Sample records for host defense system
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Carp erythrodermatitis : host defense-pathogen interaction
Pourreau, C.N.
1990-01-01
The outcome of a bacterial infection depends on the interaction between pathogen and host. The ability of the microbe to survive in the host depends on its invasive potential (i.e. spreading and multiplication), and its ability to obtain essential nutrients and to resist the host's defense system. On the other hand, the host's resistance to a bacterial attack depends on its physiological state, the intensity of the bacterial attack and the efficacy of the defense system to ...
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Coevolutionary arms race versus host defense chase in a tropical herbivore-plant system.
Endara, María-José; Coley, Phyllis D; Ghabash, Gabrielle; Nicholls, James A; Dexter, Kyle G; Donoso, David A; Stone, Graham N; Pennington, R Toby; Kursar, Thomas A
2017-09-05
Coevolutionary models suggest that herbivores drive diversification and community composition in plants. For herbivores, many questions remain regarding how plant defenses shape host choice and community structure. We addressed these questions using the tree genus Inga and its lepidopteran herbivores in the Amazon. We constructed phylogenies for both plants and insects and quantified host associations and plant defenses. We found that similarity in herbivore assemblages between Inga species was correlated with similarity in defenses. There was no correlation with phylogeny, a result consistent with our observations that the expression of defenses in Inga is independent of phylogeny. Furthermore, host defensive traits explained 40% of herbivore community similarity. Analyses at finer taxonomic scales showed that different lepidopteran clades select hosts based on different defenses, suggesting taxon-specific histories of herbivore-host plant interactions. Finally, we compared the phylogeny and defenses of Inga to phylogenies for the major lepidopteran clades. We found that closely related herbivores fed on Inga with similar defenses rather than on closely related plants. Together, these results suggest that plant defenses might be more evolutionarily labile than the herbivore traits related to host association. Hence, there is an apparent asymmetry in the evolutionary interactions between Inga and its herbivores. Although plants may evolve under selection by herbivores, we hypothesize that herbivores may not show coevolutionary adaptations, but instead "chase" hosts based on the herbivore's own traits at the time that they encounter a new host, a pattern more consistent with resource tracking than with the arms race model of coevolution.
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Lifescience Database Archive (English)
Full Text Available 15075354 Toll-like receptors and the host defense against microbial pathogens: brin...oc Biol. 2004 May;75(5):749-55. Epub 2004 Jan 14. (.png) (.svg) (.html) (.csml) Show Toll-like receptors and the host defense again...immune system. PubmedID 15075354 Title Toll-like receptors and the host defense against microbial pathogens:
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Kupffer cell complement receptor clearance function and host defense.
Loegering, D J
1986-01-01
Kupffer cells are well known to be important for normal host defense function. The development of methods to evaluate the in vivo function of specific receptors on Kupffer cells has made it possible to assess the role of these receptors in host defense. The rationale for studying complement receptors is based on the proposed important role of these receptors in host defense and on the observation that the hereditary deficiency of a complement receptor is associated with recurrent severe bacterial infections. The studies reviewed here demonstrate that forms of injury that are associated with depressed host defense including thermal injury, hemorrhagic shock, trauma, and surgery also cause a decrease in complement receptor clearance function. This decrease in Kupffer cell receptor clearance function was shown not to be the result of depressed hepatic blood flow or depletion of complement components. Complement receptor function was also depressed following the phagocytosis of particulates that are known to depress Kupffer cell host defense function. Endotoxemia and bacteremia also were associated with a depression of complement receptor function. Complement receptor function was experimentally depressed in uninjured animals by the phagocytosis of IgG-coated erythrocytes. There was a close association between the depression of complement receptor clearance function and increased susceptibility to the lethal effects of endotoxin and bacterial infection. These studies support the hypotheses that complement receptors on Kupffer cells are important for normal host defense and that depression of the function of these receptors impairs host defense.
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The Inflammasome in Host Defense
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Gang Chen
2009-12-01
Full Text Available Nod-like receptors have emerged as an important family of sensors in host defense. These receptors are expressed in macrophages, dendritic cells and monocytes and play an important role in microbial immunity. Some Nod-like receptors form the inflammasome, a protein complex that activates caspase-1 in response to several stimuli. Caspase-1 activation leads to processing and secretion of pro-inflammatory cytokines such as interleukin (IL-1β and IL-18. Here, we discuss recent advances in the inflammasome field with an emphasis on host defense. We also compare differential requirements for inflammasome activation in dendritic cells, macrophages and monocytes.
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Wu, Chia-Chou; Chen, Bor-Sen
2016-01-01
Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host-pathogen dynamic interaction networks. The consideration of host-pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host-pathogen molecular interaction networks, and consequent inferences of the host-pathogen relationship could be translated into biomedical applications.
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Evasion of host immune defenses by human papillomavirus.
Westrich, Joseph A; Warren, Cody J; Pyeon, Dohun
2017-03-02
A majority of human papillomavirus (HPV) infections are asymptomatic and self-resolving in the absence of medical interventions. Various innate and adaptive immune responses, as well as physical barriers, have been implicated in controlling early HPV infections. However, if HPV overcomes these host immune defenses and establishes persistence in basal keratinocytes, it becomes very difficult for the host to eliminate the infection. The HPV oncoproteins E5, E6, and E7 are important in regulating host immune responses. These oncoproteins dysregulate gene expression, protein-protein interactions, posttranslational modifications, and cellular trafficking of critical host immune modulators. In addition to the HPV oncoproteins, sequence variation and dinucleotide depletion in papillomavirus genomes has been suggested as an alternative strategy for evasion of host immune defenses. Since anti-HPV host immune responses are also considered to be important for antitumor immunity, immune dysregulation by HPV during virus persistence may contribute to immune suppression essential for HPV-associated cancer progression. Here, we discuss cellular pathways dysregulated by HPV that allow the virus to evade various host immune defenses. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
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CXCR1 regulates pulmonary anti-Pseudomonas host defense
Carevic, M.; Öz, H.; Fuchs, K.; Laval, J.; Schroth, C.; Frey, N.; Hector, A.; Bilich, T.; Haug, M.; Schmidt, A.; Autenrieth, S. E.; Bucher, K.; Beer-Hammer, S.; Gaggar, A.; Kneilling, M.; Benarafa, C.; Gao, J.; Murphy, P.; Schwarz, S.; Moepps, B.; Hartl, D.
2016-01-01
Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-Pseudomonas aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway Pseudomonas aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against Pseudomonas aeruginosa. Mechanistically, CXCR1 regulated anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with toll-like receptor 5 expression. These studies define CXCR1 as a novel non-canonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases. PMID:26950764
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Shigella infection of intestinal epithelium and circumvention of the host innate defense system.
Ashida, Hiroshi; Ogawa, Michinaga; Mimuro, Hitomi; Sasakawa, Chihiro
2009-01-01
Shigella, Gram-negative bacteria closely related to Escherichia coli, are highly adapted human pathogens that cause bacillary dysentery. Although Shigella have neither adherence factors nor flagella required for attaching or accessing the intestinal epithelium, Shigella are capable of colonizing the intestinal epithelium by exploiting epithelial-cell functions and circumventing the host innate immune response. During Shigella infection, they deliver many numbers of effectors through the type III secretion system into the surrounding space and directly into the host-cell cytoplasm. The effectors play pivotal roles from the onset of bacterial infection through to the establishment of the colonization of the intestinal epithelium, such as bacterial invasion, intracellular survival, subversion of the host immune defense response, and maintenance of the infectious foothold. These examples suggest that Shigella have evolved highly sophisticated infectious and intracellular strategies to establish replicative niches in the intestinal epithelium.
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Salt, chloride, bleach, and innate host defense
Wang, Guoshun; Nauseef, William M.
2015-01-01
Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense. PMID:26048979
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Salt, chloride, bleach, and innate host defense.
Wang, Guoshun; Nauseef, William M
2015-08-01
Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense. © Society for Leukocyte Biology.
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Acute radiation syndrome (ARS – treatment of the reduced host defense
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Heslet L
2012-01-01
Full Text Available Lars Heslet1, Christiane Bay2, Steen Nepper-Christensen31Serendex ApS, Gentofte; 2University of Copenhagen, Medical Faculty, Copenhagen; 3Department of Head and Neck Surgery, Otorhinolaryngology, Køge University Hospital, Køge, DenmarkBackground: The current radiation threat from the Fukushima power plant accident has prompted rethinking of the contingency plan for prophylaxis and treatment of the acute radiation syndrome (ARS. The well-documented effect of the growth factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF] in acute radiation injury has become standard treatment for ARS in the United States, based on the fact that growth factors increase number and functions of both macrophages and granulocytes.Methods: Review of the current literature.Results: The lungs have their own host defense system, based on alveolar macrophages. After radiation exposure to the lungs, resting macrophages can no longer be transformed, not even during systemic administration of growth factors because G-CSF/GM-CSF does not penetrate the alveoli. Under normal circumstances, locally-produced GM-CSF receptors transform resting macrophages into fully immunocompetent dendritic cells in the sealed-off pulmonary compartment. However, GM-CSF is not expressed in radiation injured tissue due to defervescence of the macrophages. In order to maintain the macrophage’s important role in host defense after radiation exposure, it is hypothesized that it is necessary to administer the drug exogenously in order to uphold the barrier against exogenous and endogenous infections and possibly prevent the potentially lethal systemic infection, which is the main cause of death in ARS.Recommendation: Preemptive treatment should be initiated after suspected exposure of a radiation dose of at least ~2 Gy by prompt dosing of 250–400 µg GM-CSF/m2 or 5 µg/kg G-CSF administered systemically and concomitant inhalation of
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Dühring, Sybille; Germerodt, Sebastian; Skerka, Christine; Zipfel, Peter F.; Dandekar, Thomas; Schuster, Stefan
2015-01-01
The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given. PMID:26175718
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Impact of Childhood Malnutrition on Host Defense and Infection.
Ibrahim, Marwa K; Zambruni, Mara; Melby, Christopher L; Melby, Peter C
2017-10-01
The global impact of childhood malnutrition is staggering. The synergism between malnutrition and infection contributes substantially to childhood morbidity and mortality. Anthropometric indicators of malnutrition are associated with the increased risk and severity of infections caused by many pathogens, including viruses, bacteria, protozoa, and helminths. Since childhood malnutrition commonly involves the inadequate intake of protein and calories, with superimposed micronutrient deficiencies, the causal factors involved in impaired host defense are usually not defined. This review focuses on literature related to impaired host defense and the risk of infection in primary childhood malnutrition. Particular attention is given to longitudinal and prospective cohort human studies and studies of experimental animal models that address causal, mechanistic relationships between malnutrition and host defense. Protein and micronutrient deficiencies impact the hematopoietic and lymphoid organs and compromise both innate and adaptive immune functions. Malnutrition-related changes in intestinal microbiota contribute to growth faltering and dysregulated inflammation and immune function. Although substantial progress has been made in understanding the malnutrition-infection synergism, critical gaps in our understanding remain. We highlight the need for mechanistic studies that can lead to targeted interventions to improve host defense and reduce the morbidity and mortality of infectious diseases in this vulnerable population. Copyright © 2017 American Society for Microbiology.
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Central importance of immunoglobulin A in host defense against Giardia spp.
Langford, T Dianne; Housley, Michael P; Boes, Marianne; Chen, Jianzhu; Kagnoff, Martin F; Gillin, Frances D; Eckmann, Lars
2002-01-01
The protozoan pathogen Giardia is an important cause of parasitic diarrheal disease worldwide. It colonizes the lumen of the small intestine, suggesting that effective host defenses must act luminally. Immunoglobulin A (IgA) antibodies are presumed to be important for controlling Giardia infection, but direct evidence for this function is lacking. B-cell-independent effector mechanisms also exist and may be equally important for antigiardial host defense. To determine the importance of the immunoglobulin isotypes that are transported into the intestinal lumen, IgA and IgM, for antigiardial host defense, we infected gene-targeted mice lacking IgA-expressing B-cells, IgM-secreting B-cells, or all B-cells as controls with Giardia muris or Giardia lamblia GS/M-83-H7. We found that IgA-deficient mice could not eradicate either G. muris or G. lamblia infection, demonstrating that IgA is required for their clearance. Furthermore, although neither B-cell-deficient nor IgA-deficient mice could clear G. muris infections, IgA-deficient mice controlled infection significantly better than B-cell-deficient mice, suggesting the existence of B-cell-dependent but IgA-independent antigiardial defenses. In contrast, mice deficient for secreted IgM antibodies cleared G. muris infection normally, indicating that they have no unique functions in antigiardial host defense. These data, together with the finding that B-cell-deficient mice have some, albeit limited, residual capacity to control G. muris infection, show that IgA-dependent host defenses are central for eradicating Giardia spp. Moreover, B-cell-dependent but IgA-independent and B-cell-independent antigiardial host defenses exist but are less important for controlling infection.
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The C-terminal sequence of several human serine proteases encodes host defense functions.
Kasetty, Gopinath; Papareddy, Praveen; Kalle, Martina; Rydengård, Victoria; Walse, Björn; Svensson, Bo; Mörgelin, Matthias; Malmsten, Martin; Schmidtchen, Artur
2011-01-01
Serine proteases of the S1 family have maintained a common structure over an evolutionary span of more than one billion years, and evolved a variety of substrate specificities and diverse biological roles, involving digestion and degradation, blood clotting, fibrinolysis and epithelial homeostasis. We here show that a wide range of C-terminal peptide sequences of serine proteases, particularly from the coagulation and kallikrein systems, share characteristics common with classical antimicrobial peptides of innate immunity. Under physiological conditions, these peptides exert antimicrobial effects as well as immunomodulatory functions by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, selected peptides are protective against lipopolysaccharide-induced shock. Moreover, these S1-derived host defense peptides exhibit helical structures upon binding to lipopolysaccharide and also permeabilize liposomes. The results uncover new and fundamental aspects on host defense functions of serine proteases present particularly in blood and epithelia, and provide tools for the identification of host defense molecules of therapeutic interest. Copyright © 2011 S. Karger AG, Basel.
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Insights from human studies into the host defense against candidiasis.
Filler, Scott G
2012-04-01
Candida spp. are the most common cause of mucosal and disseminated fungal infections in humans. Studies using mutant strains of mice have provided initial information about the roles of dectin-1, CARD9, and Th17 cytokines in the host defense against candidiasis. Recent technological advances have resulted in the identification of mutations in specific genes that predispose humans to develop candidal infection. The analysis of individuals with these mutations demonstrates that dectin-1 is critical for the host defense against vulvovaginal candidiasis and candidal colonization of the gastrointestinal tract. They also indicate that CARD9 is important for preventing both mucosal and disseminated candidiasis, whereas the Th17 response is necessary for the defense against mucocutaneous candidiasis. This article reviews the recent studies of genetic defects in humans that result in an increased susceptibility to candidiasis and discusses how these studies provide new insight into the host defense against different types of candidal infections. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Host Defense Mechanisms against Bark Beetle Attack Differ between Ponderosa and Lodgepole Pines
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Daniel R. West
2016-10-01
Full Text Available Conifer defenses against bark beetle attack include, but are not limited to, quantitative and qualitative defenses produced prior to attack. Our objective was to assess host defenses of lodgepole pine and ponderosa pine from ecotone stands. These stands provide a transition of host species for mountain pine beetle (Dendroctonus ponderosae; MPB. We asked two questions: (1 do the preformed quantitative host defenses (amount of resin and (2 the preformed qualitative host defenses (monoterpene constituents differ between lodgepole and ponderosa pines. We collected oleoresins at three locations in the Southern Rocky Mountains from 56 pairs of the pine species of similar size and growing conditions. The amount of preformed-ponderosa pine oleoresins exuded in 24 h (mg was almost four times that of lodgepole pine. Total qualitative preformed monoterpenes did not differ between the two hosts, though we found differences in all but three monoterpenes. No differences were detected in α-pinene, γ-terpinene, and bornyl acetate. We found greater concentrations of limonene, β-phellandrene, and cymene in lodgepole pines, whereas β-pinene, 3-carene, myrcene, and terpinolene were greater in ponderosa pine. Although we found differences both in quantitative and qualitative preformed oleoresin defenses, the ecological relevance of these differences to bark beetle susceptibility have not been fully tested.
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Herbert, Bethany A.; Novince, Chad M.; Kirkwood, Keith L.
2015-01-01
Summary Aggregatibacter actinomycetemcomitans is a perio-pathogenic bacteria that has long been associated with localized aggressive periodontitis. The mechanisms of its pathogenicity have been studied in humans and pre-clinical experimental models. Although different serotypes of A. actinomycetemcomitans have differential virulence factor expression, A. actinomycetemcomitans cytolethal distending toxin (CDT), leukotoxin, and lipopolysaccharide (LPS) have been most extensively studied in the context of modulating the host immune response. Following colonization and attachment in the oral cavity, A. actinomycetemcomitans employs CDT, leukotoxin, and LPS to evade host innate defense mechanisms and drive a pathophysiologic inflammatory response. This supra-physiologic immune response state perturbs normal periodontal tissue remodeling/turnover and ultimately has catabolic effects on periodontal tissue homeostasis. In this review, we have divided the host response into two systems: non-hematopoietic and hematopoietic. Non-hematopoietic barriers include epithelium and fibroblasts that initiate the innate immune host response. The hematopoietic system contains lymphoid and myeloid-derived cell lineages that are responsible for expanding the immune response and driving the pathophysiologic inflammatory state in the local periodontal microenvironment. Effector systems and signaling transduction pathways activated and utilized in response to A. actinomycetemcomitans will be discussed to further delineate immune cell mechanisms during A. actinomycetemcomitans infection. Finally, we will discuss the osteo-immunomodulatory effects induced by A. actinomycetemcomitans and dissect the catabolic disruption of balanced osteoclast-osteoblast mediated bone remodeling, which subsequently leads to net alveolar bone loss. PMID:26197893
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CHAOS: An SDN-Based Moving Target Defense System
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Yuan Shi
2017-01-01
Full Text Available Moving target defense (MTD has provided a dynamic and proactive network defense to reduce or move the attack surface that is available for exploitation. However, traditional network is difficult to realize dynamic and active security defense effectively and comprehensively. Software-defined networking (SDN points out a brand-new path for building dynamic and proactive defense system. In this paper, we propose CHAOS, an SDN-based MTD system. Utilizing the programmability and flexibility of SDN, CHAOS obfuscates the attack surface including host mutation obfuscation, ports obfuscation, and obfuscation based on decoy servers, thereby enhancing the unpredictability of the networking environment. We propose the Chaos Tower Obfuscation (CTO method, which uses the Chaos Tower Structure (CTS to depict the hierarchy of all the hosts in an intranet and define expected connection and unexpected connection. Moreover, we develop fast CTO algorithms to achieve a different degree of obfuscation for the hosts in each layer. We design and implement CHAOS as an application of SDN controller. Our approach makes it very easy to realize moving target defense in networks. Our experimental results show that a network protected by CHAOS is capable of decreasing the percentage of information disclosure effectively to guarantee the normal flow of traffic.
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Directory of Open Access Journals (Sweden)
Brett Williams
2011-06-01
Full Text Available Sclerotinia sclerotiorum is a necrotrophic ascomycete fungus with an extremely broad host range. This pathogen produces the non-specific phytotoxin and key pathogenicity factor, oxalic acid (OA. Our recent work indicated that this fungus and more specifically OA, can induce apoptotic-like programmed cell death (PCD in plant hosts, this induction of PCD and disease requires generation of reactive oxygen species (ROS in the host, a process triggered by fungal secreted OA. Conversely, during the initial stages of infection, OA also dampens the plant oxidative burst, an early host response generally associated with plant defense. This scenario presents a challenge regarding the mechanistic details of OA function; as OA both suppresses and induces host ROS during the compatible interaction. In the present study we generated transgenic plants expressing a redox-regulated GFP reporter. Results show that initially, Sclerotinia (via OA generates a reducing environment in host cells that suppress host defense responses including the oxidative burst and callose deposition, akin to compatible biotrophic pathogens. Once infection is established however, this necrotroph induces the generation of plant ROS leading to PCD of host tissue, the result of which is of direct benefit to the pathogen. In contrast, a non-pathogenic OA-deficient mutant failed to alter host redox status. The mutant produced hypersensitive response-like features following host inoculation, including ROS induction, callose formation, restricted growth and cell death. These results indicate active recognition of the mutant and further point to suppression of defenses by the wild type necrotrophic fungus. Chemical reduction of host cells with dithiothreitol (DTT or potassium oxalate (KOA restored the ability of this mutant to cause disease. Thus, Sclerotinia uses a novel strategy involving regulation of host redox status to establish infection. These results address a long-standing issue
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Herbert, B A; Novince, C M; Kirkwood, K L
2016-06-01
Aggregatibacter actinomycetemcomitans is a perio-pathogenic bacteria that has long been associated with localized aggressive periodontitis. The mechanisms of its pathogenicity have been studied in humans and preclinical experimental models. Although different serotypes of A. actinomycetemcomitans have differential virulence factor expression, A. actinomycetemcomitans cytolethal distending toxin (CDT), leukotoxin, and lipopolysaccharide (LPS) have been most extensively studied in the context of modulating the host immune response. Following colonization and attachment in the oral cavity, A. actinomycetemcomitans employs CDT, leukotoxin, and LPS to evade host innate defense mechanisms and drive a pathophysiologic inflammatory response. This supra-physiologic immune response state perturbs normal periodontal tissue remodeling/turnover and ultimately has catabolic effects on periodontal tissue homeostasis. In this review, we have divided the host response into two systems: non-hematopoietic and hematopoietic. Non-hematopoietic barriers include epithelium and fibroblasts that initiate the innate immune host response. The hematopoietic system contains lymphoid and myeloid-derived cell lineages that are responsible for expanding the immune response and driving the pathophysiologic inflammatory state in the local periodontal microenvironment. Effector systems and signaling transduction pathways activated and utilized in response to A. actinomycetemcomitans will be discussed to further delineate immune cell mechanisms during A. actinomycetemcomitans infection. Finally, we will discuss the osteo-immunomodulatory effects induced by A. actinomycetemcomitans and dissect the catabolic disruption of balanced osteoclast-osteoblast-mediated bone remodeling, which subsequently leads to net alveolar bone loss. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Lifescience Database Archive (English)
Full Text Available 17502370 The interferon regulatory factor family in host defense: mechanism of acti....html) (.csml) Show The interferon regulatory factor family in host defense: mechanism of action. PubmedID 1...7502370 Title The interferon regulatory factor family in host defense: mechanism
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The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis.
Ifrim, Daniela C; Quintin, Jessica; Courjol, Flavie; Verschueren, Ineke; van Krieken, J Han; Koentgen, Frank; Fradin, Chantal; Gow, Neil A R; Joosten, Leo A B; van der Meer, Jos W M; van de Veerdonk, Frank; Netea, Mihai G
2016-04-01
Despite the fact that Candida albicans is an important human fungal pathogen and Dectin-2 is a major pattern recognition receptor for fungi, our knowledge regarding the role of Dectin-2 for the host defense against disseminated candidiasis is limited. Dectin-2 deficient (Dectin-2(-/-)) mice were more susceptible to systemic candidiasis, and the susceptibility was mirrored by an elevated fungal load in the kidneys that correlated with the presence of large inflammatory foci. Phagocytosis of Candida by the macrophages lacking the Dectin-2 receptor was moderately decreased, while production of most of the macrophage-derived cytokines from Dectin-2(-/-) mice with systemic candidiasis was decreased. No striking differences among several Candida mutants defective in mannans could be detected between naïve wild-type and Dectin-2(-/-) mice, apart from the β-mannan-deficient bmt1Δ/bmt2Δ/bmt5Δ triple mutant, suggesting that β-mannan may partially mask α-mannan detection, which is the major fungal structure recognized by Dectin-2. Deciphering the mechanisms responsible for host defense against the majority of C. albicans strains represents an important step in understanding the pathophysiology of systemic candidiasis, which might lead to the development of novel immunotherapeutic strategies.
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Host defense, dendritic cells and the human lung
J.M.W. van Haarst (Jan Maarten)
1995-01-01
textabstractHost defense mechanisms protect the body against microorganisms and other foreign structures. These mechanisms can be divided in nonspecific, or innate, and specific, or acquired, immunity. In both branches of immunity the several types of leukocytes (white blood cells) play a dominant
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Directory of Open Access Journals (Sweden)
Sybille eDühring
2015-06-01
Full Text Available The diploid, polymorphic yeast Candida albicans is one of the most important humanpathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within thehuman host for a long time. Alterations in the host environment, however, can render C. albicansvirulent. In this review, we describe the immunological cross-talk between C. albicans and thehuman innate immune system. We give an overview in form of pairs of human defense strategiesincluding immunological mechanisms as well as general stressors such as nutrient limitation,pH, fever etc. and the corresponding fungal response and evasion mechanisms. FurthermoreComputational Systems Biology approaches to model and investigate these complex interactionare highlighted with a special focus on game-theoretical methods and agent-based models. Anoutlook on interesting questions to be tackled by Systems Biology regarding entangled defenseand evasion mechanisms is given.
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Progranulin Plays a Central Role in Host Defense during Sepsis by Promoting Macrophage Recruitment.
Song, Zhixin; Zhang, Xuemei; Zhang, Liping; Xu, Fang; Tao, Xintong; Zhang, Hua; Lin, Xue; Kang, Lihua; Xiang, Yu; Lai, Xaiofei; Zhang, Qun; Huang, Kun; Dai, Yubing; Yin, Yibing; Cao, Ju
2016-11-15
Progranulin, a widely expressed protein, has multiple physiological functions. The functional role of progranulin in the host response to sepsis remains unknown. To assess the role of progranulin in the host response to sepsis. Effects of progranulin on host response to sepsis were determined. Progranulin concentrations were significantly elevated in adult (n = 74) and pediatric (n = 26) patients with sepsis relative to corresponding healthy adult (n = 36) and pediatric (n = 17) control subjects, respectively. By using a low-lethality model of nonsevere sepsis, we observed that progranulin deficiency not only increased mortality but also decreased bacterial clearance during sepsis. The decreased host defense to sepsis in progranulin-deficient mice was associated with reduced macrophage recruitment, with correspondingly impaired chemokine CC receptor ligand 2 (CCL2) production in peritoneal lavages during the early phase of sepsis. Progranulin derived from hematopoietic cells contributed to host defense in sepsis. Therapeutic administration of recombinant progranulin not only rescued impaired host defense in progranulin-deficient mice after nonsevere sepsis but also protected wild-type mice against a high-lethality model of severe sepsis. Progranulin-mediated protection against sepsis was closely linked to improved peritoneal macrophage recruitment. In addition, CCL2 treatment of progranulin-deficient mice improved survival and decreased peritoneal bacterial loads during sepsis, at least in part through promotion of peritoneal macrophage recruitment. This proof-of-concept study supports a central role of progranulin-dependent macrophage recruitment in host defense to sepsis, opening new opportunities to host-directed therapeutic strategy that manipulate host immune response in the treatment of sepsis.
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Early-Life Diet Affects Host Microbiota and Later-Life Defenses Against Parasites in Frogs.
Knutie, Sarah A; Shea, Lauren A; Kupselaitis, Marinna; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R
2017-10-01
Food resources can affect the health of organisms by altering their symbiotic microbiota and affecting energy reserves for host defenses against parasites. Different diets can vary in their macronutrient content and therefore they might favor certain bacterial communities of the host and affect the development and maintenance of the immune system, such as the inflammatory or antibody responses. Thus, testing the effect of diet, especially for animals with wide diet breadths, on host-associated microbiota and defenses against parasites might be important in determining infection and disease risk. Here, we test whether the early-life diet of Cuban tree frogs (Osteopilus septentrionalis) affects early- and later-life microbiota as well as later-life defenses against skin-penetrating, gut worms (Aplectana hamatospicula). We fed tadpoles two ecologically common diets: a diet of conspecifics or a diet of algae (Arthrospira sp.). We then: (1) characterized the gut microbiota of tadpoles and adults; and (2) challenged adult frogs with parasitic worms and measured host resistance (including the antibody-mediated immune response) and tolerance of infections. Tadpole diet affected bacterial communities in the guts of tadpoles but did not have enduring effects on the bacterial communities of adults. In contrast, tadpole diet had enduring effects on host resistance and tolerance of infections in adult frogs. Frogs that were fed a conspecific-based diet as tadpoles were more resistant to worm penetration compared with frogs that were fed an alga-based diet as tadpoles, but less resistant to worm establishment, which may be related to their suppressed antibody response during worm establishment. Furthermore, frogs that were fed a conspecific-based diet as tadpoles were more tolerant to the effect of parasite abundance on host mass during worm establishment. Overall, our study demonstrates that the diet of Cuban tree frog tadpoles affects the gut microbiota and defenses against
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Directory of Open Access Journals (Sweden)
Stephen eWikel
2013-11-01
Full Text Available Ticks are unique among hematophagous arthropods by continuous attachment to host skin and blood feeding for days; complexity and diversity of biologically active molecules differentially expressed in saliva of tick species; their ability to modulate the host defenses of pain and itch, hemostasis, inflammation, innate and adaptive immunity, and wound healing; and, the diverse array of infectious agents they transmit. All of these interactions occur at the cutaneous interface in a complex sequence of carefully choreographed host defense responses and tick countermeasures resulting in an environment that facilitates successful blood feeding and establishment of tick-borne infectious agents within the host. Here, we examine diverse patterns of tick attachment to host skin, blood feeding mechanisms, salivary gland transcriptomes, bioactive molecules in tick saliva, timing of pathogen transmission, and host responses to tick bite. Ticks engage and modulate cutaneous and systemic immune defenses involving keratinocytes, natural killer cells, dendritic cells, T cell subpopulations (Th1, Th2, Th17, Treg , B cells, neutrophils, mast cells, basophils, endothelial cells, cytokines, chemokines, complement, and extracellular matrix. A framework is proposed that integrates tick induced changes of skin immune effectors with their ability to respond to tick-borne pathogens. Implications of these changes are addressed. What are the consequences of tick modulation of host cutaneous defenses? Does diversity of salivary gland transcriptomes determine differential modulation of host inflammation and immune defenses and therefore, in part, the clades of pathogens effectively transmitted by different tick species? Do ticks create an immunologically modified cutaneous environment that enhances specific pathogen establishment? Can tick saliva molecules be used to develop vaccines that block pathogen transmission?
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Histones as mediators of host defense, inflammation and thrombosis
Hoeksema, Marloes; Eijk, Martin van; Haagsman, Henk P; Hartshorn, Kevan L
2016-01-01
Histones are known for their ability to bind to and regulate expression of DNA. However, histones are also present in cytoplasm and extracellular fluids where they serve host defense functions and promote inflammatory responses. Histones are a major component of neutrophil extracellular traps that
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Chronic pyelonephritis: Modulation of host defenses by cyclosporin A
International Nuclear Information System (INIS)
Findon, G.; Miller, T.E.
1989-01-01
Chronic experimental pyelonephritis is characterized by a stable level of infection, which persists for many months. Administration of cyclosporin A (CsA) reactivated previously healed renal lesions and caused a marked increase in bacterial numbers in the kidney. Studies were then carried out to compare the effects of CsA, and the nonselective cytodepletive agents irradiation and cyclophosphamide, on both host defenses and the bacteriologic status of chronically infected kidneys. Two different responses were observed. In animals treated with CsA, bacterial numbers increased markedly, although circulating neutrophil numbers were relatively unaffected. This observation was in contrast to the severe ablation of leukocyte numbers and competence needed to achieve an equivalent effect when irradiation and cyclophosphamide were used. One possible explanation for the adverse effect of CsA on the host-parasite balance in chronic pyelonephritis is that CsA affects mediators that control the inflammatory response or induces a qualitative change in a critical cellular defense compartment
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Directory of Open Access Journals (Sweden)
Jose C Garcia-Garcia
2009-06-01
Full Text Available Intracellular bacteria have evolved mechanisms that promote survival within hostile host environments, often resulting in functional dysregulation and disease. Using the Anaplasma phagocytophilum-infected granulocyte model, we establish a link between host chromatin modifications, defense gene transcription and intracellular bacterial infection. Infection of THP-1 cells with A. phagocytophilum led to silencing of host defense gene expression. Histone deacetylase 1 (HDAC1 expression, activity and binding to the defense gene promoters significantly increased during infection, which resulted in decreased histone H3 acetylation in infected cells. HDAC1 overexpression enhanced infection, whereas pharmacologic and siRNA HDAC1 inhibition significantly decreased bacterial load. HDAC2 does not seem to be involved, since HDAC2 silencing by siRNA had no effect on A. phagocytophilum intracellular propagation. These data indicate that HDAC up-regulation and epigenetic silencing of host cell defense genes is required for A. phagocytophilum infection. Bacterial epigenetic regulation of host cell gene transcription could be a general mechanism that enhances intracellular pathogen survival while altering cell function and promoting disease.
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Wang, Jie; Chung, Seung Ho; Peiffer, Michelle; Rosa, Cristina; Hoover, Kelli; Zeng, Rensen; Felton, Gary W
2016-06-01
Insect symbiotic bacteria affect host physiology and mediate plant-insect interactions, yet there are few clear examples of symbiotic bacteria regulating defense responses in different host plants. We hypothesized that plants would induce distinct defense responses to herbivore- associated bacteria. We evaluated whether preferred hosts (horsenettle) or non-preferred hosts (tomato) respond similarly to oral secretions (OS) from the false potato beetle (FPB, Leptinotarsa juncta), and whether the induced defense triggered by OS was due to the presence of symbiotic bacteria in OS. Both horsenettle and tomato damaged by antibiotic (AB) treated larvae showed higher polyphenol oxidase (PPO) activity than those damaged by non-AB treated larvae. In addition, application of OS from AB treated larvae induced higher PPO activity compared with OS from non-AB treated larvae or water treatment. False potato beetles harbor bacteria that may provide abundant cues that can be recognized by plants and thus mediate corresponding defense responses. Among all tested bacterial isolates, the genera Pantoea, Acinetobacter, Enterobacter, and Serratia were found to suppress PPO activity in tomato, while only Pantoea sp. among these four isolates was observed to suppress PPO activity in horsenettle. The distinct PPO suppression caused by symbiotic bacteria in different plants was similar to the pattern of induced defense-related gene expression. Pantoea inoculated FPB suppressed JA-responsive genes and triggered a SA-responsive gene in both tomato and horsenettle. However, Enterobacter inoculated FPB eliminated JA-regulated gene expression and elevated SA-regulated gene expression in tomato, but did not show evident effects on the expression levels of horsenettle defense-related genes. These results indicate that suppression of plant defenses by the bacteria found in the oral secretions of herbivores may be a more widespread phenomenon than previously indicated.
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Suppression of Plant Defenses by Herbivorous Mites Is Not Associated with Adaptation to Host Plants
Directory of Open Access Journals (Sweden)
Jéssica T. Paulo
2018-06-01
Full Text Available Some herbivores suppress plant defenses, which may be viewed as a result of the coevolutionary arms race between plants and herbivores. However, this ability is usually studied in a one-herbivore-one-plant system, which hampers comparative studies that could corroborate this hypothesis. Here, we extend this paradigm and ask whether the herbivorous spider-mite Tetranychus evansi, which suppresses the jasmonic-acid pathway in tomato plants, is also able to suppress defenses in other host plants at different phylogenetic distances from tomatoes. We test this using different plants from the Solanales order, namely tomato, jimsonweed, tobacco, and morning glory (three Solanaceae and one Convolvulaceae, and bean plants (Fabales. First, we compare the performance of T. evansi to that of the other two most-commonly found species of the same genus, T. urticae and T. ludeni, on several plants. We found that the performance of T. evansi is higher than that of the other species only on tomato plants. We then showed, by measuring trypsin inhibitor activity and life history traits of conspecific mites on either clean or pre-infested plants, that T. evansi can suppress plant defenses on all plants except tobacco. This study suggests that the suppression of plant defenses may occur on host plants other than those to which herbivores are adapted.
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Reed Warbler Hosts Fine-Tune their Defenses to Track Three Decades of Cuckoo Decline
Thorogood, Rose; Davies, Nicholas B
2013-01-01
Interactions between avian hosts and brood parasites can provide a model for how animals adapt to a changing world. Reed warbler (Acrocephalus scirpaceus) hosts employ costly defenses to combat parasitism by common cuckoos (Cuculus canorus). During the past three decades cuckoos have declined markedly across England, reducing parasitism at our study site (Wicken Fen) from 24% of reed warbler nests in 1985 to 1% in 2012. Here we show with experiments that host mobbing and egg rejection defenses have tracked this decline in local parasitism risk: the proportion of reed warbler pairs mobbing adult cuckoos (assessed by responses to cuckoo mounts and models) has declined from 90% to 38%, and the proportion rejecting nonmimetic cuckoo eggs (assessed by responses to model eggs) has declined from 61% to 11%. This is despite no change in response to other nest enemies or mimetic model eggs. Individual variation in both defenses is predicted by parasitism risk during the host’s egg-laying period. Furthermore, the response of our study population to temporal variation in parasitism risk can also explain spatial variation in egg rejection behavior in other populations across Europe. We suggest that spatial and temporal variation in parasitism risk has led to the evolution of plasticity in reed warbler defenses. PMID:24299407
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Histones as mediators of host defense, inflammation and thrombosis.
Hoeksema, Marloes; van Eijk, Martin; Haagsman, Henk P; Hartshorn, Kevan L
2016-01-01
Histones are known for their ability to bind to and regulate expression of DNA. However, histones are also present in cytoplasm and extracellular fluids where they serve host defense functions and promote inflammatory responses. Histones are a major component of neutrophil extracellular traps that contribute to bacterial killing but also to inflammatory injury. Histones can act as antimicrobial peptides and directly kill bacteria, fungi, parasites and viruses, in vitro and in a variety of animal hosts. In addition, histones can trigger inflammatory responses in some cases acting through Toll-like receptors or inflammasome pathways. Extracellular histones mediate organ injury (lung, liver), sepsis physiology, thrombocytopenia and thrombin generation and some proteins can bind histones and reduce these potentially harmful effects.
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Salivary mucins in host defense and disease prevention
Directory of Open Access Journals (Sweden)
Erica Shapiro Frenkel
2015-12-01
Full Text Available Mucus forms a protective coating on wet epithelial surfaces throughout the body that houses the microbiota and plays a key role in host defense. Mucins, the primary structural components of mucus that creates its viscoelastic properties, are critical components of the gel layer that protect against invading pathogens. Altered mucin production has been implicated in diseases such as ulcerative colitis, asthma, and cystic fibrosis, which highlights the importance of mucins in maintaining homeostasis. Different types of mucins exist throughout the body in various locations such as the gastrointestinal tract, lungs, and female genital tract, but this review will focus on mucins in the oral cavity. Salivary mucin structure, localization within the oral cavity, and defense mechanisms will be discussed. These concepts will then be applied to present what is known about the protective function of mucins in oral diseases such as HIV/AIDS, oral candidiasis, and dental caries.
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Parasitism by Cuscuta pentagona attenuates host plant defenses against insect herbivores.
Runyon, Justin B; Mescher, Mark C; De Moraes, Consuelo M
2008-03-01
Considerable research has examined plant responses to concurrent attack by herbivores and pathogens, but the effects of attack by parasitic plants, another important class of plant-feeding organisms, on plant defenses against other enemies has not been explored. We investigated how attack by the parasitic plant Cuscuta pentagona impacted tomato (Solanum lycopersicum) defenses against the chewing insect beet armyworm (Spodoptera exigua; BAW). In response to insect feeding, C. pentagona-infested (parasitized) tomato plants produced only one-third of the antiherbivore phytohormone jasmonic acid (JA) produced by unparasitized plants. Similarly, parasitized tomato, in contrast to unparasitized plants, failed to emit herbivore-induced volatiles after 3 d of BAW feeding. Although parasitism impaired antiherbivore defenses, BAW growth was slower on parasitized tomato leaves. Vines of C. pentagona did not translocate JA from BAW-infested plants: amounts of JA in parasite vines grown on caterpillar-fed and control plants were similar. Parasitized plants generally contained more salicylic acid (SA), which can inhibit JA in some systems. Parasitized mutant (NahG) tomato plants deficient in SA produced more JA in response to insect feeding than parasitized wild-type plants, further suggesting cross talk between the SA and JA defense signaling pathways. However, JA induction by BAW was still reduced in parasitized compared to unparasitized NahG, implying that other factors must be involved. We found that parasitized plants were capable of producing induced volatiles when experimentally treated with JA, indicating that resource depletion by the parasite does not fully explain the observed attenuation of volatile response to herbivore feeding. Collectively, these findings show that parasitic plants can have important consequences for host plant defense against herbivores.
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Proteolytic activation transforms heparin cofactor II into a host defense molecule.
Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Tollefsen, Douglas M; Malmsten, Martin; Mörgelin, Matthias; Schmidtchen, Artur
2013-06-15
The abundant serine proteinase inhibitor heparin cofactor II (HCII) has been proposed to inhibit extravascular thrombin. However, the exact physiological role of this plasma protein remains enigmatic. In this study, we demonstrate a previously unknown role for HCII in host defense. Proteolytic cleavage of the molecule induced a conformational change, thereby inducing endotoxin-binding and antimicrobial properties. Analyses employing representative peptide epitopes mapped these effects to helices A and D. Mice deficient in HCII showed increased susceptibility to invasive infection by Pseudomonas aeruginosa, along with a significantly increased cytokine response. Correspondingly, decreased levels of HCII were observed in wild-type animals challenged with bacteria or endotoxin. In humans, proteolytically cleaved HCII forms were detected during wounding and in association with bacteria. Thus, the protease-induced uncovering of cryptic epitopes in HCII, which transforms the molecule into a host defense factor, represents a previously unknown regulatory mechanism in HCII biology and innate immunity.
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Histones as mediators of host defense, inflammation and thrombosis
Hoeksema, Marloes; van Eijk, Martin; Haagsman, Henk P; Hartshorn, Kevan L
2016-01-01
Histones are known for their ability to bind to and regulate expression of DNA. However, histones are also present in cytoplasm and extracellular fluids where they serve host defense functions and promote inflammatory responses. Histones are a major component of neutrophil extracellular traps that contribute to bacterial killing but also to inflammatory injury. Histones can act as antimicrobial peptides and directly kill bacteria, fungi, parasites and viruses, in vitro and in a variety of ani...
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Directory of Open Access Journals (Sweden)
Scott A Salger
Full Text Available Conventional antibiotics and other chemical-based drugs are currently one of the most common methods used to control disease-related mortality in animal agriculture. Use of the innate immune system to decrease disease related mortalities is a novel alternative to conventional drugs. One component of the innate immune system is the host-defense peptides, also known as antimicrobial peptides. Host-defense peptides are typically small, amphipathic, α-helical peptides with a broad-spectrum of action against viral, bacterial, fungal, and/or protozoal pathogens. Piscidins are host-defense peptides first discovered in the hybrid striped bass (white bass, Morone chrysops, x striped bass, M. saxatilis. In this paper we identify four new piscidin isoforms in the hybrid striped bass and describe their tissue distributions. We also determine the progenitor species of origin of each piscidin (orthology and propose a revised nomenclature for this newly described piscidin family based on a three class system. The Class I piscidins (22 amino acids in length; striped bass and white bass piscidin 1 and piscidin 3 show broad-spectrum activity against bacteria and ciliated protozoans, while the Class III piscidins (55 amino acids in length; striped bass and white bass piscidin 6 and striped bass piscidin 7 primarily show anti-protozoal activity. The Class II piscidins (44-46 amino acids in length; striped bass and white bass piscidin 4 and white bass piscidin 5 have a level of activity against bacteria and protozoans intermediate to Classes I and III. Knowledge of piscidin function and activity may help in the future development of disease-resistant lines of striped bass and white bass that could be used to produce superior hybrids for aquaculture.
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Salger, Scott A; Cassady, Katherine R; Reading, Benjamin J; Noga, Edward J
2016-01-01
Conventional antibiotics and other chemical-based drugs are currently one of the most common methods used to control disease-related mortality in animal agriculture. Use of the innate immune system to decrease disease related mortalities is a novel alternative to conventional drugs. One component of the innate immune system is the host-defense peptides, also known as antimicrobial peptides. Host-defense peptides are typically small, amphipathic, α-helical peptides with a broad-spectrum of action against viral, bacterial, fungal, and/or protozoal pathogens. Piscidins are host-defense peptides first discovered in the hybrid striped bass (white bass, Morone chrysops, x striped bass, M. saxatilis). In this paper we identify four new piscidin isoforms in the hybrid striped bass and describe their tissue distributions. We also determine the progenitor species of origin of each piscidin (orthology) and propose a revised nomenclature for this newly described piscidin family based on a three class system. The Class I piscidins (22 amino acids in length; striped bass and white bass piscidin 1 and piscidin 3) show broad-spectrum activity against bacteria and ciliated protozoans, while the Class III piscidins (55 amino acids in length; striped bass and white bass piscidin 6 and striped bass piscidin 7) primarily show anti-protozoal activity. The Class II piscidins (44-46 amino acids in length; striped bass and white bass piscidin 4 and white bass piscidin 5) have a level of activity against bacteria and protozoans intermediate to Classes I and III. Knowledge of piscidin function and activity may help in the future development of disease-resistant lines of striped bass and white bass that could be used to produce superior hybrids for aquaculture.
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Immune defense and host life history.
Zuk, Marlene; Stoehr, Andrew M
2002-10-01
Recent interest has focused on immune response in an evolutionary context, with particular attention to disease resistance as a life-history trait, subject to trade-offs against other traits such as reproductive effort. Immune defense has several characteristics that complicate this approach, however; for example, because of the risk of autoimmunity, optimal immune defense is not necessarily maximum immune defense. Two important types of cost associated with immunity in the context of life history are resource costs, those related to the allocation of essential but limited resources, such as energy or nutrients, and option costs, those paid not in the currency of resources but in functional or structural components of the organism. Resource and option costs are likely to apply to different aspects of resistance. Recent investigations into possible trade-offs between reproductive effort, particularly sexual displays, and immunity have suggested interesting functional links between the two. Although all organisms balance the costs of immune defense against the requirements of reproduction, this balance works out differently for males than it does for females, creating sex differences in immune response that in turn are related to ecological factors such as the mating system. We conclude that immune response is indeed costly and that future work would do well to include invertebrates, which have sometimes been neglected in studies of the ecology of immune defense.
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Parasitism by Cuscuta pentagona Attenuates Host Plant Defenses against Insect Herbivores1
Runyon, Justin B.; Mescher, Mark C.; De Moraes, Consuelo M.
2008-01-01
Considerable research has examined plant responses to concurrent attack by herbivores and pathogens, but the effects of attack by parasitic plants, another important class of plant-feeding organisms, on plant defenses against other enemies has not been explored. We investigated how attack by the parasitic plant Cuscuta pentagona impacted tomato (Solanum lycopersicum) defenses against the chewing insect beet armyworm (Spodoptera exigua; BAW). In response to insect feeding, C. pentagona-infested (parasitized) tomato plants produced only one-third of the antiherbivore phytohormone jasmonic acid (JA) produced by unparasitized plants. Similarly, parasitized tomato, in contrast to unparasitized plants, failed to emit herbivore-induced volatiles after 3 d of BAW feeding. Although parasitism impaired antiherbivore defenses, BAW growth was slower on parasitized tomato leaves. Vines of C. pentagona did not translocate JA from BAW-infested plants: amounts of JA in parasite vines grown on caterpillar-fed and control plants were similar. Parasitized plants generally contained more salicylic acid (SA), which can inhibit JA in some systems. Parasitized mutant (NahG) tomato plants deficient in SA produced more JA in response to insect feeding than parasitized wild-type plants, further suggesting cross talk between the SA and JA defense signaling pathways. However, JA induction by BAW was still reduced in parasitized compared to unparasitized NahG, implying that other factors must be involved. We found that parasitized plants were capable of producing induced volatiles when experimentally treated with JA, indicating that resource depletion by the parasite does not fully explain the observed attenuation of volatile response to herbivore feeding. Collectively, these findings show that parasitic plants can have important consequences for host plant defense against herbivores. PMID:18165323
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Directory of Open Access Journals (Sweden)
Jacqueline T Balthazar
2011-02-01
Full Text Available The strict human pathogen Neisseria gonorrhoeae has caused the sexually transmitted infection termed gonorrhea for thousands of years. Over the millennia, the gonococcus has likely evolved mechanisms to evade host defense systems that operate on the genital mucosal surfaces in both males and females. Past research has shown that the presence or modification of certain cell envelope structures can significantly impact levels of gonococcal susceptibility to host-derived antimicrobial compounds that bathe genital mucosal surfaces and participate in innate host defense against invading pathogens. In order to facilitate the identification of gonococcal genes that are important in determining levels of bacterial susceptibility to mediators of innate host defense, we used the Himar I mariner in vitro mutagenesis system to construct a transposon insertion library in strain F62. As proof of principle that this strategy would be suitable for this purpose, we screened the library for mutants expressing decreased susceptibility to the bacteriolytic action of normal human serum (NHS. We found that a transposon insertion in the lgtD gene, which encodes an N-acetylgalactosamine transferase involved in the extension of the α-chain of lipooligosaccharide (LOS, could confer decreased susceptibility of strain F62 to complement-mediated killing by NHS. By complementation and chemical analyses, we demonstrated both linkage of the transposon insertion to the NHS-resistance phenotype and chemical changes in LOS structure that resulted from loss of LgtD production. Further truncation of the LOS α-chain or loss of phosphoethanolamine (PEA from the lipid A region of LOS also impacted levels of NHS-resistance. PEA decoration of lipid A also increased gonococcal resistance to the model cationic antimicrobial polymyxin B. Taken together, we conclude that the Himar I mariner in vitro mutagenesis procedure can facilitate studies on structures involved in gonococcal
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Towards an integrated defense system for cyber security situation awareness experiment
Zhang, Hanlin; Wei, Sixiao; Ge, Linqiang; Shen, Dan; Yu, Wei; Blasch, Erik P.; Pham, Khanh D.; Chen, Genshe
2015-05-01
In this paper, an implemented defense system is demonstrated to carry out cyber security situation awareness. The developed system consists of distributed passive and active network sensors designed to effectively capture suspicious information associated with cyber threats, effective detection schemes to accurately distinguish attacks, and network actors to rapidly mitigate attacks. Based on the collected data from network sensors, image-based and signals-based detection schemes are implemented to detect attacks. To further mitigate attacks, deployed dynamic firewalls on hosts dynamically update detection information reported from the detection schemes and block attacks. The experimental results show the effectiveness of the proposed system. A future plan to design an effective defense system is also discussed based on system theory.
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Iranzo, Jaime; Lobkovsky, Alexander E; Wolf, Yuri I; Koonin, Eugene V
2015-03-13
Parasite-host arms race is one of the key factors in the evolution of life. Most cellular life forms, in particular prokaryotes, possess diverse forms of defense against pathogens including innate immunity, adaptive immunity and programmed cell death (altruistic suicide). Coevolution of these different but interacting defense strategies yields complex evolutionary regimes. We develop and extensively analyze a computational model of coevolution of different defense strategies to show that suicide as a defense mechanism can evolve only in structured populations and when the attainable degree of immunity against pathogens is limited. The general principle of defense evolution seems to be that hosts do not evolve two costly defense mechanisms when one is sufficient. Thus, the evolutionary interplay of innate immunity, adaptive immunity and suicide, leads to an equilibrium state where the combination of all three defense strategies is limited to a distinct, small region of the parameter space. The three strategies can stably coexist only if none of them are highly effective. Coupled adaptive immunity-suicide systems, the existence of which is implied by the colocalization of genes for the two types of defense in prokaryotic genomes, can evolve either when immunity-associated suicide is more efficacious than other suicide systems or when adaptive immunity functionally depends on the associated suicide system. Computational modeling reveals a broad range of outcomes of coevolution of anti-pathogen defense strategies depending on the relative efficacy of different mechanisms and population structure. Some of the predictions of the model appear compatible with recent experimental evolution results and call for additional experiments.
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Directory of Open Access Journals (Sweden)
Philipp Wiemann
2017-05-01
Full Text Available The Fenton-chemistry-generating properties of copper ions are considered a potent phagolysosome defense against pathogenic microbes, yet our understanding of underlying host/microbe dynamics remains unclear. We address this issue in invasive aspergillosis and demonstrate that host and fungal responses inextricably connect copper and reactive oxygen intermediate (ROI mechanisms. Loss of the copper-binding transcription factor AceA yields an Aspergillus fumigatus strain displaying increased sensitivity to copper and ROI in vitro, increased intracellular copper concentrations, decreased survival in challenge with murine alveolar macrophages (AMΦs, and reduced virulence in a non-neutropenic murine model. ΔaceA survival is remediated by dampening of host ROI (chemically or genetically or enhancement of copper-exporting activity (CrpA in A. fumigatus. Our study exposes a complex host/microbe multifactorial interplay that highlights the importance of host immune status and reveals key targetable A. fumigatus counter-defenses.
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Toxoplasma gondii GRA7-Targeted ASC and PLD1 Promote Antibacterial Host Defense via PKCα.
Koh, Hyun-Jung; Kim, Ye-Ram; Kim, Jae-Sung; Yun, Jin-Seung; Jang, Kiseok; Yang, Chul-Su
2017-01-01
Tuberculosis is a global health problem and at least one-third of the world's population is infected with Mycobacterium tuberculosis (MTB). MTB is a successful pathogen that enhances its own intracellular survival by inhibiting inflammation and arresting phago-lysosomal fusion. We previously demonstrated that Toxoplasma gondii (T. gondii) dense granule antigen (GRA) 7 interacts with TNF receptor-associated factor 6 via Myeloid differentiation primary response gene 88, enabling innate immune responses in macrophages. To extend these studies, we found that GRA7 interacts with host proteins involved in antimicrobial host defense mechanisms as a therapeutic strategy for tuberculosis. Here, we show that protein kinase C (PKC)α-mediated phosphorylation of T. gondii GRA7-I (Ser52) regulates the interaction of GRA7 with PYD domain of apoptosis-associated speck-like protein containing a carboxy-terminal CARD, which is capable of oligomerization and inflammasome activation can lead to antimicrobial defense against MTB. Furthermore, GRA7-III interacted with the PX domain of phospholipase D1, facilitating its enzyme activity, phago-lysosomal maturation, and subsequent antimicrobial activity in a GRA7-III (Ser135) phosphorylation-dependent manner via PKCα. Taken together, these results underscore a previously unrecognized role of GRA7 in modulating antimicrobial host defense mechanism during mycobacterial infection.
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Toxoplasma gondii GRA7-Targeted ASC and PLD1 Promote Antibacterial Host Defense via PKCα.
Directory of Open Access Journals (Sweden)
Hyun-Jung Koh
2017-01-01
Full Text Available Tuberculosis is a global health problem and at least one-third of the world's population is infected with Mycobacterium tuberculosis (MTB. MTB is a successful pathogen that enhances its own intracellular survival by inhibiting inflammation and arresting phago-lysosomal fusion. We previously demonstrated that Toxoplasma gondii (T. gondii dense granule antigen (GRA 7 interacts with TNF receptor-associated factor 6 via Myeloid differentiation primary response gene 88, enabling innate immune responses in macrophages. To extend these studies, we found that GRA7 interacts with host proteins involved in antimicrobial host defense mechanisms as a therapeutic strategy for tuberculosis. Here, we show that protein kinase C (PKCα-mediated phosphorylation of T. gondii GRA7-I (Ser52 regulates the interaction of GRA7 with PYD domain of apoptosis-associated speck-like protein containing a carboxy-terminal CARD, which is capable of oligomerization and inflammasome activation can lead to antimicrobial defense against MTB. Furthermore, GRA7-III interacted with the PX domain of phospholipase D1, facilitating its enzyme activity, phago-lysosomal maturation, and subsequent antimicrobial activity in a GRA7-III (Ser135 phosphorylation-dependent manner via PKCα. Taken together, these results underscore a previously unrecognized role of GRA7 in modulating antimicrobial host defense mechanism during mycobacterial infection.
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Directory of Open Access Journals (Sweden)
Peter Sperisen
2005-11-01
Full Text Available There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is characterized by a series of domains conserved across phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously characterized as SacB, XcbA, or WefC is encoded by subsets of strains mainly colonizing multicellular organisms, with evidence for a protective effect against the host innate immune defense. More specifically, integrating all the available information about Stealth proteins in bacteria, we propose that Stealth is a D-hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In the animal kingdom, Stealth is strongly conserved across evolution from social amoebas to simple and complex multicellular organisms, such as Dictyostelium discoideum, hydra, and human. Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system. Moreover, there is good reason to speculate that the acquisition and spread of Stealth could be responsible for future epidemic outbreaks of infectious diseases caused by a large variety of eubacterial pathogens. Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence. At a more basic level, the characterization of the molecular and cellular function of Stealth proteins may shed light on fundamental mechanisms of innate immune defense against microbial invasion.
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Directory of Open Access Journals (Sweden)
2005-11-01
Full Text Available There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is characterized by a series of domains conserved across phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously characterized as SacB, XcbA, or WefC is encoded by subsets of strains mainly colonizing multicellular organisms, with evidence for a protective effect against the host innate immune defense. More specifically, integrating all the available information about Stealth proteins in bacteria, we propose that Stealth is a D-hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In the animal kingdom, Stealth is strongly conserved across evolution from social amoebas to simple and complex multicellular organisms, such as Dictyostelium discoideum, hydra, and human. Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system. Moreover, there is good reason to speculate that the acquisition and spread of Stealth could be responsible for future epidemic outbreaks of infectious diseases caused by a large variety of eubacterial pathogens. Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence. At a more basic level, the characterization of the molecular and cellular function of Stealth proteins may shed light on fundamental mechanisms of innate immune defense against microbial invasion.
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DEFF Research Database (Denmark)
Genster, N; Cramer, E Præstekjær; Rosbjerg, A
2016-01-01
the lectin pathway of complement. Previous in vitro studies reported that ficolins bind to A. fumigatus, but their part in host defense against fungal infections in vivo is unknown. In this study, we used ficolin-deficient mice to investigate the role of ficolins during lung infection with A. fumigatus......-mediated complement activation in ficolin knockout mice and wild-type mice. In conclusion, this study demonstrates that ficolins are important in initial innate host defense against A. fumigatus infections in vivo....
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Avian Antimicrobial Host Defense Peptides: From Biology to Therapeutic Applications
Directory of Open Access Journals (Sweden)
Guolong Zhang
2014-02-01
Full Text Available Host defense peptides (HDPs are an important first line of defense with antimicrobial and immunomoduatory properties. Because they act on the microbial membranes or host immune cells, HDPs pose a low risk of triggering microbial resistance and therefore, are being actively investigated as a novel class of antimicrobials and vaccine adjuvants. Cathelicidins and β-defensins are two major families of HDPs in avian species. More than a dozen HDPs exist in birds, with the genes in each HDP family clustered in a single chromosomal segment, apparently as a result of gene duplication and diversification. In contrast to their mammalian counterparts that adopt various spatial conformations, mature avian cathelicidins are mostly α-helical. Avian β-defensins, on the other hand, adopt triple-stranded β-sheet structures similar to their mammalian relatives. Besides classical β-defensins, a group of avian-specific β-defensin-related peptides, namely ovodefensins, exist with a different six-cysteine motif. Like their mammalian counterparts, avian cathelicidins and defensins are derived from either myeloid or epithelial origin expressed in a majority of tissues with broad-spectrum antibacterial and immune regulatory activities. Structure-function relationship studies with several avian HDPs have led to identification of the peptide analogs with potential for use as antimicrobials and vaccine adjuvants. Dietary modulation of endogenous HDP synthesis has also emerged as a promising alternative approach to disease control and prevention in chickens.
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A Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP.
Spanò, Stefania; Gao, Xiang; Hannemann, Sebastian; Lara-Tejero, María; Galán, Jorge E
2016-02-10
Cell-autonomous defense mechanisms are potent strategies that protect individual cells against intracellular pathogens. The Rab-family GTPase Rab32 was previously shown to restrict the intracellular human pathogen Salmonella Typhi, but its potential broader role in antimicrobial defense remains unknown. We show that Rab32 represents a general cell-autonomous, antimicrobial defense that is counteracted by two Salmonella effectors. Mice lacking Rab-32 or its nucleotide exchange factor BLOC-3 are permissive to S. Typhi infection and exhibit increased susceptibility to S. Typhimurium. S. Typhimurium counters this defense pathway by delivering two type III secretion effectors, SopD2, a Rab32 GAP, and GtgE, a specific Rab32 protease. An S. Typhimurium mutant strain lacking these two effectors exhibits markedly reduced virulence, which is fully restored in BLOC-3-deficient mice. These results demonstrate that a cell-autonomous, Rab32-dependent host defense pathway plays a central role in the defense against vacuolar pathogens and describe a mechanism evolved by a bacterial pathogen to counter it. Copyright © 2016 Elsevier Inc. All rights reserved.
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Proteomic approaches to understanding the role of the cytoskeleton in host-defense mechanisms
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
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Coronavirus gene 7 counteracts host defenses and modulates virus virulence.
Directory of Open Access Journals (Sweden)
Jazmina L G Cruz
2011-06-01
Full Text Available Transmissible gastroenteritis virus (TGEV genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7. Both the mutant and the parental (rTGEV-wt viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c, a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the
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Directory of Open Access Journals (Sweden)
Derrick R Samuelson
2017-06-01
Full Text Available Chronic alcohol consumption perturbs the normal intestinal microbial communities (dysbiosis. To investigate the relationship between alcohol-mediated dysbiosis and pulmonary host defense we developed a fecal adoptive transfer model, which allows us to investigate the impact of alcohol-induced gut dysbiosis on host immune response to an infectious challenge at a distal organ, independent of prevailing alcohol use. Male C57BL/6 mice were treated with a cocktail of antibiotics (ampicillin, gentamicin, neomycin, vancomycin, and metronidazole via daily gavage for two weeks. A separate group of animals was fed a chronic alcohol (or isocaloric dextrose pair-fed controls liquid diet for 10 days. Microbiota-depleted mice were recolonized with intestinal microbiota from alcohol-fed or pair-fed (control animals. Following recolonization groups of mice were sacrificed prior to and 48 hrs. post respiratory infection with Klebsiella pneumoniae. Klebsiella lung burden, lung immunology and inflammation, as well as intestinal immunology, inflammation, and barrier damage were examined. Results showed that alcohol-associated susceptibility to K. pneumoniae is, in part, mediated by gut dysbiosis, as alcohol-naïve animals recolonized with a microbiota isolated from alcohol-fed mice had an increased respiratory burden of K. pneumoniae compared to mice recolonized with a control microbiota. The increased susceptibility in alcohol-dysbiosis recolonized animals was associated with an increase in pulmonary inflammatory cytokines, and a decrease in the number of CD4+ and CD8+ T-cells in the lung following Klebsiella infection but an increase in T-cell counts in the intestinal tract following Klebsiella infection, suggesting intestinal T-cell sequestration as a factor in impaired lung host defense. Mice recolonized with an alcohol-dysbiotic microbiota also had increased intestinal damage as measured by increased levels of serum intestinal fatty acid binding protein
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Directory of Open Access Journals (Sweden)
Jeanne A Robert
Full Text Available The mountain pine beetle, Dendroctonus ponderosae, is a native species of bark beetle (Coleoptera: Curculionidae that caused unprecedented damage to the pine forests of British Columbia and other parts of western North America and is currently expanding its range into the boreal forests of central and eastern Canada and the USA. We conducted a large-scale gene expression analysis (RNA-seq of mountain pine beetle male and female adults either starved or fed in male-female pairs for 24 hours on lodgepole pine host tree tissues. Our aim was to uncover transcripts involved in coniferophagous mountain pine beetle detoxification systems during early host colonization. Transcripts of members from several gene families significantly increased in insects fed on host tissue including: cytochromes P450, glucosyl transferases and glutathione S-transferases, esterases, and one ABC transporter. Other significantly increasing transcripts with potential roles in detoxification of host defenses included alcohol dehydrogenases and a group of unexpected transcripts whose products may play an, as yet, undiscovered role in host colonization by mountain pine beetle.
