulations and Visualizations with GenASiS

    Energy Technology Data Exchange (ETDEWEB)

    Budiardja, R. D. [University of Tennessee, Knoxville (UTK); Cardall, Christian Y [ORNL; Endeve, Eirik [ORNL

    2015-01-01

    Core-collapse supernovae are among the most powerful explosions in the Universe, releasing about 1053 erg of energy on timescales of a few tens of seconds. These explosion events are also responsible for the production and dissemination of most of the heavy elements, making life as we know it possible. Yet exactly how they work is still unresolved. One reason for this is the sheer complexity and cost of a self-consistent, multi-physics, and multi-dimensional core-collapse supernova simulation, which is impractical, and often impossible, even on the largest supercomputers we have available today. To advance our understanding we instead must often use simplified models, teasing out the most important ingredients for successful explosions, while helping us to interpret results from higher fidelity multi-physics models. In this paper we investigate the role of instabilities in the core-collapse supernova environment. We present here simulation and visualization results produced by our code GenASiS.

  4. Virulence meets metabolism: Cra and KdpE gene regulation in enterohemorrhagic Escherichia coli.

    Science.gov (United States)

    Njoroge, Jacqueline W; Nguyen, Y; Curtis, Meredith M; Moreira, Cristiano G; Sperandio, Vanessa

    2012-10-16

    , which causes bloody diarrhea, these two proteins influence important virulence traits. We also propose that their control of one or more of these virulence traits is due to the direct interaction of the Cra and KdpE proteins with each other, as well as with their DNA targets. This work shows how EHEC coopts established mechanisms for sensing the metabolites and stress cues in the environment, to induce virulence factors in a temporal and energy-efficient manner, culminating in disease. Understanding how pathogens commandeer nonpathogenic systems can help us develop measures to control them.

  5. Understanding the growth mechanism of graphene on Ge/Si(001) surfaces

    Science.gov (United States)

    Dabrowski, J.; Lippert, G.; Avila, J.; Baringhaus, J.; Colambo, I.; Dedkov, Yu S.; Herziger, F.; Lupina, G.; Maultzsch, J.; Schaffus, T.; Schroeder, T.; Kot, M.; Tegenkamp, C.; Vignaud, D.; Asensio, M.-C.

    2016-01-01

    The practical difficulties to use graphene in microelectronics and optoelectronics is that the available methods to grow graphene are not easily integrated in the mainstream technologies. A growth method that could overcome at least some of these problems is chemical vapour deposition (CVD) of graphene directly on semiconducting (Si or Ge) substrates. Here we report on the comparison of the CVD and molecular beam epitaxy (MBE) growth of graphene on the technologically relevant Ge(001)/Si(001) substrate from ethene (C2H4) precursor and describe the physical properties of the films as well as we discuss the surface reaction and diffusion processes that may be responsible for the observed behavior. Using nano angle resolved photoemission (nanoARPES) complemented by transport studies and Raman spectroscopy as well as density functional theory (DFT) calculations, we report the direct observation of massless Dirac particles in monolayer graphene, providing a comprehensive mapping of their low-hole doped Dirac electron bands. The micrometric graphene flakes are oriented along two predominant directions rotated by 30° with respect to each other. The growth mode is attributed to the mechanism when small graphene “molecules” nucleate on the Ge(001) surface and it is found that hydrogen plays a significant role in this process. PMID:27531322

  6. Study and understanding of the ageing mechanisms in lead-calcium alloys

    International Nuclear Information System (INIS)

    Rossi, F.

    2006-12-01

    The data available in the literature about ageing and over-ageing of lead-calcium alloys are often incomplete and inconsistent. It is undoubtedly due to the experimental difficulties encountered to observe the structure transformations which are numerous. As a result there is a certain confusion among the results of the different authors. Moreover, small variations in the process parameters and chemical composition may have some influence on the alloy behaviour. This work enabled us to obtain a set of TTT diagrams, more realistic and accurate than the ones available in the literature. Experimental techniques developed (particularly the preservation of the cold chain with is essential for the guaranty of the results repeatability), enabled particularly the study of the first transformations and better control the five stages of ageing and over-ageing. Our work have enabled to determine precisely the kinetics and the mechanisms of the transformations. This work constitutes a thorough analysis of the ageing and over-ageing of theses alloys. (author)

  7. ARHGEF9 mutations in epileptic encephalopathy/intellectual disability: toward understanding the mechanism underlying phenotypic variation.

    Science.gov (United States)

    Wang, Jing-Yang; Zhou, Peng; Wang, Jie; Tang, Bin; Su, Tao; Liu, Xiao-Rong; Li, Bing-Mei; Meng, Heng; Shi, Yi-Wu; Yi, Yong-Hong; He, Na; Liao, Wei-Ping

    2018-01-01

    ARHGEF9 resides on Xq11.1 and encodes collybistin, which is crucial in gephyrin clustering and GABA A receptor localization. ARHGEF9 mutations have been identified in patients with heterogeneous phenotypes, including epilepsy of variable severity and intellectual disability. However, the mechanism underlying phenotype variation is unknown. Using next-generation sequencing, we identified a novel mutation, c.868C > T/p.R290C, which co-segregated with epileptic encephalopathy, and validated its association with epileptic encephalopathy. Further analysis revealed that all ARHGEF9 mutations were associated with intellectual disability, suggesting its critical role in psychomotor development. Three missense mutations in the PH domain were not associated with epilepsy, suggesting that the co-occurrence of epilepsy depends on the affected functional domains. Missense mutations with severe molecular alteration in the DH domain, or located in the DH-gephyrin binding region, or adjacent to the SH3-NL2 binding site were associated with severe epilepsy, implying that the clinical severity was potentially determined by alteration of molecular structure and location of mutations. Male patients with ARHGEF9 mutations presented more severe phenotypes than female patients, which suggests a gene-dose effect and supports the pathogenic role of ARHGEF9 mutations. This study highlights the role of molecular alteration in phenotype expression and facilitates evaluation of the pathogenicity of ARHGEF9 mutations in clinical practice.

  8. Understanding physiological and degenerative natural vision mechanisms to define contrast and contour operators.

    Directory of Open Access Journals (Sweden)

    Jacques Demongeot

    Full Text Available BACKGROUND: Dynamical systems like neural networks based on lateral inhibition have a large field of applications in image processing, robotics and morphogenesis modeling. In this paper, we will propose some examples of dynamical flows used in image contrasting and contouring. METHODOLOGY: First we present the physiological basis of the retina function by showing the role of the lateral inhibition in the optical illusions and pathologic processes generation. Then, based on these biological considerations about the real vision mechanisms, we study an enhancement method for contrasting medical images, using either a discrete neural network approach, or its continuous version, i.e. a non-isotropic diffusion reaction partial differential system. Following this, we introduce other continuous operators based on similar biomimetic approaches: a chemotactic contrasting method, a viability contouring algorithm and an attentional focus operator. Then, we introduce the new notion of mixed potential Hamiltonian flows; we compare it with the watershed method and we use it for contouring. CONCLUSIONS: We conclude by showing the utility of these biomimetic methods with some examples of application in medical imaging and computed assisted surgery.

  9. Comprehensive Understanding of Ductility Loss Mechanisms in Various Steels with External and Internal Hydrogen

    Science.gov (United States)

    Takakuwa, Osamu; Yamabe, Junichiro; Matsunaga, Hisao; Furuya, Yoshiyuki; Matsuoka, Saburo

    2017-11-01

    Hydrogen-induced ductility loss and related fracture morphologies are comprehensively discussed in consideration of the hydrogen distribution in a specimen with external and internal hydrogen by using 300-series austenitic stainless steels (Types 304, 316, 316L), high-strength austenitic stainless steels (HP160, XM-19), precipitation-hardened iron-based super alloy (A286), low-alloy Cr-Mo steel (JIS-SCM435), and low-carbon steel (JIS-SM490B). External hydrogen is realized by a non-charged specimen tested in high-pressure gaseous hydrogen, and internal hydrogen is realized by a hydrogen-charged specimen tested in air or inert gas. Fracture morphologies obtained by slow-strain-rate tensile tests (SSRT) of the materials with external or internal hydrogen could be comprehensively categorized into five types: hydrogen-induced successive crack growth, ordinary void formation, small-sized void formation related to the void sheet, large-sized void formation, and facet formation. The mechanisms of hydrogen embrittlement are broadly classified into hydrogen-enhanced decohesion (HEDE) and hydrogen-enhanced localized plasticity (HELP). In the HEDE model, hydrogen weakens interatomic bonds, whereas in the HELP model, hydrogen enhances localized slip deformations. Although various fracture morphologies are produced by external or internal hydrogen, these morphologies can be explained by the HELP model rather than by the HEDE model.

  10. Understanding the mechanism of iron sulfide-induced fouling in upgrading

    Energy Technology Data Exchange (ETDEWEB)

    Panchal, C.B. [United States Dept. of Energy, Chicago, IL (United States). Argonne National Laboratory

    2006-07-01

    This presentation investigated the underlying mechanisms of iron sulfide-induced fouling and coking in upgrading processes. Experiments to determine the effects of dissolved metals on the rate of fouling were reviewed. It was noted that the presence of species such as active sulfur and diolefins can enhance the effect of dissolved metals. An investigation of a high temperature fouling unit was then conducted to investigate the effect of iron acetate and theiphenol additions to stable heavy gas oil. The deposition rate became strongly dependent on temperature in the presence of the dissolved metals. Fouling deposit analyses from various parts of the refining process consistently showed high concentrations of iron and sulfur. It was observed that the threshold tube-wall temperature corresponded to the decomposition temperature of iron salts. A review of current literature indicated that there is little information on the interactive effects of the thermal stability of dissolved organo-metallic compounds and the reactivity of organic species in generating fouling precursors. The creation of a predictive model of threshold fouling and coking conditions was recommended. It was suggested that the model should be used during the design phases of furnaces and heat exchangers. Other recommendations included the use of on-line sensors to detect iron sulfide formulation; and the monitoring of coking furnaces. Blending guidelines to minimize the interactive effects of dissolved metals and active sulfur compounds were also presented. refs., tabs., figs.

  11. Toward understanding the mechanics of hovering in insects, hummingbirds and bats

    Science.gov (United States)

    Vejdani, Hamid; Boerma, David; Swartz, Sharon; Breuer, Kenneth

    2016-11-01

    We present results on the dynamical characteristics of two different mechanisms of hovering, corresponding to the behavior of hummingbirds and bats. Using a Lagrangian formulation, we have developed a dynamical model of a body (trunk) and two rectangular wings. The trunk has 3 degrees of freedom (x, z and pitch angle) and each wing has 3 modes of actuation: flapping, pronation/supination, and wingspan extension/flexion (only present for bats). Wings can be effectively massless (hummingbird and insect wings) or relatively massive (important in the case of bats). The aerodynamic drag and lift forces are calculated using a quasi-steady blade-element model. The regions of state space in which hovering is possible are computed by over an exhaustive range of parameters. The effect of wing mass is to shrink the phase space available for viable hovering and, in general, to require higher wingbeat frequency. Moreover, by exploring hovering energy requirements, we find that the pronation angle of the wings also plays a critical role. For bats, who have relatively heavy wings, we show wing extension and flexion is critical in order to maintain a plausible hovering posture with reasonable power requirements. Comparisons with biological data show good agreement with our model predictions.

  12. Recent advances in understanding the molecular mechanism of chloroplast photorelocation movement.

    Science.gov (United States)

    Kong, Sam-Geun; Wada, Masamitsu

    2014-04-01

    Plants are photosynthetic organisms that have evolved unique systems to adapt fluctuating environmental light conditions. In addition to well-known movement responses such as phototropism, stomatal opening, and nastic leaf movements, chloroplast photorelocation movement is one of the essential cellular responses to optimize photosynthetic ability and avoid photodamage. For these adaptations, chloroplasts accumulate at the areas of cells illuminated with low light (called accumulation response), while they scatter from the area illuminated with strong light (called avoidance response). Plant-specific photoreceptors (phototropin, phytochrome, and/or neochrome) mediate these dynamic directional movements in response to incident light position and intensity. Several factors involved in the mechanisms underlying the processes from light perception to actin-based movements have also been identified through molecular genetic approach. This review aims to discuss recent findings in the field relating to how chloroplasts move at molecular levels. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Different approaches, one target: understanding cellular mechanisms of Parkinson's and Alzheimer's diseases.

    Science.gov (United States)

    Torrão, Andréa S; Café-Mendes, Cecilia C; Real, Caroline C; Hernandes, Marina S; Ferreira, Ana F B; Santos, Taisa O; Chaves-Kirsten, Gabriela P; Mazucanti, Caio H Y; Ferro, Emer S; Scavone, Cristoforo; Britto, Luiz R G

    2012-10-01

    Neurodegenerative disorders are undoubtedly an increasing problem in the health sciences, given the increase of life expectancy and occasional vicious life style. Despite the fact that the mechanisms of such diseases are far from being completely understood, a large number of studies that derive from both the basic science and clinical approaches have contributed substantial data in that direction. In this review, it is discussed several frontiers of basic research on Parkinson's and Alzheimer's diseases, in which research groups from three departments of the Institute of Biomedical Sciences of the University of São Paulo have been involved in a multidisciplinary effort. The main focus of the review involves the animal models that have been developed to study cellular and molecular aspects of those neurodegenerative diseases, including oxidative stress, insulin signaling and proteomic analyses, among others. We anticipate that this review will help the group determine future directions of joint research in the field and, more importantly, set the level of cooperation we plan to develop in collaboration with colleagues of the Nucleus for Applied Neuroscience Research that are mostly involved with clinical research in the same field.

  14. Final Report: Improving the understanding of the coupled thermal-mechanical-hydrologic behavior of consolidating granular salt

    Energy Technology Data Exchange (ETDEWEB)

    Stormont, John [Univ. of New Mexico, Albuquerque, NM (United States); Lampe, Brandon [Univ. of New Mexico, Albuquerque, NM (United States); Mills, Melissa [Univ. of New Mexico, Albuquerque, NM (United States); Paneru, Laxmi [Univ. of New Mexico, Albuquerque, NM (United States); Lynn, Timothy [Univ. of New Mexico, Albuquerque, NM (United States); Piya, Aayush [Univ. of New Mexico, Albuquerque, NM (United States)

    2017-09-09

    The goal of this project is to improve the understanding of key aspects of the coupled thermal-mechanical-hydrologic response of granular (or crushed) salt used as a seal material for shafts, drifts, and boreholes in mined repositories in salt. The project is organized into three tasks to accomplish this goal: laboratory measurements of granular salt consolidation (Task 1), microstructural observations on consolidated samples (Task 2), and constitutive model development and evaluation (Task 3). Task 1 involves laboratory measurements of salt consolidation along with thermal properties and permeability measurements conducted under a range of temperatures and stresses expected for potential mined repositories in salt. Testing focused on the role of moisture, temperature and stress state on the hydrologic (permeability) and thermal properties of consolidating granular salt at high fractional densities. Task 2 consists of microstructural observations made on samples after they have been consolidated to interpret deformation mechanisms and evaluate the ability of the constitutive model to predict operative mechanisms under different conditions. Task 3 concerns the development of the coupled thermal-mechanical-hydrologic constitutive model for granular salt consolidation. The measurements and observations in Tasks 1 and 2 were used to develop a thermal-mechanical constitutive model. Accomplishments and status from each of these efforts is reported in subsequent sections of this report

  15. Partitioning CO2 fluxes with isotopologue measurements and modeling to understand mechanisms of forest carbon sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Saleska, Scott [Univ. of Arizona, Tucson, AZ (United States); Davidson, Eric [Univ. of Arizona, Tucson, AZ (United States); Finzi, Adrien [Boston Univ., MA (United States); Wehr, Richdard [Harvard Univ., Cambridge, MA (United States); Moorcroft, Paul [Harvard Univ., Cambridge, MA (United States)

    2016-01-28

    1. Objectives This project combines automated in situ observations of the isotopologues of CO2 with root observations, novel experimental manipulations of belowground processes, and isotope-enabled ecosystem modeling to investigate mechanisms of below- vs. aboveground carbon sequestration at the Harvard Forest Environmental Measurements Site (EMS). The proposed objectives, which have now been largely accomplished, include: A. Partitioning of net ecosystem CO2 exchange (NEE) into photosynthesis and respiration using long-term continuous observations of the isotopic composition of NEE, and analysis of their dynamics ; B. Investigation of the influence of vegetation phenology on the timing and magnitude of carbon allocated belowground using measurements of root growth and indices of belowground autotrophic vs. heterotrophic respiration (via trenched plots and isotope measurements); C. Testing whether plant allocation of carbon belowground stimulates the microbial decomposition of soil organic matter, using in situ rhizosphere simulation experiments wherein realistic quantities of artificial isotopically-labeled exudates are released into the soil; and D. Synthesis and interpretation of the above data using the Ecosystem Demography Model 2 (ED2). 2. Highlights Accomplishments: • Our isotopic eddy flux record has completed its 5th full year and has been used to independently estimate ecosystem-scale respiration and photosynthesis. • Soil surface chamber isotopic flux measurements were carried out during three growing seasons, in conjunction with a trenching manipulation. Key findings to date (listed by objective): A. Partitioning of Net Ecosystem Exchange: 1. Ecosystem respiration is lower during the day than at night—the first robust evidence of the inhibition of leaf respiration by light (the “Kok effect”) at the ecosystem scale. 2. Because it neglects the Kok effect, the standard NEE partitioning approach overestimates ecosystem photosynthesis (by ~25%) and

  16. Recent Advances in Understanding Amino Acid Sensing Mechanisms that Regulate mTORC1

    Directory of Open Access Journals (Sweden)

    Liufeng Zheng

    2016-09-01

    Full Text Available The mammalian target of rapamycin (mTOR is the central regulator of mammalian cell growth, and is essential for the formation of two structurally and functionally distinct complexes: mTORC1 and mTORC2. mTORC1 can sense multiple cues such as nutrients, energy status, growth factors and hormones to control cell growth and proliferation, angiogenesis, autophagy, and metabolism. As one of the key environmental stimuli, amino acids (AAs, especially leucine, glutamine and arginine, play a crucial role in mTORC1 activation, but where and how AAs are sensed and signal to mTORC1 are not fully understood. Classically, AAs activate mTORC1 by Rag GTPases which recruit mTORC1 to lysosomes, where AA signaling initiates. Plasma membrane transceptor L amino acid transporter 1 (LAT1-4F2hc has dual transporter-receptor function that can sense extracellular AA availability upstream of mTORC1. The lysosomal AA sensors (PAT1 and SLC38A9 and cytoplasmic AA sensors (LRS, Sestrin2 and CASTOR1 also participate in regulating mTORC1 activation. Importantly, AAs can be sensed by plasma membrane receptors, like G protein-coupled receptor (GPCR T1R1/T1R3, and regulate mTORC1 without being transported into the cells. Furthermore, AA-dependent mTORC1 activation also initiates within Golgi, which is regulated by Golgi-localized AA transporter PAT4. This review provides an overview of the research progress of the AA sensing mechanisms that regulate mTORC1 activity.

  17. Understanding the mechanisms of cobalt-catalyzed hydrogenation and dehydrogenation reactions.

    Science.gov (United States)

    Zhang, Guoqi; Vasudevan, Kalyan V; Scott, Brian L; Hanson, Susan K

    2013-06-12

    Cobalt(II) alkyl complexes of aliphatic PNP pincer ligands have been synthesized and characterized. The cationic cobalt(II) alkyl complex [(PNHP(Cy))Co(CH2SiMe3)]BAr(F)4 (4) (PNHP(Cy) = bis[(2-dicyclohexylphosphino)ethyl]amine) is an active precatalyst for the hydrogenation of olefins and ketones and the acceptorless dehydrogenation of alcohols. To elucidate the possible involvement of the N-H group on the pincer ligand in the catalysis via a metal-ligand cooperative interaction, the reactivities of 4 and [(PNMeP(Cy))Co(CH2SiMe3)]BAr(F)4 (7) were compared. Complex 7 was found to be an active precatalyst for the hydrogenation of olefins. In contrast, no catalytic activity was observed using 7 as a precatalyst for the hydrogenation of acetophenone under mild conditions. For the acceptorless dehydrogenation of 1-phenylethanol, complex 7 displayed similar activity to complex 4, affording acetophenone in high yield. When the acceptorless dehydrogenation of 1-phenylethanol with precatalyst 4 was monitored by NMR spectroscopy, the formation of the cobalt(III) acetylphenyl hydride complex [(PNHP(Cy))Co(III)(κ(2)-O,C-C6H4C(O)CH3)(H)]BAr(F)4 (13) was detected. Isolated complex 13 was found to be an effective catalyst for the acceptorless dehydrogenation of alcohols, implicating 13 as a catalyst resting state during the alcohol dehydrogenation reaction. Complex 13 catalyzed the hydrogenation of styrene but showed no catalytic activity for the room temperature hydrogenation of acetophenone. These results support the involvement of metal-ligand cooperativity in the room temperature hydrogenation of ketones but not the hydrogenation of olefins or the acceptorless dehydrogenation of alcohols. Mechanisms consistent with these observations are presented for the cobalt-catalyzed hydrogenation of olefins and ketones and the acceptorless dehydrogenation of alcohols.

  18. Understanding the mechanism of DNA deactivation in ion therapy of cancer cells: hydrogen peroxide action*

    Science.gov (United States)

    Piatnytskyi, Dmytro V.; Zdorevskyi, Oleksiy O.; Perepelytsya, Sergiy M.; Volkov, Sergey N.

    2015-11-01

    Changes in the medium of biological cells under ion beam irradiation has been considered as a possible cause of cell function disruption in the living body. The interaction of hydrogen peroxide, a long-lived molecular product of water radiolysis, with active sites of DNA macromolecule was studied, and the formation of stable DNA-peroxide complexes was considered. The phosphate groups of the macromolecule backbone were picked out among the atomic groups of DNA double helix as a probable target for interaction with hydrogen peroxide molecules. Complexes consisting of combinations including: the DNA phosphate group, H2O2 and H2O molecules, and Na+ counterion, were considered. The counterions have been taken into consideration insofar as under the natural conditions they neutralise DNA sugar-phosphate backbone. The energy of the complexes have been determined by considering the electrostatic and the Van der Waals interactions within the framework of atom-atom potential functions. As a result, the stability of various configurations of molecular complexes was estimated. It was shown that DNA phosphate groups and counterions can form stable complexes with hydrogen peroxide molecules, which are as stable as the complexes with water molecules. It has been demonstrated that the formation of stable complexes of H2O2-Na+-PO4- may be detected experimentally by observing specific vibrations in the low-frequency Raman spectra. The interaction of H2O2 molecule with phosphate group of the double helix backbone can disrupt DNA biological function and induce the deactivation of the cell genetic apparatus. Thus, the production of hydrogen peroxide molecules in the nucleus of living cells can be considered as an additional mechanism by which high-energy ion beams destroy tumour cells during ion beam therapy. Contribution to the Topical Issue "COST Action Nano-IBCT: Nano-scale Processes Behind Ion-Beam Cancer Therapy", edited by Andrey Solov'yov, Nigel Mason, Gustavo García, Eugene

  19. Toward an understanding of the molecular mechanisms of barnacle larval settlement: A comparative transcriptomic approach

    KAUST Repository

    Chen, Zhang-Fan

    2011-07-29

    Background: The barnacle Balanus amphitrite is a globally distributed biofouler and a model species in intertidal ecology and larval settlement studies. However, a lack of genomic information has hindered the comprehensive elucidation of the molecular mechanisms coordinating its larval settlement. The pyrosequencing-based transcriptomic approach is thought to be useful to identify key molecular changes during larval settlement. Methodology and Principal Findings: Using 454 pyrosequencing, we collected totally 630,845 reads including 215,308 from the larval stages and 415,537 from the adults; 23,451 contigs were generated while 77,785 remained as singletons. We annotated 31,720 of the 92,322 predicted open reading frames, which matched hits in the NCBI NR database, and identified 7,954 putative genes that were differentially expressed between the larval and adult stages. Of these, several genes were further characterized with quantitative real-time PCR and in situ hybridization, revealing some key findings: 1) vitellogenin was uniquely expressed in late nauplius stage, suggesting it may be an energy source for the subsequent non-feeding cyprid stage; 2) the locations of mannose receptors suggested they may be involved in the sensory system of cyprids; 3) 20 kDa-cement protein homologues were expressed in the cyprid cement gland and probably function during attachment; and 4) receptor tyrosine kinases were expressed higher in cyprid stage and may be involved in signal perception during larval settlement. Conclusions: Our results provide not only the basis of several new hypotheses about gene functions during larval settlement, but also the availability of this large transcriptome dataset in B. amphitrite for further exploration of larval settlement and developmental pathways in this important marine species. © 2011 Chen et al.

  20. Coordinated Regulation of Virulence during Systemic Infection of Salmonella enterica serovar Typhimurium

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hyunjin; McDermott, Jason E.; Porwollik, Steffen; Mcclelland, Michael; Heffron, Fred

    2009-02-20

    Salmonella must respond to a myriad of environmental cues during infection of a mouse and express specific subsets of genes in a temporal and spatial manner to subvert the host defense mechanisms but these regulatory pathways are poorly established. To unravel how micro-environmental signals are processed and integrated into coordinated action, we constructed in-frame non-polar deletions of 84 regulators inferred to play a role in Salmonella typhimurium virulence and tested them in three virulence assays (intraperitoneal (i.p.), and intragastric (i.g.) infection in BALB/c mice, and persistence in SvJ129 mice). Overall 36 regulators were identified that were less virulent in at least one assay, and of those, 15 regulators were required for systemic mouse infection in an acute infection model. As a first step towards understanding the interplay between a pathogen and its host from a systems biology standpoint we focused on these 15 genes. Transcriptional profiles were obtained for each of these 15 regulators from strains grown under four different environmental conditions. These results as well as publicly available transcriptional profiles were analyzed using both network inference and cluster analysis algorithms. The analysis predicts a regulatory network in which all 15 regulators control a specific set of genes necessary for Salmonella to cause systemic infection. We tested the regulatory model by expressing a subset of the regulators in trans and monitoring transcription of 7 known virulence factors located within Salmonella pathogenicity island 2 (SPI-2). These experiments validated the regulatory model and showed that, for these 7 genes, the response regulator SsrB and the marR type regulator SlyA co-regulate in a regulatory cascade by integrating multiple signals.

  1. Microbial virulence and interactions with metals

    DEFF Research Database (Denmark)

    German, N.; Lüthje, Freja Lea; Hao, X.

    2016-01-01

    Transition metals, such as iron, copper, zinc, and manganese play an important role in many bacterial biological processes that add to an overall evolutional fitness of bacteria. They are often involved in regulation of bacterial virulence as a mechanism of host invasion. However, the same transi...... reconstruction of Fe-S clusters and the use of Mn as a protectant against reactive oxygen species. Therefore, tight regulation of transition metal distribution in bacteria and hosts is a vital part of host-pathogen interactions....

  2. Understanding the mechanisms of solid-water reactions through analysis of surface topography.

    Science.gov (United States)

    Bandstra, Joel Z; Brantley, Susan L

    2015-12-01

    The topography of a reactive surface contains information about the reactions that form or modify the surface and, therefore, it should be possible to characterize reactivity using topography parameters such as surface area, roughness, or fractal dimension. As a test of this idea, we consider a two-dimensional (2D) lattice model for crystal dissolution and examine a suite of topography parameters to determine which may be useful for predicting rates and mechanisms of dissolution. The model is based on the assumption that the reactivity of a surface site decreases with the number of nearest neighbors. We show that the steady-state surface topography in our model system is a function of, at most, two variables: the ratio of the rate of loss of sites with two neighbors versus three neighbors (d(2)/d(3)) and the ratio of the rate of loss of sites with one neighbor versus three neighbors (d(1)/d(3)). This means that relative rates can be determined from two parameters characterizing the topography of a surface provided that the two parameters are independent of one another. It also means that absolute rates cannot be determined from measurements of surface topography alone. To identify independent sets of topography parameters, we simulated surfaces from a broad range of d(1)/d(3) and d(2)/d(3) and computed a suite of common topography parameters for each surface. Our results indicate that the fractal dimension D and the average spacing between steps, E[s], can serve to uniquely determine d(1)/d(3) and d(2)/d(3) provided that sufficiently strong correlations exist between the steps. Sufficiently strong correlations exist in our model system when D>1.5 (which corresponds to D>2.5 for real 3D reactive surfaces). When steps are uncorrelated, surface topography becomes independent of step retreat rate and D is equal to 1.5. Under these conditions, measures of surface topography are not independent and any single topography parameter contains all of the available mechanistic

  3. Understanding dental CAD/CAM for restorations - dental milling machines from a mechanical engineering viewpoint. Part A: chairside milling machines.

    Science.gov (United States)

    Lebon, Nicolas; Tapie, Laurent; Duret, Francois; Attal, Jean-Pierre

    2016-01-01

    The dental milling machine is an important device in the dental CAD/CAM chain. Nowadays, dental numerical controlled (NC) milling machines are available for dental surgeries (chairside solution). This article provides a mechanical engineering approach to NC milling machines to help dentists understand the involvement of technology in digital dentistry practice. First, some technical concepts and definitions associated with NC milling machines are described from a mechanical engineering viewpoint. The technical and economic criteria of four chairside dental NC milling machines that are available on the market are then described. The technical criteria are focused on the capacities of the embedded technologies of these milling machines to mill both prosthetic materials and types of shape restorations. The economic criteria are focused on investment costs and interoperability with third-party software. The clinical relevance of the technology is assessed in terms of the accuracy and integrity of the restoration.

  4. Virulence determinants of diarrhoegenic Escherichia coli - A Mini ...

    African Journals Online (AJOL)

    Diarrhoegenic Escherichia coli are of a broad variety. A clear understanding of the virulence/pathogenicity determinants of pathogenic Escherichia coli is important as they affect a large section of the population in the tropical and developing areas of the world. Faecal contamination of food and water is the major route of ...

  5. Quantum interactive learning tutorial on the double-slit experiment to improve student understanding of quantum mechanics

    Directory of Open Access Journals (Sweden)

    Ryan Sayer

    2017-05-01

    Full Text Available Learning quantum mechanics is challenging, even for upper-level undergraduate and graduate students. Research-validated interactive tutorials that build on students’ prior knowledge can be useful tools to enhance student learning. We have been investigating student difficulties with quantum mechanics pertaining to the double-slit experiment in various situations that appear to be counterintuitive and contradict classical notions of particles and waves. For example, if we send single electrons through the slits, they may behave as a “wave” in part of the experiment and as a “particle” in another part of the same experiment. Here we discuss the development and evaluation of a research-validated Quantum Interactive Learning Tutorial (QuILT which makes use of an interactive simulation to improve student understanding of the double-slit experiment and strives to help students develop a good grasp of foundational issues in quantum mechanics. We discuss common student difficulties identified during the development and evaluation of the QuILT and analyze the data from the pretest and post test administered to the upper-level undergraduate and first-year physics graduate students before and after they worked on the QuILT to assess its effectiveness. These data suggest that on average, the QuILT was effective in helping students develop a more robust understanding of foundational concepts in quantum mechanics that defy classical intuition using the context of the double-slit experiment. Moreover, upper-level undergraduates outperformed physics graduate students on the post test. One possible reason for this difference in performance may be the level of student engagement with the QuILT due to the grade incentive. In the undergraduate course, the post test was graded for correctness while in the graduate course, it was only graded for completeness.

  6. Quantum interactive learning tutorial on the double-slit experiment to improve student understanding of quantum mechanics

    Science.gov (United States)

    Sayer, Ryan; Maries, Alexandru; Singh, Chandralekha

    2017-06-01

    Learning quantum mechanics is challenging, even for upper-level undergraduate and graduate students. Research-validated interactive tutorials that build on students' prior knowledge can be useful tools to enhance student learning. We have been investigating student difficulties with quantum mechanics pertaining to the double-slit experiment in various situations that appear to be counterintuitive and contradict classical notions of particles and waves. For example, if we send single electrons through the slits, they may behave as a "wave" in part of the experiment and as a "particle" in another part of the same experiment. Here we discuss the development and evaluation of a research-validated Quantum Interactive Learning Tutorial (QuILT) which makes use of an interactive simulation to improve student understanding of the double-slit experiment and strives to help students develop a good grasp of foundational issues in quantum mechanics. We discuss common student difficulties identified during the development and evaluation of the QuILT and analyze the data from the pretest and post test administered to the upper-level undergraduate and first-year physics graduate students before and after they worked on the QuILT to assess its effectiveness. These data suggest that on average, the QuILT was effective in helping students develop a more robust understanding of foundational concepts in quantum mechanics that defy classical intuition using the context of the double-slit experiment. Moreover, upper-level undergraduates outperformed physics graduate students on the post test. One possible reason for this difference in performance may be the level of student engagement with the QuILT due to the grade incentive. In the undergraduate course, the post test was graded for correctness while in the graduate course, it was only graded for completeness.

  7. Deoxyribonucleic Acid Damage and Repair: Capitalizing on Our Understanding of the Mechanisms of Maintaining Genomic Integrity for Therapeutic Purposes

    Directory of Open Access Journals (Sweden)

    Jolene Michelle Helena

    2018-04-01

    Full Text Available Deoxyribonucleic acid (DNA is the self-replicating hereditary material that provides a blueprint which, in collaboration with environmental influences, produces a structural and functional phenotype. As DNA coordinates and directs differentiation, growth, survival, and reproduction, it is responsible for life and the continuation of our species. Genome integrity requires the maintenance of DNA stability for the correct preservation of genetic information. This is facilitated by accurate DNA replication and precise DNA repair. DNA damage may arise from a wide range of both endogenous and exogenous sources but may be repaired through highly specific mechanisms. The most common mechanisms include mismatch, base excision, nucleotide excision, and double-strand DNA (dsDNA break repair. Concurrent with regulation of the cell cycle, these mechanisms are precisely executed to ensure full restoration of damaged DNA. Failure or inaccuracy in DNA repair contributes to genome instability and loss of genetic information which may lead to mutations resulting in disease or loss of life. A detailed understanding of the mechanisms of DNA damage and its repair provides insight into disease pathogeneses and may facilitate diagnosis and the development of targeted therapies.

  8. Single Nucleotide Polymorphisms in Regulator-Encoding Genes Have an Additive Effect on Virulence Gene Expression in a Vibrio cholerae Clinical Isolate.

    Science.gov (United States)

    Carignan, Bailey M; Brumfield, Kyle D; Son, Mike S

    2016-01-01

    patients suffering from increasingly severe symptoms and of disease progression at a much higher rate than previously observed has emerged. As recent cholera outbreaks caused by increasingly virulent strains have resulted in higher mortality rates, the need to investigate the mechanism(s) allowing this observed increased virulence is apparent. The significance of our research is in identifying the mechanism for increased virulence capabilities, which will allow the development of a model that will greatly enhance our understanding of cholera disease and V. cholerae pathogenesis, leading to broader biomedical impacts, as cholera serves as a model for other enteric diarrheal diseases.

  9. Evolution of virulence in heterogeneous host communities under multiple trade-offs.

    Science.gov (United States)

    Osnas, Erik E; Dobson, Andrew P

    2012-02-01

    Many pathogens and parasites are transmitted through hosts that differ in species, sex, genotype, or immune status. In addition, virulence (here defined as disease-induced mortality) and transmission can vary during the infectious period within hosts of different state. Most models of virulence evolution assume that transmission and virulence are constant over the infectious period and that the host population is homogenous. Here, we examine a multispecies susceptible-infected-recovered (SIR) model where transmission occurs within and between species, and transmission and virulence varied during the infectious period. This allows us to understand virulence evolution in a broader range of situations that characterize many emerging diseases. Because emerging pathogens are by definition new to their host populations, they should be expected to rapidly adapt after emergence. We illustrate these evolutionary effects using the framework of adaptive dynamics to examine how virulence evolves after emergence in response to the relative strength of selection on pathogen fitness and mutational variance for virulence. We illustrate the role of evolution by simulating adaptive walks to an evolutionarily stable virulence. We found that the magnitude of between-species transmission and the relative timing of transmission and mortality across species were of primary importance for determining the evolutionarily stable virulence. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

  10. Bench-to-bedside review: Bacterial virulence and subversion of host defences

    OpenAIRE

    Webb, Steven AR; Kahler, Charlene M

    2008-01-01

    Bacterial pathogens possess an array of specific mechanisms that confer virulence and the capacity to avoid host defence mechanisms. Mechanisms of virulence are often mediated by the subversion of normal aspects of host biology. In this way the pathogen modifies host function so as to promote the pathogen's survival or proliferation. Such subversion is often mediated by the specific interaction of bacterial effector molecules with host encoded proteins and other molecules. The importance of t...

  11. Transfer of the virulence-associated protein A-bearing plasmid between field strains of virulent and avirulent Rhodococcus equi

    Science.gov (United States)

    Virulent and avirulent isolates coexist in equine feces and the environment and serve as a source of infection for foals. The extent to which conjugative plasmid transfer occurs between these strains is unknown and is important for understanding the epidemiology of Rhodococcus equi infections of fo...

  12. A comparison of computational methods for identifying virulence factors.

    Directory of Open Access Journals (Sweden)

    Lu-Lu Zheng

    Full Text Available Bacterial pathogens continue to threaten public health worldwide today. Identification of bacterial virulence factors can help to find novel drug/vaccine targets against pathogenicity. It can also help to reveal the mechanisms of the related diseases at the molecular level. With the explosive growth in protein sequences generated in the postgenomic age, it is highly desired to develop computational methods for rapidly and effectively identifying virulence factors according to their sequence information alone. In this study, based on the protein-protein interaction networks from the STRING database, a novel network-based method was proposed for identifying the virulence factors in the proteomes of UPEC 536, UPEC CFT073, P. aeruginosa PAO1, L. pneumophila Philadelphia 1, C. jejuni NCTC 11168 and M. tuberculosis H37Rv. Evaluated on the same benchmark datasets derived from the aforementioned species, the identification accuracies achieved by the network-based method were around 0.9, significantly higher than those by the sequence-based methods such as BLAST, feature selection and VirulentPred. Further analysis showed that the functional associations such as the gene neighborhood and co-occurrence were the primary associations between these virulence factors in the STRING database. The high success rates indicate that the network-based method is quite promising. The novel approach holds high potential for identifying virulence factors in many other various organisms as well because it can be easily extended to identify the virulence factors in many other bacterial species, as long as the relevant significant statistical data are available for them.

  13. Differentiation in quinolone resistance by virulence genotype in Pseudomonas aeruginosa.

    Science.gov (United States)

    Agnello, Melissa; Wong-Beringer, Annie

    2012-01-01

    Pseudomonas aeruginosa is a leading pathogen that has become increasingly resistant to the fluoroquinolone antibiotics due to widespread prescribing. Adverse outcomes have been shown for patients infected with fluoroquinolone-resistant strains. The type III secretion system (TTSS) is a major virulence determinant during acute infections through the injection of effector toxins into host cells. Most strains exhibit a unique TTSS virulence genotype defined by the presence of either exoS or exoU gene encoding two of the effector toxins, ExoS and ExoU, respectively. Specific TTSS effector genotype has been shown previously to differentially impact virulence in pneumonia. In this study, we examined the relationship between TTSS effector genotype and fluoroquinolone resistance mechanisms in a collection of 270 respiratory isolates. We found that a higher proportion of exoU+ strains were fluoroquinolone-resistant compared to exoS+ strains (63% vs 49%, p = 0.03) despite its lower overall prevalence (38% exoU+ vs 56% exoS+). Results from sequencing the quinolone resistance determining regions (QRDRs) of the 4 target genes (gyrA, gyrB, parC, parE) indicated that strains containing the exoU gene were more likely to acquire ≥ 2 mutations than exoS+ strains at MICs ≤ 8 µg/ml (13% vs none) and twice as likely to have mutations in both gyrA and parC than exoS+ strains (48% vs 24% p = 0.0439). Our findings indicate that P. aeruginosa strains differentially develop resistance-conferring mutations that correlate with TTSS effector genotype and the more virulent exoU+ subpopulation. Differences in mutational processes by virulence genotype that were observed suggest co-evolution of resistance and virulence traits favoring a more virulent genotype in the quinolone-rich clinical environment.

  14. Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of emm89 Streptococcus pyogenes.

    Science.gov (United States)

    Zhu, Luchang; Olsen, Randall J; Nasser, Waleed; de la Riva Morales, Ivan; Musser, James M

    2015-10-06

    Strains of emm89 Streptococcus pyogenes have become one of the major causes of invasive infections worldwide in the last 10 years. We recently sequenced the genome of 1,125 emm89 strains and identified three major phylogenetic groups, designated clade 1, clade 2, and the epidemic clade 3. Epidemic clade 3 strains, which now cause the great majority of infections, have two distinct genetic features compared to clade 1 and clade 2 strains. First, all clade 3 organisms have a variant 3 nga promoter region pattern, which is associated with increased production of secreted cytolytic toxins SPN (S. pyogenes NADase) and SLO (streptolysin O). Second, all clade 3 strains lack the hasABC locus mediating hyaluronic acid capsule synthesis, whereas this locus is intact in clade 1 and clade 2 strains. We constructed isogenic mutant strains that produce different levels of SPN and SLO toxins and capsule (none, low, or high). Here we report that emm89 strains with elevated toxin production are significantly more virulent than low-toxin producers. Importantly, we also show that capsule production is dispensable for virulence in strains that already produce high levels of SPN and SLO. Our results provide new understanding about the molecular mechanisms contributing to the rapid emergence and molecular pathogenesis of epidemic clade 3 emm89 S. pyogenes. S. pyogenes (group A streptococcus [GAS]) causes pharyngitis ("strep throat"), necrotizing fasciitis, and other human infections. Serious infections caused by emm89 S. pyogenes strains have recently increased in frequency in many countries. Based on whole-genome sequence analysis of 1,125 strains recovered from patients on two continents, we discovered that a new emm89 clone, termed clade 3, has two distinct genetic features compared to its predecessors: (i) absence of the genes encoding antiphagocytic hyaluronic acid capsule virulence factor and (ii) increased production of the secreted cytolytic toxins SPN and SLO. emm89 S

  15. Mafia behaviour and the evolution of facultative virulence.

    Science.gov (United States)

    Soler, J J; Møller, A P; Soler, M

    1998-04-07

    Some organisms enforce "maladaptive" behaviours on others of the same or different species by imposing costs in the absence of compliance. Such enforcement is used by the enforcer to obtain benefits in the possession of the enforced individual. This mechanism is known as mafia behaviour in humans, but may be widespread in parasite-host relationships in nature, from the cellular level to societies. In this paper we describe the evolution of such mafia mechanisms, and we propose a fuzzy logic model where the mafia mechanism is based on enforcement of hosts by exponentially increasing the cost of resistance to the parasite. The benefits of host resistance can be counteracted by parasite virulence, or even a decrease in response to an increment in its resistance. This parasite response to the host defence increment can be used for the parasite to teach the host that it is better to pay part of its benefits than increase its extremely costly defence. This model differs from others because it takes into account the evolution of host defence related to the evolution of parasite virulence (host-parasite coevolution) and points out an optimum in host defence related to the facultative virulence of the parasite. We provide several potential examples of facultative virulence depending on the antiparasite responses of hosts, and we suggest that this kind of mafia behaviour may be a widespread mechanism in biological processes at a number of different levels.

  16. Amoebapore is an important virulence factor of Entamoeba histolytica

    Indian Academy of Sciences (India)

    ... ap-a genes. The silenced transfectant was not virulent at all. These results demonstrate that important factors need to be expressed at the correct cellular location and that the parasite has additional internal control mechanisms such as transcriptional gene silencing which can prevent excess amounts of gene expression.

  17. Plants and animals share functionally common bacterial virulence factors

    OpenAIRE

    Rahme, Laurence G.; Ausubel, Frederick M.; Cao, Hui; Drenkard, Eliana; Goumnerov, Boyan C.; Lau, Gee W.; Mahajan-Miklos, Shalina; Plotnikova, Julia; Tan, Man-Wah; Tsongalis, John; Walendziewicz, Cynthia L.; Tompkins, Ronald G.

    2000-01-01

    By exploiting the ability of Pseudomonas aeruginosa to infect a variety of vertebrate and nonvertebrate hosts, we have developed model systems that use plants and nematodes as adjuncts to mammalian models to help elucidate the molecular basis of P. aeruginosa pathogenesis. Our studies reveal a remarkable degree of conservation in the virulence mechanisms used by P. aeruginosa to infect hosts of divergent evolutionary origins.

  18. Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella

    Directory of Open Access Journals (Sweden)

    Heffron Fred

    2011-06-01

    Full Text Available Abstract Background Systemic bacterial infections are highly regulated and complex processes that are orchestrated by numerous virulence factors. Genes that are coordinately controlled by the set of regulators required for systemic infection are potentially required for pathogenicity. Results In this study we present a systems biology approach in which sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. Immunoblot experiments verified network-predicted virulence factors and a subset was determined to be secreted into the host cytoplasm, suggesting that they are virulence factors directly interacting with host cellular components. Two of these, SrfN and PagK2, were required for full mouse virulence and were shown to be translocated independent of either of the type III secretion systems in Salmonella or the type III injectisome-related flagellar mechanism. Conclusions Integrating multi-omic datasets from Salmonella mutants lacking virulence regulators not only identified novel virulence factors but also defined a new class of translocated effectors involved in pathogenesis. The success of this strategy at discovery of known and novel virulence factors suggests that the approach may have applicability for other bacterial pathogens.

  19. Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hyunjin; Ansong, Charles; McDermott, Jason E.; Gritsenko, Marina A.; Smith, Richard D.; Heffron, Fred; Adkins, Joshua N.

    2011-06-28

    Background: Systemic bacterial infections are highly regulated and complex processes that are orchestrated by numerous virulence factors. Genes that are coordinately controlled by the set of regulators required for systemic infection are potentially required for pathogenicity. Results: In this study we present a systems biology approach in which sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. Immunoblot experiments verified network-predicted virulence factors and a subset was determined to be secreted into the host cytoplasm, suggesting that they are virulence factors directly interacting with host cellular components. Two of these, SrfN and PagK2, were required for full mouse virulence and were shown to be translocated independent of either of the type III secretion systems in Salmonella or the type III injectisome-related flagellar mechanism. Conclusions: Integrating multi-omic datasets from Salmonella mutants lacking virulence regulators not only identified novel virulence factors but also defined a new class of translocated effectors involved in pathogenesis. The success of this strategy at discovery of known and novel virulence factors suggests that the approach may have applicability for other bacterial pathogens.

  20. Complete genomic sequences, a key residue in the spike protein and deletions in nonstructural protein 3b of US strains of the virulent and attenuated coronaviruses, transmissible gastroenteritis virus and porcine respiratory coronavirus.

    Science.gov (United States)

    Zhang, Xinsheng; Hasoksuz, Mustafa; Spiro, David; Halpin, Rebecca; Wang, Shiliang; Stollar, Sarah; Janies, Daniel; Hadya, Nagesh; Tang, Yuxin; Ghedin, Elodie; Saif, Linda

    2007-02-20

    Transmissible gastroenteritis virus (TGEV) isolates that have been adapted to passage in cell culture maintain their infectivity in vitro but may lose their pathogenicity in vivo. To better understand the genomic mechanisms for viral attenuation, we sequenced the complete genomes of two virulent TGEV strains and their attenuated counterparts: virulent TGEV Miller M6 and attenuated TGEV Miller M60 and virulent TGEV Purdue and attenuated TGEV Purdue P115, together with the ISU-1 strain of porcine respiratory coronavirus (PRCV-ISU-1), a naturally occurring TGEV deletion mutant with an altered respiratory tropism and reduced virulence. Pairwise comparison at both the nucleotide (nt) and amino acid (aa) levels between virulent and attenuated TGEV strains identified a common change in nt 1753 of the spike gene, resulting in a serine to alanine mutation at aa position 585 of the spike proteins of the attenuated TGEV strains. Alanine was also present in this protein in PRCV-ISU-1. Particularly noteworthy, the serine to alanine mutation resides in the region of the major antigenic site A/B (aa 506-706) that elicits neutralizing antibodies and within the domain mediating the cell surface receptor aminopeptidase N binding (aa 522-744). Comparison of the predicted polypeptide products of ORF3b showed significant deletions in the naturally attenuated PRCV-ISU-1 and TGEV Miller M60; these deletions occurred at a common break point, suggesting a related mechanism of recombination that may affect viral virulence or tropism. Sequence comparisons at both genomic and protein levels indicated that PRCV-ISU-1 had a closer relationship with TGEV Miller strains than Purdue strains. Phylogenetic analyses showed that virulence is an evolutionarily labile trait in TGEV and that TGEV strains as a group share a common ancestor with PRCV.

  1. Understanding the Mechanism of the Hydrogen Abstraction from Arachidonic Acid Catalyzed by the Human Enzyme 15-Lipoxygenase-2. A Quantum Mechanics/Molecular Mechanics Free Energy Simulation.

    Science.gov (United States)

    Suardíaz, Reynier; Jambrina, Pablo G; Masgrau, Laura; González-Lafont, Àngels; Rosta, Edina; Lluch, José M

    2016-04-12

    . Overall, a different binding mode from the one accepted for 15-LOX-1 is proposed, which provides a molecular basis for 15-LOX-2 exclusive 15-HPETE production in front of the double (although highly 15-) 12/15 regiospecificity of 15-LOX-1. Understanding how these different isoenzymes achieve their regiospecificity is expected to help in specific inhibitor design.

  2. From observation to understanding: Approach to analysis of wear mechanisms, Case of RCCAs and CRDM latch arms

    International Nuclear Information System (INIS)

    Hertz, D.

    2004-01-01

    Component wear can affect the ability of a component to fulfill its required function. For a designer or user, it is reasonable to expect possible wear occurrence as soon as parts are in relative motion. It is less obvious to extend this possibility to motions with small or very small amplitudes and loads. However, it has to be admitted that such cases exist. It then becomes imperative to determine the wear mechanisms so that the lifetime of the components and the optimum date of their replacement can be predicted or the degradation can be remedied. For this purpose, standard and widely accepted practice is to carry out simulator tests. Through examples of wear from nuclear reactor components such as the RCCAs (Rod Cluster Control Assembly) and the CRDM (Control Rod Drive Mechanism) latch arms, an approach for understanding the wear mechanisms and controlling their effects can be undertaken. Cases of wear have been observed on real-life parts, but the first simulator tests have shown deviations from in-reactor behaviour. Comparative examination of the wear facies of actual parts which have operated in reactor or simulators, both control rods and CRDM latch arms, was the key starting point for a new analytical approach, incorporating the formulation of wear mechanism hypotheses which can account for the observed facies. Expert assessment thus highlighted the importance of the environment by revealing that the wear featured a large component linked to friction-assisted corrosion. By including this tribo-corrosion aspect, it became possible to reach understanding of the mechanisms and account for the wear observed in reactor and on simulators. Further well-controlled simulator tests then made it possible to verify the importance of the tribo-corrosion processes in a pressurized water medium. Analysis of the physical chemical behaviour of the original materials (austenitic stainless steel) also explains why these surface modifications limit or remedy wear

  3. Systematic Understanding of Mechanisms of a Chinese Herbal Formula in Treatment of Metabolic Syndrome by an Integrated Pharmacology Approach.

    Science.gov (United States)

    Chen, Meimei; Yang, Fafu; Yang, Xuemei; Lai, Xinmei; Gao, Yuxing

    2016-12-16

    Metabolic syndrome (MS) is becoming a worldwide health problem. Wendan decoction (WDD)-a famous traditional Chinese medicine formula-has been extensively employed to relieve syndromes related to MS in clinical practice in China. However, its pharmacological mechanisms still remain vague. In this study, a comprehensive approach that integrated chemomics, principal component analysis, molecular docking simulation, and network analysis was established to elucidate the multi-component and multi-target mechanism of action of WDD in treatment of MS. The compounds in WDD were found to possess chemical diversity, complexity and drug-likeness compared to MS drugs. Six nuclear receptors were obtained to have strong binding affinity with 217 compounds of five herbs in WDD. The importance roles of targets and herbs were also identified due to network parameters. Five compounds from Radix Glycyrrhizae Preparata can hit all six targets, which can assist in screening new MS drugs. The pathway network analysis demonstrated that the main pharmacological effects of WDD might lie in maintaining lipid and glucose metabolisms and anticancer activities as well as immunomodulatory and hepatoprotective effects. This study provided a comprehensive system approach for understanding the multi-component, multi-target and multi-pathway mechanisms of WDD during the treatment of MS.

  4. Systematic Understanding of Mechanisms of a Chinese Herbal Formula in Treatment of Metabolic Syndrome by an Integrated Pharmacology Approach

    Directory of Open Access Journals (Sweden)

    Meimei Chen

    2016-12-01

    Full Text Available Metabolic syndrome (MS is becoming a worldwide health problem. Wendan decoction (WDD—a famous traditional Chinese medicine formula—has been extensively employed to relieve syndromes related to MS in clinical practice in China. However, its pharmacological mechanisms still remain vague. In this study, a comprehensive approach that integrated chemomics, principal component analysis, molecular docking simulation, and network analysis was established to elucidate the multi-component and multi-target mechanism of action of WDD in treatment of MS. The compounds in WDD were found to possess chemical diversity, complexity and drug-likeness compared to MS drugs. Six nuclear receptors were obtained to have strong binding affinity with 217 compounds of five herbs in WDD. The importance roles of targets and herbs were also identified due to network parameters. Five compounds from Radix Glycyrrhizae Preparata can hit all six targets, which can assist in screening new MS drugs. The pathway network analysis demonstrated that the main pharmacological effects of WDD might lie in maintaining lipid and glucose metabolisms and anticancer activities as well as immunomodulatory and hepatoprotective effects. This study provided a comprehensive system approach for understanding the multi-component, multi-target and multi-pathway mechanisms of WDD during the treatment of MS.

  5. Understanding the mechanical properties of DNA origami tiles and controlling the kinetics of their folding and unfolding reconfiguration.

    Science.gov (United States)

    Chen, Haorong; Weng, Te-Wei; Riccitelli, Molly M; Cui, Yi; Irudayaraj, Joseph; Choi, Jong Hyun

    2014-05-14

    DNA origami represents a class of highly programmable macromolecules that can go through conformational changes in response to external signals. Here we show that a two-dimensional origami rectangle can be effectively folded into a short, cylindrical tube by connecting the two opposite edges through the hybridization of linker strands and that this process can be efficiently reversed via toehold-mediated strand displacement. The reconfiguration kinetics was experimentally studied as a function of incubation temperature, initial origami concentration, missing staples, and origami geometry. A kinetic model was developed by introducing the j factor to describe the reaction rates in the cyclization process. We found that the cyclization efficiency (j factor) increases sharply with temperature and depends strongly on the structural flexibility and geometry. A simple mechanical model was used to correlate the observed cyclization efficiency with origami structure details. The mechanical analysis suggests two sources of the energy barrier for DNA origami folding: overcoming global twisting and bending the structure into a circular conformation. It also provides the first semiquantitative estimation of the rigidity of DNA interhelix crossovers, an essential element in structural DNA nanotechnology. This work demonstrates efficient DNA origami reconfiguration, advances our understanding of the dynamics and mechanical properties of self-assembled DNA structures, and should be valuable to the field of DNA nanotechnology.

  6. The link between morphotype transition and virulence in Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Linqi Wang

    Full Text Available Cryptococcus neoformans is a ubiquitous human fungal pathogen. This pathogen can undergo morphotype transition between the yeast and the filamentous form and such morphological transition has been implicated in virulence for decades. Morphotype transition is typically observed during mating, which is governed by pheromone signaling. Paradoxically, components specific to the pheromone signaling pathways play no or minimal direct roles in virulence. Thus, the link between morphotype transition and virulence and the underlying molecular mechanism remain elusive. Here, we demonstrate that filamentation can occur independent of pheromone signaling and mating, and both mating-dependent and mating-independent morphotype transition require the transcription factor Znf2. High expression of Znf2 is necessary and sufficient to initiate and maintain sex-independent filamentous growth under host-relevant conditions in vitro and during infection. Importantly, ZNF2 overexpression abolishes fungal virulence in murine models of cryptococcosis. Thus, Znf2 bridges the sex-independent morphotype transition and fungal pathogenicity. The impacts of Znf2 on morphological switch and pathogenicity are at least partly mediated through its effects on cell adhesion property. Cfl1, a Znf2 downstream factor, regulates morphogenesis, cell adhesion, biofilm formation, and virulence. Cfl1 is the first adhesin discovered in the phylum Basidiomycota of the Kingdom Fungi. Together with previous findings in other eukaryotic pathogens, our findings support a convergent evolution of plasticity in morphology and its impact on cell adhesion as a critical adaptive trait for pathogenesis.

  7. The Complex Relationship between Virulence and Antibiotic Resistance

    Science.gov (United States)

    Schroeder, Meredith; Brooks, Benjamin D.; Brooks, Amanda E.

    2017-01-01

    Antibiotic resistance, prompted by the overuse of antimicrobial agents, may arise from a variety of mechanisms, particularly horizontal gene transfer of virulence and antibiotic resistance genes, which is often facilitated by biofilm formation. The importance of phenotypic changes seen in a biofilm, which lead to genotypic alterations, cannot be overstated. Irrespective of if the biofilm is single microbe or polymicrobial, bacteria, protected within a biofilm from the external environment, communicate through signal transduction pathways (e.g., quorum sensing or two-component systems), leading to global changes in gene expression, enhancing virulence, and expediting the acquisition of antibiotic resistance. Thus, one must examine a genetic change in virulence and resistance not only in the context of the biofilm but also as inextricably linked pathologies. Observationally, it is clear that increased virulence and the advent of antibiotic resistance often arise almost simultaneously; however, their genetic connection has been relatively ignored. Although the complexities of genetic regulation in a multispecies community may obscure a causative relationship, uncovering key genetic interactions between virulence and resistance in biofilm bacteria is essential to identifying new druggable targets, ultimately providing a drug discovery and development pathway to improve treatment options for chronic and recurring infection. PMID:28106797

  8. Genetic Regulation of Virulence and Antibiotic Resistance in Acinetobacter baumannii

    Directory of Open Access Journals (Sweden)

    Carsten Kröger

    2016-12-01

    Full Text Available Multidrug resistant microorganisms are forecast to become the single biggest challenge to medical care in the 21st century. Over the last decades, members of the genus Acinetobacter have emerged as bacterial opportunistic pathogens, in particular as challenging nosocomial pathogens because of the rapid evolution of antimicrobial resistances. Although we lack fundamental biological insight into virulence mechanisms, an increasing number of researchers are working to identify virulence factors and to study antibiotic resistance. Here, we review current knowledge regarding the regulation of virulence genes and antibiotic resistance in Acinetobacter baumannii. A survey of the two-component systems AdeRS, BaeSR, GacSA and PmrAB explains how each contributes to antibiotic resistance and virulence gene expression, while BfmRS regulates cell envelope structures important for pathogen persistence. A. baumannii uses the transcription factors Fur and Zur to sense iron or zinc depletion and upregulate genes for metal scavenging as a critical survival tool in an animal host. Quorum sensing, nucleoid-associated proteins, and non-classical transcription factors such as AtfA and small regulatory RNAs are discussed in the context of virulence and antibiotic resistance.

  9. The Complex Relationship between Virulence and Antibiotic Resistance

    Directory of Open Access Journals (Sweden)

    Meredith Schroeder

    2017-01-01

    Full Text Available Antibiotic resistance, prompted by the overuse of antimicrobial agents, may arise from a variety of mechanisms, particularly horizontal gene transfer of virulence and antibiotic resistance genes, which is often facilitated by biofilm formation. The importance of phenotypic changes seen in a biofilm, which lead to genotypic alterations, cannot be overstated. Irrespective of if the biofilm is single microbe or polymicrobial, bacteria, protected within a biofilm from the external environment, communicate through signal transduction pathways (e.g., quorum sensing or two-component systems, leading to global changes in gene expression, enhancing virulence, and expediting the acquisition of antibiotic resistance. Thus, one must examine a genetic change in virulence and resistance not only in the context of the biofilm but also as inextricably linked pathologies. Observationally, it is clear that increased virulence and the advent of antibiotic resistance often arise almost simultaneously; however, their genetic connection has been relatively ignored. Although the complexities of genetic regulation in a multispecies community may obscure a causative relationship, uncovering key genetic interactions between virulence and resistance in biofilm bacteria is essential to identifying new druggable targets, ultimately providing a drug discovery and development pathway to improve treatment options for chronic and recurring infection.

  10. Genetic Regulation of Virulence and Antibiotic Resistance in Acinetobacter baumannii

    Science.gov (United States)

    Kröger, Carsten; Kary, Stefani C.; Schauer, Kristina; Cameron, Andrew D. S.

    2016-01-01

    Multidrug resistant microorganisms are forecast to become the single biggest challenge to medical care in the 21st century. Over the last decades, members of the genus Acinetobacter have emerged as bacterial opportunistic pathogens, in particular as challenging nosocomial pathogens because of the rapid evolution of antimicrobial resistances. Although we lack fundamental biological insight into virulence mechanisms, an increasing number of researchers are working to identify virulence factors and to study antibiotic resistance. Here, we review current knowledge regarding the regulation of virulence genes and antibiotic resistance in Acinetobacter baumannii. A survey of the two-component systems AdeRS, BaeSR, GacSA and PmrAB explains how each contributes to antibiotic resistance and virulence gene expression, while BfmRS regulates cell envelope structures important for pathogen persistence. A. baumannii uses the transcription factors Fur and Zur to sense iron or zinc depletion and upregulate genes for metal scavenging as a critical survival tool in an animal host. Quorum sensing, nucleoid-associated proteins, and non-classical transcription factors such as AtfA and small regulatory RNAs are discussed in the context of virulence and antibiotic resistance. PMID:28036056

  11. Candida albicans pathogenicity mechanisms.

    Science.gov (United States)

    Mayer, François 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.

  12. Candida albicans pathogenicity mechanisms

    Science.gov (United States)

    Mayer, François L.; Wilson, Duncan; Hube, Bernhard

    2013-01-01

    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

  13. Ferrous archaeological analogues for the understanding of the multi-secular corrosion mechanisms in an anoxic environment

    International Nuclear Information System (INIS)

    Saheb-Djahromi, M.