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Host plant invests in growth rather than chemical defense when attacked by a specialist herbivore.
Arab, Alberto; Trigo, José Roberto
2011-05-01
Plant defensive compounds may be a cost rather than a benefit when plants are attacked by specialist insects that may overcome chemical barriers by strategies such as sequestering plant compounds. Plants may respond to specialist herbivores by compensatory growth rather than chemical defense. To explore the use of defensive chemistry vs. compensatory growth we studied Brugmansia suaveolens (Solanaceae) and the specialist larvae of the ithomiine butterfly Placidina euryanassa, which sequester defensive tropane alkaloids (TAs) from this host plant. We investigated whether the concentration of TAs in B. suaveolens was changed by P. euryanassa damage, and whether plants invest in growth, when damaged by the specialist. Larvae feeding during 24 hr significantly decreased TAs in damaged plants, but they returned to control levels after 15 days without damage. Damaged and undamaged plants did not differ significantly in leaf area after 15 days, indicating compensatory growth. Our results suggest that B. suaveolens responds to herbivory by the specialist P. euryanassa by investing in growth rather than chemical defense.
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Dimarco, Romina D; Nice, Chris C; Fordyce, James A
2012-11-01
Insect herbivores contend with various plant traits that are presumed to function as feeding deterrents. Paradoxically, some specialist insect herbivores might benefit from some of these plant traits, for example by sequestering plant chemical defenses that herbivores then use as their own defense against natural enemies. Larvae of the butterfly species Battus philenor (L.) (Papilionidae) sequester toxic alkaloids (aristolochic acids) from their Aristolochia host plants, rendering larvae and adults unpalatable to a broad range of predators. We studied the importance of two putative defensive traits in Aristolochia erecta: leaf toughness and aristolochic acid content, and we examined the effect of intra- and interplant chemical variation on the chemical phenotype of B. philenor larvae. It has been proposed that genetic variation for sequestration ability is "invisible to natural selection" because intra- and interindividual variation in host-plant chemistry will largely eliminate a role for herbivore genetic variation in determining an herbivore's chemical phenotype. We found substantial intra- and interplant variation in leaf toughness and in the aristolochic acid chemistry in A. erecta. Based on field observations and laboratory experiments, we showed that first-instar larvae preferentially fed on less tough, younger leaves and avoided tougher, older leaves, and we found no evidence that aristolochic acid content influenced first-instar larval foraging. We found that the majority of variation in the amount of aristolochic acid sequestered by larvae was explained by larval family, not by host-plant aristolochic acid content. Heritable variation for sequestration is the predominant determinant of larval, and likely adult, chemical phenotype. This study shows that for these highly specialized herbivores that sequester chemical defenses, traits that offer mechanical resistance, such as leaf toughness, might be more important determinants of early-instar larval
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Directory of Open Access Journals (Sweden)
Nadine T Nehme
2011-03-01
Full Text Available Two NF-kappaB signaling pathways, Toll and immune deficiency (imd, are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense.In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus, we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response.Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen.
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Important role for Toll-like receptor 9 in host defense against meningococcal sepsis
DEFF Research Database (Denmark)
Sjölinder, Hong; Mogensen, Trine; Kilian, Mogens
2008-01-01
have been reported to be involved in the host response to N. meningitidis. While TLR4 has been suggested to play an important role in early containment of infection, the roles of TLR2 and TLR9 in meningococcal disease are not well described. Using a model for meningococcal sepsis, we report that TLR9...... and induction of cytokine gene expression were independent of TLR2 or TLR9 in macrophages and conventional dendritic cells. In contrast, plasmacytoid dendritic cells relied entirely on TLR9 to induce these activities. Thus, our data demonstrate an important role for TLR9 in host defense against N. meningitidis....
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Martins, Carlos H Z; Cunha, Beatriz P; Solferini, Vera N; Trigo, José R
2015-01-01
Sequestration of chemical defenses from host plants is a strategy widely used by herbivorous insects to avoid predation. Larvae of the arctiine moth Utetheisa ornatrix feeding on unripe seeds and leaves of many species of Crotalaria (Leguminosae) sequester N-oxides of pyrrolizidine alkaloids (PAs) from these host plants, and transfer them to adults through the pupal stage. PAs confer protection against predation on all life stages of U. ornatrix. As U. ornatrix also uses other Crotalaria species as host plants, we evaluated whether the PA chemical defense against predation is independent of host plant use. We fed larvae from hatching to pupation with either leaves or seeds of one of eight Crotalaria species (C. incana, C. juncea, C. micans, C. ochroleuca, C. pallida, C. paulina, C. spectabilis, and C. vitellina), and tested if adults were preyed upon or released by the orb-weaving spider Nephila clavipes. We found that the protection against the spider was more effective in adults whose larvae fed on seeds, which had a higher PA concentration than leaves. The exceptions were adults from larvae fed on C. paulina, C. spectabilis and C. vitellina leaves, which showed high PA concentrations. With respect to the PA profile, we describe for the first time insect-PAs in U. ornatrix. These PAs, biosynthesized from the necine base retronecine of plant origin, or monocrotaline- and senecionine-type PAs sequestered from host plants, were equally active in moth chemical defense, in a dose-dependent manner. These results are also partially explained by host plant phylogeny, since PAs of the host plants do have a phylogenetic signal (clades with high and low PA concentrations in leaves) which is reflected in the adult defense.
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Directory of Open Access Journals (Sweden)
Carlos H Z Martins
Full Text Available Sequestration of chemical defenses from host plants is a strategy widely used by herbivorous insects to avoid predation. Larvae of the arctiine moth Utetheisa ornatrix feeding on unripe seeds and leaves of many species of Crotalaria (Leguminosae sequester N-oxides of pyrrolizidine alkaloids (PAs from these host plants, and transfer them to adults through the pupal stage. PAs confer protection against predation on all life stages of U. ornatrix. As U. ornatrix also uses other Crotalaria species as host plants, we evaluated whether the PA chemical defense against predation is independent of host plant use. We fed larvae from hatching to pupation with either leaves or seeds of one of eight Crotalaria species (C. incana, C. juncea, C. micans, C. ochroleuca, C. pallida, C. paulina, C. spectabilis, and C. vitellina, and tested if adults were preyed upon or released by the orb-weaving spider Nephila clavipes. We found that the protection against the spider was more effective in adults whose larvae fed on seeds, which had a higher PA concentration than leaves. The exceptions were adults from larvae fed on C. paulina, C. spectabilis and C. vitellina leaves, which showed high PA concentrations. With respect to the PA profile, we describe for the first time insect-PAs in U. ornatrix. These PAs, biosynthesized from the necine base retronecine of plant origin, or monocrotaline- and senecionine-type PAs sequestered from host plants, were equally active in moth chemical defense, in a dose-dependent manner. These results are also partially explained by host plant phylogeny, since PAs of the host plants do have a phylogenetic signal (clades with high and low PA concentrations in leaves which is reflected in the adult defense.
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Roles of d-Amino Acids on the Bioactivity of Host Defense Peptides
Directory of Open Access Journals (Sweden)
Hao Li
2016-06-01
Full Text Available Host defense peptides (HDPs are positively-charged and amphipathic components of the innate immune system that have demonstrated great potential to become the next generation of broad spectrum therapeutic agents effective against a vast array of pathogens and tumor. As such, many approaches have been taken to improve the therapeutic efficacy of HDPs. Amongst these methods, the incorporation of d-amino acids (d-AA is an approach that has demonstrated consistent success in improving HDPs. Although, virtually all HDP review articles briefly mentioned about the role of d-AA, however it is rather surprising that no systematic review specifically dedicated to this topic exists. Given the impact that d-AA incorporation has on HDPs, this review aims to fill that void with a systematic discussion of the impact of d-AA on HDPs.
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Zhuang, Huifu; Li, Juan; Song, Juan; Hettenhausen, Christian; Schuman, Meredith C; Sun, Guiling; Zhang, Cuiping; Li, Jing; Song, Dunlun; Wu, Jianqiang
2018-06-01
Dodders (Cuscuta spp.) are shoot holoparasites, whose haustoria penetrate host tissues to enable fusion between the parasite and host vascular systems, allowing Cuscuta to extract water, nutrients and other molecules from hosts. Aphids are piercing-sucking herbivores that use specialized stylets to feed on phloem sap. Aphids are known to feed on Cuscuta, but how Cuscuta and its host plant respond to aphids attacking the parasite was unknown. Phytohormone quantification, transcriptomic analysis and bioassays were performed to determine the responses of Cuscuta australis and its soybean (Glycine max) hosts to the feeding of green peach aphid (GPA; Myzus persicae) on C. australis. Decreased salicylic acid levels and 172 differentially expressed genes (DEGs) were found in GPA-attacked C. australis, and the soybean hosts exhibited increased jasmonic acid contents and 1015 DEGs, including > 100 transcription factor genes. Importantly, GPA feeding on C. australis increased the resistance of the soybean host to subsequent feeding by the leafworm Spodoptera litura and soybean aphid Aphis glycines, resulting in 21% decreased leafworm mass and 41% reduced aphid survival rate. These data strongly suggest that GPA feeding on Cuscuta induces a systemic signal, which is translocated to hosts and activates defense against herbivores. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.
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The Role of NLR-related Protein 3 Inflammasome in Host Defense and Inflammatory Diseases
Directory of Open Access Journals (Sweden)
Chul-Su Yang
2012-03-01
Full Text Available Among a number of innate receptors, the nucleotide-binding domain leucine-rich repeat containing (NLR nucleotide oligomerization domain (NOD-like receptor families are involved in the recognition of cytosolic pathogen- or danger-associated molecules. Activation of these specific sets of receptors leads to the assembly of a multiprotein complex, the inflammasome, leading to the activation of caspase-1 and maturation of the cytokines interleukin (IL-1β, IL-18, and IL-33. Among NLRs, NLR-related protein 3 (NLRP3 is one of the best-characterized receptors that activates the inflammasome. There is no doubt that NLRP3 inflammasome activation is important for host defense and effective pathogen clearance against fungal, bacterial, and viral infection. In addition, mounting evidence indicates that the NLRP3 inflammasome plays a role in a variety of inflammatory diseases, including gout, atherosclerosis, and type II diabetes, as well as under conditions of cellular stress or injury. Here, we review recent advances in our understanding of the role of the NLRP3 inflammasome in host defense and various inflammatory diseases.
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Directory of Open Access Journals (Sweden)
Philip O Scumpia
2017-07-01
Full Text Available Successful host defense against pathogens requires innate immune recognition of the correct pathogen associated molecular patterns (PAMPs by pathogen recognition receptors (PRRs to trigger the appropriate gene program tailored to the pathogen. While many PRR pathways contribute to the innate immune response to specific pathogens, the relative importance of each pathway for the complete transcriptional program elicited has not been examined in detail. Herein, we used RNA-sequencing with wildtype and mutant macrophages to delineate the innate immune pathways contributing to the early transcriptional response to Staphylococcus aureus, a ubiquitous microorganism that can activate a wide variety of PRRs. Unexpectedly, two PRR pathways-the Toll-like receptor (TLR and Stimulator of Interferon Gene (STING pathways-were identified as dominant regulators of approximately 95% of the genes that were potently induced within the first four hours of macrophage infection with live S. aureus. TLR signaling predominantly activated a pro-inflammatory program while STING signaling activated an antiviral/type I interferon response with live but not killed S. aureus. This STING response was largely dependent on the cytosolic DNA sensor cyclic guanosine-adenosine synthase (cGAS. Using a cutaneous infection model, we found that the TLR and STING pathways played opposite roles in host defense to S. aureus. TLR signaling was required for host defense, with its absence reducing interleukin (IL-1β production and neutrophil recruitment, resulting in increased bacterial growth. In contrast, absence of STING signaling had the opposite effect, enhancing the ability to restrict the infection. These results provide novel insights into the complex interplay of innate immune signaling pathways triggered by S. aureus and uncover opposing roles of TLR and STING in cutaneous host defense to S. aureus.
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Missile Defense: Ballistic Missile Defense System Testing Delays Affect Delivery of Capabilities
2016-04-28
Page 1 GAO-16-339R Ballistic Missile Defense 441 G St. N.W. Washington, DC 20548 April 28, 2016 Congressional Committees Missile Defense... Ballistic Missile Defense System Testing Delays Affect Delivery of Capabilities For over half a century, the Department of Defense (DOD) has been...funding efforts to develop a system to detect, track, and defeat enemy ballistic missiles. The current system—the Ballistic Missile Defense System
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Defense islands in bacterial and archaeal genomes and prediction of novel defense systems.
Makarova, Kira S; Wolf, Yuri I; Snir, Sagi; Koonin, Eugene V
2011-11-01
The arms race between cellular life forms and viruses is a major driving force of evolution. A substantial fraction of bacterial and archaeal genomes is dedicated to antivirus defense. We analyzed the distribution of defense genes and typical mobilome components (such as viral and transposon genes) in bacterial and archaeal genomes and demonstrated statistically significant clustering of antivirus defense systems and mobile genes and elements in genomic islands. The defense islands are enriched in putative operons and contain numerous overrepresented gene families. A detailed sequence analysis of the proteins encoded by genes in these families shows that many of them are diverged variants of known defense system components, whereas others show features, such as characteristic operonic organization, that are suggestive of novel defense systems. Thus, genomic islands provide abundant material for the experimental study of bacterial and archaeal antivirus defense. Except for the CRISPR-Cas systems, different classes of defense systems, in particular toxin-antitoxin and restriction-modification systems, show nonrandom clustering in defense islands. It remains unclear to what extent these associations reflect functional cooperation between different defense systems and to what extent the islands are genomic "sinks" that accumulate diverse nonessential genes, particularly those acquired via horizontal gene transfer. The characteristics of defense islands resemble those of mobilome islands. Defense and mobilome genes are nonrandomly associated in islands, suggesting nonadaptive evolution of the islands via a preferential attachment-like mechanism underpinned by the addictive properties of defense systems such as toxins-antitoxins and an important role of horizontal mobility in the evolution of these islands.
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Shedding light on the role of photosynthesis in pathogen colonization and host defense
Garavaglia, Betiana S.; Thomas, Ludivine; Gottig, Natalia; Zimaro, Tamara; Garofalo, Cecilia G.; Gehring, Christoph A; Ottado, Jorgelina
2010-01-01
The role of photosynthesis in plant defense is a fundamental question awaiting further molecular and physiological elucidation. To this end we investigated host responses to infection with the bacterial pathogen Xanthomonas axonopodis pv. citri, the pathogen responsible for citrus canker. This pathogen encodes a plant-like natriuretic peptide (XacPNP) that is expressed specifically during the infection process and prevents deterioration of the physiological condition of the infected tissue. Proteomic assays of citrus leaves infected with a XacPNP deletion mutant (DeltaXacPNP) resulted in a major reduction in photosynthetic proteins such as Rubisco, Rubisco activase and ATP synthase as a compared with infection with wild type bacteria. In contrast, infiltration of citrus leaves with recombinant XacPNP caused an increase in these host proteins and a concomitant increase in photosynthetic efficiency as measured by chlorophyll fluorescence assays. Reversion of the reduction in photosynthetic efficiency in citrus leaves infected with DeltaXacPNP was achieved by the application of XacPNP or Citrus sinensis PNP lending support to a case of molecular mimicry. Finally, given that DeltaXacPNP infection is less successful than infection with the wild type, it appears that reducing photosynthesis is an effective plant defense mechanism against biotrophic pathogens.
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Shedding light on the role of photosynthesis in pathogen colonization and host defense
Garavaglia, Betiana S.
2010-09-01
The role of photosynthesis in plant defense is a fundamental question awaiting further molecular and physiological elucidation. To this end we investigated host responses to infection with the bacterial pathogen Xanthomonas axonopodis pv. citri, the pathogen responsible for citrus canker. This pathogen encodes a plant-like natriuretic peptide (XacPNP) that is expressed specifically during the infection process and prevents deterioration of the physiological condition of the infected tissue. Proteomic assays of citrus leaves infected with a XacPNP deletion mutant (DeltaXacPNP) resulted in a major reduction in photosynthetic proteins such as Rubisco, Rubisco activase and ATP synthase as a compared with infection with wild type bacteria. In contrast, infiltration of citrus leaves with recombinant XacPNP caused an increase in these host proteins and a concomitant increase in photosynthetic efficiency as measured by chlorophyll fluorescence assays. Reversion of the reduction in photosynthetic efficiency in citrus leaves infected with DeltaXacPNP was achieved by the application of XacPNP or Citrus sinensis PNP lending support to a case of molecular mimicry. Finally, given that DeltaXacPNP infection is less successful than infection with the wild type, it appears that reducing photosynthesis is an effective plant defense mechanism against biotrophic pathogens.
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S1P dependent inter organ trafficking of group 2 innate lymphoid cells suppots host defense
Innate lymphoid cells (ILCs) are considered to be the innate counterparts of adaptive T lymphocytes and play important roles in host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. ILCs are generally thought of as tissue-resident cells, but whether ILCs strictly behave in a...
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Overexpression of stress-related genes in Cuscuta campestris in response to host defense reactions
Directory of Open Access Journals (Sweden)
Hamed Rezaei
2017-07-01
Full Text Available Herb dodder ( Cuscuta spp. is one of the most important parasitic plants that can severely affect crop yields in the world. So far, interactions of this parasitic plant with hosts were not investigated adequately. Here, we conducted a differential expression analyzes and identified a number of genes that were differentially expressed in haustorium tissue compared with the stem of Cuscuta campestris growing on Alfalfa. We obtained 439 cDNA fragments from haustoria (parasite-host connection zone and stems (25 cm away from connections zones using the cDNA-AFLP (Amplified Fragment Length Polymorphism method with eight different primer combinations. Of 439 transcript-derived fragments (TDFs that were detected, 145 fragments were identified as differentially expressed genes. Five TDF sequences were similar to known functional genes involved in signal transduction, metabolism, respiration, and stress responses. Genes encoding DEAD-box ATP-dependent RNA helicase, potential heme-binding protein, lysine-specific demethylase 5A were selected for qRT-PCR. The qRT-PCR analyzes confirmed the results obtained using cDNA-AFLP. Our findings shed light on the elicitation of dodder defense responses in the connection zone to overcome plant defense reactions.
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Upadhyay, Vaibhav; Fu, Yang-Xin
2014-04-01
The lymphotoxin (LT)-pathway is a unique constituent branch of the Tumor Necrosis Superfamily (TNFSF). Use of LT is a critical mechanism by which fetal innate lymphoid cells regulate lymphoid organogenesis. Within recent years, adult innate lymphoid cells have been discovered to utilize this same pathway to regulate IL-22 and IL-23 production for host defense. Notably, genetic studies have linked polymorphisms in the genes encoding LTα to several phenotypes contributing to metabolic syndrome. The role of the LT-pathway may lay the foundation for a bridge between host immune response, microbiota, and metabolic syndrome. The contribution of the LT-pathway to innate lymphoid cell function and metabolic syndrome will be visited in this review. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Directory of Open Access Journals (Sweden)
Alessandra L. Morassutti
2012-01-01
Full Text Available Angiostrongylus cantonensis is a nematode parasite that causes eosinophilic meningoencephalitis in humans. Disease presents following the ingestion of third-stage larvae residing in the intermediate mollusk host and disease manifests as an acute inflammation of the meninges characterized by eosinophil infiltrates which release a battery of proinflammatory and cytotoxic agents in response to the pathogen. As a mechanism of neutralizing these host defenses, A. cantonensis expresses different molecules with immunomodulatory properties that are excreted or secreted (ES. In this paper we discuss the role of ES proteins on disease exacerbation and their potential use as therapeutic targets.
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Yuen, Grace J; Ausubel, Frederick M
2018-12-31
The innate immune response of the nematode Caenorhabditis elegans has been extensively studied and a variety of Toll-independent immune response pathways have been identified. Surprisingly little, however, is known about how pathogens activate the C. elegans immune response. Enterococcus faecalis and Enterococcus faecium are closely related enterococcal species that exhibit significantly different levels of virulence in C. elegans infection models. Previous work has shown that activation of the C. elegans immune response by Pseudomonas aeruginosa involves P. aeruginosa-mediated host damage. Through ultrastructural imaging, we report that infection with either E. faecalis or E. faecium causes the worm intestine to become distended with proliferating bacteria in the absence of extensive morphological changes and apparent physical damage. Genetic analysis, whole-genome transcriptional profiling, and multiplexed gene expression analysis demonstrate that both enterococcal species, whether live or dead, induce a rapid and similar transcriptional defense response dependent upon previously described immune signaling pathways. The host response to E. faecium shows a stricter dependence upon stress response signaling pathways than the response to E. faecalis. Unexpectedly, we find that E. faecium is a C. elegans pathogen and that an active wild-type host defense response is required to keep an E. faecium infection at bay. These results provide new insights into the mechanisms underlying the C. elegans immune response to pathogen infection.
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Directory of Open Access Journals (Sweden)
Wang Peng
2013-02-01
Full Text Available Abstract Background Glucocorticoids are widely regarded as the most effective treatment for asthma. However, the direct impact of glucocorticoids on the innate immune system and antibacterial host defense during asthma remain unclear. Understanding the mechanisms underlying this process is critical to the clinical application of glucocorticoids for asthma therapy. After sensitization and challenge with ovalbumin (OVA, BALB/c mice were treated with inhaled budesonide and infected with Pseudomonas aeruginosa (P. aeruginosa. The number of viable bacteria in enflamed lungs was evaluated, and levels of interleukin-4 (IL-4 and interferon-γ (IFN-γ in serum were measured. A lung epithelial cell line was pretreated with budesonide. Levels of cathelicidin-related antimicrobial peptide (CRAMP were measured by immunohistochemistry and western blot analysis. Intracellular bacteria were observed in lung epithelial cells. Results Inhaled budesonide enhanced lung infection in allergic mice exposed to P. aeruginosa and increased the number of viable bacteria in lung tissue. Higher levels of IL-4 and lower levels of IFN-γ were observed in the serum. Budesonide decreased the expression of CRAMP, increased the number of internalized P. aeruginosa in OVA-challenged mice and in lung epithelial cell lines. These data indicate that inhaled budesonide can suppress pulmonary antibacterial host defense by down-regulating CRAMP in allergic inflammation mice and in cells in vitro. Conclusions Inhaled budesonide suppressed pulmonary antibacterial host defense in an asthmatic mouse model and in lung epithelium cells in vitro. This effect was dependent on the down-regulation of CRAMP.
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Vos, J.B.; Sterkenburg, M.A. van; Rabe, K.F.; Schalkwijk, J.; Hiemstra, P.S.; Datson, N.A.
2005-01-01
The airway epithelium responds to microbial exposure by altering expression of a variety of genes to increase innate host defense. We aimed to delineate the early transcriptional response in human primary bronchial epithelial cells exposed for 6 h to a mixture of IL-1beta and TNF-alpha or
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Ali, Hydar
2017-01-01
Mast cells (MCs) are tissue-resident immune cells that contribute to host defense but are best known for their roles in allergic and inflammatory diseases. In humans, MCs are divided into two subtypes based on the protease content of their secretory granules. Thus, human lung MCs contain only tryptase and are known as MC T , whereas skin MCs contain both tryptase and chymase and are known as MC TC . Patients with severe asthma display elevated MCs in the lung, which undergo phenotypic change from MC T to MC TC . Although the human genome contains four Mas related G protein coupled receptor X (MRGPRX) genes, an important feature of MC TC is that they selectively express MRGPRX2. It is activated by antimicrobial host defense peptides such as human β-defensins and the cathelicidin LL-37 and likely contributes to host defense. MRGPRX2 is also a receptor for the neuropeptide substance P, major basic protein, eosinophil peroxidase, opioids, and many FDA-approved cationic drugs. Increased expression of MRGPRX2 or enhanced downstream signaling likely contributes to chronic inflammatory diseases such as rosacea, atopic dermatitis, chronic urticaria, and severe asthma. In this chapter, I will discuss the expression profile and function of MRGPRX1-4 and review the emerging roles of MRGPRX2 on host defense, chronic inflammatory diseases, and drug-induced pseudoallergic reactions. I will also examine the novel aspects of MRGPRX2 signaling in MCs as it related to degranulation and review the mechanisms of its regulation. © 2017 Elsevier Inc. All rights reserved.
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Characterization of a proteolytically stable multifunctional host defense peptidomimetic
DEFF Research Database (Denmark)
Jahnsen, Rasmus D; Haney, Evan F; Franzyk, Henrik
2013-01-01
The in vitro activity of a host defense peptidomimetic (HDM-4) was investigated. The compound exhibited an antimicrobial activity profile against a range of Gram-negative bacteria. HDM-4 permeabilized the outer membrane and partly depolarized the inner membrane at its minimal inhibitory...... concentration (MIC). Moreover, it was demonstrated that HDM-4 was distributed widely in the bacterial cell at lethal concentrations, and that it could bind to DNA. It was confirmed that the multimodal action of HDM-4 resulted in it being less likely to lead to resistance development as compared to single......-target antibiotics. HDM-4 exhibited multispecies anti-biofilm activity at sub-MIC levels. Furthermore, HDM-4 modulated the immune response by inducing the release of the chemoattractants interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), and MCP-3 from human peripheral blood mononuclear cells. In addition...
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Ali, Shawkat; Magne, Maxime; Chen, Shiyan; Côté, Olivier; Stare, Barbara Gerič; Obradovic, Natasa; Jamshaid, Lubna; Wang, Xiaohong; Bélair, Guy; Moffett, Peter
2015-01-01
The potato cyst nematode, Globodera rostochiensis, is an important pest of potato. Like other pathogens, plant parasitic nematodes are presumed to employ effector proteins, secreted into the apoplast as well as the host cytoplasm, to alter plant cellular functions and successfully infect their hosts. We have generated a library of ORFs encoding putative G. rostochiensis putative apoplastic effectors in vectors for expression in planta. These clones were assessed for morphological and developmental effects on plants as well as their ability to induce or suppress plant defenses. Several CLAVATA3/ESR-like proteins induced developmental phenotypes, whereas predicted cell wall-modifying proteins induced necrosis and chlorosis, consistent with roles in cell fate alteration and tissue invasion, respectively. When directed to the apoplast with a signal peptide, two effectors, an ubiquitin extension protein (GrUBCEP12) and an expansin-like protein (GrEXPB2), suppressed defense responses including NB-LRR signaling induced in the cytoplasm. GrEXPB2 also elicited defense response in species- and sequence-specific manner. Our results are consistent with the scenario whereby potato cyst nematodes secrete effectors that modulate host cell fate and metabolism as well as modifying host cell walls. Furthermore, we show a novel role for an apoplastic expansin-like protein in suppressing intra-cellular defense responses.
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Directory of Open Access Journals (Sweden)
Shawkat Ali
Full Text Available The potato cyst nematode, Globodera rostochiensis, is an important pest of potato. Like other pathogens, plant parasitic nematodes are presumed to employ effector proteins, secreted into the apoplast as well as the host cytoplasm, to alter plant cellular functions and successfully infect their hosts. We have generated a library of ORFs encoding putative G. rostochiensis putative apoplastic effectors in vectors for expression in planta. These clones were assessed for morphological and developmental effects on plants as well as their ability to induce or suppress plant defenses. Several CLAVATA3/ESR-like proteins induced developmental phenotypes, whereas predicted cell wall-modifying proteins induced necrosis and chlorosis, consistent with roles in cell fate alteration and tissue invasion, respectively. When directed to the apoplast with a signal peptide, two effectors, an ubiquitin extension protein (GrUBCEP12 and an expansin-like protein (GrEXPB2, suppressed defense responses including NB-LRR signaling induced in the cytoplasm. GrEXPB2 also elicited defense response in species- and sequence-specific manner. Our results are consistent with the scenario whereby potato cyst nematodes secrete effectors that modulate host cell fate and metabolism as well as modifying host cell walls. Furthermore, we show a novel role for an apoplastic expansin-like protein in suppressing intra-cellular defense responses.
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Directory of Open Access Journals (Sweden)
K.P. Nickerson
2018-05-01
Full Text Available Commensal microorganisms influence a variety of host functions in the gut, including immune response, glucose homeostasis, metabolic pathways and oxidative stress, among others. This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples and “mini-guts,” organoids grown from intestinal tissue taken from biopsy specimens. We analyzed gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection. This work adds novel information regarding S. Typhi infection pathogenesis in humans, by replicating work shown in traditional cell models, and providing new data that can be applied to future vaccine development strategies. Keywords: Typhoid fever, Salmonella, Snapwell™ system, Human tissue, Terminal ileum, Immune system, Innate immunity, Immune evasion, Host-pathogen interaction, Vaccine development, Intestinal organoids, Organoid monolayer
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Crop losses due to pathogens are a major threat to global food security. Plants employ a multilayer defense system against pathogens including use of physical barriers (cell wall), induction of hypersensitive defense response (HR), resistance (R) proteins, and synthesis of antimicrobial peptides (AM...
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Directory of Open Access Journals (Sweden)
Shaimaa Abdelmegid
2017-12-01
Full Text Available Staphylococcus aureus is the most common contagious pathogen associated with bovine subclinical mastitis. Current diagnosis of S. aureus mastitis is based on bacteriological culture of milk samples and somatic cell counts, which lack either sensitivity or specificity. Identification of milk proteins that contribute to host defense and their variable responses to pathogenic stimuli would enable the characterization of putative biomarkers of subclinical mastitis. To accomplish this, milk whey samples from healthy and mastitic dairy cows were analyzed using a label-free quantitative proteomics approach. In total, 90 proteins were identified, of which 25 showed significant differential abundance between healthy and mastitic samples. In silico functional analyses indicated the involvement of the differentially abundant proteins in biological mechanisms and signaling pathways related to host defense including pathogen-recognition, direct antimicrobial function, and the acute-phase response. This proteomics and bioinformatics analysis not only facilitates the identification of putative biomarkers of S. aureus subclinical mastitis but also recapitulates previous findings demonstrating the abundance of host defense proteins in intramammary infection. All mass spectrometry data are available via ProteomeXchange with identifier PXD007516.
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DEFENSE-ATTACK INTERACTION OVER OPTIMALLY DESIGNED DEFENSE SYSTEMS VIA GAMES AND RELIABILITY
Directory of Open Access Journals (Sweden)
Isis Didier Lins
2014-05-01
Full Text Available This paper analyzes defense systems taking into account the strategic interactions between two rational agents; one of them is interested in designing a defense system against purposeful attacks of the other. The interaction is characterized by a sequential game with perfect and complete information. Reliability plays a fundamental role in both defining agents' actions and in measuring performance of the defense system for which a series-parallel configuration is set up by the defender. The attacker, in turn, focuses on only one defense subsystem in order to maximize her efficiency in attacking. An algorithm involving backward induction is developed to determine the equilibrium paths of the game. Application examples are also provided.
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Walters, Edgar T
2014-08-01
Neuropathic pain after spinal cord injury (SCI) is common, often intractable, and can be severely debilitating. A number of mechanisms have been proposed for this pain, which are discussed briefly, along with methods for revealing SCI pain in animal models, such as the recently applied conditioned place preference test. During the last decade, studies of animal models have shown that both central neuroinflammation and behavioral hypersensitivity (indirect reflex measures of pain) persist chronically after SCI. Interventions that reduce neuroinflammation have been found to ameliorate pain-related behavior, such as treatment with agents that inhibit the activation states of microglia and/or astroglia (including IL-10, minocycline, etanercept, propentofylline, ibudilast, licofelone, SP600125, carbenoxolone). Reversal of pain-related behavior has also been shown with disruption by an inhibitor (CR8) and/or genetic deletion of cell cycle-related proteins, deletion of a truncated receptor (trkB.T1) for brain-derived neurotrophic factor (BDNF), or reduction by antisense knockdown or an inhibitor (AMG9810) of the activity of channels (TRPV1 or Nav1.8) important for electrical activity in primary nociceptors. Nociceptor activity is known to drive central neuroinflammation in peripheral injury models, and nociceptors appear to be an integral component of host defense. Thus, emerging results suggest that spinal and systemic effects of SCI can activate nociceptor-mediated host defense responses that interact via neuroinflammatory signaling with complex central consequences of SCI to drive chronic pain. This broader view of SCI-induced neuroinflammation suggests new targets, and additional complications, for efforts to develop effective treatments for neuropathic SCI pain. Copyright © 2014 Elsevier Inc. All rights reserved.
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Friends or Foes? Host defense (antimicrobial) peptides and proteins in human skin diseases.
Niyonsaba, François; Kiatsurayanon, Chanisa; Chieosilapatham, Panjit; Ogawa, Hideoki
2017-11-01
Host defense peptides/proteins (HDPs), also known as antimicrobial peptides/proteins (AMPs), are key molecules in the cutaneous innate immune system. AMPs/HDPs historically exhibit broad-spectrum killing activity against bacteria, enveloped viruses, fungi and several parasites. Recently, AMPs/HDPs were shown to have important biological functions, including inducing cell proliferation, migration and differentiation; regulating inflammatory responses; controlling the production of various cytokines/chemokines; promoting wound healing; and improving skin barrier function. Despite the fact that AMPs/HDPs protect our body, several studies have hypothesized that these molecules actively contribute to the pathogenesis of various skin diseases. For example, AMPs/HDPs play crucial roles in the pathological processes of psoriasis, atopic dermatitis, rosacea, acne vulgaris, systemic lupus erythematosus and systemic sclerosis. Thus, AMPs/HDPs may be a double-edged sword, promoting cutaneous immunity while simultaneously initiating the pathogenesis of some skin disorders. This review will describe the most common skin-derived AMPs/HDPs (defensins, cathelicidins, S100 proteins, ribonucleases and dermcidin) and discuss the biology and both the positive and negative aspects of these AMPs/HDPs in skin inflammatory/infectious diseases. Understanding the regulation, functions and mechanisms of AMPs/HDPs may offer new therapeutic opportunities in the treatment of various skin disorders. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Defense Islands in Bacterial and Archaeal Genomes and Prediction of Novel Defense Systems ▿†‡
Makarova, Kira S.; Wolf, Yuri I.; Snir, Sagi; Koonin, Eugene V.
2011-01-01
The arms race between cellular life forms and viruses is a major driving force of evolution. A substantial fraction of bacterial and archaeal genomes is dedicated to antivirus defense. We analyzed the distribution of defense genes and typical mobilome components (such as viral and transposon genes) in bacterial and archaeal genomes and demonstrated statistically significant clustering of antivirus defense systems and mobile genes and elements in genomic islands. The defense islands are enriched in putative operons and contain numerous overrepresented gene families. A detailed sequence analysis of the proteins encoded by genes in these families shows that many of them are diverged variants of known defense system components, whereas others show features, such as characteristic operonic organization, that are suggestive of novel defense systems. Thus, genomic islands provide abundant material for the experimental study of bacterial and archaeal antivirus defense. Except for the CRISPR-Cas systems, different classes of defense systems, in particular toxin-antitoxin and restriction-modification systems, show nonrandom clustering in defense islands. It remains unclear to what extent these associations reflect functional cooperation between different defense systems and to what extent the islands are genomic “sinks” that accumulate diverse nonessential genes, particularly those acquired via horizontal gene transfer. The characteristics of defense islands resemble those of mobilome islands. Defense and mobilome genes are nonrandomly associated in islands, suggesting nonadaptive evolution of the islands via a preferential attachment-like mechanism underpinned by the addictive properties of defense systems such as toxins-antitoxins and an important role of horizontal mobility in the evolution of these islands. PMID:21908672
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Sandia National Laboratories: National Security Missions: Defense Systems
; Technology Defense Systems & Assessments About Defense Systems & Assessments Program Areas Audit Sandia's Economic Impact Licensing & Technology Transfer Browse Technology Portfolios ; Culture Work-Life Balance Special Programs Nuclear Weapons Defense Systems Global Security Energy Facebook
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Interplay between Candida albicans and the Mammalian Innate Host Defense
Cheng, Shih-Chin; Joosten, Leo A. B.; Kullberg, Bart-Jan
2012-01-01
Candida albicans is both the most common fungal commensal microorganism in healthy individuals and the major fungal pathogen causing high mortality in at-risk populations, especially immunocompromised patients. In this review, we summarize the interplay between the host innate system and C. albicans, ranging from how the host recognizes, responds, and clears C. albicans infection to how C. albicans evades, dampens, and escapes from host innate immunity. PMID:22252867
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DEFF Research Database (Denmark)
Bommarius, B.; Jenssen, Håvard; Elliott, M.
2010-01-01
Cationic antimicrobial host defense peptides (HDPs) combat infection by directly killing a wide variety of microbes, and/or modulating host immunity. HDPs have great therapeutic potential against antibioticresistant bacteria, viruses and even parasites, but there are substantial roadblocks......, we describe (i) a method, using fusions to SUMO, for producing high yields of intact recombinant HDPs in bacteria without significant toxicity and (ii) a simplified 2-step purification method appropriate for industrial use. We have used this method to produce seven HDPs to date (IDR1, MX226, LL37......, CRAMP, HHC-10, E5 and E6). Using this technology, pilot-scale fermentation (10 L) was performed to produce large quantities of biologically active cationic peptides. Together, these data indicate that this new method represents a cost-effective means to enable commercial enterprises to produce HDPs...
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REQUIREMENTS FOR SYSTEMS DEVELOPMENT LIFE CYCLE MODELS FOR LARGE-SCALE DEFENSE SYSTEMS
Directory of Open Access Journals (Sweden)
Kadir Alpaslan DEMIR
2015-10-01
Full Text Available TLarge-scale defense system projects are strategic for maintaining and increasing the national defense capability. Therefore, governments spend billions of dollars in the acquisition and development of large-scale defense systems. The scale of defense systems is always increasing and the costs to build them are skyrocketing. Today, defense systems are software intensive and they are either a system of systems or a part of it. Historically, the project performances observed in the development of these systems have been signifi cantly poor when compared to other types of projects. It is obvious that the currently used systems development life cycle models are insuffi cient to address today’s challenges of building these systems. Using a systems development life cycle model that is specifi cally designed for largescale defense system developments and is effective in dealing with today’s and near-future challenges will help to improve project performances. The fi rst step in the development a large-scale defense systems development life cycle model is the identifi cation of requirements for such a model. This paper contributes to the body of literature in the fi eld by providing a set of requirements for system development life cycle models for large-scale defense systems. Furthermore, a research agenda is proposed.
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2015 Assessment of the Ballistic Missile Defense System (BMDS)
2016-04-01
Director, Operational Test and Evaluation 2015 Assessment of the Ballistic Missile Defense System (BMDS...Evaluation (DOT&E) as they pertain to the Ballistic Missile Defense System (BMDS). Congress specified these requirements in the fiscal year 2002 (FY02...systems are the Ground-based Midcourse Defense (GMD), Aegis Ballistic Missile Defense (Aegis BMD), Terminal High-Altitude Area Defense (THAAD), and
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Directory of Open Access Journals (Sweden)
Glen McGillivary
2010-10-01
Full Text Available Otitis media (OM is a highly prevalent pediatric disease caused by normal flora of the nasopharynx that ascend the Eustachian tube and enter the middle ear. As OM is a disease of opportunity, it is critical to gain an increased understanding of immune system components that are operational in the upper airway and aid in prevention of this disease. SPLUNC1 is an antimicrobial host defense peptide that is hypothesized to contribute to the health of the airway both through bactericidal and non-bactericidal mechanisms. We used small interfering RNA (siRNA technology to knock down expression of the chinchilla ortholog of human SPLUNC1 (cSPLUNC1 to begin to determine the role that this protein played in prevention of OM. We showed that knock down of cSPLUNC1 expression did not impact survival of nontypeable Haemophilus influenzae, a predominant causative agent of OM, in the chinchilla middle ear under the conditions tested. In contrast, expression of cSPLUNC1 was essential for maintenance of middle ear pressure and efficient mucociliary clearance, key defense mechanisms of the tubotympanum. Collectively, our data have provided the first in vivo evidence that cSPLUNC1 functions to maintain homeostasis of the upper airway and, thereby, is critical for protection of the middle ear.
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Directory of Open Access Journals (Sweden)
Benjamin D Greenbaum
Full Text Available The innate immune response provides a first line of defense against pathogens by targeting generic differential features that are present in foreign organisms but not in the host. These innate responses generate selection forces acting both in pathogens and hosts that further determine their co-evolution. Here we analyze the nucleic acid sequence fingerprints of these selection forces acting in parallel on both host innate immune genes and ssRNA viral genomes. We do this by identifying dinucleotide biases in the coding regions of innate immune response genes in plasmacytoid dendritic cells, and then use this signal to identify other significant host innate immune genes. The persistence of these biases in the orthologous groups of genes in humans and chickens is also examined. We then compare the significant motifs in highly expressed genes of the innate immune system to those in ssRNA viruses and study the evolution of these motifs in the H1N1 influenza genome. We argue that the significant under-represented motif pattern of CpG in an AU context--which is found in both the ssRNA viruses and innate genes, and has decreased throughout the history of H1N1 influenza replication in humans--is immunostimulatory and has been selected against during the co-evolution of viruses and host innate immune genes. This shows how differences in host immune biology can drive the evolution of viruses that jump into species with different immune priorities than the original host.
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Cooperative microbial tolerance behaviors in host-microbiota mutualism
Ayres, Janelle S.
2016-01-01
Animal defense strategies against microbes are most often thought of as a function of the immune system, the primary function of which is to sense and kill microbes through the execution of resistance mechanisms. However, this antagonistic view creates complications for our understanding of beneficial host-microbe interactions. Pathogenic microbes are described as employing a few common behaviors that promote their fitness at the expense of host health and fitness. Here, a complementary framework is proposed to suggest that in addition to pathogens, beneficial microbes have evolved behaviors to manipulate host processes in order to promote their own fitness and do so through the promotion of host health and fitness. In this Perspective, I explore the idea that patterns or behaviors traditionally ascribed to pathogenic microbes are also employed by beneficial microbes to promote host tolerance defense strategies. Such strategies would promote host health without having a negative impact on microbial fitness and would thereby yield cooperative evolutionary dynamics that are likely required to drive mutualistic co-evolution of hosts and microbes. PMID:27259146
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DEFF Research Database (Denmark)
Tan, Demeng
The disease vibriosis is caused by the bacterial pathogen Vibrio anguillarum and results in large losses in aquaculture both in Denmark and around the world. Antibiotics have been widely used in antimicrobial prophylaxis and treatment of vibriosis. Recently, numerous multidrug-resistant strains...... of V. anguillarum have been isolated, indicating that antibiotic use has to be restricted and alternatives have to be developed. Lytic phages have been demonstrated to play an essential role in preventing bacterial infection. However, phages are also known to play a critical role in the evolution...... of bacterial pathogenicity development. Therefore, successful application of phage therapy in the treatment of vibriosis requires a detailed understanding of phage-host interactions, especially with regards to anti-phage defense mechanisms in the host. Part I. As a first approach, 24 V. anguillarum and 13...
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Strategic variation in mobbing as a front line of defense against brood parasitism.
Welbergen, Justin A; Davies, Nicholas B
2009-02-10
Coevolutionary arms races, where adaptations in one party select for counter-adaptations in another and vice versa, are fundamental to interactions between organisms and their predators, pathogens, and parasites [1]. Avian brood parasites and their hosts have emerged as model systems for studying such reciprocal coevolutionary processes [2, 3]. For example, hosts have evolved changes in egg appearance and rejection of foreign eggs in response to brood parasitism from cuckoos, and cuckoos have evolved host-egg mimicry as a counter-response [4-6]. However, the host's front line of defense is protecting the nest from being parasitized in the first place [7-10], yet little is known about the effectiveness of nest defense as an antiparasite adaptation, and its coevolutionary significance remains poorly understood [10]. Here we show first that mobbing of common cuckoos Cuculus canorus by reed warblers Acrocephalus scirpaceus is an effective defense against parasitism. Second, mobbing of cuckoos is a phenotypically plastic trait that is modified strategically according to local parasitism risk. This supports the view that hosts use a "defense in-depth strategy," with successive flexible lines of defense that coevolve with corresponding offensive lines of the parasite. This highlights the need for more holistic research into the coevolutionary consequences when multiple adaptations and counter-adaptations evolve in concert [11].
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Peripheral blood leukocyte count as an index of defense status in the leukopenic host
International Nuclear Information System (INIS)
Cawley, S.; Findon, G.; Miller, T.E.
1988-01-01
These experimental studies have investigated the reliability of the peripheral blood leukocyte count to predict whether the leukopenic host can contain or eliminate infection. Additionally, we have investigated the possibility that determination of leukocyte recruitment, supplementary to peripheral blood leukocyte counts, might allow individuals with neutropenia at risk from serious infection to be distinguished with greater certainty. Varying doses of radiation, cyclophosphamide, and methylprednisolone were used to induce distinct levels of leukopenia in rats. Leukocyte recruitment was measured by quantifying the response of neutropenic animals to evocative, subcutaneous stimuli, and the results of this assay were then compared with circulating leukocyte counts in the same individuals. Six models of experimentally induced infection were used to compare circulating and recruitable leukocytes as indicators of the susceptibility of the leukopenic host to infection. Response curves relating leukocyte numbers to host resistance were similar when circulating or recruitable leukocytes were used as an index of defense capability. These findings support the use of peripheral blood leukocyte numbers as an index of resistance to infection in individuals with leukopenia and suggest that functional analyses such as leukocyte recruitment are unlikely to provide additional information
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Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Mörgelin, Matthias; van der Plas, Mariena J A; Rydengård, Victoria; Malmsten, Martin; Albiger, Barbara; Schmidtchen, Artur
2012-01-01
Gram-negative sepsis is accompanied by a disproportionate innate immune response and excessive coagulation mainly induced by endotoxins released from bacteria. Due to rising antibiotic resistance and current lack of other effective treatments there is an urgent need for new therapies. We here present a new treatment concept for sepsis and endotoxin-mediated shock, based on host defense peptides from the C-terminal part of human thrombin, found to have a broad and inhibitory effect on multiple sepsis pathologies. Thus, the peptides abrogate pro-inflammatory cytokine responses to endotoxin in vitro and in vivo. Furthermore, they interfere with coagulation by modulating contact activation and tissue factor-mediated clotting in vitro, leading to normalization of coagulation responses in vivo, a previously unknown function of host defense peptides. In a mouse model of Pseudomonas aeruginosa sepsis, the peptide GKY25, while mediating a modest antimicrobial effect, significantly inhibited the pro-inflammatory response, decreased fibrin deposition and leakage in the lungs, as well as reduced mortality. Taken together, the capacity of such thrombin-derived peptides to simultaneously modulate bacterial levels, pro-inflammatory responses, and coagulation, renders them attractive therapeutic candidates for the treatment of invasive infections and sepsis.
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Directory of Open Access Journals (Sweden)
Martina Kalle
Full Text Available Gram-negative sepsis is accompanied by a disproportionate innate immune response and excessive coagulation mainly induced by endotoxins released from bacteria. Due to rising antibiotic resistance and current lack of other effective treatments there is an urgent need for new therapies. We here present a new treatment concept for sepsis and endotoxin-mediated shock, based on host defense peptides from the C-terminal part of human thrombin, found to have a broad and inhibitory effect on multiple sepsis pathologies. Thus, the peptides abrogate pro-inflammatory cytokine responses to endotoxin in vitro and in vivo. Furthermore, they interfere with coagulation by modulating contact activation and tissue factor-mediated clotting in vitro, leading to normalization of coagulation responses in vivo, a previously unknown function of host defense peptides. In a mouse model of Pseudomonas aeruginosa sepsis, the peptide GKY25, while mediating a modest antimicrobial effect, significantly inhibited the pro-inflammatory response, decreased fibrin deposition and leakage in the lungs, as well as reduced mortality. Taken together, the capacity of such thrombin-derived peptides to simultaneously modulate bacterial levels, pro-inflammatory responses, and coagulation, renders them attractive therapeutic candidates for the treatment of invasive infections and sepsis.
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Insect host/parasitoid interactions are co-evolved systems in which host defenses are balanced by parasitoid mechanisms to disable or hide from host immune effectors. Although there is a rich literature on these systems, parasitoid immune-disabling mechanisms have not been fully elucidated. Here we ...
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Ming, Zhenping; Gong, Ai-Yu; Wang, Yang; Zhang, Xin-Tian; Li, Min; Dolata, Courtney E; Chen, Xian-Ming
2018-03-01
To counteract host immunity, Cryptosporidium parvum has evolved multiple strategies to suppress host antimicrobial defense. One such strategy is to reduce the production of the antimicrobial peptide beta-defensin 1 (DEFB1) by host epithelial cells but the underlying mechanisms remain unclear. Recent studies demonstrate that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected host cells and may modulate host gene transcription. Using in vitro models of intestinal cryptosporidiosis, in this study, we analyzed the expression profile of host beta-defensin genes in host cells following infection. We found that C. parvum infection caused a significant downregulation of the DEFB1 gene. Interestingly, downregulation of DEFB1 gene was associated with host delivery of Cdg7_FLc_1000 RNA transcript, a C. parvum RNA that has previously demonstrated to be delivered into the nuclei of infected host cells. Knockdown of Cdg7_FLc_1000 in host cells could attenuate the trans-suppression of host DEFB1 gene and decreased the parasite burden. Therefore, our data suggest that trans-suppression of DEFB1 gene in intestinal epithelial cells following C. parvum infection involves host delivery of parasite Cdg7_FLc_1000 RNA, a process that may be relevant to the epithelial defense evasion by C. parvum at the early stage of infection.
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Carp erythrodermatitis : host defense-pathogen interaction
Pourreau, C.N.
1990-01-01
The outcome of a bacterial infection depends on the interaction between pathogen and host. The ability of the microbe to survive in the host depends on its invasive potential (i.e. spreading and multiplication), and its ability to obtain essential nutrients and to resist the
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Bioprospecting the American alligator (Alligator mississippiensis host defense peptidome.
Directory of Open Access Journals (Sweden)
Barney M Bishop
Full Text Available Cationic antimicrobial peptides and their therapeutic potential have garnered growing interest because of the proliferation of bacterial resistance. However, the discovery of new antimicrobial peptides from animals has proven challenging due to the limitations associated with conventional biochemical purification and difficulties in predicting active peptides from genomic sequences, if known. As an example, no antimicrobial peptides have been identified from the American alligator, Alligator mississippiensis, although their serum is antimicrobial. We have developed a novel approach for the discovery of new antimicrobial peptides from these animals, one that capitalizes on their fundamental and conserved physico-chemical properties. This sample-agnostic process employs custom-made functionalized hydrogel microparticles to harvest cationic peptides from biological samples, followed by de novo sequencing of captured peptides, eliminating the need to isolate individual peptides. After evaluation of the peptide sequences using a combination of rational and web-based bioinformatic analyses, forty-five potential antimicrobial peptides were identified, and eight of these peptides were selected to be chemically synthesized and evaluated. The successful identification of multiple novel peptides, exhibiting antibacterial properties, from Alligator mississippiensis plasma demonstrates the potential of this innovative discovery process in identifying potential new host defense peptides.
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PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing.
Chereddy, Kiran Kumar; Her, Charles-Henry; Comune, Michela; Moia, Claudia; Lopes, Alessandra; Porporato, Paolo E; Vanacker, Julie; Lam, Martin C; Steinstraesser, Lars; Sonveaux, Pierre; Zhu, Huijun; Ferreira, Lino S; Vandermeulen, Gaëlle; Préat, Véronique
2014-11-28
Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. LL37 is an endogenous human host defense peptide that modulates wound healing and angiogenesis and fights infection. Hence, we hypothesized that the administration of LL37 encapsulated in PLGA nanoparticles (PLGA-LL37 NP) promotes wound closure due to the sustained release of both LL37 and lactate. In full thickness excisional wounds, the treatment with PLGA-LL37 NP significantly accelerated wound healing compared to PLGA or LL37 administration alone. PLGA-LL37 NP-treated wounds displayed advanced granulation tissue formation by significant higher collagen deposition, re-epithelialized and neovascularized composition. PLGA-LL37 NP improved angiogenesis, significantly up-regulated IL-6 and VEGFa expression, and modulated the inflammatory wound response. In vitro, PLGA-LL37 NP induced enhanced cell migration but had no effect on the metabolism and proliferation of keratinocytes. It displayed antimicrobial activity on Escherichia coli. In conclusion, we developed a biodegradable drug delivery system that accelerated healing processes due to the combined effects of lactate and LL37 released from the nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.
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APOBEC3G: a Double Agent in Defense
Smith, Harold C.
2011-01-01
APOBEC3G (A3G) is an effective cellular host defense factor under experimental conditions in which a functional form of the HIV-encoded protein Vif cannot be expressed. Wild type Vif targets A3G for proteasomal degradation and along with it, any host defense advantage A3G might provide is severely diminished or lost. Recent evidence cast doubt on the potency of A3G in host defense and suggested that it could, under some circumstances, promote the emergence of more virulent HIV strains. In thi...
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Directory of Open Access Journals (Sweden)
Jean Michel Hily
2014-11-01
Full Text Available Identification of the determinants of pathogen reservoir potential is central to understand disease emergence. It has been proposed that host lifespan is one such determinant: short-lived hosts will invest less in costly defenses against pathogens, so that they will be more susceptible to infection, more competent as sources of infection and/or will sustain larger vector populations, thus being effective reservoirs for the infection of long-lived hosts. This hypothesis is sustained by analyses of different hosts of multihost pathogens, but not of different genotypes of the same host species. Here we examined this hypothesis by comparing two genotypes of the plant Arabidopsis thaliana that differ largely both in life-span and in tolerance to its natural pathogen Cucumber mosaic virus (CMV. Experiments with the aphid vector Myzus persicae showed that both genotypes were similarly competent as sources for virus transmission, but the short-lived genotype was more susceptible to infection and was able to sustain larger vector populations. To explore how differences in defense against CMV and its vector relate to reservoir potential, we developed a model that was run for a set of experimentally-determined parameters, and for a realistic range of host plant and vector population densities. Model simulations showed that the less efficient defenses of the short-lived genotype resulted in higher reservoir potential, which in heterogeneous host populations may be balanced by the longer infectious period of the long-lived genotype. This balance was modulated by the demography of both host and vector populations, and by the genetic composition of the host population. Thus, within-species genetic diversity for lifespan and defenses against pathogens will result in polymorphisms for pathogen reservoir potential, which will condition within-population infection dynamics. These results are relevant for a better understanding of host-pathogen co-evolution, and of
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Redesigning the Structure of Republic Indonesian Defense System; An Analysis of Systems Thinking
Directory of Open Access Journals (Sweden)
Ade Muhammad
2013-09-01
Full Text Available The phenomenon of Shrinking Defense Capabilities is only the tip of the iceberg of Indonesian Defense System’s problem. The root of the problem that lies beneath and outside is keep untouched. This journal is the part of the efforts to reveal the phenomenon’s structure that binding as a system. The present structure is a cause of that phenomenon and the basis of the current organization responsible for Republic Indonesia Defense sector. With the Systems thinking analysis, the research has revealed the structure that become the problem cause and give a holistic solution trough redesigning new structure based on two theories namely the Strategic-Operational Management with Vision Dissemination of Prof. Dr. Jürgen Strohhecker and the Defense System Generic Dr. Ir. Muhammad Tasrif, M.Eng and Ir. Ade Muhammad, M.Han. The logical consequences would also changing of formation of Indonesian Defense Organization. Keywords : Design, Redesigning, Defense System, System, Defense, Holistic
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Yamada, Noriaki; Martin, Lukas B; Zechendorf, Elisabeth; Purvis, Gareth S D; Chiazza, Fausto; Varrone, Barbara; Collino, Massimo; Shepherd, Joanna; Heinbockel, Lena; Gutsmann, Thomas; Correa, Wilmar; Brandenburg, Klaus; Marx, Gernot; Schuerholz, Tobias; Brohi, Karim; Thiemermann, Christoph
2017-03-10
To evaluate (1) levels of the host-defense/antimicrobial peptide LL-37 in patients with trauma and hemorrhagic shock (HS) and (2) the effects of a synthetic host-defense peptide; Pep19-4LF on multiple organ failure (MOF) associated with HS. HS is a common cause of death in severely injured patients. There is no specific therapy that reduces HS-associated MOF. (1) LL-37 was measured in 47 trauma/HS patients admitted to an urban major trauma center. (2) Male Wistar rats were submitted to HS (90 min, target mean arterial pressure: 27-32 mm Hg) or sham operation. Rats were treated with Pep19-4LF [66 (n = 8) or 333 μg/kg · h (n = 8)] or vehicle (n = 12) for 4 hours following resuscitation. Plasma LL-37 was 12-fold higher in patients with trauma/HS compared to healthy volunteers. HS rats treated with Pep19-4LF (high dose) had a higher mean arterial pressure at the end of the 4-hour resuscitation period (79 ± 4 vs 54 ± 5 mm Hg) and less renal dysfunction, liver injury, and lung inflammation than HS rats treated with vehicle. Pep19-4LF enhanced (kidney/liver) the phosphorylation of (1) protein kinase B and (2) endothelial nitric oxide synthase. Pep19-4LF attenuated the HS-induced (1) translocation of p65 from cytosol to nucleus, (2) phosphorylation of IκB kinase on Ser, and (3) phosphorylation of IκBα on Ser resulting in inhibition of nuclear factor kappa B and formation of proinflammatory cytokines. Pep19-4LF prevented the release of tumor necrosis factor alpha caused by heparan sulfate in human mononuclear cells by binding to this damage-associated molecular pattern. Trauma-associated HS results in release of LL-37. The synthetic host-defense/antimicrobial peptide Pep19-4LF attenuates the organ injury/dysfunction associated with HS.
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Haematophagous arthropod saliva and host defense system: a tale of tear and blood
Directory of Open Access Journals (Sweden)
Andrade Bruno B.
2005-01-01
Full Text Available The saliva from blood-feeding arthropod vectors is enriched with molecules that display diverse functions that mediate a successful blood meal. They function not only as weapons against host's haemostatic, inflammatory and immune responses but also as important tools to pathogen establishment. Parasites, virus and bacteria taking advantage of vectors' armament have adapted to facilitate their entry in the host. Today, many salivary molecules have been identified and characterized as new targets to the development of future vaccines. Here we focus on current information on vector's saliva and the molecules responsible to modify host's hemostasis and immune response, also regarding their role in disease transmission.
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Bernard, Quentin; Jaulhac, Benoit; Boulanger, Nathalie
2014-05-01
The skin is a critical barrier between hosts and pathogens in arthropod-borne diseases. It harbors many resident cells and specific immune cells to arrest or limit infections by secreting inflammatory molecules or by directly killing pathogens. However, some pathogens are able to use specific skin cells and arthropod saliva for their initial development, to hide from the host immune system, and to establish persistent infection in the vertebrate host. A better understanding of the initial mechanisms taking place in the skin should allow the development of new strategies to fight these vector-borne pathogens that are spread worldwide and are of major medical importance.
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Auld, Stuart K J R; Edel, Kai H; Little, Tom J
2012-10-01
In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.
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Elahi, Shokrollah; Buchanan, Rachelle M; Attah-Poku, Sam; Townsend, Hugh G G; Babiuk, Lorne A; Gerdts, Volker
2006-04-01
Innate immunity plays an important role in protection against respiratory infections in humans and animals. Host defense peptides such as beta-defensins represent major components of innate immunity. We recently developed a novel porcine model of pertussis, an important respiratory disease of young children and infants worldwide. Here, we investigated the role of porcine beta-defensin 1 (pBD-1), a porcine defensin homologue of human beta-defensin 2, in conferring protection against respiratory infection with Bordetella pertussis. In this model, newborn piglets were fully susceptible to infection and developed severe bronchopneumonia. In contrast, piglets older than 4 weeks of age were protected against infection with B. pertussis. Protection was associated with the expression of pBD-1 in the upper respiratory tract. In fact, pBD-1 expression was developmentally regulated, and the absence of pBD-1 was thought to contribute to the increased susceptibility of newborn piglets to infection with B. pertussis. Bronchoalveolar lavage specimens collected from older animals as well as chemically synthesized pBD-1 displayed strong antimicrobial activity against B. pertussis in vitro. Furthermore, in vivo treatment of newborn piglets with only 500 mug pBD-1 at the time of challenge conferred protection against infection with B. pertussis. Interestingly, pBD-1 displayed no bactericidal activity in vitro against Bordetella bronchiseptica, a closely related natural pathogen of pigs. Our results demonstrate that host defense peptides play an important role in protection against pertussis and are essential in modulating innate immune responses against respiratory infections.
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Microbial Genomics: The Expanding Universe of Bacterial Defense Systems.
Forsberg, Kevin J; Malik, Harmit S
2018-04-23
Bacteria protect themselves against infection using multiple defensive systems that move by horizontal gene transfer and accumulate in genomic 'defense islands'. A recent study exploited these features to uncover ten novel defense systems, substantially expanding the catalog of bacterial defense systems and predicting the discovery of many more. Copyright © 2018 Elsevier Ltd. All rights reserved.
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Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model
Directory of Open Access Journals (Sweden)
Grassian Vicki H
2011-09-01
Full Text Available Abstract Background Human exposure to nanoparticles (NPs and environmental bacteria can occur simultaneously. NPs induce inflammatory responses and oxidative stress but may also have immune-suppressive effects, impairing macrophage function and altering epithelial barrier functions. The purpose of this study was to assess the potential pulmonary effects of inhalation and instillation exposure to copper (Cu NPs using a model of lung inflammation and host defense. Methods We used Klebsiella pneumoniae (K.p. in a murine lung infection model to determine if pulmonary bacterial clearance is enhanced or impaired by Cu NP exposure. Two different exposure modes were tested: sub-acute inhalation (4 hr/day, 5 d/week for 2 weeks, 3.5 mg/m3 and intratracheal instillation (24 hr post-exposure, 3, 35, and 100 μg/mouse. Pulmonary responses were evaluated by lung histopathology plus measurement of differential cell counts, total protein, lactate dehydrogenase (LDH activity, and inflammatory cytokines in bronchoalveolar lavage (BAL fluid. Results Cu NP exposure induced inflammatory responses with increased recruitment of total cells and neutrophils to the lungs as well as increased total protein and LDH activity in BAL fluid. Both inhalation and instillation exposure to Cu NPs significantly decreased the pulmonary clearance of K.p.-exposed mice measured 24 hr after bacterial infection following Cu NP exposure versus sham-exposed mice also challenged with K.p (1.4 × 105 bacteria/mouse. Conclusions Cu NP exposure impaired host defense against bacterial lung infections and induced a dose-dependent decrease in bacterial clearance in which even our lowest dose demonstrated significantly lower clearance than observed in sham-exposed mice. Thus, exposure to Cu NPs may increase the risk of pulmonary infection.
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Detection technique of targets for missile defense system
Guo, Hua-ling; Deng, Jia-hao; Cai, Ke-rong
2009-11-01
Ballistic missile defense system (BMDS) is a weapon system for intercepting enemy ballistic missiles. It includes ballistic-missile warning system, target discrimination system, anti-ballistic-missile guidance systems, and command-control communication system. Infrared imaging detection and laser imaging detection are widely used in BMDS for surveillance, target detection, target tracking, and target discrimination. Based on a comprehensive review of the application of target-detection techniques in the missile defense system, including infrared focal plane arrays (IRFPA), ground-based radar detection technology, 3-dimensional imaging laser radar with a photon counting avalanche photodiode (APD) arrays and microchip laser, this paper focuses on the infrared and laser imaging detection techniques in missile defense system, as well as the trends for their future development.
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Massive activation of archaeal defense genes during viral infection.
Quax, Tessa E F; Voet, Marleen; Sismeiro, Odile; Dillies, Marie-Agnes; Jagla, Bernd; Coppée, Jean-Yves; Sezonov, Guennadi; Forterre, Patrick; van der Oost, John; Lavigne, Rob; Prangishvili, David
2013-08-01
Archaeal viruses display unusually high genetic and morphological diversity. Studies of these viruses proved to be instrumental for the expansion of knowledge on viral diversity and evolution. The Sulfolobus islandicus rod-shaped virus 2 (SIRV2) is a model to study virus-host interactions in Archaea. It is a lytic virus that exploits a unique egress mechanism based on the formation of remarkable pyramidal structures on the host cell envelope. Using whole-transcriptome sequencing, we present here a global map defining host and viral gene expression during the infection cycle of SIRV2 in its hyperthermophilic host S. islandicus LAL14/1. This information was used, in combination with a yeast two-hybrid analysis of SIRV2 protein interactions, to advance current understanding of viral gene functions. As a consequence of SIRV2 infection, transcription of more than one-third of S. islandicus genes was differentially regulated. While expression of genes involved in cell division decreased, those genes playing a role in antiviral defense were activated on a large scale. Expression of genes belonging to toxin-antitoxin and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems was specifically pronounced. The observed different degree of activation of various CRISPR-Cas systems highlights the specialized functions they perform. The information on individual gene expression and activation of antiviral defense systems is expected to aid future studies aimed at detailed understanding of the functions and interplay of these systems in vivo.
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DEFF Research Database (Denmark)
Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath
2012-01-01
Gram-negative sepsis is accompanied by a disproportionate innate immune response and excessive coagulation mainly induced by endotoxins released from bacteria. Due to rising antibiotic resistance and current lack of other effective treatments there is an urgent need for new therapies. We here...... present a new treatment concept for sepsis and endotoxin-mediated shock, based on host defense peptides from the C-terminal part of human thrombin, found to have a broad and inhibitory effect on multiple sepsis pathologies. Thus, the peptides abrogate pro-inflammatory cytokine responses to endotoxin...
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Seasonal forcing in a host-macroparasite system.
Taylor, Rachel A; White, Andrew; Sherratt, Jonathan A
2015-01-21
Seasonal forcing represents a pervasive source of environmental variability in natural systems. Whilst it is reasonably well understood in interacting populations and host-microparasite systems, it has not been studied in detail for host-macroparasite systems. In this paper we analyse the effect of seasonal forcing in a general host-macroparasite system with explicit inclusion of the parasite larval stage and seasonal forcing applied to the birth rate of the host. We emphasise the importance of the period of the limit cycles in the unforced system on the resulting dynamics in the forced system. In particular, when subject to seasonal forcing host-macroparasite systems are capable of multi-year cycles, multiple solution behaviour, quasi-periodicity and chaos. The host-macroparasite systems show a larger potential for multiple solution behaviour and a wider range of periodic solutions compared to similar interacting population and microparasite systems. By examining the system for parameters that represent red grouse and the macroparasite nematode Trichostrongylus tenuis we highlight how seasonality could be an important factor in explaining the wide range of seemingly uncorrelated cycle periods observed in grouse abundance in England and Scotland. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Deception used for Cyber Defense of Control Systems
Energy Technology Data Exchange (ETDEWEB)
Wayne F. Boyer; Miles A. McQueen
2009-05-01
Control system cyber security defense mechanisms may employ deception to make it more difficult for attackers to plan and execute successful attacks. These deceptive defense mechanisms are organized and initially explored according to a specific deception taxonomy and the seven abstract dimensions of security previously proposed as a framework for the cyber security of control systems.
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Energy Technology Data Exchange (ETDEWEB)
Crosby, Sean Michael; Doak, Justin E.; Haas, Jason Juedes.; Helinski, Ryan; Lamb, Christopher C.
2013-02-01
On September 5th and 6th, 2012, the Dynamic Defense Workshop: From Research to Practice brought together researchers from academia, industry, and Sandia with the goals of increasing collaboration between Sandia National Laboratories and external organizations, de ning and un- derstanding dynamic, or moving target, defense concepts and directions, and gaining a greater understanding of the state of the art for dynamic defense. Through the workshop, we broadened and re ned our de nition and understanding, identi ed new approaches to inherent challenges, and de ned principles of dynamic defense. Half of the workshop was devoted to presentations of current state-of-the-art work. Presentation topics included areas such as the failure of current defenses, threats, techniques, goals of dynamic defense, theory, foundations of dynamic defense, future directions and open research questions related to dynamic defense. The remainder of the workshop was discussion, which was broken down into sessions on de ning challenges, applications to host or mobile environments, applications to enterprise network environments, exploring research and operational taxonomies, and determining how to apply scienti c rigor to and investigating the eld of dynamic defense.
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CRISPR-Cas Targeting of Host Genes as an Antiviral Strategy.
Chen, Shuliang; Yu, Xiao; Guo, Deyin
2018-01-16
Currently, a new gene editing tool-the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated (Cas) system-is becoming a promising approach for genetic manipulation at the genomic level. This simple method, originating from the adaptive immune defense system in prokaryotes, has been developed and applied to antiviral research in humans. Based on the characteristics of virus-host interactions and the basic rules of nucleic acid cleavage or gene activation of the CRISPR-Cas system, it can be used to target both the virus genome and host factors to clear viral reservoirs and prohibit virus infection or replication. Here, we summarize recent progress of the CRISPR-Cas technology in editing host genes as an antiviral strategy.
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Directory of Open Access Journals (Sweden)
Iovanna Pandelova
Full Text Available Pyrenophora tritici-repentis (Ptr, a necrotrophic fungus and the causal agent of tan spot of wheat, produces one or a combination of host-selective toxins (HSTs necessary for disease development. The two most studied toxins produced by Ptr, Ptr ToxA (ToxA and Ptr ToxB (ToxB, are proteins that cause necrotic or chlorotic symptoms respectively. Investigation of host responses induced by HSTs provides better insight into the nature of the host susceptibility. Microarray analysis of ToxA has provided evidence that it can elicit responses similar to those associated with defense. In order to evaluate whether there are consistent host responses associated with susceptibility, a similar analysis of ToxB-induced changes in the same sensitive cultivar was conducted. Comparative analysis of ToxA- and ToxB-induced transcriptional changes showed that similar groups of genes encoding WRKY transcription factors, RLKs, PRs, components of the phenylpropanoid and jasmonic acid pathways are activated. ROS accumulation and photosystem dysfunction proved to be common mechanism-of-action for these toxins. Despite similarities in defense responses, transcriptional and biochemical responses as well as symptom development occur more rapidly for ToxA compared to ToxB, which could be explained by differences in perception as well as by differences in activation of a specific process, for example, ethylene biosynthesis in ToxA treatment. Results of this study suggest that perception of HSTs will result in activation of defense responses as part of a susceptible interaction and further supports the hypothesis that necrotrophic fungi exploit defense responses in order to induce cell death.
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Ehret, Totta; Spork, Simone; Dieterich, Christoph; Lucius, Richard; Heitlinger, Emanuel
2017-09-05
Parasites can either respond to differences in immune defenses that exist between individual hosts plastically or, alternatively, follow a genetically canalized ("hard wired") program of infection. Assuming that large-scale functional plasticity would be discernible in the parasite transcriptome we have performed a dual RNA-seq study of the lifecycle of Eimeria falciformis using infected mice with different immune status as models for coccidian infections. We compared parasite and host transcriptomes (dual transcriptome) between naïve and challenge infected mice, as well as between immune competent and immune deficient ones. Mice with different immune competence show transcriptional differences as well as differences in parasite reproduction (oocyst shedding). Broad gene categories represented by differently abundant host genes indicate enrichments for immune reaction and tissue repair functions. More specifically, TGF-beta, EGF, TNF and IL-1 and IL-6 are examples of functional annotations represented differently depending on host immune status. Much in contrast, parasite transcriptomes were neither different between Coccidia isolated from immune competent and immune deficient mice, nor between those harvested from naïve and challenge infected mice. Instead, parasite transcriptomes have distinct profiles early and late in infection, characterized largely by biosynthesis or motility associated functional gene groups, respectively. Extracellular sporozoite and oocyst stages showed distinct transcriptional profiles and sporozoite transcriptomes were found enriched for species specific genes and likely pathogenicity factors. We propose that the niche and host-specific parasite E. falciformis uses a genetically canalized program of infection. This program is likely fixed in an evolutionary process rather than employing phenotypic plasticity to interact with its host. This in turn might limit the potential of the parasite to adapt to new host species or niches, forcing
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Selected General Controls Over the Defense Business Management System
National Research Council Canada - National Science Library
1996-01-01
.... The Defense Business Management System performs appropriation accounting, cost accounting, personnel, payroll, manpower, and management information functions for the Navy, the Air Force, five Defense...
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Host exploitation strategies of the social parasite Maculinea alcon
DEFF Research Database (Denmark)
Fürst, Matthias Alois
as model systems. These enable the study of adaptations and counter-adaptations that might evolve in the arms-race between a parasite pursuing maximum gain and a host trying to avoid exploitation. One such system is the socially parasitic butterfly Maculinea alcon and its host the ant Myrmica rubra....... Throughout the first instars M. alcon lives on a specific food plant, however, in the last instar before pupation it develops into an obligate social parasite, posing a considerably cost to its host ant colony. I here focus on the different exploitation strategies of M. alcon throughout its lifecycle...... a fitness cost to infected host ant colonies, the host ants are expected to have developed defense mechanisms in response to the presence of the social parasite. I was able to demonstrate that the efficiency of ant colonies to defend themselves against intruders depends on a multitude of often correlated...
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Host genetics affect microbial ecosystems via host immunity.
El Kafsi, Hela; Gorochov, Guy; Larsen, Martin
2016-10-01
Genetic evolution of multicellular organisms has occurred in response to environmental challenges, including competition for nutrients, climate change, physical and chemical stressors, and pathogens. However, fitness of an organism is dependent not only on defense efficacy, but also on the ability to take advantage of symbiotic organisms. Indeed, microbes not only encompass pathogenicity, but also enable efficient nutrient uptake from diets nondegradable by the host itself. Moreover, microbes play important roles in the development of host immunity. Here we review associations between specific host genes and variance in microbiota composition and compare with interactions between microbes and host immunity. Recent genome-wide association studies reveal that symbiosis between host and microbiota is the exquisite result of genetic coevolution. Moreover, a subset of microbes from human and mouse microbiota have been identified to interact with humoral and cellular immunity. Interestingly, microbes associated with both host genetics and host immunity are taxonomically related. Most involved are Bifidobacterium, Lactobacillus, and Akkermansia, which are dually associated with both host immunity and host genetics. We conclude that future therapeutics targeting microbiota in the context of chronic inflammatory diseases need to consider both immune and genetic host features associated with microbiota homeostasis.
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Studies on the hepatic antioxidant defense system in &lambda ...
African Journals Online (AJOL)
Studies on the hepatic antioxidant defense system in λ cyhalothrin-induced ... Significant (P<0.05) elevation in the level of lipid peroxidation was observed in λ ... The results of the present investigation have indicated that the tissue antioxidant defense system is operating at a lower rate despite ... HOW TO USE AJOL.
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Defense High Level Waste Disposal Container System Description Document
International Nuclear Information System (INIS)
2000-01-01
The Defense High Level Waste Disposal Container System supports the confinement and isolation of waste within the Engineered Barrier System of the Monitored Geologic Repository (MGR). Disposal containers are loaded and sealed in the surface waste handling facilities, transferred to the underground through the accesses using a rail mounted transporter, and emplaced in emplacement drifts. The defense high level waste (HLW) disposal container provides long-term confinement of the commercial HLW and defense HLW (including immobilized plutonium waste forms (IPWF)) placed within disposable canisters, and withstands the loading, transfer, emplacement, and retrieval loads and environments. U.S. Department of Energy (DOE)-owned spent nuclear fuel (SNF) in disposable canisters may also be placed in a defense HLW disposal container along with commercial HLW waste forms, which is known as 'co-disposal'. The Defense High Level Waste Disposal Container System provides containment of waste for a designated period of time, and limits radionuclide release. The disposal container/waste package maintains the waste in a designated configuration, withstands maximum handling and rockfall loads, limits the individual canister temperatures after emplacement, resists corrosion in the expected handling and repository environments, and provides containment of waste in the event of an accident. Defense HLW disposal containers for HLW disposal will hold up to five HLW canisters. Defense HLW disposal containers for co-disposal will hold up to five HLW canisters arranged in a ring and one DOE SNF canister in the ring. Defense HLW disposal containers also will hold two Multi-Canister Overpacks (MCOs) and two HLW canisters in one disposal container. The disposal container will include outer and inner cylinders, outer and inner cylinder lids, and may include a canister guide. An exterior label will provide a means by which to identify the disposal container and its contents. Different materials
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Membrane rafts: a potential gateway for bacterial entry into host cells.
Hartlova, Anetta; Cerveny, Lukas; Hubalek, Martin; Krocova, Zuzana; Stulik, Jiri
2010-04-01
Pathogenic bacteria have developed various mechanisms to evade host immune defense systems. Invasion of pathogenic bacteria requires interaction of the pathogen with host receptors, followed by activation of signal transduction pathways and rearrangement of the cytoskeleton to facilitate bacterial entry. Numerous bacteria exploit specialized plasma membrane microdomains, commonly called membrane rafts, which are rich in cholesterol, sphingolipids and a special set of signaling molecules which allow entry to host cells and establishment of a protected niche within the host. This review focuses on the current understanding of the raft hypothesis and the means by which pathogenic bacteria subvert membrane microdomains to promote infection.
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Reyes, José L.; Terrazas, Luis I.; Espinoza, Bertha; Cruz-Robles, David; Soto, Virgilia; Rivera-Montoya, Irma; Gómez-García, Lorena; Snider, Heidi; Satoskar, Abhay R.; Rodríguez-Sosa, Miriam
2006-01-01
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is involved in the host defense against several pathogens. Here we used MIF−/− mice to determine the role of endogenous MIF in the regulation of the host immune response against Trypanosoma cruzi infection. MIF−/− mice displayed high levels of blood and tissue parasitemia, developed severe heart and skeletal muscle immunopathology, and succumbed to T. cruzi infection faster than MIF+/+ mice. The enhanced susceptibility of MIF−/− mice to T. cruzi was associated with reduced levels of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-12 (IL-12), IL-18, gamma interferon (IFN-γ), and IL-1β, in their sera and reduced production of IL-12, IFN-γ, and IL-4 by spleen cells during the early phase of infection. At all time points, antigen-stimulated splenocytes from MIF+/+ and MIF−/− mice produced comparable levels of IL-10. MIF−/− mice also produced significantly less Th1-associated antigen-specific immunoglobulin G2a (IgG2a) throughout the infection, but both groups produced comparable levels of Th2-associated IgG1. Lastly, inflamed hearts from T. cruzi-infected MIF−/− mice expressed increased transcripts for IFN-γ, but fewer for IL-12 p35, IL-12 p40, IL-23, and inducible nitric oxide synthase, compared to MIF+/+ mice. Taken together, our findings show that MIF plays a role in controlling acute T. cruzi infection. PMID:16714544
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The Road from Host-Defense Peptides to a New Generation of Antimicrobial Drugs
Directory of Open Access Journals (Sweden)
Alicia Boto
2018-02-01
Full Text Available Host-defense peptides, also called antimicrobial peptides (AMPs, whose protective action has been used by animals for millions of years, fulfill many requirements of the pharmaceutical industry, such as: (1 broad spectrum of activity; (2 unlike classic antibiotics, they induce very little resistance; (3 they act synergically with conventional antibiotics; (4 they neutralize endotoxins and are active in animal models. However, it is considered that many natural peptides are not suitable for drug development due to stability and biodisponibility problems, or high production costs. This review describes the efforts to overcome these problems and develop new antimicrobial drugs from these peptides or inspired by them. The discovery process of natural AMPs is discussed, as well as the development of synthetic analogs with improved pharmacological properties. The production of these compounds at acceptable costs, using different chemical and biotechnological methods, is also commented. Once these challenges are overcome, a new generation of versatile, potent and long-lasting antimicrobial drugs is expected.
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Acquisition: Allegations to the Defense Hotline on the Management of the Defense Travel System
National Research Council Canada - National Science Library
2002-01-01
.... The Defense Travel System was envisioned as a general support system designed to make business travel quicker, easier, and more efficient by providing automated commercial and Government travel...
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Modi, Bhavi P; Teves, Maria E; Pearson, Laurel N; Parikh, Hardik I; Haymond-Thornburg, Hannah; Tucker, John L; Chaemsaithong, Piya; Gomez-Lopez, Nardhy; York, Timothy P; Romero, Roberto; Strauss, Jerome F
2017-11-01
Twin studies have revealed a significant contribution of the fetal genome to risk of preterm birth. Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm delivery. Infection and inflammation of the fetal membranes is commonly found associated with PPROM. We carried out whole exome sequencing (WES) of genomic DNA from neonates born of African-American mothers whose pregnancies were complicated by PPROM (76) or were normal term pregnancies (N = 43) to identify mutations in 35 candidate genes involved in innate immunity and host defenses against microbes. Targeted genotyping of mutations in the candidates discovered by WES was conducted on an additional 188 PPROM cases and 175 controls. We identified rare heterozygous nonsense and frameshift mutations in several of the candidate genes, including CARD6, CARD8, DEFB1, FUT2, MBL2, NLP10, NLRP12, and NOD2. We discovered that some mutations (CARD6, DEFB1, FUT2, MBL2, NLRP10, NOD2) were present only in PPROM cases. We conclude that rare damaging mutations in innate immunity and host defense genes, the majority being heterozygous, are more frequent in neonates born of pregnancies complicated by PPROM. These findings suggest that the risk of preterm birth in African-Americans may be conferred by mutations in multiple genes encoding proteins involved in dampening the innate immune response or protecting the host against microbial infection and microbial products. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
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Vries, de L.J.; Langevelde, van F.
2018-01-01
Trophically transmitted parasites start their development in an intermediate host, before they finish the development in their definitive host when the definitive host preys on the intermediate host. In intermediate-definitive host systems, two strategies of host manipulation have been evolved:
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Defense High Level Waste Disposal Container System Description Document
International Nuclear Information System (INIS)
Pettit, N. E.
2001-01-01
The Defense High Level Waste Disposal Container System supports the confinement and isolation of waste within the Engineered Barrier System of the Monitored Geologic Repository (MGR). Disposal containers are loaded and sealed in the surface waste handling facilities, transferred to the underground through the accesses using a rail mounted transporter, and emplaced in emplacement drifts. The defense high level waste (HLW) disposal container provides long-term confinement of the commercial HLW and defense HLW (including immobilized plutonium waste forms [IPWF]) placed within disposable canisters, and withstands the loading, transfer, emplacement, and retrieval loads and environments. US Department of Energy (DOE)-owned spent nuclear fuel (SNF) in disposable canisters may also be placed in a defense HLW disposal container along with commercial HLW waste forms, which is known as co-disposal. The Defense High Level Waste Disposal Container System provides containment of waste for a designated period of time, and limits radionuclide release. The disposal container/waste package maintains the waste in a designated configuration, withstands maximum handling and rockfall loads, limits the individual canister temperatures after emplacement, resists corrosion in the expected handling and repository environments, and provides containment of waste in the event of an accident. Defense HLW disposal containers for HLW disposal will hold up to five HLW canisters. Defense HLW disposal containers for co-disposal will hold up to five HLW canisters arranged in a ring and one DOE SNF canister inserted in the center and/or one or more DOE SNF canisters displacing a HLW canister in the ring. Defense HLW disposal containers also will hold two Multi-Canister Overpacks (MCOs) and two HLW canisters in one disposal container. The disposal container will include outer and inner cylinders, outer and inner cylinder lids, and may include a canister guide. An exterior label will provide a means by
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Acquisition: Allegations to the Defense Hotline on the Management of the Defense Travel System
National Research Council Canada - National Science Library
2002-01-01
Who Should Read This Report and Why? This report concerns those managers who are specifically involved with managing the Defense Travel System, as well as those managing the development of information technology systems...
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Defense Enterprise Accounting and Management System-Increment 1 (DEAMS Inc 1)
2016-03-01
information accurately and in conformance with Generally Accepted Accounting Principles , to comply with Congressional requirements of the Chief Financial ...2016 Major Automated Information System Annual Report Defense Enterprise Accounting and Management System-Increment 1 (DEAMS Inc 1) Defense...Phone: 937-257-2714 Fax: DSN Phone: 787-2714 DSN Fax: Date Assigned: August 17, 2015 Program Information Program Name Defense Enterprise Accounting
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Directory of Open Access Journals (Sweden)
David Proud
Full Text Available Human rhinovirus (HRV infections trigger acute exacerbations of chronic obstructive pulmonary disease (COPD and asthma. The human airway epithelial cell is the primary site of HRV infection and responds to infection with altered expression of multiple genes, the products of which could regulate the outcome to infection. Cigarette smoking aggravates asthma symptoms, and is also the predominant risk factor for the development and progression of COPD. We, therefore, examined whether cigarette smoke extract (CSE modulates viral responses by altering HRV-induced epithelial gene expression. Primary cultures of human bronchial epithelial cells were exposed to medium alone, CSE alone, purified HRV-16 alone or to HRV-16+ CSE. After 24 h, supernatants were collected and total cellular RNA was isolated. Gene array analysis was performed to examine mRNA expression. Additional experiments, using real-time RT-PCR, ELISA and/or western blotting, validated altered expression of selected gene products. CSE and HRV-16 each induced groups of genes that were largely independent of each other. When compared to gene expression in response to CSE alone, cells treated with HRV+CSE showed no obvious differences in CSE-induced gene expression. By contrast, compared to gene induction in response to HRV-16 alone, cells exposed to HRV+CSE showed marked suppression of expression of a number of HRV-induced genes associated with various functions, including antiviral defenses, inflammation, viral signaling and airway remodeling. These changes were not associated with altered expression of type I or type III interferons. Thus, CSE alters epithelial responses to HRV infection in a manner that may negatively impact antiviral and host defense outcomes.
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Born in an alien nest: how do social parasite male offspring escape from host aggression?
Directory of Open Access Journals (Sweden)
Patrick Lhomme
Full Text Available Social parasites exploit the colony resources of social insects. Some of them exploit the host colony as a food resource or as a shelter whereas other species also exploit the brood care behavior of their social host. Some of these species have even lost the worker caste and rely completely on the host's worker force to rear their offspring. To avoid host defenses and bypass their recognition code, these social parasites have developed several sophisticated chemical infiltration strategies. These infiltration strategies have been highly studied in several hymenopterans. Once a social parasite has successfully entered a host nest and integrated its social system, its emerging offspring still face the same challenge of avoiding host recognition. However, the strategy used by the offspring to survive within the host nest without being killed is still poorly documented. In cuckoo bumblebees, the parasite males completely lack the morphological and chemical adaptations to social parasitism that the females possess. Moreover, young parasite males exhibit an early production of species-specific cephalic secretions, used as sexual pheromones. Host workers might thus be able to recognize them. Here we used a bumblebee host-social parasite system to test the hypothesis that social parasite male offspring exhibit a chemical defense strategy to escape from host aggression during their intranidal life. Using behavioral assays, we showed that extracts from the heads of young cuckoo bumblebee males contain a repellent odor that prevents parasite males from being attacked by host workers. We also show that social parasitism reduces host worker aggressiveness and helps parasite offspring acceptance.
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Readiness of the Defense Message System to Replace the Automatic Digital Network
National Research Council Canada - National Science Library
1998-01-01
.... The Defense Information Systems Agency began developing the Defense Message System (DMS) in 1988 to replace messaging functions provided by AUTODIN and electronic mail systems. Audit Objectives...
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Influenza A Virus-Host Protein Interactions Control Viral Pathogenesis.
Zhao, Mengmeng; Wang, Lingyan; Li, Shitao
2017-08-01
The influenza A virus (IAV), a member of the Orthomyxoviridae family, is a highly transmissible respiratory pathogen and represents a continued threat to global health with considerable economic and social impact. IAV is a zoonotic virus that comprises a plethora of strains with different pathogenic profiles. The different outcomes of viral pathogenesis are dependent on the engagement between the virus and the host cellular protein interaction network. The interactions may facilitate virus hijacking of host molecular machinery to fulfill the viral life cycle or trigger host immune defense to eliminate the virus. In recent years, much effort has been made to discover the virus-host protein interactions and understand the underlying mechanisms. In this paper, we review the recent advances in our understanding of IAV-host interactions and how these interactions contribute to host defense and viral pathogenesis.
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Isaac, Dervla T; Isberg, Ralph
2014-01-01
Macrophages are the front line of immune defense against invading microbes. Microbes, however, have evolved numerous and diverse mechanisms to thwart these host immune defenses and thrive intracellularly. Legionella pneumophila, a Gram-negative pathogen of amoebal and mammalian phagocytes, is one such microbe. In humans, it causes a potentially fatal pneumonia referred to as Legionnaires' disease. Armed with the Icm/Dot type IV secretion system, which is required for virulence, and approximately 300 translocated proteins, Legionella is able to enter host cells, direct the biogenesis of its own vacuolar compartment, and establish a replicative niche, where it grows to high levels before lysing the host cell. Efforts to understand the pathogenesis of this bacterium have focused on characterizing the molecular activities of its many effectors. In this article, we highlight recent strides that have been made in understanding how Legionella effectors mediate host-pathogen interactions. PMID:24762308
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Information Management Principles Applied to the Ballistic Missile Defense System
National Research Council Canada - National Science Library
Koehler, John M
2007-01-01
.... Similarly several military systems with the single mission of missile defense have evolved in service stovepipes, and are now being integrated into a national and global missile defense architecture...
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Myxoma virus in the European rabbit: interactions between the virus and its susceptible host.
Stanford, Marianne M; Werden, Steven J; McFadden, Grant
2007-01-01
Myxoma virus (MV) is a poxvirus that evolved in Sylvilagus lagomorphs, and is the causative agent of myxomatosis in European rabbits (Oryctolagus cuniculus). This virus is not a natural pathogen of O. cuniculus, yet is able to subvert the host rabbit immune system defenses and cause a highly lethal systemic infection. The interaction of MV proteins and the rabbit immune system has been an ideal model to help elucidate host/poxvirus interactions, and has led to a greater understanding of how other poxvirus pathogens are able to cause disease in their respective hosts. This review will examine how MV causes myxomatosis, by examining a selection of the identified immunomodulatory proteins that this virus expresses to subvert the immune and inflammatory pathways of infected rabbit hosts.
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2010-10-25
... Accounting Service or Missile Defense Agency. (2) For DoD, the authority to acknowledge receipt or reject... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 219 and 252 [DFARS Case 2009-D002] Defense Federal Acquisition Regulation Supplement; Electronic Subcontracting Reporting...
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Coevolution in host-parasite systems: behavioural strategies of slave-making ants and their hosts.
Foitzik, S.; DeHeer, C. J.; Hunjan, D. N.; Herbers, J. M.
2001-01-01
Recently, avian brood parasites and their hosts have emerged as model systems for the study of host-parasite coevolution. However, empirical studies of the highly analogous social parasites, which use the workers of another eusocial species to raise their own young, have never explicitly examined the dynamics of these systems from a coevolutionary perspective. Here, we demonstrate interpopulational variation in behavioural interactions between a socially parasitic slave-maker ant and its host...
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Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium.
Pukkila-Worley, Read; Ausubel, Frederick M
2012-02-01
Intestinal epithelial cells provide an essential line of defense for Caernohabditis elegans against ingested pathogens. Because nematodes consume microorganisms as their food source, there has presumably been selection pressure to evolve and maintain immune defense mechanisms within the intestinal epithelium. Here we review recent advances that further define the immune signaling network within these cells and suggest mechanisms used by the nematode to monitor for infection. In reviewing studies of pathogenesis that use this simple model system, we hope to illustrate some of the basic principles of epithelial immunity that may also be of relevance in higher order hosts. Copyright © 2012. Published by Elsevier Ltd.
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Flood risk and economically optimal safety targets for coastal flood defense systems
Dupuits, E.J.C.; Schweckendiek, T.
2015-01-01
A front defense can improve the reliability of a rear defense in a coastal flood defense system. The influence of this interdependency on the accompanying economically optimal safety targets of both front and rear defense is investigated. The results preliminary suggest that the optimal safety level
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Research on moving target defense based on SDN
Chen, Mingyong; Wu, Weimin
2017-08-01
An address mutation strategy was proposed. This strategy provided an unpredictable change in address, replacing the real address of the packet forwarding process and path mutation, thus hiding the real address of the host and path. a mobile object defense technology based on Spatio-temporal Mutation on this basis is proposed, Using the software Defined Network centralized control architecture advantage combines sFlow traffic monitoring technology and Moving Target Defense. A mutated time period which can be changed in real time according to the network traffic is changed, and the destination address is changed while the controller abruptly changes the address while the data packet is transferred between the switches to construct a moving target, confusing the host within the network, thereby protecting the host and network.
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Alamillo, Josefa M; Saénz, Pilar; García, Juan Antonio
2006-10-01
Plum pox virus (PPV) is able to replicate in inoculated leaves of Nicotiana tabacum, but is defective in systemic movement in this host. However, PPV produces a systemic infection in transgenic tobacco expressing the silencing suppressor P1/HC-Pro from tobacco etch virus (TEV). In this work we show that PPV is able to move to upper non-inoculated leaves of tobacco plants expressing bacterial salicylate hydroxylase (NahG) that degrades salicylic acid (SA). Replication and accumulation of PPV is higher in the locally infected leaves of plants deficient in SA or expressing TEV P1/HC-Pro silencing suppressor. Accumulation of viral derived small RNAs was reduced in the NahG transgenic plants, suggesting that SA might act as an enhancer of the RNA-silencing antiviral defense in tobacco. Besides, expression of SA-mediated defense transcripts, such as those of pathogenesis-related (PR) proteins PR-1 and PR-2 or alternative oxidase-1, as well as that of the putative RNA-dependent RNA polymerase NtRDR1, is induced in response to PPV infection, and the expression patterns of these defense transcripts are altered in the TEV P1/HC-Pro transgenic plants. Long-distance movement of PPV is highly enhanced in NahG x P1/HC-Pro double-transgenic plants and systemic symptoms in these plants reveal that the expression of an RNA-silencing suppressor and the lack of SA produce additive but distinct effects. Our results suggest that SA might act as an enhancer of the RNA-silencing antiviral defense in tobacco, and that silencing suppressors, such as P1/HC-Pro, also alter the SA-mediated defense. Both an RNA-silencing and an SA-mediated defense mechanism could act together to limit PPV infection.
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Identification of Novel Host Interactors of Effectors Secreted by Salmonella and Citrobacter
Energy Technology Data Exchange (ETDEWEB)
Sontag, Ryan L.; Nakayasu, Ernesto S.; Brown, Roslyn N.; Niemann, George S.; Sydor, Michael A.; Sanchez, Octavio; Ansong, Charles; Lu, Shao-Yeh; Choi, Hyungwon; Valleau, Dylan; Weitz, Karl K.; Savchenko, Alexei; Cambronne, Eric D.; Adkins, Joshua N.; McFall-Ngai, Margaret J.
2016-07-12
Many pathogenic bacteria of the family
Enterobacteriaceae use type III secretion systems to inject virulence proteins, termed “effectors,” into the host cell cytosol. Although host-cellular activities of several effectors have been demonstrated, the function and host-targeted pathways of most of the effectors identified to date are largely undetermined. To gain insight into host proteins targeted by bacterial effectors, we performed coaffinity purification of host proteins from cell lysates using recombinant effectors from theEnterobacteriaceae intracellular pathogensSalmonella enterica serovar Typhimurium andCitrobacter rodentium . We identified 54 high-confidence host interactors for theSalmonella effectors GogA, GtgA, GtgE, SpvC, SrfH, SseL, SspH1, and SssB collectively and 21 interactors for theCitrobacter effectors EspT, NleA, NleG1, and NleK. We biochemically validated the interaction between the SrfHSalmonella protein and the extracellular signal-regulated kinase 2 (ERK2) host protein kinase, which revealed a role for this effector in regulating phosphorylation levels of this enzyme, which plays a central role in signal transduction.IMPORTANCE During infection, pathogenic bacteria face an adverse environment of factors driven by both cellular and humoral defense mechanisms. To help evade the immune response and ultimately proliferate inside the host, many bacteria evolved specialized secretion systems to deliver effector proteins directly into host cells. Translocated effector proteins function to subvert host defense mechanisms. Numerous pathogenic bacteria use a specialized secretion system called type III secretion to deliver effectors into the host cell cytosol. Here, we identified 75 new host targets ofSalmonella andCitrobacter effectors, which will help elucidate their mechanisms of -
Defense.gov Special Report: A Nation's Gratitude
Department of Defense Submit Search 'A Nation's Gratitude' White House hosts dinner to honor veterans of nation's gratitude to the men and women who served in Operations Iraqi Freedom and New Dawn. Top Stories , First Lady Host Iraq War Veterans Iraq War Veterans Attend Reception More Photos A Nation's Gratitude
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Vries, de Lana; Langevelde, van F.
2017-01-01
Trophically-transmitted parasites start their development in an intermediate host, before they finish the development in their definitive host when the definitive host preys on the intermediate host. In intermediate-definitive host systems, two strategies of host manipulation have been evolved:
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75 FR 3178 - Defense Federal Acquisition Regulation Supplement; Lead System Integrators
2010-01-20
... Government procurement. Amy G. Williams, Editor, Defense Acquisition Regulations System. 0 Accordingly, the..., without change, an interim rule amending the Defense Federal Acquisition Regulation Supplement (DFARS) to... limitations on the award of new contracts for lead system integrator functions in the acquisition of major DoD...
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Demeter's Resilience: an International Food Defense exercise.
Hennessey, Morgan; Kennedy, Shaun; Busta, Frank
2010-07-01
The National Center for Food Protection and Defense (NCFPD), which is led by the University of Minnesota, hosted an international food defense exercise on 27 to 29 May 2008. Established in 2004, NCFPD is a Department of Homeland Security Center of Excellence with the mission of defending the food system through research and education. Tabletop exercises are practice-based scenarios intended to mimic real life experiences. The objective of the exercise discussed in this article was to facilitate discussion to increase awareness among exercise participants of both the threat that would be posed by an intentional attack on the food supply and the international impact of such an attack. Through facilitated discussion, exercise participants agreed on the following themes: (i) recognition of a foodborne disease outbreak is driven by the characteristics of the illness rather than the actual number of ill individuals; (ii) during the course of a foodborne outbreak there are generally multiple levels of communication; (iii) a common case definition for a foodborne disease is difficult to develop on a global scale; and (iv) the safety and health of all individuals is the number one priority of all parties involved. Several challenges were faced during the development of the exercise, but these were overcome to produce a more robust exercise. The following discussion will provide an overview of the challenges and the strategies used to overcome them. The lessons learned provide insight into how to plan, prepare, and host an international food defense exercise.
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System justification and the defense of committed relationship ideology.
Day, Martin V; Kay, Aaron C; Holmes, John G; Napier, Jaime L
2011-08-01
A consequential ideology in Western society is the uncontested belief that a committed relationship is the most important adult relationship and that almost all people want to marry or seriously couple (DePaulo & Morris, 2005). In the present article, we investigated the extent to which the system justification motive may contribute to the adoption of this ideology. In Studies 1 and 2, we examined whether a heightened motive to maintain the status quo would increase defense of committed relationship values. In Study 3, we examined the reverse association, that is, whether a threat to committed relationship ideology would also affect sociopolitical system endorsement. As past research has found that the justification of political systems depends upon how much these systems are perceived as controlling, in Study 4 we tested whether the defense of the system of committed relationships would also increase when framed as controlling. Results from Studies 1-4 were consistent with our hypotheses, but only for men. In Study 5, using cross-cultural data, we sought to replicate these findings correlationally and probe for a cause of the gender effect. Results from more than 33,000 respondents indicated a relationship (for men) between defense of the sociopolitical system and defense of marriage in countries where the traditional advantages of men over women were most threatened. In Studies 6 and 7, we investigated when this gender difference disappears. Results revealed that when we measured (Study 6) or manipulated (Study 7) personal relationship identity rather than relationship ideology, effects also emerge for women.
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Mycobacterium tuberculosis Transcription Machinery: Ready To Respond to Host Attacks
Flentie, Kelly; Garner, Ashley L.
2016-01-01
Regulating responses to stress is critical for all bacteria, whether they are environmental, commensal, or pathogenic species. For pathogenic bacteria, successful colonization and survival in the host are dependent on adaptation to diverse conditions imposed by the host tissue architecture and the immune response. Once the bacterium senses a hostile environment, it must enact a change in physiology that contributes to the organism's survival strategy. Inappropriate responses have consequences; hence, the execution of the appropriate response is essential for survival of the bacterium in its niche. Stress responses are most often regulated at the level of gene expression and, more specifically, transcription. This minireview focuses on mechanisms of regulating transcription initiation that are required by Mycobacterium tuberculosis to respond to the arsenal of defenses imposed by the host during infection. In particular, we highlight how certain features of M. tuberculosis physiology allow this pathogen to respond swiftly and effectively to host defenses. By enacting highly integrated and coordinated gene expression changes in response to stress, M. tuberculosis is prepared for battle against the host defense and able to persist within the human population. PMID:26883824
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Study on combat effectiveness of air defense missile weapon system based on queuing theory
Zhao, Z. Q.; Hao, J. X.; Li, L. J.
2017-01-01
Queuing Theory is a method to analyze the combat effectiveness of air defense missile weapon system. The model of service probability based on the queuing theory was constructed, and applied to analyzing the combat effectiveness of "Sidewinder" and "Tor-M1" air defense missile weapon system. Finally aimed at different targets densities, the combat effectiveness of different combat units of two types' defense missile weapon system is calculated. This method can be used to analyze the usefulness of air defense missile weapon system.
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Drone Defense System Architecture for U.S. Navy Strategic Facilities
2017-09-01
unlimited. DRONE DEFENSE SYSTEM ARCHITECTURE FOR U.S. NAVY STRATEGIC FACILITIES by David Arteche, Kenneth Chivers, Bryce Howard, Terrell Long, Walter...and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction...project report 4. TITLE AND SUBTITLE DRONE DEFENSE SYSTEM ARCHITECTURE FOR U.S. NAVY STRATEGIC FACILITIES 5. FUNDING NUMBERS 6. AUTHOR(S) David Arteche
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The pathogen-actin connection: A platform for defense signaling in plants
Energy Technology Data Exchange (ETDEWEB)
Day, B; Henty, Jessica L; Porter, K J; Staiger, Chris J
2011-09-08
The cytoskeleton, a dynamic network of cytoplasmic polymers, plays a central role in numerous fundamental processes, such as development, reproduction, and cellular responses to biotic and abiotic stimuli. As a platform for innate immune responses in mammalian cells, the actin cytoskeleton is a central component in the organization and activation of host defenses, including signaling and cellular repair. In plants, our understanding of the genetic and biochemical responses in both pathogen and host that are required for virulence and resistance has grown enormously. Additional advances in live-cell imaging of cytoskeletal dynamics have markedly altered our view of actin turnover in plants. In this review, we outline current knowledge of host resistance following pathogen perception, both in terms of the genetic interactions that mediate defense signaling, as well as the biochemical and cellular processes that are required for defense signaling.
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Defense Logistics Standard Systems Functional Requirements.
1987-03-01
the design of retaillintermediate-level data bases to support end-user requisition control files. The wholesale system could then be restructured to... organza - Sale tions, the residual is sold Sales and merchandising responsibility rests Vitl the Defense Reutilization and Marketing Regions Those...File (DDF) advanced by ANSI Technical Committee X3L5 and ISO TC97/SC15 • The Data Extraction, Processing, and Restructuring System (EXPRESS) designed by
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Strategic Framework for the Defense Acquisition System Understanding Defense Consolidation
National Research Council Canada - National Science Library
Potts, Anthony W
2007-01-01
...% of defense product sales annually. Defense consolidation has diminished the flexibility required for surge capacity, diminished competitive innovations in products, and reduced competitive pricing based on multiple sources for products...
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Hologenomics: Systems-Level Host Biology.
Theis, Kevin R
2018-01-01
The hologenome concept of evolution is a hypothesis explaining host evolution in the context of the host microbiomes. As a hypothesis, it needs to be evaluated, especially with respect to the extent of fidelity of transgenerational coassociation of host and microbial lineages and the relative fitness consequences of repeated associations within natural holobiont populations. Behavioral ecologists are in a prime position to test these predictions because they typically focus on animal phenotypes that are quantifiable, conduct studies over multiple generations within natural animal populations, and collect metadata on genetic relatedness and relative reproductive success within these populations. Regardless of the conclusion on the hologenome concept as an evolutionary hypothesis, a hologenomic perspective has applied value as a systems-level framework for host biology, including in medicine. Specifically, it emphasizes investigating the multivarious and dynamic interactions between patient genomes and the genomes of their diverse microbiota when attempting to elucidate etiologies of complex, noninfectious diseases.
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Host resistance of CD18 knockout mice against systemic infection with Listeria monocytogenes
Wu, Huaizhu; Prince, Joseph E.; Brayton, Cory F.; Shah, Chirayu; Zeve, Daniel; Gregory, Stephen H.; Smith, C. Wayne; Ballantyne, Christie M.
2003-01-01
Mice with targeted mutations of CD18, the common beta2 subunit of CD11/CD18 integrins, have leukocytosis, impaired transendothelial neutrophil emigration, and reduced host defense to Streptococcus pneumoniae, a gram-positive extracellular bacterium. Previous studies using blocking monoclonal antibodies suggested roles for CD18 and CD11b in hepatic neutrophil recruitment and host innate response to Listeria monocytogenes, a gram-positive intracellular bacterium. We induced systemic listeriosis in CD18 knockout (CD18-ko) and wild-type (WT) mice by tail vein injection with Listeria. By 14 days postinjection (dpi), 8 of 10 WT mice died, compared with 2 of 10 CD18-ko mice (P Listeria organisms in livers and spleens were similar in both groups at 20 min postinfection. By 3, 5, and 7 dpi, however, numbers of Listeria organisms were significantly lower in livers and spleens of CD18-ko mice than in WT mice. Histopathology showed that following Listeria infection, CD18-ko mice had milder inflammatory and necrotizing lesions in both spleens and livers than did WT mice. Cytokine assays indicated that baseline interleukin-1beta and granulocyte colony-stimulating factor (G-CSF) levels were higher in CD18-ko mice than in WT mice and that CD18-ko splenocytes produced higher levels of interleukin-1beta and G-CSF than WT splenocytes under the same amount of Listeria stimulation. These findings show that CD18 is not an absolute requirement for antilisterial innate immunity or hepatic neutrophil recruitment. We propose that the absence of CD18 in the mice results in the priming of innate immunity, as evidenced by elevated cytokine expression, and neutrophilic leukocytosis, which augments antilisterial defense.
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Expression of host defense peptides in the intestine of Eimeria-challenged chickens.
Su, S; Dwyer, D M; Miska, K B; Fetterer, R H; Jenkins, M C; Wong, E A
2017-07-01
Avian coccidiosis is caused by the intracellular protozoan Eimeria, which produces intestinal lesions leading to weight gain depression. Current control methods include vaccination and anticoccidial drugs. An alternative approach involves modulating the immune system. The objective of this study was to profile the expression of host defense peptides such as avian beta-defensins (AvBDs) and liver expressed antimicrobial peptide 2 (LEAP2), which are part of the innate immune system. The mRNA expression of AvBD family members 1, 6, 8, 10, 11, 12, and 13 and LEAP2 was examined in chickens challenged with either E. acervulina, E. maxima, or E. tenella. The duodenum, jejunum, ileum, and ceca were collected 7 d post challenge. In study 1, E. acervulina challenge resulted in down-regulation of AvBD1, AvBD6, AvBD10, AvBD11, AvBD12, and AvBD13 in the duodenum. E. maxima challenge caused down-regulation of AvBD6, AvBD10, and AvBD11 in the duodenum, down-regulation of AvBD10 in the jejunum, but up-regulation of AvBD8 and AvBD13 in the ceca. E. tenella challenge showed no change in AvBD expression in any tissue. In study 2, which involved challenge with only E. maxima, there was down-regulation of AvBD1 in the ileum, AvBD11 in the jejunum and ileum, and LEAP2 in all 3 segments of the small intestine. The expression of LEAP2 was further examined by in situ hybridization in the jejunum of chickens from study 2. LEAP2 mRNA was expressed similarly in the enterocytes lining the villi, but not in the crypts of control and Eimeria challenged chickens. The lengths of the villi in the Eimeria challenged chickens were less than those in the control chickens, which may in part account for the observed down-regulation of LEAP2 mRNA quantified by PCR. Overall, the AvBD response to Eimeria challenge was not consistent; whereas LEAP2 was consistently down-regulated, which suggests that LEAP2 plays an important role in modulating an Eimeria infection. Published by Oxford University Press on
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Defense and attack of complex and dependent systems
International Nuclear Information System (INIS)
Hausken, Kjell
2010-01-01
A framework is constructed for how to analyze the strategic defense of an infrastructure subject to attack by a strategic attacker. Merging operations research, reliability theory, and game theory for optimal analytical impact, the optimization program for the defender and attacker is specified. Targets can be in parallel, series, combined series-parallel, complex, k-out-of-n redundancy, independent, interdependent, and dependent. The defender and attacker determine how much to invest in defending versus attacking each of multiple targets. A target can have economic, human, and symbolic values, subjectively assessed by the defender and attacker. A contest success function determines the probability of a successful attack on each target, dependent on the investments by the defender and attacker into each target, and on characteristics of the contest. The defender minimizes the expected damage plus the defense costs. The attacker maximizes the expected damage minus the attack costs. Each agent is concerned about how his investments vary across the targets, and the impact on his utilities. Interdependent systems are analyzed where the defense and attack on one target impacts all targets. Dependent systems are analyzed applying Markov analysis and repeated games where a successful attack on one target in the first period impacts the unit costs of defense and attack, and the contest intensity, for the other target in the second period.
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Defense and attack of complex and dependent systems
Energy Technology Data Exchange (ETDEWEB)
Hausken, Kjell, E-mail: kjell.hausken@uis.n [Faculty of Social Sciences, University of Stavanger, N-4036 Stavanger (Norway)
2010-01-15
A framework is constructed for how to analyze the strategic defense of an infrastructure subject to attack by a strategic attacker. Merging operations research, reliability theory, and game theory for optimal analytical impact, the optimization program for the defender and attacker is specified. Targets can be in parallel, series, combined series-parallel, complex, k-out-of-n redundancy, independent, interdependent, and dependent. The defender and attacker determine how much to invest in defending versus attacking each of multiple targets. A target can have economic, human, and symbolic values, subjectively assessed by the defender and attacker. A contest success function determines the probability of a successful attack on each target, dependent on the investments by the defender and attacker into each target, and on characteristics of the contest. The defender minimizes the expected damage plus the defense costs. The attacker maximizes the expected damage minus the attack costs. Each agent is concerned about how his investments vary across the targets, and the impact on his utilities. Interdependent systems are analyzed where the defense and attack on one target impacts all targets. Dependent systems are analyzed applying Markov analysis and repeated games where a successful attack on one target in the first period impacts the unit costs of defense and attack, and the contest intensity, for the other target in the second period.
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Defense against common-mode failures in protection system design
International Nuclear Information System (INIS)
Wyman, R.H.; Johnson, G.L.
1998-01-01
The introduction of digital instrumentation and control into reactor safety systems creates a heightened concern about common-mode failure. This paper discusses the concern and methods of cope with the concern. Common-mode failures have been a 'fact-of-life' in existing systems. The informal introduction of defense-in-depth and diversity (D-in-D and D) - coupled with the fact that hardware common-mode failures are often distributed in time - has allowed systems to deal with past common-mode failures. However, identical software operating in identical redundant systems presents the potential for simultaneous failure. Consequently, the use of digital systems raises the concern about common-mode failure to a new level. A more methodical approach to mitigating common-mode failure is needed to address these concerns. Purposeful introduction of D-in-D and D has been used as a defense against common-mode failure in reactor protection systems. At least two diverse systems are provided to mitigate any potential initiating event. Additionally, diverse displays and controls are provided to allow the operator to monitor plant status and manually initiate engineered safety features. A special form of common-mode failure analysis called 'defense-in-depth and diversity analysis' has been developed to identify possible common-mode failure vulnerabilities in digital systems. An overview of this analysis technique is provided. (author)
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Defense against common-mode failures in protection system design
International Nuclear Information System (INIS)
Wyman, R.H.; Johnson, G.L.
1997-01-01
The introduction of digital instrumentation and control into reactor safety systems creates a heightened concern about common-mode failure. This paper discusses the concern and methods to cope with the concern. Common-mode failures have been a ''fact-of-life'' in existing systems. The informal introduction of defense-in-depth and diversity (D-in-D ampersand D)-coupled with the fact that hardware common-mode failures are often distributed in time-has allowed systems to deal with past common-mode failures. However, identical software operating in identical redundant systems presents the potential for simultaneous failure. Consequently, the use of digital systems raises the concern about common-mode failure to a new level. A more methodical approach to mitigating common-mode failure is needed to address these concerns. Purposeful introduction of D-in-D ampersand D has been used as a defense against common-mode failure in reactor protection systems. At least two diverse systems are provided to mitigate any potential initiating event. Additionally, diverse displays and controls are provided to allow the operator to monitor plant status and manually initiate engineered safety features. A special form of conimon-mode failure analysis called ''defense-in-depth and diversity analysis'' has been developed to identify possible conimon-mode failure vulnerabilities in digital systems. An overview of this analysis technique is provided
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Strategic Framework for the Defense Acquisition System Understanding Defense Consolidation
National Research Council Canada - National Science Library
Potts, Anthony W
2007-01-01
The 1993 policy to promote the consolidation of the United States defense industry began a series of acquisitions and mergers that went beyond the intent of the policy and left the Department of Defense (DoD...
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Radville, Laura; Chaves, Arielle; Preisser, Evan L
2011-06-01
Herbivores can trigger a wide array of morphological and chemical changes in their host plants. Feeding by some insects induces a defensive hypersensitive response, a defense mechanism consisting of elevated H(2)O(2) levels and tissue death at the site of herbivore feeding. The invasive hemlock woolly adelgid Adelges tsugae ('HWA') and elongate hemlock scale Fiorinia externa ('EHS') feed on eastern hemlocks; although both are sessile sap feeders, HWA causes more damage than EHS. The rapid rate of tree death following HWA infestation has led to the suggestion that feeding induces a hypersensitive response in hemlock trees. We assessed the potential for an herbivore-induced hypersensitive response in eastern hemlocks by measuring H(2)O(2) levels in foliage from HWA-infested, EHS-infested, and uninfested trees. Needles with settled HWA or EHS had higher H(2)O(2) levels than control needles, suggesting a localized hypersensitive plant response. Needles with no direct contact to settled HWA also had high H(2)O(2) levels, suggesting that HWA infestation may induce a systemic defense response in eastern hemlocks. There was no similar systemic defensive response in the EHS treatment. Our results showed that two herbivores in the same feeding guild had dramatically different outcomes on the health of their shared host.
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Interplay of Pathogen-Induced Defense Responses and Symbiotic Establishment in Medicago truncatula
Directory of Open Access Journals (Sweden)
Tao Chen
2017-05-01
Full Text Available Suppression of host innate immunity appears to be required for the establishment of symbiosis between rhizobia and host plants. In this study, we established a system that included a host plant, a bacterial pathogen and a symbiotic rhizobium to study the role of innate immunity during symbiotic interactions. A pathogenic bacterium, Pseudomonas syringae pv. tomato strain DC3000 (Pst DC3000, was shown to cause chlorosis in Medicago truncatula A17. Sinorhizobium meliloti strain Sm2011 (Sm2011 and Pst DC3000 strain alone induced similar defense responses in M. truncatula. However, when co-inoculated, Sm2011 specifically suppressed the defense responses induced by Pst DC3000, such as MAPK activation and ROS production. Inoculation with Sm2011 suppressed the transcription of defense-related genes triggered by Pst DC3000 infection, including the receptor of bacterial flagellin (FLS2, pathogenesis-related protein 10 (PR10, and the transcription factor WRKY33. Interestingly, inoculation with Pst DC3000 specifically inhibited the expression of the symbiosis marker genes nodule inception and nodulation pectate lyase and reduced the numbers of infection threads and nodules on M. truncatula A17 roots, indicating that Pst DC3000 inhibits the establishment of symbiosis in M. truncatula. In addition, defense-related genes, such as MAPK3/6, RbohC, and WRKY33, exhibited a transient increase in their expression in the early stage of symbiosis with Sm2011, but the expression dropped down to normal levels at later symbiotic stages. Our results suggest that plant innate immunity plays an antagonistic role in symbiosis by directly reducing the numbers of infection threads and nodules.
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2010-12-03
..., et al. Defense Federal Acquisition Regulation Supplement; Business Systems-- Definition and... Regulation Supplement; Business Systems--Definition and Administration (DFARS Case 2009-D038) AGENCY: Defense.... SUPPLEMENTARY INFORMATION: I. Background DoD published a proposed rule for Business Systems--Definition and...
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Directory of Open Access Journals (Sweden)
Brown Sam P
2005-11-01
Full Text Available Abstract Background Confronted with well-defended, novel hosts, should an enemy invest in avoidance of these hosts (behavioral adaptation, neutralization of the defensive innovation (physiological adaptation or both? Although simultaneous investment in both adaptations may first appear to be redundant, several empirical studies have suggested a reinforcement of physiological resistance to host defenses with additional avoidance behaviors. To explain this paradox, we develop a mathematical model describing the joint evolution of behavioral and physiological adaptations on the part of natural enemies to their host defenses. Our specific goals are (i to derive the conditions that may favor the simultaneous investment in avoidance and physiological resistance and (ii to study the factors that govern the relative investment in each adaptation mode. Results Our results show that (i a simultaneous investment may be optimal if the fitness costs of the adaptive traits are accelerating and the probability of encountering defended hosts is low. When (i holds, we find that (ii the more that defended hosts are rare and/or spatially aggregated, the more behavioral adaptation is favored. Conclusion Despite their interference, physiological resistance to host defensive innovations and avoidance of these same defenses are two strategies in which it may be optimal for an enemy to invest in simultaneously. The relative allocation to each strategy greatly depends on host spatial structure. We discuss the implications of our findings for the management of invasive plant species and the management of pest resistance to new crop protectants or varieties.
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Defense IRM: Alternatives Should Be Considered in Developing the New Civilian Personnel System
National Research Council Canada - National Science Library
1999-01-01
... regional centers, and attempting to improve personnel management business processes. A key part of this initiative is Defense's development of a new information management system-the Defense Civilian Personnel Data System (DCPDs...
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A host defense mechanism involving CFTR-mediated bicarbonate secretion in bacterial prostatitis.
Directory of Open Access Journals (Sweden)
Chen Xie
Full Text Available BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(- and HCO(3(-, in mediating prostate HCO(3(- secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II, along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3(- content (>50 mM, rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3(- on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3(- secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3(- secretion may be up-regulated in prostatitis as a host defense mechanism.
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Risk Assessment Using The Homeland-Defense Operational Planning System (HOPS)
International Nuclear Information System (INIS)
Durling, R L; Price, D E; Spero, K K
2005-01-01
For over ten years, the Counterproliferation Analysis and Planning System (CAPS) at Lawrence Livermore National Laboratory (LLNL) has been a planning tool used by U.S. combatant commands for mission support planning against foreign programs engaged in the manufacture of weapons of mass destruction (WMD). CAPS is endorsed by the Secretary of Defense as the preferred counterproliferation tool to be used by the nation's armed services. A sister system, the Homeland-Defense Operational Planning System (HOPS), is a new operational planning tool leveraging CAPS expertise designed to support the defense of the U.S. homeland. HOPS provides planners with a basis to make decisions to protect against acts of terrorism, focusing on the defense of facilities critical to U.S. infrastructure. Criticality of facilities, structures, and systems is evaluated on a composite matrix of specific projected casualty, economic, and sociopolitical impact bins. Based on these criteria, significant unidentified vulnerabilities are identified and secured. To provide insight into potential successes by malevolent actors, HOPS analysts strive to base their efforts mainly on unclassified open-source data. However, more cooperation is needed between HOPS analysts and facility representatives to provide an advantage to those whose task is to defend these facilities. Evaluated facilities include: refineries, major ports, nuclear power plants and other nuclear licensees, dams, government installations, convention centers, sports stadiums, tourist venues, and public and freight transportation systems. A generalized summary of analyses of U.S. infrastructure facilities will be presented
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Kandhavelu, Jeyalakshmi; Demonte, Naveen Luke; Namperumalsamy, Venkatesh Prajna; Prajna, Lalitha; Thangavel, Chitra; Jayapal, Jeya Maheshwari; Kuppamuthu, Dharmalingam
2017-01-30
Aspergillus flavus and Fusarium sp. are primary causative agents of keratitis that results in corneal tissue damage leading to vision loss particularly in individuals from the tropical parts of the world. Proteins in the tear film collected from control and keratitis patients was profiled and compared. A total of 1873 proteins from control and 1400 proteins from patient tear were identified by mass spectrometry. While 847 proteins were found to be glycosylated in the patient tear, only 726 were glycosylated in control tear. And, some of the tear proteins showed alterations in their glycosylation pattern after infection. Complement system proteins, proteins specific for neutrophil extracellular traps and proteins involved in would healing were found only in the patient tear. The presence of these innate immune system proteins in the tear film of patients supports the previous data indicating the involvement of neutrophil and complement pathways in antifungal defense. High levels of wound healing proteins in keratitis patient tear implied activation of tissue repair during infection. The early appearance of the host defense proteins and wound healing response indicates that tear proteins could be used as an early marker system for monitoring the progression of pathogenesis. Identification of negative regulators of the above defense pathways in keratitis tear indicates an intricate balance of pro and anti-defense mechanisms operating in fungal infection of the eye. Tear proteins from control and mycotic keratitis patients were separated into glycoproteins and non-glycosylated proteins and then identified by mass spectrometry. Tear proteins from keratitis patients showed alteration in the glycosylation pattern indicating the alteration of glycosylation machinery due to infection. Neutrophil extracellular traps specific proteins, complement pathway proteins, as well as wound healing proteins, were found only in patient tear showing the activation of antifungal defense
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Directory of Open Access Journals (Sweden)
Tijmen J Hommes
Full Text Available Streptococcus (S. pneumoniae is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2-/- and wild-type (Wt alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2-/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39, an isogenic capsule locus deletion mutant (D39Δcps or serotype 3 S. pneumoniae (6303 via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2-/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2-/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2-/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2-/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δcps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2.
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Stress responses in Streptococcus species and their effects on the host.
Nguyen, Cuong Thach; Park, Sang-Sang; Rhee, Dong-Kwon
2015-11-01
Streptococci cause a variety of diseases, such as dental caries, pharyngitis, meningitis, pneumonia, bacteremia, endocarditis, erysipelas, and necrotizing fasciitis. The natural niche of this genus of bacteria ranges from the mouth and nasopharynx to the skin, indicating that the bacteria will inevitably be subjected to environmental changes during invasion into the host, where it is exposed to the host immune system. Thus, the Streptococcus-host interaction determines whether bacteria are cleared by the host's defenses or whether they survive after invasion to cause serious diseases. If this interaction was to be deciphered, it could aid in the development of novel preventive and therapeutic agents. Streptococcus species possess many virulent factors, such as peroxidases and heat-shock proteins (HSPs), which play key roles in protecting the bacteria from hostile host environments. This review will discuss insights into the mechanism(s) by which streptococci adapt to host environments. Additionally, we will address how streptococcal infections trigger host stress responses; however, the mechanism by which bacterial components modulate host stress responses remains largely unknown.