    2009-12-01

    Understanding the long term corrosion mechanisms of iron in an anoxic environment is essential in the field of the radioactive waste storage. In France, it is planned to store high level nuclear wastes in a multi-barrier system containing a glassy matrix surrounded by a stainless steel container, embedded in a low-carbon steel over-container. This system would be placed in a deep geological repository, which would impose anoxic conditions. As it must be efficient for a period of several thousands of years, one should understand the alteration mechanisms that are expected to occur in such a long time. To this purpose, a specific approach is developed on ferrous archaeological analogues with thick corrosion layer formed in natural conditions. In this study, the corrosion mechanisms have been assessed by examining nails aged of 400 years coming from the archaeological site of Glinet, selected as a reference site. The first point was a fine characterisation of the entire corrosion system metal / corrosion products / medium, through the use of coupled multi-scale analytical tools. The first results showed that the samples were corroded in an anoxic calco-carbonated environment. Moreover, the coupling of X-ray micro-diffraction, Raman microspectroscopy and dispersive energy spectroscopy has enabled to identify three corrosion systems composed of iron carbonates, siderite and chukanovite, and magnetite. Depending on the phase's layout in the system, the electronic resistance of the corrosion layers has been established, from resistive to conductive. In a second stage, re-corroding experiments in laboratory were performed. Firstly, the electrochemical behaviour of the corrosion system has shown that water reduction at the metallic interface is negligible. Furthermore, reaction tracing with copper and deuterium has allowed identifying the electron consumptions sites mainly localised on the external part, and the precipitation sites on the internal part of the corrosion

  14. Genetic Modulation of c-di-GMP Turnover Affects Multiple Virulence Traits and Bacterial Virulence in Rice Pathogen Dickeya zeae.

    Directory of Open Access Journals (Sweden)

    Yufan Chen

    Full Text Available The frequent outbreaks of rice foot rot disease caused by Dickeya zeae have become a significant concern in rice planting regions and countries, but the regulatory mechanisms that govern the virulence of this important pathogen remain vague. Given that the second messenger cyclic di-GMP (c-di-GMP is associated with modulation of various virulence-related traits in various microorganisms, here we set to investigate the role of the genes encoding c-di-GMP metabolism in the regulation of the bacterial physiology and virulence by construction all in-frame deletion mutants targeting the annotated c-di-GMP turnover genes in D. zeae strain EC1. Phenotype analyses identified individual mutants showing altered production of exoenzymes and phytotoxins, biofilm formation and bacterial motilities. The results provide useful clues and a valuable toolkit for further characterization and dissection of the regulatory complex that modulates the pathogenesis and persistence of this important bacterial pathogen.

  15. Genetic Modulation of c-di-GMP Turnover Affects Multiple Virulence Traits and Bacterial Virulence in Rice Pathogen Dickeya zeae.

    Science.gov (United States)

    Chen, Yufan; Lv, Mingfa; Liao, Lisheng; Gu, Yanfang; Liang, Zhibin; Shi, Zurong; Liu, Shiyin; Zhou, Jianuan; Zhang, Lianhui

    2016-01-01

    The frequent outbreaks of rice foot rot disease caused by Dickeya zeae have become a significant concern in rice planting regions and countries, but the regulatory mechanisms that govern the virulence of this important pathogen remain vague. Given that the second messenger cyclic di-GMP (c-di-GMP) is associated with modulation of various virulence-related traits in various microorganisms, here we set to investigate the role of the genes encoding c-di-GMP metabolism in the regulation of the bacterial physiology and virulence by construction all in-frame deletion mutants targeting the annotated c-di-GMP turnover genes in D. zeae strain EC1. Phenotype analyses identified individual mutants showing altered production of exoenzymes and phytotoxins, biofilm formation and bacterial motilities. The results provide useful clues and a valuable toolkit for further characterization and dissection of the regulatory complex that modulates the pathogenesis and persistence of this important bacterial pathogen.

  16. Insight into the specific virulence related genes and toxin-antitoxin virulent pathogenicity islands in swine streptococcosis pathogen Streptococcus equi ssp. zooepidemicus strain ATCC35246.

    Science.gov (United States)

    Ma, Zhe; Geng, Jianing; Yi, Li; Xu, Bin; Jia, Ruoyu; Li, Yue; Meng, Qingshu; Fan, Hongjie; Hu, Songnian

    2013-06-07

    Streptococcus equi ssp. zooepidemicus (S. zooepidemicus) is an important pathogen causing swine streptococcosis in China. Pathogenicity islands (PAIs) of S. zooepidemicus have been transferred among bacteria through horizontal gene transfer (HGT) and play important roles in the adaptation and increased virulence of S. zooepidemicus. The present study used comparative genomics to examine the different pathogenicities of S. zooepidemicus. Genome of S. zooepidemicus ATCC35246 (Sz35246) comprises 2,167,264-bp of a single circular chromosome, with a GC content of 41.65%. Comparative genome analysis of Sz35246, S. zooepidemicus MGCS10565 (Sz10565), Streptococcus equi. ssp. equi. 4047 (Se4047) and S. zooepidemicus H70 (Sz70) identified 320 Sz35246-specific genes, clustered into three toxin-antitoxin (TA) systems PAIs and one restriction modification system (RM system) PAI. These four acquired PAIs encode proteins that may contribute to the overall pathogenic capacity and fitness of this bacterium to adapt to different hosts. Analysis of the in vivo and in vitro transcriptomes of this bacterium revealed differentially expressed PAI genes and non-PAI genes, suggesting that Sz35246 possess mechanisms for infecting animals and adapting to a wide range of host environments. Analysis of the genome identified potential Sz35246 virulence genes. Genes of the Fim III operon were presumed to be involved in breaking the host-restriction of Sz35246. Genome wide comparisons of Sz35246 with three other strains and transcriptome analysis revealed novel genes related to bacterial virulence and breaking the host-restriction. Four specific PAIs, which were judged to have been transferred into Sz35246 genome through HGT, were identified for the first time. Further analysis of the TA and RM systems in the PAIs will improve our understanding of the pathogenicity of this bacterium and could lead to the development of diagnostics and vaccines.

  17. Contributions of human tissue analysis to understanding the mechanisms of loosening and osteolysis in total hip replacement

    DEFF Research Database (Denmark)

    Gallo, Jiri; Vaculova, Jana; Goodman, Stuart B

    2014-01-01

    Aseptic loosening and osteolysis are the most frequent late complications of total hip arthroplasty (THA) leading to revision of the prosthesis. This review aims to demonstrate how histopathological studies contribute to our understanding of the mechanisms of aseptic loosening...... of pathophysiological events that lead to prosthetic loosening and osteolysis. One possible solution is to examine tissues harvested from stable total hip arthroplasties that have been revised at various time periods due to dislocation or periprosthetic fracture in multicenter studies....... molecules of the host response at the protein level (chemokines, cytokines, nitric oxide metabolites, metalloproteinases). However, these studies also have important limitations. Tissues harvested at revision surgery reflect specifically end-stage failure and may not adequately reveal the evolution...

  18. Toward understanding the anticorrosive mechanism of some thiourea derivatives for carbon steel corrosion: A combined DFT and molecular dynamics investigation.

    Science.gov (United States)

    Guo, Lei; Kaya, Savaş; Obot, Ime Bassey; Zheng, Xingwen; Qiang, Yujie

    2017-11-15

    The mutually corroborated density functional theory (DFT) and molecular dynamics (MD) simulation methodology were employed to evaluate the inhibition performance of three thiourea derivatives (Inh1, Inh2, and Inh3) on carbon steel corrosion. Experimental results have shown that the corrosion rate follows the order: Inh3>Inh2>Inh1. Quantum chemical descriptors such as the frontier orbital energies (E HOMO and E LUMO ), the energy gap between E LUMO and E HOMO (ΔE), dipole moment (μ), and Fukui index have been calculated and discussed. Some significant factors such as solvent, temperature, and coverage have been considered when investigating the adsorption of aforementioned thiourea derivatives on Fe(110) surface. Our results provide important atomic/molecular insights into the anticorrosive mechanism of inhibitor molecules, which could help in understanding the organic-metal interface and designing more appropriate organic corrosion inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Understanding the Mechanisms behind Changing People’s Recycling Behavior at Work by Applying a Comprehensive Action Determination Model

    Directory of Open Access Journals (Sweden)

    Sunita Prugsamatz Ofstad

    2017-02-01

    Full Text Available This study moves toward a better understanding of the mechanisms behind changing people’s recycling behavior at work by mapping out which pathways and variables change in recycling behavior as triggered by interventions. A questionnaire was designed based on the theory of planned behaviour, the norm-activation model, habits, and a comprehensive action determination model (CADM. The data was collected in two rounds: before the intervention and after a three-month pilot period with implemented interventions using a sample of n = 1269 students and employees. The CADM model appears to be a good fit with the data. The results from the structural equation modelling indicate the pathways to influencing behavioural change. The most important psychological variables accounting for waste separation behaviour are intentions, perceived behavioural control, personal norms, social norms and habits. No difference in waste separation behaviour was observed in the control building. Interventions targeting the increase in waste separation raised participants’ intentions to engage in such behaviour. Results indicate that waste separation at work must go beyond technical aspects to include various key elements of sustainability to ensure success. Furthermore, understanding human behavior is key in determining the performance and success of an integrated and effective recycling intervention strategy.

  20. Proteomics As a Tool for Studying Bacterial Virulence and Antimicrobial Resistance

    Science.gov (United States)

    Pérez-Llarena, Francisco J.; Bou, Germán

    2016-01-01

    Proteomic studies have improved our understanding of the microbial world. The most recent advances in this field have helped us to explore aspects beyond genomics. For example, by studying proteins and their regulation, researchers now understand how some pathogenic bacteria have adapted to the lethal actions of antibiotics. Proteomics has also advanced our knowledge of mechanisms of bacterial virulence and some important aspects of how bacteria interact with human cells and, thus, of the pathogenesis of infectious diseases. This review article addresses these issues in some of the most important human pathogens. It also reports some applications of Matrix-Assisted Laser Desorption/Ionization-Time-Of-Flight (MALDI-TOF) mass spectrometry that may be important for the diagnosis of bacterial resistance in clinical laboratories in the future. The reported advances will enable new diagnostic and therapeutic strategies to be developed in the fight against some of the most lethal bacteria affecting humans. PMID:27065974

  1. Proteomics as a tool for studying bacterial virulence and antimicrobial resistance

    Directory of Open Access Journals (Sweden)

    Francisco José Pérez -Llarena

    2016-03-01

    Full Text Available Proteomic studies have improved our understanding of the microbial world. The most recent advances in this field have helped us to explore aspects beyond genomics. For example, by studying proteins and their regulation, researchers now understand how some pathogenic bacteria have adapted to the lethal actions of antibiotics. Proteomics has also advanced our knowledge of mechanisms of bacterial virulence and some important aspects of how bacteria interact with human cells and, thus, of the pathogenesis of infectious diseases. This review article addresses these issues in some of the most important human pathogens. It also reports some applications of MALDI-TOF mass spectrometry that may be important for the diagnosis of bacterial resistance in clinical laboratories in the future. The reported advances will enable new diagnostic and therapeutic strategies to be developed in the fight against some of the most lethal bacteria affecting humans.

  2. Bacterial human virulence genes across diverse habitats as assessed by In silico analysis of environmental metagenomes

    DEFF Research Database (Denmark)

    Søborg, Ditte Andreasen; Hendriksen, Niels B.; Kilian, Mogens

    2016-01-01

    The occurrence and distribution of clinically relevant bacterial virulence genes across natural (non-human) environments is not well understood. We aimed to investigate the occurrence of homologs to bacterial human virulence genes in a variety of ecological niches to better understand the role...... of natural environments in the evolution of bacterial virulence. Twenty four bacterial virulence genes were analyzed in 46 diverse environmental metagenomic datasets, representing various soils, seawater, freshwater, marine sediments, hot springs, the deep-sea, hypersaline mats, microbialites, gutless worms...... and glacial ice. Homologs to 16 bacterial human virulence genes, involved in urinary tract infections, gastrointestinal diseases, skin diseases, and wound and systemic infections, showed global ubiquity. A principal component analysis did not demonstrate clear trends across the metagenomes with respect...

  3. Computational Design of a pH Stable Enzyme: Understanding Molecular Mechanism of Penicillin Acylase's Adaptation to Alkaline Conditions

    Science.gov (United States)

    Suplatov, Dmitry; Panin, Nikolay; Kirilin, Evgeny; Shcherbakova, Tatyana; Kudryavtsev, Pavel; Švedas, Vytas

    2014-01-01

    Protein stability provides advantageous development of novel properties and can be crucial in affording tolerance to mutations that introduce functionally preferential phenotypes. Consequently, understanding the determining factors for protein stability is important for the study of structure-function relationship and design of novel protein functions. Thermal stability has been extensively studied in connection with practical application of biocatalysts. However, little work has been done to explore the mechanism of pH-dependent inactivation. In this study, bioinformatic analysis of the Ntn-hydrolase superfamily was performed to identify functionally important subfamily-specific positions in protein structures. Furthermore, the involvement of these positions in pH-induced inactivation was studied. The conformational mobility of penicillin acylase in Escherichia coli was analyzed through molecular modeling in neutral and alkaline conditions. Two functionally important subfamily-specific residues, Gluβ482 and Aspβ484, were found. Ionization of these residues at alkaline pH promoted the collapse of a buried network of stabilizing interactions that consequently disrupted the functional protein conformation. The subfamily-specific position Aspβ484 was selected as a hotspot for mutation to engineer enzyme variant tolerant to alkaline medium. The corresponding Dβ484N mutant was produced and showed 9-fold increase in stability at alkaline conditions. Bioinformatic analysis of subfamily-specific positions can be further explored to study mechanisms of protein inactivation and to design more stable variants for the engineering of homologous Ntn-hydrolases with improved catalytic properties. PMID:24959852

  4. Multiple stressor effects in Chlamydomonas reinhardtii--toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants.

    Science.gov (United States)

    Korkaric, Muris; Behra, Renata; Fischer, Beat B; Junghans, Marion; Eggen, Rik I L

    2015-05-01

    The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Computational design of a pH stable enzyme: understanding molecular mechanism of penicillin acylase's adaptation to alkaline conditions.

    Directory of Open Access Journals (Sweden)

    Dmitry Suplatov

    Full Text Available Protein stability provides advantageous development of novel properties and can be crucial in affording tolerance to mutations that introduce functionally preferential phenotypes. Consequently, understanding the determining factors for protein stability is important for the study of structure-function relationship and design of novel protein functions. Thermal stability has been extensively studied in connection with practical application of biocatalysts. However, little work has been done to explore the mechanism of pH-dependent inactivation. In this study, bioinformatic analysis of the Ntn-hydrolase superfamily was performed to identify functionally important subfamily-specific positions in protein structures. Furthermore, the involvement of these positions in pH-induced inactivation was studied. The conformational mobility of penicillin acylase in Escherichia coli was analyzed through molecular modeling in neutral and alkaline conditions. Two functionally important subfamily-specific residues, Gluβ482 and Aspβ484, were found. Ionization of these residues at alkaline pH promoted the collapse of a buried network of stabilizing interactions that consequently disrupted the functional protein conformation. The subfamily-specific position Aspβ484 was selected as a hotspot for mutation to engineer enzyme variant tolerant to alkaline medium. The corresponding Dβ484N mutant was produced and showed 9-fold increase in stability at alkaline conditions. Bioinformatic analysis of subfamily-specific positions can be further explored to study mechanisms of protein inactivation and to design more stable variants for the engineering of homologous Ntn-hydrolases with improved catalytic properties.

  6. Scanning electron microscopy-based approach to understand the mechanism underlying the adhesion of dengue viruses on ceramic hydroxyapatite columns.

    Directory of Open Access Journals (Sweden)

    Maiko Saito

    Full Text Available Although ceramic hydroxyapatite (HAp chromatography has been used as an alternative method ultracentrifugation for the production of vaccines, the mechanism of virus separation is still obscure. In order to begin to understand the mechanisms of virus separation, HAp surfaces were observed by scanning electron microscopy after chromatography with dengue viruses. When these processes were performed without elution and with a 10-207 mM sodium phosphate buffer gradient elution, dengue viruses that were adsorbed to HAp were disproportionately located in the columns. However, when eluted with a 10-600 mM sodium phosphate buffer gradient, few viruses were observed on the HAp surface. After incubating the dengue viruses that were adsorbed on HAp beads at 37°C and 2°C, the sphericity of the dengue viruses were reduced with an increase in incubation temperature. These results suggested that dengue virus was adsorbed to the HAp surface by electronic interactions and could be eluted by high-salt concentration buffers, which are commonly used in protein purification. Furthermore, virus fusion was thought to occur with increasing temperature, which implied that virus-HAp adhesion was similar to virus-cell adhesion.

  7. Antimicrobial Resistance and Virulence: a Successful or Deleterious Association in the Bacterial World?

    Science.gov (United States)

    Beceiro, Alejandro; Tomás, María

    2013-01-01

    SUMMARY Hosts and bacteria have coevolved over millions of years, during which pathogenic bacteria have modified their virulence mechanisms to adapt to host defense systems. Although the spread of pathogens has been hindered by the discovery and widespread use of antimicrobial agents, antimicrobial resistance has increased globally. The emergence of resistant bacteria has accelerated in recent years, mainly as a result of increased selective pressure. However, although antimicrobial resistance and bacterial virulence have developed on different timescales, they share some common characteristics. This review considers how bacterial virulence and fitness are affected by antibiotic resistance and also how the relationship between virulence and resistance is affected by different genetic mechanisms (e.g., coselection and compensatory mutations) and by the most prevalent global responses. The interplay between these factors and the associated biological costs depend on four main factors: the bacterial species involved, virulence and resistance mechanisms, the ecological niche, and the host. The development of new strategies involving new antimicrobials or nonantimicrobial compounds and of novel diagnostic methods that focus on high-risk clones and rapid tests to detect virulence markers may help to resolve the increasing problem of the association between virulence and resistance, which is becoming more beneficial for pathogenic bacteria. PMID:23554414

  8. Life history trade-offs and relaxed selection can decrease bacterial virulence in environmental reservoirs.

    Directory of Open Access Journals (Sweden)

    Lauri Mikonranta

    Full Text Available Pathogen virulence is usually thought to evolve in reciprocal selection with the host. While this might be true for obligate pathogens, the life histories of opportunistic pathogens typically alternate between within-host and outside-host environments during the infection-transmission cycle. As a result, opportunistic pathogens are likely to experience conflicting selection pressures across different environments, and this could affect their virulence through life-history trait correlations. We studied these correlations experimentally by exposing an opportunistic bacterial pathogen Serratia marcescens to its natural protist predator Tetrahymena thermophila for 13 weeks, after which we measured changes in bacterial traits related to both anti-predator defence and virulence. We found that anti-predator adaptation (producing predator-resistant biofilm caused a correlative attenuation in virulence. Even though the direct mechanism was not found, reduction in virulence was most clearly connected to a predator-driven loss of a red bacterial pigment, prodigiosin. Moreover, life-history trait evolution was more divergent among replicate populations in the absence of predation, leading also to lowered virulence in some of the 'predator absent' selection lines. Together these findings suggest that the virulence of non-obligatory, opportunistic bacterial pathogens can decrease in environmental reservoirs through life history trade-offs, or random accumulation of mutations that impair virulence traits under relaxed selection.

  9. Teachers' Beliefs about the Role of Interaction in Teaching Newtonian Mechanics and Its Influence on Students' Conceptual Understanding of Newton's Third Law

    Science.gov (United States)

    Jauhiainen, Johanna; Koponen, Ismo T.; Lavonen, Jari

    2006-01-01

    Students' conceptual understanding of Newton's third law has been the subject of numerous studies. These studies have often pointed out the importance of addressing the concept of interaction in teaching Newtonian mechanics. In this study, teachers were interviewed in order to examine how they understand interaction and use it in their…

  10. Understanding mechanisms of rarity in pteridophytes: competition and climate change threaten the rare fern Asplenium scolopendrium var. americanum (Aspleniaceae).

    Science.gov (United States)

    Testo, Weston L; Watkins, James E

    2013-11-01

    Understanding the ecology of rare species can inform aspects of conservation strategies; however, the mechanisms of rarity remain elusive for most pteridophytes, which possess independent and ecologically distinct gametophyte and sporophyte generations. To elucidate factors contributing to recent declines of the rare fern Asplenium scolopendrium var. americanum, we studied the ecology and ecophysiology of its gametophyte generation, focusing on responses to competition, temperature, and water stress. Gametophytes of A. scolopendrium var. americanum, its widespread European relative A. scolopendrium var. scolopendrium, and five co-occurring fern species were grown from spores. Gametophytes were grown at 20°C and 25°C, and germination rates, intra- and interspecific competition, desiccation tolerance, and sporophyte production were determined for all species. Gametophytes of A. scolopendrium var. americanum had the lowest rates of germination and sporophyte production among all species studied and exhibited the greatest sensitivity to interspecific competition, temperature increases, and desiccation. Mature gametophytes of A. scolopendrium var. americanum grown at 25°C were 84.6% smaller than those grown at 20°C, and only 1.5% produced sporophytes after 200 d in culture. Similar responses were not observed in other species studied. The recent declines and current status of populations of A. scolopendrium var. americanum are linked to its gametophyte's limited capacity to tolerate competition and physiological stress linked to climate change. This is the first study to develop a mechanistic understanding of rarity and decline in a fern and demonstrates the importance of considering the ecology of the gametophyte in plants with independent sporophyte and gametophyte generations.

  11. Multiple stressor effects in Chlamydomonas reinhardtii – Toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Korkaric, Muris [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich (Switzerland); Behra, Renata; Fischer, Beat B. [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); Junghans, Marion [Swiss Center for Applied Ecotoxicology Eawag-EPFL, 8600, Duebendorf (Switzerland); Eggen, Rik I.L., E-mail: rik.eggen@eawag.ch [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich (Switzerland)

    2015-05-15

    Highlights: • Systematic study of multiple stressor effects of UVR and chemicals in C. reinhardtii. • UVR and chemicals did not act independently on algal photosynthesis and reproduction. • Multiple stressor effects of UVR and chemicals depended on chemical MOA. • Synergistic effect interactions not limited to oxidative stress inducing chemicals. • Multiple MOAs of UVR may limit applicability of current prediction models. - Abstract: The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are

  12. Multiple stressor effects in Chlamydomonas reinhardtii – Toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants

    International Nuclear Information System (INIS)

    Korkaric, Muris; Behra, Renata; Fischer, Beat B.; Junghans, Marion; Eggen, Rik I.L.

    2015-01-01

    Highlights: • Systematic study of multiple stressor effects of UVR and chemicals in C. reinhardtii. • UVR and chemicals did not act independently on algal photosynthesis and reproduction. • Multiple stressor effects of UVR and chemicals depended on chemical MOA. • Synergistic effect interactions not limited to oxidative stress inducing chemicals. • Multiple MOAs of UVR may limit applicability of current prediction models. - Abstract: The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are

  13. Virulence evolution in response to anti-infection resistance: toxic food plants can select for virulent parasites of monarch butterflies.

    Science.gov (United States)

    de Roode, J C; de Castillejo, C Lopez Fernandez; Faits, T; Alizon, S

    2011-04-01

    Host resistance to parasites can come in two main forms: hosts may either reduce the probability of parasite infection (anti-infection resistance) or reduce parasite growth after infection has occurred (anti-growth resistance). Both resistance mechanisms are often imperfect, meaning that they do not fully prevent or clear infections. Theoretical work has suggested that imperfect anti-growth resistance can select for higher parasite virulence by favouring faster-growing and more virulent parasites that overcome this resistance. In contrast, imperfect anti-infection resistance is thought not to select for increased parasite virulence, because it is assumed that it reduces the number of hosts that become infected, but not the fitness of parasites in successfully infected hosts. Here, we develop a theoretical model to show that anti-infection resistance can in fact select for higher virulence when such resistance reduces the effective parasite dose that enters a host. Our model is based on a monarch butterfly-parasite system in which larval food plants confer resistance to the monarch host. We carried out an experiment and showed that this environmental resistance is most likely a form of anti-infection resistance, through which toxic food plants reduce the effective dose of parasites that initiates an infection. We used these results to build a mathematical model to investigate the evolutionary consequences of food plant-induced resistance. Our model shows that when the effective infectious dose is reduced, parasites can compensate by evolving a higher per-parasite growth rate, and consequently a higher intrinsic virulence. Our results are relevant to many insect host-parasite systems, in which larval food plants often confer imperfect anti-infection resistance. Our results also suggest that - for parasites where the infectious dose affects the within-host dynamics - vaccines that reduce the effective infectious dose can select for increased parasite virulence.

  14. Thermosensing coordinates a cis-regulatory module for transcriptional activation of the intracellular virulence system in Salmonella enterica serovar Typhimurium.

    Science.gov (United States)

    Duong, Nancy; Osborne, Suzanne; Bustamante, Víctor H; Tomljenovic, Ana M; Puente, José L; Coombes, Brian K

    2007-11-23

    The expression of bacterial virulence genes is tightly controlled by the convergence of multiple extracellular signals. As a zoonotic pathogen, virulence gene regulation in Salmonella enterica serovar Typhimurium must be responsive to multiple cues from the general environment as well as from multiple niches within animal and human hosts. Previous work has identified combined magnesium and phosphate limitation as an environmental cue that activates genes required for intracellular virulence. One unanswered question is how virulence genes that are expressed within the host are inhibited in non-host environments that satisfy the phosphate and magnesium limitation cues. We report here that thermosensing is the major mechanism controlling incongruous activation of the intracellular virulence phenotype. Bacteria grown at 30 degrees C or lower were unable to activate the intracellular type III secretion system even under strong inducing signals such as synthetic medium, contact with macrophages, and exposure to the murine gut. Thermoregulation was fully recapitulated in a Salmonella bongori strain engineered to contain the intracellular virulence genes of S. enterica sv. Typhimurium, suggesting that orthologous thermoregulators were available. Accordingly, virulence gene repression at the nonpermissive temperature required Hha and H-NS, two nucleoid-like proteins involved in virulence gene control. The use of combined environmental cues to control transcriptional "logic gates" allows for transcriptional selectivity of virulence genes that would otherwise be superfluous if activated in the non-host environment. Thus, thermosensing by Salmonella provides integrated control of host niche-specific virulence factors.

  15. The Composition and Spatial Patterns of Bacterial Virulence Factors and Antibiotic Resistance Genes in 19 Wastewater Treatment Plants

    OpenAIRE

    Zhang, Bing; Xia, Yu; Wen, Xianghua; Wang, Xiaohui; Yang, Yunfeng; Zhou, Jizhong; Zhang, Yu

    2016-01-01

    Bacterial pathogenicity and antibiotic resistance are of concern for environmental safety and public health. Accumulating evidence suggests that wastewater treatment plants (WWTPs) are as an important sink and source of pathogens and antibiotic resistance genes (ARGs). Virulence genes (encoding virulence factors) are good indicators for bacterial pathogenic potentials. To achieve a comprehensive understanding of bacterial pathogenic potentials and antibiotic resistance in WWTPs, bacterial vir...

  16. A new application of the phase-field method for understanding the mechanisms of nuclear architecture reorganization.

    Science.gov (United States)

    Lee, S Seirin; Tashiro, S; Awazu, A; Kobayashi, R

    2017-01-01

    Specific features of nuclear architecture are important for the functional organization of the nucleus, and chromatin consists of two forms, heterochromatin and euchromatin. Conventional nuclear architecture is observed when heterochromatin is enriched at nuclear periphery, and it represents the primary structure in the majority of eukaryotic cells, including the rod cells of diurnal mammals. In contrast to this, inverted nuclear architecture is observed when the heterochromatin is distributed at the center of the nucleus, which occurs in the rod cells of nocturnal mammals. The inverted architecture found in the rod cells of the adult mouse is formed through the reorganization of conventional architecture during terminal differentiation. Although a previous experimental approach has demonstrated the relationship between these two nuclear architecture types at the molecular level, the mechanisms underlying long-range reorganization processes remain unknown. The details of nuclear structures and their spatial and temporal dynamics remain to be elucidated. Therefore, a comprehensive approach, using mathematical modeling, is required, in order to address these questions. Here, we propose a new mathematical approach to the understanding of nuclear architecture dynamics using the phase-field method. We successfully recreated the process of nuclear architecture reorganization, and showed that it is robustly induced by physical features, independent of a specific genotype. Our study demonstrates the potential of phase-field method application in the life science fields.

  17. Contribution of proteomics of Leishmania spp. to the understanding of differentiation, drug resistance mechanisms, vaccine and drug development.

    Science.gov (United States)

    Paape, Daniel; Aebischer, Toni

    2011-08-24

    Leishmania spp., protozoan parasites with a digenetic life cycle, cause a spectrum of diseases in humans. Recently several Leishmania spp. have been sequenced which significantly boosted the number and quality of proteomic studies conducted. Here a historic review will summarize work of the pre-genomic era and then focus on studies after genome information became available. Firstly works comparing the different life cycle stages, in order to identify stage specific proteins, will be discussed. Identifying post-translational modifications by proteomics especially phosphorylation events will be discussed. Further the contribution of proteomics to the understanding of the molecular mechanism of drug resistance and the investigation of immunogenic proteins for the identification of vaccine candidates will be summarized. Approaches of how potentially secreted proteins were identified are discussed. So far 30-35% of the total predicted proteome of Leishmania spp. have been identified. This comprises mainly the abundant proteins, therefore the last section will look into technological approaches on how this coverage may be increased and what the gel-free and gel-based proteomics have to offer will be compared. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Adult and juvenile dermatomyositis: are the distinct clinical features explained by our current understanding of serological subgroups and pathogenic mechanisms?

    Science.gov (United States)

    2013-01-01

    Adult and juvenile dermatomyositis share the hallmark features of pathognomic skin rash and muscle inflammation, but are heterogeneous disorders with a range of additional disease features and complications. The frequency of important clinical features such as calcinosis, interstitial lung disease and malignancy varies markedly between adult and juvenile disease. These differences may reflect different disease triggers between children and adults, but whilst various viral and other environmental triggers have been implicated, results are so far conflicting. Myositis-specific autoantibodies can be detected in both adults and children with idiopathic inflammatory myopathies. They are associated with specific disease phenotypes and complications, and divide patients into clinically homogenous subgroups. Interestingly, whilst the same autoantibodies are found in both adults and children, the disease features remain different within autoantibody subgroups, particularly with regard to life-threatening disease associations, such as malignancy and rapidly progressive interstitial lung disease. Our understanding of the mechanisms that underlie these differences is limited by a lack of studies directly comparing adults and children. Dermatomyositis is an autoimmune disease, which is believed to develop as a result of an environmental trigger in a genetically predisposed individual. Age-specific host immune responses and muscle physiology may be additional complicating factors that have significant impact on disease presentation. Further study into this area may produce new insights into disease pathogenesis. PMID:23566358

  19. Copper-based opaque red glasses - Understanding the colouring mechanism of copper nanoparticles in archaeological glass samples

    Science.gov (United States)

    Drünert, F.; Blanz, M.; Pollok, K.; Pan, Z.; Wondraczek, L.; Möncke, D.

    2018-02-01

    Red opaque glasses of two different sites in central Germany, a medieval glassworks in Glashütten, Taunus Mountains, and an early modern glassworks in Wieda, Harz Mountains, were analysed with regard to their optical appearance. By scanning electron microscopy and X-ray diffraction, metallic copper nanoparticles were identified as a conspicuous constituent in these glasses. In addition, similar opaque red glasses were reproduced in the laboratory in order to better understand the manufacturing process. Detailed analysis of the optical scattering was conducted in order to evaluate the role of Cu0 nanoparticles in the colouring mechanism relative to other possible reasons of colouration. We find clear differences between the possible contributions of Cu2O (cuprite) particles and metallic copper (Cu0) nanoparticles. Through simulated backscattering spectra we were able to calculate an average copper particle radius in the archaeological glass samples resulting in a value of up to 95 nm, which matches well the results of SEM investigation (minimum 65 nm). Using the methods we applied in this study, it becomes possible to reconstruct various processing conditions as they were applied in medieval manufacture of these particular materials.