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Carbonell, Alberto; Maliogka, Varvara I; Pérez, José de Jesús; Salvador, Beatriz; León, David San; García, Juan Antonio; Simón-Mateo, Carmen
2013-10-01
Plum pox virus (PPV)-D and PPV-R are two isolates from strain D of PPV that differ in host specificity. Previous analyses of chimeras originating from PPV-R and PPV-D suggested that the N terminus of the coat protein (CP) includes host-specific pathogenicity determinants. Here, these determinants were mapped precisely by analyzing the infectivity in herbaceous and woody species of chimeras containing a fragment of the 3' region of PPV-D (including the region coding for the CP) in a PPV-R backbone. These chimeras were not infectious in Prunus persica, but systemically infected Nicotiana clevelandii and N. benthamiana when specific amino acids were modified or deleted in a short 30-amino-acid region of the N terminus of the CP. Most of these mutations did not reduce PPV fitness in Prunus spp. although others impaired systemic infection in this host. We propose a model in which the N terminus of the CP, highly relevant for virus systemic movement, is targeted by a host defense mechanism in Nicotiana spp. Mutations in this short region allow PPV to overcome the defense response in this host but can compromise the efficiency of PPV systemic movement in other hosts such as Prunus spp.
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Risk Assessment Using The Homeland-Defense Operational Planning System (HOPS)
International Nuclear Information System (INIS)
Price, D E; Durling, R L
2005-01-01
The Homeland-Defense Operational Planning System (HOPS), is a new operational planning tool leveraging Lawrence Livermore National Laboratory's expertise in weapons systems and in sparse information analysis to support the defense of the U.S. homeland. HOPS provides planners with a basis to make decisions to protect against acts of terrorism, focusing on the defense of facilities critical to U.S. infrastructure. Criticality of facilities, structures, and systems is evaluated on a composite matrix of specific projected casualty, economic, and sociopolitical impact bins. Based on these criteria, significant unidentified vulnerabilities are identified and secured. To provide insight into potential successes by malevolent actors, HOPS analysts strive to base their efforts mainly on unclassified open-source data. However, more cooperation is needed between HOPS analysts and facility representatives to provide an advantage to those whose task is to defend these facilities. Evaluated facilities include: refineries, major ports, nuclear power plants and other nuclear licensees, dams, government installations, convention centers, sports stadiums, tourist venues, and public and freight transportation systems. A generalized summary of analyses of U.S. infrastructure facilities will be presented
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Performance Analysis and Optimal Allocation of Layered Defense M/M/N Queueing Systems
Directory of Open Access Journals (Sweden)
Longyue Li
2016-01-01
Full Text Available One important mission of strategic defense is to develop an integrated layered Ballistic Missile Defense System (BMDS. Motivated by the queueing theory, we presented a work for the representation, modeling, performance simulation, and channels optimal allocation of the layered BMDS M/M/N queueing systems. Firstly, in order to simulate the process of defense and to study the Defense Effectiveness (DE, we modeled and simulated the M/M/N queueing system of layered BMDS. Specifically, we proposed the M/M/N/N and M/M/N/C queueing model for short defense depth and long defense depth, respectively; single target channel and multiple target channels were distinguished in each model. Secondly, we considered the problem of assigning limited target channels to incoming targets, we illustrated how to allocate channels for achieving the best DE, and we also proposed a novel and robust search algorithm for obtaining the minimum channel requirements across a set of neighborhoods. Simultaneously, we presented examples of optimal allocation problems under different constraints. Thirdly, several simulation examples verified the effectiveness of the proposed queueing models. This work may help to understand the rules of queueing process and to provide optimal configuration suggestions for defense decision-making.
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Host Defence to Pulmonary Mycosis
Directory of Open Access Journals (Sweden)
Christopher H Mody
1999-01-01
Full Text Available OBJECTIVE: To provide a basic understanding of the mechanisms of host defense to pathogenic fungi. This will help physicians understand why some patients are predisposed to fungal infections and update basic scientists on how microbial immunology applies to fungal disease.
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Combining Host-based and network-based intrusion detection system
African Journals Online (AJOL)
These attacks were simulated using hping. The proposed system is implemented in Java. The results show that the proposed system is able to detect attacks both from within (host-based) and outside sources (network-based). Key Words: Intrusion Detection System (IDS), Host-based, Network-based, Signature, Security log.
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Directory of Open Access Journals (Sweden)
Shuiqing Hu
2015-12-01
Full Text Available Microbial pattern molecules in the intestine play immunoregulatory roles via diverse pattern recognition receptors. However, the role of the cytosolic DNA sensor AIM2 in the maintenance of intestinal homeostasis is unknown. Here, we show that Aim2−/− mice are highly susceptible to dextran sodium sulfate-induced colitis that is associated with microbial dysbiosis as represented by higher colonic burden of commensal Escherichia coli. Colonization of germ-free mice with Aim2−/− mouse microbiota leads to higher colitis susceptibility. In-depth investigation of AIM2-mediated host defense responses reveals that caspase-1 activation and IL-1β and IL-18 production are compromised in Aim2−/− mouse colons, consistent with defective inflammasome function. Moreover, IL-18 infusion reduces E. coli burden as well as colitis susceptibility in Aim2−/− mice. Altered microbiota in inflammasome-defective mice correlate with reduced expression of several antimicrobial peptides in intestinal epithelial cells. Together, these findings implicate DNA sensing by AIM2 as a regulatory mechanism for maintaining intestinal homeostasis.
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Context Dependency of a Marine Defensive Symbiosis over a Wide Geographic Distribution
Lopanik, N.; Linneman, J.; Mathew, M.
2016-02-01
The invasive, temperate marine bryozoan Bugula neritina possesses an uncultured, vertically-transmitted bacterial symbiont that produces natural products known as bryostatins. These unpalatable polyketides protect the host larvae from predation. In the western Atlantic, two host genotypes were thought to be restricted to differing latitudes based on the presence of the defensive symbiont: undefended aposymbiotic Type N animals were found at high latitudes, while defended symbiotic Type S colonies were found at low latitudes, where predation pressure is higher. We found that the host genotypes are more widespread than previously thought, but that the symbiont appeared to be restricted to hosts at lower latitudes, regardless of host phylotype, leading to the question of what factors are involved in restricting the symbiont's range. We performed reciprocal transplant experiments of symbiotic and antibiotic-cured hosts, and measured host growth, a proxy for fitness. Our data indicate that possession of the symbiont appears to present a physiological cost to the host. This cost may be more pronounced at higher latitudes where the benefit of symbiosis is less apparent. In addition, preliminary evidence suggests that symbiont titer in a Type S colony from North Carolina transplanted to Virginia is reduced over a period of nearly 4 months. Taken together, these results suggest that a combination of factors may play a role in the distribution of the defensive symbiont: (i) hosts that possess the symbiont are outcompeted by aposymbiotic conspecifics at high latitude and reduced levels of predation pressure; and (ii) symbiont growth may be inhibited or sanctioned by the host at high latitudes. As defensive symbiosis is an important trait in marine habitats, understanding factors that affect the distribution of both the host and symbiont are necessary to fully appreciate the ecological impact of symbiosis.
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Year 2000 Reporting for Defense Finance and Accounting Service Cleveland Center Systems
National Research Council Canada - National Science Library
Lane, F
1998-01-01
.... For this report, we evaluated whether DFAS: entered all required data elements into the Defense Integration Support Tools for each system, and verified that information in the Defense Integration Support Tools database was consistent...
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Evolution of System Safety at NASA as Related to Defense-in-Depth
Dezfuli, Homayoon
2015-01-01
Presentation given at the Defense-in-Depth Inter-Agency Workshop on August 26, 2015 in Rockville, MD by Homayoon Dezfuli. The presentation addresses the evolution of system safety at NASA as related to Defense-in-Depth.
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Website Fingerprinting Defenses at the Application Layer
Directory of Open Access Journals (Sweden)
Cherubin Giovanni
2017-04-01
Full Text Available Website Fingerprinting (WF allows a passive network adversary to learn the websites that a client visits by analyzing traffic patterns that are unique to each website. It has been recently shown that these attacks are particularly effective against .onion sites, anonymous web servers hosted within the Tor network. Given the sensitive nature of the content of these services, the implications of WF on the Tor network are alarming. Prior work has only considered defenses at the client-side arguing that web servers lack of incentives to adopt countermeasures. Furthermore, most of these defenses have been designed to operate on the stream of network packets, making practical deployment difficult. In this paper, we propose two application-level defenses including the first server-side defense against WF, as .onion services have incentives to support it. The other defense is a lightweight client-side defense implemented as a browser add-on, improving ease of deployment over previous approaches. In our evaluations, the server-side defense is able to reduce WF accuracy on Tor .onion sites from 69.6% to 10% and the client-side defense reduces accuracy from 64% to 31.5%.
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Bletz, Molly C.; Archer, Holly; Harris, Reid N.; McKenzie, Valerie J.; Rabemananjara, Falitiana C. E.; Rakotoarison, Andolalao; Vences, Miguel
2017-01-01
Host-associated microbiotas of vertebrates are diverse and complex communities that contribute to host health. In particular, for amphibians, cutaneous microbial communities likely play a significant role in pathogen defense; however, our ecological understanding of these communities is still in its infancy. Here, we take advantage of the fully endemic and locally species-rich amphibian fauna of Madagascar to investigate the factors structuring amphibian skin microbiota on a large scale. Usin...
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Using Organizational Systems Theory to Improve Defense Acquisition and Warfighter Requirements
National Research Council Canada - National Science Library
Alexander, Michael J
2007-01-01
.... Hence, this MBA study employed a systems approach to more credibly pinpoint improvement areas in the Defense Acquisition System through the use of systems theory and an organizational systems model...
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Anatomy and Physiology of the Urinary Tract: Relation to Host Defense and Microbial Infection.
Hickling, Duane R; Sun, Tung-Tien; Wu, Xue-Ru
2015-08-01
The urinary tract exits to a body surface area that is densely populated by a wide range of microbes. Yet, under most normal circumstances, it is typically considered sterile, i.e., devoid of microbes, a stark contrast to the gastrointestinal and upper respiratory tracts where many commensal and pathogenic microbes call home. Not surprisingly, infection of the urinary tract over a healthy person's lifetime is relatively infrequent, occurring once or twice or not at all for most people. For those who do experience an initial infection, the great majority (70% to 80%) thankfully do not go on to suffer from multiple episodes. This is a far cry from the upper respiratory tract infections, which can afflict an otherwise healthy individual countless times. The fact that urinary tract infections are hard to elicit in experimental animals except with inoculum 3-5 orders of magnitude greater than the colony counts that define an acute urinary infection in humans (105 cfu/ml), also speaks to the robustness of the urinary tract defense. How can the urinary tract be so effective in fending off harmful microbes despite its orifice in a close vicinity to that of the microbe-laden gastrointestinal tract? While a complete picture is still evolving, the general consensus is that the anatomical and physiological integrity of the urinary tract is of paramount importance in maintaining a healthy urinary tract. When this integrity is breached, however, the urinary tract can be at a heightened risk or even recurrent episodes of microbial infections. In fact, recurrent urinary tract infections are a significant cause of morbidity and time lost from work and a major challenge to manage clinically. Additionally, infections of the upper urinary tract often require hospitalization and prolonged antibiotic therapy. In this chapter, we provide an overview of the basic anatomy and physiology of the urinary tract with an emphasis on their specific roles in host defense. We also highlight the
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Jasmonic acid and salicylic acid activate a common defense system in rice.
Tamaoki, Daisuke; Seo, Shigemi; Yamada, Shoko; Kano, Akihito; Miyamoto, Ayumi; Shishido, Hodaka; Miyoshi, Seika; Taniguchi, Shiduku; Akimitsu, Kazuya; Gomi, Kenji
2013-06-01
Jasmonic acid (JA) and salicylic acid (SA) play important roles in plant defense systems. JA and SA signaling pathways interact antagonistically in dicotyledonous plants, but, the status of crosstalk between JA and SA signaling is unknown in monocots. Our rice microarray analysis showed that more than half of the genes upregulated by the SA analog BTH are also upregulated by JA, suggesting that a major portion of the SA-upregulated genes are regulated by JA-dependent signaling in rice. A common defense system that is activated by both JA and SA is thus proposed which plays an important role in pathogen defense responses in rice.
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Energy Technology Data Exchange (ETDEWEB)
Wu, Chase Qishi [Univ. of Tennessee, Memphis, TN (United States)
2016-12-01
achieve source-to-sink high-performance flows, and (2) develop tools that provide these capabilities through simple interfaces to users and applications. In terms of the former, we propose to develop (1) optimization methods that align and transition multiple storage flows to multiple network flows on multicore, multibus hosts; and (2) edge and long-haul network path realization and maintenance using advanced provisioning methods including OSCARS and OpenFlow. We also propose synthesis methods that combine these individual technologies to compose high-performance flows using a collection of constituent storage-network flows, and realize them across the storage and local network connections as well as long-haul connections. We propose to develop automated user tools that profile the hosts, storage systems, and network connections; compose the source-to-sink complex flows; and set up and maintain the needed network connections. These solutions will be tested using (1) 100 Gbps connection(s) between Oak Ridge National Laboratory (ORNL) and Argonne National Laboratory (ANL) with storage systems supported by Lustre and GPFS file systems with an asymmetric connection to University of Memphis (UM); (2) ORNL testbed with multicore and multibus hosts, switches with OpenFlow capabilities, and network emulators; and (3) 100 Gbps connections from ESnet and their Openflow testbed, and other experimental connections. This proposal brings together the expertise and facilities of the two national laboratories, ORNL and ANL, and UM. It also represents a collaboration between DOE and the Department of Defense (DOD) projects at ORNL by sharing technical expertise and personnel costs, and leveraging the existing DOD Extreme Scale Systems Center (ESSC) facilities at ORNL.
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Lev-Yadun, Simcha
2013-07-01
Aposematism (warning) signaling is a common defensive mechanism toward predatory or herbivorous animals, i.e., interactions between different trophic levels. I propose that it should be considered at least as a working hypothesis that chemical aposematism operates between certain host plants and their plant predators, parasitic plants, and that although they are also plants, they belong to a higher trophic level. Specific host plant genotypes emit known repelling chemical signals toward parasitic plants, which reduce the level of, slow the directional parasite growth (attack) toward the signaling hosts, or even cause parasitic plants to grow away from them in response to these chemicals. Chemical host aposematism toward parasitic plants may be a common but overlooked defense from parasitic plants.
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Directory of Open Access Journals (Sweden)
Georgina Fabro
2011-11-01
Full Text Available Oomycete pathogens cause diverse plant diseases. To successfully colonize their hosts, they deliver a suite of effector proteins that can attenuate plant defenses. In the oomycete downy mildews, effectors carry a signal peptide and an RxLR motif. Hyaloperonospora arabidopsidis (Hpa causes downy mildew on the model plant Arabidopsis thaliana (Arabidopsis. We investigated if candidate effectors predicted in the genome sequence of Hpa isolate Emoy2 (HaRxLs were able to manipulate host defenses in different Arabidopsis accessions. We developed a rapid and sensitive screening method to test HaRxLs by delivering them via the bacterial type-three secretion system (TTSS of Pseudomonas syringae pv tomato DC3000-LUX (Pst-LUX and assessing changes in Pst-LUX growth in planta on 12 Arabidopsis accessions. The majority (~70% of the 64 candidates tested positively contributed to Pst-LUX growth on more than one accession indicating that Hpa virulence likely involves multiple effectors with weak accession-specific effects. Further screening with a Pst mutant (ΔCEL showed that HaRxLs that allow enhanced Pst-LUX growth usually suppress callose deposition, a hallmark of pathogen-associated molecular pattern (PAMP-triggered immunity (PTI. We found that HaRxLs are rarely strong avirulence determinants. Although some decreased Pst-LUX growth in particular accessions, none activated macroscopic cell death. Fewer HaRxLs conferred enhanced Pst growth on turnip, a non-host for Hpa, while several reduced it, consistent with the idea that turnip's non-host resistance against Hpa could involve a combination of recognized HaRxLs and ineffective HaRxLs. We verified our results by constitutively expressing in Arabidopsis a sub-set of HaRxLs. Several transgenic lines showed increased susceptibility to Hpa and attenuation of Arabidopsis PTI responses, confirming the HaRxLs' role in Hpa virulence. This study shows TTSS screening system provides a useful tool to test whether
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Strategic Defense Initiative: Splendid Defense or Pipe Dream? Headline Series No. 275.
Armstrong, Scott; Grier, Peter
This pamphlet presents a discussion of the various components of President Reagan's Strategic Defense Initiative (SDI) including the problem of pulling together various new technologies into an effective defensive system and the politics of the so-called "star wars" system. An important part of the defense initiative is the…
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Rodríguez, Sara M; Valdivia, Nelson
2017-01-01
Parasites are essential components of natural communities, but the factors that generate skewed distributions of parasite occurrences and abundances across host populations are not well understood. Here, we analyse at a seascape scale the spatiotemporal relationships of parasite exposure and host body-size with the proportion of infected hosts (i.e., prevalence) and aggregation of parasite burden across ca. 150 km of the coast and over 22 months. We predicted that the effects of parasite exposure on prevalence and aggregation are dependent on host body-sizes. We used an indirect host-parasite interaction in which migratory seagulls, sandy-shore molecrabs, and an acanthocephalan worm constitute the definitive hosts, intermediate hosts, and endoparasite, respectively. In such complex systems, increments in the abundance of definitive hosts imply increments in intermediate hosts' exposure to the parasite's dispersive stages. Linear mixed-effects models showed a significant, albeit highly variable, positive relationship between seagull density and prevalence. This relationship was stronger for small (cephalothorax length >15 mm) than large molecrabs (analysis of the variance-to-mean ratio of per capita parasite burden showed no relationship between seagull density and mean parasite aggregation across host populations. However, the amount of unexplained variability in aggregation was strikingly higher in larger than smaller intermediate hosts. This unexplained variability was driven by a decrease in the mean-variance scaling in heavily infected large molecrabs. These results show complex interdependencies between extrinsic and intrinsic population attributes on the structure of host-parasite interactions. We suggest that parasite accumulation-a characteristic of indirect host-parasite interactions-and subsequent increasing mortality rates over ontogeny underpin size-dependent host-parasite dynamics.
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Management of Contract Waivers and Deviations for Defense Systems
National Research Council Canada - National Science Library
1998-01-01
This report is the fourth and final in a series of reports resulting from our audit of management of contract waivers and deviations for Defense systems and summarizes our overall evaluation. Report...
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Multiple operating system rotation environment moving target defense
Evans, Nathaniel; Thompson, Michael
2016-03-22
Systems and methods for providing a multiple operating system rotation environment ("MORE") moving target defense ("MTD") computing system are described. The MORE-MTD system provides enhanced computer system security through a rotation of multiple operating systems. The MORE-MTD system increases attacker uncertainty, increases the cost of attacking the system, reduces the likelihood of an attacker locating a vulnerability, and reduces the exposure time of any located vulnerability. The MORE-MTD environment is effectuated by rotation of the operating systems at a given interval. The rotating operating systems create a consistently changing attack surface for remote attackers.
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Krüger, Thomas; Luo, Ting; Schmidt, Hella; Shopova, Iordana; Kniemeyer, Olaf
2015-12-14
Opportunistic human pathogenic fungi including the saprotrophic mold Aspergillus fumigatus and the human commensal Candida albicans can cause severe fungal infections in immunocompromised or critically ill patients. The first line of defense against opportunistic fungal pathogens is the innate immune system. Phagocytes such as macrophages, neutrophils and dendritic cells are an important pillar of the innate immune response and have evolved versatile defense strategies against microbial pathogens. On the other hand, human-pathogenic fungi have sophisticated virulence strategies to counteract the innate immune defense. In this context, proteomic approaches can provide deeper insights into the molecular mechanisms of the interaction of host immune cells with fungal pathogens. This is crucial for the identification of both diagnostic biomarkers for fungal infections and therapeutic targets. Studying host-fungal interactions at the protein level is a challenging endeavor, yet there are few studies that have been undertaken. This review draws attention to proteomic techniques and their application to fungal pathogens and to challenges, difficulties, and limitations that may arise in the course of simultaneous dual proteome analysis of host immune cells interacting with diverse morphotypes of fungal pathogens. On this basis, we discuss strategies to overcome these multifaceted experimental and analytical challenges including the viability of immune cells during co-cultivation, the increased and heterogeneous protein complexity of the host proteome dynamically interacting with the fungal proteome, and the demands on normalization strategies in terms of relative quantitative proteome analysis.
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Allowable residual contamination levels: transuranic advanced disposal systems for defense waste
International Nuclear Information System (INIS)
Kennedy, W.E. Jr.; Napier, B.A.
1982-01-01
An evaluation of advanced disposal systems for defense transuranic (TRU) wastes is being conducted using the Allowable Residual Contamination Level (ARCL) method. The ARCL method is based on compliance with a radiation dose rate limit through a site-specific analysis of the potential for radiation exposure to individuals. For defense TRU wastes at the Hanford Site near Richland, Washington, various advanced disposal techniques are being studied to determine their potential for application. This paper presents a discussion of the results of the first stage of the TRU advanced disposal systems project
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MLDS: Multi-Layer Defense System for Preventing Advanced Persistent Threats
Directory of Open Access Journals (Sweden)
Daesung Moon
2014-12-01
Full Text Available Here we report on the issue of Advanced Persistent Threats (APT, which use malware for the purpose of leaking the data of large corporations and government agencies. APT attacks target systems continuously by utilizing intelligent and complex technologies. To overthrow the elaborate security network of target systems, it conducts an attack after undergoing a pre-reconnaissance phase. An APT attack causes financial loss, information leakage, etc. They can easily bypass the antivirus system of a target system. In this paper, we propose a Multi-Layer Defense System (MLDS that can defend against APT. This system applies a reinforced defense system by collecting and analyzing log information and various information from devices, by installing the agent on the network appliance, server and end-user. It also discusses how to detect an APT attack when one cannot block the initial intrusion while continuing to conduct other activities. Thus, this system is able to minimize the possibility of initial intrusion and damages of the system by promptly responding through rapid detection of an attack when the target system is attacked.
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Fedele, Giorgio; Schiavoni, Ilaria; Adkins, Irena; Klimova, Nela; Sebo, Peter
2017-09-21
Adenylate cyclase toxin (CyaA) is released in the course of B. pertussis infection in the host's respiratory tract in order to suppress its early innate and subsequent adaptive immune defense. CD11b-expressing dendritic cells (DC), macrophages and neutrophils are professional phagocytes and key players of the innate immune system that provide a first line of defense against invading pathogens. Recent findings revealed the capacity of B. pertussis CyaA to intoxicate DC with high concentrations of 3',5'-cyclic adenosine monophosphate (cAMP), which ultimately skews the host immune response towards the expansion of Th17 cells and regulatory T cells. CyaA-induced cAMP signaling swiftly incapacitates opsonophagocytosis, oxidative burst and NO-mediated killing of bacteria by neutrophils and macrophages. The subversion of host immune responses by CyaA after delivery into DC, macrophages and neutrophils is the subject of this review.
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International Nuclear Information System (INIS)
1998-01-01
AEMS project is destined for the development and improving of 'Defense' system of the Civil Defense Department of Ukraine. 'Defense' system is destined for prevention and operation prognosis of emergencies of technological and natural character on the territory of Ukraine as well as for the elaboration of the solutions on protection and rescue of the population and national economy resources. The data are processed at national, regional, district and town levels. By the results of task solutions possible losses of human and material resources as well as necessary forces and means for removal of these consequences are defined. (R.P.)
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Directory of Open Access Journals (Sweden)
Sara M. Rodríguez
2017-08-01
Full Text Available Background Parasites are essential components of natural communities, but the factors that generate skewed distributions of parasite occurrences and abundances across host populations are not well understood. Methods Here, we analyse at a seascape scale the spatiotemporal relationships of parasite exposure and host body-size with the proportion of infected hosts (i.e., prevalence and aggregation of parasite burden across ca. 150 km of the coast and over 22 months. We predicted that the effects of parasite exposure on prevalence and aggregation are dependent on host body-sizes. We used an indirect host-parasite interaction in which migratory seagulls, sandy-shore molecrabs, and an acanthocephalan worm constitute the definitive hosts, intermediate hosts, and endoparasite, respectively. In such complex systems, increments in the abundance of definitive hosts imply increments in intermediate hosts’ exposure to the parasite’s dispersive stages. Results Linear mixed-effects models showed a significant, albeit highly variable, positive relationship between seagull density and prevalence. This relationship was stronger for small (cephalothorax length >15 mm than large molecrabs (<15 mm. Independently of seagull density, large molecrabs carried significantly more parasites than small molecrabs. The analysis of the variance-to-mean ratio of per capita parasite burden showed no relationship between seagull density and mean parasite aggregation across host populations. However, the amount of unexplained variability in aggregation was strikingly higher in larger than smaller intermediate hosts. This unexplained variability was driven by a decrease in the mean-variance scaling in heavily infected large molecrabs. Conclusions These results show complex interdependencies between extrinsic and intrinsic population attributes on the structure of host-parasite interactions. We suggest that parasite accumulation—a characteristic of indirect host
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Directory of Open Access Journals (Sweden)
Ky Van Hoang
2012-03-01
Full Text Available Antimicrobial peptides (AMPs are critical components of host defense limiting bacterial infections at the gastrointestinal mucosal surface. Bacterial pathogens have co-evolved with host innate immunity and developed means to counteract the effect of endogenous AMPs. However, molecular mechanisms of AMP resistance in Campylobacter, an important human food borne pathogen with poultry as a major reservoir, are still largely unknown. In this study, random transposon mutagenesis and targeted site-directed mutagenesis approaches were used to identify genetic loci contributing Campylobacter resistance to fowlicidin-1, a chicken AMP belonging to cathelicidin family. An efficient transposon mutagenesis approach (EZ::TNTM
Transposome in conjunction with a microtiter plate screening identified three mutants whose susceptibilities to fowlicidin-1 were significantly increased. Backcrossing of the transposon mutations into parent strain confirmed that the AMP-sensitive phenotype in each mutant was linked to the specific transposon insertion. Direct sequencing showed that these mutants have transposon inserted in the genes encoding two-component regulator CbrR, transporter CjaB, and putative trigger factor Tig. Genomic analysis also revealed an operon (Cj1580c-1584c that is homologous to sapABCDF, an operon conferring resistance to AMP in other pathogens. Insertional inactivation of Cj1583c (sapB significantly increased susceptibility of Campylobacter to fowlicidin-1. The sapB as well as tig and cjaB mutants were significantly impaired in their ability to compete with their wild-type strain 81-176 to colonize the chicken cecum. Together, this study identified four genetic loci in Campylobacter that will be useful for characterizing molecular basis of Campylobacter resistance to AMPs, a significant knowledge gap in Campylobacter pathogenesis. -
Structure-activity studies and therapeutic potential of host defense peptides of human thrombin.
Kasetty, Gopinath; Papareddy, Praveen; Kalle, Martina; Rydengård, Victoria; Mörgelin, Matthias; Albiger, Barbara; Malmsten, Martin; Schmidtchen, Artur
2011-06-01
Peptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus, and the fungus Candida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length- and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (>12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock and P. aeruginosa sepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest.
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Cooperative Autonomous Resilient Defense Platform for Cyber-Physical Systems
Azab, Mohamed Mahmoud Mahmoud
2013-01-01
Cyber-Physical Systems (CPS) entail the tight integration of and coordination between computational and physical resources. These systems are increasingly becoming vital to modernizing the national critical infrastructure systems ranging from healthcare, to transportation and energy, to homeland security and national defense. Advances in CPS technology are needed to help improve their current capabilities as well as their adaptability, autonomicity, efficiency, reliability, safety and usabili...
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Pathogen-Induced Defense Signaling and Signal Crosstalk in Arabidopsis
Kariola, Tarja
2006-01-01
Erwinia carotovora subsp. carotovora is a bacterial phytopathogen that causes soft rot in various agronomically important crop plants. A genetically specified resistance to E. carotovora has not been defined, and plant resistance to this pathogen is established through nonspecific activation of basal defense responses. This, together with the broad host range, makes this pathogen a good model for studying the activation of plant defenses. Production and secretion of plant cell wall-degrading ...
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Ben Bacha, Abir; Abid, Islem
2013-03-01
The best known physiologic function of secreted phospholipase A2 (sPLA2) group IIA (sPLA2-IIA) is defense against bacterial infection through hydrolytic degradation of bacterial membrane phospholipids. In fact, sPLA2-IIA effectively kills Gram-positive bacteria and to a lesser extent Gram-negative bacteria and is considered a major component of the eye's innate immune defense system. The antibacterial properties of sPLA2 have been demonstrated in rabbit and human tears. In this report, we have analyzed the bactericidal activity of dromedary tears and the subsequently purified sPLA2 on several Gram-positive bacteria. Our results showed that the sPLA2 displays a potent bactericidal activity against all the tested bacteria particularly against the Staphylococcus strains when tested in the ionic environment of tears. There is a synergic action of the sPLA2 with lysozyme when added to the bacteria culture prior to sPLA2. Interestingly, lysozyme purified from dromedary tears showed a significant bactericidal activity against Listeria monocytogene and Staphylococcus epidermidis, whereas the one purified from human tears displayed no activity against these two strains. We have also demonstrated that Ca(2+) is crucial for the activity of dromedary tear sPLA2 and to a less extent Mg(2+) ions. Given the presence of sPLA2 in tears and intestinal secretions, this enzyme may play a substantial role in innate mucosal and systemic bactericidal defenses against Gram-positive bacteria.
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An effector of the Irish potato famine pathogen antagonizes a host autophagy cargo receptor
Dagdas, Yasin F; Belhaj, Khaoula; Maqbool, Abbas; Chaparro-Garcia, Angela; Pandey, Pooja; Petre, Benjamin; Tabassum, Nadra; Cruz-Mireles, Neftaly; Hughes, Richard K; Sklenar, Jan; Win, Joe; Menke, Frank; Findlay, Kim; Banfield, Mark J; Kamoun, Sophien; Bozkurt, Tolga O
2016-01-01
Plants use autophagy to safeguard against infectious diseases. However, how plant pathogens interfere with autophagy-related processes is unknown. Here, we show that PexRD54, an effector from the Irish potato famine pathogen Phytophthora infestans, binds host autophagy protein ATG8CL to stimulate autophagosome formation. PexRD54 depletes the autophagy cargo receptor Joka2 out of ATG8CL complexes and interferes with Joka2's positive effect on pathogen defense. Thus, a plant pathogen effector has evolved to antagonize a host autophagy cargo receptor to counteract host defenses. DOI: http://dx.doi.org/10.7554/eLife.10856.001 PMID:26765567
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Vulnerability And Risk Assessment Using The Homeland-Defense Operational Planning System (HOPS)
International Nuclear Information System (INIS)
Durling, R.L. Jr.; Price, D.E.; Spero, K.K.
2005-01-01
For over ten years, the Counterproliferation Analysis and Planning System (CAPS) at Lawrence Livermore National Laboratory (LLNL) has been a planning tool used by U.S. combatant commands for mission support planning against foreign programs engaged in the manufacture of weapons of mass destruction (WMD). CAPS is endorsed by the Secretary of Defense as the preferred counterproliferation tool to be used by the nation's armed services. A sister system, the Homeland-Defense Operational Planning System (HOPS), is a new operational planning tool leveraging CAPS expertise designed to support the defense of the U.S. homeland. HOPS provides planners with a basis to make decisions to protect against acts of terrorism, focusing on the defense of facilities critical to U.S. infrastructure. Criticality of facilities, structures, and systems is evaluated on a composite matrix of specific projected casualty, economic, and sociopolitical impact bins. Based on these criteria, significant unidentified vulnerabilities are identified and secured. To provide insight into potential successes by malevolent actors, HOPS analysts strive to base their efforts mainly on unclassified open-source data. However, more cooperation is needed between HOPS analysts and facility representatives to provide an advantage to those whose task is to defend these facilities. Evaluated facilities include: refineries, major ports, nuclear power plants and other nuclear licensees, dams, government installations, convention centers, sports stadiums, tourist venues, and public and freight transportation systems. A generalized summary of analyses of U.S. infrastructure facilities is presented
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Proteomic Characterization of Host Response to Yersinia pestis
Energy Technology Data Exchange (ETDEWEB)
Chromy, B; Perkins, J; Heidbrink, J; Gonzales, A; Murhpy, G; Fitch, J P; McCutchen-Maloney, S
2004-05-11
Host-pathogen interactions result in protein expression changes within both the host and the pathogen. Here, results from proteomic characterization of host response following exposure to Yersinia pestis, the causative agent of plague, and to two near neighbors, Y. pseudotuberculosis and Y. enterocolitica, are reported. Human monocyte-like cells were chosen as a model for macrophage immune response to pathogen exposure. Two-dimensional electrophoresis followed by mass spectrometry was used to identify host proteins with differential expression following exposure to these three closely related Yersinia species. This comparative proteomic characterization of host response clearly shows that host protein expression patterns are distinct for the different pathogen exposures, and contributes to further understanding of Y. pestis virulence and host defense mechanisms. This work also lays the foundation for future studies aimed at defining biomarkers for presymptomatic detection of plague.
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Parasitic Cuscuta factor(s) and the detection by tomato initiates plant defense.
Fürst, Ursula; Hegenauer, Volker; Kaiser, Bettina; Körner, Max; Welz, Max; Albert, Markus
2016-01-01
Dodders ( Cuscuta spp.) are holoparasitic plants that enwind stems of host plants and penetrate those by haustoria to connect to the vascular bundles. Having a broad host plant spectrum, Cuscuta spp infect nearly all dicot plants - only cultivated tomato as one exception is mounting an active defense specifically against C. reflexa . In a recent work we identified a pattern recognition receptor of tomato, "Cuscuta Receptor 1" (CuRe1), which is critical to detect a "Cuscuta factor" (CuF) and initiate defense responses such as the production of ethylene or the generation of reactive oxygen species. CuRe1 also contributes to the tomato resistance against C. reflexa . Here we point to the fact that CuRe1 is not the only relevant component for full tomato resistance but it requires additional defense mechanisms, or receptors, respectively, to totally fend off the parasite.
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A viral suppressor protein inhibits host RNA silencing by hooking up with Argonautes
Jin, Hailing
2010-05-01
RNA viruses are particularly vulnerable to RNAi-based defenses in the host, and thus have evolved specific proteins, known as viral suppressors of RNA silencing (VSRs), as a counterdefense. In this issue of Genes & Development, Azevedo and colleagues (pp. 904-915) discovered that P38, the VSR of Turnip crinkle virus, uses its glycine/tryptophane (GW) motifs as an ARGONAUTE (AGO) hook to attract and disarm the host\\'s essential effector of RNA silencing. Several GW motif-containing cellular proteins are known to be important partners of AGOs in RNA silencing effector complexes in yeast, plants, and animals. The GW motif appears to be a versatile and effective tool for regulating the activities of RNA silencing pathways, and the use of GW mimicry to compete for and inhibit host AGOs may be a strategy used by many pathogens to counteract host RNAi-based defenses. © 2010 by Cold Spring Harbor Laboratory Press.
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Bacterial Serine/Threonine Protein Kinases in Host-Pathogen Interactions*
Canova, Marc J.; Molle, Virginie
2014-01-01
In bacterial pathogenesis, monitoring and adapting to the dynamically changing environment in the host and an ability to disrupt host immune responses are critical. The virulence determinants of pathogenic bacteria include the sensor/signaling proteins of the serine/threonine protein kinase (STPK) family that have a dual role of sensing the environment and subverting specific host defense processes. STPKs can sense a wide range of signals and coordinate multiple cellular processes to mount an appropriate response. Here, we review some of the well studied bacterial STPKs that are essential virulence factors and that modify global host responses during infection. PMID:24554701
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Bacterial serine/threonine protein kinases in host-pathogen interactions.
Canova, Marc J; Molle, Virginie
2014-04-04
In bacterial pathogenesis, monitoring and adapting to the dynamically changing environment in the host and an ability to disrupt host immune responses are critical. The virulence determinants of pathogenic bacteria include the sensor/signaling proteins of the serine/threonine protein kinase (STPK) family that have a dual role of sensing the environment and subverting specific host defense processes. STPKs can sense a wide range of signals and coordinate multiple cellular processes to mount an appropriate response. Here, we review some of the well studied bacterial STPKs that are essential virulence factors and that modify global host responses during infection.
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Use of the Homeland-Defense Operational Planning System (HOPS) for Emergency Management
International Nuclear Information System (INIS)
Durling, Jr. R.L.; Price, D.E.
2005-01-01
The Homeland-Defense Operational Planning System (HOPS), is a new operational planning tool leveraging Lawrence Livermore National Laboratory's expertise in weapons systems and in sparse information analysis to support the defense of the U.S. homeland. HOPS provides planners with a basis to make decisions to protect against acts of terrorism, focusing on the defense of facilities critical to U.S. infrastructure. Criticality of facilities, structures, and systems is evaluated on a composite matrix of specific projected casualty, economic, and sociopolitical impact bins. Based on these criteria, significant unidentified vulnerabilities are identified and secured. To provide insight into potential successes by malevolent actors, HOPS analysts strive to base their efforts mainly on unclassified open-source data. However, more cooperation is needed between HOPS analysts and facility representatives to provide an advantage to those whose task is to defend these facilities. Evaluated facilities include: refineries, major ports, nuclear power plants and other nuclear licensees, dams, government installations, convention centers, sports stadiums, tourist venues, and public and freight transportation systems. A generalized summary of analyses of U.S. infrastructure facilities will be presented
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Conlon, J Michael; Mechkarska, Milena; Kolodziejek, Jolanta; Leprince, Jérôme; Coquet, Laurent; Jouenne, Thierry; Vaudry, Hubert; Nowotny, Norbert; King, Jay D
2015-10-01
Peptidomic analysis of norepinephrine-stimulated skin secretions from the octoploid Mawa clawed frog Xenopus boumbaensis Loumont, 1983 led to the identification and characterization of 15 host-defense peptides belonging to the magainin (two peptides), peptide glycine-leucine-amide (PGLa; three peptides), xenopsin precursor fragment (XPF; three peptides), caerulein precursor fragment (CPF; two peptides), and caerulein precursor fragment-related peptide (CPF-RP; five peptides) families. In addition, caerulein and three peptides with structural similarity to the trefoil factor family (TFF) peptides, xP2 and xP4 from Xenopus laevis were also present in the secretions. Consistent with data from comparisons of the nucleotides sequence of mitochondrial and nuclear genes, the primary structures of the peptides suggest a close phylogenetic relationship between X. boumbaensis and the octoploid frogs Xenopus amieti and Xenopus andrei. As the three species occupy disjunct ranges within Cameroon, it is suggested that they diverged from a common ancestor by allopatric speciation. Copyright © 2015 Elsevier Inc. All rights reserved.
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Evasion of Human Neutrophil-Mediated Host Defense during Toxoplasma gondii Infection.
Lima, Tatiane S; Gov, Lanny; Lodoen, Melissa B
2018-02-13
Neutrophils are a major player in host immunity to infection; however, the mechanisms by which human neutrophils respond to the intracellular protozoan parasite Toxoplasma gondii are still poorly understood. In the current study, we found that, whereas primary human monocytes produced interleukin-1beta (IL-1β) in response to T. gondii infection, human neutrophils from the same blood donors did not. Moreover, T. gondii inhibited lipopolysaccharide (LPS)-induced IL-1β synthesis in human peripheral blood neutrophils. IL-1β suppression required active parasite invasion, since heat-killed or mycalolide B-treated parasites did not inhibit IL-1β release. By investigating the mechanisms involved in this process, we found that T. gondii infection of neutrophils treated with LPS resulted in reduced transcript levels of IL-1β and NLRP3 and reduced protein levels of pro-IL-1β, mature IL-1β, and the inflammasome sensor NLRP3. In T. gondii -infected neutrophils stimulated with LPS, the levels of MyD88, TRAF6, IKKα, IKKβ, and phosphorylated IKKα/β were not affected. However, LPS-induced IκBα degradation and p65 phosphorylation were reduced in T. gondii- infected neutrophils, and degradation of IκBα was reversed by treatment with the proteasome inhibitor MG-132. Finally, we observed that T. gondii inhibited the cleavage and activity of caspase-1 in human neutrophils. These results indicate that T. gondii suppression of IL-1β involves a two-pronged strategy whereby T. gondii inhibits both NF-κB signaling and activation of the NLRP3 inflammasome. These findings represent a novel mechanism of T. gondii evasion of human neutrophil-mediated host defense by targeting the production of IL-1β. IMPORTANCE Toxoplasma gondii is an obligate intracellular parasite that infects approximately one-third of humans worldwide and can invade virtually any nucleated cell in the human body. Although it is well documented that neutrophils infiltrate the site of acute T
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Directory of Open Access Journals (Sweden)
Ala E. Tabor
2017-12-01
Full Text Available Ticks are able to transmit tick-borne infectious agents to vertebrate hosts which cause major constraints to public and livestock health. The costs associated with mortality, relapse, treatments, and decreased production yields are economically significant. Ticks adapted to a hematophagous existence after the vertebrate hemostatic system evolved into a multi-layered defense system against foreign invasion (pathogens and ectoparasites, blood loss, and immune responses. Subsequently, ticks evolved by developing an ability to suppress the vertebrate host immune system with a devastating impact particularly for exotic and crossbred cattle. Host genetics defines the immune responsiveness against ticks and tick-borne pathogens. To gain an insight into the naturally acquired resistant and susceptible cattle breed against ticks, studies have been conducted comparing the incidence of tick infestation on bovine hosts from divergent genetic backgrounds. It is well-documented that purebred and crossbred Bos taurus indicus cattle are more resistant to ticks and tick-borne pathogens compared to purebred European Bos taurus taurus cattle. Genetic studies identifying Quantitative Trait Loci markers using microsatellites and SNPs have been inconsistent with very low percentages relating phenotypic variation with tick infestation. Several skin gene expression and immunological studies have been undertaken using different breeds, different samples (peripheral blood, skin with tick feeding, infestation protocols and geographic environments. Susceptible breeds were commonly found to be associated with the increased expression of toll like receptors, MHC Class II, calcium binding proteins, and complement factors with an increased presence of neutrophils in the skin following tick feeding. Resistant breeds had higher levels of T cells present in the skin prior to tick infestation and thus seem to respond to ticks more efficiently. The skin of resistant breeds also
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Endoparasites must breach host barriers to establish infection and then must survive host internal defenses to cause disease. Such barriers may frustrate attempts to experimentally transmit parasites by ?natural' methods. In addition, the host's condition may affect a study's out...
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Activity of Potent and Selective Host Defense Peptide Mimetics in Mouse Models of Oral Candidiasis
Ryan, Lisa K.; Freeman, Katie B.; Masso-Silva, Jorge A.; Falkovsky, Klaudia; Aloyouny, Ashwag; Markowitz, Kenneth; Hise, Amy G.; Fatahzadeh, Mahnaz; Scott, Richard W.
2014-01-01
There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of Candida, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical properties. Here we describe the identification of several HDP mimetics that are broadly active against C. albicans and other species of Candida, rapidly fungicidal, and active against yeast and hyphal cultures and that exhibit low cytotoxicity for mammalian cells. Importantly, specificity for Candida over commensal bacteria was also evident, thereby minimizing potential damage to the endogenous microbiome which otherwise could favor fungal overgrowth. Three compounds were tested as topical agents in two different mouse models of oral candidiasis and were found to be highly active. Following single-dose administrations, total Candida burdens in tongues of infected animals were reduced up to three logs. These studies highlight the potential of HDP mimetics as a new tool in the antifungal arsenal for the treatment of oral candidiasis. PMID:24752272
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Rasmann, Sergio; Agrawal, Anurag A
2011-06-01
Specialization is common in most lineages of insect herbivores, one of the most diverse groups of organisms on earth. To address how and why specialization is maintained over evolutionary time, we hypothesized that plant defense and other ecological attributes of potential host plants would predict the performance of a specialist root-feeding herbivore (the red milkweed beetle, Tetraopes tetraophthalmus). Using a comparative phylogenetic and functional trait approach, we assessed the determinants of insect host range across 18 species of Asclepias. Larval survivorship decreased with increasing phylogenetic distance from the true host, Asclepias syriaca, suggesting that adaptation to plant traits drives specialization. Among several root traits measured, only cardenolides (toxic defense chemicals) correlated with larval survival, and cardenolides also explained the phylogenetic distance effect in phylogenetically controlled multiple regression analyses. Additionally, milkweed species having a known association with other Tetraopes beetles were better hosts than species lacking Tetraopes herbivores, and milkweeds with specific leaf area values (a trait related to leaf function and habitat affiliation) similar to those of A. syriaca were better hosts than species having divergent values. We thus conclude that phylogenetic distance is an integrated measure of phenotypic and ecological attributes of Asclepias species, especially defensive cardenolides, which can be used to explain specialization and constraints on host shifts over evolutionary time.
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Integrated defense system framework and high fidelity hardware-in-the-loop sensor stimulators
Buford, James A., Jr.; Barnett, Thomas C., Jr.; Vatz, Bernard W., II; Williams, M. Joshua; Van Bebber, James; Burson, Cliff
2008-04-01
The Strategic Defense Center of the U.S. Army Aviation and Missile Research, Development and Engineering Center (AMRDEC), System Simulation and Development Directorate (SS&DD) provides modeling and simulation (M&S) tools, providing medium and hi-fi sensor stimulation, and test control frameworks to evaluate performance of integrated defense systems. These systems include hardware and software representations provided by and operated by Service Program Offices or their representatives. The representations are geographically distributed, but linked together to provide a dynamic, real-time, interactive test environment that is centrally controlled and synchronized through Global Positioning System (GPS) sources. The distributed nodes and the central control facility communicate through the Single Stimulation Framework (SSF). Operation of the SSF provides characterization and assessment of the integrated defense systems. This paper will summarize the concept, features, and functions of the SSF. The complex communications will be discussed, as well as the philosophy of stimulating the participating system components externally with consistent scenarios and truth state data that will bypass the simulation of these events by the individual participants.
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Directory of Open Access Journals (Sweden)
Chul Han
Full Text Available Glutathione reductase (GSR, a key member of the glutathione antioxidant defense system, converts oxidized glutathione (GSSG to reduced glutathione (GSH and maintains the intracellular glutathione redox state to protect the cells from oxidative damage. Previous reports have shown that Gsr deficiency results in defects in host defense against bacterial infection, while diquat induces renal injury in Gsr hypomorphic mice. In flies, overexpression of GSR extended lifespan under hyperoxia. In the current study, we investigated the roles of GSR in cochlear antioxidant defense using Gsr homozygous knockout mice that were backcrossed onto the CBA/CaJ mouse strain, a normal-hearing strain that does not carry a specific Cdh23 mutation that causes progressive hair cell degeneration and early onset of hearing loss. Gsr-/- mice displayed a significant decrease in GSR activity and GSH/GSSG ratios in the cytosol of the inner ears. However, Gsr deficiency did not affect ABR (auditory brainstem response hearing thresholds, wave I amplitudes or wave I latencies in young mice. No histological abnormalities were observed in the cochlea of Gsr-/- mice. Furthermore, there were no differences in the activities of cytosolic glutathione-related enzymes, including glutathione peroxidase and glutamate-cysteine ligase, or the levels of oxidative damage markers in the inner ears between WT and Gsr-/- mice. In contrast, Gsr deficiency resulted in increased activities of cytosolic thioredoxin and thioredoxin reductase in the inner ears. Therefore, under normal physiological conditions, GSR is not essential for the maintenance of antioxidant defenses in mouse cochlea. Given that the thioredoxin system is known to reduce GSSG to GSH in multiple species, our findings suggest that the thioredoxin system can support GSSG reduction in the mouse peripheral auditory system.
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Effectors from Wheat Rust Fungi Suppress Multiple Plant Defense Responses.
Ramachandran, Sowmya R; Yin, Chuntao; Kud, Joanna; Tanaka, Kiwamu; Mahoney, Aaron K; Xiao, Fangming; Hulbert, Scot H
2017-01-01
Fungi that cause cereal rust diseases (genus Puccinia) are important pathogens of wheat globally. Upon infection, the fungus secretes a number of effector proteins. Although a large repository of putative effectors has been predicted using bioinformatic pipelines, the lack of available high-throughput effector screening systems has limited functional studies on these proteins. In this study, we mined the available transcriptomes of Puccinia graminis and P. striiformis to look for potential effectors that suppress host hypersensitive response (HR). Twenty small (wheat, confirming its activity in a homologous system. Overall, this study provides the first evidence for the presence of effectors in Puccinia species suppressing multiple plant defense responses.
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The Role of IL-33 in Host Response to Candida albicans
Directory of Open Access Journals (Sweden)
C. Rodríguez-Cerdeira
2014-01-01
Full Text Available Background. Interleukin (IL 33 is a recently identified pleiotropic cytokine that influences the activity of multiple cell types and orchestrates complex innate and adaptive immune responses. Methods. We performed an extensive review of the literature published between 2005 and 2013 on IL-33 and related cytokines, their functions, and their regulation of the immune system following Candida albicans colonization. Our literature review included cross-references from retrieved articles and specific data from our own studies. Results. IL-33 (IL-1F11 is a recently identified member of the IL-1 family of cytokines. Accumulating evidence suggests a pivotal role of the IL-33/ST2 axis in host immune defense against fungal pathogens, including C. albicans. IL-33 induces a Th2-type inflammatory response and activates both innate and adaptive immunity. Studies in animal models have shown that Th2 inflammatory responses have a beneficial role in immunity against gastrointestinal and systemic infections by Candida spp. Conclusions. This review summarizes the most important clinical studies and case reports describing the beneficial role of IL-33 in immunity and host defense mechanisms against pathogenic fungi. The finding that the IL-33/ST2 axis is involved in therapeutic target has implications for the prevention and treatment of inflammatory diseases, including acute or chronic candidiasis.
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2016-07-01
prompting folding foot-pegs. The human-motorcycle interface maturity followed the technical maturity at the expense of safety. Early airplanes were...this paper shows matrix notation in both reduced tensor notation and matrix notation as a convenience for a multidisciplinary audience. SRLj, [SRL...index for managing the acquisition of defense systems. Paper presented at National Defense Industrial Association 13th Annual Systems Engineering
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A viral suppressor protein inhibits host RNA silencing by hooking up with Argonautes
Jin, Hailing; Zhu, Jian-Kang
2010-01-01
RNA viruses are particularly vulnerable to RNAi-based defenses in the host, and thus have evolved specific proteins, known as viral suppressors of RNA silencing (VSRs), as a counterdefense. In this issue of Genes & Development, Azevedo and colleagues (pp. 904-915) discovered that P38, the VSR of Turnip crinkle virus, uses its glycine/tryptophane (GW) motifs as an ARGONAUTE (AGO) hook to attract and disarm the host's essential effector of RNA silencing. Several GW motif-containing cellular proteins are known to be important partners of AGOs in RNA silencing effector complexes in yeast, plants, and animals. The GW motif appears to be a versatile and effective tool for regulating the activities of RNA silencing pathways, and the use of GW mimicry to compete for and inhibit host AGOs may be a strategy used by many pathogens to counteract host RNAi-based defenses. © 2010 by Cold Spring Harbor Laboratory Press.
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National Research Council Canada - National Science Library
2001-01-01
The Standard Automated Materiel Management System Automated Small Purchase System is a fully automated micro-purchases system used by the General and Industrial Directorate at the Defense Supply Center Philadelphia...
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UNIPOLAR, BIPOLAR OR MULTIPOLAR INTERNATIONAL SYSTEM? THE DEFENSE INDUSTRY FACTOR
ÖZKAN, Gökhan
2008-01-01
International system can be defined as a complex system of systems that is comprised of economic, political, scientific, technological and military systems. It is hard to analyze this complex system. It is even harder to forecast its future. Nonetheless, there are factors such as the defense industry and military power that affect the dynamics of the international system much more than other factors. After the Revolution in Military Affairs, which transformed the military paradigm, significa...
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Killing of trypanosomatid parasites by a modified bovine host defense peptide, BMAP-18.
Directory of Open Access Journals (Sweden)
Lee R Haines
Full Text Available BACKGROUND: Tropical diseases caused by parasites continue to cause socioeconomic devastation that reverberates worldwide. There is a growing need for new control measures for many of these diseases due to increasing drug resistance exhibited by the parasites and problems with drug toxicity. One new approach is to apply host defense peptides (HDP; formerly called antimicrobial peptides to disease control, either to treat infected hosts, or to prevent disease transmission by interfering with parasites in their insect vectors. A potent anti-parasite effector is bovine myeloid antimicrobial peptide-27 (BMAP-27, a member of the cathelicidin family. Although BMAP-27 is a potent inhibitor of microbial growth, at higher concentrations it also exhibits cytotoxicity to mammalian cells. We tested the anti-parasite activity of BMAP-18, a truncated peptide that lacks the hydrophobic C-terminal sequence of the BMAP-27 parent molecule, an alteration that confers reduced toxicity to mammalian cells. METHODOLOGY/PRINCIPAL FINDINGS: BMAP-18 showed strong growth inhibitory activity against several species and life cycle stages of African trypanosomes, fish trypanosomes and Leishmania parasites in vitro. When compared to native BMAP-27, the truncated BMAP-18 peptide showed reduced cytotoxicity on a wide variety of mammalian and insect cells and on Sodalis glossindius, a bacterial symbiont of the tsetse vector. The fluorescent stain rhodamine 123 was used in immunofluorescence microscopy and flow cytometry experiments to show that BMAP-18 at low concentrations rapidly disrupted mitochondrial potential without obvious alteration of parasite plasma membranes, thus inducing death by apoptosis. Scanning electron microscopy revealed that higher concentrations of BMAP-18 induced membrane lesions in the parasites as early as 15 minutes after exposure, thus killing them by necrosis. In addition to direct killing of parasites, BMAP-18 was shown to inhibit LPS
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2012-07-01
Training Systems Acquisition IDA Document D-4648 Log: H 12-001032 July 2012 Approved for public release; distribution is unlimited...Background The Patriot system began because of the need to replace an aging and limited air defense system in the 1970s, the Nike -Hercules, and...simulation technology, embedded training and distributed learning (DoD Instruction 1322.26), and instrumentation systems that provide “anytime, anyplace
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THE DEFENSE PLANNING SYSTEMS AND THEIR IMPLICATIONS
Directory of Open Access Journals (Sweden)
Laszlo STICZ
2010-01-01
Full Text Available Defense planning in the Alliance is a fundamental element of the arrangements which enable its member countries to enjoy the crucial political, military and resource advantages of collective defense and other common military efforts to enhance security and stability. In this respect, the aim of this paper is to outline the role of the Armed Forces and the specific processes aiming to achieve the ultimate goal of a nation regarding national security, with focus on defense planning and the PDPS.
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The interferon response circuit in antiviral host defense.
Haller, O; Weber, F
2009-01-01
Viruses have learned to multiply in the face of a powerful innate and adaptive immune response of the host. They have evolved multiple strategies to evade the interferon (IFN) system which would otherwise limit virus growth at an early stage of infection. IFNs induce the synthesis of a range of antiviral proteins which serve as cell-autonomous intrinsic restriction factors. For example, the dynamin-like MxA GTPase inhibits the multiplication of influenza and bunyaviruses (such as La Crosse virus, Hantaan virus, Rift Valley Fever virus, and Crimean-Congo hemorrhagic fever virus) by binding and sequestering the nucleocapsid protein into large perinuclear complexes. To overcome such intracellular restrictions, virulent viruses either inhibit IFN synthesis, bind and inactivate secreted IFN molecules, block IFN-activated signaling, or disturb the action of IFN-induced antiviral proteins. Many viruses produce specialized proteins to disarm the danger signal or express virulence genes that target members of the IFN regulatory factor family (IRFs) or components of the JAK-STAT signaling pathway. An alternative evasion strategy is based on extreme viral replication speed which out-competes the IFN response. The identification of viral proteins with IFN antagonistic functions has great implications for disease prevention and therapy. Virus mutants lacking IFN antagonistic properties represent safe yet highly immunogenic candidate vaccines. Furthermore, novel drugs intercepting viral IFN-antagonists could be used to disarm the viral intruders.
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Commensal microbes provide first line defense against Listeria monocytogenes infection
Littmann, Eric R.; Kim, Sohn G.; Morjaria, Sejal M.; Ling, Lilan; Gyaltshen, Yangtsho; Taur, Ying; Leiner, Ingrid M.
2017-01-01
Listeria monocytogenes is a foodborne pathogen that causes septicemia, meningitis and chorioamnionitis and is associated with high mortality. Immunocompetent humans and animals, however, can tolerate high doses of L. monocytogenes without developing systemic disease. The intestinal microbiota provides colonization resistance against many orally acquired pathogens, and antibiotic-mediated depletion of the microbiota reduces host resistance to infection. Here we show that a diverse microbiota markedly reduces Listeria monocytogenes colonization of the gut lumen and prevents systemic dissemination. Antibiotic administration to mice before low dose oral inoculation increases L. monocytogenes growth in the intestine. In immunodeficient or chemotherapy-treated mice, the intestinal microbiota provides nonredundant defense against lethal, disseminated infection. We have assembled a consortium of commensal bacteria belonging to the Clostridiales order, which exerts in vitro antilisterial activity and confers in vivo resistance upon transfer into germ free mice. Thus, we demonstrate a defensive role of the gut microbiota against Listeria monocytogenes infection and identify intestinal commensal species that, by enhancing resistance against this pathogen, represent potential probiotics. PMID:28588016
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Navarro-Meléndez, Ariana L; Heil, Martin
2014-07-01
Symptomless ‘type II’ fungal endophytes colonize their plant host horizontally and exert diverse effects on its resistance phenotype. Here, we used wild Lima bean (Phaseolus lunatus) plants that were experimentally colonized with one of three strains of natural endophytes (Bartalinia pondoensis, Fusarium sp., or Cochliobolus lunatus) to investigate the effects of fungal colonization on the endogenous levels of salicylic acid (SA) and jasmonic acid (JA) and on two JA-dependent indirect defense traits. Colonization with Fusarium sp. enhanced JA levels in intact leaves, whereas B. pondoensis suppressed the induction of endogenous JA in mechanically damaged leaves. Endogenous SA levels in intact leaves were significantly decreased by all strains and B. pondoensis and Fusarium sp. decreased SA levels after mechanical damage. Colonization with Fusarium sp. or C. lunatus enhanced the number of detectable volatile organic compounds (VOCs) emitted from intact leaves, and all three strains enhanced the relative amount of several VOCs emitted from intact leaves as well as the number of detectable VOCs emitted from slightly damaged leaves. All three strains completely suppressed the induced secretion of extrafloral nectar (EFN) after the exogenous application of JA. Symptomless endophytes interact in complex and strain-specific ways with the endogenous levels of SA and JA and with the defense traits that are controlled by these hormones. These interactions can occur both upstream and downstream of the defense hormones.
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Effector-triggered immunity: from pathogen perception to robust defense.
Cui, Haitao; Tsuda, Kenichi; Parker, Jane E
2015-01-01
In plant innate immunity, individual cells have the capacity to sense and respond to pathogen attack. Intracellular recognition mechanisms have evolved to intercept perturbations by pathogen virulence factors (effectors) early in host infection and convert it to rapid defense. One key to resistance success is a polymorphic family of intracellular nucleotide-binding/leucine-rich-repeat (NLR) receptors that detect effector interference in different parts of the cell. Effector-activated NLRs connect, in various ways, to a conserved basal resistance network in order to transcriptionally boost defense programs. Effector-triggered immunity displays remarkable robustness against pathogen disturbance, in part by employing compensatory mechanisms within the defense network. Also, the mobility of some NLRs and coordination of resistance pathways across cell compartments provides flexibility to fine-tune immune outputs. Furthermore, a number of NLRs function close to the nuclear chromatin by balancing actions of defense-repressing and defense-activating transcription factors to program cells dynamically for effective disease resistance.
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THE PLANNING, PROGRAMING, BUDGETING SYSTEM AND ITS IMPLEMENTATION IN THE SERBIAN MINISTRY OF DEFENSE
Directory of Open Access Journals (Sweden)
Sasa RADUSKI
2010-01-01
Full Text Available The main purpose of introducing the PPBES to the Serbian Ministry of Defense and the Serbian Armed Forces is to provide a rational management of resources and to maintain and build capacity of the Ministry and the Serbian Armed Forces in order to achieve their goals, objectives and missions.Expected results of implementation of the PPBES are reflected in increasing the efficiency and rationalization of the defense planning to a higher level, ensuring compatibility with defense planning and budgeting system of the state and developing a foundation for the effective management of defense resources.
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van Schaik, J; Kerth, G
2017-02-01
For non-mobile parasites living on social hosts, infection dynamics are strongly influenced by host life history and social system. We explore the impact of host social systems on parasite population dynamics by comparing the infection intensity and transmission opportunities of three mite species of the genus Spinturnix across their three European bat hosts (Myotis daubentonii, Myotis myotis, Myotis nattereri) during the bats' autumn mating season. Mites mainly reproduce in host maternity colonies in summer, but as these colonies are closed, opportunities for inter-colony transmission are limited to host interactions during the autumn mating season. The three investigated hosts differ considerably in their social system, most notably in maternity colony size, mating system, and degree of male summer aggregation. We observed marked differences in parasite infection during the autumn mating period between the species, closely mirroring the predictions made based on the social systems of the hosts. Increased host aggregation sizes in summer yielded higher overall parasite prevalence and intensity, both in male and female hosts. Moreover, parasite levels in male hosts differentially increased throughout the autumn mating season in concordance with the degree of contact with female hosts afforded by the different mating systems of the hosts. Critically, the observed host-specific differences have important consequences for parasite population structure and will thus affect the coevolutionary dynamics between the interacting species. Therefore, in order to accurately characterize host-parasite dynamics in hosts with complex social systems, a holistic approach that investigates parasite infection and transmission across all periods is warranted.
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Swarupa, V; Ravishankar, K V; Rekha, A
2014-04-01
Soil-borne fungal pathogen, Fusarium oxysporum causes major economic losses by inducing necrosis and wilting symptoms in many crop plants. Management of fusarium wilt is achieved mainly by the use of chemical fungicides which affect the soil health and their efficiency is often limited by pathogenic variability. Hence understanding the nature of interaction between pathogen and host may help to select and improve better cultivars. Current research evidences highlight the role of oxidative burst and antioxidant enzymes indicating that ROS act as an important signaling molecule in banana defense response against Fusarium oxysporum f.sp. cubense. The role of jasmonic acid signaling in plant defense against necrotrophic pathogens is well recognized. But recent studies show that the role of salicylic acid is complex and ambiguous against necrotrophic pathogens like Fusarium oxysporum, leading to many intriguing questions about its relationship between other signaling compounds. In case of banana, a major challenge is to identify specific receptors for effector proteins like SIX proteins and also the components of various signal transduction pathways. Significant progress has been made to uncover the role of defense genes but is limited to only model plants such as Arabidopsis and tomato. Keeping this in view, we review the host response, pathogen diversity, current understanding of biochemical and molecular changes that occur during host and pathogen interaction. Developing resistant cultivars through mutation, breeding, transgenic and cisgenic approaches have been discussed. This would help us to understand host defenses against Fusarium oxysporum and to formulate strategies to develop tolerant cultivars.