  20. Toward a better understanding of the mechanisms of symbiosis: a comprehensive proteome map of a nascent insect symbiont

    Directory of Open Access Journals (Sweden)

    François Renoz

    2017-05-01

    Full Text Available Symbiotic bacteria are common in insects and can affect various aspects of their hosts’ biology. Although the effects of insect symbionts have been clarified for various insect symbiosis models, due to the difficulty of cultivating them in vitro, there is still limited knowledge available on the molecular features that drive symbiosis. Serratia symbiotica is one of the most common symbionts found in aphids. The recent findings of free-living strains that are considered as nascent partners of aphids provide the opportunity to examine the molecular mechanisms that a symbiont can deploy at the early stages of the symbiosis (i.e., symbiotic factors. In this work, a proteomic approach was used to establish a comprehensive proteome map of the free-living S. symbiotica strain CWBI-2.3T. Most of the 720 proteins identified are related to housekeeping or primary metabolism. Of these, 76 were identified as candidate proteins possibly promoting host colonization. Our results provide strong evidence that S. symbiotica CWBI-2.3T is well-armed for invading insect host tissues, and suggest that certain molecular features usually harbored by pathogenic bacteria are no longer present. This comprehensive proteome map provides a series of candidate genes for further studies to understand the molecular cross-talk between insects and symbiotic bacteria.

  1. From genomes to metabolomes: Understanding mechanisms of symbiosis and cell-cell signaling using the archaeal system Ignicoccus-Nanoarchaeum

    Energy Technology Data Exchange (ETDEWEB)

    Podar, Mircea [Univ. of Tennessee, Knoxville, TN (United States). Biosciences Division; Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hettich, Robert [Univ. of Tennessee, Knoxville, TN (United States). Biosciences Division; Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Copie, Valerie [Montana State Univ., Bozeman, MT (United States). Dept. of Chemistry and Biochemistry; Bothner, Brian [Montana State Univ., Bozeman, MT (United States). Dept. of Chemistry and Biochemistry

    2016-12-16

    The main objective of this project was to use symbiotic Nanoarchaeaota, a group of thermophilic Archaea that are obligate symbionts/parasites on other Archaea, to develop an integrated multi-omic approach to study inter-species interactions as well as to understand fundamental mechanism that enable such relationships. As part of this grant we have achieved a number of important milestone on both technical and scientific levels. On the technical side, we developed immunofluorescence labeling and tracking methods to follow Nanoarchaeota in cultures and in environmental samples, we applied such methods in conjunction with flow cytometry to quantify and isolate uncultured representatives from the environment and characterized them by single cell genomics. On the proteomics side, we developed a more efficient and sensitive method to recover and semi-quantitatively measure membrane proteins, while achieving high total cellular proteome coverage (70-80% of the predicted proteome). Metabolomic analyses used complementary NMR and LC/GC mass spectrometry and led to the identification of novel lipids in these organisms as well as quantification of some of the major metabolites. Importantly, using several informatics approaches we were also able to integrate the transcriptomic, proteomic and metabolomic datasets, revealing aspects of the interspecies interaction that were not evident in the single omic analyses (manuscript in review). On the science side we determined that N. equitans and I. hospitalis are metabolically coupled and that N. equitans is strictly dependent on its host both for metabolic precursors and energetic needs. The actual mechanism by which small molecules move across the cell membrane remains unknown. The Ignicoccus host responds to the metabolic and energetic burned by upregulating of key primary metabolism steps and ATP synthesis. The two species have co-evolved, aspect that we determined by comparative genomics with other species of Ignicoccus

  2. Proteomic profiles of mouse neuro N2a cells infected with variant virulence of rabies viruses.

    Science.gov (United States)

    Wang, Xiaohu; Zhang, Shoufeng; Sun, Chenglong; Yuan, Zi-Guo; Wu, Xianfu; Wang, Dongxia; Ding, Zhuang; Hu, Rongliang

    2011-04-01

    We characterized the proteomes of murine N2a cells following infection with three rabies virus (RV) strains, characterized by distinct virulence phenotypes (i.e., virulent BD06, fixed CVS-11, and attenuated SRV9 strains), and identified 35 changes to protein expression using two-dimensional gel electrophoresis in whole-cell lysates. The annotated functions of these proteins are involved in various cytoskeletal, signal transduction, stress response, and metabolic processes. Specifically, a-enolase, prx-4, vimentin, cytokine-induced apoptosis inhibitor 1 (CIAPIN1) and prx-6 were significantly up-regulated, whereas Trx like-1 and galectin-1 were down-regulated following infection of N2a cells with all three rabies virus strains. However, comparing expressions of all 35 proteins affected between BD06-, CVS-11-, and SRV9-infected cells, specific changes in expression were also observed. The up-regulation of vimentin, CIAPIN1, prx-4, and 14-3-3 theta/delta, and downregulation of NDPK-B and HSP-1 with CVS and SRV9 infection were ≥ 2 times greater than with BD06. Meanwhile, Zfp12 protein, splicing factor, and arginine/serine-rich 1 were unaltered in the cells infected with BD06 and CVS- 11, but were up-regulated in the group infected with SRV9. The proteomic alterations described here may suggest that these changes to protein expression correlate with the rabies virus' adaptability and virulence in N2a cells, and hence provides new clues as to the response of N2a host cells to rabies virus infections, and may also aid in uncovering new pathways in these cells that are involved in rabies infections. Further characterization of the functions of the affected proteins may contribute to our understanding of the mechanisms of RV infection and pathogenesis.

  3. Norepinephrine and dopamine increase motility, biofilm formation and virulence of Vibrio harveyi

    Directory of Open Access Journals (Sweden)

    Qian eYang

    2014-11-01

    Full Text Available Vibrio harveyi is one of the major pathogens of aquatic organisms, affecting both vertebrates and invertebrates, and causes important losses in the aquaculture industry. In order to develop novel methods to control disease caused by this pathogen, we need to obtain a better understanding of pathogenicity mechanisms. Sensing of catecholamines increases both growth and production of virulence-related factors in pathogens of terrestrial animals and humans. However, at this moment, knowledge on the impact of catecholamines on the virulence of pathogens of aquatic organisms is lacking. In the present study, we report that in V. harveyi, norepinephrine and dopamine increased growth in serum-supplemented medium, siderophore production, swimming motility and expression of genes involved in flagellar motility, biofilm formation, and exopolysaccharide production. Consistent with this, pretreatment of V. harveyi with catecholamines prior to inoculation into the rearing water resulted in significantly decreased survival of gnotobiotic brine shrimp larvae, when compared to larvae challenged with untreated V. harveyi. Further, norepinephrine-induced effects could be neutralized by α-adrenergic antagonists or by the bacterial catecholamine receptor antagonist LED209, but not by β-adrenergic or dopaminergic antagonists. Dopamine-induced effects could be neutralized by dopaminergic antagonists or LED209, but not by adrenergic antagonists. Together, our results indicate that catecholamine sensing increases the success of transmission of V. harveyi and that interfering with catecholamine sensing might be an interesting strategy to control vibriosis in aquaculture. We hypothesise that upon tissue and/or hemocyte damage during infection, pathogens come into contact with elevated catecholamine levels, and that this stimulates the expression of virulence factors that are required to colonize a new host.

  4. PhoB activates Escherichia coli O157:H7 virulence factors in response to inorganic phosphate limitation.

    Science.gov (United States)

    Chekabab, Samuel Mohammed; Jubelin, Grégory; Dozois, Charles M; Harel, Josée

    2014-01-01

    Enterohemorrhagic Escherichia coli (EHEC), an emerging food- and water-borne hazard, is highly pathogenic to humans. In the environment, EHEC must survive phosphate (Pi) limitation. The response to such Pi starvation is an induction of the Pho regulon including the Pst system that senses Pi variation. The interplay between the virulence of EHEC, Pho-Pst system and environmental Pi remains unknown. To understand the effects of Pi deprivation on the molecular mechanisms involved in EHEC survival and virulence under Pho regulon control, we undertook transcriptome profiling of the EDL933 wild-type strain grown under high Pi and low Pi conditions and its isogenic ΔphoB mutant grown in low Pi conditions. The differentially expressed genes included 1067 Pi-dependent genes and 603 PhoB-dependent genes. Of these 131 genes were both Pi and PhoB-dependent. Differentially expressed genes that were selected included those involved in Pi homeostasis, cellular metabolism, acid stress, oxidative stress and RpoS-dependent stress responses. Differentially expressed virulence systems included the locus of enterocyte effacement (LEE) encoding the type-3 secretion system (T3SS) and its effectors, as well as BP-933W prophage encoded Shiga toxin 2 genes. Moreover, PhoB directly regulated LEE and stx2 gene expression through binding to specific Pho boxes. However, in Pi-rich medium, constitutive activation of the Pho regulon decreased LEE gene expression and reduced adherence to HeLa cells. Together, these findings reveal that EHEC has evolved a sophisticated response to Pi limitation involving multiple biochemical strategies that contribute to its ability to respond to variations in environmental Pi and to coordinating the virulence response.

  5. PhoB activates Escherichia coli O157:H7 virulence factors in response to inorganic phosphate limitation.

    Directory of Open Access Journals (Sweden)

    Samuel Mohammed Chekabab

    Full Text Available Enterohemorrhagic Escherichia coli (EHEC, an emerging food- and water-borne hazard, is highly pathogenic to humans. In the environment, EHEC must survive phosphate (Pi limitation. The response to such Pi starvation is an induction of the Pho regulon including the Pst system that senses Pi variation. The interplay between the virulence of EHEC, Pho-Pst system and environmental Pi remains unknown. To understand the effects of Pi deprivation on the molecular mechanisms involved in EHEC survival and virulence under Pho regulon control, we undertook transcriptome profiling of the EDL933 wild-type strain grown under high Pi and low Pi conditions and its isogenic ΔphoB mutant grown in low Pi conditions. The differentially expressed genes included 1067 Pi-dependent genes and 603 PhoB-dependent genes. Of these 131 genes were both Pi and PhoB-dependent. Differentially expressed genes that were selected included those involved in Pi homeostasis, cellular metabolism, acid stress, oxidative stress and RpoS-dependent stress responses. Differentially expressed virulence systems included the locus of enterocyte effacement (LEE encoding the type-3 secretion system (T3SS and its effectors, as well as BP-933W prophage encoded Shiga toxin 2 genes. Moreover, PhoB directly regulated LEE and stx2 gene expression through binding to specific Pho boxes. However, in Pi-rich medium, constitutive activation of the Pho regulon decreased LEE gene expression and reduced adherence to HeLa cells. Together, these findings reveal that EHEC has evolved a sophisticated response to Pi limitation involving multiple biochemical strategies that contribute to its ability to respond to variations in environmental Pi and to coordinating the virulence response.

  6. Bench-to-bedside review: Bacterial virulence and subversion of host defences.

    Science.gov (United States)

    Webb, Steven A R; Kahler, Charlene M

    2008-01-01

    Bacterial pathogens possess an array of specific mechanisms that confer virulence and the capacity to avoid host defence mechanisms. Mechanisms of virulence are often mediated by the subversion of normal aspects of host biology. In this way the pathogen modifies host function so as to promote the pathogen's survival or proliferation. Such subversion is often mediated by the specific interaction of bacterial effector molecules with host encoded proteins and other molecules. The importance of these mechanisms for bacterial pathogens that cause infections leading to severe community-acquired infections is well established. In contrast, the importance of specialised mechanisms of virulence in the genesis of nosocomial bacterial infections, which occur in the context of local or systemic defects in host immune defences, is less well established. Specific mechanisms of bacterial resistance to host immunity might represent targets for therapeutic intervention. The clinical utility of such an approach for either prevention or treatment of bacterial infection, however, has not been determined.

  7. Mechanics

    CERN Document Server

    Chester, W

    1979-01-01

    When I began to write this book, I originally had in mind the needs of university students in their first year. May aim was to keep the mathematics simple. No advanced techniques are used and there are no complicated applications. The emphasis is on an understanding of the basic ideas and problems which require expertise but do not contribute to this understanding are not discussed. How­ ever, the presentation is more sophisticated than might be considered appropri­ ate for someone with no previous knowledge of the subject so that, although it is developed from the beginning, some previous acquaintance with the elements of the subject would be an advantage. In addition, some familiarity with element­ ary calculus is assumed but not with the elementary theory of differential equations, although knowledge of the latter would again be an advantage. It is my opinion that mechanics is best introduced through the motion of a particle, with rigid body problems left until the subject is more fully developed. Howev...

  8. Increased plasmid copy number is essential for Yersinia T3SS function and virulence.

    Science.gov (United States)

    Wang, He; Avican, Kemal; Fahlgren, Anna; Erttmann, Saskia F; Nuss, Aaron M; Dersch, Petra; Fallman, Maria; Edgren, Tomas; Wolf-Watz, Hans

    2016-07-29

    Pathogenic bacteria have evolved numerous virulence mechanisms that are essential for establishing infections. The enterobacterium Yersinia uses a type III secretion system (T3SS) encoded by a 70-kilobase, low-copy, IncFII-class virulence plasmid. We report a novel virulence strategy in Y. pseudotuberculosis in which this pathogen up-regulates the plasmid copy number during infection. We found that an increased dose of plasmid-encoded genes is indispensable for virulence and substantially elevates the expression and function of the T3SS. Remarkably, we observed direct, tight coupling between plasmid replication and T3SS function. This regulatory pathway provides a framework for further exploration of the environmental sensing mechanisms of pathogenic bacteria. Copyright © 2016, American Association for the Advancement of Science.

  9. Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence

    Science.gov (United States)

    Mahdavi, Jafar; Royer, Pierre-Joseph; Sjölinder, Hong S.; Azimi, Sheyda; Self, Tim; Stoof, Jeroen; Wheldon, Lee M.; Brännström, Kristoffer; Wilson, Raymond; Moreton, Joanna; Moir, James W. B.; Sihlbom, Carina; Borén, Thomas; Jonsson, Ann-Beth; Soultanas, Panos; Ala'Aldeen, Dlawer A. A.

    2013-01-01

    Interactions between commensal pathogens and hosts are critical for disease development but the underlying mechanisms for switching between the commensal and virulent states are unknown. We show that the human pathogen Neisseria meningitidis, the leading cause of pyogenic meningitis, can modulate gene expression via uptake of host pro-inflammatory cytokines leading to increased virulence. This uptake is mediated by type IV pili (Tfp) and reliant on the PilT ATPase activity. Two Tfp subunits, PilE and PilQ, are identified as the ligands for TNF-α and IL-8 in a glycan-dependent manner, and their deletion results in decreased virulence and increased survival in a mouse model. We propose a novel mechanism by which pathogens use the twitching motility mode of the Tfp machinery for sensing and importing host elicitors, aligning with the inflamed environment and switching to the virulent state. PMID:24107297

  10. Current Understanding of Physicochemical Mechanisms for Cell Membrane Penetration of Arginine-rich Cell Penetrating Peptides: Role of Glycosaminoglycan Interactions.

    Science.gov (United States)

    Takechi-Haraya, Yuki; Saito, Hiroyuki

    2018-01-01

    Arginine-rich cell penetrating peptides (CPPs) are very promising drug carriers to deliver membrane-impermeable pharmaceuticals, such as siRNA, bioactive peptides and proteins. CPPs directly penetrate into cells across cell membranes via a spontaneous energy-independent process, in which CPPs appear to interact with acidic lipids in the outer leaflet of the cell membrane. However, acidic lipids represent only 10 to 20% of the total membrane lipid content and in mammalian cell membranes they are predominantly located in the inner leaflet. Alternatively, CPPs favorably bind in a charge density- dependent manner to negatively charged, sulfated glycosaminoglycans (GAGs), such as heparan sulfate and chondroitin sulfate, which are abundant on the cell surface and are involved in many biological functions. We have recently demonstrated that the interaction of CPPs with sulfated GAGs plays a critical role in their direct cell membrane penetration: the favorable enthalpy contribution drives the high-affinity binding of arginine-rich CPPs to sulfated GAGs, initiating an efficient cell membrane penetration. The favorable enthalpy gain is presumably mainly derived from a unique property of the guanidino group of arginine residues forming multidentate hydrogen bonding with sulfate and carboxylate groups in GAGs. Such interactions can be accompanied with charge neutralization of arginine-rich CPPs, promoting their partition into cell membranes. This review summarizes the current understanding of the physicochemical mechanism for lipid membrane penetration of CPPs, and discusses the role of the GAG interactions on the cell membrane penetration of CPPs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Application of isotope exchange based mass spectrometry to understand the mechanism of inhibition of sickle hemoglobin polymerization upon oxygenation.

    Science.gov (United States)

    Das, Rajdeep; Mitra, Amrita; Bhat, Vijay; Mandal, Amit Kumar

    2017-07-01

    Sickle hemoglobin (HbS) polymerization initiates in the deoxy state with the binding of hydrophobic patch formed by the isopropyl group of βVal6 residue of a hemoglobin tetramer with the hydrophobic pocket of another tetramer, whose hydrophobic patch binds to the hydrophobic groove of a third molecule. Subsequent elongation of a single stranded polymer followed by the formation of a double strand and finally combination of seven such pairs of double strands results in a fourteen stranded fibrous polymer. Precipitation of this fiber inside the erythrocytes results in sickling of red blood cells. Surprisingly, the polymerization does not occur in the oxy state of HbS. Due to the unavailability of crystal structure of oxy form of HbS, the molecular basis of inhibition of polymerization in the oxy state is unknown to date. In the present study, we have attempted to understand the molecular mechanism of inhibition of polymerization by exploiting the exchange of backbone amide hydrogens of HbS with deuterated solvent. Hydrogen/deuterium exchange kinetics of peptide amide hydrogens of both oxy and deoxy form of HbS were monitored through ESI mass spectrometry. Upon oxygenation changes in the conformational flexibility across different regions of α and β globin chains in the tetrameric HbS molecule were investigated. It was observed that oxygenation led to perturbation in the conformation of several residues around the hydrophobic patch, groove of a tetramer and axial, lateral contacts across the double strands that are involved in HbS polymerization. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Understanding the undelaying mechanism of HA-subtyping in the level of physic-chemical characteristics of protein.

    Science.gov (United States)

    Ebrahimi, Mansour; Aghagolzadeh, Parisa; Shamabadi, Narges; Tahmasebi, Ahmad; Alsharifi, Mohammed; Adelson, David L; Hemmatzadeh, Farhid; Ebrahimie, Esmaeil

    2014-01-01

    The evolution of the influenza A virus to increase its host range is a major concern worldwide. Molecular mechanisms of increasing host range are largely unknown. Influenza surface proteins play determining roles in reorganization of host-sialic acid receptors and host range. In an attempt to uncover the physic-chemical attributes which govern HA subtyping, we performed a large scale functional analysis of over 7000 sequences of 16 different HA subtypes. Large number (896) of physic-chemical protein characteristics were calculated for each HA sequence. Then, 10 different attribute weighting algorithms were used to find the key characteristics distinguishing HA subtypes. Furthermore, to discover machine leaning models which can predict HA subtypes, various Decision Tree, Support Vector Machine, Naïve Bayes, and Neural Network models were trained on calculated protein characteristics dataset as well as 10 trimmed datasets generated by attribute weighting algorithms. The prediction accuracies of the machine learning methods were evaluated by 10-fold cross validation. The results highlighted the frequency of Gln (selected by 80% of attribute weighting algorithms), percentage/frequency of Tyr, percentage of Cys, and frequencies of Try and Glu (selected by 70% of attribute weighting algorithms) as the key features that are associated with HA subtyping. Random Forest tree induction algorithm and RBF kernel function of SVM (scaled by grid search) showed high accuracy of 98% in clustering and predicting HA subtypes based on protein attributes. Decision tree models were successful in monitoring the short mutation/reassortment paths by which influenza virus can gain the key protein structure of another HA subtype and increase its host range in a short period of time with less energy consumption. Extracting and mining a large number of amino acid attributes of HA subtypes of influenza A virus through supervised algorithms represent a new avenue for understanding and

  13. Use of rheometry and {sup 1}H NMR spectroscopy for understanding the mechanisms behind the generation of coking pressure

    Energy Technology Data Exchange (ETDEWEB)

    Karen M. Steel; Miguel Castro Diaz; John W. Patrick; Colin E. Snape [Nottingham University, Nottingham (United Kingdom). Nottingham Fuel and Energy Centre, School of Chemical, Environmental and Mining Engineering

    2004-10-01

    The fluid phase which forms during carbonization of a range of coals was studied using rheometry and {sup 1}H NMR spectroscopy to study the mechanisms behind the generation of excessive wall pressures during coking. It is proposed that high coking pressures are generated for low volatile matter coals when the temperature of maximum fluidity (T{sub mf}) is {gt} 465{degree}C, the minimum complex viscosity ({eta}{asterisk}) is {gt} 10{sup 5} Pa s, the percentage of mobile 1H (fluid phase) is {lt} 40%, and the {sup 1}H mobility in the fluid phase is {lt} 65 {mu}s. It is suggested for these coals that the particles fuse to form a rigid network containing pockets of fluid material which have a low fluidity and do not link up. This arrangement could present an impermeable barrier for gas flow and force the gas to the coal side where it builds up in a diminishing region to a critical level, causing pressure on the walls. The magnitude of the pressure generated may be proportional to T{sub mf} and {eta}{asterisk} and inversely proportional to the percentage and mobility of mobile {sup 1}H. It was also found that a high volatile coal which formed a highly fluid phase over a broad temperature range gave rise to a significant coking pressure. In this case, it is proposed that the sheer expansion of the coal charge as it converts to gas and liquid phases is the reason for pressure on the oven walls. These proposals agree with current thinking on the generation of coking pressure. This work is based on the testing of only nine samples and further work is planned to gain a greater fundamental understanding of fluidity development from which models for predicting coking pressure and coke quality for coal blends may be developed. 20 refs., 10 figs., 5 tabs.

  14. Understanding the undelaying mechanism of HA-subtyping in the level of physic-chemical characteristics of protein.

    Directory of Open Access Journals (Sweden)

    Mansour Ebrahimi

    Full Text Available The evolution of the influenza A virus to increase its host range is a major concern worldwide. Molecular mechanisms of increasing host range are largely unknown. Influenza surface proteins play determining roles in reorganization of host-sialic acid receptors and host range. In an attempt to uncover the physic-chemical attributes which govern HA subtyping, we performed a large scale functional analysis of over 7000 sequences of 16 different HA subtypes. Large number (896 of physic-chemical protein characteristics were calculated for each HA sequence. Then, 10 different attribute weighting algorithms were used to find the key characteristics distinguishing HA subtypes. Furthermore, to discover machine leaning models which can predict HA subtypes, various Decision Tree, Support Vector Machine, Naïve Bayes, and Neural Network models were trained on calculated protein characteristics dataset as well as 10 trimmed datasets generated by attribute weighting algorithms. The prediction accuracies of the machine learning methods were evaluated by 10-fold cross validation. The results highlighted the frequency of Gln (selected by 80% of attribute weighting algorithms, percentage/frequency of Tyr, percentage of Cys, and frequencies of Try and Glu (selected by 70% of attribute weighting algorithms as the key features that are associated with HA subtyping. Random Forest tree induction algorithm and RBF kernel function of SVM (scaled by grid search showed high accuracy of 98% in clustering and predicting HA subtypes based on protein attributes. Decision tree models were successful in monitoring the short mutation/reassortment paths by which influenza virus can gain the key protein structure of another HA subtype and increase its host range in a short period of time with less energy consumption. Extracting and mining a large number of amino acid attributes of HA subtypes of influenza A virus through supervised algorithms represent a new avenue for

  15. MrSkn7 controls sporulation, cell wall integrity, autolysis, and virulence in Metarhizium robertsii.

    Science.gov (United States)

    Shang, Yanfang; Chen, Peilin; Chen, Yixiong; Lu, Yuzhen; Wang, Chengshu

    2015-04-01

    Two-component signaling pathways generally include sensor histidine kinases and response regulators. We identified an ortholog of the response regulator protein Skn7 in the insect-pathogenic fungus Metarhizium robertsii, which we named MrSkn7. Gene deletion assays and functional characterizations indicated that MrSkn7 functions as a transcription factor. The MrSkn7 null mutant of M. robertsii lost the ability to sporulate and had defects in cell wall biosynthesis but was not sensitive to oxidative and osmotic stresses compared to the wild type. However, the mutant was able to produce spores under salt stress. Insect bioassays using these spores showed that the virulence of the mutant was significantly impaired compared to that of the wild type due to the failures to form the infection structure appressorium and evade host immunity. In particular, deletion of MrSkn7 triggered cell autolysis with typical features such as cell vacuolization, downregulation of repressor genes, and upregulation of autolysis-related genes such as extracellular chitinases and proteases. Promoter binding assays confirmed that MrSkn7 could directly or indirectly control different putative target genes. Taken together, the results of this study help us understand the functional divergence of Skn7 orthologs as well as the mechanisms underlying the development and control of virulence in insect-pathogenic fungi. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Identification of genes preferentially expressed by highly virulent piscine Streptococcus agalactiae upon interaction with macrophages.

    Directory of Open Access Journals (Sweden)

    Chang-Ming Guo

    Full Text Available Streptococcus agalactiae, long recognized as a mammalian pathogen, is an emerging concern with regard to fish. In this study, we used a mouse model and in vitro cell infection to evaluate the pathogenetic characteristics of S. agalactiae GD201008-001, isolated from tilapia in China. This bacterium was found to be highly virulent and capable of inducing brain damage by migrating into the brain by crossing the blood-brain barrier (BBB. The phagocytosis assays indicated that this bacterium could be internalized by murine macrophages and survive intracellularly for more than 24 h, inducing injury to macrophages. Further, selective capture of transcribed sequences (SCOTS was used to investigate microbial gene expression associated with intracellular survival. This positive cDNA selection technique identified 60 distinct genes that could be characterized into 6 functional categories. More than 50% of the differentially expressed genes were involved in metabolic adaptation. Some genes have previously been described as associated with virulence in other bacteria, and four showed no significant similarities to any other previously described genes. This study constitutes the first step in further gene expression analyses that will lead to a better understanding of the molecular mechanisms used by S. agalactiae to survive in macrophages and to cross the BBB.

  17. Virulence-associated plasmids in Rhodococcus equi.

    Science.gov (United States)

    Takai, S; Watanabe, Y; Ikeda, T; Ozawa, T; Matsukura, S; Tamada, Y; Tsubaki, S; Sekizaki, T

    1993-01-01

    Twenty-three strains of Rhodococcus equi from independent clinical cases were analyzed for the presence of virulence plasmid DNA. Of the clinical isolates, 19 contained an 85-kb plasmid and the remaining 4 contained a 90-kb plasmid. All of the isolates expressed 15- to 17-kDa antigens and were virulent in mice. Restriction enzyme and Southern blot analyses showed large regions of DNA homology between the 85- and 90-kb virulence plasmids. It was concluded tentatively that there are at least two virulence plasmids in R. equi and that they have a common origin. Images PMID:8349748

  18. Candida albicans Secreted Aspartyl Proteinases in Virulence and Pathogenesis

    OpenAIRE

    Naglik, Julian R.; Challacombe, Stephen J.; Hube, Bernhard

    2003-01-01

    Candida albicans is the most common fungal pathogen of humans and has developed an extensive repertoire of putative virulence mechanisms that allows successful colonization and infection of the host under suitable predisposing conditions. Extracellular proteolytic activity plays a central role in Candida pathogenicity and is produced by a family of 10 secreted aspartyl proteinases (Sap proteins). Although the consequences of proteinase secretion during human infections is not precisely known,...

  19. The impact of transgenic mosquitoes on dengue virulence to humans and mosquitoes.

    Science.gov (United States)

    Medlock, Jan; Luz, Paula M; Struchiner, Claudio J; Galvani, Alison P

    2009-10-01

    Dengue is a major public health concern in the tropics and subtropics. Innovative transgenic strategies to render Aedes aegypti mosquitoes, the primary vector of dengue, incompetent for dengue transmission are under development. We modeled the evolutionary impact of different transgenic mosquito strategies on dengue-induced mortality, that is, dengue virulence, to both humans and mosquitoes. This model incorporates various evolutionary trade-offs in dengue virus epidemiological traits, for example, a trade-off between dengue transmission rate and its virulence to humans. Our results indicate that strategies that block transmission or reduce mosquito biting impose selection on dengue virulence in humans. This selection can be for either higher or lower virulence, depending on the interaction between the effect of the transgene and the trade-offs in epidemiological traits, highlighting the need for detailed quantitative data to understand more fully the impact of mosquito transgenesis on dengue virulence. Dengue virulence in mosquitoes can be selected on by transgenic strategies of blocking transmission, decreased mosquito biting, increased mosquito background mortality, and increased mosquito infection-induced mortality. Our results suggest that dengue control strategies that raise mosquito background mortality or mosquito infection-induced mortality pose less risk of causing increased virulence to humans than strategies that block transmission or reduce mosquito biting.

  20. Virulence and genetic diversity among isolates of Mycosphaerella fijiensis in two regions of Brazil.

    Science.gov (United States)

    Silva, G F; Santos, V S; Sousa, N R; Hanada, R E; Gasparotto, L

    2016-04-27

    Black sigatoka, caused by the fungus Mycosphaerella fijiensis (anamorphic stage: Paracercospora fijiensis), was first detected in Brazil in early 1998 in the Benjamin Constant and Tabatinga municipalities in the State of Amazonas, near to where the borders of Brazil, Colombia, and Peru converge. Understanding how cultivars react to the pathogen, and characterizing the genetic variability of isolates from two distant and distinct banana-producing regions, are important for determining the virulence of M. fijiensis. In the present study, the genetic diversity of 22 M. fijiensis isolates was assessed using simple sequence repeats (SSR) markers, and their virulence was determined following inoculation on three different banana tree cultivars. All 22 isolates caused symptoms of the disease in the Maçã and Prata Comum cultivars 45 days after inoculation, and at least two virulence groups were identified for the Maçã and Prata Comum cultivars. For the D'Angola cultivars, two virulence groups were observed only after 60 days post-inoculation, and three of the isolates were not virulent. Using SSR markers, the isolates from two different regions of Brazil were placed into two genetic groups, both genetically distant from the Mf 138 isolate collected in Leticia, Colombia. There was no evidence of correlation between the virulence groups and the genetic diversity groups. These results demonstrate variability in virulence between isolates as measured by the severity of black sigatoka in the analyzed cultivars.

  1. The Composition and Spatial Patterns of Bacterial Virulence Factors and Antibiotic Resistance Genes in 19 Wastewater Treatment Plants.

    Science.gov (United States)

    Zhang, Bing; Xia, Yu; Wen, Xianghua; Wang, Xiaohui; Yang, Yunfeng; Zhou, Jizhong; Zhang, Yu

    2016-01-01

    Bacterial pathogenicity and antibiotic resistance are of concern for environmental safety and public health. Accumulating evidence suggests that wastewater treatment plants (WWTPs) are as an important sink and source of pathogens and antibiotic resistance genes (ARGs). Virulence genes (encoding virulence factors) are good indicators for bacterial pathogenic potentials. To achieve a comprehensive understanding of bacterial pathogenic potentials and antibiotic resistance in WWTPs, bacterial virulence genes and ARGs in 19 WWTPs covering a majority of latitudinal zones of China were surveyed by using GeoChip 4.2. A total of 1610 genes covering 13 virulence factors and 1903 genes belonging to 11 ARG families were detected respectively. The bacterial virulence genes exhibited significant spatial distribution patterns of a latitudinal biodiversity gradient and a distance-decay relationship across China. Moreover, virulence genes tended to coexist with ARGs as shown by their strongly positive associations. In addition, key environmental factors shaping the overall virulence gene structure were identified. This study profiles the occurrence, composition and distribution of virulence genes and ARGs in current WWTPs in China, and uncovers spatial patterns and important environmental variables shaping their structure, which may provide the basis for further studies of bacterial virulence factors and antibiotic resistance in WWTPs.

  2. NEMS Oscillators as Sensors and Actuators: Understanding the Mechanical Properties of Nanoresonators and Their Applications for Molecular Sensing

    Data.gov (United States)

    National Aeronautics and Space Administration — Development of nanotechnology and enhancement of nanostructures for future applications requires a good understanding of a material's behavior at the nanoscale, as...

  3. Effect of Dietary Minerals on Virulence Attributes of Vibrio cholerae

    Directory of Open Access Journals (Sweden)

    Varunkumar Bhattaram

    2017-05-01

    Full Text Available Vibrio cholerae is a water-borne pathogen responsible for causing a toxin-mediated profuse diarrhea in humans, leading to severe dehydration and death in unattended patients. With increasing reports of antibiotic resistance in V. cholerae, there is a need for alternate interventional strategies for controlling cholera. A potential new strategy for treating infectious diseases involves targeting bacterial virulence rather than growth, where a pathogen’s specific mechanisms critical for causing infection in hosts are inhibited. Since bacterial motility, intestinal colonization and cholera toxin are critical components in V. cholerae pathogenesis, attenuating these virulence factors could potentially control cholera in humans. In this study, the efficacy of sub-inhibitory concentration (SIC, highest concentration not inhibiting bacterial growth of essential minerals, zinc (Zn, selenium (Se, and manganese (Mn in reducing V. cholerae motility and adhesion to intestinal epithelial cells (Caco-2, cholera toxin production, and toxin binding to the ganglioside receptor (GM1 was investigated. Additionally, V. cholerae attachment and toxin production in an ex vivo mouse intestine model was determined. Further, the effect of Zn, Se and Mn on V. cholerae virulence genes, ctxAB (toxin production, fliA (motility, tcpA (intestinal colonization, and toxR (master regulon was determined using real-time quantitative PCR. All three minerals significantly reduced V. cholerae motility, adhesion to Caco-2 cells, and cholera toxin production in vitro, and decreased adhesion and toxin production in mouse intestine ex vivo (P < 0.05. In addition, Zn, Se, and Mn down-regulated the transcription of virulence genes, ctxAB, fliA, and toxR. Results suggest that Zn, Se, and Mn could be potentially used to reduce V. cholerae virulence. However, in vivo studies in an animal model are necessary to validate these results.

  4. Complete genome sequence of hypervirulent and outbreak-associated Acinetobacter baumannii strain LAC-4: epidemiology, resistance genetic determinants and potential virulence factors

    Science.gov (United States)

    Ou, Hong-Yu; Kuang, Shan N.; He, Xinyi; Molgora, Brenda M.; Ewing, Peter J.; Deng, Zixin; Osby, Melanie; Chen, Wangxue; Xu, H. Howard

    2015-01-01

    Acinetobacter baumannii is an important human pathogen due to its multi-drug resistance. In this study, the genome of an ST10 outbreak A. baumannii isolate LAC-4 was completely sequenced to better understand its epidemiology, antibiotic resistance genetic determinants and potential virulence factors. Compared with 20 other complete genomes of A. baumannii, LAC-4 genome harbors at least 12 copies of five distinct insertion sequences. It contains 12 and 14 copies of two novel IS elements, ISAba25 and ISAba26, respectively. Additionally, three novel composite transposons were identified: Tn6250, Tn6251 and Tn6252, two of which contain resistance genes. The antibiotic resistance genetic determinants on the LAC-4 genome correlate well with observed antimicrobial susceptibility patterns. Moreover, twelve genomic islands (GI) were identified in LAC-4 genome. Among them, the 33.4-kb GI12 contains a large number of genes which constitute the K (capsule) locus. LAC-4 harbors several unique putative virulence factor loci. Furthermore, LAC-4 and all 19 other outbreak isolates were found to harbor a heme oxygenase gene (hemO)-containing gene cluster. The sequencing of the first complete genome of an ST10 A. baumannii clinical strain should accelerate our understanding of the epidemiology, mechanisms of resistance and virulence of A. baumannii. PMID:25728466

  5. Pleiotropic Regulation of Virulence Genes in Streptococcus mutans by the Conserved Small Protein SprV.

    Science.gov (United States)

    Shankar, Manoharan; Hossain, Mohammad S; Biswas, Indranil

    2017-04-15

    Streptococcus mutans , an oral pathogen associated with dental caries, colonizes tooth surfaces as polymicrobial biofilms known as dental plaque. S. mutans expresses several virulence factors that allow the organism to tolerate environmental fluctuations and compete with other microorganisms. We recently identified a small hypothetical protein (90 amino acids) essential for the normal growth of the bacterium. Inactivation of the gene, SMU.2137, encoding this protein caused a significant growth defect and loss of various virulence-associated functions. An S. mutans strain lacking this gene was more sensitive to acid, temperature, osmotic, oxidative, and DNA damage-inducing stresses. In addition, we observed an altered protein profile and defects in biofilm formation, bacteriocin production, and natural competence development, possibly due to the fitness defect associated with SMU.2137 deletion. Transcriptome sequencing revealed that nearly 20% of the S. mutans genes were differentially expressed upon SMU.2137 deletion, thereby suggesting a pleiotropic effect. Therefore, we have renamed this hitherto uncharacterized gene as sprV ( s treptococcal p leiotropic r egulator of v irulence). The transcript levels of several relevant genes in the sprV mutant corroborated the phenotypes observed upon sprV deletion. Owing to its highly conserved nature, inactivation of the sprV ortholog in Streptococcus gordonii also resulted in poor growth and defective UV tolerance and competence development as in the case of S. mutans Our experiments suggest that SprV is functionally distinct from its homologs identified by structure and sequence homology. Nonetheless, our current work is aimed at understanding the importance of SprV in the S. mutans biology. IMPORTANCE Streptococcus mutans employs several virulence factors and stress resistance mechanisms to colonize tooth surfaces and cause dental caries. Bacterial pathogenesis is generally controlled by regulators of fitness that are

  6. Anaerobiosis induced virulence of Salmonella typhi

    DEFF Research Database (Denmark)

    Kapoor, Sarika; Singh, R D; Sharma, P C

    2002-01-01

    , we examined the effect of anaerobiosis on the virulence of Salmonella Typhi, a Gram negative bacteria which invades through the gut mucosa and is responsible for typhoid fever. METHODS: Salmonella Typhi (ty2) was cultured in aerobic and anaerobic conditions to compare its virulence by rabbit ileal...

  7. Anaerobiosis induced virulence of Salmonella typhi

    DEFF Research Database (Denmark)

    Kapoor, Sarika; Singh, R D; Sharma, P C

    2002-01-01

    BACKGROUND & OBJECTIVES: Anaerobic conditions are frequently encountered by pathogens invading the gastrointestinal tract due to low/limiting oxygen conditions prevalent in the small intestine. This anaerobic stress has been suggested to enhance the virulence of gut pathogens. In the present stud...... dismutase (SOD) and catalase. INTERPRETATION & CONCLUSION: Our results suggest that exposure of S. Typhi to anaerobic conditions enhances its virulence....

  8. Evolution of viral virulence: empirical studies

    Science.gov (United States)

    Kurath, Gael; Wargo, Andrew R.

    2016-01-01

    The concept of virulence as a pathogen trait that can evolve in response to selection has led to a large body of virulence evolution theory developed in the 1980-1990s. Various aspects of this theory predict increased or decreased virulence in response to a complex array of selection pressures including mode of transmission, changes in host, mixed infection, vector-borne transmission, environmental changes, host vaccination, host resistance, and co-evolution of virus and host. A fundamental concept is prediction of trade-offs between the costs and benefits associated with higher virulence, leading to selection of optimal virulence levels. Through a combination of observational and experimental studies, including experimental evolution of viruses during serial passage, many of these predictions have now been explored in systems ranging from bacteriophage to viruses of plants, invertebrates, and vertebrate hosts. This chapter summarizes empirical studies of viral virulence evolution in numerous diverse systems, including the classic models myxomavirus in rabbits, Marek's disease virus in chickens, and HIV in humans. Collectively these studies support some aspects of virulence evolution theory, suggest modifications for other aspects, and show that predictions may apply in some virus:host interactions but not in others. Finally, we consider how virulence evolution theory applies to disease management in the field.

  9. Evolution, Clonality and Some Virulence Characteristics of ...

    African Journals Online (AJOL)

    All these changes together with other factors which may be genetic in origin have resulted in evolution, the existence of clones and the occurrence and acquisition of virulence characteristics of enterohaemorrhagic Escherichia coli. Keywords: Evolution, clonality, enterohaemorrhagic E. coli, virulence characteristics.

  10. Virulence, serotype and phylogenetic groups of diarrhoeagenic ...

    African Journals Online (AJOL)

    Dr DADIE Thomas

    2014-02-17

    Feb 17, 2014 ... The virulence, serotype and phylogenetic traits of diarrhoeagenic Escherichia coli were detected in 502 strains isolated during digestive infections. Molecular detection of the target virulence genes, rfb gene of operon O and phylogenetic grouping genes Chua, yjaA and TSPE4.C2 was performed.

  11. Modulation of the enterohemorrhagic E. coli virulence program through the human gastrointestinal tract

    Science.gov (United States)

    Barnett Foster, Debora

    2013-01-01

    Enteric pathogens must not only survive passage through the gastrointestinal tract but must also coordinate expression of virulence determinants in response to localized microenvironments with the host. Enterohemorrhagic Escherichia coli (EHEC), a serious food and waterborne human pathogen, is well equipped with an arsenal of molecular factors that allows it to survive passage through the gastrointestinal tract and successfully colonize the large intestine. This review will explore how EHEC responds to various environmental cues associated with particular microenvironments within the host and how it employs these cues to modulate virulence factor expression, with a view to developing a conceptual framework for understanding modulation of EHEC’s virulence program in response to the host. In vitro studies offer significant insights into the role of individual environmental cues but in vivo studies using animal models as well as data from natural infections will ultimately provide a more comprehensive picture of the highly regulated virulence program of this pathogen. PMID:23552827

  12. Quantum Interactive Learning Tutorial on the Double-Slit Experiment to Improve Student Understanding of Quantum Mechanics

    Science.gov (United States)

    Sayer, Ryan; Maries, Alexandru; Singh, Chandralekha

    2017-01-01

    Learning quantum mechanics is challenging, even for upper-level undergraduate and graduate students. Research-validated interactive tutorials that build on students' prior knowledge can be useful tools to enhance student learning. We have been investigating student difficulties with quantum mechanics pertaining to the double-slit experiment in…

  13. Virulence of Fusarium species to alfalfa seedlings

    Directory of Open Access Journals (Sweden)

    Krnjaja Vesna

    2005-01-01

    Full Text Available In in vitro conditions, virulence of 91 isolates of species Fusarium genus (F. oxysporum, F. solani, F. acuminatum, F. equiseti, F. arthrosporioides, F. prolifera- tum, F. avenaceum, F. semitectum, F. tricinctum, F. sporotrichioides and F. graminearum towards alfalfa seedlings was investigated. Isolates of investigated species originated from diseased alfalfa plants collected at four locations in Serbia based on symptoms of wilting caused by Fusarium and root rotting. Pathogenicity and virulence of investigated isolates of Fusarium spp. were determined by visual evaluation of inoculated seedlings of cultivar K28 in laboratory conditions. All isolated of investigated species had pathogenic effect on alfalfa seedlings which expressed symptoms such as necrosis of root, moist rotting and "melting of seedlings". Colour of necrotic root tissue varied from light brown, brown lipstick red to explicit black, depending on the Fusarium species. Strong virulence was established in 48 isolates, medium virulence in 31 and weak virulence in 12 isolates.

  14. Virulence of Fusarium species to alfalfa seedlings

    Directory of Open Access Journals (Sweden)

    Krnjaja Vesna

    2005-01-01

    Full Text Available In in vitro conditions, virulence of 91 isolates of species Fusarium genus (F. oxysporum, F. solani, F. acuminatum, F. equiseti, F. arthrosporioides, F. proliferatum, F. avenaceum, F. semitectum, F. tricinctum, F. sporotrichioides and F. graminearum towards alfalfa seedlings was investigated. Isolates of investigated species originated from diseased alfalfa plants collected on four locations in Serbia based on symptoms of wilting caused by fusarium and root rotting. Pathogenicity and virulence of investigated isolates of Fusarium spp. were determined by visual evaluation of inoculated seedlings of cultivars K28 in laboratory conditions. All isolated of investigated species had pathogenic effect on alfalfa seedlings, which expressed symptoms such as necrosis of root, moist rotting and "melting of seedlings". Colour of necrotic root tissue varied from light brown, brown, lipstick red to explicit black, depending on the Fusarium species. Strong virulence was established in 48 isolates, medium virulence in 31 and weak virulence in 12 isolates.

  15. Addressing the Don't Ask, Don't Tell Practice in Observational Studies: Using Interviews to Understand the Assignment Mechanism

    Science.gov (United States)

    Rickles, Jordan H.

    2010-01-01

    This paper illustrates how information collected through interviews can develop a richer understanding of the assignment mechanism, which can result in more plausible causal effect estimates from observational studies and provides a roadmap for sensitivity analysis. Focusing on the issue of assignment to algebra in 8th grade, the author shows how…

  16. Microgravity as a novel environmental signal affecting Salmonella enterica serovar Typhimurium virulence

    Science.gov (United States)

    Nickerson, C. A.; Ott, C. M.; Mister, S. J.; Morrow, B. J.; Burns-Keliher, L.; Pierson, D. L.

    2000-01-01

    The effects of spaceflight on the infectious disease process have only been studied at the level of the host immune response and indicate a blunting of the immune mechanism in humans and animals. Accordingly, it is necessary to assess potential changes in microbial virulence associated with spaceflight which may impact the probability of in-flight infectious disease. In this study, we investigated the effect of altered gravitational vectors on Salmonella virulence in mice. Salmonella enterica serovar Typhimurium grown under modeled microgravity (MMG) were more virulent and were recovered in higher numbers from the murine spleen and liver following oral infection compared to organisms grown under normal gravity. Furthermore, MMG-grown salmonellae were more resistant to acid stress and macrophage killing and exhibited significant differences in protein synthesis than did normal-gravity-grown cells. Our results indicate that the environment created by simulated microgravity represents a novel environmental regulatory factor of Salmonella virulence.

  17. Regulation of bacterial virulence gene expression by cell envelope stress responses.

    Science.gov (United States)

    Flores-Kim, Josué; Darwin, Andrew J

    2014-01-01

    The bacterial cytoplasm lies within a multilayered envelope that must be protected from internal and external hazards. This protection is provided by cell envelope stress responses (ESRs), which detect threats and reprogram gene expression to ensure survival. Pathogens frequently need these ESRs to survive inside the host, where their envelopes face dangerous environmental changes and attack from antimicrobial molecules. In addition, some virulence genes have become integrated into ESR regulons. This might be because these genes can protect the cell envelope from damage by host molecules, or it might help ESRs to reduce stress by moderating the assembly of virulence factors within the envelope. Alternatively, it could simply be a mechanism to coordinate the induction of virulence gene expression with entry into the host. Here, we briefly describe some of the bacterial ESRs, followed by examples where they control virulence gene expression in both Gram-negative and Gram-positive pathogens.

  18. Association between virulence and triazole tolerance in the phytopathogenic fungus Mycosphaerella graminicola.

    Directory of Open Access Journals (Sweden)

    Lina Yang

    Full Text Available Host resistance and synthetic antimicrobials such as fungicides are two of the main approaches used to control plant diseases in conventional agriculture. Although pathogens often evolve to overcome host resistance and antimicrobials, the majority of reports have involved qualitative host - pathogen interactions or antimicrobials targeting a single pathogen protein or metabolic pathway. Studies that consider jointly the evolution of virulence, defined as the degree of damage caused to a host by parasite infection, and antimicrobial resistance are rare. Here we compared virulence and fungicide tolerance in the fungal pathogen Mycosphaerella graminicola sampled from wheat fields across three continents and found a positive correlation between virulence and tolerance to a triazole fungicide. We also found that quantitative host resistance selected for higher pathogen virulence. The possible mechanisms responsible for these observations and their consequences for sustainable disease management are discussed.

  19. Stress corrosion cracking of alloy 600 in water at high temperature: contribution to a phenomenological approach to the understanding of mechanisms

    International Nuclear Information System (INIS)

    Abadie, Pascale

    1998-01-01

    This research thesis aims at being a contribution to the understanding of mechanisms of stress corrosion cracking of an alloy 600 in water at high temperature. More precisely, it aimed at determining, by using quantitative data characterizing cracking phenomenology, which mechanism(s) is (are) able to explain crack initiation and crack growth. These data concern quantitative characterization of crack initiation, of crack growth and of the influence of two cracking parameters (strain rate, medium hydrogen content). They have been obtained by quantifying cracking through the application of a morphological model. More precisely, these data are: evolution of crack density during a tensile test at slow rate, value of initial crack width with respect to grain boundary length, and relationship between crack density and medium hydrogen content. It appears that hydrogen absorption seems to be involved in the crack initiation mechanism. Crack growth mechanisms and crack growth rates are also discussed [fr

  20. Control of Candida albicans morphology and pathogenicity by post-transcriptional mechanisms

    Science.gov (United States)

    2017-01-01

    Candida albicans is a major human fungal pathogen responsible for both systemic and mucosal infections in a wide variety of immunocompromised individuals. Because the ability of C. albicans to undergo a reversible morphological transition from yeast to filaments is important for virulence, significant research efforts have focused on mechanisms that control this transition. While transcriptional and post-translational mechanisms have been well-studied, considerably less is known about the role of post-transcriptional mechanisms. However, in recent years several discoveries have begun to shed light on this important, but understudied, area. Here, I will review a variety of post-transcriptional mechanisms that have recently been shown to control C. albicans morphology, virulence and/or virulence-related processes, including those involving alternative transcript localization, mRNA stability and translation. I will also discuss the role that these mechanisms play in other pathogens as well as the potential they may hold to serve as targets for new antifungal strategies. Ultimately, gaining a better understanding of C. albicans post-transcriptional mechanisms will significantly improve our knowledge of how morphogenesis and virulence are controlled in fungal pathogens and open new avenues for the development of novel and more effective antifungals. PMID:27312239

  1. Understanding mechanisms of raveling to extend open graded friction course (OGFC) service life : Florida Department of Transportation Research.

    Science.gov (United States)

    2016-04-01

    Texas A&M Transportation Institute researchers, working with the Universidad de los Andes in Bogot, Colombia, studied the mechanisms of raveling in OGFCs through experimental analysis and finite element modeling.

  2. Regulation of bacterial virulence by Csr (Rsm) systems.

    Science.gov (United States)

    Vakulskas, Christopher A; Potts, Anastasia H; Babitzke, Paul; Ahmer, Brian M M; Romeo, Tony

    2015-06-01

    Most bacterial pathogens have the remarkable ability to flourish in the external environment and in specialized host niches. This ability requires their metabolism, physiology, and virulence factors to be responsive to changes in their surroundings. It is no surprise that the underlying genetic circuitry that supports this adaptability is multilayered and exceedingly complex. Studies over the past 2 decades have established that the CsrA/RsmA proteins, global regulators of posttranscriptional gene expression, play important roles in the expression of virulence factors of numerous proteobacterial pathogens. To accomplish these tasks, CsrA binds to the 5' untranslated and/or early coding regions of mRNAs and alters translation, mRNA turnover, and/or transcript elongation. CsrA activity is regulated by noncoding small RNAs (sRNAs) that contain multiple CsrA binding sites, which permit them to sequester multiple CsrA homodimers away from mRNA targets. Environmental cues sensed by two-component signal transduction systems and other regulatory factors govern the expression of the CsrA-binding sRNAs and, ultimately, the effects of CsrA on secretion systems, surface molecules and biofilm formation, quorum sensing, motility, pigmentation, siderophore production, and phagocytic avoidance. This review presents the workings of the Csr system, the paradigm shift that it generated for understanding posttranscriptional regulation, and its roles in virulence networks of animal and plant pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. An investigation of virulence factors of Legionella pneumophila environmental isolates

    Directory of Open Access Journals (Sweden)

    Elif Özlem Arslan-Aydoğdu

    Full Text Available ABSTRACT Nine Legionella pneumophila strains isolated from cooling towers and a standard strain (L. pneumophila serogroup 1, ATCC 33152, Philadelphia 1 were analyzed and compared in terms of motility, flagella structure, ability to form biofilms, enzymatic activities (hemolysin, nucleases, protease, phospholipase A, phospholipase C, acid phosphatase, alkaline phosphatase and lipase, hemagglutination capabilities, and pathogenicity in various host cells (Acanthamoeba castellanii ATCC 30234, mouse peritoneal macrophages and human peripheral monocytes. All the isolates of bacteria appeared to be motile and polar-flagellated and possessed the type-IV fimbria. Upon the evaluation of virulence factors, isolate 4 was found to be the most pathogenic strain, while 6 out of the 9 isolates (the isolates 1, 2, 3, 4, 5, and 7 were more virulent than the ATCC 33152 strain. The different bacterial strains exhibited differences in properties such as adhesion, penetration and reproduction in the hosts, and preferred host type. To our knowledge, this is the first study to compare the virulence of environmental L. pneumophila strains isolated in Turkey, and it provides important information relevant for understanding the epidemiology of L. pneumophila.

  4. Molecular mechanisms of Escherichia coli pathogenicity.

    Science.gov (United States)

    Croxen, Matthew A; Finlay, B Brett

    2010-01-01

    Escherichia coli is a remarkable and diverse organism. This normally harmless commensal needs only to acquire a combination of mobile genetic elements to become a highly adapted pathogen capable of causing a range of diseases, from gastroenteritis to extraintestinal infections of the urinary tract, bloodstream and central nervous system. The worldwide burden of these diseases is staggering, with hundreds of millions of people affected annually. Eight E. coli pathovars have been well characterized, and each uses a large arsenal of virulence factors to subvert host cellular functions to potentiate its virulence. In this Review, we focus on the recent advances in our understanding of the different pathogenic mechanisms that are used by various E. coli pathovars and how they cause disease in humans.

  5. Mucosal fluid glycoprotein DMBT1 suppresses twitching motility and virulence of the opportunistic pathogen Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Jianfang Li

    2017-05-01

    Full Text Available It is generally thought that mucosal fluids protect underlying epithelial surfaces against opportunistic infection via their antimicrobial activity. However, our published data show that human tear fluid can protect against the major opportunistic pathogen Pseudomonas aeruginosa independently of bacteriostatic activity. Here, we explored the mechanisms for tear protection, focusing on impacts of tear fluid on bacterial virulence factor expression. Results showed that tear fluid suppressed twitching motility, a type of surface-associated movement conferred by pili. Previously, we showed that twitching is critical for P. aeruginosa traversal of corneal epithelia, exit from epithelial cells after internalization, and corneal virulence. Inhibition of twitching by tear fluid was dose-dependent with dilutions to 6.25% retaining activity. Purified lactoferrin, lysozyme, and contrived tears containing these, and many other, tear components lacked the activity. Systematic protein fractionation, mass spectrometry, and immunoprecipitation identified the glycoprotein DMBT1 (Deleted in Malignant Brain Tumors 1 in tear fluid as required. DMBT1 purified from human saliva also inhibited twitching, as well as P. aeruginosa traversal of human corneal epithelial cells in vitro, and reduced disease pathology in a murine model of corneal infection. DMBT1 did not affect PilA expression, nor bacterial intracellular cyclicAMP levels, and suppressed twitching motility of P. aeruginosa chemotaxis mutants (chpB, pilK, and an adenylate cyclase mutant (cyaB. However, dot-immunoblot assays showed purified DMBT1 binding of pili extracted from PAO1 suggesting that twitching inhibition may involve a direct interaction with pili. The latter could affect extension or retraction of pili, their interactions with biotic or abiotic surfaces, or cause their aggregation. Together, the data suggest that DMBT1 inhibition of twitching motility contributes to the mechanisms by which

  6. Understanding and modelling of the aniso-thermal cyclic mechanical behaviour of the AISI 316LN austenitic stainless steel

    International Nuclear Information System (INIS)

    Gentet, D.

    2009-11-01

    The main subject of this report consists in proposing a mechanical model of the viscoplastic behaviour of an austenitic stainless steel under isothermal and aniso-thermal low cycle fatigue loadings at high temperatures (550-900 K). In this domain, numerous phenomena linked to dynamic strain ageing (DSA) and to dipolar dislocation structure formation may appear. Isothermal and aniso-thermal low cycle fatigue tension-compression tests were performed in order to verify some aspects about the effect of temperature on the mechanical behaviour. The study of the hysteresis loops and the observation of dislocation structures carried on transmission electron microscopy establish two different DSA mechanisms during isothermal tests. The effect of temperature history is shown for for particular temperature sequences. It is demonstrated that the stress amplitude increase when the sample is submitted to cycles at 'high temperature' is linked to the second mechanism of DSA. It comes from the increase of short range interaction between dislocations (chromium segregation), but it is also the consequence of the lack of dipolar structure annihilation at low temperature. From the experimental analysis of DSA mechanisms and dipolar restoration, a macroscopic aniso-thermal model is developed using physical internal variables (densities of dislocations). The equations of a polycrystalline model are rewritten with the aim of getting a simple multi-scale approach which can be used on finite elements analysis software. Between 550 and 873 K, the simulation results are in good accordance with the macroscopic and microscopic observations of low cycle fatigue, relaxation, and 2D-ratchetting tests. (author)

  7. Differential mechanisms of action understanding in left and right handed subjects: the role of perspective and handedness.

    Science.gov (United States)

    Kelly, Rachel L; Wheaton, Lewis A

    2013-01-01

    The ability to comprehend outcomes of skilled action is important for understanding the world around us. Prior studies have evaluated the perspective an action is performed in, but few have evaluated how handedness of the actor and the observer interact with action perspective. Understanding handedness affords the opportunity to identify the role of mirroring and matched limb action encoding, which may display unique strategies of action understanding. Right and left-handed subjects were presented with images of tools from egocentric or allocentric perspectives performing movements by either a left or right hand. Subjects had to judge the outcome of the task, and accuracy and latency were evaluated. Our hypothesis was that both left and right-handed subjects would predict action best from an egocentric perspective. In allocentric perspectives, identification of action outcomes would occur best in the mirror-matched dominant limb for all subjects. Results showed there was a significant effect on accuracy and latency with respect to perspective for both right and left-handed subjects. The highest accuracies and fastest latencies were found in the egocentric perspective. Handedness of subject also showed an effect on accuracy, where right-handed subjects were significantly more accurate in the task than left-handed subjects. An interaction effect revealed that left-handed subjects were less accurate at judging images from an allocentric viewpoint compared to all other conditions. These findings suggest that action outcomes are best facilitated in an internal perspective, regardless of the hand being used. The decreased accuracy for left-handed subjects on allocentric images could be due to asymmetrical lateralization of encoding action and motoric dominance, which may interfere with translating allocentric limb action outcomes. Further neurophysiological studies will help us understand the specific processes of how left and right-handed subjects may encode actions.

  8. Differential mechanisms of action understanding in left and right handed subjects: the role of perspective and handedness

    Directory of Open Access Journals (Sweden)

    Rachel Louise Kelly

    2013-12-01

    Full Text Available The ability to comprehend outcomes of skilled action is important for understanding the world around us. Prior studies have evaluated the perspective an action is performed in, but few have evaluated how handedness of the actor and the observer interact with action perspective. Understanding handedness affords the opportunity to identify the role of mirroring and matched limb action encoding, which may display unique strategies of action understanding. Right and left-handed subjects were presented with images of tools from egocentric or allocentric perspectives performing movements by either a left or right hand. Subjects had to judge the outcome of the task, and accuracy and latency were evaluated. Our hypothesis was that both left and right-handed subjects would predict action best from an egocentric perspective. In allocentric perspectives, identification of action outcomes would occur best in the mirror matched dominant limb for all subjects. Results showed there was a significant effect on accuracy and latency with respect to perspective for both right and left-handed subjects. The highest accuracies and fastest latencies were found in the egocentric perspective. Handedness of subject also showed an effect on accuracy, where right-handed subjects were significantly more accurate in the task than left-handed subjects. An interaction effect revealed that left-handed subjects were less accurate at judging images from an allocentric viewpoint compared to all other conditions. These findings suggest that action outcomes are best facilitated in an internal perspective, regardless of the hand being used. The decreased accuracy for left-handed subjects on allocentric images could be due to asymmetrical lateralization of encoding action and motoric dominance, which may interfere with translating allocentric limb action outcomes. Further neurophysiological studies will help us understand the specific processes of how left and right-handed subjects

  9. Assessment of Listeria monocytogenes virulence in the Galleria mellonella insect larvae model.

    Science.gov (United States)

    Rakic Martinez, Mira; Wiedmann, Martin; Ferguson, Martine; Datta, Atin R

    2017-01-01

    Several animal models have been used to understand the molecular basis of the pathogenicity, infectious dose and strain to strain variation of Listeria monocytogenes. The greater wax worm Galleria mellonella, as an alternative model, provides some useful advantages not available with other models and has already been described as suitable for the virulence assessment of various pathogens including L. monocytogenes. The objectives of this study are: 1) confirming the usefulness of this model with a wide panel of Listeria spp. including non-pathogenic L. innocua, L. seeligeri, L. welshimeri and animal pathogen L. ivanovii; 2) assessment of virulence of several isogenic in-frame deletion mutants in virulence and stress related genes of L. monocytogenes and 3) virulence assessment of paired food and clinical isolates of L. monocytogenes from 14 major listeriosis outbreaks occurred worldwide between 1980 and 2015. Larvae injected with different concentrations of Listeria were incubated at 37°C and monitored over seven days for time needed to kill 50% of larvae (LT50) and to determine change of bacterial population in G. mellonella, 2 and 24 hours post-inoculation. Non-pathogenic members of Listeria and L. ivanovii showed significantly (P < 0.05) higher LT50 (lower virulence) than the wild type L. monocytogenes strains. Isogenic mutants of L. monocytogenes with the deletions in prfA, plcA, hly, actA and virR genes, also showed significantly (P < 0.05) higher LT50 than the wild type strain at the inoculum of 106CFU/larva. Food isolates had significantly (P < 0.05) lower virulence than the paired clinical isolates, at all three inoculum concentrations. L. monocytogenes strains related to non-invasive (gastroenteritis) outbreaks of listeriosis showed significantly (P < 0.05) lower virulence than isolates of the same serotype obtained from outbreaks with invasive symptoms. The difference, however, was dose and strain- dependent. No significant differences in virulence were

  10. Bacterial human virulence genes across diverse habitats as assessed by in silico analysis of environmental metagenomes

    Directory of Open Access Journals (Sweden)

    Ditte Andreasen Søborg

    2016-11-01

    Full Text Available The occurrence and distribution of clinically relevant bacterial virulence genes across natural (non-human environments is not well understood. We aimed to investigate the occurrence of homologues to bacterial human virulence genes in a variety of ecological niches to better understand the role of natural environments in the evolution of bacterial virulence. Twentyfour bacterial virulence genes were analyzed in 47 diverse environmental metagenomic datasets, representing various soils, seawater, freshwater, marine sediments, hot springs, the deep-sea, hypersaline mats, microbialites, gutless worms and glacial ice. Homologues to 17 bacterial human virulence genes, involved in urinary tract infections, gastrointestinal diseases, skin diseases, and wound and systemic infections, showed global ubiquity. A principal component analysis did not demonstrate clear trends across the metagenomes with respect to occurrence and frequency of observed gene homologues. Full-length (>95% homologues of several virulence genes were identified, and translated sequences of the environmental and clinical genes were up to 50-100% identical. Furthermore, phylogenetic analyses indicated deep branching positions of some of the environmental gene homologues, suggesting that they represent ancient lineages in the phylogeny of the clinical genes. Fifteen virulence gene homologues were detected in metagenomes based on metatranscriptomic data, providing evidence of environmental expression. The ubiquitous presence and transcription of the virulence gene homologues in non-human environments point to an important ecological role of the genes for the activity and survival of environmental bacteria. Furthermore, the high degree of sequence conservation between several of the environmental and clinical genes suggests common ancestral origins.