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Gupta, Om Prakash; Permar, Vipin; Koundal, Vikas; Singh, Uday Dhari; Praveen, Shelly
2012-02-01
Plants have evolved diverse mechanism to recognize pathogen attack and triggers defense responses. These defense responses alter host cellular function regulated by endogenous, small, non-coding miRNAs. To understand the mechanism of miRNAs regulated cellular functions during stem rust infection in wheat, we investigated eight different miRNAs viz. miR159, miR164, miR167, miR171, miR444, miR408, miR1129 and miR1138, involved in three different independent cellular defense response to infection. The investigation reveals that at the initiation of disease, accumulation of miRNAs might be playing a key role in hypersensitive response (HR) from host, which diminishes at the maturation stage. This suggests a possible host-fungal synergistic relation leading to susceptibility. Differential expression of these miRNAs in presence and absence of R gene provides a probable explanation of miRNA regulated R gene mediated independent pathways.
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Antifungal Potential of Host Defense Peptide Mimetics in a Mouse Model of Disseminated Candidiasis
Directory of Open Access Journals (Sweden)
Mobaswar Hossain Chowdhury
2018-02-01
Full Text Available Invasive candidiasis caused by Candida albicans and non-albicans Candida (NAC present a serious disease threat. Although the echinocandins are recommended as the first line of antifungal drug class, resistance to these agents is beginning to emerge, demonstrating the need for new antifungal agents. Host defense peptides (HDP exhibit potent antifungal activity, but as drugs they are difficult to manufacture efficiently, and they are often inactivated by serum proteins. HDP mimetics are low molecular weight non-peptide compounds that can alleviate these problems and were shown to be membrane-active against C. albicans and NAC. Here, we expand upon our previous works to describe the in vitro and in vivo activity of 11 new HDP mimetics that are active against C. albicans and NAC that are both sensitive and resistant to standard antifungal drugs. These compounds exhibit minimum inhibitory/fungicidal concentration (MIC/MFC in the µg/mL range in the presence of serum and are inhibited by divalent cations. Rapid propidium iodide influx into the yeast cells following in vitro exposure suggested that these HDP mimetics were also membrane active. The lead compounds were able to kill C. albicans in an invasive candidiasis CD-1 mouse model with some mimetic candidates decreasing kidney burden by 3–4 logs after 24 h in a dose-dependent manner. The data encouraged further development of this new anti-fungal drug class for invasive candidiasis.
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Anti-endotoxic and antibacterial effects of a dermal substitute coated with host defense peptides.
Kasetty, Gopinath; Kalle, Martina; Mörgelin, Matthias; Brune, Jan C; Schmidtchen, Artur
2015-01-01
Biomaterials used during surgery and wound treatment are of increasing importance in modern medical care. In the present study we set out to evaluate the addition of thrombin-derived host defense peptides to human acellular dermis (hAD, i.e. epiflex(®)). Antimicrobial activity of the functionalized hAD was demonstrated using radial diffusion and viable count assays against Gram-negative Escherichia coli, Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus bacteria. Electron microscopy analyses showed that peptide-mediated bacterial killing led to reduced hAD degradation. Furthermore, peptide-functionalized hAD displayed endotoxin-binding activity in vitro, as evidenced by inhibition of NF-κB activation in human monocytic cells (THP-1 cells) and a reduction of pro-inflammatory cytokine production in whole blood in response to lipopolysaccharide stimulation. The dermal substitute retained its anti-endotoxic activity after washing, compatible with results showing that the hAD bound a significant amount of peptide. Furthermore, bacteria-induced contact activation was inhibited by peptide addition to the hAD. E. coli infected hAD, alone, or after treatment with the antiseptic substance polyhexamethylenebiguanide (PHMB), yielded NF-κB activation in THP-1 cells. The activation was abrogated by peptide addition. Thus, thrombin-derived HDPs should be of interest in the further development of new biomaterials with combined antimicrobial and anti-endotoxic functions for use in surgery and wound treatment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Nanoparticles functionalized with supramolecular host-guest systems for nanomedicine and healthcare.
Wu, Zilong; Song, Nan; Menz, Ryan; Pingali, Bharadwaj; Yang, Ying-Wei; Zheng, Yuebing
2015-05-01
Synthetic macrocyclic host compounds can interact with suitable guest molecules via noncovalent interactions to form functional supramolecular systems. With the synergistic integration of the response of molecules and the unique properties at the nanoscale, nanoparticles functionalized with the host-guest supramolecular systems have shown great potentials for a broad range of applications in the fields of nanoscience and nanotechnology. In this review article, we focus on the applications of the nanoparticles functionalized with supramolecular host-guest systems in nanomedicine and healthcare, including therapeutic delivery, imaging, sensing and removal of harmful substances. A large number of examples are included to elucidate the working mechanisms, advantages, limitations and future developments of the nanoparticle-supramolecule systems in these applications.
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Department of Defense Quality Management Systems and ISO 9000:2000
National Research Council Canada - National Science Library
Lucius, Tommie
2002-01-01
...) to the Department of Defense (DoD) quality management system (QMS) in procurement. In particular, the researcher will examine the new standard and its utility for DoD procurement, focusing on changes from the previous ISO 9000 series...
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Design and Acquisition of Software for Defense Systems
2018-02-14
embrace of iterative development has benefited bottom lines and cost , schedule, and testing performance, while the Department and its defense industrial...February 2018 CLEARED FOR OPEN PUBLICATION February 14, 2018 DEPARTMENT OF DEFENSE OFFICE OF PREPUBLICATION AND SECURITY REVIEW...Force concluded that the Department of Defense would benefit from the implementation of continuous iterative development best practices as software
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Acquisition Planning at the Defense Communications Agency.
1984-04-01
guidelines for interaction are developed under the leadership of DCA agencywide integrators with the participation of personnel from DCA, the Services...Communications System DCSO - Defense Communications System Organizatin . DDN - Defense Data Network DEC - Decision Making DG - Defense Guidance DIA - Defense
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Serpin functions in host-pathogen interactions
Directory of Open Access Journals (Sweden)
Jialing Bao
2018-04-01
Full Text Available Serpins are a broadly distributed superfamily of protease inhibitors that are present in all kingdoms of life. The acronym, serpin, is derived from their function as potent serine proteases inhibitors. Early studies of serpins focused on their functions in haemostasis since modulating serine proteases activities are essential for coagulation. Additional research has revealed that serpins function in infection and inflammation, by modulating serine and cysteine proteases activities. The aim of this review is to summarize the accumulating findings and current understanding of the functions of serpins in host-pathogen interactions, serving as host defense proteins as well as pathogenic factors. We also discuss the potential crosstalk between host and pathogen serpins. We anticipate that future research will elucidate the therapeutic value of this novel target.
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Directory of Open Access Journals (Sweden)
Marchès Olivier
2011-05-01
Full Text Available Abstract The intestinal immune system and the epithelium are the first line of defense in the gut. Constantly exposed to microorganisms from the environment, the gut has complex defense mechanisms to prevent infections, as well as regulatory pathways to tolerate commensal bacteria and food antigens. Intestinal pathogens have developed strategies to regulate intestinal immunity and inflammation in order to establish or prolong infection. The organisms that employ a type III secretion system use a molecular syringe to deliver effector proteins into the cytoplasm of host cells. These effectors target the host cell cytoskeleton, cell organelles and signaling pathways. This review addresses the multiple mechanisms by which the type III secretion system targets the intestinal immune response, with a special focus on pathogenic E. coli.
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National Research Council Canada - National Science Library
1996-01-01
This is the third in a series of followup audits made to evaluate the corrective actions taken by the Defense Finance and Accounting Service, the Defense Information Systems Agency, and the Defense...
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PHIDIAS: a pathogen-host interaction data integration and analysis system
Xiang, Zuoshuang; Tian, Yuying; He, Yongqun
2007-01-01
The Pathogen-Host Interaction Data Integration and Analysis System (PHIDIAS) is a web-based database system that serves as a centralized source to search, compare, and analyze integrated genome sequences, conserved domains, and gene expression data related to pathogen-host interactions (PHIs) for pathogen species designated as high priority agents for public health and biological security. In addition, PHIDIAS allows submission, search and analysis of PHI genes and molecular networks curated ...
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A systems biology approach to study systemic inflammation.
Chen, Bor-Sen; Wu, Chia-Chou
2014-01-01
Systemic inflammation needs a precise control on the sequence and magnitude of occurring events. The high throughput data on the host-pathogen interactions gives us an opportunity to have a glimpse on the systemic inflammation. In this article, a dynamic Candida albicans-zebrafish interactive infectious network is built as an example to demonstrate how systems biology approach can be used to study systematic inflammation. In particular, based on microarray data of C. albicans and zebrafish during infection, the hyphal growth, zebrafish, and host-pathogen intercellular PPI networks were combined to form an integrated infectious PPI network that helps us understand the systematic mechanisms underlying the pathogenicity of C. albicans and the immune response of the host. The signaling pathways for morphogenesis and hyphal growth of C. albicans were 2 significant interactions found in the intercellular PPI network. Two cellular networks were also developed corresponding to the different infection stages (adhesion and invasion), and then compared with each other to identify proteins to gain more insight into the pathogenic role of hyphal development in the C. albicans infection process. Important defense-related proteins in zebrafish were predicted using the same approach. This integrated network consisting of intercellular invasion and cellular defense processes during infection can improve medical therapies and facilitate development of new antifungal drugs.
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Directory of Open Access Journals (Sweden)
Raluca Mihaela LEVONIAN
2012-01-01
Full Text Available This study aims to investigate Romanian media discourse on the current standing of the relations between Romania and the United States of America in the military fi eld. The main topic investigated is connected to Romania’s decision to host the land-based component of the Balllistic Missile Defense System on its ground, an event which attracted signifi cant media coverage during the year 2011. The corpus analyzed consisted of 37 news and opinion items and reports published on the site of three Romanian newspapers. The main research questions were to assess whether the evaluations of this event were positive or negative, who were the actors issuing these statements and what objects were discussed in association to this event. The results showed that positive evaluations were more common than negative evaluations and that the offi cial stances on this topic formed a very coherent perspective, endorsing the project.
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National Research Council Canada - National Science Library
2001-01-01
The meeting proceedings from this symposium on System Concepts for Integrated Air Defense of Multinational Mobile Crisis Reaction Forces was organized and sponsored by the Systems Concepts and Integration (SCI...
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Roadmap Modeling and Assessment Approach for Defense Technology System of Systems
Directory of Open Access Journals (Sweden)
Hui Lu
2018-06-01
Full Text Available Advanced defense technology plays a crucial role in safeguarding national safety and development interests. Aiming to handle the problems of current research and development (R&D management approaches faced with the rocketing complexities of system of systems, the authors propose a novel roadmap modeling and assessment methodology through studying the driving forces of general technology development and analyzing realistic requirements of defense technology management in this article. First, a requirement decomposition framework is designed based on multi-view theories and text-mining tools are used to construct a multi-layer knowledge-flow network model. Second, the contribution rates of requirement elements at different levels are evaluated using a multi-criteria decision-making approach and the node importance is assessed based on the topological structure of multi-layer network. Third, it is utilized to demonstrate the effectiveness of the proposed approaches that illustrative examples of the technology requirements in maritime security strategy investigating and a dual-layer knowledge-flow network consists of patents that belong to the “Coherent Light Generator (CLC” classification from the United States Patent and Trademark Office (USPTO database and the related academic papers from Web of Science. Finally, the contributions, potential applications, and drawbacks of this work are discussed and research outlooks are provided.
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Zúñiga, Martha C
2002-09-01
The poxviruses have evolved a diverse array of proteins which serve to subvert innate and adaptive host responses that abort or at least limit viral infections. Myxoma virus and its rabbit host are considered to represent an ideal poxvirus-host system in which to study the effects of these immunomodulatory proteins. Studies of laboratory rabbits (Oryctolagus cuniculus) infected with gene knockout variants of myxoma virus have provided compelling evidence that several myxoma virus gene products contribute to the pathogenic condition known as myxomatosis. However, myxomatosis, which is characterized by skin lesions, systemic immunosuppression, and a high mortality rate, does not occur in the virus' natural South American host, Sylvilogus brasiliensis. Moreover, in Australia where myxoma virus was willfully introduced to control populations of O. cuniculus, myxomatosis-resistant rabbits emerged within a year of myxoma virus introduction into the field. In this review I discuss the characterized immunomodulatory proteins of myxoma virus, their biochemical properties, their pathogenic effects in laboratory rabbits, the role of the host immune system in the susceptibility or resistance to myxomatosis, and the evidence that immunomodulatory genes may have been attenuated during the co-adaptation of myxoma virus and O. cuniculus in Australia.
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A novel lung slice system with compromised antioxidant defenses
Energy Technology Data Exchange (ETDEWEB)
Hardwick, S.J.; Adam, A.; Cohen, G.M. (Univ. of London (England)); Smith, L.L. (Imperial Chemical Industries PLC, Cheshire (England))
1990-04-01
In order to facilitate the study of oxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 {mu}M) in an amino acid-rich medium for 45 min produced a near-maximal (approximately 85%), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15%) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADP{sup +}, and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of {sup 14}CO{sub 2} from D-({sup 14}C(U))-glucose. The rates of evolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone.
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A novel lung slice system with compromised antioxidant defenses
International Nuclear Information System (INIS)
Hardwick, S.J.; Adam, A.; Cohen, G.M.; Smith, L.L.
1990-01-01
In order to facilitate the study of oxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 μM) in an amino acid-rich medium for 45 min produced a near-maximal (approximately 85%), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15%) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADP + , and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of 14 CO 2 from D-[ 14 C(U)]-glucose. The rates of evolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone
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Mukherjee, Krishnendu; Vilcinskas, Andreas
2018-01-01
Parasitic fungi are the only pathogens that can infect insect hosts directly through their proteinaceous exoskeleton. Penetration of the cuticle requires the release of fungal enzymes, including proteinases, which act as virulence factors. Insects can sense fungal infections and activate innate immune responses, including the synthesis of antifungal peptides and proteinase inhibitors that neutralize the incoming proteinases. This well-studied host response is epigenetically regulated by histone acetylation/deacetylation. Here we show that entomopathogenic fungi can in turn sense the presence of insect-derived antifungal peptides and proteinase inhibitors, and respond by inducing the synthesis of chymotrypsin-like proteinases and metalloproteinases that degrade the host-derived defense molecules. The rapidity of this response is dependent on the virulence of the fungal strain. We confirmed the specificity of the pathogen response to host-derived defense molecules by LC/MS and RT-PCR analysis, and correlated this process with the epigenetic regulation of histone acetylation/deacetylation. This cascade of responses reveals that the coevolution of pathogens and hosts can involve a complex series of attacks and counterattacks based on communication between the invading fungal pathogen and its insect host. The resolution of this process determines whether or not pathogenesis is successful.
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Type III CRISPR-Cas systems can provide redundancy to counteract viral escape from type I systems.
Silas, Sukrit; Lucas-Elio, Patricia; Jackson, Simon A; Aroca-Crevillén, Alejandra; Hansen, Loren L; Fineran, Peter C; Fire, Andrew Z; Sánchez-Amat, Antonio
2017-08-17
CRISPR-Cas-mediated defense utilizes information stored as spacers in CRISPR arrays to defend against genetic invaders. We define the mode of target interference and role in antiviral defense for two CRISPR-Cas systems in Marinomonas mediterranea . One system (type I-F) targets DNA. A second system (type III-B) is broadly capable of acquiring spacers in either orientation from RNA and DNA, and exhibits transcription-dependent DNA interference. Examining resistance to phages isolated from Mediterranean seagrass meadows, we found that the type III-B machinery co-opts type I-F CRISPR-RNAs. Sequencing and infectivity assessments of related bacterial and phage strains suggests an 'arms race' in which phage escape from the type I-F system can be overcome through use of type I-F spacers by a horizontally-acquired type III-B system. We propose that the phage-host arms race can drive selection for horizontal uptake and maintenance of promiscuous type III interference modules that supplement existing host type I CRISPR-Cas systems.
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Szűcs, Zsolt; Plaszkó, Tamás; Cziáky, Zoltán; Kiss-Szikszai, Attila; Emri, Tamás; Bertóti, Regina; Sinka, László Tamás; Vasas, Gábor; Gonda, Sándor
2018-05-09
The health of plants is heavily influenced by the intensively researched plant microbiome. The microbiome has to cope with the plant's defensive secondary metabolites to survive and develop, but studies that describe this interaction are rare. In the current study, we describe interactions of endophytic fungi with a widely researched chemical defense system, the glucosinolate - myrosinase - isothiocyanate system. The antifungal isothiocyanates are also of special interest because of their beneficial effects on human consumers. Seven endophytic fungi were isolated from horseradish roots (Armoracia rusticana), from the genera Fusarium, Macrophomina, Setophoma, Paraphoma and Oidiodendron. LC-ESI-MS analysis of the horseradish extract incubated with these fungi showed that six of seven strains could decompose different classes of glucosinolates. Aliphatic, aromatic, thiomethylalkyl and indolic glucosinolates were decomposed by different strains at different rates. SPME-GC-MS measurements showed that two strains released significant amounts of allyl isothiocyanate into the surrounding air, but allyl nitrile was not detected. The LC-ESI-MS analysis of many strains' media showed the presence of allyl isothiocyanate - glutathione conjugate during the decomposition of sinigrin. Four endophytic strains also accepted sinigrin as the sole carbon source. Isothiocyanates inhibited the growth of fungi at various concentrations, phenylethyl isothiocyanate was more potent than allyl isothiocyanate (mean IC 50 was 2.30-fold lower). As a control group, ten soil fungi from the same soil were used. They decomposed glucosinolates with lower overall efficiency: six of ten strains had insignificant or weak activities and only three could use sinigrin as a carbon source. The soil fungi also showed lower AITC tolerance in the growth inhibition assay: the median IC 50 values were 0.1925 mM for endophytes and 0.0899 mM for soil fungi. The host's glucosinolates can be used by the tested
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Host-pathogen interplay of Haemophilus ducreyi.
Janowicz, Diane M; Li, Wei; Bauer, Margaret E
2010-02-01
Haemophilus ducreyi, the causative agent of the sexually transmitted infection chancroid, is primarily a pathogen of human skin. During infection, H. ducreyi thrives extracellularly in a milieu of professional phagocytes and other antibacterial components of the innate and adaptive immune responses. This review summarizes our understanding of the interplay between this pathogen and its host that leads to development and persistence of disease. H. ducreyi expresses key virulence mechanisms to resist host defenses. The secreted LspA proteins are tyrosine-phosphorylated by host kinases, which may contribute to their antiphagocytic effector function. The serum resistance and adherence functions of DsrA map to separate domains of this multifunctional virulence factor. An influx transporter protects H. ducreyi from killing by the antimicrobial peptide LL37. Regulatory genes have been identified that may coordinate virulence factor expression during disease. Dendritic cells and natural killer cells respond to H. ducreyi and may be involved in determining the differential outcomes of infection observed in humans. A human model of H. ducreyi infection has provided insights into virulence mechanisms that allow this human-specific pathogen to survive immune pressures. Components of the human innate immune system may also determine the ultimate fate of H. ducreyi infection by driving either clearance of the organism or an ineffective response that allows disease progression.
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Information Management Principles Applied to the Ballistic Missile Defense System
2007-03-01
of a BMDS. From this, the Army produced the Nike -Zeus system comprised of four radars, the Zeus missile, and a computer fire control system (General...made the Nike -Zeus our first National Missile Defense (NMD) system named Sentinel. The architecture was to cover 14 locations, 10 of which were...1999). Additionally, there are cultural impacts (Gordon & Gordon, 1999). A company choosing an Apple OS may have to wage a big fight against the
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Dynamical System and Nonlinear Regression for Estimate Host-Parasitoid Relationship
Directory of Open Access Journals (Sweden)
Ileana Miranda Cabrera
2010-01-01
Full Text Available The complex relationships of a crop with the pest, its natural enemies, and the climate factors exist in all the ecosystems, but the mathematic models has studied only some components to know the relation cause-effect. The most studied system has been concerned with the relationship pest-natural enemies such as prey-predator or host-parasitoid. The present paper shows a dynamical system for studying the relationship host-parasitoid (Diaphorina citri, Tamarixia radiata and shows that a nonlinear model permits the estimation of the parasite nymphs using nymphs healthy as the known variable. The model showed the functional answer of the parasitoid, in which a point arrives that its density is not augmented although the number host increases, and it becomes necessary to intervene in the ecosystem. A simple algorithm is used to estimate the parasitoids level using the priori relationship between the host and the climate factors and then the nonlinear model.
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Natural selection on immune defense: A field experiment.
Langeloh, Laura; Behrmann-Godel, Jasminca; Seppälä, Otto
2017-02-01
Predicting the evolution of phenotypic traits requires an understanding of natural selection on them. Despite its indispensability in the fight against parasites, selection on host immune defense has remained understudied. Theory predicts immune traits to be under stabilizing selection due to associated trade-offs with other fitness-related traits. Empirical studies, however, report mainly positive directional selection. This discrepancy could be caused by low phenotypic variation in the examined individuals and/or variation in host resource level that confounds trade-offs in empirical studies. In a field experiment where we maintained Lymnaea stagnalis snails individually in cages in a lake, we investigated phenotypic selection on two immune defense traits, phenoloxidase (PO)-like activity and antibacterial activity, in hemolymph. We used a diverse laboratory population and manipulated snail resource level by limiting their food supply. For six weeks, we followed immune activity, growth, and two fitness components, survival and fecundity of snails. We found that PO-like activity and growth were under stabilizing selection, while antibacterial activity was under positive directional selection. Selection on immune traits was mainly driven by variation in survival. The form of selection on immune defense apparently depends on the particular trait, possibly due to its importance for countering the present parasite community. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.
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Smith, Jason D; Woldemariam, Melkamu G; Mescher, Mark C; Jander, Georg; De Moraes, Consuelo M
2016-09-01
Parasitic plants acquire diverse secondary metabolites from their hosts, including defense compounds that target insect herbivores. However, the ecological implications of this phenomenon, including the potential enhancement of parasite defenses, remain largely unexplored. We studied the translocation of glucosinolates from the brassicaceous host plant Arabidopsis (Arabidopsis thaliana) into parasitic dodder vines (Convolvulaceae; Cuscuta gronovii) and its effects on the parasite itself and on dodder-aphid interactions. Aliphatic and indole glucosinolates reached concentrations in parasite tissues higher than those observed in corresponding host tissues. Dodder growth was enhanced on cyp79B2 cyp79B3 hosts (without indole glucosinolates) but inhibited on atr1D hosts (with elevated indole glucosinolates) relative to wild-type hosts, which responded to parasitism with localized elevation of indole and aliphatic glucosinolates. These findings implicate indole glucosinolates in defense against parasitic plants. Rates of settling and survival on dodder vines by pea aphids (Acyrthosiphon pisum) were reduced significantly when dodder parasitized glucosinolate-producing hosts (wild type and atr1D) compared with glucosinolate-free hosts (cyp79B2 cyp79B3 myb28 myb29). However, settling and survival of green peach aphids (Myzus persicae) were not affected. M. persicae population growth was actually reduced on dodder parasitizing glucosinolate-free hosts compared with wild-type or atr1D hosts, even though stems of the former contain less glucosinolates and more amino acids. Strikingly, this effect was reversed when the aphids fed directly upon Arabidopsis, which indicates an interactive effect of parasite and host genotype on M. persicae that stems from host effects on dodder. Thus, our findings indicate that glucosinolates may have both direct and indirect effects on dodder-feeding herbivores. © 2016 American Society of Plant Biologists. All rights reserved.
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Modulation of legume defense signaling pathways by native and non-native pea aphid clones
Directory of Open Access Journals (Sweden)
Carlos Sanchez-Arcos
2016-12-01
Full Text Available The pea aphid (Acyrthosiphon pisum is a complex of at least 15 genetically different host races that are native to specific legume plants, but can all develop on the universal host plant Vicia faba. Despite much research it is still unclear why pea aphid host races (biotypes are able to colonize their native hosts while other host races are not. All aphids penetrate the plant and salivate into plant cells when they test plant suitability. Thus plants might react differently to the various pea aphid host races. To find out whether legume species vary in their defense responses to different pea aphid host races, we measured the amounts of salicylic acid (SA, the jasmonic acid-isoleucine conjugate (JA-Ile, other jasmonate precursors and derivatives, and abscisic acid (ABA in four different species (Medicago sativa, Trifolium pratense, Pisum sativum, V. faba after infestation by native and non-native pea aphid clones of various host races. Additionally, we assessed the performance of the clones on the four plant species. On M. sativa and T. pratense, non-native clones that were barely able to survive or reproduce, triggered a strong SA and JA-Ile response, whereas infestation with native clones led to lower levels of both phytohormones. On P. sativum, non-native clones, which survived or reproduced to a certain extent, induced fluctuating SA and JA-Ile levels, whereas the native clone triggered only a weak SA and JA-Ile response. On the universal host V. faba all aphid clones triggered only low SA levels initially, but induced clone-specific patterns of SA and JA-Ile later on. The levels of the active JA-Ile conjugate and of the other JA-pathway metabolites measured showed in many cases similar patterns, suggesting that the reduction in JA signaling was due to an effect upstream of OPDA. ABA levels were downregulated in all aphid clone-plant combinations and were therefore probably not decisive factors for aphid-plant compatibility. Our results
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Policy implications of the Strategic Defense Initiative
International Nuclear Information System (INIS)
Goodwin, R.C.
1991-01-01
Specific topics include: the technological feasibility of proposed components and architectures; the compatibility of the proposed systems with existing and proposed arms control agreements, with special emphasis upon the ABM Treaty, Outer Space Treaty, the Defense and Space Treaty, and the START Treaty; the compatibility of proposed systems with classical warfare doctrine and the four modern strategic nuclear doctrines of Massive Retaliation, Assured Destruction, Countervailing and Flexible Response; the economics of strategic defense including an assessment of overall governmental spending, of the suballocation for defense, and of the feasibility of defensive systems which are cost-effective at the margin; and, in summary, an assessment of the New Strategic Concept which balances arms control, offensive forces, and defensive forces. This study falls within the realm of defense policy analysis in that it attempts to determine whether the administration's proposed Strategic Defense Initiative, as well as the long-term strategic defensive systems derived from SDI research, constitute efficient, desirable allocation of scarce government resources - especially in a period of seemingly relaxed superpower tensions and numerous demands upon those resources
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Garavaglia, Betiana S; Thomas, Ludivine; Gottig, Natalia; Dunger, Germán; Garofalo, Cecilia G; Daurelio, Lucas D; Ndimba, Bongani; Orellano, Elena G; Gehring, Chris; Ottado, Jorgelina
2010-01-28
Xanthomonas citri pv. citri, the bacteria responsible for citrus canker posses a biological active plant natriuretic peptide (PNP)-like protein, not present in any other bacteria. PNPs are a class of extracellular, systemically mobile peptides that elicit a number of plant responses important in homeostasis and growth. Previously, we showed that a Xanthomonas citri pv. citri mutant lacking the PNP-like protein XacPNP produced more necrotic lesions in citrus leaves than wild type infections and suggested a role for XacPNP in the regulation of host homeostasis. Here we have analyzed the proteome modifications observed in citrus leaves infected with the wild type and XacPNP deletion mutant bacteria. While both of them cause down-regulation of enzymes related to photosynthesis as well as chloroplastic ribosomal proteins, proteins related to defense responses are up-regulated. However, leaves infiltrated with the XacPNP deletion mutant show a more pronounced decrease in photosynthetic proteins while no reduction in defense related proteins as compared to the wild-type pathogen. This suggests that XacPNP serves the pathogen to maintain host photosynthetic efficiency during pathogenesis. The results from the proteomics analyses are consistent with our chlorophyll fluorescence data and transcript analyses of defense genes that show a more marked reduction in photosynthesis in the mutant but no difference in the induction of genes diagnostic for biotic-stress responses. We therefore conclude that XacPNP counteracts the shut-down of host photosynthesis during infection and in that way maintains the tissue in better conditions, suggesting that the pathogen has adapted a host gene to modify its natural host and render it a better reservoir for prolonged bacterial survival and thus for further colonization.
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Ouaissi, Ali; Ouaissi, Mehdi
2005-01-01
A number of features occurring during host-parasite interactions in Chagas disease caused by the protozoan parasite, Trypanosoma cruzi, and Leishmaniasis, caused by a group of kinetoplastid protozoan parasites are reminiscent of those observed in cancer diseases. In fact,although the cancer is not a single disease, and that T.cruzi and Leishmania are sophisticated eukaryotic parasites presenting a high level of genotypic variability the growth of the parasites in their host and that of cancer cells share at least one common feature, that is their mutual capacity for rapid cell division. Surprisingly, the parasitic diseases and cancers share some immune evasion strategies. Consideration of these immunological alterations must be added to the evaluation of the pathogenic processes. The molecular and functional characterization of virulence factors and the study of their effect on the arms of the immune system have greatly improved understanding of the regulation of immune effectors functions. The purpose of this review is to analyze some of the current data related to the regulatory components or processes originating from the parasite that control or interfere with host cell physiology. Attempts are also made to delineate some similarities between the immune evasion strategies that parasites and tumors employ. The elucidation of the mode of action of parasite virulence factors toward the host cell allow not only provide us with a more comprehensive view of the host-parasite relationships but may also represent a step forward in efforts aimed to identify new target molecules for therapeutic intervention.
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2012-02-24
...D published an initial proposed rule for Business Systems-- Definition and Administration (DFARS... the definition and administration of contractor business systems as follows: A. Contractor business..., 245, and 252 RIN 0750-AG58 Defense Federal Acquisition Regulation Supplement; Business Systems...
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Pedrotti, Lorenzo; Mueller, Martin J; Waller, Frank
2013-01-01
Piriformosporaindica is a basidiomycete fungus colonizing roots of a wide range of higher plants, including crop plants and the model plant Arabidopsis thaliana. Previous studies have shown that P. indica improves growth, and enhances systemic pathogen resistance in leaves of host plants. To investigate systemic effects within the root system, we established a hydroponic split-root cultivation system for Arabidopsis. Using quantitative real-time PCR, we show that initial P. indica colonization triggers a local, transient response of several defense-related transcripts, of which some were also induced in shoots and in distal, non-colonized roots of the same plant. Systemic effects on distal roots included the inhibition of secondary P. indica colonization. Faster and stronger induction of defense-related transcripts during secondary inoculation revealed that a P. indica pretreatment triggers root-wide priming of defense responses, which could cause the observed reduction of secondary colonization levels. Secondary P. indica colonization also induced defense responses in distant, already colonized parts of the root. Endophytic fungi therefore trigger a spatially specific response in directly colonized and in systemic root tissues of host plants.
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Cdc42 promotes host defenses against fatal infection
DEFF Research Database (Denmark)
Lee, Keunwook; Boyd, Kelli L; Parekh, Diptiben V
2013-01-01
attempted to specifically delete it in these cells by crossing the Cdc42(fl/fl) mouse with a FSP-1 cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP-1cre;Cdc42(fl/fl) mice died at 3 weeks of age due to overwhelming suppurative upper airway infections...... showed that in addition to fibroblasts, the FSP-1 cre deleted Cdc42 very efficiently in all leukocytes. Thus, by using this non-specific cre mouse we inadvertently demonstrated the importance of Cdc42 in host protection from lethal infections and suggest a critical role for this small GTPase in innate...
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PRINCIPLES OF THE SYSTEM OF "CUSTOMIZABLE” DEFENSE ON THE FULL BASKETBALL COURT
Directory of Open Access Journals (Sweden)
Pavle Rubin
2010-09-01
Full Text Available The problem of this work stems from the fact that the tactics (not just applications, but also to create the principles of basketball games and variants belongs to the domain experts of this sport (coaches, theorists, etc.. Every devising, selecting and applying specific tactics should satisfy two main objectives, to: be the greater surprise and provide adequate "response" to the opponent's tactics. The possibility of surprising opponent is primarily associated with the phase of defense, till firstly from an offense is expected to find and implement an adequate solution ("response". Prerequisite that this defense could be successfully adopted is that the players (they know, and they can play quality individual defense (one - on - one. Another prerequisite is that the basketball players fully adopted the principles of the system: zone pressing and "man to man" (variations of "pressing" on the full court. The defense in the foul court is, even more demanding because of the space that is defended, which allows players to adapt to the possible, at least the first time, adequate "response" on offense.
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Switchable host-guest systems on surfaces.
Yang, Ying-Wei; Sun, Yu-Long; Song, Nan
2014-07-15
CONSPECTUS: For device miniaturization, nanotechnology follows either the "top-down" approach scaling down existing larger-scale devices or the "bottom-up' approach assembling the smallest possible building blocks to functional nanoscale entities. For synthetic nanodevices, self-assembly on surfaces is a superb method to achieve useful functions and enable their interactions with the surrounding world. Consequently, adaptability and responsiveness to external stimuli are other prerequisites for their successful operation. Mechanically interlocked molecules such as rotaxanes and catenanes, and their precursors, that is, molecular switches and supramolecular switches including pseudorotaxanes, are molecular machines or prototypes of machines capable of mechanical motion induced by chemical signals, biological inputs, light or redox processes as the external stimuli. Switching of these functional host-guest systems on surfaces becomes a fundamental requirement for artificial molecular machines to work, mimicking the molecular machines in nature, such as proteins and their assemblies operating at dynamic interfaces such as the surfaces of cell membranes. Current research endeavors in material science and technology are focused on developing either a new class of materials or materials with novel/multiple functionalities by shifting host-guest chemistry from solution phase to surfaces. In this Account, we present our most recent attempts of building monolayers of rotaxanes/pseudorotaxanes on surfaces, providing stimuli-induced macroscopic effects and further understanding on the switchable host-guest systems at interfaces. Biocompatible versions of molecular machines based on synthetic macrocycles, such as cucurbiturils, pillararenes, calixarenes, and cyclodextrins, have been employed to form self-assembled monolayers of gates on the surfaces of mesoporous silica nanoparticles to regulate the controlled release of cargo/drug molecules under a range of external stimuli
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Planning a transportation system for US Defense Transuranic waste
International Nuclear Information System (INIS)
Gilbert, K.V.; Hurley, J.D.; Smith, L.J.; McFadden, M.H.; Raudenbush, M.H.; Fedie, M.L.
1983-05-01
The development and planning of a transportation system for US Department of Energy (USDOE) Defense Transuranic (TRU) waste has required the talents and expertise of many people. Coordination activities, design activities, fabrication, research and development, operations, and transportation are but a few of the areas around which this system is built. Due to the large number of organizations, regulations and personalities the planning task becomes extremely complex. The intent of this paper is to discuss the steps taken in planning this system, to identify the various organizations around which this system is designed, and to discuss program progress to date, scheduling, and future plans. 9 figures, 1 table
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Planning a transportation system for US defense transuranic waste
International Nuclear Information System (INIS)
Gilbert, K.V.; Hurley, J.D.; Smith, L.J.; McFadden, M.H.; Raudenbush, M.H.; Fedie, M.L.
1983-01-01
The development and planning of a transportation system for US Department of Energy (USDOE) Defense Transuranic (TRU) waste has required the talents and expertise of many people. Coordination activities, design activities, fabrication, research and development, operations, and transportation are but a few of the areas around which this system is built. Due to the large number of organizations, regulations and personalities the planning task becomes extremely complex. The intent of this paper is to discuss the steps taken in planning this system, to identify the various organizations around which this system is designed, and to discuss program progress to date, scheduling, and future plans
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2011-05-18
...; Business Systems-- Definition and Administration; Interim Rule #0;#0;Federal Register / Vol. 76 , No. 96...-AG58 Defense Federal Acquisition Regulation Supplement; Business Systems--Definition and Administration... an initial proposed rule for Business Systems-- Definition and Administration (DFARS Case 2009-D038...
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PHIDIAS: a pathogen-host interaction data integration and analysis system.
Xiang, Zuoshuang; Tian, Yuying; He, Yongqun
2007-01-01
The Pathogen-Host Interaction Data Integration and Analysis System (PHIDIAS) is a web-based database system that serves as a centralized source to search, compare, and analyze integrated genome sequences, conserved domains, and gene expression data related to pathogen-host interactions (PHIs) for pathogen species designated as high priority agents for public health and biological security. In addition, PHIDIAS allows submission, search and analysis of PHI genes and molecular networks curated from peer-reviewed literature. PHIDIAS is publicly available at http://www.phidias.us.
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Proteomic characterization of host response to Yersinia pestis and near neighbors
International Nuclear Information System (INIS)
Chromy, Brett A.; Perkins, Julie; Heidbrink, Jenny L.; Gonzales, Arlene D.; Murphy, Gloria A.; Fitch, J. Patrick; McCutchen-Maloney, Sandra L.
2004-01-01
Host-pathogen interactions result in protein expression changes within both the host and the pathogen. Here, results from proteomic characterization of host response following exposure to Yersinia pestis, the causative agent of plague, and to two near neighbors, Yersinia pseudotuberculosis and Yersinia enterocolitica, are reported. Human monocyte-like cells were chosen as a model for macrophage immune response to pathogen exposure. Two-dimensional electrophoresis followed by mass spectrometry was used to identify host proteins with differential expression following exposure to these three closely related Yersinia species. This comparative proteomic characterization of host response clearly shows that host protein expression patterns are distinct for the different pathogen exposures, and contributes to further understanding of Y. pestis virulence and host defense mechanisms. This work also lays the foundation for future studies aimed at defining biomarkers for presymptomatic detection of plague
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Energy Technology Data Exchange (ETDEWEB)
McDermott, Jason E.; Braun, Pascal; Bonneau, Richard A.; Hyduke, Daniel R.
2011-12-01
Pathogenic infections are a major cause of both human disease and loss of crop yields and animal stocks and thus cause immense damage to the worldwide economy. The significance of infectious diseases is expected to increase in an ever more connected warming world, in which new viral, bacterial and fungal pathogens can find novel hosts and ecologic niches. At the same time, the complex and sophisticated mechanisms by which diverse pathogenic agents evade defense mechanisms and subvert their hosts networks to suit their lifestyle needs is still very incompletely understood especially from a systems perspective [1]. Thus, understanding host-pathogen interactions is both an important and a scientifically fascinating topic. Recently, technology has offered the opportunity to investigate host-pathogen interactions on a level of detail and scope that offers immense computational and analytical possibilities. Genome sequencing was pioneered on some of these pathogens, and the number of strains and variants of pathogens sequenced to date vastly outnumbers the number of host genomes available. At the same time, for both plant and human hosts more and more data on population level genomic variation becomes available and offers a rich field for analysis into the genetic interactions between host and pathogen.
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International Nuclear Information System (INIS)
Thuy, N. N. Q.
2006-01-01
Inappropriately designed inter-channel and inter-system digital communications could initiate common cause failure of multiple channels or multiple systems. Defensive measures were introduced in EPRI report TR-1002835 (Guideline for Performing Defense-in-Depth and Diversity Assessments for Digital Upgrades) to assess, on a deterministic basis, the susceptibility of digital systems architectures to common-cause failures. This paper suggests how this approach could be applied to assess inter-channel and inter-system digital communications from a safety standpoint. The first step of the approach is to systematically identify the so called 'influence factors' that one end of the data communication path can have on the other. Potential factors to be considered would typically include data values, data volumes and data rates. The second step of the approach is to characterize the ways possible failures of a given end of the communication path could affect these influence factors (e.g., incorrect data values, excessive data rates, time-outs, incorrect data volumes). The third step is to analyze the designed-in measures taken to guarantee independence of the other end. In addition to classical error detection and correction codes, typical defensive measures are one-way data communication, fixed-rate data communication, fixed-volume data communication, validation of data values. (authors)
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Defense nuclear energy systems selection methodology for civil nuclear power applications
International Nuclear Information System (INIS)
Scarborough, J.C.
1986-01-01
A methodology developed to select a preferred nuclear power system for a US Department of Defense (DOD) application has been used to evaluate preferred nuclear power systems for a remote island community in Southeast Asia. The plant would provide ∼10 MW of electric power, possibly low-temperature process heat for the local community, and would supplement existing island diesel electric capacity. The nuclear power system evaluation procedure was evolved from a disciplined methodology for ranking ten nuclear power designs under joint development by the US Department of Energy (DOE) and DOD. These included six designs proposed by industry for the Secure Military Power Plant Program (now termed Multimegawatt Terrestrial Reactor Program), the SP-100 Program, the North Warning System Program, and the Modular Advanced High-Temperature Gas-Cooled Reactor (HTGR) and Liquid-Metal Reactor (LMR) programs. The 15 evaluation criteria established for the civil application were generally similar to those developed and used for the defense energy systems evaluation, except that the weighting factor applied to each individual criterion differed. The criteria and their weighting (importance) functions for the civil application are described
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Silverleaf whitefly induces salicylic acid defenses and suppresses effectual jasmonic acid defenses.
Zarate, Sonia I; Kempema, Louisa A; Walling, Linda L
2007-02-01
The basal defenses important in curtailing the development of the phloem-feeding silverleaf whitefly (Bemisia tabaci type B; SLWF) on Arabidopsis (Arabidopsis thaliana) were investigated. Sentinel defense gene RNAs were monitored in SLWF-infested and control plants. Salicylic acid (SA)-responsive gene transcripts accumulated locally (PR1, BGL2, PR5, SID2, EDS5, PAD4) and systemically (PR1, BGL2, PR5) during SLWF nymph feeding. In contrast, jasmonic acid (JA)- and ethylene-dependent RNAs (PDF1.2, VSP1, HEL, THI2.1, FAD3, ERS1, ERF1) were repressed or not modulated in SLWF-infested leaves. To test for a role of SA and JA pathways in basal defense, SLWF development on mutant and transgenic lines that constitutively activate or impair defense pathways was determined. By monitoring the percentage of SLWF nymphs in each instar, we show that mutants that activate SA defenses (cim10) or impair JA defenses (coi1) accelerated SLWF nymphal development. Reciprocally, mutants that activate JA defenses (cev1) or impair SA defenses (npr1, NahG) slowed SLWF nymphal development. Furthermore, when npr1 plants, which do not activate downstream SA defenses, were treated with methyl jasmonate, a dramatic delay in nymph development was observed. Collectively, these results showed that SLWF-repressed, JA-regulated defenses were associated with basal defense to the SLWF.
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Hahn, Caldwell; Wingfield, John C.; Fox, David M.; Walker, Brian G.; Thomley, Jill E
2017-01-01
In the coevolutionary dynamic of avian brood parasites and their hosts, maternal (or transgenerational) effects have rarely been investigated. We examined the potential role of elevated yolk testosterone in eggs of the principal brood parasite in North America, the brown-headed cowbird, and three of its frequent host species. Elevated maternal androgens in eggs are a common maternal effect observed in many avian species when breeding conditions are unfavorable. These steroids accelerate embryo development, shorten incubation period, increase nestling growth rate, and enhance begging vigor, all traits that can increase the survival of offspring. We hypothesized that elevated maternal androgens in host eggs are a defense against brood parasitism. Our second hypothesis was that elevated maternal androgens in cowbird eggs are a defense against intra-specific competition. For host species, we found that elevated yolk testosterone was correlated with parasitized nests of small species, those whose nest success is most reduced by cowbird parasitism. For cowbirds, we found that elevated yolk testosterone was correlated with eggs in multiply-parasitized nests, which indicate intra-specific competition for nests due to high cowbird density. We propose experimental work to further examine the use of maternal effects by cowbirds and their hosts.
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Runyon, Justin B; Mescher, Mark C
2010-01-01
Herbivores and pathogens come quickly to mind when one thinks of the biotic challenges faced by plants. Important but less appreciated enemies are parasitic plants, which can have important consequences for the fitness and survival of their hosts. Our knowledge of plant perception, signaling and response to herbivores and pathogens has expanded rapidly in recent years, but information is generally lacking for parasitic species. In a recent paper we reported that some of the same defense responses induced by herbivores and pathogens—notably increases in jasmonic acid (JA), salicylic acid (SA), and a hypersensitive-like response (HLR)—also occur in tomato plants upon attack by the parasitic plant Cuscuta pentagona (field dodder). Parasitism induced a distinct pattern of JA and SA accumulation, and growth trials using genetically-altered tomato hosts suggested that both JA and SA govern effective defenses against the parasite, though the extent of the response varied with host plant age. Here we discuss similarities between the induced responses we observed in response to Cuscuta parasitism to those previously described for herbivores and pathogens and present new data showing that trichomes should be added to the list of plant defenses that act against multiple enemies and across kingdoms. PMID:20495380
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Strategic Defense Initiative Overview
National Research Council Canada - National Science Library
1990-01-01
... to Third World and other nations. I will then discuss the scope of the SDI effort, the evolving strategic defense system architectures and theater defense, our compliancy with the ABM Treaty, technology spinoffs resulting from SDI...
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Of poisons and parasites-the defensive role of tetrodotoxin against infections in newts.
Johnson, Pieter T J; Calhoun, Dana M; Stokes, Amber N; Susbilla, Calvin B; McDevitt-Galles, Travis; Briggs, Cheryl J; Hoverman, Jason T; Tkach, Vasyl V; de Roode, Jacobus C
2018-02-24
Classical research on animal toxicity has focused on the role of toxins in protection against predators, but recent studies suggest these same compounds can offer a powerful defense against parasites and infectious diseases. Newts in the genus Taricha are brightly coloured and contain the potent neurotoxin, tetrodotoxin (TTX), which is hypothesized to have evolved as a defense against vertebrate predators such as garter snakes. However, newt populations often vary dramatically in toxicity, which is only partially explained by predation pressure. The primary aim of this study was to evaluate the relationships between TTX concentration and infection by parasites. By systematically assessing micro- and macroparasite infections among 345 adult newts (sympatric populations of Taricha granulosa and T. torosa), we detected 18 unique taxa of helminths, fungi, viruses and protozoans. For both newt species, per-host concentrations of TTX, which varied from undetectable to >60 μg/cm 2 skin, negatively predicted overall parasite richness as well as the likelihood of infection by the chytrid fungus, Batrachochytrium dendrobatidis, and ranavirus. No such effect was found on infection load among infected hosts. Despite commonly occurring at the same wetlands, T. torosa supported higher parasite richness and average infection load than T. granulosa. Host body size and sex (females > males) tended to positively predict infection levels in both species. For hosts in which we quantified leucocyte profiles, total white blood cell count correlated positively with both parasite richness and total infection load. By coupling data on host toxicity and infection by a broad range of micro- and macroparasites, these results suggest that-alongside its effects on predators-tetrodotoxin may help protect newts against parasitic infections, highlighting the importance of integrative research on animal chemistry, immunological defenses and natural enemy ecology. © 2018 The Authors. Journal
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Global Positioning Systems (GPS) Technology to Study Vector-Pathogen-Host Interactions
2016-12-01
Award Number: W81XWH-11-2-0175 TITLE: Global Positioning Systems (GPS) Technology to Study Vector-Pathogen-Host Interactions PRINCIPAL...Positioning Systems (GPS) Technology to Study Vector-Pathogen-Host Interactions 5b. GRANT NUMBER W81XWH-11-2-0175 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...genetic diversity in the population, in hospitalized children with severe dengue illness and cluster investigation of their neighborhoods, and by using
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2016-02-16
into areas where there is no access to maritime platforms. Sea-based interceptor platforms have the ability to intercept targets at each stage of the...argues that the most efficient concept for integrating active defense weapon systems is a multi- layered architecture with redundant intercept ...faster data transfer and will prevent data loss. The need for almost 100% interception successes is increasing as the threat becomes more
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Department of Defense Systems Engineering FY 2012 Annual Report
2013-03-01
by the Utility Helicopter PMO, is utilizing the latest Defense Acquisition Guidelines and previously approved PEO AVN SEP examples to develop all...efforts. As a whole, all of PEO AVN Program Management Offices understand the importance of systems engineering. They stress the continued use of...established SE guidelines, practices and procedures throughout our acquisition processes. PEO AVN , working with the AMRDEC SE Division, has
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Zhou, Jincheng; Meng, Ling; Li, Baoping
2017-01-01
This study examined defensive behaviors of Mythimna separata (Lepidoptera: Noctuidae) larvae varying in body size in response to two parasitoids varying in oviposition behavior; Microplitis mediator females sting the host with the ovipositor after climbing onto it while Meteorus pulchricornis females make the sting by standing at a close distance from the host. Mythimna separata larvae exhibited evasive (escaping and dropping) and aggressive (thrashing) behaviors to defend themselves against parasitoids M. mediator and M. pulchricornis . Escaping and dropping did not change in probability with host body size or parasitoid species. Thrashing did not vary in frequency with host body size, yet performed more frequently in response to M. mediator than to M. pulchricornis . Parasitoid handling time and stinging likelihood varied depending not only on host body size but also on parasitoid species. Parasitoid handling time increased with host thrashing frequency, similar in slope for both parasitoids yet on a higher intercept for M. mediator than for M. pulchricornis . Handling time decreased with host size for M. pulchricornis but not for M. mediator . The likelihood of realizing an ovipositor sting decreased with thrashing frequency of both small and large hosts for M. pulchricornis , while this was true only for large hosts for M. mediator . Our results suggest that the thrashing behavior of M. separata larvae has a defensive effect on parasitism, depending on host body size and parasitoid species with different oviposition behaviors.
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Directory of Open Access Journals (Sweden)
Jincheng Zhou
2017-08-01
Full Text Available This study examined defensive behaviors of Mythimna separata (Lepidoptera: Noctuidae larvae varying in body size in response to two parasitoids varying in oviposition behavior; Microplitis mediator females sting the host with the ovipositor after climbing onto it while Meteorus pulchricornis females make the sting by standing at a close distance from the host. Mythimna separata larvae exhibited evasive (escaping and dropping and aggressive (thrashing behaviors to defend themselves against parasitoids M. mediator and M. pulchricornis. Escaping and dropping did not change in probability with host body size or parasitoid species. Thrashing did not vary in frequency with host body size, yet performed more frequently in response to M. mediator than to M. pulchricornis. Parasitoid handling time and stinging likelihood varied depending not only on host body size but also on parasitoid species. Parasitoid handling time increased with host thrashing frequency, similar in slope for both parasitoids yet on a higher intercept for M. mediator than for M. pulchricornis. Handling time decreased with host size for M. pulchricornis but not for M. mediator. The likelihood of realizing an ovipositor sting decreased with thrashing frequency of both small and large hosts for M. pulchricornis, while this was true only for large hosts for M. mediator. Our results suggest that the thrashing behavior of M. separata larvae has a defensive effect on parasitism, depending on host body size and parasitoid species with different oviposition behaviors.
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RNAi and Antiviral Defense in the Honey Bee
Brutscher, Laura M.; Flenniken, Michelle L.
2015-01-01
Honey bees play an important agricultural and ecological role as pollinators of numerous agricultural crops and other plant species. Therefore, investigating the factors associated with high annual losses of honey bee colonies in the US is an important and active area of research. Pathogen incidence and abundance correlate with Colony Collapse Disorder- (CCD-) affected colonies in the US and colony losses in the US and in some European countries. Honey bees are readily infected by single-stranded positive sense RNA viruses. Largely dependent on the host immune response, virus infections can either remain asymptomatic or result in deformities, paralysis, or death of adults or larvae. RNA interference (RNAi) is an important antiviral defense mechanism in insects, including honey bees. Herein, we review the role of RNAi in honey bee antiviral defense and highlight some parallels between insect and mammalian immune systems. A more thorough understanding of the role of pathogens on honey bee health and the immune mechanisms bees utilize to combat infectious agents may lead to the development of strategies that enhance honey bee health and result in the discovery of additional mechanisms of immunity in metazoans. PMID:26798663
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RNAi and Antiviral Defense in the Honey Bee
Directory of Open Access Journals (Sweden)
Laura M. Brutscher
2015-01-01
Full Text Available Honey bees play an important agricultural and ecological role as pollinators of numerous agricultural crops and other plant species. Therefore, investigating the factors associated with high annual losses of honey bee colonies in the US is an important and active area of research. Pathogen incidence and abundance correlate with Colony Collapse Disorder- (CCD- affected colonies in the US and colony losses in the US and in some European countries. Honey bees are readily infected by single-stranded positive sense RNA viruses. Largely dependent on the host immune response, virus infections can either remain asymptomatic or result in deformities, paralysis, or death of adults or larvae. RNA interference (RNAi is an important antiviral defense mechanism in insects, including honey bees. Herein, we review the role of RNAi in honey bee antiviral defense and highlight some parallels between insect and mammalian immune systems. A more thorough understanding of the role of pathogens on honey bee health and the immune mechanisms bees utilize to combat infectious agents may lead to the development of strategies that enhance honey bee health and result in the discovery of additional mechanisms of immunity in metazoans.
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Development of fusion fuel cycles: Large deviations from US defense program systems
Energy Technology Data Exchange (ETDEWEB)
Klein, James Edward, E-mail: james.klein@srnl.doe.gov; Poore, Anita Sue; Babineau, David W.
2015-10-15
Highlights: • All tritium fuel cycles start with a “Tritium Process.” All have similar tritium processing steps. • Fusion tritium fuel cycles minimize process tritium inventories for various reasons. • US defense program facility designs did not minimize in-process inventories. • Reduced inventory tritium facilities will lower public risk. - Abstract: Fusion energy research is dominated by plasma physics and materials technology development needs with smaller levels of effort and funding dedicated to tritium fuel cycle development. The fuel cycle is necessary to supply and recycle tritium at the required throughput rate; additionally, tritium confinement throughout the facility is needed to meet regulatory and environmental release limits. Small fuel cycle development efforts are sometimes rationalized by stating that tritium processing technology has already been developed by nuclear weapons programs and these existing processes only need rescaling or engineering design to meet the needs of fusion fuel cycles. This paper compares and contrasts features of tritium fusion fuel cycles to United States Cold War era defense program tritium systems. It is concluded that further tritium fuel cycle development activities are needed to provide technology development beneficial to both fusion and defense programs tritium systems.
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Buron-Moles, Gemma; Wisniewski, Michael; Viñas, Inmaculada; Teixidó, Neus; Usall, Josep; Droby, Samir; Torres, Rosario
2015-01-30
Apples are subjected to both abiotic and biotic stresses during the postharvest period, which lead to large economic losses worldwide. To obtain biochemical insights into apple defense response, we monitored the protein abundance changes (proteome), as well as the protein carbonyls (oxi-proteome) formed by reactive oxygen species (ROS) in 'Golden Smoothee' apple in response to wounding, Penicillium expansum (host) and Penicillium digitatum (non-host) pathogens with select transcriptional studies. To examine the biological relevance of the results, we described quantitative and oxidative protein changes into the gene ontology functional categories, as well as into de KEGG pathways. We identified 26 proteins that differentially changed in abundance in response to wounding, P. expansum or P. digitatum infection. While these changes showed some similarities between the apple responses and abiotic and biotic stresses, Mal d 1.03A case, other proteins as Mal d 1.03E and EF-Tu were specifically induced in response to P. digitatum infection. Using a protein carbonyl detection method based on fluorescent Bodipy, we detected and identified 27 oxidized proteins as sensitive ROS targets. These ROS target proteins were related to metabolism processes, suggesting that this process plays a leading role in apple fruit defense response against abiotic and biotic stresses. ACC oxidase and two glutamine synthetases showed the highest protein oxidation level in response to P. digitatum infection. Documenting changes in the proteome and, specifically in oxi-proteome of apple can provide information that can be used to better understand how impaired protein functions may affect apple defense mechanisms. Possible mechanisms by which these modified proteins are involved in fruit defense response are discussed. Mechanical damage in apple fruits is linked annually to large economic losses due to opportunistic infection by postharvest pathogens, such as P. expansum. Despite the current use
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2010-12-09
..., and 252 RIN 0750-AG58 Defense Federal Acquisition Regulation Supplement; Business Systems--Definition... for Business Systems--Definition and Administration (DFARS Case 2009-D038) in the Federal Register on... improve the effectiveness of DoD oversight of contractor business systems. The comment period is being...
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Pas de deux: An Intricate Dance of Anther Smut and Its Host
Directory of Open Access Journals (Sweden)
Su San Toh
2018-02-01
Full Text Available The successful interaction between pathogen/parasite and host requires a delicate balance between fitness of the former and survival of the latter. To optimize fitness a parasite/pathogen must effectively create an environment conducive to reproductive success, while simultaneously avoiding or minimizing detrimental host defense response. The association between Microbotryum lychnidis-dioicae and its host Silene latifolia serves as an excellent model to examine such interactions. This fungus is part of a species complex that infects species of the Caryophyllaceae, replacing pollen with the fungal spores. In the current study, transcriptome analyses of the fungus and its host were conducted during discrete stages of bud development so as to identify changes in fungal gene expression that lead to spore development and to identify changes associated with infection in the host plant. In contrast to early biotrophic phase stages of infection for the fungus, the latter stages involve tissue necrosis and in the case of infected female flowers, further changes in the developmental program in which the ovary aborts and a pseudoanther is produced. Transcriptome analysis via Illumina RNA sequencing revealed enrichment of fungal genes encoding small secreted proteins, with hallmarks of effectors and genes found to be relatively unique to the Microbotryum species complex. Host gene expression analyses also identified interesting sets of genes up-regulated, including those involving stress response, host defense response, and several agamous-like MADS-box genes (AGL61 and AGL80, predicted to interact and be involved in male gametophyte development.
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Control Systems Cyber Security:Defense in Depth Strategies
Energy Technology Data Exchange (ETDEWEB)
David Kuipers; Mark Fabro
2006-05-01
Information infrastructures across many public and private domains share several common attributes regarding IT deployments and data communications. This is particularly true in the control systems domain. A majority of the systems use robust architectures to enhance business and reduce costs by increasing the integration of external, business, and control system networks. However, multi-network integration strategies often lead to vulnerabilities that greatly reduce the security of an organization, and can expose mission-critical control systems to cyber threats. This document provides guidance and direction for developing ‘defense-in-depth’ strategies for organizations that use control system networks while maintaining a multi-tier information architecture that requires: Maintenance of various field devices, telemetry collection, and/or industrial-level process systems Access to facilities via remote data link or modem Public facing services for customer or corporate operations A robust business environment that requires connections among the control system domain, the external Internet, and other peer organizations.
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2016-01-01
Parasitic plants acquire diverse secondary metabolites from their hosts, including defense compounds that target insect herbivores. However, the ecological implications of this phenomenon, including the potential enhancement of parasite defenses, remain largely unexplored. We studied the translocation of glucosinolates from the brassicaceous host plant Arabidopsis (Arabidopsis thaliana) into parasitic dodder vines (Convolvulaceae; Cuscuta gronovii) and its effects on the parasite itself and on dodder-aphid interactions. Aliphatic and indole glucosinolates reached concentrations in parasite tissues higher than those observed in corresponding host tissues. Dodder growth was enhanced on cyp79B2 cyp79B3 hosts (without indole glucosinolates) but inhibited on atr1D hosts (with elevated indole glucosinolates) relative to wild-type hosts, which responded to parasitism with localized elevation of indole and aliphatic glucosinolates. These findings implicate indole glucosinolates in defense against parasitic plants. Rates of settling and survival on dodder vines by pea aphids (Acyrthosiphon pisum) were reduced significantly when dodder parasitized glucosinolate-producing hosts (wild type and atr1D) compared with glucosinolate-free hosts (cyp79B2 cyp79B3 myb28 myb29). However, settling and survival of green peach aphids (Myzus persicae) were not affected. M. persicae population growth was actually reduced on dodder parasitizing glucosinolate-free hosts compared with wild-type or atr1D hosts, even though stems of the former contain less glucosinolates and more amino acids. Strikingly, this effect was reversed when the aphids fed directly upon Arabidopsis, which indicates an interactive effect of parasite and host genotype on M. persicae that stems from host effects on dodder. Thus, our findings indicate that glucosinolates may have both direct and indirect effects on dodder-feeding herbivores. PMID:27482077
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Strategic Missile Defense & Nuclear Deterrence
Grego, Laura
The United States has pursued defenses against nuclear-armed long-range ballistic missiles since at least the 1950s. At the same time, concerns that missile defenses could undermine nuclear deterrence and potentially spark an arms race led the United States and Soviet Union to negotiate limits on these systems. The 1972 Anti-Ballistic Missile Treaty constrained strategic missile defenses for thirty years. After abandoning the treaty in 2002, President George W. Bush began fielding the Ground-based Midcourse Defense (GMD) homeland missile defense system on an extremely aggressive schedule, nominally to respond to threats from North Korea and Iran. Today, nearly fifteen years after its initial deployment, the potential and the limits of this homeland missile defense are apparent. Its test record is poor and it has no demonstrated ability to stop an incoming missile under real-world conditions. No credible strategy is in place to solve the issue of discriminating countermeasures. Insufficient oversight has not only exacerbated the GMD system's problems, but has obscured their full extent, which could encourage politicians and military leaders to make decisions that actually increase the risk of a missile attack against the United States. These are not the only costs. Both Russia and China have repeatedly expressed concerns that U.S. missile defenses adversely affect their own strategic capabilities and interests, particularly taken in light of the substantial US nuclear forces. This in turn affects these countries' nuclear modernization priorities. This talk will provide a technical overview of the US strategic missile defense system, and how it relates to deterrence against non-peer adversaries as well as how it affects deterrence with Russia and China and the long-term prospects for nuclear reductions
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Mayer, Michael
2011-01-01
At the 2010 NATO summit in Lisbon, the alliance decided to move forward on the development of a territorial ballistic missile defense (BMD) system and explore avenues for cooperation with Russia in this endeavor. Substantial progress on BMD has been made over the past decade, but some questions remain regarding the ultimate strategic utility of such a system and whether its benefi ts outweigh the possible opportunity costs. Missile defense has been a point of contention between the US and its...
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Directory of Open Access Journals (Sweden)
Giorgio Fedele
2017-09-01
Full Text Available Adenylate cyclase toxin (CyaA is released in the course of B. pertussis infection in the host’s respiratory tract in order to suppress its early innate and subsequent adaptive immune defense. CD11b-expressing dendritic cells (DC, macrophages and neutrophils are professional phagocytes and key players of the innate immune system that provide a first line of defense against invading pathogens. Recent findings revealed the capacity of B. pertussis CyaA to intoxicate DC with high concentrations of 3′,5′-cyclic adenosine monophosphate (cAMP, which ultimately skews the host immune response towards the expansion of Th17 cells and regulatory T cells. CyaA-induced cAMP signaling swiftly incapacitates opsonophagocytosis, oxidative burst and NO-mediated killing of bacteria by neutrophils and macrophages. The subversion of host immune responses by CyaA after delivery into DC, macrophages and neutrophils is the subject of this review.