  11. A functional gene array for detection of bacterial virulence elements

    Energy Technology Data Exchange (ETDEWEB)

    Jaing, C

    2007-11-01

    We report our development of the first of a series of microarrays designed to detect pathogens with known mechanisms of virulence and antibiotic resistance. By targeting virulence gene families as well as genes unique to specific biothreat agents, these arrays will provide important data about the pathogenic potential and drug resistance profiles of unknown organisms in environmental samples. To validate our approach, we developed a first generation array targeting genes from Escherichia coli strains K12 and CFT073, Enterococcus faecalis and Staphylococcus aureus. We determined optimal probe design parameters for microorganism detection and discrimination, measured the required target concentration, and assessed tolerance for mismatches between probe and target sequences. Mismatch tolerance is a priority for this application, due to DNA sequence variability among members of gene families. Arrays were created using the NimbleGen Maskless Array Synthesizer at Lawrence Livermore National Laboratory. Purified genomic DNA from combinations of one or more of the four target organisms, pure cultures of four related organisms, and environmental aerosol samples with spiked-in genomic DNA were hybridized to the arrays. Based on the success of this prototype, we plan to design further arrays in this series, with the goal of detecting all known virulence and antibiotic resistance gene families in a greatly expanded set of organisms.

  12. Phosphate Acquisition and Virulence in Human Fungal Pathogens.

    Science.gov (United States)

    Ikeh, Mélanie; Ahmed, Yasmin; Quinn, Janet

    2017-08-22

    The ability of pathogenic fungi to acquire essential macro and micronutrients during infection is a well-established virulence trait. Recent studies in the major human fungal pathogens Candida albicans and Cryptococcus neoformans have revealed that acquisition of the essential macronutrient, phosphate, is essential for virulence. The phosphate sensing and acquisition pathway in fungi, known as the PHO pathway, has been extensively characterized in the model yeast Saccharomyces cerevisiae . In this review, we highlight recent advances in phosphate sensing and signaling mechanisms, and use the S. cerevisiae PHO pathway as a platform from which to compare the phosphate acquisition and storage strategies employed by several human pathogenic fungi. We also explore the multi-layered roles of phosphate acquisition in promoting fungal stress resistance to pH, cationic, and oxidative stresses, and describe emerging roles for the phosphate storage molecule polyphosphate (polyP). Finally, we summarize the recent studies supporting the necessity of phosphate acquisition in mediating the virulence of human fungal pathogens, highlighting the concept that this requirement is intimately linked to promoting resistance to host-imposed stresses.

  13. Genome analysis and in vivo virulence of porcine extraintestinal pathogenic Escherichia coli strain PCN033.

    Science.gov (United States)

    Liu, Canying; Zheng, Huajun; Yang, Minjun; Xu, Zhuofei; Wang, Xiangru; Wei, Liuya; Tang, Biao; Liu, Feng; Zhang, Yanyan; Ding, Yi; Tang, Xibiao; Wu, Bin; Johnson, Timothy J; Chen, Huanchun; Tan, Chen

    2015-09-21

    Strains of extraintestinal pathogenic Escherichia coli (ExPEC) can invade and colonize extraintestinal sites and cause a wide range of infections. Genomic analysis of ExPEC has mainly focused on isolates of human and avian origins, with porcine ExPEC isolates yet to be sequenced. To better understand the genomic attributes underlying the pathogenicity of porcine ExPEC, we isolated two E. coli strains PCN033 and PCN061 from pigs, assessed their in vivo virulence, and completed and compared their genomes. Animal experiments demonstrated that strain PCN033, but not PCN061, was pathogenic in a pig model. The chromosome of PCN033 was 384 kb larger than that of PCN061. Among the PCN033-specific sequences, genes encoding adhesins, unique lipopolysaccharide, unique capsular polysaccharide, iron acquisition and transport systems, and metabolism were identified. Additionally, a large plasmid PCN033p3 harboring many typical ExPEC virulence factors was identified in PCN033. Based on the genetic variation between PCN033 and PCN061, corresponding phenotypic differences in flagellum-dependent swarming motility and metabolism were verified. Furthermore, the comparative genomic analyses showed that the PCN033 genome shared many similarities with genomic sequences of human ExPEC strains. Additionally, comparison of PCN033 genome with other nine characteristic E. coli genomes revealed 425 PCN033-special coding sequences. Genes of this subset included those encoding type I restriction-modification (R-M) system, type VI secretion system (T6SS) and membrane-associated proteins. The genetic and phenotypic differences between PCN033 and PCN061 could partially explain their differences in virulence, and also provide insight towards the molecular mechanisms of porcine ExPEC infections. Additionally, the similarities between the genomes of PCN033 and human ExPEC strains suggest that some connections between porcine and human ExPEC strains exist. The first completed genomic sequence for

  14. Bicarbonate increases binding affinity of Vibrio cholerae ToxT to virulence gene promoters.

    Science.gov (United States)

    Thomson, Joshua J; Withey, Jeffrey H

    2014-11-01

    The major Vibrio cholerae virulence gene transcription activator, ToxT, is responsible for the production of the diarrhea-inducing cholera toxin (CT) and the major colonization factor, toxin coregulated pilus (TCP). In addition to the two primary virulence factors mentioned, ToxT is responsible for the activation of accessory virulence genes, such as aldA, tagA, acfA, acfD, tcpI, and tarAB. ToxT activity is negatively modulated by bile and unsaturated fatty acids found in the upper small intestine. Conversely, previous work identified another intestinal signal, bicarbonate, which enhances the ability of ToxT to activate production of CT and TCP. The work presented here further elucidates the mechanism for the enhancement of ToxT activity by bicarbonate. Bicarbonate was found to increase the activation of ToxT-dependent accessory virulence promoters in addition to those that produce CT and TCP. Bicarbonate is taken up into the V. cholerae cell, where it positively affects ToxT activity by increasing DNA binding affinity for the virulence gene promoters that ToxT activates regardless of toxbox configuration. The increase in ToxT binding affinity in the presence of bicarbonate explains the elevated level of virulence gene transcription. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  15. Virulence and genomic feature of multidrug resistant Campylobacter jejuni isolated from broiler chicken

    Directory of Open Access Journals (Sweden)

    Haihong Hao

    2016-10-01

    Full Text Available The aim of this study was to reveal the molecular mechanism involved in multidrug resistance and virulence of Campylobacter jejuni isolated from broiler chickens. The virulence of six multidrug resistant C. jejuni was determined by in vitro and in vivo methods. The de novo whole genome sequencing technology and molecular biology methods were used to analyze the genomic features associated with the multidrug resistance and virulence of a selected isolate (C. jejuni 1655. The comparative genomic analyses revealed a large number of single nucleotide polymorphisms, deletions, rearrangements, and inversions in C. jejuni 1655 compared to reference C. jejuni genomes. The co-emergence of Thr-86-Ile mutation in gyrA gene, A2075G mutation in 23S rRNA gene, tetO, aphA and aadE genes and pTet plasmid in C. jejuni 1655 contributed its multidrug resistance to fluoroquinolones, macrolides, tetracycline and aminoglycosides. The combination of multiple virulence genes may work together to confer the relative higher virulence in C. jejuni 1655. The co-existence of mobile gene elements (e.g. pTet and CRISPR-Cas system in C. jejuni 1655 may play an important role in the gene transfer and immune defense. The present study provides basic information of phenotypic and genomic features of C. jejuni 1655, a strain recently isolated from a chicken displaying multidrug resistance and relatively high level of virulence.

  16. An approach to understanding tribological behaviour of dental composites through volumetric wear loss and wear mechanism determination; beyond material ranking.

    Science.gov (United States)

    Altaie, Asmaa; Bubb, Nigel L; Franklin, Paul; Dowling, Adam H; Fleming, Garry J P; Wood, David J

    2017-04-01

    To investigate the fundamental wear mechanisms of six resin-based composite (RBC) formulations during short-term in vitro wear testing. RBC materials were condensed into rectangular bar-shaped specimens and light irradiated using the ISO 4049 specimen manufacture and irradiation protocol. Wear testing (n=10 specimens for each RBC) was performed on a modified pin-on-plate wear test apparatus and wear facets were analysed for wear volume loss using a white light profilometer. The wear tested RBC specimens and their corresponding antagonists were analysed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), respectively to determine the wear mechanism. Data generated using the profilometer showed variations in the mean total wear volume (mm 3 ) between the RBCs tested (ptribology of the system rather than relying on a simple wear ranking for the RBC materials as is routinely the case in dental research studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Hydrolytic enzymes as virulence factors of Candida albicans.

    Science.gov (United States)

    Schaller, Martin; Borelli, Claudia; Korting, Hans C; Hube, Bernhard

    2005-11-01

    Candida albicans is a facultative pathogenic micro-organism that has developed several virulence traits enabling invasion of host tissues and avoidance of host defence mechanisms. Virulence factors that contribute to this process are the hydrolytic enzymes. Most of them are extracellularly secreted by the fungus. The most discussed hydrolytic enzymes produced by C. albicans are secreted aspartic proteinases (Saps). The role of these Saps for C. albicans infections was carefully evaluated in numerous studies, whereas only little is known about the physiological role of the secreted phospholipases (PL) and almost nothing about the involvement of lipases (Lip) in virulence. They may play an important role in the pathogenicity of candidosis and their hydrolytic activity probably has a number of possible functions in addition to the simple role of digesting molecules for nutrition. Saps as the best-studied member of this group of hydrolytic enzymes contribute to host tissue invasion by digesting or destroying cell membranes and by degrading host surface molecules. There is also some evidence that hydrolytic enzymes are able to attack cells and molecules of the host immune system to avoid or resist antimicrobial activity. High hydrolytic activity with broad substrate specificity has been found in several Candida species, most notably in C. albicans. This activity is attributed to multigene families with at least 10 members for Saps and Lips and several members for PL B. Distinct members of these gene families are differentially regulated in various Candida infections. In future, prevention and control of Candida infections might be achieved by pharmacological or immunological tools specifically modulated to inhibit virulence factors, e.g. the family of Saps.

  18. Phosphotyrosine-Mediated Regulation of Enterohemorrhagic Escherichia coli Virulence

    Science.gov (United States)

    Robertson, Colin D.; Hazen, Tracy H.; Kaper, James B.

    2018-01-01

    ABSTRACT Enteric pathogens with low infectious doses rely on the ability to orchestrate the expression of virulence and metabolism-associated genes in response to environmental cues for successful infection. Accordingly, the human pathogen enterohemorrhagic Escherichia coli (EHEC) employs a complex multifaceted regulatory network to link the expression of type III secretion system (T3SS) components to nutrient availability. While phosphorylation of histidine and aspartate residues on two-component system response regulators is recognized as an integral part of bacterial signaling, the involvement of phosphotyrosine-mediated control is minimally explored in Gram-negative pathogens. Our recent phosphotyrosine profiling study of E. coli identified 342 phosphorylated proteins, indicating that phosphotyrosine modifications in bacteria are more prevalent than previously anticipated. The present study demonstrates that tyrosine phosphorylation of a metabolite-responsive LacI/GalR family regulator, Cra, negatively affects T3SS expression under glycolytic conditions that are typical for the colonic lumen environment where production of the T3SS is unnecessary. Our data suggest that Cra phosphorylation affects T3SS expression by modulating the expression of ler, which encodes the major activator of EHEC virulence gene expression. Phosphorylation of the Cra Y47 residue diminishes DNA binding to fine-tune the expression of virulence-associated genes, including those of the locus of enterocyte effacement pathogenicity island that encode the T3SS, and thereby negatively affects the formation of attaching and effacing lesions. Our data indicate that tyrosine phosphorylation provides an additional mechanism to control the DNA binding of Cra and other LacI/GalR family regulators, including LacI and PurR. This study describes an initial effort to unravel the role of global phosphotyrosine signaling in the control of EHEC virulence potential. PMID:29487233

  19. Phosphotyrosine-Mediated Regulation of Enterohemorrhagic Escherichia coli Virulence

    Directory of Open Access Journals (Sweden)

    Colin D. Robertson

    2018-02-01

    Full Text Available Enteric pathogens with low infectious doses rely on the ability to orchestrate the expression of virulence and metabolism-associated genes in response to environmental cues for successful infection. Accordingly, the human pathogen enterohemorrhagic Escherichia coli (EHEC employs a complex multifaceted regulatory network to link the expression of type III secretion system (T3SS components to nutrient availability. While phosphorylation of histidine and aspartate residues on two-component system response regulators is recognized as an integral part of bacterial signaling, the involvement of phosphotyrosine-mediated control is minimally explored in Gram-negative pathogens. Our recent phosphotyrosine profiling study of E. coli identified 342 phosphorylated proteins, indicating that phosphotyrosine modifications in bacteria are more prevalent than previously anticipated. The present study demonstrates that tyrosine phosphorylation of a metabolite-responsive LacI/GalR family regulator, Cra, negatively affects T3SS expression under glycolytic conditions that are typical for the colonic lumen environment where production of the T3SS is unnecessary. Our data suggest that Cra phosphorylation affects T3SS expression by modulating the expression of ler, which encodes the major activator of EHEC virulence gene expression. Phosphorylation of the Cra Y47 residue diminishes DNA binding to fine-tune the expression of virulence-associated genes, including those of the locus of enterocyte effacement pathogenicity island that encode the T3SS, and thereby negatively affects the formation of attaching and effacing lesions. Our data indicate that tyrosine phosphorylation provides an additional mechanism to control the DNA binding of Cra and other LacI/GalR family regulators, including LacI and PurR. This study describes an initial effort to unravel the role of global phosphotyrosine signaling in the control of EHEC virulence potential.

  20. Understanding Demographic and Behavioral Mechanisms that Guide Responses of Neotropical Migratory Birds to Urbanization: a Simulation Approach

    Directory of Open Access Journals (Sweden)

    Daniel P. Shustack

    2008-12-01

    Full Text Available Although studies often report that densities of many forest birds are negatively related to urbanization, the mechanisms guiding this pattern are poorly understood. Our objective was to use a population simulation to examine the relative influence of six demographic and behavioral processes on patterns of avian abundance in urbanizing landscapes. We constructed an individual-based population simulation model representing the annual cycle of a Neotropical migratory songbird. Each simulation was performed under two landscape scenarios. The first scenario had similar proportions of high- and low-quality habitat across the urban to rural gradient. Under the first scenario, avian density was negatively related to urbanization only when rural habitats were perceived to be of higher quality than they actually were. The second landscape scenario had declining proportions of high-quality habitat as urbanization increased. Under the second scenario, each mechanism generated a negative relationship between density and urbanization. The strongest effect on density resulted when birds preferentially selected habitats in landscapes from which they fledged or were constrained from dispersing. The next strongest patterns occurred when birds directly evaluated habitat quality and accurately selected the highest-quality available territories. When birds selected habitats based on the presence of conspecifics, the density-urbanization relationship was only one-third the strength of other habitat selection mechanisms and only occurred under certain levels of population survival. Although differences in adult or nest survival in the face of random habitat selection still elicited reduced densities in urban landscapes, the relationships between urbanization and density were weaker than those produced by the conspecific attraction mechanism. Results from our study identify key predictions and areas for future research, including assessing habitat quality in urban and

  1. Final Report: Tolerance to phytoalexins and its implication for the evolution of host specific virulence traits, July 1, 1996 - June 30, 1998

    Energy Technology Data Exchange (ETDEWEB)

    VanEtten, Hans

    1998-06-30

    This research focused on determining the importance of non-degradative tolerance (NDT) to pisatin for the virulence of N. haematococca MPVI on pea. An attempt was also made to determine the importance of pda for virulence of F. oxysporum f.sp.pisi,A. pisi and M. pinodes. This research aided in refining the author's understanding of those characteristics of the pda genes that contribute to virulence and the role of non-degradative tolerance in the virulence of other pea pathogens.

  2. Removal of acrylic coatings from works of art by means of nanofluids: understanding the mechanism at the nanoscale

    Science.gov (United States)

    Baglioni, Michele; Rengstl, Doris; Berti, Debora; Bonini, Massimo; Giorgi, Rodorico; Baglioni, Piero

    2010-09-01

    Conservation of works of art often involves the inappropriate application of synthetic polymers. We have proposed the use of alternative methodologies for conservation and formulated innovative cleaning nanostructured systems to remove previously applied polymer films and grime from painted surfaces. In particular, a novel ``micellar system'' composed of water, SDS, 1-pentanol, ethyl acetate and propylene carbonate was recently formulated and successfully used to remove acrylic and vinyl/acrylic copolymers from Mesoamerican wall paintings in the archeological site of Cholula, Mexico. This contribution reports on the mechanism of the interaction process that takes place between the nanostructured fluid and the polymer coating at the nanoscale. The structural properties of the ``micellar solution'' and of the polymer film are investigated before, during and after the interaction process using several surface and solution techniques. Rather than a classical detergency mechanism, we demonstrate that micelles act as solvent containers and interact with the polymer film leading to its swelling and detachment from the surface and to its segregation in a liquid droplet, which phase-separates from the aqueous bulk. After the removal process the micelles become smaller in size and undergo a structural re-arrangement due to the depletion of the organic solvents. These findings can be framed in an interaction mechanism which describes the removal process, opening up new perspectives in the design and formulation of new cleaning systems specifically tailored for intervention on particular conservation issues.

  3. IscR Is Essential for Yersinia pseudotuberculosis Type III Secretion and Virulence

    Science.gov (United States)

    Miller, Halie K.; Kwuan, Laura; Schwiesow, Leah; Bernick, David L.; Mettert, Erin; Ramirez, Hector A.; Ragle, James M.; Chan, Patricia P.; Kiley, Patricia J.; Lowe, Todd M.; Auerbuch, Victoria

    2014-01-01

    Type III secretion systems (T3SS) are essential for virulence in dozens of pathogens, but are not required for growth outside the host. Therefore, the T3SS of many bacterial species are under tight regulatory control. To increase our understanding of the molecular mechanisms behind T3SS regulation, we performed a transposon screen to identify genes important for T3SS function in the food-borne pathogen Yersinia pseudotuberculosis. We identified two unique transposon insertions in YPTB2860, a gene that displays 79% identity with the E. coli iron-sulfur cluster regulator, IscR. A Y. pseudotuberculosis iscR in-frame deletion mutant (ΔiscR) was deficient in secretion of Ysc T3SS effector proteins and in targeting macrophages through the T3SS. To determine the mechanism behind IscR control of the Ysc T3SS, we carried out transcriptome and bioinformatic analysis to identify Y. pseudotuberculosis genes regulated by IscR. We discovered a putative IscR binding motif upstream of the Y. pseudotuberculosis yscW-lcrF operon. As LcrF controls transcription of a number of critical T3SS genes in Yersinia, we hypothesized that Yersinia IscR may control the Ysc T3SS through LcrF. Indeed, purified IscR bound to the identified yscW-lcrF promoter motif and mRNA levels of lcrF and 24 other T3SS genes were reduced in Y. pseudotuberculosis in the absence of IscR. Importantly, mice orally infected with the Y. pseudotuberculosis ΔiscR mutant displayed decreased bacterial burden in Peyer's patches, mesenteric lymph nodes, spleens, and livers, indicating an essential role for IscR in Y. pseudotuberculosis virulence. This study presents the first characterization of Yersinia IscR and provides evidence that IscR is critical for virulence and type III secretion through direct regulation of the T3SS master regulator, LcrF. PMID:24945271

  4. IscR is essential for yersinia pseudotuberculosis type III secretion and virulence.

    Directory of Open Access Journals (Sweden)

    Halie K Miller

    2014-06-01

    Full Text Available Type III secretion systems (T3SS are essential for virulence in dozens of pathogens, but are not required for growth outside the host. Therefore, the T3SS of many bacterial species are under tight regulatory control. To increase our understanding of the molecular mechanisms behind T3SS regulation, we performed a transposon screen to identify genes important for T3SS function in the food-borne pathogen Yersinia pseudotuberculosis. We identified two unique transposon insertions in YPTB2860, a gene that displays 79% identity with the E. coli iron-sulfur cluster regulator, IscR. A Y. pseudotuberculosis iscR in-frame deletion mutant (ΔiscR was deficient in secretion of Ysc T3SS effector proteins and in targeting macrophages through the T3SS. To determine the mechanism behind IscR control of the Ysc T3SS, we carried out transcriptome and bioinformatic analysis to identify Y. pseudotuberculosis genes regulated by IscR. We discovered a putative IscR binding motif upstream of the Y. pseudotuberculosis yscW-lcrF operon. As LcrF controls transcription of a number of critical T3SS genes in Yersinia, we hypothesized that Yersinia IscR may control the Ysc T3SS through LcrF. Indeed, purified IscR bound to the identified yscW-lcrF promoter motif and mRNA levels of lcrF and 24 other T3SS genes were reduced in Y. pseudotuberculosis in the absence of IscR. Importantly, mice orally infected with the Y. pseudotuberculosis ΔiscR mutant displayed decreased bacterial burden in Peyer's patches, mesenteric lymph nodes, spleens, and livers, indicating an essential role for IscR in Y. pseudotuberculosis virulence. This study presents the first characterization of Yersinia IscR and provides evidence that IscR is critical for virulence and type III secretion through direct regulation of the T3SS master regulator, LcrF.

  5. IscR is essential for yersinia pseudotuberculosis type III secretion and virulence.

    Science.gov (United States)

    Miller, Halie K; Kwuan, Laura; Schwiesow, Leah; Bernick, David L; Mettert, Erin; Ramirez, Hector A; Ragle, James M; Chan, Patricia P; Kiley, Patricia J; Lowe, Todd M; Auerbuch, Victoria

    2014-06-01

    Type III secretion systems (T3SS) are essential for virulence in dozens of pathogens, but are not required for growth outside the host. Therefore, the T3SS of many bacterial species are under tight regulatory control. To increase our understanding of the molecular mechanisms behind T3SS regulation, we performed a transposon screen to identify genes important for T3SS function in the food-borne pathogen Yersinia pseudotuberculosis. We identified two unique transposon insertions in YPTB2860, a gene that displays 79% identity with the E. coli iron-sulfur cluster regulator, IscR. A Y. pseudotuberculosis iscR in-frame deletion mutant (ΔiscR) was deficient in secretion of Ysc T3SS effector proteins and in targeting macrophages through the T3SS. To determine the mechanism behind IscR control of the Ysc T3SS, we carried out transcriptome and bioinformatic analysis to identify Y. pseudotuberculosis genes regulated by IscR. We discovered a putative IscR binding motif upstream of the Y. pseudotuberculosis yscW-lcrF operon. As LcrF controls transcription of a number of critical T3SS genes in Yersinia, we hypothesized that Yersinia IscR may control the Ysc T3SS through LcrF. Indeed, purified IscR bound to the identified yscW-lcrF promoter motif and mRNA levels of lcrF and 24 other T3SS genes were reduced in Y. pseudotuberculosis in the absence of IscR. Importantly, mice orally infected with the Y. pseudotuberculosis ΔiscR mutant displayed decreased bacterial burden in Peyer's patches, mesenteric lymph nodes, spleens, and livers, indicating an essential role for IscR in Y. pseudotuberculosis virulence. This study presents the first characterization of Yersinia IscR and provides evidence that IscR is critical for virulence and type III secretion through direct regulation of the T3SS master regulator, LcrF.

  6. Understanding the adsorptive interactions of arsenate-iron nanoparticles with curved fullerene-like sheets in activated carbon using a quantum mechanics/molecular mechanics computational approach.

    Science.gov (United States)

    Ha, Nguyen Ngoc; Cam, Le Minh; Ha, Nguyen Thi Thu; Goh, Bee-Min; Saunders, Martin; Jiang, Zhong-Tao; Altarawneh, Mohammednoor; Dlugogorski, Bogdan Z; El-Harbawi, Mohanad; Yin, Chun-Yang

    2017-06-07

    The prevalence of global arsenic groundwater contamination has driven widespread research on developing effective treatment systems including adsorption using various sorbents. The uptake of arsenic-based contaminants onto established sorbents such as activated carbon (AC) can be effectively enhanced via immobilization/impregnation of iron-based elements on the porous AC surface. Recent suggestions that AC pores structurally consist of an eclectic mix of curved fullerene-like sheets may affect the arsenic adsorption dynamics within the AC pores and is further complicated by the presence of nano-sized iron-based elements. We have therefore, attempted to shed light on the adsorptive interactions of arsenate-iron nanoparticles with curved fullerene-like sheets by using hybridized quantum mechanics/molecular mechanics (QMMM) calculations and microscopy characterization. It is found that, subsequent to optimization, chemisorption between HAsO 4 2- and the AC carbon sheet (endothermic process) is virtually non-existent - this observation is supported by experimental results. Conversely, the incorporation of iron nanoparticles (FeNPs) into the AC carbon sheet greatly facilitates chemisorption of HAsO 4 2- . Our calculation implies that iron carbide is formed at the junction between the iron and the AC interface and this tightly chemosorbed layer prevents detachment of the FeNPs on the AC surface. Other aspects including electronic structure/properties, carbon arrangement defects and rate of adsorptive interaction, which are determined using the Climbing-Image NEB method, are also discussed.

  7. Salmonella enterica Serovar Typhimurium Skills To Succeed in the Host: Virulence and Regulation

    Science.gov (United States)

    Fàbrega, Anna

    2013-01-01

    SUMMARY Salmonella enterica serovar Typhimurium is a primary enteric pathogen infecting both humans and animals. Infection begins with the ingestion of contaminated food or water so that salmonellae reach the intestinal epithelium and trigger gastrointestinal disease. In some patients the infection spreads upon invasion of the intestinal epithelium, internalization within phagocytes, and subsequent dissemination. In that case, antimicrobial therapy, based on fluoroquinolones and expanded-spectrum cephalosporins as the current drugs of choice, is indicated. To accomplish the pathogenic process, the Salmonella chromosome comprises several virulence mechanisms. The most important virulence genes are those located within the so-called Salmonella pathogenicity islands (SPIs). Thus far, five SPIs have been reported to have a major contribution to pathogenesis. Nonetheless, further virulence traits, such as the pSLT virulence plasmid, adhesins, flagella, and biofilm-related proteins, also contribute to success within the host. Several regulatory mechanisms which synchronize all these elements in order to guarantee bacterial survival have been described. These mechanisms govern the transitions from the different pathogenic stages and drive the pathogen to achieve maximal efficiency inside the host. This review focuses primarily on the virulence armamentarium of this pathogen and the extremely complicated regulatory network controlling its success. PMID:23554419

  8. The evolution of virulence and emerging diseases

    OpenAIRE

    Ewald, Paul W.

    1998-01-01

    Insights into the evolution of virulence may aid efforts to control or even prevent emerging diseases. Specifically, dangerous pathogens can be distinguished from those that pose relatively little threat by identifying characteristics that favor intense exploitation of hosts by pathogens, hence causing high virulence. Studies to date have implicated several such characteristics, including transmission by vectors, attendants, water, and durable propagules. These insights may improve the return...

  9. Rapid Identification of Bacterial Virulence Factors

    Science.gov (United States)

    2014-04-15

    anti-5. melitensis antibodies. In Brucella this protein shares homology with that of plant pathogen Agrobacterium tumefaciens wherein it is involved...Brucella suis homologue of the Agrobacterium tumefaciens chromosomal virulence operon ChvE is essential for sugar utilization but not for survival in...Phosphoenolpyruvate Carboxykinase Is an Acid-Induced, Chromosomally Encoded Virulence Factor in Agrobacterium tumefaciens . J. Bacteriol 187:6039-6045. Martin-Martin

  10. Towards a better understanding of flood generation and surface water inundation mechanisms using NASA remote sensing data products

    Science.gov (United States)

    Lucey, J.; Reager, J. T., II; Lopez, S. R.

    2017-12-01

    Floods annually cause several weather-related fatalities and financial losses. According to NOAA and FEMA, there were 43 deaths and 18 billion dollars paid out in flood insurance policies during 2005. The goal of this work is to improve flood prediction and flood risk assessment by creating a general model of predictability of extreme runoff generation using various NASA products. Using satellite-based flood inundation observations, we can relate surface water formation processes to changes in other hydrological variables, such as precipitation, storage and soil moisture, and understand how runoff generation response to these forcings is modulated by local topography and land cover. Since it is known that a flood event would cause an abnormal increase in surface water, we examine these underlying physical relationships in comparison with the Dartmouth Flood Observatory archive of historic flood events globally. Using ground water storage observations (GRACE), precipitation (TRMM or GPCP), land use (MODIS), elevation (SRTM) and surface inundation levels (SWAMPS), an assessment of geological and climate conditions can be performed for any location around the world. This project utilizes multiple linear regression analysis evaluating the relationship between surface water inundation, total water storage anomalies and precipitation values, grouped by average slope or land use, to determine their statistical relationships and influences on inundation data. This research demonstrates the potential benefits of using global data products for early flood prediction and will improve our understanding of runoff generation processes.

  11. Multiscale modelling to understand the self-assembly mechanism of human β2-adrenergic receptor in lipid bilayer.

    Science.gov (United States)

    Ghosh, Anirban; Sonavane, Uddhavesh; Joshi, Rajendra

    2014-02-01

    The long perceived notion that G-Protein Coupled Receptors (GPCRs) function in monomeric form has recently been changed by the description of a number of GPCRs that are found in oligomeric states. The mechanism of GPCR oligomerization, and its effect on receptor function, is not well understood. In the present study, coarse grained molecular dynamics (CGMD) approach was adopted for studying the self-assembly process of the human GPCR, β2-adrenergic receptor (β2-AR), for which several experimental evidences of the dimerization process and its effect on cellular functions are available. Since the crystal structure of β2-AR lacks the third intracellular loop, initially it was modelled and simulated using restrained MD in order to get a stable starting conformation. This structure was then converted to CG representation and 16 copies of it, inserted into a hydrated lipid bilayer, were simulated for 10 μs using the MARTINI force field. At the end of 10μs, oligomers of β2-AR were found to be formed through the self-assembly mechanism which were further validated through various analyses of the receptors. The lipid bilayer analysis also helped to quantify this assembly mechanism. In order to identify the domains which are responsible for this oligomerization, a reverse transformation of the CG system back to all-atom structure and simulated annealing run were carried out at the end of 10 μs CGMD run. Analysis of the all-atom dimers thus obtained, revealed that TM1/TM1, H8/H8, TM1/TM5 and TM6/TM6 regions formed most of the dimerization surfaces, which is in accordance with some of the experimental observations and recent simulation results. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Understanding the mechanism of drug resistance due to a codon deletion in protoporphyrinogen oxidase through computational modeling.

    Science.gov (United States)

    Hao, Ge-Fei; Zhu, Xiao-Lei; Ji, Feng-Qin; Zhang, Li; Yang, Guang-Fu; Zhan, Chang-Guo

    2009-04-09

    Protoporphyrinogen oxidase (PPO; EC 1.3.3.4) is the last common enzyme for the enzymatic transformation of protoporphyrinogen-IX to protoporphyrin-IX, which is the key common intermediate leading to heme and chlorophyll. Hence, PPO has been identified as one of the most importance action targets for the treatment of some important diseases including cancer and variegated porphyria (VP). In the agricultural field, PPO inhibitors have been used as herbicides for many years. Recently, a unique drug resistance was found to be associated with a nonactive site residue (Gly210) deletion rather than substitution in A. tuberculatus PPO. In the present study, extensive computational simulations, including homology modeling, molecular dynamics (MD) simulations, and molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) calculations, have been carried out to uncover the detailed molecular mechanism of drug resistance associated with Gly210 deletion. Although Gly210 in the wild-type A. tuberculatus PPO has no direct interaction with the inhibitors, all the computational models and energetic results indicated that Gly210 deletion has great effects on the hydrogen-bonding network and the conformational change of the binding pocket. An interchain hydrogen bond between Gly210 with Ser424, playing an important role in stabilizing the local conformation of the wild-type enzyme, disappeared after Gly210 deletion. As a result, the mutant-type PPO has a lower affinity than the wild-type enzyme, which accounts for the molecular mechanism of drug resistance. The structural and mechanistic insights obtained from the present study provide a new starting point for future rational design of novel PPO inhibitors to overcome drug resistance associated with Gly210 deletion.

  13. An anatomical and mechanical analysis of the douc monkey (genus Pygathrix), and its role in understanding the evolution of brachiation.

    Science.gov (United States)

    Byron, C D; Granatosky, M C; Covert, H H

    2017-12-01

    Pygathrix is an understudied Asian colobine unusual among the Old World monkeys for its use of arm-swinging. Little data exists on the anatomy and mechanics of brachiation in this genus. Here, we consider this colobine to gain insight into the parallel evolution of suspensory behavior in primates. This study compares axial and appendicular morphological variables of Pygathrix with other Asian colobines. Additionally, to assess the functional consequences of Pygathrix limb anatomy, kinematic and kinetic data during arm-swinging are included to compare the douc monkey to other suspensory primates (Ateles and Hylobates). Compared to more pronograde species, Pygathrix and Nasalis share morphology consistent with suspensory locomotion such as its narrower scapulae and elongated clavicles. More distally, Pygathrix displays a gracile humerus, radius, and ulna, and shorter olecranon process. During suspensory locomotion, Pygathrix, Ateles, and Hylobates all display mechanical convergence in limb loading and movements of the shoulder and elbow, but Pygathrix uses pronated wrist postures that include substantial radial deviation during arm-swinging. The adoption of arm-swinging represents a major shift within at least three anthropoid clades and little data exist about its transition. Across species, few mechanical differences are observed during arm-swinging. Apparently, there are limited functional solutions to the challenges associated with moving bimanually below branches, especially in more proximal forelimb regions. Morphological data support this idea that the Pygathrix distal forelimb differs from apes more than its proximal end. These results can inform other studies of ape evolution, the pronograde to orthograde transition, and the convergent ways in which suspensory locomotion evolved in primates. © 2017 Wiley Periodicals, Inc.

  14. Nonlinear Hamiltonian mechanics applied to molecular dynamics theory and computational methods for understanding molecular spectroscopy and chemical reactions

    CERN Document Server

    Farantos, Stavros C

    2014-01-01

    This brief presents numerical methods for describing and calculating invariant phase space structures, as well as solving the classical and quantum equations of motion for polyatomic molecules. Examples covered include simple model systems to realistic cases of molecules spectroscopically studied. Vibrationally excited and reacting molecules are nonlinear dynamical systems, and thus, nonlinear mechanics is the proper theory to elucidate molecular dynamics by investigating invariant structures in phase space. Intramolecular energy transfer, and the breaking and forming of a chemical bond have now found a rigorous explanation by studying phase space structures.

  15. Mechanisms of Antimicrobial Peptide Resistance in Gram-Negative Bacteria

    Directory of Open Access Journals (Sweden)

    Victor I. Band

    2014-12-01

    Full Text Available Cationic antimicrobial peptides (CAMPs are important innate immune defenses that inhibit colonization by pathogens and contribute to clearance of infections. Gram-negative bacterial pathogens are a major target, yet many of them have evolved mechanisms to resist these antimicrobials. These resistance mechanisms can be critical contributors to bacterial virulence and are often crucial for survival within the host. Here, we summarize methods used by Gram-negative bacteria to resist CAMPs. Understanding these mechanisms may lead to new therapeutic strategies against pathogens with extensive CAMP resistance.

  16. Investigation of selected outcomes of the Dynamic Physics learning environment: Understanding of mechanics concepts and achievement by male and female students

    Science.gov (United States)

    Mackin, Joan E.

    The study investigated the Dynamic Physics learning environment to determine its effectiveness in promoting understanding of mechanics concepts and achievement as well as the differences between male and female students in understanding of physics concepts and progress in the course. The Dynamic Physics learning environment was chosen for research since it offered an opportunity to study an introductory calculus based physics that incorporated recommendations, goals, and strategies for effective learning outlined in recent reports on physics education. Data were collected using pretests and posttests, course assessments, surveys, students' evaluations, and midterm feedback interviews. The data from the pretest, posttest, and course assessments were analyzed using a difference of means t test (pphysics education studies. Analysis of interviews and evaluations of the course indicated students perceived they were understanding physics concepts in this learning environment and realized this understanding was important background for future courses. Students suggested that connections to real world applications, the format of the course, and collaborative learning were factors that helped them to understand physics concepts by making them more meaningful. Students' responses suggested that teaching strategies used in the course not only helped them to develop understanding, but confidence in their ability to learn physic. The sample of female students had significantly lower average scores in the pretest and posttest compared to male students; however, the sample of female students made the same or higher average gains in conceptual understanding when compared to the male students. Additional findings included that groups with one or more female member earned higher averages in group assessments than all male groups. Female students' perceptions of physics changed during the course; female students indicated an increase in relating personal experiences and real world

  17. Mechanism

    Directory of Open Access Journals (Sweden)

    Yao Yu

    2010-01-01

    Full Text Available The kinematics analysis method of a novel 3-DOF wind tunnel mechanism based on cable-driven parallel mechanism is provided. Rodrigues' parameters are applied to express the transformation matrix of the wire-driven mechanism in the paper. The analytical forward kinematics model is described as three quadratic equations using three Rodridgues' parameters based on the fundamental theory of parallel mechanism. Elimination method is used to remove two of the variables, so that an eighth-order polynomial with one variable is derived. From the equation, the eight sets of Rodridgues' parameters and corresponding Euler angles for the forward kinematical problem can be obtained. In the end, numerical example of both forward and inverse kinematics is included to demonstrate the presented forward-kinematics solution method. The numerical results show that the method for the position analysis of this mechanism is effective.

  18. Towards the Understanding of Resistance Mechanisms in Clinically Isolated Trimethoprim-resistant, Methicillin-resistant Staphylococcus aureus Dihydrofolate Reductase

    Energy Technology Data Exchange (ETDEWEB)

    Frey, K.; Lombardo, M; Wright, D; Anderson, A

    2010-01-01

    Resistance to therapeutics such as trimethoprim-sulfamethoxazole has become an increasing problem in strains of methicillin-resistant Staphylococcus aureus (MRSA). Clinically isolated trimethoprim-resistant strains reveal a double mutation, H30N/F98Y, in dihydrofolate reductase (DHFR). In order to develop novel and effective therapeutics against these resistant strains, we evaluated a series of propargyl-linked antifolate lead compounds for inhibition of the mutant enzyme. For the propargyl-linked antifolates, the F98Y mutation generates minimal (between 1.2- and 6-fold) losses of affinity and the H30N mutation generates greater losses (between 2.4- and 48-fold). Conversely, trimethoprim affinity is largely diminished by the F98Y mutation (36-fold) and is not affected by the H30N mutation. In order to elucidate a mechanism of resistance, we determined a crystal structure of a complex of this double mutant with a lead propargyl-linked antifolate. This structure suggests a resistance mechanism consistent both for the propargyl-linked class of antifolates and for trimethoprim that is based on the loss of a conserved water-mediated hydrogen bond.

  19. The Winding Road to Relapse: Forging a New Understanding of Cue-Induced Reinstatement Models and Their Associated Neural Mechanisms

    Directory of Open Access Journals (Sweden)

    Mark D. Namba

    2018-02-01

    Full Text Available In drug addiction, cues previously associated with drug use can produce craving and frequently trigger the resumption of drug taking in individuals vulnerable to relapse. Environmental stimuli associated with drugs or natural reinforcers can become reliably conditioned to increase behavior that was previously reinforced. In preclinical models of addiction, these cues enhance both drug self-administration and reinstatement of drug seeking. In this review, we will dissociate the roles of conditioned stimuli as reinforcers from their modulatory or discriminative functions in producing drug-seeking behavior. As well, we will examine possible differences in neurobiological encoding underlying these functional differences. Specifically, we will discuss how models of drug addiction and relapse should more systematically evaluate these different types of stimuli to better understand the neurobiology underlying craving and relapse. In this way, behavioral and pharmacotherapeutic interventions may be better tailored to promote drug use cessation outcomes and long-term abstinence.

  20. Understanding the mechanism of toxicity of carbon nanoparticles in humans in the new millennium: A systemic review

    Science.gov (United States)

    Sharma, Mukesh

    2010-01-01

    Manmade nanoparticles range from the well-established multi-ton production of carbon black and fumed silica for applications in plastic fillers and car tyres to microgram quantities of fluorescent quantum dots used as markers in biological imaging. While benefits of nanotechnology are widely publicized, the discussion of the potential effects of their widespread use in the consumer and industrial products are just beginning to emerge. Acceptance of nanoparticle toxicity led to wide acceptance of the fact that nanotoxicology, as a scientific discipline shall be quite different from occupational hygiene in approach and context. Understanding the toxicity of nanomaterials and nano-enabled products is important for human and environmental health and safety as well as public acceptance. Assessing the state of knowledge about nanotoxicology is an important step in promoting comprehensive understanding of the health and environmental implications of these new materials. Very limited data exist for health effects secondary to inhalation of very fine respirable particles in the occupational environment. Nanomaterials may have effects on health due to their size, surface, shape, charge, or other factors, which are not directly predictable from mass concentration measurements. Numerous epidemiological studies have associated exposure to small particles such as combustion-generated fine particles with lung cancer, heart disease, asthma and/or increased mortality. The omnipresence of nanoparticles shifts focus of research toward efforts to mitigate the health effects of nanoparticles. Newer health assessment methods and newer techniques need to be developed for diagnosing sub-optimal health in populations exposed to carbon nanoparticles. PMID:20808660

  1. Docking based 3d-QSAR studies applied at the BRAF inhibitors to understand the binding mechanism

    International Nuclear Information System (INIS)

    Mahmood, U.; Haq, Z.U.

    2011-01-01

    BRAF is a great therapeutic target in a wide variety of human cancers. It is the member of Ras Activating Factor (RAF) family of serine/throenine kinase. The mutated form of the BRAF has diverted all the attention towards itself because of increase severity and elevated kinase activity. The RAF signal transduction cascade is a conserved protein pathway that is involved in cell cycle progression and apoptosis. The ERK regulates phosphorylation of different proteins either in cytosol or in nucleus but disorders in ERK signaling pathway cause mutation in BRAF. This cascade in these cells may provide selection of mutated BRAF in which valine is substituted with glutamatic acid at position 600. This mutation occurs in activation loop. A number of inhibitors reported to target different members of RAF, some of them have potential to target the BRAF as well. Major reason for failure of previously reported inhibitors was due to the highly conserved sequence and confirmation of catalytic cleft which is always a center of consideration for binding of inhibitors to suppress the kinase activity. This is the first attempt to study and understand the BARF inhibitors - protein interactions in detail by utilizing 3D-QSAR and molecular docking techniques. Most reliable techniques of 3D QSAR i.e Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) were applied for three different data sets. The data sets selected for better evaluation of BRAF inhibitors belongs to 2, 6-Disubstituted Pyrazine, Pyridoimidazolones and its derivatives. Our models would offer help to better understand the structure-activity relationships that exist for these classes of compounds and also facilitate the design of novel inhibitors with good chemical diversity. (Author)

  2. Effect of ethanol on differential protein production and expression of potential virulence functions in the opportunistic pathogen Acinetobacter baumannii.

    Directory of Open Access Journals (Sweden)

    Chika C Nwugo

    Full Text Available Acinetobacter baumannii persists in the medical environment and causes severe human nosocomial infections. Previous studies showed that low-level ethanol exposure increases the virulence of A. baumannii ATCC 17978. To better understand the mechanisms involved in this response, 2-D gel electrophoresis combined with mass spectrometry was used to investigate differential protein production in bacteria cultured in the presence or absence of ethanol. This approach showed that the presence of ethanol significantly induces and represses the production of 22 and 12 proteins, respectively. Although over 25% of the ethanol-induced proteins were stress-response related, the overall bacterial viability was uncompromised when cultured under these conditions. Production of proteins involved in lipid and carbohydrate anabolism was increased in the presence of ethanol, a response that correlates with increased carbohydrate biofilm content, enhanced biofilm formation on abiotic surfaces and decrease bacterial motility on semi-solid surfaces. The presence of ethanol also induced the acidification of bacterial cultures and the production of indole-3-acetic acid (IAA, a ubiquitous plant hormone that signals bacterial stress-tolerance and promotes plant-bacteria interactions. These responses could be responsible for the significantly enhanced virulence of A. baumannii ATCC 17978 cells cultured in the presence of ethanol when tested with the Galleria mellonella experimental infection model. Taken together, these observations provide new insights into the effect of ethanol in bacterial virulence. This alcohol predisposes the human host to infections by A. baumannii and could favor the survival and adaptation of this pathogen to medical settings and adverse host environments.

  3. Synergistic interactions between the NS3(hel and E proteins contribute to the virulence of dengue virus type 1.

    Directory of Open Access Journals (Sweden)

    Luana de Borba

    Full Text Available BACKGROUND: Dengue includes a broad range of symptoms, ranging from fever to hemorrhagic fever and may occasionally have alternative clinical presentations. Many possible viral genetic determinants of the intrinsic virulence of dengue virus (DENV in the host have been identified, but no conclusive evidence of a correlation between viral genotype and virus transmissibility and pathogenicity has been obtained. METHODOLOGY/PRINCIPAL FINDINGS: We used reverse genetics techniques to engineer DENV-1 viruses with subsets of mutations found in two different neuroadapted derivatives. The mutations were inserted into an infectious clone of DENV-1 not adapted to mice. The replication and viral production capacity of the recombinant viruses were assessed in vitro and in vivo. The results demonstrated that paired mutations in the envelope protein (E and in the helicase domain of the NS3 (NS3(hel protein had a synergistic effect enhancing viral fitness in human and mosquito derived cell lines. E mutations alone generated no detectable virulence in the mouse model; however, the combination of these mutations with NS3(hel mutations, which were mildly virulent on their own, resulted in a highly neurovirulent phenotype. CONCLUSIONS/SIGNIFICANCE: The generation of recombinant viruses carrying specific E and NS3(hel proteins mutations increased viral fitness both in vitro and in vivo by increasing RNA synthesis and viral load (these changes being positively correlated with central nervous system damage, the strength of the immune response and animal mortality. The introduction of only pairs of amino acid substitutions into the genome of a non-mouse adapted DENV-1 strain was sufficient to alter viral fitness substantially. Given current limitations to our understanding of the molecular basis of dengue neuropathogenesis, these results could contribute to the development of attenuated strains for use in vaccinations and provide insights into virus/host interactions

  4. Understanding the removal mechanisms of PPCPs and the influence of main technological parameters in anaerobic UASB and aerobic CAS reactors.

    Science.gov (United States)

    Alvarino, T; Suarez, S; Lema, J M; Omil, F

    2014-08-15

    The removal of 16 Pharmaceutical and Personal Care Products (PPCPs) were studied in a conventional activated sludge (CAS) unit and an upflow anaerobic sludge blanket (UASB) reactor. Special attention was paid to each biomass conformation and activity as well as to operational conditions. Biodegradation was the main PPCP removal mechanism, being higher removals achieved under aerobic conditions, except in the case of sulfamethoxazole and trimetrophim. Under anaerobic conditions, PPCP biodegradation was correlated with the methanogenic rate, while in the aerobic reactor a relationship with nitrification was found. Sorption onto sludge was influenced by biomass conformation, being only significant for musk fragrances in the UASB reactor, in which an increase of the upward velocity and hydraulic retention time improved this removal. Additionally, PPCP sorption increased with time in the UASB reactor, due to the granular biomass structure which suggests the existence of intra-molecular diffusion. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Influence of osmolytes on protein and water structure: a step to understanding the mechanism of protein stabilization.

    Science.gov (United States)

    Bruździak, Piotr; Panuszko, Aneta; Stangret, Janusz

    2013-10-03

    Results concerning the thermostability of hen egg white lysozyme in aqueous solutions with stabilizing osmolytes, trimethylamine-N-oxide (TMAO), glycine (Gly), and its N-methyl derivatives, N-methylglycine (NMG), N,N-dimethylglycine (DMG), and N,N,N-trimethylglycine (betaine, TMG), have been presented. The combination of spectroscopic (IR) and calorimetric (DSC) data allowed us to establish a link between osmolytes' influence on water structure and their ability to thermally stabilize protein molecule. Structural and energetic characteristics of stabilizing osmolytes' and lysozyme's hydration water appear to be very similar. The osmolytes increase lysozyme stabilization in the order bulk water molecules affected by osmolytes in their surrounding. Obtained results verified the hypothesis concerning the role of water molecules in protein stabilization, explained the osmophobic effect, and finally helped to bring us nearer to the exact mechanism of protein stabilization by osmolytes.

  6. The Potential Link between Thermal Resistance and Virulence in Salmonella: A Review

    Directory of Open Access Journals (Sweden)

    Turki M. Dawoud

    2017-06-01

    Full Text Available In some animals, the typical body temperature can be higher than humans, for example, 42°C in poultry and 40°C in rabbits which can be a potential thermal stress challenge for pathogens. Even in animals with lower body temperatures, when infection occurs, the immune system may increase body temperature to reduce the chance of survival for pathogens. However, some pathogens can still easily overcome higher body temperatures and/or rise in body temperatures through expression of stress response mechanisms. Salmonella is the causative agent of one of the most prevalent foodborne illnesses, salmonellosis, and can readily survive over a wide range of temperatures due to the efficient expression of the heat (thermal stress response. Therefore, thermal resistance mechanisms can provide cross protection against other stresses including the non-specific host defenses found within the human body thus increasing pathogenic potential. Understanding the molecular mechanisms associated with thermal responses in Salmonella is crucial in designing and developing more effective or new treatments for reducing and eliminating infection caused by Salmonella that have survived heat stress. In this review, Salmonella thermal resistance is assessed followed by an overview of the thermal stress responses with a focus on gene regulation by sigma factors, heat shock proteins, along with the corresponding thermosensors and their association with virulence expression including a focus on a potential link between heat resistance and potential for infection.

  7. Modes of competition: adding and removing brown trout in the wild to understand the mechanisms of density-dependence.

    Directory of Open Access Journals (Sweden)

    Rasmus Kaspersson

    Full Text Available While the prevalence of density-dependence is well-established in population ecology, few field studies have investigated its underlying mechanisms and their relative population-level importance. Here, we address these issues, and more specifically, how differences in body-size influence population regulation. For this purpose, two experiments were performed in a small coastal stream on the Swedish west coast, using juvenile brown trout (Salmo trutta as a study species. We manipulated densities of large and small individuals, and observed effects on survival, migration, condition and individual growth rate in a target group of intermediate-sized individuals. The generality of the response was investigated by reducing population densities below and increasing above the natural levels (removing and adding large and small individuals. Reducing the density (relaxing the intensity of competition had no influence on the response variables, suggesting that stream productivity was not a limiting factor at natural population density. Addition of large individuals resulted in a negative density-dependent response, while no effect was detected when adding small individuals or when maintaining the natural population structure. We found that the density-dependent response was revealed as reduced growth rate rather than increased mortality and movement, an effect that may arise from exclusion to suboptimal habitats or increased stress levels among inferior individuals. Our findings confirm the notion of interference competition as the primary mode of competition in juvenile salmonids, and also show that the feedback-mechanisms of density-dependence are primarily acting when increasing densities above their natural levels.

  8. Developing strong concurrent multiphysics multiscale coupling to understand the impact of microstructural mechanisms on the structural scale

    Energy Technology Data Exchange (ETDEWEB)

    Foulk, James W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Alleman, Coleman N. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mota, Alejandro [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lim, Hojun [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Littlewood, David John [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bergel, Guy Leshem [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Popova, Evdokia [Georgia Inst. of Technology, Atlanta, GA (United States). Woodruff School of Mechanical Engineering; Montes de Oca Zapiain, David [Georgia Inst. of Technology, Atlanta, GA (United States). Woodruff School of Mechanical Engineering; Kalidindi, Suryanarayana Raju [Georgia Inst. of Technology, Atlanta, GA (United States). Woodruff School of Mechanical Engineering; Ernst, Corey [Elemental Technologies, Provo, UT (United States)

    2017-09-01

    The heterogeneity in mechanical fields introduced by microstructure plays a critical role in the localization of deformation. To resolve this incipient stage of failure, it is therefore necessary to incorporate microstructure with sufficient resolution. On the other hand, computational limitations make it infeasible to represent the microstructure in the entire domain at the component scale. In this study, the authors demonstrate the use of concurrent multi- scale modeling to incorporate explicit, finely resolved microstructure in a critical region while resolving the smoother mechanical fields outside this region with a coarser discretization to limit computational cost. The microstructural physics is modeled with a high-fidelity model that incorporates anisotropic crystal elasticity and rate-dependent crystal plasticity to simulate the behavior of a stainless steel alloy. The component-scale material behavior is treated with a lower fidelity model incorporating isotropic linear elasticity and rate-independent J 2 plas- ticity. The microstructural and component scale subdomains are modeled concurrently, with coupling via the Schwarz alternating method, which solves boundary-value problems in each subdomain separately and transfers solution information between subdomains via Dirichlet boundary conditions. Beyond cases studies in concurrent multiscale, we explore progress in crystal plastic- ity through modular designs, solution methodologies, model verification, and extensions to Sierra/SM and manycore applications. Advances in conformal microstructures having both hexahedral and tetrahedral workflows in Sculpt and Cubit are highlighted. A structure-property case study in two-phase metallic composites applies the Materials Knowledge System to local metrics for void evolution. Discussion includes lessons learned, future work, and a summary of funded efforts and proposed work. Finally, an appendix illustrates the need for two-way coupling through a single degree of

  9. Use of a Phosphorylation Site Mutant To Identify Distinct Modes of Gene Repression by the Control of Virulence Regulator (CovR) in Streptococcus pyogenes.

    Science.gov (United States)

    Horstmann, Nicola; Sahasrabhojane, Pranoti; Yao, Hui; Su, Xiaoping; Shelburne, Samuel A

    2017-09-15

    Control of the virulence regulator/sensor kinase (CovRS) two-component system (TCS) serves as a model for investigating the impact of signaling pathways on the pathogenesis of Gram-positive bacteria. However, the molecular mechanisms by which CovR, an OmpR/PhoB family response regulator, controls virulence gene expression are poorly defined, partly due to the labile nature of its aspartate phosphorylation site. To better understand the regulatory effect of phosphorylated CovR, we generated the phosphorylation site mutant strain 10870-CovR-D53E, which we predicted to have a constitutive CovR phosphorylation phenotype. Interestingly, this strain showed CovR activity only for a subset of the CovR regulon, which allowed for classification of CovR-influenced genes into D53E-regulated and D53E-nonregulated groups. Inspection of the promoter sequences of genes belonging to each group revealed distinct promoter architectures with respect to the location and number of putative CovR-binding sites. Electrophoretic mobility shift analysis demonstrated that recombinant CovR-D53E protein retains its ability to bind promoter DNA from both CovR-D53E-regulated and -nonregulated groups, implying that factors other than mere DNA binding are crucial for gene regulation. In fact, we found that CovR-D53E is incapable of dimerization, a process thought to be critical to OmpR/PhoB family regulator function. Thus, our global analysis of CovR-D53E indicates dimerization-dependent and dimerization-independent modes of CovR-mediated repression, thereby establishing distinct mechanisms by which this critical regulator coordinates virulence gene expression. IMPORTANCE Streptococcus pyogenes causes a wide variety of diseases, ranging from superficial skin and throat infections to life-threatening invasive infections. To establish these various disease manifestations, Streptococcus pyogenes requires tightly coordinated production of its virulence factor repertoire. Here, the response regulator

  10. Quorum Sensing and Expression of Virulence in Pectobacteria

    Directory of Open Access Journals (Sweden)

    Andres Mäe

    2012-03-01

    Full Text Available Quorum sensing (QS is a population density-dependent regulatory mechanism in which gene expression is coupled to the accumulation of a chemical signaling molecule. QS systems are widespread among the plant soft-rotting bacteria. In Pectobacterium carotovorum, at least two QS systems exist being specified by the nature of chemical signals involved. QS in Pectobacterium carotovorum uses N-acylhomoserine lactone (AHL based, as well as autoinducer-2 (AI-2 dependent signaling systems. This review will address the importance of the QS in production of virulence factors and interaction of QS with other regulatory systems in Pectobacterium carotovorum.

  11. Teaching Teaching & Understanding Understanding

    DEFF Research Database (Denmark)

    2006-01-01

    "Teaching Teaching & Understanding Understanding" is a 19-minute award-winning short-film about teaching at university and higher-level educational institutions. It is based on the "Constructive Alignment" theory developed by Prof. John Biggs. The film delivers a foundation for understanding what...

  12. Developmental song learning as a model to understand neural mechanisms that limit and promote the ability to learn.

    Science.gov (United States)

    London, Sarah E

    2017-11-20

    Songbirds famously learn their vocalizations. Some species can learn continuously, others seasonally, and still others just once. The zebra finch (Taeniopygia guttata) learns to sing during a single developmental "Critical Period," a restricted phase during which a specific experience has profound and permanent effects on brain function and behavioral patterns. The zebra finch can therefore provide fundamental insight into features that promote and limit the ability to acquire complex learned behaviors. For example, what properties permit the brain to come "on-line" for learning? How does experience become encoded to prevent future learning? What features define the brain in receptive compared to closed learning states? This piece will focus on epigenomic, genomic, and molecular levels of analysis that operate on the timescales of development and complex behavioral learning. Existing data will be discussed as they relate to Critical Period learning, and strategies for future studies to more directly address these questions will be considered. Birdsong learning is a powerful model for advancing knowledge of the biological intersections of maturation and experience. Lessons from its study not only have implications for understanding developmental song learning, but also broader questions of learning potential and the enduring effects of early life experience on neural systems and behavior. Copyright © 2017. Published by Elsevier B.V.

  13. Molecular-level understanding of the adsorption mechanism of a graphite-binding peptide at the water/graphite interface.

    Science.gov (United States)

    Penna, M J; Mijajlovic, M; Tamerler, C; Biggs, M J

    2015-07-14

    The association of proteins and peptides with inorganic material has vast technological potential. An understanding of the adsorption of peptides at liquid/solid interfaces on a molecular-level is fundamental to fully realising this potential. Combining our prior work along with the statistical analysis of 100+ molecular dynamics simulations of adsorption of an experimentally identified graphite binding peptide, GrBP5, at the water/graphite interface has been used here to propose a model for the adsorption of a peptide at a liquid/solid interface. This bottom-up model splits the adsorption process into three reversible phases: biased diffusion, anchoring and lockdown. Statistical analysis highlighted the distinct roles played by regions of the peptide studied here throughout the adsorption process: the hydrophobic domain plays a significant role in the biased diffusion and anchoring phases suggesting that the initial impetus for association between the peptide and the interface may be hydrophobic in origin; aromatic residues dominate the interaction between the peptide and the surface in the adsorbed state and the polar region in the middle of the peptide affords a high conformational flexibility allowing strongly interacting residues to maximise favourable interactions with the surface. Reversible adsorption was observed here, unlike in our prior work focused on a more strongly interacting surface. However, this reversibility is unlikely to be seen once the peptide-surface interaction exceeds 10 kcal mol(-1).

  14. Understanding the removal mechanisms of PPCPs and the influence of main technological parameters in anaerobic UASB and aerobic CAS reactors

    International Nuclear Information System (INIS)

    Alvarino, T.; Suarez, S.; Lema, J.M.; Omil, F.

    2014-01-01

    Highlights: • Removals of 16 PPCPs under aerobic and anaerobic conditions were quantified. • Operation conditions (HRT, v up , biomass activity and conformation) influenced removal. • Highest removals associated to aerobic biodegradation. • Sorption was only relevant for lipophilic compounds in the UASB reactor. - Abstract: The removal of 16 Pharmaceutical and Personal Care Products (PPCPs) were studied in a conventional activated sludge (CAS) unit and an upflow anaerobic sludge blanket (UASB) reactor. Special attention was paid to each biomass conformation and activity as well as to operational conditions. Biodegradation was the main PPCP removal mechanism, being higher removals achieved under aerobic conditions, except in the case of sulfamethoxazole and trimetrophim. Under anaerobic conditions, PPCP biodegradation was correlated with the methanogenic rate, while in the aerobic reactor a relationship with nitrification was found. Sorption onto sludge was influenced by biomass conformation, being only significant for musk fragrances in the UASB reactor, in which an increase of the upward velocity and hydraulic retention time improved this removal. Additionally, PPCP sorption increased with time in the UASB reactor, due to the granular biomass structure which suggests the existence of intra-molecular diffusion

  15. Understanding the removal mechanisms of PPCPs and the influence of main technological parameters in anaerobic UASB and aerobic CAS reactors

    Energy Technology Data Exchange (ETDEWEB)

    Alvarino, T., E-mail: teresa.alvarino@usc.es; Suarez, S., E-mail: Sonia.suarez@usc.es; Lema, J.M., E-mail: juan.lema@usc.es; Omil, F., E-mail: francisco.omil@usc.es

    2014-08-15

    Highlights: • Removals of 16 PPCPs under aerobic and anaerobic conditions were quantified. • Operation conditions (HRT, v{sub up}, biomass activity and conformation) influenced removal. • Highest removals associated to aerobic biodegradation. • Sorption was only relevant for lipophilic compounds in the UASB reactor. - Abstract: The removal of 16 Pharmaceutical and Personal Care Products (PPCPs) were studied in a conventional activated sludge (CAS) unit and an upflow anaerobic sludge blanket (UASB) reactor. Special attention was paid to each biomass conformation and activity as well as to operational conditions. Biodegradation was the main PPCP removal mechanism, being higher removals achieved under aerobic conditions, except in the case of sulfamethoxazole and trimetrophim. Under anaerobic conditions, PPCP biodegradation was correlated with the methanogenic rate, while in the aerobic reactor a relationship with nitrification was found. Sorption onto sludge was influenced by biomass conformation, being only significant for musk fragrances in the UASB reactor, in which an increase of the upward velocity and hydraulic retention time improved this removal. Additionally, PPCP sorption increased with time in the UASB reactor, due to the granular biomass structure which suggests the existence of intra-molecular diffusion.