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Kesimer, Mehmet; Kirkham, Sara; Pickles, Raymond J.; Henderson, Ashley G.; Alexis, Neil E.; DeMaria, Genevieve; Knight, David; Thornton, David J.; Sheehan, John K.
2009-01-01
Human tracheobronchial epithelial cells grown in air-liquid interface culture have emerged as a powerful tool for the study of airway biology. In this study, we have investigated whether this culture system produces “mucus” with a protein composition similar to that of in vivo, induced airway secretions. Previous compositional studies of mucous secretions have greatly underrepresented the contribution of mucins, which are major structural components of normal mucus. To overcome this limitation, we have used a mass spectrometry-based approach centered on prior separation of the mucins from the majority of the other proteins. Using this approach, we have compared the protein composition of apical secretions (AS) from well-differentiated primary human tracheobronchial cells grown at air-liquid interface and human tracheobronchial normal induced sputum (IS). A total of 186 proteins were identified, 134 from AS and 136 from IS; 84 proteins were common to both secretions, with host defense proteins being predominant. The epithelial mucins MUC1, MUC4, and MUC16 and the gel-forming mucins MUC5B and MUC5AC were identified in both secretions. Refractometry showed that the gel-forming mucins were the major contributors by mass to both secretions. When the composition of the IS was corrected for proteins that were most likely derived from saliva, serum, and migratory cells, there was considerable similarity between the two secretions, in particular, in the category of host defense proteins, which includes the mucins. This shows that the primary cell culture system is an important model for study of aspects of innate defense of the upper airways related specifically to mucus consisting solely of airway cell products. PMID:18931053
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DEFF Research Database (Denmark)
Schou, Kirstine Klitgaard; Rundsten, Carsten Friis; Jensen, Tim Kåre
2012-01-01
and survive within the hostile environment of host macrophages. This persistence within macrophages may be related to urease activity, mobilization of various stress responses and active evasion of the host defenses by cell surface sialylation. Conclusions/Significance The data presented here highlight...
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Garavaglia, Betiana S.
2010-01-28
Xanthomonas citri pv. citri, the bacteria responsible for citrus canker posses a biological active plant natriuretic peptide (PNP)-like protein, not present in any other bacteria. PNPs are a class of extracellular, systemically mobile peptides that elicit a number of plant responses important in homeostasis and growth. Previously, we showed that a Xanthomonas citri pv. citri mutant lacking the PNP-like protein XacPNP produced more necrotic lesions in citrus leaves than wild type infections and suggested a role for XacPNP in the regulation of host homeostasis. Here we have analyzed the proteome modifications observed in citrus leaves infected with the wild type and XacPNP deletion mutant bacteria. While both of them cause downregulation of enzymes related to photosynthesis as well as chloroplastic ribosomal proteins, proteins related to defense responses are up-regulated. However, leaves infiltrated with the XacPNP deletion mutant show a more pronounced decrease in photosynthetic proteins while no reduction in defense related proteins as compared to the wild-type pathogen. This suggests that XacPNP serves the pathogen to maintain host photosynthetic efficiency during pathogenesis. The results from the proteomics analyses are consistent with our chlorophyll fluorescence data and transcript analyses of defense genes that show a more marked reduction in photosynthesis in the mutant but no difference in the induction of genes diagnostic for biotic-stress responses. We therefore conclude that XacPNP counteracts the shut-down of host photosynthesis during infection and in that way maintains the tissue in better conditions, suggesting that the pathogen has adapted a host gene to modify its natural host and render it a better reservoir for prolonged bacterial survival and thus for further colonization. 2010 Garavaglia et al.
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Directory of Open Access Journals (Sweden)
Betiana S Garavaglia
Full Text Available Xanthomonas citri pv. citri, the bacteria responsible for citrus canker posses a biological active plant natriuretic peptide (PNP-like protein, not present in any other bacteria. PNPs are a class of extracellular, systemically mobile peptides that elicit a number of plant responses important in homeostasis and growth. Previously, we showed that a Xanthomonas citri pv. citri mutant lacking the PNP-like protein XacPNP produced more necrotic lesions in citrus leaves than wild type infections and suggested a role for XacPNP in the regulation of host homeostasis. Here we have analyzed the proteome modifications observed in citrus leaves infected with the wild type and XacPNP deletion mutant bacteria. While both of them cause down-regulation of enzymes related to photosynthesis as well as chloroplastic ribosomal proteins, proteins related to defense responses are up-regulated. However, leaves infiltrated with the XacPNP deletion mutant show a more pronounced decrease in photosynthetic proteins while no reduction in defense related proteins as compared to the wild-type pathogen. This suggests that XacPNP serves the pathogen to maintain host photosynthetic efficiency during pathogenesis. The results from the proteomics analyses are consistent with our chlorophyll fluorescence data and transcript analyses of defense genes that show a more marked reduction in photosynthesis in the mutant but no difference in the induction of genes diagnostic for biotic-stress responses. We therefore conclude that XacPNP counteracts the shut-down of host photosynthesis during infection and in that way maintains the tissue in better conditions, suggesting that the pathogen has adapted a host gene to modify its natural host and render it a better reservoir for prolonged bacterial survival and thus for further colonization.
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Garavaglia, Betiana S.; Thomas, Ludivine; Gottig, Natalia; Dunger, Germá n; Garofalo, Cecilia G.; Daurelio, Lucas D.; Ndimba, Bongani; Orellano, Elena G.; Gehring, Christoph A; Ottado, Jorgelina
2010-01-01
Xanthomonas citri pv. citri, the bacteria responsible for citrus canker posses a biological active plant natriuretic peptide (PNP)-like protein, not present in any other bacteria. PNPs are a class of extracellular, systemically mobile peptides that elicit a number of plant responses important in homeostasis and growth. Previously, we showed that a Xanthomonas citri pv. citri mutant lacking the PNP-like protein XacPNP produced more necrotic lesions in citrus leaves than wild type infections and suggested a role for XacPNP in the regulation of host homeostasis. Here we have analyzed the proteome modifications observed in citrus leaves infected with the wild type and XacPNP deletion mutant bacteria. While both of them cause downregulation of enzymes related to photosynthesis as well as chloroplastic ribosomal proteins, proteins related to defense responses are up-regulated. However, leaves infiltrated with the XacPNP deletion mutant show a more pronounced decrease in photosynthetic proteins while no reduction in defense related proteins as compared to the wild-type pathogen. This suggests that XacPNP serves the pathogen to maintain host photosynthetic efficiency during pathogenesis. The results from the proteomics analyses are consistent with our chlorophyll fluorescence data and transcript analyses of defense genes that show a more marked reduction in photosynthesis in the mutant but no difference in the induction of genes diagnostic for biotic-stress responses. We therefore conclude that XacPNP counteracts the shut-down of host photosynthesis during infection and in that way maintains the tissue in better conditions, suggesting that the pathogen has adapted a host gene to modify its natural host and render it a better reservoir for prolonged bacterial survival and thus for further colonization. 2010 Garavaglia et al.
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Wallace, S K; Eigenbrode, Sanford D
2002-02-01
Optimal defense theory (ODT) predicts that plant defenses will be allocated to plant organs and tissues in proportion to their relative fitness values and susceptibilities to attack. This study was designed to test ODT predictions on the myrosinase-glucosinolate defense system in Brassica juncea by examining the relationships between the fitness value of B. juncea cotyledons and the levels and effectiveness of cotyledon defenses. Specifically, we estimated fitness value of cotyledons during plant development by measuring plant growth and seed production after cotyledon damage or removal at successive seedling ages. Cotyledon removal within five days of emergence had a significant impact on growth and seed production, but cotyledon removal at later stages did not. Consistent with ODT, glucosinolate and myrosinase levels in cotyledons also declined with seedling age, as did relative defenses against a generalist herbivore, Spodoptera eridania, as estimated by bioassay. Declines in glucosinolates were as predicted by a passive, allometric dilution model based on cotyledon expansion. Declines in myrosinase activity were significantly more gradual than predicted by allometric dilution, suggesting active retention of myrosinase activity as young cotyledons expand.
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Khan, Shahneaz Ali; Waugh, Courtney; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Gerdts, Volker; Potter, Andrew; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter
2014-10-07
Chlamydial infections are wide spread in koalas across their range and a solution to this debilitating disease has been sought for over a decade. Antibiotics are the currently accepted therapeutic measure, but are not an effective treatment due to the asymptomatic nature of some infections and a low efficacy rate. Thus, a vaccine would be an ideal way to address this infectious disease threat in the wild. Previous vaccine trials have used a three-dose regimen; however this is very difficult to apply in the field as it would require multiple capture events, which are stressful and invasive processes for the koala. In addition, it requires skilled koala handlers and a significant monetary investment. To overcome these challenges, in this study we utilized a polyphosphazine based poly I:C and a host defense peptide adjuvant combined with recombinant chlamydial major outer membrane protein (rMOMP) antigen to induce long lasting (54 weeks) cellular and humoral immunity in female koalas with a novel single immunizing dose. Immunized koalas produced a strong IgG response in plasma, as well as at mucosal sites. Moreover, they showed high levels of C. pecorum specific neutralizing antibodies in the plasma as well as vaginal and conjunctival secretions. Lastly, Chlamydia-specific lymphocyte proliferation responses were produced against both whole chlamydial elementary bodies and rMOMP protein, over the 12-month period. The results of this study suggest that a single dose rMOMP vaccine incorporating a poly I:C, host defense peptide and polyphosphazine adjuvant is able to stimulate both arms of the immune system in koalas, thereby providing an alternative to antibiotic treatment and/or a three-dose vaccine regime. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Patriot/Medium Extended Air Defense System Combined Aggregate Program (Patriot/MEADS CAP)
2013-12-01
SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION /AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY...States, Germany, and Italy to replace the U.S. Patriot air defense systems, Patriot and Hawk systems in Germany, and the Nike system in Italy. The MEADS...combat demonstrated capability against these threats. MEADS will employ a netted distributed architecture with modular components to increase
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Modeling of Target Tracking System for Homing Missiles and Air Defense Systems
Directory of Open Access Journals (Sweden)
Yunes Sh. ALQUDSI
2018-06-01
Full Text Available One reason of why the guidance and control systems are imperfect is due to the dynamics of both the tracker and the missile, which appears as an error in the alignment with the LOS and delay in the response of the missile to change its orientation. Other reasons are the bias and disturbances as well as the noise about and within the system such as the thermal noise. This paper deals with the tracking system used in the homing guidance and air defense systems. A realistic model for the tracking system model is developed including the receiver servo dynamics and the possible disturbance and noise that may affect the accuracy of the tracking signals measured by the seeker sensor. Modeling the parameters variability and uncertainty is also examined to determine the robustness margin of the tracking system.
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Defense Systems Management Review. Volume 3, Number 2, Spring 1980. Managing the Process.
1980-01-01
and no one did. As a result, many literally curled up and died, and for no known medical reason. Major Mayer ended a lecture on the subject with a plea...November 6, 1978. 10. Fred E. Rosell, Jr., "’ rip Report-Visit to Defense Documentation Center (DDC), May 16, 1978," Defense Systems Management College...easily expandable to splits among three or more producers. To do this for three companies, you must determine the split between Companies A and B as a
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Minmax defense strategy for complex multi-state systems
International Nuclear Information System (INIS)
Hausken, Kjell; Levitin, Gregory
2009-01-01
This paper presents a general optimization methodology that merges game theory and multi-state system survivability theory. The defender has multiple alternatives of defense strategy that presumes separation and protection of system elements. The attacker also has multiple alternatives of its attack strategy based on a combination of different possible attack actions against different groups of system elements. The defender minimizes, and the attacker maximizes, the expected damage caused by the attack (taking into account the unreliability of system elements and the multi-state nature of complex series-parallel systems). The problem is defined as a two-period minmax non-cooperative game between the defender who moves first and the attacker who moves second. An exhaustive minmax optimization algorithm is presented based on a double-loop genetic algorithm for determining the solution. A universal generating function technique is applied for evaluating the losses caused by system performance reduction. Illustrative examples with solutions are presented
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Host-microbe interactions that shape the pathogenesis of Acinetobacter baumannii infection
Mortensen, Brittany L.; Skaar, Eric P.
2013-01-01
Summary Acinetobacter baumannii is an opportunistic pathogen that has emerged as a prevalent source of nosocomial infections, most frequently causing ventilator-associated pneumonia. The emergence of pan-drug resistant strains magnifies the problem by reducing viable treatment options and effectively increasing the mortality rate associated with Acinetobacter infections. In light of this rising threat, research on A. baumannii epidemiology, antibiotic resistance, and pathogenesis is accelerating. The recent development of both in vitro and in vivo models has enabled studies probing the host-Acinetobacter interface. Bacterial genetic screens and comparative genomic studies have led to the identification of several A. baumannii virulence factors. Additionally, investigations into host defense mechanisms using animal models or cell culture have provided insight into the innate immune response to infection. This review highlights some of the key attributes of A. baumannii virulence with an emphasis on bacterial interactions with the innate immune system. PMID:22640368
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Do host species evolve a specific response to slave-making ants?
Directory of Open Access Journals (Sweden)
Delattre Olivier
2012-12-01
Full Text Available Abstract Background Social parasitism is an important selective pressure for social insect species. It is particularly the case for the hosts of dulotic (so called slave-making ants, which pillage the brood of host colonies to increase the worker force of their own colony. Such raids can have an important impact on the fitness of the host nest. An arms race which can lead to geographic variation in host defenses is thus expected between hosts and parasites. In this study we tested whether the presence of a social parasite (the dulotic ant Myrmoxenus ravouxi within an ant community correlated with a specific behavioral defense strategy of local host or non-host populations of Temnothorax ants. Social recognition often leads to more or less pronounced agonistic interactions between non-nestmates ants. Here, we monitored agonistic behaviors to assess whether ants discriminate social parasites from other ants. It is now well-known that ants essentially rely on cuticular hydrocarbons to discriminate nestmates from aliens. If host species have evolved a specific recognition mechanism for their parasite, we hypothesize that the differences in behavioral responses would not be fully explained simply by quantitative dissimilarity in cuticular hydrocarbon profiles, but should also involve a qualitative response due to the detection of particular compounds. We scaled the behavioral results according to the quantitative chemical distance between host and parasite colonies to test this hypothesis. Results Cuticular hydrocarbon profiles were distinct between species, but host species did not show a clearly higher aggression rate towards the parasite than toward non-parasite intruders, unless the degree of response was scaled by the chemical distance between intruders and recipient colonies. By doing so, we show that workers of the host and of a non-host species in the parasitized site displayed more agonistic behaviors (bites and ejections towards parasite
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Wong, Xiu Ming; Younger, Susan; Peters, Christian J; Jan, Yuh Nung; Jan, Lily Y
2013-11-05
TMEM16A and TMEM16B are calcium-activated chloride channels (CaCCs) with important functions in mammalian physiology. Whether distant relatives of the vertebrate TMEM16 families also form CaCCs is an intriguing open question. Here we report that a TMEM16 family member from Drosophila melanogaster, Subdued (CG16718), is a CaCC. Amino acid substitutions of Subdued alter the ion selectivity and kinetic properties of the CaCC channels heterologously expressed in HEK 293T cells. This Drosophila channel displays characteristics of classic CaCCs, thereby providing evidence for evolutionarily conserved biophysical properties in the TMEM16 family. Additionally, we show that knockout flies lacking subdued gene activity more readily succumb to death caused by ingesting the pathogenic bacteria Serratia marcescens, suggesting that subdued has novel functions in Drosophila host defense. DOI: http://dx.doi.org/10.7554/eLife.00862.001.
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Directory of Open Access Journals (Sweden)
Inka eLusebrink
2016-02-01
Full Text Available The mountain pine beetle (MPB; Dendroctonus ponderosae has recently expanded its range from lodgepole pine forest into the lodgepole × jack pine hybrid zone in central Alberta, within which it has attacked pure jack pine. This study tested the effects of water limitation on tree defense response of mature lodgepole and jack pine (Pinus contorta and Pinus banksiana trees in the field. Tree defense response was initiated by inoculation of trees with the MPB-associated fungus Grosmannia clavigera and measured through monoterpene emission from tree boles and concentration of defensive compounds in phloem, needles, and necrotic tissues. Lodgepole pine generally emitted higher amounts of monoterpenes than jack pine; particularly from fungal-inoculated trees. Compared to non-inoculated trees, fungal inoculation increased monoterpene emission in both species, whereas water treatment had no effect on monoterpene emission. The phloem of both pine species contains (--α-pinene, the precursor of the beetle’s aggregation pheromone, however lodgepole pine contains two times as much as jack pine. The concentration of defensive compounds was 70-fold greater in the lesion tissue in jack pine, but only 10-fold in lodgepole pine compared to healthy phloem tissue in each species, respectively. Water-deficit treatment inhibited an increase of L-limonene as response to fungal inoculation in lodgepole pine phloem. The amount of myrcene in jack pine phloem was higher in water-deficit trees compared to ambient trees. Beetles reared in jack pine were not affected by either water or biological treatment, whereas beetles reared in lodgepole pine benefited from fungal inoculation by producing larger and heavier female offspring. Female beetles that emerged from jack pine bolts contained more fat than those that emerged from lodgepole pine, even though lodgepole pine phloem had a higher nitrogen content than jack pine phloem. These results suggest that jack pine chemistry
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Long non-coding RNAs as molecular players in plant defense against pathogens.
Zaynab, Madiha; Fatima, Mahpara; Abbas, Safdar; Umair, Muhammad; Sharif, Yasir; Raza, Muhammad Ammar
2018-05-31
Long non-coding RNAs (lncRNAs) has significant role in of gene expression and silencing pathways for several biological processes in eukaryotes. lncRNAs has been reported as key player in remodeling chromatin and genome architecture, RNA stabilization and transcription regulation, including enhancer-associated activity. Host lncRNAs are reckoned as compulsory elements of plant defense. In response to pathogen attack, plants protect themselves with the help of lncRNAs -dependent immune systems in which lncRNAs regulate pathogen-associated molecular patterns (PAMPs) and other effectors. Role of lncRNAs in plant microbe interaction has been studied extensively but regulations of several lncRNAs still need extensive research. In this study we discussed and provide as overview the topical advancements and findings relevant to pathogen attack and plant defense mediated by lncRNAs. It is hoped that lncRNAs would be exploited as a mainstream player to achieve food security by tackling different plant diseases. Copyright © 2018. Published by Elsevier Ltd.
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Host age modulates within-host parasite competition.
Izhar, Rony; Routtu, Jarkko; Ben-Ami, Frida
2015-05-01
In many host populations, one of the most striking differences among hosts is their age. While parasite prevalence differences in relation to host age are well known, little is known on how host age impacts ecological and evolutionary dynamics of diseases. Using two clones of the water flea Daphnia magna and two clones of its bacterial parasite Pasteuria ramosa, we examined how host age at exposure influences within-host parasite competition and virulence. We found that multiply-exposed hosts were more susceptible to infection and suffered higher mortality than singly-exposed hosts. Hosts oldest at exposure were least often infected and vice versa. Furthermore, we found that in young multiply-exposed hosts competition was weak, allowing coexistence and transmission of both parasite clones, whereas in older multiply-exposed hosts competitive exclusion was observed. Thus, age-dependent parasite exposure and host demography (age structure) could together play an important role in mediating parasite evolution. At the individual level, our results demonstrate a previously unnoticed interaction of the host's immune system with host age, suggesting that the specificity of immune function changes as hosts mature. Therefore, evolutionary models of parasite virulence might benefit from incorporating age-dependent epidemiological parameters. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
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Charges Assessed the Army by the Defense Logistics Agency for Deployable Medical Systems
National Research Council Canada - National Science Library
1995-01-01
.... Deployable medical systems are standardized modular field hospitals that can be prepositioned in the event of a contingency, national emergency, or war operations. In FY 1994, the Defense Personnel Support Center billed the Army $25 million for acquiring and assembling deployable medical systems.
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International Nuclear Information System (INIS)
Bin Abas, Faizulsalihin; Takayama, Shigeru
2015-01-01
This paper proposes multiple host nodes in Wireless Sensing Node Network System (WSNNS) for landslide monitoring. As landslide disasters damage monitoring system easily, one major demand in landslide monitoring is the flexibility and robustness of the system to evaluate the current situation in the monitored area. For various reasons WSNNS can provide an important contribution to reach that aim. In this system, acceleration sensors and GPS are deployed in sensing nodes. Location information by GPS, enable the system to estimate network topology and enable the system to perceive the location in emergency by monitoring the node mode. Acceleration sensors deployment, capacitate this system to detect slow mass movement that can lead to landslide occurrence. Once deployed, sensing nodes self-organize into an autonomous wireless ad hoc network. The measurement parameter data from sensing nodes is transmitted to Host System via host node and ''Cloud'' System. The implementation of multiple host nodes in Local Sensing Node Network System (LSNNS), improve risk- management of the WSNNS for real-time monitoring of landslide disaster
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Abas, Faizulsalihin bin; Takayama, Shigeru
2015-02-01
This paper proposes multiple host nodes in Wireless Sensing Node Network System (WSNNS) for landslide monitoring. As landslide disasters damage monitoring system easily, one major demand in landslide monitoring is the flexibility and robustness of the system to evaluate the current situation in the monitored area. For various reasons WSNNS can provide an important contribution to reach that aim. In this system, acceleration sensors and GPS are deployed in sensing nodes. Location information by GPS, enable the system to estimate network topology and enable the system to perceive the location in emergency by monitoring the node mode. Acceleration sensors deployment, capacitate this system to detect slow mass movement that can lead to landslide occurrence. Once deployed, sensing nodes self-organize into an autonomous wireless ad hoc network. The measurement parameter data from sensing nodes is transmitted to Host System via host node and "Cloud" System. The implementation of multiple host nodes in Local Sensing Node Network System (LSNNS), improve risk- management of the WSNNS for real-time monitoring of landslide disaster.
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Directory of Open Access Journals (Sweden)
Brian K. Lohman
2017-09-01
Full Text Available Heritable population differences in immune gene expression following infection can reveal mechanisms of host immune evolution. We compared gene expression in infected and uninfected threespine stickleback (Gasterosteus aculeatus from two natural populations that differ in resistance to a native cestode parasite, Schistocephalus solidus. Genes in both the innate and adaptive immune system were differentially expressed as a function of host population, infection status, and their interaction. These genes were enriched for loci controlling immune functions known to differ between host populations or in response to infection. Coexpression network analysis identified two distinct processes contributing to resistance: parasite survival and suppression of growth. Comparing networks between populations showed resistant fish have a dynamic expression profile while susceptible fish are static. In summary, recent evolutionary divergence between two vertebrate populations has generated population-specific gene expression responses to parasite infection, affecting parasite establishment and growth.
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Organoid culture systems to study host-pathogen interactions
Dutta, Devanjali; Clevers, Hans
2017-01-01
Recent advances in host-microbe interaction studies in organoid cultures have shown great promise and have laid the foundation for much more refined future studies using these systems. Modeling of Zika virus (ZIKV) infection in cerebral organoids have helped us understand its association with
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The design about the intrusion defense system for IHEP
International Nuclear Information System (INIS)
Liu Baoxu; Xu Rongsheng; Yu Chuansong; Wu Chunzhen
2003-01-01
With the development of network technologies, limitations on traditional methods of network security protection are becoming more and more obvious. An individual network security product or the simple combination of several products can hardly complete the goal of keeping from hackers' intrusion. Therefore, on the basis of the analyses about the security problems of IHEPNET which is an open and scientific research network, the author designs an intrusion defense system especially for IHEPNET
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2010-03-15
... Allocations System regulation (15 CFR part 700) must retain the records for at least 3 years. II. Method of... Request; Defense Priorities and Allocations System AGENCY: Bureau of Industry and Security, Commerce...: Direct all written comments to Diana Hynek, Departmental Paperwork Clearance Officer, Department of...
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Sleeping to fuel the immune system: mammalian sleep and resistance to parasites
Directory of Open Access Journals (Sweden)
Opp Mark R
2009-01-01
Full Text Available Abstract Sleep is an enigma. Why animals forgo eating and reproducing, while potentially increasing their risk of predation remains unknown. Although some may question whether all animals sleep, it is clear that all living organisms possess defenses against attack by pathogens. Immune responses of humans and animals are impaired by sleep loss, and responses to immune challenge include altered sleep. Thus, sleep is hypothesized to be a component of the acute phase response to infection and to function in host defense. Examining phylogenetic relationships among sleep parameters, components of the mammalian immune system and resistance to infection may provide insight into the evolution of sleep and lead to a greater appreciation for the role of sleep in host defense.
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Energy Technology Data Exchange (ETDEWEB)
Newhouse, Robert N.
2010-01-01
Report on the Operational Testing and Evaluation to validate and baseline an operable system that meets the Second Line of Defense (SLD) mission requirements. An SLD system is defined as the detection technology and associated equipment, the system operators from the host country, the standard operating procedures (SOPs), and other elements such as training and maintenance which support long-term system sustainment. To this end, the activities conducted during the OT&E phase must demonstrate that the Megaports System can be operated effectively in real-time by Panama Direccion General de Aduanas (DGA Panama Customs) personnel to the standards of the U.S. Department of Energy/National Nuclear Security Administration (DOE/NNSA).
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DEFF Research Database (Denmark)
Lazado, Carlo Cabacang; Caipang, Christopher Marlowe A.; Estante, Erish G.
2015-01-01
Aquatic animals harbor a great number of microorganisms with interesting biological and biochemical diversity. Besides serving as the natural defense system of the host, the utilization potential of this microbial association has been identified particularly as reservoirs of candidate probiotics....... Host-derived probiotics have gained popularity in recent years as they offer an alternative source of beneficial microbes to the industry that is customarily dependent on the use of terrestrial microorganisms. At present, there is an overwhelming number of candidate probiotics in aquaculture...... but their large-scale application is restricted by bio-technological concerns and fragmentary documented probiotic actions. This paper presents the current understanding on the use of probiotics as a sustainable alternative that promotes health and welfare in fish and penaeids. In particular, this paper discusses...
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A novel mechanism for NETosis provides antimicrobial defense at the oral mucosa
DEFF Research Database (Denmark)
Mohanty, Tirthankar; Sjögren, Jonathan; Kahn, Fredrik
2015-01-01
Neutrophils are essential for host defense at the oral mucosa and neutropenia or functional neutrophil defects lead to disordered oral homeostasis. We found that neutrophils from the oral mucosa harvested from morning saliva had released neutrophil extracellular traps (undergone NETosis) in vivo...
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Host Diet Affects the Morphology of Monarch Butterfly Parasites.
Hoang, Kevin; Tao, Leiling; Hunter, Mark D; de Roode, Jacobus C
2017-06-01
Understanding host-parasite interactions is essential for ecological research, wildlife conservation, and health management. While most studies focus on numerical traits of parasite groups, such as changes in parasite load, less focus is placed on the traits of individual parasites such as parasite size and shape (parasite morphology). Parasite morphology has significant effects on parasite fitness such as initial colonization of hosts, avoidance of host immune defenses, and the availability of resources for parasite replication. As such, understanding factors that affect parasite morphology is important in predicting the consequences of host-parasite interactions. Here, we studied how host diet affected the spore morphology of a protozoan parasite ( Ophryocystis elektroscirrha ), a specialist parasite of the monarch butterfly ( Danaus plexippus ). We found that different host plant species (milkweeds; Asclepias spp.) significantly affected parasite spore size. Previous studies have found that cardenolides, secondary chemicals in host plants of monarchs, can reduce parasite loads and increase the lifespan of infected butterflies. Adding to this benefit of high cardenolide milkweeds, we found that infected monarchs reared on milkweeds of higher cardenolide concentrations yielded smaller parasites, a potentially hidden characteristic of cardenolides that may have important implications for monarch-parasite interactions.
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National Research Council Canada - National Science Library
Hichkad, Ravi R; Bolkcom, Christopher
2005-01-01
Congress has expressed interest in cruise missile defense for years. Cruise missiles (CMs) are essentially unmanned attack aircraft -- vehicles composed of an airframe, propulsion system, guidance system, and weapons payload...
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National Research Council Canada - National Science Library
Hichkad, Ravi R; Bolkcom, Christopher
2004-01-01
Congress has expressed interest in cruise missile defense for years. Cruise missiles (CMs) are essentially unmanned attack aircraft -- vehicles composed of an airframe, propulsion system, guidance system, and weapons payload...
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Cost of space-based laser ballistic missile defense.
Field, G; Spergel, D
1986-03-21
Orbiting platforms carrying infrared lasers have been proposed as weapons forming the first tier of a ballistic missile defense system under the President's Strategic Defense Initiative. As each laser platform can destroy a limited number of missiles, one of several methods of countering such a system is to increase the number of offensive missiles. Hence it is important to know whether the cost-exchange ratio, defined as the ratio of the cost to the defense of destroying a missile to the cost to the offense of deploying an additional missile, is greater or less than 1. Although the technology to be used in a ballistic missile defense system is still extremely uncertain, it is useful to examine methods for calculating the cost-exchange ratio. As an example, the cost of an orbiting infrared laser ballistic missile defense system employed against intercontinental ballistic missiles launched simultaneously from a small area is compared to the cost of additional offensive missiles. If one adopts lower limits to the costs for the defense and upper limits to the costs for the offense, the cost-exchange ratio comes out substantially greater than 1. If these estimates are confirmed, such a ballistic missile defense system would be unable to maintain its effectiveness at less cost than it would take to proliferate the ballistic missiles necessary to overcome it and would therefore not satisfy the President's requirements for an effective strategic defense. Although the method is illustrated by applying it to a space-based infrared laser system, it should be straightforward to apply it to other proposed systems.
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2011-04-30
learning. Recommendations are also presented for additional research into a more effective systems engineering andragogy . 15. SUBJECT TERMS 16...into a more effective systems engineering andragogy . Purpose Competency-based training for defense acquisition workers in the systems engineering
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Variation in plant defense suppresses herbivore performance
Pearse, Ian; Paul, Ryan; Ode, Paul J.
2018-01-01
Defensive variability of crops and natural systems can alter herbivore communities and reduce herbivory. However, it is still unknown how defense variability translates into herbivore suppression. Nonlinear averaging and constraints in physiological tracking (also more generally called time-dependent effects) are the two mechanisms by which defense variability might impact herbivores. We conducted a set of experiments manipulating the mean and variability of a plant defense, showing that defense variability does suppress herbivore performance and that it does so through physiological tracking effects that cannot be explained by nonlinear averaging. While nonlinear averaging predicted higher or the same herbivore performance on a variable defense than on an invariable defense, we show that variability actually decreased herbivore performance and population growth rate. Defense variability reduces herbivore performance in a way that is more than the average of its parts. This is consistent with constraints in physiological matching of detoxification systems for herbivores experiencing variable toxin levels in their diet and represents a more generalizable way of understanding the impacts of variability on herbivory. Increasing defense variability in croplands at a scale encountered by individual herbivores can suppress herbivory, even if that is not anticipated by nonlinear averaging.
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Energy Technology Data Exchange (ETDEWEB)
Krishnan, A
2006-08-30
The threats of bio-terrorism and newly emerging infectious diseases pose serious challenges to the national security infrastructure. Rapid detection and diagnosis of infectious disease in human populations, as well as characterizing pathogen biology, are critical for reducing the morbidity and mortality associated with such threats. One of the key challenges in managing an infectious disease outbreak, whether through natural causes or acts of overt terrorism, is detection early enough to initiate effective countermeasures. Much recent attention has been directed towards the utility of biomarkers or molecular signatures that result from the interaction of the pathogen with the host for improving our ability to diagnose and mitigate the impact of a developing infection during the time window when effective countermeasures can be instituted. Host responses may provide early signals in blood even from localized infections. Multiple innate and adaptive immune molecules, in combination with other biochemical markers, may provide disease-specific information and new targets for countermeasures. The presence of pathogen specific markers and an understanding of the molecular capabilities and adaptations of the pathogen when it interacts with its host may likewise assist in early detection and provide opportunities for targeting countermeasures. An important question that needs to be addressed is whether these molecular-based approaches will prove useful for early diagnosis, complement current methods of direct agent detection, and aid development and use of countermeasures. Lawrence Livermore National Laboratory (LLNL) will host a workshop to explore the utility of host- and pathogen-based molecular diagnostics, prioritize key research issues, and determine the critical steps needed to transition host-pathogen research to tools that can be applied towards a more effective national bio-defense strategy. The workshop will bring together leading researchers/scientists in the
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Directory of Open Access Journals (Sweden)
Johannes Strauß
2017-11-01
Full Text Available The defense glands in the dorsal prothorax are an important autapomorphic trait of stick insects (Phasmatodea. Here, we study the functional anatomy and neuronal innervation of the defense glands in Anisomorpha paromalus (Westwood, 1859 (Pseudophasmatinae, a species which sprays its defense secretions when disturbed or attacked. We use a neuroanatomical approach to identify the nerves innervating the gland muscles and the motoneurons with axons in the different nerves. The defense gland is innervated by nerves originating from two segments, the subesophageal ganglion (SOG, and the prothoracic ganglion. Axonal tracing confirms the gland innervation via the anterior subesophageal nerve, and two intersegmental nerves, the posterior subesophageal nerve, and the anterior prothoracic nerve. Axonal tracing of individual nerves reveals eight identified neuron types in the subesophageal or prothoracic ganglion. The strongest innervating nerve of the gland is the anterior subesophageal nerve, which also supplies dorsal longitudinal thorax muscles (neck muscles by separate nerve branches. Tracing of individual nerve branches reveals different sets of motoneurons innervating the defense gland (one ipsilateral and one contralateral subesophageal neuron or the neck muscle (ventral median neurons. The ipsilateral and contralateral subesophageal neurons have no homologs in related taxa like locusts and crickets, and thus evolved within stick insects with the differentiation of the defense glands. The overall innervation pattern suggests that the longitudinal gland muscles derived from dorsal longitudinal neck muscles. In sum, the innervating nerves for dorsal longitudinal muscles are conserved in stick insects, while the neuronal control system was specialized with conserved motoneurons for the persisting neck muscles, and evolutionarily novel subesophageal and prothoracic motoneurons innervating the defense gland.
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Department of Defense perspective
International Nuclear Information System (INIS)
Devine, R.
1985-01-01
This paper examines radiation instrumentation from the Department of Defense perspective. Radiation survey instruments and calibration, or RADIAC, as it is called in the services, while administratively falling under the Assistant Secretary of Defense for Atomic Energy, has generally been managed at a lower level. The Naval Electronics Systems Command and Army Signal Corp are the two principles in the Department of Defense for RADIAC. The actions of the services are coordinated through the tri-service RADIAC working group, which meets about every year and a half. Several points from this organization are highlighted
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External Quality Control Review of the Defense Information Systems Agency Audit Organization
2012-08-07
We are providing this report for your information and use. We have reviewed the system of quality control for the audit organization of the Defense...audit organization encompasses the audit organization’s leadership, emphasis on performing high quality work, and policies and procedures established
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CLASSIFICATION OF THE MGR DEFENSE HIGH-LEVEL WASTE DISPOSAL CONTAINER SYSTEM
International Nuclear Information System (INIS)
J.A. Ziegler
1999-01-01
The purpose of this analysis is to document the Quality Assurance (QA) classification of the Monitored Geologic Repository (MGR) defense high-level waste disposal container system structures, systems and components (SSCs) performed by the MGR Safety Assurance Department. This analysis also provides the basis for revision of YMP/90-55Q, Q-List (YMP 1998). The Q-List identifies those MGR SSCs subject to the requirements of DOE/RW-0333PY ''Quality Assurance Requirements and Description'' (QARD) (DOE 1998)
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Application of SYNROC to high-level defense wastes
International Nuclear Information System (INIS)
Tewhey, J.D.; Hoenig, C.L.; Newkirk, H.W.; Rozsa, R.B.; Coles, D.G.; Ryerson, F.J.
1981-01-01
The SYNROC method for immobilization of high-level nuclear reactor wastes is currently being applied to US defense wastes in tank storage at Savannah River, South Carolina. The minerals zirconolite, perovskite, and hollandite are used in SYNROC D formulations to immobilize fission products and actinides that comprise up to 10% of defense waste sludges and coexisting solutions. Additional phase in SYNROC D are nepheline, the host phase for sodium; and spinel, the host for excess aluminum and iron. Up to 70 wt % of calcined sludge can be incorporated with 30 wt % of SYNROC additives to produce a waste form consisting of 10% nepheline, 30% spinel, and approximately 20% each of the radioactive waste-bearing phases. Urea coprecipitation and spray drying/calcining methods have been used in the laboratory to produce homogeneous, reactive ceramic powders. Hot pressing and sintering at temperatures from 1000 to 1100 0 C result in waste form products with greater than 97% of theoretical density. Hot isostatic pressing has recently been implemented as a processing alternative. Characterization of waste-form mineralogy has been done by means of XRD, SEM, and electron microprobe. Leaching of SYNROC D samples is currently being carried out. Assessment of radiation damage effects and physical properties of SYNROC D will commence in FY81
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Claudia Cano-Ramirez; Maria Fernanda Lopez; Ana K. Cesar-Ayala; Veronica Pineda-Martinez; Brian T. Sullivan; Gerardo and Zuniga
2013-01-01
Bark beetles oxidize the defensive monoterpenes of their host trees both to detoxify them and convert them into components of their pheromone system. This oxidation is catalyzed by cytochrome P450 enzymes and occurs in different tissues of the insect, including the gut (i.e., the site where the beetle's pheromones are produced and accumulated) and the antennae (i....
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Zarate, Sonia I.; Kempema, Louisa A.; Walling, Linda L.
2007-01-01
The basal defenses important in curtailing the development of the phloem-feeding silverleaf whitefly (Bemisia tabaci type B; SLWF) on Arabidopsis (Arabidopsis thaliana) were investigated. Sentinel defense gene RNAs were monitored in SLWF-infested and control plants. Salicylic acid (SA)-responsive gene transcripts accumulated locally (PR1, BGL2, PR5, SID2, EDS5, PAD4) and systemically (PR1, BGL2, PR5) during SLWF nymph feeding. In contrast, jasmonic acid (JA)- and ethylene-dependent RNAs (PDF1.2, VSP1, HEL, THI2.1, FAD3, ERS1, ERF1) were repressed or not modulated in SLWF-infested leaves. To test for a role of SA and JA pathways in basal defense, SLWF development on mutant and transgenic lines that constitutively activate or impair defense pathways was determined. By monitoring the percentage of SLWF nymphs in each instar, we show that mutants that activate SA defenses (cim10) or impair JA defenses (coi1) accelerated SLWF nymphal development. Reciprocally, mutants that activate JA defenses (cev1) or impair SA defenses (npr1, NahG) slowed SLWF nymphal development. Furthermore, when npr1 plants, which do not activate downstream SA defenses, were treated with methyl jasmonate, a dramatic delay in nymph development was observed. Collectively, these results showed that SLWF-repressed, JA-regulated defenses were associated with basal defense to the SLWF. PMID:17189328
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Directory of Open Access Journals (Sweden)
Johan Panek
Full Text Available Intracellular pathogens including bacteria, viruses and protozoa hijack host cell functions to access nutrients and to bypass cellular defenses and immune responses. These strategies have been acquired through selective pressure and allowed pathogens to reach an appropriate cellular niche for their survival and growth. To get new insights on how parasites hijack host cellular functions, we developed a SILAC (Stable Isotope Labeling by Amino Acids in Cell culture quantitative proteomics workflow. Our study focused on deciphering the cross-talk in a host-parasite association, involving human foreskin fibroblasts (HFF and the microsporidia Anncaliia algerae, a fungus related parasite with an obligate intracellular lifestyle and a strong host dependency. The host-parasite cross-talk was analyzed at five post-infection times 1, 6, 12 and 24 hours post-infection (hpi and 8 days post-infection (dpi. A significant up-regulation of four interferon-induced proteins with tetratricopeptide repeats IFIT1, IFIT2, IFIT3 and MX1 was observed at 8 dpi suggesting a type 1 interferon (IFN host response. Quantitative alteration of host proteins involved in biological functions such as signaling (STAT1, Ras and reduction of the translation activity (EIF3 confirmed a host type 1 IFN response. Interestingly, the SILAC approach also allowed the detection of 148 A. algerae proteins during the kinetics of infection. Among these proteins many are involved in parasite proliferation, and an over-representation of putative secreted effectors proteins was observed. Finally our survey also suggests that A. algerae could use a transposable element as a lure strategy to escape the host innate immune system.
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Computational neural network regression model for Host based Intrusion Detection System
Directory of Open Access Journals (Sweden)
Sunil Kumar Gautam
2016-09-01
Full Text Available The current scenario of information gathering and storing in secure system is a challenging task due to increasing cyber-attacks. There exists computational neural network techniques designed for intrusion detection system, which provide security to single machine and entire network's machine. In this paper, we have used two types of computational neural network models, namely, Generalized Regression Neural Network (GRNN model and Multilayer Perceptron Neural Network (MPNN model for Host based Intrusion Detection System using log files that are generated by a single personal computer. The simulation results show correctly classified percentage of normal and abnormal (intrusion class using confusion matrix. On the basis of results and discussion, we found that the Host based Intrusion Systems Model (HISM significantly improved the detection accuracy while retaining minimum false alarm rate.
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2013-05-16
... Management Name Changes, Phase 1 Implementation (DFARS Case 2012- D053) AGENCY: Defense Acquisition... Excluded Parties Listing System (EPLS) databases into the System for Award Management (SAM) database. DATES... enacted in an effort to improve the management and promotion of electronic Government services and...
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Photovoltaics in the Department of Defense
International Nuclear Information System (INIS)
Chapman, R.N.
1997-01-01
This paper documents the history of photovoltaic use within the Department of Defense leading up to the installation of 2.1 MW of photovoltaics underway today. This history describes the evolution of the Department of Defense's Tri-Service Photovoltaic Review Committee and the committee's strategic plan to realize photovoltaic's full potential through outreach, conditioning of the federal procurement system, and specific project development. The Photovoltaic Review Committee estimates photovoltaic's potential at nearly 4,000 MW, of which about 700 MW are considered to be cost-effective at today's prices. The paper describes photovoltaic's potential within the Department of Defense, the status and features of the 2.1-MW worth of photovoltaic systems under installation, and how these systems are selected and implemented. The paper also documents support provided to the Department of Defense by the Department of Energy dating back to the late 70s. copyright 1997 American Institute of Physics
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Self-Assembly of Multi-nanozymes to Mimic an Intracellular Antioxidant Defense System.
Huang, Yanyan; Liu, Zhen; Liu, Chaoqun; Ju, Enguo; Zhang, Yan; Ren, Jinsong; Qu, Xiaogang
2016-06-01
In this work, for the first time, we constructed a novel multi-nanozymes cooperative platform to mimic intracellular antioxidant enzyme-based defense system. V2 O5 nanowire served as a glutathione peroxidase (GPx) mimic while MnO2 nanoparticle was used to mimic superoxide dismutase (SOD) and catalase (CAT). Dopamine was used as a linker to achieve the assembling of the nanomaterials. The obtained V2 O5 @pDA@MnO2 nanocomposite could serve as one multi-nanozyme model to mimic intracellular antioxidant enzyme-based defense procedure in which, for example SOD, CAT, and GPx co-participate. In addition, through assembling with dopamine, the hybrid nanocomposites provided synergistic antioxidative effect. Importantly, both in vitro and in vivo experiments demonstrated that our biocompatible system exhibited excellent intracellular reactive oxygen species (ROS) removal ability to protect cell components against oxidative stress, showing its potential application in inflammation therapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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2015-06-01
and systems, even monopolistic ) essence of the supply side of the defense market . There are only a few suppliers that can meet today’s complex...DEFENSE PROCUREMENT IN ACHIEVING A MORE COMPETITIVE AND STRONGER EUROPEAN DEFENSE EQUIPMENT MARKET by Kiril O. Angelov June 2015 Thesis Advisor...COMPETITIVE AND STRONGER EUROPEAN DEFENSE EQUIPMENT MARKET 5. FUNDING NUMBERS 6. AUTHOR(S) Kiril O. Angelov 7. PERFORMING ORGANIZATION NAME(S) AND
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Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells.
Liao, Hsin-Kai; Gu, Ying; Diaz, Arturo; Marlett, John; Takahashi, Yuta; Li, Mo; Suzuki, Keiichiro; Xu, Ruo; Hishida, Tomoaki; Chang, Chan-Jung; Esteban, Concepcion Rodriguez; Young, John; Izpisua Belmonte, Juan Carlos
2015-03-10
To combat hostile viruses, bacteria and archaea have evolved a unique antiviral defense system composed of clustered regularly interspaced short palindromic repeats (CRISPRs), together with CRISPR-associated genes (Cas). The CRISPR/Cas9 system develops an adaptive immune resistance to foreign plasmids and viruses by creating site-specific DNA double-stranded breaks (DSBs). Here we adapt the CRISPR/Cas9 system to human cells for intracellular defense against foreign DNA and viruses. Using HIV-1 infection as a model, our results demonstrate that the CRISPR/Cas9 system disrupts latently integrated viral genome and provides long-term adaptive defense against new viral infection, expression and replication in human cells. We show that engineered human-induced pluripotent stem cells stably expressing HIV-targeted CRISPR/Cas9 can be efficiently differentiated into HIV reservoir cell types and maintain their resistance to HIV-1 challenge. These results unveil the potential of the CRISPR/Cas9 system as a new therapeutic strategy against viral infections.
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HOMA: Israel's National Missile Defense Strategy (Abridged Version)
National Research Council Canada - National Science Library
Lailari, Guermantes
2002-01-01
... (Hebrew for Fortress Wall), Chapter 1 discusses the fundamentals of missile defense and the reason why Israel's missile defense system affects US national security interests, Chapter 2 describes Israel's missile defense...
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2017-12-01
SYSTEM ARCHITECTURE TO INVESTIGATE THE IMPACT OF INTEGRATED AIR AND MISSILE DEFENSE IN A DISTRIBUTED LETHALITY ENVIRONMENT by Justin K. Davis...TO INVESTIGATE THE IMPACT OF INTEGRATED AIR AND MISSILE DEFENSE IN A DISTRIBUTED LETHALITY ENVIRONMENT 5. FUNDING NUMBERS 6. AUTHOR(S) Justin K...ARCHITECTURE TO INVESTIGATE THE IMPACT OF INTEGRATED AIR AND MISSILE DEFENSE IN A DISTRIBUTED LETHALITY ENVIRONMENT Justin K. Davis Lieutenant
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Directory of Open Access Journals (Sweden)
Christina Alba
Full Text Available Intra-specific variation in host-plant quality affects herbivore foraging decisions and, in turn, herbivore foraging decisions mediate plant fitness. In particular, variation in defenses against herbivores, both among and within plants, shapes herbivore behavior. If variation in defenses is genetically based, it can respond to natural selection by herbivores. We quantified intra-specific variation in iridoid glycosides, trichome length, and leaf strength in common mullein (Verbascum thapsus L, Scrophulariaceae among maternal lines within a population and among leaves within plants, and related this variation to feeding preferences of a generalist herbivore, Trichopulsia ni Hübner. We found significant variation in all three defenses among maternal lines, with T. ni preferring plants with lower investment in chemical, but not mechanical, defense. Within plants, old leaves had lower levels of all defenses than young leaves, and were strongly preferred by T. ni. Caterpillars also preferred leaves with trichomes removed to leaves with trichomes intact. Differences among maternal lines indicate that phenotypic variation in defenses likely has a genetic basis. Furthermore, these results reveal that the feeding behaviors of T. ni map onto variation in plant defense in a predictable way. This work highlights the importance of variation in host-plant quality in driving interactions between plants and their herbivores.
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Alba, Christina; Bowers, M Deane; Blumenthal, Dana; Hufbauer, Ruth A
2014-01-01
Intra-specific variation in host-plant quality affects herbivore foraging decisions and, in turn, herbivore foraging decisions mediate plant fitness. In particular, variation in defenses against herbivores, both among and within plants, shapes herbivore behavior. If variation in defenses is genetically based, it can respond to natural selection by herbivores. We quantified intra-specific variation in iridoid glycosides, trichome length, and leaf strength in common mullein (Verbascum thapsus L, Scrophulariaceae) among maternal lines within a population and among leaves within plants, and related this variation to feeding preferences of a generalist herbivore, Trichopulsia ni Hübner. We found significant variation in all three defenses among maternal lines, with T. ni preferring plants with lower investment in chemical, but not mechanical, defense. Within plants, old leaves had lower levels of all defenses than young leaves, and were strongly preferred by T. ni. Caterpillars also preferred leaves with trichomes removed to leaves with trichomes intact. Differences among maternal lines indicate that phenotypic variation in defenses likely has a genetic basis. Furthermore, these results reveal that the feeding behaviors of T. ni map onto variation in plant defense in a predictable way. This work highlights the importance of variation in host-plant quality in driving interactions between plants and their herbivores.
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Schimmel, Bernardus C J; Ataide, Livia M S; Chafi, Rachid; Villarroel, Carlos A; Alba, Juan M; Schuurink, Robert C; Kant, Merijn R
2017-06-01
Spider mites are destructive arthropod pests on many crops. The generalist herbivorous mite Tetranychus urticae induces defenses in tomato (Solanum lycopersicum) and this constrains its fitness. By contrast, the Solanaceae-specialist Tetranychus evansi maintains a high reproductive performance by suppressing tomato defenses. Tetranychus evansi outcompetes T. urticae when infesting the same plant, but it is unknown whether this is facilitated by the defenses of the plant. We assessed the extent to which a secondary infestation by a competitor affects local plant defense responses (phytohormones and defense genes), mite gene expression and mite performance. We observed that T. evansi switches to hyper-suppression of defenses after its tomato host is also invaded by its natural competitor T. urticae. Jasmonate (JA) and salicylate (SA) defenses were suppressed more strongly, albeit only locally at the feeding site of T. evansi, upon introduction of T. urticae to the infested leaflet. The hyper-suppression of defenses coincided with increased expression of T. evansi genes coding for salivary defense-suppressing effector proteins and was paralleled by an increased reproductive performance. Together, these observations suggest that T. evansi overcompensates its reproduction through hyper-suppression of plant defenses in response to nearby competitors. We hypothesize that the competitor-induced overcompensation promotes competitive population growth of T. evansi on tomato. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.
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Directory of Open Access Journals (Sweden)
Stella E Autenrieth
2012-02-01
Full Text Available Dendritic cells (DCs as professional antigen-presenting cells play an important role in the initiation and modulation of the adaptive immune response. However, their role in the innate immune response against bacterial infections is not completely defined. Here we have analyzed the role of DCs and their impact on the innate anti-bacterial host defense in an experimental infection model of Yersinia enterocolitica (Ye. We used CD11c-diphtheria toxin (DT mice to deplete DCs prior to severe infection with Ye. DC depletion significantly increased animal survival after Ye infection. The bacterial load in the spleen of DC-depleted mice was significantly lower than that of control mice throughout the infection. DC depletion was accompanied by an increase in the serum levels of CXCL1, G-CSF, IL-1α, and CCL2 and an increase in the numbers of splenic phagocytes. Functionally, splenocytes from DC-depleted mice exhibited an increased bacterial killing capacity compared to splenocytes from control mice. Cellular studies further showed that this was due to an increased production of reactive oxygen species (ROS by neutrophils. Adoptive transfer of neutrophils from DC-depleted mice into control mice prior to Ye infection reduced the bacterial load to the level of Ye-infected DC-depleted mice, suggesting that the increased number of phagocytes with additional ROS production account for the decreased bacterial load. Furthermore, after incubation with serum from DC-depleted mice splenocytes from control mice increased their bacterial killing capacity, most likely due to enhanced ROS production by neutrophils, indicating that serum factors from DC-depleted mice account for this effect. In summary, we could show that DC depletion triggers phagocyte accumulation in the spleen and enhances their anti-bacterial killing capacity upon bacterial infection.
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Defenses and morality: Adam Smith, Sigmund Freud, and contemporary psychoanalysis.
Gabrinetti, Paul A; Özler, Sule
2014-10-01
In this paper we follow the development and transmission of moral learning from Adam Smith's impartial spectator to Sigmund Freud's superego and then to contemporary psychoanalysis. We argue that defenses are an integral component in the acquisition of any moral system. Elaborating on this argument, we assert that there is a progression from defensive systems that are "closed" to defensive systems that are "open," as defined in a recent work by Novick and Novick. The former system is "static, avoids reality, and is characterized by power dynamics, sadomasochism, and omnipotent defense." The latter, on the other hand, is a system that allows for "joy, creativity, spontaneity, love and it is attuned to reality." Furthermore, while Smith and Freud's systems are more one-person systems of defense, contemporary psychoanalysis has moved to more of a two-person system.
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The potential for host switching via ecological fitting in the emerald ash borer-host plant system.
Cipollini, Don; Peterson, Donnie L
2018-02-27
The traits used by phytophagous insects to find and utilize their ancestral hosts can lead to host range expansions, generally to closely related hosts that share visual and chemical features with ancestral hosts. Host range expansions often result from ecological fitting, which is the process whereby organisms colonize and persist in novel environments, use novel resources, or form novel associations with other species because of the suites of traits that they carry at the time they encounter the novel environment. Our objective in this review is to discuss the potential and constraints on host switching via ecological fitting in emerald ash borer, Agrilus planipennis, an ecologically and economically important invasive wood boring beetle. Once thought of as an ash (Fraxinus spp.) tree specialist, recent studies have revealed a broader potential host range than was expected for this insect. We discuss the demonstrated host-use capabilities of this beetle, as well as the potential for and barriers to the adoption of additional hosts by this beetle. We place our observations in the context of biochemical mechanisms that mediate the interaction of these beetles with their host plants and discuss whether evolutionary host shifts are a possible outcome of the interaction of this insect with novel hosts.
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Directory of Open Access Journals (Sweden)
Vladimir López
2016-03-01
Full Text Available Mycobacteria of the Mycobacterium tuberculosis complex (MTBC greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB. In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB- and M. bovis-infected young (TB+ and adult animals with different infection status [TB lesions localized in the head (TB+ or affecting multiple organs (TB++]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to
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López, Vladimir; Villar, Margarita; Queirós, João; Vicente, Joaquín; Mateos-Hernández, Lourdes; Díez-Delgado, Iratxe; Contreras, Marinela; Alves, Paulo C; Alberdi, Pilar; Gortázar, Christian; de la Fuente, José
2016-03-01
Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to limit pathogen
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Directory of Open Access Journals (Sweden)
Bentancor Marcel
2007-10-01
Full Text Available Abstract Background Vascular plants respond to pathogens by activating a diverse array of defense mechanisms. Studies with these plants have provided a wealth of information on pathogen recognition, signal transduction and the activation of defense responses. However, very little is known about the infection and defense responses of the bryophyte, Physcomitrella patens, to well-studied phytopathogens. The purpose of this study was to determine: i whether two representative broad host range pathogens, Erwinia carotovora ssp. carotovora (E.c. carotovora and Botrytis cinerea (B. cinerea, could infect Physcomitrella, and ii whether B. cinerea, elicitors of a harpin (HrpN producing E.c. carotovora strain (SCC1 or a HrpN-negative strain (SCC3193, could cause disease symptoms and induce defense responses in Physcomitrella. Results B. cinerea and E.c. carotovora were found to readily infect Physcomitrella gametophytic tissues and cause disease symptoms. Treatments with B. cinerea spores or cell-free culture filtrates from E.c. carotovoraSCC1 (CF(SCC1, resulted in disease development with severe maceration of Physcomitrella tissues, while CF(SCC3193 produced only mild maceration. Although increased cell death was observed with either the CFs or B. cinerea, the occurrence of cytoplasmic shrinkage was only visible in Evans blue stained protonemal cells treated with CF(SCC1 or inoculated with B. cinerea. Most cells showing cytoplasmic shrinkage accumulated autofluorescent compounds and brown chloroplasts were evident in a high proportion of these cells. CF treatments and B. cinerea inoculation induced the expression of the defense-related genes: PR-1, PAL, CHS and LOX. Conclusion B. cinerea and E.c. carotovora elicitors induce a defense response in Physcomitrella, as evidenced by enhanced expression of conserved plant defense-related genes. Since cytoplasmic shrinkage is the most common morphological change observed in plant PCD, and that harpins and B
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Air defense planning for an area with the use of very short range air defense sets
Directory of Open Access Journals (Sweden)
Tadeusz Pietkiewicz
2017-12-01
Full Text Available This paper presents a heuristic method of planning the deployment of very short-range anti-air missile and artillery sets (VSHORAD around an area (‘protected area’ in order to protect it. A function dependent on the distance between the earliest feasible points of destroying targets and the centre of the protected area was taken as an objective function. This is a different indicator from those commonly used in the literature, and based on the likelihood of a defense zone penetration by means of an air attack (MAA: the kill probability of the MAA and the probability of area losses. The model constraints resulted directly from the restrictions imposed by real air defense systems and the nature of the area being defended. This paper assumes that the VSHORAD system operates as a part of a general, superordinate air defense command and control system based on the idea of network-centric warfare, which provides the VSHORAD system with a recognized air picture, air defense plans, and combat mission specifications. The presented method has been implemented. The final part of the paper presents the computational results. Keywords: optimal planning, air defense system, area installation protection, deployment of very short range anti-air missile and artillery sets (VSHORAD
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Cell-autonomous defense, re-organization and trafficking of membranes in plant-microbe interactions.
Dörmann, Peter; Kim, Hyeran; Ott, Thomas; Schulze-Lefert, Paul; Trujillo, Marco; Wewer, Vera; Hückelhoven, Ralph
2014-12-01
Plant cells dynamically change their architecture and molecular composition following encounters with beneficial or parasitic microbes, a process referred to as host cell reprogramming. Cell-autonomous defense reactions are typically polarized to the plant cell periphery underneath microbial contact sites, including de novo cell wall biosynthesis. Alternatively, host cell reprogramming converges in the biogenesis of membrane-enveloped compartments for accommodation of beneficial bacteria or invasive infection structures of filamentous microbes. Recent advances have revealed that, in response to microbial encounters, plasma membrane symmetry is broken, membrane tethering and SNARE complexes are recruited, lipid composition changes and plasma membrane-to-cytoskeleton signaling is activated, either for pre-invasive defense or for microbial entry. We provide a critical appraisal on recent studies with a focus on how plant cells re-structure membranes and the associated cytoskeleton in interactions with microbial pathogens, nitrogen-fixing rhizobia and mycorrhiza fungi. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.
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Host density increases parasite recruitment but decreases host risk in a snail-trematode system.
Buck, J C; Hechinger, R F; Wood, A C; Stewart, T E; Kuris, A M; Lafferty, K D
2017-08-01
Most species aggregate in local patches. High host density in patches increases contact rate between hosts and parasites, increasing parasite transmission success. At the same time, for environmentally transmitted parasites, high host density can decrease infection risk to individual hosts, because infective stages are divided among all hosts in a patch, leading to safety in numbers. We tested these predictions using the California horn snail, Cerithideopsis californica (=Cerithidea californica), which is the first intermediate host for at least 19 digenean trematode species in California estuaries. Snails become infected by ingesting trematode eggs or through penetration by free-swimming miracidia that hatch from trematode eggs deposited with final-host (bird or mammal) feces. This complex life cycle decouples infective-stage production from transmission, raising the possibility of an inverse relationship between host density and infection risk at local scales. In a field survey, higher snail density was associated with increased trematode (infected snail) density, but decreased trematode prevalence, consistent with either safety in numbers, parasitic castration, or both. To determine the extent to which safety in numbers drove the negative snail-density-trematode-prevalence association, we manipulated uninfected snail density in 83 cages at eight sites within Carpinteria Salt Marsh (California, USA). At each site, we quantified snail density and used data on final-host (bird and raccoon) distributions to control for between-site variation in infective-stage supply. After three months, overall trematode infections per cage increased with snail biomass density. For egg-transmitted trematodes, per-snail infection risk decreased with snail biomass density in the cage and surrounding area, whereas per-snail infection risk did not decrease for miracidium-transmitted trematodes. Furthermore, both trematode recruitment and infection risk increased with infective
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Gehring, Christoph A.
2010-09-01
Immunologic evidence has suggested the presence of biologically active natriuretic peptide (NPs) hormones in plants because antiatrial NP antibodies affinity purify biologically active plant NPs (PNP). In the model plant, an Arabidopsis thaliana PNP (AtPNP-A) has been identified and characterized. AtPNP-A belongs to a novel class of molecules that share some similarity with the cell wall loosening expansins but do not contain the carbohydrate-binding wall anchor thus suggesting that PNPs and atrial natriuretic peptides are heterologs. AtPNP-A acts systemically, and this is consistent with its localization in the apoplastic extracellular space and the conductive tissue. Furthermore, AtPNP-A signals via the second messenger cyclic guanosine 3′,5′-monophosphate and modulates ion and water transport and homeostasis. It also plays a critical role in host defense against pathogens. AtPNP-A can be classified as novel paracrine plant hormone because it is secreted into the apoplastic space in response to stress and can enhance its own expression. Interestingly, purified recombinant PNP induces apo-ptosis in a dose-dependent manner and was most effective on cardiac myoblast cell lines. Because PNP is mimicking the effect of ANP in some instances, PNP may prove to provide useful leads for development of novel therapeutic NPs. Copyright © 2013 by The American Federation for Medical Research.
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Gehring, Christoph A; Irving, Helen R.
2010-01-01
Immunologic evidence has suggested the presence of biologically active natriuretic peptide (NPs) hormones in plants because antiatrial NP antibodies affinity purify biologically active plant NPs (PNP). In the model plant, an Arabidopsis thaliana PNP (AtPNP-A) has been identified and characterized. AtPNP-A belongs to a novel class of molecules that share some similarity with the cell wall loosening expansins but do not contain the carbohydrate-binding wall anchor thus suggesting that PNPs and atrial natriuretic peptides are heterologs. AtPNP-A acts systemically, and this is consistent with its localization in the apoplastic extracellular space and the conductive tissue. Furthermore, AtPNP-A signals via the second messenger cyclic guanosine 3′,5′-monophosphate and modulates ion and water transport and homeostasis. It also plays a critical role in host defense against pathogens. AtPNP-A can be classified as novel paracrine plant hormone because it is secreted into the apoplastic space in response to stress and can enhance its own expression. Interestingly, purified recombinant PNP induces apo-ptosis in a dose-dependent manner and was most effective on cardiac myoblast cell lines. Because PNP is mimicking the effect of ANP in some instances, PNP may prove to provide useful leads for development of novel therapeutic NPs. Copyright © 2013 by The American Federation for Medical Research.
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Directory of Open Access Journals (Sweden)
Namgyu Kim
2016-10-01
Full Text Available Tomato yellow leaf curl virus (TYLCV, a member of the genus Begomovirus, is one of the most important viruses of cultivated tomatoes worldwide, mainly causing yellowing and curling of leaves with stunting in plants. TYLCV causes severe problems in sub-tropical and tropical countries, as well as in Korea. However, the mechanism of TYLCV infection remains unclear, although the function of each viral component has been identified. TYLCV C4 codes for a small protein involved in various cellular functions, including symptom determination, gene silencing, viral movement, and induction of the plant defense response. In this study, through yeast-two hybrid screenings, we identified TYLCV C4-interacting host proteins from both healthy and symptom-exhibiting tomato tissues, to determine the role of TYLCV C4 proteins in the infection processes. Comparative analyses of 28 proteins from healthy tissues and 36 from infected tissues showing interactions with TYLCV C4 indicated that TYLCV C4 mainly interacts with host proteins involved in translation, ubiquitination, and plant defense, and most interacting proteins differed between the two tissues but belong to similar molecular functional categories. Four proteins—two ribosomal proteins, S-adenosyl-L-homocysteine hydrolase, and 14-3-3 family protein—were detected in both tissues. Furthermore, the identified proteins in symptom-exhibiting tissues showed greater involvement in plant defenses. Some are key regulators, such as receptor-like kinases and pathogenesis-related proteins, of plant defenses. Thus, TYLCV C4 may contribute to the suppression of host defense during TYLCV infection and be involved in ubiquitination for viral infection.
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Symbiotic and antibiotic interactions between gut commensal microbiota and host immune system
Directory of Open Access Journals (Sweden)
Mantas Kazimieras Malys
2015-01-01
Full Text Available The human gut commensal microbiota forms a complex population of microorganisms that survive by maintaining a symbiotic relationship with the host. Amongst the metabolic benefits it brings, formation of adaptive immune system and maintenance of its homeostasis are functions that play an important role. This review discusses the integral elements of commensal microbiota that stimulate responses of different parts of the immune system and lead to health or disease. It aims to establish conditions and factors that contribute to gut commensal microbiota's transformation from symbiotic to antibiotic relationship with human. We suggest that the host-microbiota relationship has been evolved to benefit both parties and any changes that may lead to disease, are not due to unfriendly properties of the gut microbiota but due to host genetics or environmental changes such as diet or infection.
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Directory of Open Access Journals (Sweden)
Yao Qin
2017-01-01
Full Text Available Infectious bursal disease (IBD is an acute, highly contagious and immunosuppressive poultry disease caused by IBD virus (IBDV. The consequent immunosuppression increases susceptibility to other infectious diseases and the risk of subsequent vaccination failure as well. Since the genome of IBDV is relatively small, it has a limited number of proteins inhibiting the cellular antiviral responses and acting as destroyers to the host defense system. Thus, these virulence factors must be multifunctional in order to complete the viral replication cycle in a host cell. Insights into the roles of these viral proteins along with their multiple cellular targets in different pathways will give rise to a rational design for safer and effective vaccines. Here we summarize the recent findings that focus on the virus–cell interactions during IBDV infection at the protein level.
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Directory of Open Access Journals (Sweden)
Verdugo, JA.
2016-01-01
Full Text Available Introduction. Insect-plant interactions are affected directly or indirectly by stress factors. The effect of environmental resource availability on insect-plant interactions is here reviewed. Subsequently, the analysis focuses on aphid-host plant interactions, particularly in the system composed by the green peach aphid Myzus persicae and its primary host plant Prunus persica. Literature. Plant defenses arise in two ways: resistance and tolerance, both are affected by abiotic factors. The information gathered from studies (n = 29 on plant-aphid interactions addressing the reduction in water availability on plant resistance, showed that in 41,4% of the studies, drought stress elicits lower resistance, while 34.5%, 20.1% and 3.4%, showed higher, no change and conditional effects on plant resistance, respectively. Conclusions. Water stress elicits mixed effects on plant resistance to aphids. However, the literature review also suggests that cultural practices play a role in the fate of the peach-aphid interactions, whereas the development of predictive models aimed to assist crop-pest management systems still requires more basic information. Aphid responses to plant defenses under stressed conditions are still largely unexplored.
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Directory of Open Access Journals (Sweden)
Xiangfang Zeng
Full Text Available Dietary modulation of the synthesis of endogenous host defense peptides (HDPs represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections. However, HDP regulation by dietary compounds such as butyrate is species-dependent. To examine whether butyrate could induce HDP expression in pigs, we evaluated the expressions of a panel of porcine HDPs in IPEC-J2 intestinal epithelial cells, 3D4/31 macrophages, and primary monocytes in response to sodium butyrate treatment by real-time PCR. We revealed that butyrate is a potent inducer of multiple, but not all, HDP genes. Porcine β-defensin 2 (pBD2, pBD3, epididymis protein 2 splicing variant C (pEP2C, and protegrins were induced markedly in response to butyrate, whereas pBD1 expression remained largely unaltered in any cell type. Additionally, a comparison of the HDP-inducing efficacy among saturated free fatty acids of different aliphatic chain lengths revealed that fatty acids containing 3-8 carbons showed an obvious induction of HDP expression in IPEC-J2 cells, with butyrate being the most potent and long-chain fatty acids having only a marginal effect. We further investigated a panel of butyrate analogs for their efficacy in HDP induction, and found glyceryl tributyrate, benzyl butyrate, and 4-phenylbutyrate to be comparable with butyrate. Identification of butyrate and several analogs with a strong capacity to induce HDP gene expression in pigs provides attractive candidates for further evaluation of their potential as novel alternatives to antibiotics in augmenting innate immunity and disease resistance of pigs.
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Distance and sex determine host plant choice by herbivorous beetles.
Directory of Open Access Journals (Sweden)
Daniel J Ballhorn
Full Text Available Plants respond to herbivore damage with the release of volatile organic compounds (VOCs. This indirect defense can cause ecological costs when herbivores themselves use VOCs as cues to localize suitable host plants. Can VOCs reliably indicate food plant quality to herbivores?We determined the choice behavior of herbivorous beetles (Chrysomelidae: Gynandrobrotica guerreroensis and Cerotoma ruficornis when facing lima bean plants (Fabaceae: Phaseolus lunatus with different cyanogenic potential, which is an important constitutive direct defense. Expression of inducible indirect defenses was experimentally manipulated by jasmonic acid treatment at different concentrations. The long-distance responses of male and female beetles to the resulting induced plant volatiles were investigated in olfactometer and free-flight experiments and compared to the short-distance decisions of the same beetles in feeding trials.Female beetles of both species were repelled by VOCs released from all induced plants independent of the level of induction. In contrast, male beetles were repelled by strongly induced plants, showed no significant differences in choice behavior towards moderately induced plants, but responded positively to VOCs released from little induced plants. Thus, beetle sex and plant VOCs had a significant effect on host searching behavior. By contrast, feeding behavior of both sexes was strongly determined by the cyanogenic potential of leaves, although females again responded more sensitively than males. Apparently, VOCs mainly provide information to these beetles that are not directly related to food quality. Being induced by herbivory and involved in indirect plant defense, such VOCs might indicate the presence of competitors and predators to herbivores. We conclude that plant quality as a food source and finding a potentially enemy-free space is more important for female than for male insect herbivores, whereas the presence of a slightly damaged
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Peterson, Julie A; Ode, Paul J; Oliveira-Hofman, Camila; Harwood, James D
2016-01-01
Crop plants exhibit a wide diversity of defensive traits and strategies to protect themselves from damage by herbivorous pests and disease. These defensive traits may be naturally occurring or artificially selected through crop breeding, including introduction via genetic engineering. While these traits can have obvious and direct impacts on herbivorous pests, many have profound effects on higher trophic levels, including the natural enemies of herbivores. Multi-trophic effects of host plant resistance have the potential to influence, both positively and negatively, biological control. Plant defense traits can influence both the numerical and functional responses of natural enemies; these interactions can be semiochemically, plant toxin-, plant nutrient-, and/or physically mediated. Case studies involving predators, parasitoids, and pathogens of crop pests will be presented and discussed. These diverse groups of natural enemies may respond differently to crop plant traits based on their own unique biology and the ecological niches they fill. Genetically modified crop plants that have been engineered to express transgenic products affecting herbivorous pests are an additional consideration. For the most part, transgenic plant incorporated protectant (PIP) traits are compatible with biological control due to their selective toxicity to targeted pests and relatively low non-target impacts, although transgenic crops may have indirect effects on higher trophic levels and arthropod communities mediated by lower host or prey number and/or quality. Host plant resistance and biological control are two of the key pillars of integrated pest management; their potential interactions, whether they are synergistic, complementary, or disruptive, are key in understanding and achieving sustainable and effective pest management.
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Directory of Open Access Journals (Sweden)
Julie A Peterson
2016-11-01
Full Text Available Crop plants exhibit a wide diversity of defensive traits and strategies to protect themselves from damage by herbivorous pests and disease. These defensive traits may be naturally occurring or artificially selected through crop breeding, including introduction via genetic engineering. While these traits can have obvious and direct impacts on herbivorous pests, many have profound effects on higher trophic levels, including the natural enemies of herbivores. Multi-trophic effects of host plant resistance have the potential to influence, both positively and negatively, biological control. Plant defense traits can influence both the numerical and functional responses of natural enemies; these interactions can be semiochemically-, plant toxin-, plant nutrient-, and/or physically-mediated. Case studies involving predators, parasitoids, and pathogens of crop pests will be presented and discussed. These diverse groups of natural enemies may respond differently to crop plant traits based on their own unique biology and the ecological niches they fill. Genetically modified crop plants that have been engineered to express transgenic products affecting herbivorous pests are an additional consideration. For the most part, transgenic plant incorporated protectant (PIP traits are compatible with biological control due to their selective toxicity to targeted pests and relatively low non-target impacts, although transgenic crops may have indirect effects on higher trophic levels and arthropod communities mediated by lower host or prey number and/or quality. Host plant resistance and biological control are two of the key pillars of integrated pest management; their potential interactions, whether they are synergistic, complementary, or disruptive, are key in understanding and achieving sustainable and effective pest management.
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National Research Council Canada - National Science Library
McKinney, Terry
1994-01-01
This is the final in a series of three audits of management controls over the operating systems and security software used by the information processing centers that support the Defense Finance and Accounting Centers (DFAS...
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The phage-host arms race: Shaping the evolution of microbes
Energy Technology Data Exchange (ETDEWEB)
Stern, Adi [Weizmann Inst. of Science, Rehovot (Israel). Dept. of Molecular Genetics; Sorek, Rotem [Weizmann Inst. of Science, Rehovot (Israel). Dept. of Molecular Genetics
2010-10-26
Bacteria, the most abundant organisms on the planet, are outnumbered by a factor of 10 to 1 by phages that infect them. Faced with the rapid evolution and turnover of phage particles, bacteria have evolved various mechanisms to evade phage infection and killing, leading to an evolutionary arms race. The extensive co-evolution of both phage and host has resulted in considerable diversity on the part of both bacterial and phage defensive and offensive strategies. In this paper, we discuss the unique and common features of phage resistance mechanisms and their role in global biodiversity. Finally, the commonalities between defense mechanisms suggest avenues for the discovery of novel forms of these mechanisms based on their evolutionary traits.
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Dacer, Marc; Kargl, Frank; König, Hartmut; Valdes, Alfonso
2014-01-01
This report documents the program and the outcomes of Dagstuhl Seminar 14292 “Network Attack Detection and Defense: Securing Industrial Control Systems for Critical Infrastructures”. The main objective of the seminar was to discuss new approaches and ideas for securing industrial control systems. It
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Cost Effective Regional Ballistic Missile Defense
2016-02-16
deploying advanced air defense systems18, such as the Russian S-300 and S-500, and concealing them in hardened, camouflaged sites, such as extensive... Russian objections to the European Phased Adaptive Approach (EPAA) and fund homeland defense priorities.39 Furthermore, the PTSS system was also... Theatre Ballistic Missile Defence Capability Becomes Operational,” Jane’s Missiles & Rockets, 1 February 2011. 55 Joseph W. Kirschbaum, REGIONAL MISSILE
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Adaptation to the Host Environment by Plant-Pathogenic Fungi.
van der Does, H Charlotte; Rep, Martijn
2017-08-04
Many fungi can live both saprophytically and as endophyte or pathogen inside a living plant. In both environments, complex organic polymers are used as sources of nutrients. Propagation inside a living host also requires the ability to respond to immune responses of the host. We review current knowledge of how plant-pathogenic fungi do this. First, we look at how fungi change their global gene expression upon recognition of the host environment, leading to secretion of effectors, enzymes, and secondary metabolites; changes in metabolism; and defense against toxic compounds. Second, we look at what is known about the various cues that enable fungi to sense the presence of living plant cells. Finally, we review literature on transcription factors that participate in gene expression in planta or are suspected to be involved in that process because they are required for the ability to cause disease.
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Interleukin-1 signaling is essential for host defense during murine pulmonary tuberculosis
Juffermans, N. P.; Florquin, S.; Camoglio, L.; Verbon, A.; Kolk, A. H.; Speelman, P.; van Deventer, S. J.; van der Poll, T.
2000-01-01
Interleukin (IL)-1 signaling is required for the containment of infections with intracellular microorganisms, such as Listeria monocytogenes and Leishmania major. To determine the role of IL-1 in the host response to tuberculosis, we infected IL-1 type I receptor-deficient (IL-1R(-/-)) mice, in
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Repeatability of host female and male aggression towards a brood parasite
Czech Academy of Sciences Publication Activity Database
Trnka, A.; Požgayová, Milica; Samaš, P.; Honza, Marcel
2013-01-01
Roč. 119, č. 10 (2013), s. 907-917 ISSN 0179-1613 R&D Projects: GA ČR(CZ) GAP506/12/2404 Institutional support: RVO:68081766 Keywords : Cuckoo Cuculus canorus * Great reed warblers * Nest defense * Behavioral syndromes * Plumage polymorphism * Enemy recognition * Potential hosts * Practical guide * Zebra finches Subject RIV: EG - Zoology Impact factor: 1.556, year: 2013
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The natural defense system and the normative self model [version 1; referees: 2 approved
Directory of Open Access Journals (Sweden)
Philippe Kourilsky
2016-05-01
Full Text Available Infectious agents are not the only agressors, and the immune system is not the sole defender of the organism. In an enlarged perspective, the ‘normative self model’ postulates that a ‘natural defense system’ protects man and other complex organisms against the environmental and internal hazards of life, including infections and cancers. It involves multiple error detection and correction mechanisms that confer robustness to the body at all levels of its organization. According to the model, the self relies on a set of physiological norms, and NONself (meaning : Non Obedient to the Norms of the self is anything ‘off-norms’. The natural defense system comprises a set of ‘civil defenses’ (to which all cells in organs and tissues contribute, and a ‘professional army ‘, made of a smaller set of mobile cells. Mobile and non mobile cells differ in their tuning abilities. Tuning extends the recognition capabilities of NONself by the mobile cells, which increase their defensive function. To prevent them to drift, which would compromise self/NONself discrimination, the more plastic mobile cells need to periodically refer to the more stable non mobile cells to keep within physiological standards.
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Yersinia pestis and host macrophages: immunodeficiency of mouse macrophages induced by YscW.
Bi, Yujing; Du, Zongmin; Han, Yanping; Guo, Zhaobiao; Tan, Yafang; Zhu, Ziwen; Yang, Ruifu
2009-09-01
The virulence of the pathogenic Yersinia species depends on a plasmid-encoded type III secretion system (T3SS) that transfers six Yersinia outer protein (Yop) effector proteins into the cytoplasm of eukaryotic cells, leading to disruption of host defence mechanisms. It is shown in this study that Yersinia pestis YscW, a protein of the T3SS injectisome, contributes to the induction of a deficiency in phagocytosis in host macrophages and a reduction in their antigen-presenting capacity. A Y. pestis strain lacking yscW had no effect on uptake by host macrophages. In mice infected with wild-type Y. pestis, the yscW mutant or a complement strain, immunodeficiency was observed in host macrophages compared with those from uninfected mice. However, the phagocytosis and antigen presenting capacities of macrophages infected by yscW mutant strain both in vivo and in vitro were significantly higher than those by wild type strain. Consistent with this finding, when YscW was expressed in the RAW264.7 macrophage cell line, phagocytosis and antigen-presenting capacities were significantly lower than those of the control groups. These results indicate that Y. pestis YscW may directly induce immunodeficiency in murine macrophages by crippling their phagocytosis and antigen-presenting capacities. These data provide evidences to Y. pestis pathogenesis that some proteins in T3SS injectisome, such as YscW protein, might play independent roles in disrupting host defense apart from their known functions.
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Whole body exposure to low-dose γ-radiation enhances the antioxidant defense system
International Nuclear Information System (INIS)
Pathak, C.M.; Avti, P.K.; Khanduja, K.L.; Sharma, S.C.
2008-01-01
It is believed that the extent of cellular damage by low- radiation dose is proportional to the effects observed at high radiation dose as per the Linear-No-Threshold (LNT) hypothesis. However, this notion may not be true at low-dose radiation exposure in the living system. Recent evidence suggest that the living organisms do not respond to ionizing radiations in a linear manner in the low dose range 0.01-0.5Gy and rather restore the homeostasis both in vivo and in vitro by normal physiological mechanisms such as cellular and DNA repair processes, immune reactions, antioxidant defense, adaptive responses, activation of immune functions, stimulation of growth etc. In this study, we have attempted to find the critical radiation dose range and the post irradiation period during which the antioxidant defense systems in the lungs, liver and kidneys remain stimulated in these organs after whole body exposure of the animals to low-dose radiation
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Role of immune system in type 1 diabetes mellitus pathogenesis.
Szablewski, Leszek
2014-09-01
The immune system is the body's natural defense system against invading pathogens. It protects the body from infection and works to communicate an individual's well-being through a complex network of interconnected cells and cytokines. This system is an associated host defense. An uncontrolled immune system has the potential to trigger negative complications in the host. Type 1 diabetes results from the destruction of pancreatic β-cells by a β-cell-specific autoimmune process. Examples of β-cell autoantigens are insulin, glutamic acid decarboxylase, tyrosine phosphatase, and insulinoma antigen. There are many autoimmune diseases, but type 1 diabetes mellitus is one of the well-characterized autoimmune diseases. The mechanisms involved in the β-cell destruction are still not clear; it is generally believed that β-cell autoantigens, macrophages, dendritic cells, B lymphocytes, and T lymphocytes are involved in the β-cell-specific autoimmune process. It is necessary to determine what exact factors are causing the immune system to become unregulated in such a manner as to promote an autoimmune response. Copyright © 2014 Elsevier B.V. All rights reserved.
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2012-12-31
... Security Cooperation Agency, the Defense Security Service, the Defense Threat Reduction Agency, the Missile... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 202 RIN 0750-AH81 Defense...: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY: DoD is...
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Directory of Open Access Journals (Sweden)
Joshua eMessinger
2015-12-01
Full Text Available Chlamydiae, obligate intracellular bacteria, cause significant human and veterinary associated diseases. Having emerged an estimated 700-million years ago, these bacteria have twice adapted to humans as a host species, causing sexually transmitted infection (C. trachomatis and respiratory associated disease (C. pneumoniae. The principle mechanism of host cell defense against these intracellular bacteria is the induction of cell death via apoptosis. However, in the arms race of co-evolution, Chlamydiae have developed mechanisms to promote cell viability and inhibit cell death. Herein we examine the impact of Chlamydiae infection across multiple host species on transcription of anti-apoptotic genes. We found mostly distinct patterns of gene expression (Mcl1 and cIAPs elicited by each pathogen-host pair indicating Chlamydiae infection across host species boundaries does not induce a universally shared host response. Understanding species specific host-pathogen interactions is paramount to deciphering how potential pathogens become emerging diseases.
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A Recommender System in the Cyber Defense Domain
2014-03-27
monitoring software is a java based program sending updates to the database on the sensor machine. The host monitoring program gathers information about...3.2.2 Database. A MySQL database located on the sensor machine acts as the storage for the sensors on the network. Snort, Nmap, vulnerability scores, and...machine with the IDS and the recommender is labeled “sensor”. The recommender system code is written in java and compiled using java version 1.6.024
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2012-06-29
... market research/industry communication. In 2008, the Office of Management and Budget and Office of... unique or brand name specifications, and enhancing acquisition planning. In 2010, the Government... strategic defense capabilities, because of a shift to ``lowest price possible.'' Further, according to this...
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Insect endosymbionts influence many important metabolic and developmental processes of their host. It has been speculated that they may also help to manipulate and suppress plant defenses to the benefit of herbivores. Recently, endosymbionts of the root herbivore Diabrotica virgifera virgifera have ...
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Second Line of Defense Spares Program
Energy Technology Data Exchange (ETDEWEB)
Henderson, Dale L.; Holmes, Aimee E.; Muller, George; Mercier, Theresa M.; Brigantic, Robert T.; Perkins, Casey J.; Cooley, Scott K.; Thorsen, Darlene E.
2012-11-20
During Fiscal Year 2012, a team from the Pacific Northwest National Laboratory (PNNL) conducted an assessment and analysis of the Second Line of Defense (SLD) Sustainability spare parts program. Spare parts management touches many aspects of the SLD Sustainability Program including contracting and integration of Local Maintenance Providers (LMP), equipment vendors, analyses and metrics on program performance, system state of health, and maintenance practices. Standardized spares management will provide better data for decisions during site transition phase and will facilitate transition to host country sustainability ownership. The effort was coordinated with related SLD Sustainability Program initiatives, including a configuration items baselining initiative, a metrics initiative, and a maintenance initiative. The spares study has also led to pilot programs for sourcing alternatives that include regional intermediate inventories and partnering agreements that leverage existing supply chains. Many partners from the SLD Sustainability program contributed to and were consulted in the course of the study. This document provides a description of the findings, recommendations, and implemented solutions that have resulted from the study.
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Skip to main content (Press Enter). Toggle navigation Defense Business Board Search Search Defense Business Board: Search Search Defense Business Board: Search Defense Business Board Business Excellence in Defense of the Nation Defense Business Board Home Charter Members Meetings Studies Contact Us The Defense
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Cellular Aspects of Shigella Pathogenesis: Focus on the Manipulation of Host Cell Processes.
Killackey, Samuel A; Sorbara, Matthew T; Girardin, Stephen E
2016-01-01
Shigella is a Gram-negative bacterium that is responsible for shigellosis. Over the years, the study of Shigella has provided a greater understanding of how the host responds to bacterial infection, and how bacteria have evolved to effectively counter the host defenses. In this review, we provide an update on some of the most recent advances in our understanding of pivotal processes associated with Shigella infection, including the invasion into host cells, the metabolic changes that occur within the bacterium and the infected cell, cell-to-cell spread mechanisms, autophagy and membrane trafficking, inflammatory signaling and cell death. This recent progress sheds a new light into the mechanisms underlying Shigella pathogenesis, and also more generally provides deeper understanding of the complex interplay between host cells and bacterial pathogens in general.
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Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice
de Stoppelaar, Sacha F.; van 't Veer, Cornelis; Claushuis, Theodora A. M.; Albersen, Bregje J. A.; Roelofs, Joris J. T. H.; van der Poll, Tom
2014-01-01
Thrombocytopenia is a common finding in sepsis and associated with a worse outcome. We used a mouse model of pneumonia-derived sepsis caused by the human pathogen Klebsiella pneumoniae to study the role of platelets in host response to sepsis. Platelet counts (PCs) were reduced to less than a median
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Directory of Open Access Journals (Sweden)
Mark Eppinger
2006-07-01
Full Text Available Helicobacter pylori infection of humans is so old that its population genetic structure reflects that of ancient human migrations. A closely related species, Helicobacter acinonychis, is specific for large felines, including cheetahs, lions, and tigers, whereas hosts more closely related to humans harbor more distantly related Helicobacter species. This observation suggests a jump between host species. But who ate whom and when did it happen? In order to resolve this question, we determined the genomic sequence of H. acinonychis strain Sheeba and compared it to genomes from H. pylori. The conserved core genes between the genomes are so similar that the host jump probably occurred within the last 200,000 (range 50,000-400,000 years. However, the Sheeba genome also possesses unique features that indicate the direction of the host jump, namely from early humans to cats. Sheeba possesses an unusually large number of highly fragmented genes, many encoding outer membrane proteins, which may have been destroyed in order to bypass deleterious responses from the feline host immune system. In addition, the few Sheeba-specific genes that were found include a cluster of genes encoding sialylation of the bacterial cell surface carbohydrates, which were imported by horizontal genetic exchange and might also help to evade host immune defenses. These results provide a genomic basis for elucidating molecular events that allow bacteria to adapt to novel animal hosts.
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Directory of Open Access Journals (Sweden)
Rosalind A. Gilbert
2017-12-01
Full Text Available The rumen is known to harbor dense populations of bacteriophages (phages predicted to be capable of infecting a diverse range of rumen bacteria. While bacterial genome sequencing projects are revealing the presence of phages which can integrate their DNA into the genome of their host to form stable, lysogenic associations, little is known of the genetics of phages which utilize lytic replication. These phages infect and replicate within the host, culminating in host lysis, and the release of progeny phage particles. While lytic phages for rumen bacteria have been previously isolated, their genomes have remained largely uncharacterized. Here we report the first complete genome sequences of lytic phage isolates specifically infecting three genera of rumen bacteria: Bacteroides, Ruminococcus, and Streptococcus. All phages were classified within the viral order Caudovirales and include two phage morphotypes, representative of the Siphoviridae and Podoviridae families. The phage genomes displayed modular organization and conserved viral genes were identified which enabled further classification and determination of closest phage relatives. Co-examination of bacterial host genomes led to the identification of several genes responsible for modulating phage:host interactions, including CRISPR/Cas elements and restriction-modification phage defense systems. These findings provide new genetic information and insights into how lytic phages may interact with bacteria of the rumen microbiome.
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Review of defense display research programs
Tulis, Robert W.; Hopper, Darrel G.; Morton, David C.; Shashidhar, Ranganathan
2001-09-01
Display research has comprised a substantial portion of the defense investment in new technology for national security for the past 13 years. These investments have been made by the separate service departments and, especially, via several Defense Research Projects Agency (DARPA) programs, known collectively as the High Definition Systems (HDS) Program (which ended in 2001) and via the Office of the Secretary of Defense (OSD) Defense Production Act (DPA) Title III Program (efforts ended in 2000). Using input from the Army, Navy, and Air Force to focus research and identify insertion opportunities, DARPA and the Title III Program Office have made investments to develop the national technology base and manufacturing infrastructure necessary to meet the twin challenge of providing affordable displays in current systems and enabling the DoD strategy of winning future conflicts by getting more information to all participants during the battle. These completed DARPA and DPA research and infrastructure programs are reviewed. Service investments have been and are being made to transition display technology; examples are described. Display science and technology (S&T) visions are documented for each service to assist the identification of areas meriting consideration for future defense research.
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Shigella Iron Acquisition Systems and their Regulation.
Wei, Yahan; Murphy, Erin R
2016-01-01
Survival of Shigella within the host is strictly dependent on the ability of the pathogen to acquire essential nutrients, such as iron. As an innate immune defense against invading pathogens, the level of bio-available iron within the human host is maintained at exceeding low levels, by sequestration of the element within heme and other host iron-binding compounds. In response to sequestration mediated iron limitation, Shigella produce multiple iron-uptake systems that each function to facilitate the utilization of a specific host-associated source of nutrient iron. As a mechanism to balance the essential need for iron and the toxicity of the element when in excess, the production of bacterial iron acquisition systems is tightly regulated by a variety of molecular mechanisms. This review summarizes the current state of knowledge on the iron-uptake systems produced by Shigella species, their distribution within the genus, and the molecular mechanisms that regulate their production.
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Mageroy, Jon H; Grepperud, Eldfrid J; Jensen, Knut Helge
2011-12-01
We investigated whether parasites or hosts benefit from reduced reproduction in infected hosts. When parasites castrate their hosts, the regain of host reproduction is necessary for castration to be a host adaptation. When infecting Daphnia magna with Pasteuria ramosa, in a lake water based medium, 49 2% of the castrated females regained reproduction. We investigated the relationship between castration level, and parasite and host fitness proxies to determine the adaptive value of host castration. Hosts which regained reproduction contained less spores and had a higher lifetime reproduction than permanently castrated hosts. We also found a negative correlation between parasite and host lifetime reproduction. For hosts which regained reproduction we found no optimal level of castration associated with lifetime reproduction. These results support the view that host castration only is adaptive to the parasite in this system. In addition, we suggest that permanent castration might not be the norm under natural conditions in this system. Finally, we argue that a reduction in host reproduction is more likely to evolve as a property favouring parasites rather than hosts. To our knowledge this is the only experimental study to investigate the adaptive value of reduced host reproduction when castrated hosts can regain reproduction.
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Dynamics and profiles of a diffusive host-pathogen system with distinct dispersal rates
Wu, Yixiang; Zou, Xingfu
2018-04-01
In this paper, we investigate a diffusive host-pathogen model with heterogeneous parameters and distinct dispersal rates for the susceptible and infected hosts. We first prove that the solution of the model exists globally and the model system possesses a global attractor. We then identify the basic reproduction number R0 for the model and prove its threshold role: if R0 ≤ 1, the disease free equilibrium is globally asymptotically stable; if R0 > 1, the solution of the model is uniformly persistent and there exists a positive (pathogen persistent) steady state. Finally, we study the asymptotic profiles of the positive steady state as the dispersal rate of the susceptible or infected hosts approaches zero. Our result suggests that the infected hosts concentrate at certain points which can be characterized as the pathogen's most favoured sites when the mobility of the infected host is limited.
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Entomopathogenic Fungi: New Insights into Host-Pathogen Interactions.
Butt, T M; Coates, C J; Dubovskiy, I M; Ratcliffe, N A
2016-01-01
Although many insects successfully live in dangerous environments exposed to diverse communities of microbes, they are often exploited and killed by specialist pathogens. Studies of host-pathogen interactions (HPI) provide valuable insights into the dynamics of the highly aggressive coevolutionary arms race between entomopathogenic fungi (EPF) and their arthropod hosts. The host defenses are designed to exclude the pathogen or mitigate the damage inflicted while the pathogen responds with immune evasion and utilization of host resources. EPF neutralize their immediate surroundings on the insect integument and benefit from the physiochemical properties of the cuticle and its compounds that exclude competing microbes. EPF also exhibit adaptations aimed at minimizing trauma that can be deleterious to both host and pathogen (eg, melanization of hemolymph), form narrow penetration pegs that alleviate host dehydration and produce blastospores that lack immunogenic sugars/enzymes but facilitate rapid assimilation of hemolymph nutrients. In response, insects deploy an extensive armory of hemocytes and macromolecules, such as lectins and phenoloxidase, that repel, immobilize, and kill EPF. New evidence suggests that immune bioactives work synergistically (eg, lysozyme with antimicrobial peptides) to combat infections. Some proteins, including transferrin and apolipophorin III, also demonstrate multifunctional properties, participating in metabolism, homeostasis, and pathogen recognition. This review discusses the molecular intricacies of these HPI, highlighting the interplay between immunity, stress management, and metabolism. Increased knowledge in this area could enhance the efficacy of EPF, ensuring their future in integrated pest management programs. Copyright © 2016 Elsevier Inc. All rights reserved.
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Host evasion by Burkholderia cenocepacia
Directory of Open Access Journals (Sweden)
Shyamala eGanesan
2012-01-01
Full Text Available Burkholderia cenocepacia is an opportunistic respiratory pathogen of individuals with cystic fibrosis (CF. It is one of the highly transmissible species of Burkholderia cepacia complex and very resistant to almost all the antibiotics. Approximately 1/3rd of B. cenocepacia infected CF patients go on to develop fatal ‘cepacia syndrome’. During the last two decades, substantial progress has been made with regards to evasion of host innate defense mechanisms by B. cenocepacia. Almost all strains of B. cenocepacia has capacity to survive and replicate intracellularly in both airway epithelial cells and macrophages, which are primary centennials of the lung and play a pivotal role in clearance of infecting bacteria. Some strains of B. cenocepaica, which express cable pili and the associated 22kDa adhesin are also capable of transmigrating across airway epithelium and persist in mouse models of infection. In this review, we will discuss how this type of interaction between B. cenocepacia and host may lead to persistence of bacteria and contribute to lung inflammation in CF patients.
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Second Line of Defense Virtual Private Network Guidance for Deployed and New CAS Systems
Energy Technology Data Exchange (ETDEWEB)
Singh, Surya V.; Thronas, Aaron I.
2010-01-01
This paper discusses the importance of remote access via virtual private network (VPN) for the Second Line of Defense (SLD) Central Alarm System (CAS) sites, the requirements for maintaining secure channels while using VPN and implementation requirements for current and future sites.
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Seasly, Elaine
2015-01-01
To combat contamination of physical assets and provide reliable data to decision makers in the space and missile defense community, a modular open system architecture for creation of contamination models and standards is proposed. Predictive tools for quantifying the effects of contamination can be calibrated from NASA data of long-term orbiting assets. This data can then be extrapolated to missile defense predictive models. By utilizing a modular open system architecture, sensitive data can be de-coupled and protected while benefitting from open source data of calibrated models. This system architecture will include modules that will allow the designer to trade the effects of baseline performance against the lifecycle degradation due to contamination while modeling the lifecycle costs of alternative designs. In this way, each member of the supply chain becomes an informed and active participant in managing contamination risk early in the system lifecycle.
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Transportation System Risk Assessment on DOE Defense Program shipments
International Nuclear Information System (INIS)
Brumburgh, G.P.; Kimura, C.Y.; Alesso, H.P.; Prassinos, P.G.
1992-01-01
Substantial effort has been expended concerning the level of safety provided to persons, property, and the environment from the hazards associated with transporting radioactive material. This work provided an impetus for the Department of Energy to investigate the use of probabilistic risk assessment techniques to supplement the deterministic approach to transportation safety. The DOE recently decided to incorporate the methodologies associated with PRAs in the process for authorizing the transportation of nuclear components, special assemblies, and radioactive materials affiliated with the DOE Defense Program. Accordingly, the LLNL, sponsored by the DOE/AL, is tasked with developing a safety guide series to provide guidance to preparers performing a transportation system risk assessment
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Adams, Aaron S; Aylward, Frank O; Adams, Sandye M; Erbilgin, Nadir; Aukema, Brian H; Currie, Cameron R; Suen, Garret; Raffa, Kenneth F
2013-06-01
The mountain pine beetle, Dendroctonus ponderosae, is a subcortical herbivore native to western North America that can kill healthy conifers by overcoming host tree defenses, which consist largely of high terpene concentrations. The mechanisms by which these beetles contend with toxic compounds are not well understood. Here, we explore a component of the hypothesis that beetle-associated bacterial symbionts contribute to the ability of D. ponderosae to overcome tree defenses by assisting with terpene detoxification. Such symbionts may facilitate host tree transitions during range expansions currently being driven by climate change. For example, this insect has recently breached the historical geophysical barrier of the Canadian Rocky Mountains, providing access to näive tree hosts and unprecedented connectivity to eastern forests. We use culture-independent techniques to describe the bacterial community associated with D. ponderosae beetles and their galleries from their historical host, Pinus contorta, and their more recent host, hybrid P. contorta-Pinus banksiana. We show that these communities are enriched with genes involved in terpene degradation compared with other plant biomass-processing microbial communities. These pine beetle microbial communities are dominated by members of the genera Pseudomonas, Rahnella, Serratia, and Burkholderia, and the majority of genes involved in terpene degradation belong to these genera. Our work provides the first metagenome of bacterial communities associated with a bark beetle and is consistent with a potential microbial contribution to detoxification of tree defenses needed to survive the subcortical environment.
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Molecular model of a type III secretion system needle: Implications for host-cell sensing.
Deane, Janet E; Roversi, Pietro; Cordes, Frank S; Johnson, Steven; Kenjale, Roma; Daniell, Sarah; Booy, Frank; Picking, William D; Picking, Wendy L; Blocker, Ariel J; Lea, Susan M
2006-08-15
Type III secretion systems are essential virulence determinants for many Gram-negative bacterial pathogens. The type III secretion system consists of cytoplasmic, transmembrane, and extracellular domains. The extracellular domain is a hollow needle protruding above the bacterial surface and is held within a basal body that traverses both bacterial membranes. Effector proteins are translocated, via this external needle, directly into host cells, where they subvert normal cell functions to aid infection. Physical contact with host cells initiates secretion and leads to formation of a pore, thought to be contiguous with the needle channel, in the host-cell membrane. Here, we report the crystal structure of the Shigella flexneri needle subunit MxiH and a complete model for the needle assembly built into our three-dimensional EM reconstruction. The model, combined with mutagenesis data, reveals that signaling of host-cell contact is relayed through the needle via intersubunit contacts and suggests a mode of binding for a tip complex.
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Directory of Open Access Journals (Sweden)
Luis Latournerie-Moreno
2015-03-01
Full Text Available The whitefly Bemisia tabaci (Gennadius, 1889 is a major plant pest of horticultural crops from the families Solanaceae, Fabaceae and Cucurbitaceae in Neotropical areas. The exploration of host plant resistance and their biochemical mechanisms offers an excellent alternative to better understand factors affecting the interaction between phytophagous insect and host plant. We evaluated the survival of B. tabaci in landrace genotypes of Capsicum annuum L., and the activity of plant defense-related enzymes (chitinase, polyphenoloxidase, and peroxidase. The landrace genotypes Amaxito, Tabaquero, and Simojovel showed resistance to B. tabaci, as we observed more than 50% nymphal mortality, while in the commercial susceptible genotype Jalapeño mortality of B. tabaci nymphs was not higher than 20%. The activities of plant defense-related enzymes were significantly different among pepper genotypes (P < 0.05. Basal activities of chitinase, polyphenoloxidase and peroxidase were significantly lower or equal in landrace genotypes than that of the commercial genotype Jalapeño. The activity of plant enzymes was differential among pepper genotypes (P < 0.05. For example, the activity of chitinase enzyme generally was higher in non-infested plants with B. tabaci than those infested. Instead polyphenoloxidase ('Amaxito' and 'Simojovel' and peroxidase enzymes activities ('Tabaquero' increased in infested plants (P < 0.05. We conclude that basal activities of plant defense-related enzymes could be act through other mechanism plant induction, since plant defense-related enzymes showed a different induction response to B. tabaci. We underlined the role of polyphenoloxidase as plant defense in the pepper genotype Simojovel related to B. tabaci.
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Social Hackers: Integration in the Host Chemical Recognition System by a Paper Wasp Social Parasite
Turillazzi, S.; Sledge, M. F.; Dani, F. R.; Cervo, R.; Massolo, A.; Fondelli, L.
Obligate social parasites in the social insects have lost the worker caste and the ability to establish nests. As a result, parasites must usurp a host nest, overcome the host recognition system, and depend on the host workers to rear their offspring. We analysed cuticular hydrocarbon profiles of live parasite females of the paper wasp social parasite Polistes sulcifer before and after usurpation of host nests, using the non-destructive technique of solid-phase micro-extraction. Our results reveal that hydrocarbon profiles of parasites change after usurpation of host nests to match the cuticular profile of the host species. Chemical evidence further shows that the parasite queen changes the odour of the nest by the addition of a parasite-specific hydrocarbon. We discuss the possible role of this in the recognition and acceptance of the parasite and its offspring in the host colony.
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Instant OSSEC host-based intrusion detection system
Lhotsky, Brad
2013-01-01
Filled with practical, step-by-step instructions and clear explanations for the most important and useful tasks. A fast-paced, practical guide to OSSEC-HIDS that will help you solve host-based security problems.This book is great for anyone concerned about the security of their servers-whether you are a system administrator, programmer, or security analyst, this book will provide you with tips to better utilize OSSEC-HIDS. Whether you're new to OSSEC-HIDS or a seasoned veteran, you'll find something in this book you can apply today!This book assumes some knowledge of basic security concepts an
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The role of lipids in host microbe interactions.
Lang, Roland; Mattner, Jochen
2017-06-01
Lipids are one of the major subcellular constituents and serve as signal molecules, energy sources, metabolic precursors and structural membrane components in various organisms. The function of lipids can be modified by multiple biochemical processes such as (de-)phosphorylation or (de-)glycosylation, and the organization of fatty acids into distinct cellular pools and subcellular compartments plays a pivotal role for the morphology and function of various cell populations. Thus, lipids regulate, for example, phagosome formation and maturation within host cells and thus, are critical for the elimination of microbial pathogens. Vice versa, microbial pathogens can manipulate the lipid composition of phagosomal membranes in host cells, and thus avoid their delivery to phagolysosomes. Lipids of microbial origin belong also to the strongest and most versatile inducers of mammalian immune responses upon engagement of distinct receptors on myeloid and lymphoid cells. Furthermore, microbial lipid toxins can induce membrane injuries and cell death. Thus, we will review here selected examples for mutual host-microbe interactions within the broad and divergent universe of lipids in microbial defense, tissue injury and immune evasion.
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Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids
Geiger, Anne; Bossard, Géraldine; Sereno, Denis; Pissarra, Joana; Lemesre, Jean-Loup; Vincendeau, Philippe; Holzmuller, Philippe
2016-01-01
The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, Trypanosoma cruzi, and Leishmania spp. are important human pathogens causing human African trypanosomiasis (HAT or sleeping sickness), Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs, or sandflies, and affect millions of people worldwide. In humans, extracellular African trypanosomes (T. brucei) evade the hosts’ immune defenses, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response. This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite–host interactions and will focus on: clinical and epidemiological importance of diseases; life cycles: parasites–hosts–vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen-presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation. PMID:27303406
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Reflecting on 20+ Years of “Executive Program in Defense Decision Making” Curriculum
2017-01-01
CCMR News Article CCMR hosted a version of its biannual “Executive Program in Defense Decision Making” offering for 21 international military and civilian participants, from November 6-17, 2017. Often described as CCMR’s “flagship” course, this curriculum has been offered at the Naval Postgraduate School (NPS) in Monterey, California for over 20 years.
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Qian, Suhong; Fan, Wenchun; Liu, Tingting; Wu, Mengge; Zhang, Huawei; Cui, Xiaofang; Zhou, Yun; Hu, Junjie; Wei, Shaozhong; Chen, Huanchun; Li, Xiangmin; Qian, Ping
2017-08-15
Seneca Valley virus (SVV) is an oncolytic RNA virus belonging to the Picornaviridae family. Its nucleotide sequence is highly similar to those of members of the Cardiovirus genus. SVV is also a neuroendocrine cancer-selective oncolytic picornavirus that can be used for anticancer therapy. However, the interaction between SVV and its host is yet to be fully characterized. In this study, SVV inhibited antiviral type I interferon (IFN) responses by targeting different host adaptors, including mitochondrial antiviral signaling (MAVS), Toll/interleukin 1 (IL-1) receptor domain-containing adaptor inducing IFN-β (TRIF), and TRAF family member-associated NF-κB activator (TANK), via viral 3C protease (3C pro ). SVV 3C pro mediated the cleavage of MAVS, TRIF, and TANK at specific sites, which required its protease activity. The cleaved MAVS, TRIF, and TANK lost the ability to regulate pattern recognition receptor (PRR)-mediated IFN production. The cleavage of TANK also facilitated TRAF6-induced NF-κB activation. SVV was also found to be sensitive to IFN-β. Therefore, SVV suppressed antiviral IFN production to escape host antiviral innate immune responses by cleaving host adaptor molecules. IMPORTANCE Host cells have developed various defenses against microbial pathogen infection. The production of IFN is the first line of defense against microbial infection. However, viruses have evolved many strategies to disrupt this host defense. SVV, a member of the Picornavirus genus, is an oncolytic virus that shows potential functions in anticancer therapy. It has been demonstrated that IFN can be used in anticancer therapy for certain tumors. However, the relationship between oncolytic virus and innate immune response in anticancer therapy is still not well known. In this study, we showed that SVV has evolved as an effective mechanism to inhibit host type I IFN production by using its 3C pro to cleave the molecules MAVS, TRIF, and TANK directly. These molecules are crucial for
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Padul, Manohar V; Tak, Rajesh D; Kachole, Manvendra S
2012-03-01
More than 200 insect pests are found growing on pigeonpea. Insects lay eggs, attack and feed on leaves, flowers and developing pods. Plants have developed elaborate defenses against these insect pests. The present work evaluates protease inhibitor (PI) based defense of pigeonpea in leaves and flowers. PIs in the extracts of these tender tissues were detected by using gel X-ray film contact print method. Up to three PIs (PI-3, PI-4 and PI-5) were detected in these tissues as against nine (PI-1-PI-9) in mature seeds. PI-3 is the major component of these tissues. Mechanical wounding, insect chewing, fungal pathogenesis and application of salicylic acid induced PIs in pigeonpea in these tissues. Induction was found to be local as well as systemic but local response was stronger than systemic response. During both local and systemic induction, PI-3 appeared first. In spite of the presence and induction of PIs in these tender tissues and seeds farmers continue to suffer yield loses. This is due to the weak expression of PIs. However the ability of the plant to respond to external stimuli by producing defense proteins does not seem to be compromised. This study therefore indicates that PIs are components of both constitutive and inducible defense and provide a ground for designing stronger inducible defense (PIs or other insect toxin based) in pigeonpea. Copyright © 2011 Elsevier Masson SAS. All rights reserved.
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Chaili, Siyang; Cheung, Ambrose L; Bayer, Arnold S; Xiong, Yan Q; Waring, Alan J; Memmi, Guido; Donegan, Niles; Yang, Soo-Jin; Yeaman, Michael R
2016-02-01
Staphylococcus aureus uses the two-component regulatory system GraRS to sense and respond to host defense peptides (HDPs). However, the mechanistic impact of GraS or its extracellular sensing loop (EL) on HDP resistance is essentially unexplored. Strains with null mutations in the GraS holoprotein (ΔgraS) or its EL (ΔEL) were compared for mechanisms of resistance to HDPs of relevant immune sources: neutrophil α-defensin (human neutrophil peptide 1 [hNP-1]), cutaneous β-defensin (human β-defensin 2 [hBD-2]), or the platelet kinocidin congener RP-1. Actions studied by flow cytometry included energetics (ENR); membrane permeabilization (PRM); annexin V binding (ANX), and cell death protease activation (CDP). Assay conditions simulated bloodstream (pH 7.5) or phagolysosomal (pH 5.5) pH contexts. S. aureus strains were more susceptible to HDPs at pH 7.5 than at pH 5.5, and each HDP exerted a distinct effect signature. The impacts of ΔgraS and ΔΕL on HDP resistance were peptide and pH dependent. Both mutants exhibited defects in ANX response to hNP-1 or hBD-2 at pH 7.5, but only hNP-1 did so at pH 5.5. Both mutants exhibited hyper-PRM, -ANX, and -CDP responses to RP-1 at both pHs and hypo-ENR at pH 5.5. The actions correlated with ΔgraS or ΔΕL hypersusceptibility to hNP-1 or RP-1 (but not hBD-2) at pH 7.5 and to all study HDPs at pH 5.5. An exogenous EL mimic protected mutant strains from hNP-1 and hBD-2 but not RP-1, indicating that GraS and its EL play nonredundant roles in S. aureus survival responses to specific HDPs. These findings suggest that GraS mediates specific resistance countermeasures to HDPs in immune contexts that are highly relevant to S. aureus pathogenesis in humans. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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Host Rock Classification (HRC) system for nuclear waste disposal in crystalline bedrock
International Nuclear Information System (INIS)
Hagros, A.
2006-01-01
A new rock mass classification scheme, the Host Rock Classification system (HRC-system) has been developed for evaluating the suitability of volumes of rock mass for the disposal of high-level nuclear waste in Precambrian crystalline bedrock. To support the development of the system, the requirements of host rock to be used for disposal have been studied in detail and the significance of the various rock mass properties have been examined. The HRC-system considers both the long-term safety of the repository and the constructability in the rock mass. The system is specific to the KBS-3V disposal concept and can be used only at sites that have been evaluated to be suitable at the site scale. By using the HRC-system, it is possible to identify potentially suitable volumes within the site at several different scales (repository, tunnel and canister scales). The selection of the classification parameters to be included in the HRC-system is based on an extensive study on the rock mass properties and their various influences on the long-term safety, the constructability and the layout and location of the repository. The parameters proposed for the classification at the repository scale include fracture zones, strength/stress ratio, hydraulic conductivity and the Groundwater Chemistry Index. The parameters proposed for the classification at the tunnel scale include hydraulic conductivity, Q' and fracture zones and the parameters proposed for the classification at the canister scale include hydraulic conductivity, Q', fracture zones, fracture width (aperture + filling) and fracture trace length. The parameter values will be used to determine the suitability classes for the volumes of rock to be classified. The HRC-system includes four suitability classes at the repository and tunnel scales and three suitability classes at the canister scale and the classification process is linked to several important decisions regarding the location and acceptability of many components of
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De novo transcriptome analyses of host-fungal interactions in oil palm (Elaeis guineensis Jacq.).
Ho, Chai-Ling; Tan, Yung-Chie; Yeoh, Keat-Ai; Ghazali, Ahmad-Kamal; Yee, Wai-Yan; Hoh, Chee-Choong
2016-01-19
Basal stem rot (BSR) is a fungal disease in oil palm (Elaeis guineensis Jacq.) which is caused by hemibiotrophic white rot fungi belonging to the Ganoderma genus. Molecular responses of oil palm to these pathogens are not well known although this information is crucial to strategize effective measures to eradicate BSR. In order to elucidate the molecular interactions between oil palm and G. boninense and its biocontrol fungus Trichoderma harzianum, we compared the root transcriptomes of untreated oil palm seedlings with those inoculated with G. boninense and T. harzianum, respectively. Differential gene expression analyses revealed that jasmonate (JA) and salicylate (SA) may act in an antagonistic manner in affecting the hormone biosynthesis, signaling, and downstream defense responses in G. boninense-treated oil palm roots. In addition, G. boninense may compete with the host to control disease symptom through the transcriptional regulation of ethylene (ET) biosynthesis, reactive oxygen species (ROS) production and scavenging. The strengthening of host cell walls and production of pathogenesis-related proteins as well as antifungal secondary metabolites in host plants, are among the important defense mechanisms deployed by oil palm against G. boninense. Meanwhile, endophytic T. harzianum was shown to improve the of nutrition status and nutrient transportation in host plants. The findings of this analysis have enhanced our understanding on the molecular interactions of G. boninense and oil palm, and also the biocontrol mechanisms involving T. harzianum, thus contributing to future formulations of better strategies for prevention and treatment of BSR.
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The effects of host-feeding on stability of discrete-time host-parasitoid population dynamic models.
Emerick, Brooks; Singh, Abhyudai
2016-02-01
Discrete-time models are the traditional approach for capturing population dynamics of a host-parasitoid system. Recent work has introduced a semi-discrete framework for obtaining model update functions that connect host-parasitoid population levels from year-to-year. In particular, this framework uses differential equations to describe the host-parasitoid interaction during the time of year when they come in contact, allowing specific behaviors to be mechanistically incorporated. We use the semi-discrete approach to study the effects of host-feeding, which occurs when a parasitoid consumes a potential host larva without ovipositing. We find that host-feeding by itself cannot stabilize the system, and both populations exhibit behavior similar to the Nicholson-Bailey model. However, when combined with stabilizing mechanisms such as density-dependent host mortality, host-feeding contracts the region of parameter space that allows for a stable host-parasitoid equilibrium. In contrast, when combined with a density-dependent parasitoid attack rate, host-feeding expands the non-zero equilibrium stability region. Our results show that host-feeding causes inefficiency in the parasitoid population, which yields a higher population of hosts per generation. This suggests that host-feeding may have limited long-term impact in terms of suppressing host levels for biological control applications. Copyright © 2015 Elsevier Inc. All rights reserved.
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Host response to biomaterials the impact of host response on biomaterial selection
Badylak, Stephen F
2015-01-01
Host Response to Biomaterials: The Impact of Host Response on Biomaterial Selection explains the various categories of biomaterials and their significance for clinical applications, focusing on the host response to each biomaterial. It is one of the first books to connect immunology and biomaterials with regard to host response. The text also explores the role of the immune system in host response, and covers the regulatory environment for biomaterials, along with the benefits of synthetic versus natural biomaterials, and the transition from simple to complex biomaterial solutions. Fiel
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Insights into Host Cell Modulation and Induction of New Cells by the Corn Smut Ustilago maydis
Directory of Open Access Journals (Sweden)
Amey Redkar
2017-05-01
Full Text Available Many filamentous fungal pathogens induce drastic modulation of host cells causing abnormal infectious structures such as galls, or tumors that arise as a result of re-programming in the original developmental cell fate of a colonized host cell. Developmental consequences occur predominantly with biotrophic phytopathogens. This suggests that these host structures result as an outcome of efficient defense suppression and intimate fungal–host interaction to suit the pathogen’s needs for completion of its infection cycle. This mini-review mainly summarizes host cell re-programming that occurs in the Ustilago maydis – maize interaction, in which the pathogen deploys cell-type specific effector proteins with varying activities. The fungus senses the physiological status and identity of colonized host cells and re-directs the endogenous developmental program of its host. The disturbance of host cell physiology and cell fate leads to novel cell shapes, increased cell size, and/or the number of host cells. We particularly highlight the strategies of U. maydis to induce physiologically varied host organs to form the characteristic tumors in both vegetative and floral parts of maize.
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Effects of Gain/Loss Framing in Cyber Defense Decision-Making
Energy Technology Data Exchange (ETDEWEB)
Bos, Nathan; Paul, Celeste; Gersh, John; Greenberg, Ariel; Piatko, Christine; Sperling, Scott; Spitaletta, Jason; Arendt, Dustin L.; Burtner, Edwin R.
2016-10-24
Cyber defense requires decision making under uncertainty. Yet this critical area has not been a strong focus of research in judgment and decision-making. Future defense systems, which will rely on software-defined networks and may employ ‘moving target’ defenses, will increasingly automate lower level detection and analysis, but will still require humans in the loop for higher level judgment. We studied the decision making process and outcomes of 17 experienced network defense professionals who worked through a set of realistic network defense scenarios. We manipulated gain versus loss framing in a cyber defense scenario, and found significant effects in one of two focal problems. Defenders that began with a network already in quarantine (gain framing) used a quarantine system more than those that did not (loss framing). We also found some difference in perceived workload and efficacy. Alternate explanations of these findings and implications for network defense are discussed.
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Host-pathogen interactions: A cholera surveillance system
Energy Technology Data Exchange (ETDEWEB)
Wright, Aaron T.
2016-02-22
Bacterial pathogen-secreted proteases may play a key role in inhibiting a potentially widespread host-pathogen interaction. Activity-based protein profiling enabled the identification of a major Vibrio cholerae serine protease that limits the ability of a host-derived intestinal lectin to bind to the bacterial pathogen in vivo.
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Adaptation to toxic hosts as a factor in the evolution of insecticide resistance.
Alyokhin, Andrei; Chen, Yolanda H
2017-06-01
Insecticide resistance is a serious economic problem that jeopardizes sustainability of chemical control of herbivorous insects and related arthropods. It can be viewed as a specific case of adaptation to toxic chemicals, which has been driven in large part, but not exclusively, by the necessity for insect pests to tolerate defensive compounds produced by their host plants. Synthetic insecticides may simply change expression of specific sets of detoxification genes that have evolved due to ancestral associations with host plants. Feeding on host plants with more abundant or novel secondary metabolites has even been shown to prime insect herbivores to tolerate pesticides. Clear understanding of basic evolutionary processes is important for achieving lasting success in managing herbivorous arthropods. Copyright © 2017 Elsevier Inc. All rights reserved.
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Role of Soluble Innate Effector Molecules in Pulmonary Defense against Fungal Pathogens
Directory of Open Access Journals (Sweden)
Soledad R. Ordonez
2017-10-01
Full Text Available Fungal infections of the lung are life-threatening but rarely occur in healthy, immunocompetent individuals, indicating efficient clearance by pulmonary defense mechanisms. Upon inhalation, fungi will first encounter the airway surface liquid which contains several soluble effector molecules that form the first barrier of defense against fungal infections. These include host defense peptides, like LL-37 and defensins that can neutralize fungi by direct killing of the pathogen, and collectins, such as surfactant protein A and D, that can aggregate fungi and stimulate phagocytosis. In addition, these molecules have immunomodulatory activities which can aid in fungal clearance from the lung. However, existing observations are based on in vitro studies which do not reflect the complexity of the lung and its airway surface liquid. Ionic strength, pH, and the presence of mucus can have strong detrimental effects on antifungal activity, while the potential synergistic interplay between soluble effector molecules is largely unknown. In this review, we describe the current knowledge on soluble effector molecules that contribute to antifungal activity, the importance of environmental factors and discuss the future directions required to understand the innate antifungal defense in the lung.
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Role of Soluble Innate Effector Molecules in Pulmonary Defense against Fungal Pathogens
Ordonez, Soledad R.; Veldhuizen, Edwin J. A.; van Eijk, Martin; Haagsman, Henk P.
2017-01-01
Fungal infections of the lung are life-threatening but rarely occur in healthy, immunocompetent individuals, indicating efficient clearance by pulmonary defense mechanisms. Upon inhalation, fungi will first encounter the airway surface liquid which contains several soluble effector molecules that form the first barrier of defense against fungal infections. These include host defense peptides, like LL-37 and defensins that can neutralize fungi by direct killing of the pathogen, and collectins, such as surfactant protein A and D, that can aggregate fungi and stimulate phagocytosis. In addition, these molecules have immunomodulatory activities which can aid in fungal clearance from the lung. However, existing observations are based on in vitro studies which do not reflect the complexity of the lung and its airway surface liquid. Ionic strength, pH, and the presence of mucus can have strong detrimental effects on antifungal activity, while the potential synergistic interplay between soluble effector molecules is largely unknown. In this review, we describe the current knowledge on soluble effector molecules that contribute to antifungal activity, the importance of environmental factors and discuss the future directions required to understand the innate antifungal defense in the lung. PMID:29163395
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Directory of Open Access Journals (Sweden)
María Luisa ePérez-Bueno
2016-01-01
Full Text Available The necrotrophic bacteria Dickeya dadantii is the causal agent of soft-rot disease in a broad range of hosts. The model plant Nicotiana benthamiana, commonly used as experimental host for a very broad range of plant pathogens, is susceptible to infection by D. dadantii. The inoculation with D. dadantii at high dose seems to overcome the plant defense capacity, inducing maceration and death of the tissue, although restricted to the infiltrated area. By contrast, the output of the defense response to low dose inoculation is inhibition of maceration and limitation in the growth, or even eradication, of bacteria. Responses of tissue invaded by bacteria (neighbouring the infiltrated areas after 2-3 days post-inoculation included: i inhibition of photosynthesis in terms of photosystem II efficiency; ii activation of energy dissipation as non-photochemical quenching in photosystem II, which is related to the activation of plant defense mechanisms; and iii accumulation of secondary metabolites in cell walls of the epidermis (lignins and the apoplast of the mesophyll (phytoalexins. Infiltrated tissues showed an increase in the content of the main hormones regulating stress responses, including abscisic acid (ABA, jasmonic acid (JA and salicylic acid (SA. We propose a mechanism involving the three hormones by which N. benthamiana could activate an efficient defense response against D. dadantii.
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National Research Council Canada - National Science Library
Granetto, Paul J; Peek, Marvin L; Armstrong, Jack L; Wenzel, Paul C; Furey, Kathleen A; Zimmerman, Craig W
2004-01-01
... are: the Corps of Engineers Financial Management System, the Corps of Engineers Enterprise Management Information System, and the Defense Departmental Reporting System - Audited Financial Statements...
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Directory of Open Access Journals (Sweden)
Justyna Nowakowska
2014-08-01
Full Text Available The number of implanted medical devices is steadily increasing and has become an effective intervention improving life quality, but still carries the risk of infection. These infections are mainly caused by biofilm-forming staphylococci that are difficult to treat due to the decreased susceptibility to both antibiotics and host defense mechanisms. To understand the particular pathogenesis and treatment tolerance of implant-associated infection (IAI animal models that closely resemble human disease are needed. Applications of the tissue cage and catheter abscess foreign body infection models in the mouse will be discussed herein. Both models allow the investigation of biofilm and virulence of various bacterial species and a comprehensive insight into the host response at the same time. They have also been proven to serve as very suitable tools to study the anti-adhesive and anti-infective efficacy of different biomaterial coatings. The tissue cage model can additionally be used to determine pharmacokinetics, efficacy and cytotoxicity of antimicrobial compounds as the tissue cage fluid can be aspirated repeatedly without the need to sacrifice the animal. Moreover, with the advance in innovative imaging systems in rodents, these models may offer new diagnostic measures of infection. In summary, animal foreign body infection models are important tools in the development of new antimicrobials against IAI and can help to elucidate the complex interactions between bacteria, the host immune system, and prosthetic materials.
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Herath, H M L P B; Wickramasinghe, P D S U; Bathige, S D N K; Jayasooriya, R G P T; Kim, Gi-Young; Park, Myoung Ae; Kim, Chul; Lee, Jehee
2017-01-01
: Vibrio parahaemolyticus, Listeria monocytogenes, and lipopolysaccharide (LPS), thus indicating its possible involvement in host defense mechanisms during pathogenic infections. Taken together, the results of the current study suggest that AbGSR plays an important role in antioxidant-mediated host defense mechanisms and also provide insights into the immunological contribution of AbGSR. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Directory of Open Access Journals (Sweden)
2017-05-01
Full Text Available Background and Objectives: According to the previous findings, brain ischemia attenuates the brain antioxidant defense system. This study aimed to investigate the effect of hydroxylated fullerene nanoparticle on antioxidant defense system in ischemic brain rat. Methods: In this Experimental study, rats were divided into three groups (n=6 in each group: sham, ischemic control, and ischemic treatment group. Brain ischemia was induced by middle cerebral artery (MCA occlusion for 90 minutes followed by a 24-hour reperfusion. Ischemic treatment animals received fullerene nanoparticles intraperitoneally at a dose of 10mg/kg immediately after the end of MCA occlusion. After 24-h reperfusion period, brain catalase and superoxide dismutase (SOD, and glutathione activities were assessed by biochemical methods. The data were analyzed using one-way ANOVA and Tukey post-hoc test. Results: The mean glutathione level and catalase and SOD activities in sham animals were 1±0.18%, 1±0.20%, and 1±0.04%, respectively. Induction of brain ischemia decreased the value of glutathione level and catalase and SOD activities in control ischemic rats and their values were obtained to be 0.55±0.09%, 0.44±0.05%, and 0.86±0.02%, respectively. Fullerene significantly increased the activities of catalase (0.93±0.29% and SOD (1.33±0.22% in ischemic treatment group compared to ischemic control rats, but did not change the glutathione level (0.52±0.25%. Conclusion: The results of this study showed that treatment with fullerene nanoparticles improves the brain antioxidant defense system, which is weakened during brain ischemia, through increasing catalase and SOD activities.