  16. Partitioning CO2 fluxes with isotopologue measurements and modeling to understand mechanisms of forest carbon sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Saleska, Scott [Univ. of Arizona, Tucson, AZ (United States). Dept. of Ecology and Evolutionary Biology; Davidson, Eric [Woods Hole Research Center, Falmouth, MA (United States); Finzi, Adrien [Boston Univ., MA (United States). Dept. of Biology; Wehr, Richard [Univ. of Arizona, Tucson, AZ (United States); Moorcroft, Paul [Harvard Univ., Cambridge, MA (United States). Dept. of Organismic and Evolutionary Biology

    2016-01-28

    This project combines automated in situ observations of the isotopologues of CO2 with root observations, novel experimental manipulations of below ground processes, and isotope-enabled ecosystem modeling to investigate mechanisms of below- vs. above ground carbon sequestration at the Harvard Forest Environmental Measurements Site (EMS). The proposed objectives, which have now been largely accomplished, include: (A) Partitioning of net ecosystem CO2 exchange (NEE) into photosynthesis and respiration using long-term continuous observations of the isotopic composition of NEE, and analysis of their dynamics; (B) Investigation of the influence of vegetation phenology on the timing and magnitude of carbon allocated below ground using measurements of root growth and indices of below ground autotrophic vs. heterotrophic respiration (via trenched plots andisotope measurements); (C) Testing whether plant allocation of carbon below ground stimulates the microbial decomposition of soil organic matter, using in situ rhizosphere simulation experiments wherein realistic quantities of artificial isotopically-labeled exudates are released into the soil; and (D) Synthesis and interpretation of the above data using the Ecosystem Demography Model 2 (ED2).

  17. Partitioning CO2 fluxes with isotopologue measurements and modeling to understand mechanisms of forest carbon sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, Eric A. [Woods Hole Research Center, Falmouth, MA (United States); Saleska, Scott [Univ. of Arizona, Tucson, AZ (United States); Savage, Kathleen [Woods Hole Research Center, Falmouth, MA (United States); Finzi, Adrien [Boston Univ., MA (United States); Moorcroft, Paul [Harvard Univ., Cambridge, MA (United States); Wehr, Richard [Univ. of Arizona, Tucson, AZ (United States)

    2016-02-18

    1. Project Summary and Objectives This project combines automated in situ observations of the isotopologues of CO2 with root observations, novel experimental manipulations of belowground processes, and isotope-enabled ecosystem modeling to investigate mechanisms of below- vs. aboveground carbon sequestration at the Harvard Forest Environmental Measurements Site (EMS). The proposed objectives, which have now been largely accomplished, include: A. Partitioning of net ecosystem CO2 exchange (NEE) into photosynthesis and respiration using long-term continuous observations of the isotopic composition of NEE, and analysis of their dynamics ; B. Investigation of the influence of vegetation phenology on the timing and magnitude of carbon allocated belowground using measurements of root growth and indices of belowground autotrophic vs. heterotrophic respiration (via trenched plots and isotope measurements); C. Testing whether plant allocation of carbon belowground stimulates the microbial decomposition of soil organic matter, using in situ rhizosphere simulation experiments wherein realistic quantities of artificial isotopically-labeled exudates are released into the soil; and D. Synthesis and interpretation of the above data using the Ecosystem Demography Model 2 (ED2).

  18. Understanding the performance and mechanism of Mg-containing oxides as support catalysts in the thermal dry reforming of methane.

    Science.gov (United States)

    Khairudin, Nor Fazila; Sukri, Mohd Farid Fahmi; Khavarian, Mehrnoush; Mohamed, Abdul Rahman

    2018-01-01

    Dry reforming of methane (DRM) is one of the more promising methods for syngas (synthetic gas) production and co-utilization of methane and carbon dioxide, which are the main greenhouse gases. Magnesium is commonly applied in a Ni-based catalyst in DRM to improve catalyst performance and inhibit carbon deposition. The aim of this review is to gain better insight into recent developments on the use of Mg as a support or promoter for DRM catalysts. Its high basicity and high thermal stability make Mg suitable for introduction into the highly endothermic reaction of DRM. The introduction of Mg as a support or promoter for Ni-based catalysts allows for good metal dispersion on the catalyst surface, which consequently facilitates high catalytic activity and low catalyst deactivation. The mechanism of DRM and carbon formation and reduction are reviewed. This work further explores how different constraints, such as the synthesis method, metal loading, pretreatment, and operating conditions, influence the dry reforming reactions and product yields. In this review, different strategies for enhancing catalytic activity and the effect of metal dispersion on Mg-containing oxide catalysts are highlighted.

  19. Membrane-mediated action of the endocannabinoid anandamide on membrane proteins: implications for understanding the receptor-independent mechanism

    Science.gov (United States)

    Medeiros, Djalma; Silva-Gonçalves, Laíz Da Costa; da Silva, Annielle Mendes Brito; Dos Santos Cabrera, Marcia Perez; Arcisio-Miranda, Manoel

    2017-01-01

    Endocannabinoids are amphiphilic molecules that play crucial neurophysiological functions acting as lipid messengers. Antagonists and knockdown of the classical CB1 and CB2 cannabinoid receptors do not completely abolish many endocannabinoid activities, supporting the idea of a mechanism independent of receptors whose mode of action remains unclear. Here we combine gramicidin A (gA) single channel recordings and membrane capacitance measurements to investigate the lipid bilayer-modifying activity of endocannabinoids. Single channel recordings show that the incorporation of endocannabinoids into lipid bilayers reduces the free energy necessary for gramicidin channels to transit from the monomeric to the dimeric conformation. Membrane capacitance demonstrates that the endocannabinoid anandamide has limited effects on the overall structure of the lipid bilayers. Our results associated with the theory of membrane elastic deformation reveal that the action of endocannabinoids on membrane proteins can involve local adjustments of the lipid/protein hydrophobic interface. The current findings shed new light on the receptor-independent mode of action of endocannabinoids on membrane proteins, with important implications towards their neurobiological function.

  20. Does More Respect from Leaders Postpone the Desire to Retire? Understanding the Mechanisms of Retirement Decision-Making.

    Science.gov (United States)

    Wöhrmann, Anne M; Fasbender, Ulrike; Deller, Jürgen

    2017-01-01

    The demographic trends (i.e., low birth rates and increasing longevity) pose challenges with regard to the increase of the average employee age along with a lack of skilled personnel on the labor market. Society, organizations, and individuals are confronted with the question on how to prolong working lives in the future. Based on socioemotional selectivity theory, the purpose of this study was to investigate the relationship between respectful leadership and older workers' desired retirement age. In particular, we took a closer look at job satisfaction, subjective health, and work-to-private life conflict as underlying mechanisms. Further, we tested for the moderating role of occupational self-efficacy as an auxiliary condition for the assumed relationships of respectful leadership. We tested our hypothesized model using data from 1,130 blue- and white-collar workers aged 45-65 years. The results of structural equation modeling indicated that respectful leadership was positively related to older workers' desired retirement age and that this relationship was mediated by subjective health and work-to-private life conflict but not by job satisfaction. The findings add to the literature on resources in retirement decision-making; notably, they highlight the importance of leadership behavior for older workers' motivation and socioemotional needs.

  1. Does More Respect from Leaders Postpone the Desire to Retire? Understanding the Mechanisms of Retirement Decision-Making

    Directory of Open Access Journals (Sweden)

    Anne M. Wöhrmann

    2017-08-01

    Full Text Available The demographic trends (i.e., low birth rates and increasing longevity pose challenges with regard to the increase of the average employee age along with a lack of skilled personnel on the labor market. Society, organizations, and individuals are confronted with the question on how to prolong working lives in the future. Based on socioemotional selectivity theory, the purpose of this study was to investigate the relationship between respectful leadership and older workers’ desired retirement age. In particular, we took a closer look at job satisfaction, subjective health, and work-to-private life conflict as underlying mechanisms. Further, we tested for the moderating role of occupational self-efficacy as an auxiliary condition for the assumed relationships of respectful leadership. We tested our hypothesized model using data from 1,130 blue- and white-collar workers aged 45–65 years. The results of structural equation modeling indicated that respectful leadership was positively related to older workers’ desired retirement age and that this relationship was mediated by subjective health and work-to-private life conflict but not by job satisfaction. The findings add to the literature on resources in retirement decision-making; notably, they highlight the importance of leadership behavior for older workers’ motivation and socioemotional needs.

  2. Quantitative Fermi level tuning in amorphous organic semiconductor by molecular doping: Toward full understanding of the doping mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jin-Peng, E-mail: yangjp@yzu.edu.cn, E-mail: uenon@faculty.chiba-u.jp; Wang, Wen-Qing; Cheng, Li-Wen; Zeng, Xiang-Hua [College of Physical Science and Technology, Yangzhou University, Jiangsu 225009 (China); Bussolotti, Fabio [Institute for Molecular Science, Okazaki 444-8585 (Japan); Li, Yan-Qing; Tang, Jian-Xin [Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123 (China); Kera, Satoshi [Institute for Molecular Science, Okazaki 444-8585 (Japan); Graduate School of Advanced Integration Science, Chiba University, Chiba 263–8522 (Japan); Ueno, Nobuo, E-mail: yangjp@yzu.edu.cn, E-mail: uenon@faculty.chiba-u.jp [Graduate School of Advanced Integration Science, Chiba University, Chiba 263–8522 (Japan)

    2016-08-29

    The doping mechanism in organic-semiconductor films has been quantitatively studied via ultrahigh-sensitivity ultraviolet photoelectron spectroscopy of N,N-bis(1-naphthyl)-N,N-diphenyl-1,1-biphenyl-4,4-diamine (α-NPD) films doped with hexaazatriphenylene-hexacarbonitrile [HAT(CN){sub 6}]. We observed that HOMO of α-NPD shifts to the Fermi level (E{sub F}) in two different rates with the doping concentration of HAT(CN){sub 6}, but HOMO distributions of both pristine and doped amorphous α-NPD films are excellently approximated with a same Gaussian distribution without exponential tail states over ∼5 × 10{sup 18} cm{sup −3} eV{sup −1}. From the theoretical simulation of the HAT(CN){sub 6}-concentration dependence of the HOMO in doped films, we show that the passivation of Gaussian-distributed hole traps, which peak at 1.1 eV above the HOMO onset, occurs at ultralow doping [HAT(CN){sub 6} molecular ratio (MR) < 0.01], leading to a strong HOMO shift of ∼0.40 eV towards E{sub F}, and MR dependence of HOMO changes abruptly at MR ∼ 0.01 to a weaker dependence for MR > 0.01 due to future of the dopant acceptor level.

  3. Understanding the mechanism of atovaquone drug resistance in Plasmodium falciparum cytochrome b mutation Y268S using computational methods.

    Directory of Open Access Journals (Sweden)

    Bashir A Akhoon

    Full Text Available The rapid appearance of resistant malarial parasites after introduction of atovaquone (ATQ drug has prompted the search for new drugs as even single point mutations in the active site of Cytochrome b protein can rapidly render ATQ ineffective. The presence of Y268 mutations in the Cytochrome b (Cyt b protein is previously suggested to be responsible for the ATQ resistance in Plasmodium falciparum (P. falciparum. In this study, we examined the resistance mechanism against ATQ in P. falciparum through computational methods. Here, we reported a reliable protein model of Cyt bc1 complex containing Cyt b and the Iron-Sulphur Protein (ISP of P. falciparum using composite modeling method by combining threading, ab initio modeling and atomic-level structure refinement approaches. The molecular dynamics simulations suggest that Y268S mutation causes ATQ resistance by reducing hydrophobic interactions between Cyt bc1 protein complex and ATQ. Moreover, the important histidine contact of ATQ with the ISP chain is also lost due to Y268S mutation. We noticed the induced mutation alters the arrangement of active site residues in a fashion that enforces ATQ to find its new stable binding site far away from the wild-type binding pocket. The MM-PBSA calculations also shows that the binding affinity of ATQ with Cyt bc1 complex is enough to hold it at this new site that ultimately leads to the ATQ resistance.

  4. Understanding mechanisms of vitiligo development in Smyth line of chickens by transcriptomic microarray analysis of evolving autoimmune lesions

    Directory of Open Access Journals (Sweden)

    Shi Fengying

    2012-04-01

    Full Text Available Abstract Background The Smyth line (SL of chicken is an excellent avian model for human autoimmune vitiligo. The etiology of vitiligo is complicated and far from clear. In order to better understand critical components leading to vitiligo development, cDNA microarray technology was used to compare gene expression profiles in the target tissue (the growing feather of SL chickens at different vitiligo (SLV states. Results Compared to the reference sample, which was from Brown line chickens (the parental control, 395, 522, 524 and 526 out of the 44 k genes were differentially expressed (DE (P ≤ 0.05 in feather samples collected from SL chickens that never developed SLV (NV, from SLV chickens prior to SLV onset (EV, during active loss of pigmentation (AV, and after complete loss of melanocytes (CV. Comparisons of gene expression levels within SL samples (NV, EV, AV and CV revealed 206 DE genes, which could be categorized into immune system-, melanocyte-, stress-, and apoptosis-related genes based on the biological functions of their corresponding proteins. The autoimmune nature of SLV was supported by predominant presence of immune system related DE genes and their remarkably elevated expression in AV samples compared to NV, EV and/or CV samples. Melanocyte loss was confirmed by decreased expression of genes for melanocyte related proteins in AV and CV samples compared to NV and EV samples. In addition, SLV development was also accompanied by altered expression of genes associated with disturbed redox status and apoptosis. Ingenuity Pathway Analysis of DE genes provided functional interpretations involving but not limited to innate and adaptive immune response, oxidative stress and cell death. Conclusions The microarray results provided comprehensive information at the transcriptome level supporting the multifactorial etiology of vitiligo, where together with apparent inflammatory/innate immune activity and oxidative stress, the adaptive immune

  5. Profiling of glycan receptors for minute virus of mice in permissive cell lines towards understanding the mechanism of cell recognition.

    Directory of Open Access Journals (Sweden)

    Sujata Halder

    Full Text Available The recognition of sialic acids by two strains of minute virus of mice (MVM, MVMp (prototype and MVMi (immunosuppressive, is an essential requirement for successful infection. To understand the potential for recognition of different modifications of sialic acid by MVM, three types of capsids, virus-like particles, wild type empty (no DNA capsids, and DNA packaged virions, were screened on a sialylated glycan microarray (SGM. Both viruses demonstrated a preference for binding to 9-O-methylated sialic acid derivatives, while MVMp showed additional binding to 9-O-acetylated and 9-O-lactoylated sialic acid derivatives, indicating recognition differences. The glycans recognized contained a type-2 Galβ1-4GlcNAc motif (Neu5Acα2-3Galβ1-4GlcNAc or 3'SIA-LN and were biantennary complex-type N-glycans with the exception of one. To correlate the recognition of the 3'SIA-LN glycan motif as well as the biantennary structures to their natural expression in cell lines permissive for MVMp, MVMi, or both strains, the N- and O-glycans, and polar glycolipids present in three cell lines used for in vitro studies, A9 fibroblasts, EL4 T lymphocytes, and the SV40 transformed NB324K cells, were analyzed by MALDI-TOF/TOF mass spectrometry. The cells showed an abundance of the sialylated glycan motifs recognized by the viruses in the SGM and previous glycan microarrays supporting their role in cellular recognition by MVM. Significantly, the NB324K showed fucosylation at the non-reducing end of their biantennary glycans, suggesting that recognition of these cells is possibly mediated by the Lewis X motif as in 3'SIA-Le(X identified in a previous glycan microarray screen.

  6. CRH Affects the Phenotypic Expression of Sepsis-Associated Virulence Factors by Streptococcus pneumoniae Serotype 1 In vitro

    Directory of Open Access Journals (Sweden)

    Colette G. Ngo Ndjom

    2017-06-01

    Full Text Available Sepsis is a life-threatening health condition caused by infectious pathogens of the respiratory tract, and accounts for 28–50% of annual deaths in the US alone. Current treatment regimen advocates the use of corticosteroids as adjunct treatment with antibiotics, for their broad inhibitory effect on the activity and production of pro-inflammatory mediators. However, despite their use, corticosteroids have not proven to be able to reverse the death incidence among septic patients. We have previously demonstrated the potential for neuroendocrine factors to directly influence Streptococcus pneumoniae virulence, which may in turn mediate disease outcome leading to sepsis and septic shock. The current study investigated the role of Corticotropin-releasing hormone (CRH in mediating key markers of pneumococcal virulence as important phenotypic determinants of sepsis and septic shock risks. In vitro cultures of serotype 1 pneumococcal strain with CRH promoted growth rate, increased capsule thickness and penicillin resistance, as well as induced pneumolysin gene expression. These results thus provide significant insights of CRH–pathogen interactions useful in understanding the underlying mechanisms of neuroendocrine factor's role in the onset of community acquired pneumonias (CAP, sepsis and septic shock.

  7. The copper-responsive RicR regulon contributes to Mycobacterium tuberculosis virulence.

    Science.gov (United States)

    Shi, Xiaoshan; Festa, Richard A; Ioerger, Thomas R; Butler-Wu, Susan; Sacchettini, James C; Darwin, K Heran; Samanovic, Marie I

    2014-02-18

    As with most life on Earth, the transition metal copper (Cu) is essential for the viability of the human pathogen Mycobacterium tuberculosis. However, infected hosts can also use Cu to control microbial growth. Several Cu-responsive pathways are present in M. tuberculosis, including the regulated in copper repressor (RicR) regulon, which is unique to pathogenic mycobacteria. In this work, we describe the contribution of each RicR-regulated gene to Cu resistance in vitro and to virulence in animals. We found that the deletion or disruption of individual RicR-regulated genes had no impact on virulence in mice, although several mutants had Cu hypersensitivity. In contrast, a mutant unable to activate the RicR regulon was not only highly susceptible to Cu but also attenuated in mice. Thus, these data suggest that several genes of the RicR regulon are required simultaneously to combat Cu toxicity in vivo or that this regulon is also important for resistance against Cu-independent mechanisms of host defense. Mycobacterium tuberculosis is the causative agent of tuberculosis, killing millions of people every year. Therefore, understanding the biology of M. tuberculosis is crucial for the development of new therapies to treat this devastating disease. Our studies reveal that although host-supplied Cu can suppress bacterial growth, M. tuberculosis has a unique pathway, the RicR regulon, to defend against Cu toxicity. These findings suggest that Cu homeostasis pathways in both the host and the pathogen could be exploited for the treatment of tuberculosis.

  8. Partitioning CO2 fluxes with isotopologue measurements and modeling to understand mechanisms of forest carbon sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Saleska, Scott [Univ. of Arizona, Tucson, AZ (United States); Davidson, Eric [Univ. of Arizona, Tucson, AZ (United States); Finzi, Adrien [Univ. of Arizona, Tucson, AZ (United States); Wehr, Richard [Univ. of Arizona, Tucson, AZ (United States); Moorcroft, Paul [Univ. of Arizona, Tucson, AZ (United States)

    2016-01-28

    1. Objectives This project combines automated in situ observations of the isotopologues of CO2 with root observations, novel experimental manipulations of belowground processes, and isotope-enabled ecosystem modeling to investigate mechanisms of below- vs. aboveground carbon sequestration at the Harvard Forest Environmental Measurements Site (EMS). The proposed objectives, which have now been largely accomplished, include: A. Partitioning of net ecosystem CO2 exchange (NEE) into photosynthesis and respiration using long-term continuous observations of the isotopic composition of NEE, and analysis of their dynamics ; B. Investigation of the influence of vegetation phenology on the timing and magnitude of carbon allocated belowground using measurements of root growth and indices of belowground autotrophic vs. heterotrophic respiration (via trenched plots and isotope measurements); C. Testing whether plant allocation of carbon belowground stimulates the microbial decomposition of soil organic matter, using in situ rhizosphere simulation experiments wherein realistic quantities of artificial isotopically-labeled exudates are released into the soil; and D. Synthesis and interpretation of the above data using the Ecosystem Demography Model 2 (ED2). 2. Highlights Accomplishments: • Our isotopic eddy flux record has completed its 5th full year and has been used to independently estimate ecosystem-scale respiration and photosynthesis. • Soil surface chamber isotopic flux measurements were carried out during three growing seasons, in conjunction with a trenching manipulation. Key findings to date (listed by objective): A. Partitioning of Net Ecosystem Exchange: 1. Ecosystem respiration is lower during the day than at night—the first robust evidence of the inhibition of leaf respiration by light (the “Kok effect”) at the ecosystem scale. 2. Because it neglects the Kok effect, the standard NEE partitioning approach overestimates ecosystem

  9. Understanding the sorption mechanisms of aflatoxin B1 to kaolinite, illite, and smectite clays via a comparative computational study.

    Science.gov (United States)

    Kang, Fuxing; Ge, Yangyang; Hu, Xiaojie; Goikavi, Caspar; Waigi, Michael Gatheru; Gao, Yanzheng; Ling, Wanting

    2016-12-15

    In current adsorption studies of biotoxins to phyllosilicate clays, multiply weak bonding types regarding these adsorptions are not well known; the major attractive forces, especially for kaolinite and illite, are difficult to be identified as compared to smectite with exchangeable cations. Here, we discriminated the bonding types of aflatoxin B1 (AFB1) contaminant to these clays by combined batch experiment with model computation, expounded their bonding mechanisms which have been not quantitatively described by researchers. The observed adsorbent-to-solution distribution coefficients (K d ) of AFB1 presented in increasing order of 18.5-37.1, 141.6-158.3, and 354.6-484.7L/kg for kaolinite, illite, and smectite, respectively. Normalization of adsorbent-specific surface areas showed that adsorption affinity of AFB1 is mainly dependent on the outside surfaces of clay aggregates. The model computation and test of ionic effect further suggested that weakly electrostatic attractions ((Si/Al-OH) 2 ⋯(OC) 2 ) are responsible for AFB1-kaolinite adsorption (K d , 18.5-37.1L/kg); a moderate electron-donor-acceptor attraction ((CO) 2 ⋯K + ⋯(O-Al) 3 ) is related to AFB1-illite adsorption (K d , 141.6-158.3L/kg); a strong calcium-bridging linkage ((CO) 2 ⋯Ca 2+ ⋯(O-Si) 4 ) is involved in AFB1-smectite adsorption (K d , 354.6-484.7L/kg). Changes in Gibbs free energy (ΔG°) suggested that the computed result is reliable, providing a good reproduction of AFB1-clay interaction. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Chemical disguise of myrmecophilous cockroaches and its implications for understanding nestmate recognition mechanisms in leaf-cutting ants.

    Science.gov (United States)

    Nehring, Volker; Dani, Francesca R; Calamai, Luca; Turillazzi, Stefano; Bohn, Horst; Klass, Klaus-Dieter; d'Ettorre, Patrizia

    2016-08-05

    Cockroaches of the genus Attaphila regularly occur in leaf-cutting ant colonies. The ants farm a fungus that the cockroaches also appear to feed on. Cockroaches disperse between colonies horizontally (via foraging trails) and vertically (attached to queens on their mating flights). We analysed the chemical strategies used by the cockroaches to integrate into colonies of Atta colombica and Acromyrmex octospinosus. Analysing cockroaches from nests of two host species further allowed us to test the hypothesis that nestmate recognition is based on an asymmetric mechanism. Specifically, we test the U-present nestmate recognition model, which assumes that detection of undesirable cues (non-nestmate specific substances) leads to strong rejection of the cue-bearers, while absence of desirable cues (nestmate-specific substances) does not necessarily trigger aggression. We found that nests of Atta and Acromyrmex contained cockroaches of two different and not yet described Attaphila species. The cockroaches share the cuticular chemical substances of their specific host species and copy their host nest's colony-specific cuticular profile. Indeed, the cockroaches are accepted by nestmate but attacked by non-nestmate ant workers. Cockroaches from Acromyrmex colonies bear a lower concentration of cuticular substances and are less likely to be attacked by non-nestmate ants than cockroaches from Atta colonies. Nest-specific recognition of Attaphila cockroaches by host workers in combination with nest-specific cuticular chemical profiles suggest that the cockroaches mimic their host's recognition labels, either by synthesizing nest-specific substances or by substance transfer from ants. Our finding that the cockroach species with lower concentration of cuticular substances receives less aggression by both host species fully supports the U-present nestmate recognition model. Leaf-cutting ant nestmate recognition is thus asymmetric, responding more strongly to differences than to

  11. Understanding inhibitory mechanisms of lumbar spinal manipulation using H-reflex and F-wave responses: a methodological approach.

    Science.gov (United States)

    Dishman, J Donald; Weber, Kenneth A; Corbin, Roger L; Burke, Jeanmarie R

    2012-09-30

    The purpose of this research was to characterize unique neurophysiologic events following a high velocity, low amplitude (HVLA) spinal manipulation (SM) procedure. Descriptive time series analysis techniques of time plots, outlier detection and autocorrelation functions were applied to time series of tibial nerve H-reflexes that were evoked at 10-s intervals from 100 s before the event until 100 s after three distinct events L5-S1 HVLA SM, or a L5-S1 joint pre-loading procedure, or the control condition. Sixty-six subjects were randomly assigned to three procedures, i.e., 22 time series per group. If the detection of outliers and correlograms revealed a pattern of non-randomness that was only time-locked to a single, specific event in the normalized time series, then an experimental effect would be inferred beyond the inherent variability of H-reflex responses. Tibial nerve F-wave responses were included to determine if any new information about central nervous function following a HVLA SM procedure could be ascertained. Time series analyses of H(max)/M(max) ratios, pre-post L5-S1 HVLA SM, substantiated the hypothesis that the specific aspects of the manipulative thrust lead to a greater attenuation of the H(max)/M(max) ratio as compared to the non-specific aspects related to the postural perturbation and joint pre-loading. The attenuation of the H(max)/M(max) ratio following the HVLA SM procedure was reliable and may hold promise as a translational tool to measure the consistency and accuracy of protocol implementation involving SM in clinical trials research. F-wave responses were not sensitive to mechanical perturbations of the lumbar spine. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Towards understanding the E. coli PNP binding mechanism and FRET absence between E. coli PNP and formycin A.

    Science.gov (United States)

    Prokopowicz, Małgorzata; Greń, Bartosz; Cieśla, Joanna; Kierdaszuk, Borys

    2017-11-01

    The aim of this study is threefold: (1) augmentation of the knowledge of the E. coli PNP binding mechanism; (2) explanation of the previously observed 'lack of FRET' phenomenon and (3) an introduction of the correction (modified method) for FRET efficiency calculation in the PNP-FA complexes. We present fluorescence studies of the two E. coli PNP mutants (F159Y and F159A) with formycin A (FA), that indicate that the aromatic amino acid is indispensable in the nucleotide binding, additional hydroxyl group at position 159 probably enhances the strength of binding and that the amino acids pair 159-160 has a great impact on the spectroscopic properties of the enzyme. The experiments were carried out in hepes and phosphate buffers, at pH7 and 8.3. Two methods, a conventional and a modified one, that utilizes the dissociation constant, for calculations of the energy transfer efficiency (E) and the acceptor-to-donor distance (r) between FA and the Tyr (energy donor) were employed. Total difference spectra were calculated for emission spectra (λ ex 280nm, 295nm, 305nm and 313nm) for all studied systems. Time-resolved techniques allowed to conclude the existence of a specific structure formed by amino acids at positions 159 and 160. The results showed an unexpected pattern change of FRET in the mutants, when compared to the wild type enzyme and a probable presence of a structure created between 159 and 160 residue, that might influence the binding efficiency. Additionally, we confirmed the indispensable role of the modification of the FRET efficiency (E) calculation on the fraction of enzyme saturation in PNP-FA systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Virulence factors of avian pathogenic Escherichia coli (APEC Fatores de virulência de Escherichia coli aviária patogênica (APEC

    Directory of Open Access Journals (Sweden)

    Gerson Nakazato

    2009-07-01

    Full Text Available Avian pathogenic Escherichia coli (APEC strains cause a great diversity of diseases in birds and are responsible for great economic losses in the avian industry. To date, several studies have been carried out to better understand the APEC pathogenesis for a possible development of tools which could prevent the economics losses caused by these strains. This review discusses the virulence factors described do date to be expressed by these strains and the advances made to understand and identify virulence determinants present in APEC.Linhagens de Escherichia coli patogênicas para aves (APEC causam uma grande diversidade de doenças em aves e são responsáveis por grandes prejuízos na indústria aviária. Nos últimos anos, vários estudos foram realizados para melhor entender a patogênese de linhagens APEC e para desenvolver ferramentas que podem prevenir as perdas econômicas causadas por estas linhagens. Esta revisão discute os fatores de virulência descritos nestas linhagens e os avanços realizados para entender e identificar os determinantes de virulência presentes em APEC.

  14. Virulence-Associated Genome Mutations of Murine Rotavirus Identified by Alternating Serial Passages in Mice and Cell Cultures

    Science.gov (United States)

    Tatsumi, Masatoshi; Tsutsumi, Hiroyuki

    2014-01-01

    ABSTRACT Although significant clinical efficacy and safety of rotavirus vaccines were recently revealed in many countries, the mechanism of their attenuation is not well understood. We passaged serially a cell culture-adapted murine rotavirus EB strain in mouse pups or in cell cultures alternately and repeatedly and fully sequenced all 11 genes of 21 virus samples passaged in mice or in cell cultures. Sequence analysis revealed that mouse-passaged viruses that regained virulence almost consistently acquired four kinds of amino acid (aa) substitutions in VP4 and substitution in aa 37 (Val to Ala) in NSP4. In addition, they gained and invariably conserved the 3′ consensus sequence in NSP1. The molecular changes occurred along with the acquisition of virulence during passages in mice and then disappeared following passages in cell cultures. Intraperitoneal injection of recombinant NSP4 proteins confirmed the aa 37 site as important for its diarrheagenic activity in mice. These genome changes are likely to be correlated with rotavirus virulence. IMPORTANCE Serial passage of a virulent wild-type virus in vitro often results in loss of virulence of the virus in an original animal host, while serial passage of a cell culture-adapted avirulent virus in vivo often gains virulence in an animal host. Actually, live attenuated virus vaccines were originally produced by serial passage in cell cultures. Although clinical efficacy and safety of rotavirus vaccines were recently revealed, the mechanism of their attenuation is not well understood. We passaged serially a murine rotavirus by alternating switch of host (mice or cell cultures) repeatedly and sequenced the eleven genes of the passaged viruses to identify mutations associated with the emergence or disappearance of virulence. Sequence analysis revealed that changes in three genes (VP4, NSP1, and NSP4) were associated with virulence in mice. Intraperitoneal injection of recombinant NSP4 proteins confirmed its

  15. The Listeria monocytogenes ChiA chitinase enhances virulence through suppression of host innate immunity.

    Science.gov (United States)

    Chaudhuri, Swarnava; Gantner, Benjamin N; Ye, Richard D; Cianciotto, Nicholas P; Freitag, Nancy E

    2013-03-19

    Environmental pathogens survive and replicate within the outside environment while maintaining the capacity to infect mammalian hosts. For some microorganisms, mammalian infection may be a relatively rare event. Understanding how environmental pathogens retain their ability to cause disease may provide insight into environmental reservoirs of disease and emerging infections. Listeria monocytogenes survives as a saprophyte in soil but is capable of causing serious invasive disease in susceptible individuals. The bacterium secretes virulence factors that promote cell invasion, bacterial replication, and cell-to-cell spread. Recently, an L. monocytogenes chitinase (ChiA) was shown to enhance bacterial infection in mice. Given that mammals do not synthesize chitin, the function of ChiA within infected animals was not clear. Here we have demonstrated that ChiA enhances L. monocytogenes survival in vivo through the suppression of host innate immunity. L. monocytogenes ΔchiA mutants were fully capable of establishing bacterial replication within target organs during the first 48 h of infection. By 72 to 96 h postinfect