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Department of Defense Agency Financial Report for FY 2011
2011-11-01
able to distribute resources across hospitals and clinics within a market to meet the needs of the entire population of eligible beneficiaries. In...WRAMC), Washington, DC. This entailed construction of a new community hospital and a dental clinic at Fort Belvoir and an expansion of the National...Department of Defense DSB Defense Science Board DSS Defense Security Service DTM Directive-type Memorandum DTS Defense Travel System EBF Education
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MECHANISMS OF MICROBE-HOST-INTERACTION IN CROHN'S DISEASE: DYSBIOSIS VS. PATHOBIONT SELECTION
Directory of Open Access Journals (Sweden)
Ludovica F. Buttó
2015-11-01
Full Text Available Crohn’s disease (CD is a systemic chronic inflammatory condition mainly characterized by discontinuous transmural pathology of the gastrointestinal tract and frequent extra-intestinal manifestations with intermittent episodes of remission and relapse. Genome-wide association studies identified a number of risk loci that, catalyzed by environmental triggers, result in the loss of tolerance towards commensal bacteria based on dysregulated innate effector functions and anti-microbial defense, leading to exacerbated adaptive immune responses responsible for chronic immune-mediated tissue damage. In this review, we discuss the interrelated role of changes in the intestinal microbiota, epithelial barrier integrity and immune cell functions on the pathogenesis of CD, describing the current approaches available to investigate the molecular mechanisms underlying the disease. Substantial effort has been dedicated to define disease-associated changes in the intestinal microbiota (dysbiosis and to link pathobionts to the aetiology of IBD. A cogent definition of dysbiosis is lacking, as well as an agreement of whether pathobionts or complex shifts in the microbiota trigger inflammation in the host. Among the rarely available animal models, SAMP/Yit and TNFdeltaARE mice are the best known displaying a transmural CD-like phenotype. New hypothesis-driven mouse models e.g. epithelial-specific Caspase8-/-, ATG16L1-/- and XBP-1-/- mice validate pathway-focused function of specific CD-associated risk genes highlighting the role of Paneth cells in antimicrobial defense. To study the causal role of bacteria in initiating inflammation in the host, the use of germfree mouse models is indispensable. Unraveling the interactions of genes, immune cells and microbes constitute a criterion for the development of safe, reliable and effective treatment options for CD.
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Staphylococcal Superantigens Spark Host-Mediated Danger Signals
Directory of Open Access Journals (Sweden)
Terry eKrakauer
2016-02-01
Full Text Available Staphylococcal enterotoxin B (SEB of Staphylococcus aureus, and related superantigenic toxins produced by myriad microbes, are potent stimulators of the immune system causing a variety of human diseases from transient food poisoning to lethal toxic shock. These protein toxins bind directly to specific V regions of T-cell receptors (TCR and major histocompatibility complex (MHC class II on antigen-presenting cells, resulting in hyperactivation of T lymphocytes and monocytes / macrophages. Activated host cells produce excessive amounts of proinflammatory cytokines and chemokines, especially tumor necrosis factor α, interleukin 1 (IL-1, IL-2, interferon γ (IFNγ, and macrophage chemoattractant protein 1 causing clinical symptoms of fever, hypotension, and shock. Because of superantigen-induced T cells skewed towards TH1 helper cells, and the induction of proinflammatory cytokines, superantigens can exacerbate autoimmune diseases. Upon TCR / MHC ligation, pathways induced by superantigens include the mitogen-activated protein kinase cascades and cytokine receptor signaling, resulting in activation of NFκB and the phosphoinositide 3-kinase / mammalian target of rapamycin pathways. Various mouse models exist to study SEB-induced shock including those with potentiating agents, transgenic mice and an SEB-only model. However, therapeutics to treat toxic shock remain elusive as host response genes central to pathogenesis of superantigens have only been identified recently. Gene profiling of a murine model for SEB-induced shock reveals novel molecules upregulated in multiple organs not previously associated with SEB-induced responses. The pivotal genes include intracellular DNA / RNA sensors, apoptosis / DNA damage-related molecules, immunoproteasome components, as well as anti-viral and IFN-stimulated genes. The host-wide induction of these, and other, anti-microbial defense genes provide evidence that SEB elicits danger signals resulting in multi
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Diverse evolutionary roots and mechanistic variations of the CRISPR-Cas systems
Mohanraju, Prarthana; Makarova, Kira S.; Zetsche, Bernd; Zhang, Feng; Koonin, Eugene V.; Oost, van der John
2016-01-01
Adaptive immunity had been long thought of as an exclusive feature of animals. However, the discovery of the CRISPR-Cas defense system, present in almost half of prokaryotic genomes, proves otherwise. Because of the everlasting parasite-host arms race, CRISPR-Cas has rapidly evolved through
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S100A8/A9 is not involved in host defense against murine urinary tract infection.
Directory of Open Access Journals (Sweden)
Mark C Dessing
Full Text Available BACKGROUND: Inflammation is commonly followed by the release of endogenous proteins called danger associated molecular patterns (DAMPs that are able to warn the host for eminent danger. S100A8/A9 subunits are DAMPs that belong to the S100 family of calcium binding proteins. S100A8/A9 complexes induce an inflammatory response and their expression correlates with disease severity in several inflammatory disorders. S100A8/A9 promote endotoxin- and Escherichia (E. coli-induced sepsis showing its contribution in systemic infection. The role of S100A8/A9 during a local infection of the urinary tract system caused by E. coli remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the contribution of S100A8/A9 in acute urinary tract infection (UTI by instilling 2 different doses of uropathogenic E. coli transurethrally in wild type (WT and S100A9 knockout (KO mice. Subsequently, we determined bacterial outgrowth, neutrophilic infiltrate and inflammatory mediators in bladder and kidney 24 and 48 hours later. UTI resulted in a substantial increase of S100A8/A9 protein in bladder and kidney tissue of WT mice. S100A9 KO mice displayed similar bacterial load in bladder or kidney homogenate compared to WT mice using 2 different doses at 2 different time points. S100A9 deficiency had little effect on the inflammatory responses to E. Coli-induced UTI infection, as assessed by myeloperoxidase activity in bladder and kidneys, histopathologic analysis, and renal and bladder cytokine concentrations. CONCLUSIONS: We show that despite high S100A8/A9 expression in bladder and kidney tissue upon UTI, S100A8/A9 does not contribute to an effective host response against E. Coli in the urinary tract system.
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Department of Defense high power laser program guidance
Muller, Clifford H.
1994-06-01
The DoD investment of nominally $200 million per year is focused on four high power laser (HPL) concepts: Space-Based Laser (SBL), a Ballistic Missile Defense Organization effort that addresses boost-phase intercept for Theater Missile Defense and National Missile Defense; Airborne Laser (ABL), an Air Force effort that addresses boost-phase intercept for Theater Missile Defense; Ground-Based Laser (GBL), an Air Force effort addressing space control; and Anti-Ship Missile Defense (ASMD), a Navy effort addressing ship-based defense. Each organization is also supporting technology development with the goal of achieving less expensive, brighter, and lighter high power laser systems. These activities represent the building blocks of the DoD program to exploit the compelling characteristics of the high power laser. Even though DoD's HPL program are focused and moderately strong, additional emphasis in a few technical areas could help reduce risk in these programs. In addition, a number of options are available for continuing to use the High-Energy Laser System Test Facility (HELSTF) at White Sands Missile Range. This report provides a brief overview and guidance for the five efforts which comprise the DoD HPL program (SBL, ABL, GBL, ASMD, HELSTF).
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2010-10-01
... Missile Defense research, development, test, and evaluation. 225.7016 Section 225.7016 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS... Acquisition 225.7016 Restriction on Ballistic Missile Defense research, development, test, and evaluation. [68...
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Chen, Yan; Cai, Shasha; Qiao, Xue; Wu, Mali; Guo, Zhilai; Wang, Renping; Kuang, Yi-Qun; Yu, Haining; Wang, Yipeng
2017-08-10
Crocodilians are regarded as possessing a powerful immune system. However, the composition and action of the crocodilian immune system have remained unclear until now. Cathelicidins, the principal family of host defense peptides, play pivotal roles in vertebrate immune defense against microbial invasions. However, cathelicidins from crocodilians have not been extensively studied to date. In the present study, six novel cathelicidins (As-CATH1-6) were identified and characterized from the endangered Chinese alligator ( Alligator sinensis ). As-CATH1-6 exhibit no sequence similarity with any of the known cathelicidins. Structure analysis indicated that As-CATH1-3 adopt a random coil secondary conformation, whereas As-CATH4-6 were predicted to mainly adopt an amphipathic α-helix conformation. Among them, As-CATH4-6 exhibited potent, broad-spectrum and rapid antimicrobial activity by inducing the disruption of cell membrane integrity. They also exhibited strong ability to prevent the formation of bacterial biofilms and eradicate preformed biofilms. Furthermore, As-CATH4-6 exhibited potent anti-inflammatory activity by inhibiting the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and pro-inflammatory cytokines in mouse peritoneal macrophages. They directly neutralized LPS toxicity and therefore inhibited the binding of LPS to the TLR4 receptor and the subsequent activation of inflammatory response pathways. In a peritonitis mice model, As-CATH2-6 provided effective protection against bacterial infection through enhanced immune cell recruitment. In the host Chinese alligator, As-CATH1-6 are mainly expressed in immune organs and epithelial tissues. Bacterial infection significantly enhances their expression, which implies an important role in host anti-infective response. Taken together, the diversity and multiple functions of As-CATH1-6 partially reveal the powerful immune system of the Chinese alligator. © 2017 The Author(s). Published by Portland
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Directory of Open Access Journals (Sweden)
Jonathan Linneman
Full Text Available Mutualistic relationships are beneficial for both partners and are often studied within a single environment. However, when the range of the partners is large, geographical differences in selective pressure may shift the relationship outcome from positive to negative. The marine bryozoan Bugula neritina is a colonial invertebrate common in temperate waters worldwide. It is the source of bioactive polyketide metabolites, the bryostatins. Evidence suggests that an uncultured vertically transmitted symbiont, "Candidatus Endobugula sertula", hosted by B. neritina produces the bryostatins, which protect the vulnerable larvae from predation. Studies of B. neritina along the North American Atlantic coast revealed a complex of two morphologically similar sibling species separated by an apparent biogeographic barrier: the Type S sibling species was found below Cape Hatteras, North Carolina, while Type N was found above. Interestingly, the Type N colonies lack "Ca. Endobugula sertula" and, subsequently, defensive bryostatins; their documented northern distribution was consistent with traditional biogeographical paradigms of latitudinal variation in predation pressure. Upon further sampling of B. neritina populations, we found that both host types occur in wider distribution, with Type N colonies living south of Cape Hatteras, and Type S to the north. Distribution of the symbiont, however, was not restricted to Type S hosts. Genetic and microscopic evidence demonstrates the presence of the symbiont in some Type N colonies, and larvae from these colonies are endowed with defensive bryostatins and contain "Ca. Endobugula sertula". Molecular analysis of the symbiont from Type N colonies suggests an evolutionarily recent acquisition, which is remarkable for a symbiont thought to be transmitted only vertically. Furthermore, most Type S colonies found at higher latitudes lack the symbiont, suggesting that this host-symbiont relationship is more flexible than
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Energy Technology Data Exchange (ETDEWEB)
Maiden, Wendy M.
2009-12-01
Cooperative Infrastructure Defense (CID) is a hierarchical, agent-based, adaptive, cyber-security framework designed to collaboratively protect multiple enclaves or organizations participating in a complex infrastructure. CID employs a swarm of lightweight, mobile agents called Sensors designed to roam hosts throughout a security enclave to find indications of anomalies and report them to host-based Sentinels. The Sensors’ findings become pieces of a larger puzzle, which the Sentinel puts together to determine the problem and respond per policy as given by the enclave-level Sergeant agent. Horizontally across multiple enclaves and vertically within each enclave, authentication and access control technologies are necessary but insufficient authorization mechanisms to ensure that CID agents continue to fulfill their roles in a trustworthy manner. Trust management fills the gap, providing mechanisms to detect malicious agents and offering more robust mechanisms for authorization. This paper identifies the trust relationships throughout the CID hierarchy, the types of trust evidence that could be gathered, and the actions that the CID system could take if an entity is determined to be untrustworthy.
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2017-04-01
worldwide • $23 billion in sales for 2015 Raytheon Integrated Defense Systems (IDS) is one of five businesses within Raytheon Company and is headquartered...Raytheon Integrated Defense Systems DFSS team has developed and implemented numerous leading-edge improvement and optimization methodologies resulting in...our software systems . In this section, we explain the first methodology, the application of statistical test optimization (STO) using Design of
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CXC chemokine receptor 2 contributes to host defense in murine urinary tract infection
Olszyna, D. P.; Florquin, S.; Sewnath, M.; Branger, J.; Speelman, P.; van Deventer, S. J.; Strieter, R. M.; van der Poll, T.
2001-01-01
CXC chemokines have been implicated in the recruitment of neutrophils to sites of infection. To determine the role of CXC chemokines in the host response to urinary tract infection (UTI), female mice were treated with an antibody against the major CXC chemokine receptor in the mouse, CXCR2, before
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76 FR 13297 - Defense Federal Acquisition Regulation Supplement; Technical Amendments
2011-03-11
... 215 Government procurement. Ynette R. Shelkin, Editor, Defense Acquisition Regulations System... Director, Defense Procurement and Acquisition Policy. DATES: Effective Date: March 11, 2011. Applicability... adding a section at 215.300 with a reference to Director, Defense Procurement and Acquisition Policy...
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Directory of Open Access Journals (Sweden)
Toshihiro Nagamine
Full Text Available Although phylogenic analysis often suggests co-evolutionary relationships between viruses and host organisms, few examples have been reported at the microevolutionary level. Here, we show a possible example in which a species-specific anti-viral response may drive phylogenic divergence in insect virus evolution. Two baculoviruses, Autographa californica multiple nucleopolyhedrovirus (AcMNPV and Bombyx mori nucleopolyhedrovirus (BmNPV, have a high degree of DNA sequence similarity, but exhibit non-overlapping host specificity. In our study of their host-range determination, we found that BmNPV replication in B. mori cells was prevented by AcMNPV-P143 (AcP143, but not BmNPV-P143 (BmP143 or a hybrid P143 protein from a host-range expanded phenotype. This suggests that AcMNPV resistance in B. mori cells depends on AcP143 recognition and that BmNPV uses BmP143 to escapes this recognition. Based on these data, we propose an insect-baculovirus co-evolution scenario in which an ancestor of silkworms exploited an AcMNPV-resistant mechanism; AcMNPV counteracted this resistance via P143 mutations, resulting in the birth of BmNPV.
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Space-based ballistic-missile defense
International Nuclear Information System (INIS)
Bethe, H.A.; Garwin, R.L.; Gottfried, K.; Kendall, H.W.
1984-01-01
This article, based on a forthcoming book by the Union for Concerned Scientists, focuses on the technical aspects of the issue of space-based ballistic-missile defense. After analysis, the authors conclude that the questionable performance of the proposed defense, the ease with which it could be overwhelmed or circumvented, and its potential as an antisatellite system would cause grievous damage to the security of the US if the Strategic Defense Initiative were to be pursued. The path toward greater security lies in quite another direction, they feel. Although research on ballistic-missile defense should continue at the traditional level of expenditure and within the constraints of the ABM Treaty, every effort should be made to negotiate a bilateral ban on the testing and use of space weapons. The authors think it is essential that such an agreement cover all altitudes, because a ban on high-altitude antisatellite weapons alone would not viable if directed energy weapons were developed for ballistic-missile defense. Further, the Star Wars program, unlikely ever to protect the entire nation against a nuclear attack, would nonetheless trigger a major expansion of the arms race
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The science, technology, and politics of ballistic missile defense
Coyle, Philip E.
2014-05-01
America's missile defense systems are deployed at home and abroad. This includes the Groundbased Missile Defense (GMD) system in Alaska and California, the Phased Adaptive Approach in Europe (EPAA), and regional systems in the Middle East and Asia. Unfortunately these systems lack workable architectures, and many of the required elements either don't work or are missing. Major review and reconsideration is needed of all elements of these systems. GMD performance in tests has gotten worse with time, when it ought to be getting better. A lack of political support is not to blame as the DoD spends about 10 billion per year, and proposes to add about 5 billion over the next five years. Russia objects to the EPAA as a threat to its ICBM forces, and to the extensive deployment of U.S. military forces in countries such as Poland, the Czech Republic and Romania, once part of the Soviet Union. Going forward the U.S. should keep working with Russia whose cooperation will be key to diplomatic gains in the Middle East and elsewhere. Meanwhile, America's missile defenses face an enduring set of issues, especially target discrimination in the face of attacks designed to overwhelm the defenses, stage separation debris, chaff, decoys, and stealth. Dealing with target discrimination while also replacing, upgrading, or adding to the many elements of U.S. missiles defenses presents daunting budget priorities. A new look at the threat is warranted, and whether the U.S. needs to consider every nation that possesses even short-range missiles a threat to America. The proliferation of missiles of all sizes around the world is a growing problem, but expecting U.S. missile defenses to deal with all those missiles everywhere is unrealistic, and U.S. missile defenses, effective or not, are justifying more and more offensive missiles.
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The science, technology, and politics of ballistic missile defense
International Nuclear Information System (INIS)
Coyle, Philip E.
2014-01-01
America's missile defense systems are deployed at home and abroad. This includes the Groundbased Missile Defense (GMD) system in Alaska and California, the Phased Adaptive Approach in Europe (EPAA), and regional systems in the Middle East and Asia. Unfortunately these systems lack workable architectures, and many of the required elements either don't work or are missing. Major review and reconsideration is needed of all elements of these systems. GMD performance in tests has gotten worse with time, when it ought to be getting better. A lack of political support is not to blame as the DoD spends about $10 billion per year, and proposes to add about $5 billion over the next five years. Russia objects to the EPAA as a threat to its ICBM forces, and to the extensive deployment of U.S. military forces in countries such as Poland, the Czech Republic and Romania, once part of the Soviet Union. Going forward the U.S. should keep working with Russia whose cooperation will be key to diplomatic gains in the Middle East and elsewhere. Meanwhile, America's missile defenses face an enduring set of issues, especially target discrimination in the face of attacks designed to overwhelm the defenses, stage separation debris, chaff, decoys, and stealth. Dealing with target discrimination while also replacing, upgrading, or adding to the many elements of U.S. missiles defenses presents daunting budget priorities. A new look at the threat is warranted, and whether the U.S. needs to consider every nation that possesses even short-range missiles a threat to America. The proliferation of missiles of all sizes around the world is a growing problem, but expecting U.S. missile defenses to deal with all those missiles everywhere is unrealistic, and U.S. missile defenses, effective or not, are justifying more and more offensive missiles
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The science, technology, and politics of ballistic missile defense
Energy Technology Data Exchange (ETDEWEB)
Coyle, Philip E. [Center for Arms Control and Non-Proliferation, Washington, DC (United States)
2014-05-09
America's missile defense systems are deployed at home and abroad. This includes the Groundbased Missile Defense (GMD) system in Alaska and California, the Phased Adaptive Approach in Europe (EPAA), and regional systems in the Middle East and Asia. Unfortunately these systems lack workable architectures, and many of the required elements either don't work or are missing. Major review and reconsideration is needed of all elements of these systems. GMD performance in tests has gotten worse with time, when it ought to be getting better. A lack of political support is not to blame as the DoD spends about $10 billion per year, and proposes to add about $5 billion over the next five years. Russia objects to the EPAA as a threat to its ICBM forces, and to the extensive deployment of U.S. military forces in countries such as Poland, the Czech Republic and Romania, once part of the Soviet Union. Going forward the U.S. should keep working with Russia whose cooperation will be key to diplomatic gains in the Middle East and elsewhere. Meanwhile, America's missile defenses face an enduring set of issues, especially target discrimination in the face of attacks designed to overwhelm the defenses, stage separation debris, chaff, decoys, and stealth. Dealing with target discrimination while also replacing, upgrading, or adding to the many elements of U.S. missiles defenses presents daunting budget priorities. A new look at the threat is warranted, and whether the U.S. needs to consider every nation that possesses even short-range missiles a threat to America. The proliferation of missiles of all sizes around the world is a growing problem, but expecting U.S. missile defenses to deal with all those missiles everywhere is unrealistic, and U.S. missile defenses, effective or not, are justifying more and more offensive missiles.
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Bletz, Molly C.; Archer, Holly; Harris, Reid N.; McKenzie, Valerie J.; Rabemananjara, Falitiana C. E.; Rakotoarison, Andolalao; Vences, Miguel
2017-01-01
Host-associated microbiotas of vertebrates are diverse and complex communities that contribute to host health. In particular, for amphibians, cutaneous microbial communities likely play a significant role in pathogen defense; however, our ecological understanding of these communities is still in its infancy. Here, we take advantage of the fully endemic and locally species-rich amphibian fauna of Madagascar to investigate the factors structuring amphibian skin microbiota on a large scale. Using amplicon-based sequencing, we evaluate how multiple host species traits and site factors affect host bacterial diversity and community structure. Madagascar is home to over 400 native frog species, all of which are endemic to the island; more than 100 different species are known to occur in sympatry within multiple rainforest sites. We intensively sampled frog skin bacterial communities, from over 800 amphibians from 89 species across 30 sites in Madagascar during three field visits, and found that skin bacterial communities differed strongly from those of the surrounding environment. Richness of bacterial operational taxonomic units (OTUs) and phylogenetic diversity differed among host ecomorphs, with arboreal frogs exhibiting lower richness and diversity than terrestrial and aquatic frogs. Host ecomorphology was the strongest factor influencing microbial community structure, with host phylogeny and site parameters (latitude and elevation) explaining less but significant portions of the observed variation. Correlation analysis and topological congruency analyses revealed little to no phylosymbiosis for amphibian skin microbiota. Despite the observed geographic variation and low phylosymbiosis, we found particular OTUs that were differentially abundant between particular ecomorphs. For example, the genus Pigmentiphaga (Alcaligenaceae) was significantly enriched on arboreal frogs, Methylotenera (Methylophilaceae) was enriched on aquatic frogs, and Agrobacterium (Rhizobiaceae
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Directory of Open Access Journals (Sweden)
Molly C. Bletz
2017-08-01
Full Text Available Host-associated microbiotas of vertebrates are diverse and complex communities that contribute to host health. In particular, for amphibians, cutaneous microbial communities likely play a significant role in pathogen defense; however, our ecological understanding of these communities is still in its infancy. Here, we take advantage of the fully endemic and locally species-rich amphibian fauna of Madagascar to investigate the factors structuring amphibian skin microbiota on a large scale. Using amplicon-based sequencing, we evaluate how multiple host species traits and site factors affect host bacterial diversity and community structure. Madagascar is home to over 400 native frog species, all of which are endemic to the island; more than 100 different species are known to occur in sympatry within multiple rainforest sites. We intensively sampled frog skin bacterial communities, from over 800 amphibians from 89 species across 30 sites in Madagascar during three field visits, and found that skin bacterial communities differed strongly from those of the surrounding environment. Richness of bacterial operational taxonomic units (OTUs and phylogenetic diversity differed among host ecomorphs, with arboreal frogs exhibiting lower richness and diversity than terrestrial and aquatic frogs. Host ecomorphology was the strongest factor influencing microbial community structure, with host phylogeny and site parameters (latitude and elevation explaining less but significant portions of the observed variation. Correlation analysis and topological congruency analyses revealed little to no phylosymbiosis for amphibian skin microbiota. Despite the observed geographic variation and low phylosymbiosis, we found particular OTUs that were differentially abundant between particular ecomorphs. For example, the genus Pigmentiphaga (Alcaligenaceae was significantly enriched on arboreal frogs, Methylotenera (Methylophilaceae was enriched on aquatic frogs, and Agrobacterium
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Bletz, Molly C; Archer, Holly; Harris, Reid N; McKenzie, Valerie J; Rabemananjara, Falitiana C E; Rakotoarison, Andolalao; Vences, Miguel
2017-01-01
Host-associated microbiotas of vertebrates are diverse and complex communities that contribute to host health. In particular, for amphibians, cutaneous microbial communities likely play a significant role in pathogen defense; however, our ecological understanding of these communities is still in its infancy. Here, we take advantage of the fully endemic and locally species-rich amphibian fauna of Madagascar to investigate the factors structuring amphibian skin microbiota on a large scale. Using amplicon-based sequencing, we evaluate how multiple host species traits and site factors affect host bacterial diversity and community structure. Madagascar is home to over 400 native frog species, all of which are endemic to the island; more than 100 different species are known to occur in sympatry within multiple rainforest sites. We intensively sampled frog skin bacterial communities, from over 800 amphibians from 89 species across 30 sites in Madagascar during three field visits, and found that skin bacterial communities differed strongly from those of the surrounding environment. Richness of bacterial operational taxonomic units (OTUs) and phylogenetic diversity differed among host ecomorphs, with arboreal frogs exhibiting lower richness and diversity than terrestrial and aquatic frogs. Host ecomorphology was the strongest factor influencing microbial community structure, with host phylogeny and site parameters (latitude and elevation) explaining less but significant portions of the observed variation. Correlation analysis and topological congruency analyses revealed little to no phylosymbiosis for amphibian skin microbiota. Despite the observed geographic variation and low phylosymbiosis, we found particular OTUs that were differentially abundant between particular ecomorphs. For example, the genus Pigmentiphaga (Alcaligenaceae) was significantly enriched on arboreal frogs, Methylotenera (Methylophilaceae) was enriched on aquatic frogs, and Agrobacterium (Rhizobiaceae
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Defense Strategies for Asymmetric Networked Systems with Discrete Components
Directory of Open Access Journals (Sweden)
Nageswara S. V. Rao
2018-05-01
Full Text Available We consider infrastructures consisting of a network of systems, each composed of discrete components. The network provides the vital connectivity between the systems and hence plays a critical, asymmetric role in the infrastructure operations. The individual components of the systems can be attacked by cyber and physical means and can be appropriately reinforced to withstand these attacks. We formulate the problem of ensuring the infrastructure performance as a game between an attacker and a provider, who choose the numbers of the components of the systems and network to attack and reinforce, respectively. The costs and benefits of attacks and reinforcements are characterized using the sum-form, product-form and composite utility functions, each composed of a survival probability term and a component cost term. We present a two-level characterization of the correlations within the infrastructure: (i the aggregate failure correlation function specifies the infrastructure failure probability given the failure of an individual system or network, and (ii the survival probabilities of the systems and network satisfy first-order differential conditions that capture the component-level correlations using multiplier functions. We derive Nash equilibrium conditions that provide expressions for individual system survival probabilities and also the expected infrastructure capacity specified by the total number of operational components. We apply these results to derive and analyze defense strategies for distributed cloud computing infrastructures using cyber-physical models.
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Defense Strategies for Asymmetric Networked Systems with Discrete Components.
Rao, Nageswara S V; Ma, Chris Y T; Hausken, Kjell; He, Fei; Yau, David K Y; Zhuang, Jun
2018-05-03
We consider infrastructures consisting of a network of systems, each composed of discrete components. The network provides the vital connectivity between the systems and hence plays a critical, asymmetric role in the infrastructure operations. The individual components of the systems can be attacked by cyber and physical means and can be appropriately reinforced to withstand these attacks. We formulate the problem of ensuring the infrastructure performance as a game between an attacker and a provider, who choose the numbers of the components of the systems and network to attack and reinforce, respectively. The costs and benefits of attacks and reinforcements are characterized using the sum-form, product-form and composite utility functions, each composed of a survival probability term and a component cost term. We present a two-level characterization of the correlations within the infrastructure: (i) the aggregate failure correlation function specifies the infrastructure failure probability given the failure of an individual system or network, and (ii) the survival probabilities of the systems and network satisfy first-order differential conditions that capture the component-level correlations using multiplier functions. We derive Nash equilibrium conditions that provide expressions for individual system survival probabilities and also the expected infrastructure capacity specified by the total number of operational components. We apply these results to derive and analyze defense strategies for distributed cloud computing infrastructures using cyber-physical models.
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Symbiotic Bacteria Enable Olive Fly Larvae to Overcome Host Defenses
International Nuclear Information System (INIS)
Ben-Yosef, Michael; Yuval, Boaz; Pasternak, Zohar; Jurkevitch, Edouard
2016-01-01
Ripe fruit offer readily available nutrients for many animals, including fruit fly larvae (Diptera: Tephritidae) and their associated rot-inducing bacteria. Yet, during most of their ontogeny, fruit remain chemically defended and effectively suppress herbivores and pathogens by high levels of secondary metabolites. Olive flies (Bactrocera oleae) are uniquely able to develop in unripe olives. Unlike other frugivorous tephritids, the larvae maintain bacteria confined within their midgut caeca. We examined the interaction between larvae, their associated bacteria, and fruit chemical defence, hypothesizing that bacterial contribution to larval development is contingent on the phenology of fruit defensive chemistry. We demonstrate that larvae require their natural complement of bacteria (Candidatus Erwinia dacicola: Enterobacteriaceae) in order to develop in unripe olives. Conversely, when feeding on ripe fruit, larval development proceeds independently of these bacteria. Our experiments suggest that bacteria counteract the inhibitory effect of oleuropein—the principal phenolic glycoside in unripe olives. In light of these results, we suggest that the unique symbiosis in olive flies, compared with other frugivorous tephritids, is understood by considering the relationship between the fly, bacteria and fruit chemistry. When applied in an evolutionary context, this approach may also point out the forces which shaped symbioses across the Tephritidae. (author)
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Duhamel, Marie; Pel, Roel; Ooms, Astra; Bücking, Heike; Jansa, Jan; Ellers, Jacintha; van Straalen, Nico M; Wouda, Tjalf; Vandenkoornhuyse, Philippe; Kiers, E Toby
2013-09-01
A key objective in ecology is to understand how cooperative strategies evolve and are maintained in species networks. Here, we focus on the tri-trophic relationship between arbuscular mycorrhizal (AM) fungi, host plants, and fungivores to ask if host plants are able to protect their mutualistic mycorrhizal partners from being grazed. Specifically, we test whether secondary metabolites are transferred from hosts to fungal partners to increase their defense against fungivores. We grew Plantago lanceolata hosts with and without mycorrhizal inoculum, and in the presence or absence of fungivorous springtails. We then measured fungivore effects on host biomass and mycorrhizal abundance (using quantitative PCR) in roots and soil. We used high-performance liquid chromatography to measure host metabolites in roots, shoots, and hyphae, focusing on catalpol, aucubin, and verbascoside. Our most striking result was that the metabolite catalpol was consistently found in AM fungal hyphae in host plants exposed to fungivores. When fungivores were absent, catalpol was undetectable in hyphae. Our results highlight the potential for plant-mediated protection of the mycorrhizal hyphal network.
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Buerger, Patrick; Wood-Charlson, Elisha M; Weynberg, Karen D; Willis, Bette L; van Oppen, Madeleine J H
2016-01-01
Understanding how pathogens maintain their virulence is critical to developing tools to mitigate disease in animal populations. We sequenced and assembled the first draft genome of Roseofilum reptotaenium AO1, the dominant cyanobacterium underlying pathogenicity of the virulent coral black band disease (BBD), and analyzed parts of the BBD-associated Geitlerinema sp. BBD_1991 genome in silico . Both cyanobacteria are equipped with an adaptive, heritable clustered regularly interspaced short palindromic repeats (CRISPR)-Cas defense system type I-D and have potential virulence genes located within several prophage regions. The defense system helps to prevent infection by viruses and mobile genetic elements via identification of short fingerprints of the intruding DNA, which are stored as templates in the bacterial genome, in so-called "CRISPRs." Analysis of CRISPR target sequences (protospacers) revealed an unusually high number of self-targeting spacers in R. reptotaenium AO1 and extraordinary long CRIPSR arrays of up to 260 spacers in Geitlerinema sp. BBD_1991. The self-targeting spacers are unlikely to be a form of autoimmunity; instead these target an incomplete lysogenic bacteriophage. Lysogenic virus induction experiments with mitomycin C and UV light did not reveal an actively replicating virus population in R. reptotaenium AO1 cultures, suggesting that phage functionality is compromised or excision could be blocked by the CRISPR-Cas system. Potential prophages were identified in three regions of R. reptotaenium AO1 and five regions of Geitlerinema sp. BBD_1991, containing putative BBD relevant virulence genes, such as an NAD-dependent epimerase/dehydratase (a homolog in terms of functionality to the third and fourth most expressed gene in BBD), lysozyme/metalloendopeptidases and other lipopolysaccharide modification genes. To date, viruses have not been considered to be a component of the BBD consortium or a contributor to the virulence of R. reptotaenium AO1
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2010-11-24
... also asked what allowance is provided for contractors with accounting software that does not... RIN 0750-AG46 Defense Federal Acquisition Regulation Supplement; Cost and Software Data Reporting... Regulation Supplement (DFARS) to address DoD Cost and Software Data Reporting system requirements for Major...
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Gupta, Kshitij; Idahosa, Chizobam; Roy, Saptarshi; Lee, Donguk; Subramanian, Hariharan; Dhingra, Anuradha; Boesze-Battaglia, Kathleen; Korostoff, Jonathan; Ali, Hydar
2017-10-01
Porphyromonas gingivalis is a keystone pathogen that contributes to periodontal pathogenesis by disrupting host-microbe homeostasis and promoting dysbiosis. The virulence of P. gingivalis likely reflects an alteration in the lipid A composition of its lipopolysaccharide (LPS) from the penta-acylated ( Pg LPS 1690 ) to the tetra-acylated ( Pg LPS 1435/1449 ) form. Mast cells play an important role in periodontitis, but the mechanisms of their activation and regulation remain unknown. The expression of epithelium- and neutrophil-derived host defense peptides (HDPs) (LL-37 and human β-defensin-3), which activate mast cells via Mas-related G protein-coupled receptor X2 (MRGPRX2), is increased in periodontitis. We found that MRGPRX2-expressing mast cells are present in normal gingiva and that their numbers are elevated in patients with chronic periodontitis. Furthermore, HDPs stimulated degranulation in a human mast cell line (LAD2) and in RBL-2H3 cells stably expressing MRGPRX2 (RBL-MRGPRX2). Pg LPS 1690 caused substantial inhibition of HDP-induced mast cell degranulation, but Pg LPS 1435/1449 had no effect. A fluorescently labeled HDP (FAM-LL-37) bound to RBL-MRGPRX2 cells, and Pg LPS 1690 inhibited this binding, but Pg LPS 1435/1449 had no effect. These findings suggest that low-level inflammation induced by HDP/MRGPRX2-mediated mast cell degranulation contributes to gingival homeostasis but that sustained inflammation due to elevated levels of both HDPs and MRGPRX2-expressing mast cells promotes periodontal disease. Furthermore, differential regulation of HDP-induced mast cell degranulation by Pg LPS 1690 and Pg LPS 1435/1449 may contribute to the modulation of disease progression. Copyright © 2017 American Society for Microbiology.
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Directory of Open Access Journals (Sweden)
Shunyi Li
2013-01-01
Full Text Available A predator-prey system with generalized group defense and impulsive control strategy is investigated. By using Floquet theorem and small amplitude perturbation skills, a local asymptotically stable prey-eradication periodic solution is obtained when the impulsive period is less than some critical value. Otherwise, the system is permanent if the impulsive period is larger than the critical value. By using bifurcation theory, we show the existence and stability of positive periodic solution when the pest eradication lost its stability. Numerical examples show that the system considered has more complicated dynamics, including (1 high-order quasiperiodic and periodic oscillation, (2 period-doubling and halving bifurcation, (3 nonunique dynamics (meaning that several attractors coexist, and (4 chaos and attractor crisis. Further, the importance of the impulsive period, the released amount of mature predators and the degree of group defense effect are discussed. Finally, the biological implications of the results and the impulsive control strategy are discussed.
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McCollom, Thomas M
2007-12-01
Numerical models are employed to investigate sources of chemical energy for autotrophic microbial metabolism that develop during mixing of oxidized seawater with strongly reduced fluids discharged from ultramafic-hosted hydrothermal systems on the seafloor. Hydrothermal fluids in these systems are highly enriched in H(2) and CH(4) as a result of alteration of ultramafic rocks (serpentinization) in the subsurface. Based on the availability of chemical energy sources, inferences are made about the likely metabolic diversity, relative abundance, and spatial distribution of microorganisms within ultramafic-hosted systems. Metabolic reactions involving H(2) and CH(4), particularly hydrogen oxidation, methanotrophy, sulfate reduction, and methanogenesis, represent the predominant sources of chemical energy during fluid mixing. Owing to chemical gradients that develop from fluid mixing, aerobic metabolisms are likely to predominate in low-temperature environments (energy per kilogram of hydrothermal fluid, while anaerobic metabolic reactions can supply about 1 kJ, which is sufficient to support a maximum of approximately 120 mg (dry weight) of primary biomass production by aerobic organisms and approximately 20-30 mg biomass by anaerobes. The results indicate that ultramafic-hosted systems are capable of supplying about twice as much chemical energy as analogous deep-sea hydrothermal systems hosted in basaltic rocks.
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Schistosome serine protease inhibitors: parasite defense or homeostasis?
Directory of Open Access Journals (Sweden)
Landys A. Lopez Quezada
2011-06-01
Full Text Available Serpins are a structurally conserved family of macromolecular inhibitors found in numerous biological systems. The completion and annotation of the genomes of Schistosoma mansoni and Schistosoma japonicum has enabled the identification by phylogenetic analysis of two major serpin clades. S. mansoni shows a greater multiplicity of serpin genes, perhaps reflecting adaptation to infection of a human host. Putative targets of schistosome serpins can be predicted from the sequence of the reactive center loop (RCL. Schistosome serpins may play important roles in both post-translational regulation of schistosome-derived proteases, as well as parasite defense mechanisms against the action of host proteases.Serpinas são uma família de inibidores macromoleculares estruturalmente conservados encontrados em inúmeros sistemas biológicos. O término e a anotação dos genomas de Schistosoma mansoni e de Schistosoma japonicum permitiram a identificação por análise filogenética de dois principais clados de serpinas. S. mansoni mostra uma multiplicidade maior de genes de serpinas, talvez refletindo uma adaptação à infecção de um hospedeiro humano. Alvos putativos das serpinas de esquistossomos podem ser preditos a partir da sequência do "loop" do centro reativo. Serpinas de esquistossomos podem ter importantes papeis tanto na regulação pós-traducional de proteases derivadas do esquistossoma, quanto nos mecanismos de defesa contra a ação de proteases do hospedeiro.
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The journal of medical chemical, biological and radiological defense, an update
International Nuclear Information System (INIS)
Price, B. B. S.; Peitersen, L.E.
2009-01-01
The Journal of Medical Chemical, Biological, and Radiological Defense (www.JMedCBR.org) is a peer-reviewed scientific online journal focusing on the biology, chemistry, physiology, toxicology and treatment of exposure to threat agents. JMedCBR provides a central international forum for the publication of current research and development information on medical chemical, biological and radiological defense, as well as training, doctrine, and problems related to chemical, biological and radiological casualties. JMedCBR is sponsored by the US Defense Threat Reduction Agency (DTRA) Chem-Bio Technologies Directorate as part of its scientific outreach program in chemical and biological defense solutions for the Department of Defense. In addition to scientific and medical research, JMedCBR hosts an archive of related papers from authors in the field. Although organized into annual issues, articles are published on the web continuously. The complete JMedCBR is published electronically and is made available to the scientific community free of charge. JMedCBR is committed to providing its readers with quality scientific information and critical analyses. All submissions are peer-reviewed by an editorial board of recognized and respected international scientists who represent expertise in different aspects of medical chemical, biological and radiological defense. Contributions to JMedCBR must be original works of the author(s) and must not have been previously published or simultaneously submitted to other publications. The author(s) transfer the copyright of articles published in JMedCBR to the journal. A copyright transfer form must accompany each manuscript submission. For more information on submitting to JMedCBR, see the Authors' Guide, available at http://www.jmedcbr.org/authorGuide.html.(author)
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Contribution to the improvement of management in defense logistics
Directory of Open Access Journals (Sweden)
Srđan D. Ljubojević
2013-12-01
Full Text Available Introduction Changes in social environment require adequate answers of all organizational systems, including defense systems and their logistic systems. Improvement of management in defense logistics involves good knowledge of management theory and practice, knowledge of the impact of ownership and market on management, knowledge of public and other macroeconomic sectors functioning, broader opening towards environment and the exchange of knowledge, information and lessons learned with international environment. The paper presents theoretical and practical knowledge that is prerequisite for improving the management of defense and the management of defense logistic systems. Definition and the essence of management Regarding its complexity and a lack of a comprehensive definition, the concept of management is nowadays considered in three ways: as a skill, as social categories - structure of management, as well as a theory - a scientific discipline. When we aanalyze the phenomenon of management, with respect to the historical aspect of its development, there is a necessity to distinguish between management as a scientific discipline and management practice. Relation between organizational science and management In theory and practice, management is associated with the achievements of many other scientific fields. One of the areas closest to management is organizational science. Today, in the management theory and organization theory, the prevailing attitudes state that these two areas are non-separable and that they are focused on the explaination of the same phenomenon, with the same desire to improve effectivity and development of different purpose systems. There is no clear boundary between organizational science and management, both from theoretical and practical aspects. Achievements and shortcomings of organizational schools As a result of solving problems in real systems, a number of opinions and different organizational
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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
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A Binary System in the Hyades Cluster Hosting a Neptune-Sized Planet
Feinstein, Adina; Ciardi, David; Crossfield, Ian; Schlieder, Joshua; Petigura, Erik; David, Trevor J.; Bristow, Makennah; Patel, Rahul; Arnold, Lauren; Benneke, Björn; Christiansen, Jessie; Dressing, Courtney; Fulton, Benjamin; Howard, Andrew; Isaacson, Howard; Sinukoff, Evan; Thackeray, Beverly
2018-01-01
We report the discovery of a Neptune-size planet (Rp = 3.0Rearth) in the Hyades Cluster. The host star is in a binary system, comprising a K5V star and M7/8V star with a projected separation of 40 AU. The planet orbits the primary star with an orbital period of 17.3 days and a transit duration of 3 hours. The host star is bright (V = 11.2, J = 9.1) and so may be a good target for precise radial velocity measurements. The planet is the first Neptune-sized planet to be found orbiting in a binary system within an open cluster. The Hyades is the nearest star cluster to the Sun, has an age of 625-750 Myr, and forms one of the fundamental rungs in the distance ladder; understanding the planet population in such a well-studied cluster can help us understand and set contraints on the formation and evolution of planetary systems.
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Directory of Open Access Journals (Sweden)
Nishanth Makthal
2017-07-01
Full Text Available Bacterial pathogens must overcome host immune mechanisms to acquire micronutrients for successful replication and infection. Streptococcus pyogenes, also known as group A streptococcus (GAS, is a human pathogen that causes a variety of clinical manifestations, and disease prevention is hampered by lack of a human GAS vaccine. Herein, we report that the mammalian host recruits calprotectin (CP to GAS infection sites and retards bacterial growth by zinc limitation. However, a GAS-encoded zinc importer and a nuanced zinc sensor aid bacterial defense against CP-mediated growth inhibition and contribute to GAS virulence. Immunization of mice with the extracellular component of the zinc importer confers protection against systemic GAS challenge. Together, we identified a key early stage host-GAS interaction and translated that knowledge into a novel vaccine strategy against GAS infection. Furthermore, we provided evidence that a similar struggle for zinc may occur during other streptococcal infections, which raises the possibility of a broad-spectrum prophylactic strategy against multiple streptococcal pathogens.
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2010-06-11
... Certain Contracts with Foreign Entities for the Conduct of Ballistic Missile Defense Research, Development..., development, test, or evaluation in connection with the Ballistic Missile Defense Program. The provision... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [OMB Control Number 0704-0229...
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A Phosphorylation Switch on Lon Protease Regulates Bacterial Type III Secretion System in Host
Directory of Open Access Journals (Sweden)
Xiaofeng Zhou
2018-01-01
Full Text Available Most pathogenic bacteria deliver virulence factors into host cytosol through type III secretion systems (T3SS to perturb host immune responses. The expression of T3SS is often repressed in rich medium but is specifically induced in the host environment. The molecular mechanisms underlying host-specific induction of T3SS expression is not completely understood. Here we demonstrate in Xanthomonas citri that host-induced phosphorylation of the ATP-dependent protease Lon stabilizes HrpG, the master regulator of T3SS, conferring bacterial virulence. Ser/Thr/Tyr phosphoproteome analysis revealed that phosphorylation of Lon at serine 654 occurs in the citrus host. In rich medium, Lon represses T3SS by degradation of HrpG via recognition of its N terminus. Genetic and biochemical data indicate that phosphorylation at serine 654 deactivates Lon proteolytic activity and attenuates HrpG proteolysis. Substitution of alanine for Lon serine 654 resulted in repression of T3SS gene expression in the citrus host through robust degradation of HrpG and reduced bacterial virulence. Our work reveals a novel mechanism for distinct regulation of bacterial T3SS in different environments. Additionally, our data provide new insight into the role of protein posttranslational modification in the regulation of bacterial virulence.
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Dual role of Fcγ receptors in host defense and disease in Borrelia burgdorferi-infected mice
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Alexia Anne Belperron
2014-06-01
Full Text Available Arthritis in mice infected with the Lyme disease spirochete, Borrelia burgdorferi, results from the influx of innate immune cells responding to the pathogen in the joint and is influenced in part by mouse genetics. Production of inflammatory cytokines by innate immune cells in vitro is largely mediated by Toll-like receptor (TLR interaction with Borrelia lipoproteins, yet surprisingly mice deficient in TLR2 or the TLR signaling molecule MyD88 still develop arthritis comparable to that seen in wild type mice after B. burgdorferi infection. These findings suggest that other, MyD88-independent inflammatory pathways can contribute to arthritis expression. Clearance of B. burgdorferi is dependent on the production of specific antibody and phagocytosis of the organism. As Fc receptors (FcγR are important for IgG-mediated clearance of immune complexes and opsonized particles by phagocytes, we examined the role that FcγR play in host defense and disease in B. burgdorferi-infected mice. B. burgdorferi-infected mice deficient in the Fc receptor common gamma chain (FcεRγ-/- mice harbored ~10 fold more spirochetes than similarly infected wild type mice, and this was associated with a transient increase in arthritis severity. While the elevated pathogen burdens seen in B. burgdorferi-infected MyD88-/- mice were not affected by concomitant deficiency in FcγR, arthritis was reduced in FcεRγ-/-MyD88-/- mice in comparison to wild type or single knockout mice. Gene expression analysis from infected joints demonstrated that absence of both MyD88 and FcγR lowers mRNA levels of proteins involved in inflammation, including Cxcl1 (KC, Xcr1 (Gpr5, IL-1beta, and C reactive protein. Taken together, our results demonstrate a role for FcγR-mediated immunity in limiting pathogen burden and arthritis in mice during the acute phase of B. burgdorferi infection, and further suggest that this pathway contributes to the arthritis that develops in B. burgdorferi
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Bernsdorff, Friederike; Döring, Anne-Christin; Gruner, Katrin; Schuck, Stefan; Bräutigam, Andrea; Zeier, Jürgen
2016-01-01
We investigated the relationships of the two immune-regulatory plant metabolites, salicylic acid (SA) and pipecolic acid (Pip), in the establishment of plant systemic acquired resistance (SAR), SAR-associated defense priming, and basal immunity. Using SA-deficient sid2, Pip-deficient ald1, and sid2 ald1 plants deficient in both SA and Pip, we show that SA and Pip act both independently from each other and synergistically in Arabidopsis thaliana basal immunity to Pseudomonas syringae. Transcriptome analyses reveal that SAR establishment in Arabidopsis is characterized by a strong transcriptional response systemically induced in the foliage that prepares plants for future pathogen attack by preactivating multiple stages of defense signaling and that SA accumulation upon SAR activation leads to the downregulation of photosynthesis and attenuated jasmonate responses systemically within the plant. Whereas systemic Pip elevations are indispensable for SAR and necessary for virtually the whole transcriptional SAR response, a moderate but significant SA-independent component of SAR activation and SAR gene expression is revealed. During SAR, Pip orchestrates SA-dependent and SA-independent priming of pathogen responses in a FLAVIN-DEPENDENT-MONOOXYGENASE1 (FMO1)-dependent manner. We conclude that a Pip/FMO1 signaling module acts as an indispensable switch for the activation of SAR and associated defense priming events and that SA amplifies Pip-triggered responses to different degrees in the distal tissue of SAR-activated plants. © 2016 American Society of Plant Biologists. All rights reserved.
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Soviet civil defense plans make nuclear war winnable
International Nuclear Information System (INIS)
Goure, L.
1985-01-01
In this paper, the author expresses his opinion that the U.S. is naive and suicidal in its lack of civil defense preparation for nuclear war. The Soviets' extensive civil defense planning is evidence that they plan to use their nuclear weapons and survive a counterattack by the U.S. The author compares the two systems and explains why the Soviets' system is superior
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Hitting the Sweet Spot: Glycans as Targets of Fungal Defense Effector Proteins
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Markus Künzler
2015-05-01
Full Text Available Organisms which rely solely on innate defense systems must combat a large number of antagonists with a comparatively low number of defense effector molecules. As one solution of this problem, these organisms have evolved effector molecules targeting epitopes that are conserved between different antagonists of a specific taxon or, if possible, even of different taxa. In order to restrict the activity of the defense effector molecules to physiologically relevant taxa, these target epitopes should, on the other hand, be taxon-specific and easily accessible. Glycans fulfill all these requirements and are therefore a preferred target of defense effector molecules, in particular defense proteins. Here, we review this defense strategy using the example of the defense system of multicellular (filamentous fungi against microbial competitors and animal predators.
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Contribution to the improvement of management in defense logistics
LJUBOJEVIC SRDJAN D.; ANDREJIC MARKO D.; DRAGOVIC NEBOJSA K.
2013-01-01
Introduction Changes in social environment require adequate answers of all organizational systems, including defense systems and their logistic systems. Improvement of management in defense logistics involves good knowledge of management theory and practice, knowledge of the impact of ownership and market on management, knowledge of public and other macroeconomic sectors functioning, broader opening towards environment and the exchange of knowledge, information and lessons learned with inter...
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DEFF Research Database (Denmark)
Hartshorn, Kevan L.; White, Mitchell R.; Tecle, Tesfaldet
2006-01-01
Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection, in part by modifying interactions with neutrophils. Human neutrophil defensins (HNPs) inhibit infectivity of enveloped viruses, including IAV. Our goal in this study...
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Plant RNA binding proteins for control of RNA virus infection
Directory of Open Access Journals (Sweden)
Sung Un eHuh
2013-12-01
Full Text Available Plant RNA viruses have effective strategies to infect host plants through either direct or indirect interactions with various host proteins, thus suppressing the host immune system. When plant RNA viruses enter host cells exposed RNAs of viruses are recognized by the host immune system through processes such as siRNA-dependent silencing. Interestingly, some host RNA binding proteins have been involved in the inhibition of RNA virus replication, movement, and translation through RNA-specific binding. Host plants intensively use RNA binding proteins for defense against viral infections in nature. In this mini review, we will summarize the function of some host RNA binding proteins which act in a sequence-specific binding manner to the infecting virus RNA. It is important to understand how plants effectively suppresses RNA virus infections via RNA binding proteins, and this defense system can be potentially developed as a synthetic virus defense strategy for use in crop engineering.
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Directory of Open Access Journals (Sweden)
Jay Zhang
Full Text Available Mycobacterium tuberculosis (MTB infects an estimated one-third of the global population and is one of the main causes of mortality from an infectious agent. The characteristics of macrophages challenged by MTB with a high multiplicity of infection (MOI, which mimics both clinical disseminated infection and granuloma formation, are distinct from macrophages challenged with a low MOI. To better understand the cross talk between macrophage host cells and mycobacteria, we compared the transcription patterns of mouse macrophages infected with bacille Calmette-Guérin, H37Ra and M. smegmatis. Attention was focused on the changes in the abundance of transcripts related to immune system function. From the results of a transcriptome profiling study with a high mycobacterial MOI, we defined a pathogen-specific host gene expression pattern. The present study suggests that two integrins, ITGA5 and ITGAV, are novel cell surface receptors mediating mycobacterium entry into macrophages challenged with high MOI. Our results indicate that SRC likely plays a central role in regulating multiple unique signaling pathways activated by MTB infection. The integrated results increase our understanding of the molecular networks behind the host innate immune response and identify important targets that might be useful for the development of tuberculosis therapy.
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2013-11-22
... and Procedures AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION... proposed information collection; (c) ways to enhance the quality, utility, and clarity of the information..., withhold, or withdraw purchasing system approval at the conclusion of a purchasing system review...
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VirHostNet 2.0: surfing on the web of virus/host molecular interactions data.
Guirimand, Thibaut; Delmotte, Stéphane; Navratil, Vincent
2015-01-01
VirHostNet release 2.0 (http://virhostnet.prabi.fr) is a knowledgebase dedicated to the network-based exploration of virus-host protein-protein interactions. Since the previous VirhostNet release (2009), a second run of manual curation was performed to annotate the new torrent of high-throughput protein-protein interactions data from the literature. This resource is shared publicly, in PSI-MI TAB 2.5 format, using a PSICQUIC web service. The new interface of VirHostNet 2.0 is based on Cytoscape web library and provides a user-friendly access to the most complete and accurate resource of virus-virus and virus-host protein-protein interactions as well as their projection onto their corresponding host cell protein interaction networks. We hope that the VirHostNet 2.0 system will facilitate systems biology and gene-centered analysis of infectious diseases and will help to identify new molecular targets for antiviral drugs design. This resource will also continue to help worldwide scientists to improve our knowledge on molecular mechanisms involved in the antiviral response mediated by the cell and in the viral strategies selected by viruses to hijack the host immune system. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
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Anorexia and Attachment: Dysregulated Defense and Pathological Mourning
Directory of Open Access Journals (Sweden)
elisa edelvecchio
2014-10-01
Full Text Available The role of Defensive exclusion (Deactivation and Segregated Systems in the development of early relationships and related to subsequent manifestations of symptoms of eating disorders was assessed using the Adult Attachment Projective Picture System (AAP. Fifty-one DSM-IV diagnosed women with anorexia participated in the study. Anorexic patients were primarily classified as dismissing or unresolved. Quantitative and qualitative analyses of defensive exclusion were carried out. Results showed potential benefits of using the AAP defense exclusion coding system, in addition to the main attachment classifications, in order to better understand the developmental issues involved in anorexia. Discussion concerned the processes, such as pathological mourning, that may underlie the associations between dismissing and unresolved attachment and anorexia. Implications for developmental research and clinical nosology are discussed.
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Technical Soddi Defenses: The Trojan Horse Defense Revisited
Directory of Open Access Journals (Sweden)
Chad Steel
2014-12-01
Full Text Available In 2004, the Trojan horse defense was at a crossroads, with two child pornography cases where it was successfully employed in the United Kingdom, resulting in acquittals. The original Trojan horse defense has now become part of the more general “technical SODDI” defense, which includes the possibility of unknown actors using unsecured Wi-Fi connections or having physical access to a computer to perform criminal acts. In the past ten years, it has failed to be effective in the United States for criminal cases, with no published acquittals in cases where it was the primary defense. In the criminal cases where it has been used as leverage in plea negotiations, there has been either poor forensics performed by the prosecution or political pressure to resolve a matter. On the civil side, however, the defense has been wildly successful, effectively shutting down large John Doe copyright infringement litigation against non-commercial violators.
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Directory of Open Access Journals (Sweden)
Gilberto Santos Andrade
Full Text Available Interactions of the parasitoids Palmistichus elaeisis Delvare & LaSalle and Trichospilus diatraeae Cherian & Margabandhu (Hymenoptera: Eulophidae with its alternative host Anticarsia gemmatalis (Hübner (Lepidoptera: Noctuidae affect the success or failure of the mass production of these parasitoids for use in integrated pest management programs. The aim of this study was to evaluate changes in the cellular defense and encapsulation ability of A. gemmatalis pupae against P. elaeisis or T. diatraeae in adult parasitoid densities of 1, 3, 5, 7, 9, 11 or 13 parasitoids/pupae. We evaluated the total quantity of circulating hemocytes and the encapsulation rate versus density. Increasing parasitoid density reduced the total number of hemocytes in the hemolymph and the encapsulation rate by parasitized pupae. Furthermore, densities of P. elaeisis above 5 parasitoids/pupae caused higher reduction in total hemocyte numbers. The encapsulation rate fell with increasing parasitoid density. However, parasitic invasion by both species induced generally similar responses. The reduction in defensive capacity of A. gemmatalis is related to the adjustment of the density of these parasitoids to their development in this host. Thus, the role of the density of P. elaeisis or T. diatraeae by pupa is induced suppression of cellular defense and encapsulation of the host, even without them possesses a co-evolutionary history. Furthermore, these findings can predict the success of P. elaeisis and T. diatraeae in the control of insect pests through the use of immunology as a tool for evaluation of natural enemies.
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Panngom, Kamonporn; Lee, Sang Hark; Park, Dae Hoon; Sim, Geon Bo; Kim, Yong Hee; Uhm, Han Sup; Park, Gyungsoon; Choi, Eun Ha
2014-01-01
Reactive oxygen and nitrogen species can have either harmful or beneficial effects on biological systems depending on the dose administered and the species of organism exposed, suggesting that application of reactive species can possibly produce contradictory effects in disease control, pathogen inactivation and activation of host resistance. A novel technology known as atmospheric-pressure non-thermal plasma represents a means of generating various reactive species that adversely affect pathogens (inactivation) while simultaneously up-regulating host defense genes. The anti-microbial efficacy of this technology was tested on the plant fungal pathogen Fusarium oxysporum f.sp. lycopersici and its susceptible host plant species Solanum lycopercicum. Germination of fungal spores suspended in saline was decreased over time after exposed to argon (Ar) plasma for 10 min. Although the majority of treated spores exhibited necrotic death, apoptosis was also observed along with the up-regulation of apoptosis related genes. Increases in the levels of peroxynitrite and nitrite in saline following plasma treatment may have been responsible for the observed spore death. In addition, increased transcription of pathogenesis related (PR) genes was observed in the roots of the susceptible tomato cultivar (S. lycopercicum) after exposure to the same Ar plasma dose used in fungal inactivation. These data suggest that atmospheric-pressure non-thermal plasma can be efficiently used to control plant fungal diseases by inactivating fungal pathogens and up-regulating mechanisms of host resistance.
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IRAK-M regulation and function in host defense and immune homeostasis
Directory of Open Access Journals (Sweden)
Leah L.N. Hubbard
2010-06-01
Full Text Available Antigen presenting cells (APCs of the innate immune system sense a wide range of pathogens via pattern recognition receptors (PRRs. Engagement of certain PRRs can induce production of pro-inflammatory mediators that facilitate effective clearance of pathogen. Toll-like receptors (TLRs are a well described group of PRRs that belong to the TLR/Interleukin-1 receptor (IL-1R superfamily. However, TLR/IL-1R induction of pro-inflammatory mediators must be regulated to prevent excessive inflammation and tissue damage. One molecule of recent interest that is known to inhibit TLR/IL-1R signaling is interleukin-1 receptor associated kinase (IRAK-M, also known as IRAK-3. IRAK-M is expressed in a number of immune and epithelial cells types, and through its inhibition of pro-inflammatory cytokine production, IRAK-M can regulate immune homeostasis and tolerance in a number of infectious and non-infectious diseases. Furthermore, use of IRAK-M deficient animals has increased our understanding of the importance of IRAK-M in regulating immune responsiveness to a variety of pathogens. Although IRAK-M expression is typically induced through TLR signaling, IRAK-M can also be expressed in response to various endogenous and exogenous soluble factors as well as cell surface and intracellular signaling molecules. This review will focus on clinical scenarios in which expression of IRAK-M is beneficial (as in early sepsis and those situations where IRAK-M expression is harmful to the host (as in cancer and following bone marrow transplant. There is strong rationale for therapeutic targeting of IRAK-M for clinical benefit. However, effective targeting will require a greater understanding of the transcriptional regulation of this gene.
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Rizzetto, Lisa; De Filippo, Carlotta; Rivero, Damariz; Riccadonna, Samantha; Beltrame, Luca; Cavalieri, Duccio
2013-11-01
Modelling the networks sustaining the fruitful coexistence between fungi and their mammalian hosts is becoming increasingly important to control emerging fungal pathogens. The C-type lectins Dectin-1 and Dectin-2 are involved in host defense mechanisms against fungal infection driving inflammatory and adaptive immune responses and complement in containing fungal burdens. Recognizing carbohydrate structures in pathogens, their engagement induces maturation of dendritic cells (DCs) into potent immuno-stimulatory cells endowed with the capacity to efficiently prime T cells. Owing to these properties, Dectin-1 and Dectin-2 agonists are currently under investigation as promising adjuvants in vaccination procedures for the treatment of fungal infection. Thus, a detailed understanding of events' cascade specifically triggered in DCs upon engagement is of great interest in translational research. Here, we summarize the current knowledge on Dectin-1 and Dectin-2 signalling in DCs highlighting similarities and differences. Detailed maps are annotated, using the Biological Connection Markup Language (BCML) data model, and stored in DC-ATLAS, a versatile resource for the interpretation of high-throughput data generated perturbing the signalling network of DCs. Copyright © 2013 Elsevier GmbH. All rights reserved.
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Plant methyl salicylate induces defense responses in the rhizobacterium Bacillus subtilis.
Kobayashi, Kazuo
2015-04-01
Bacillus subtilis is a rhizobacterium that promotes plant growth and health. Cultivation of B. subtilis with an uprooted weed on solid medium produced pleat-like architectures on colonies near the plant. To test whether plants emit signals that affect B. subtilis colony morphology, we examined the effect of plant-related compounds on colony morphology. Bacillus subtilis formed mucoid colonies specifically in response to methyl salicylate, which is a plant-defense signal released in response to pathogen infection. Methyl salicylate induced mucoid colony formation by stimulating poly-γ-glutamic acid biosynthesis, which formed enclosing capsules that protected the cells from exposure to antimicrobial compounds. Poly-γ-glutamic acid synthesis depended on the DegS-DegU two-component regulatory system, which activated DegSU-dependent gene transcription in response to methyl salicylate. Bacillus subtilis did not induce plant methyl salicylate production, indicating that the most probable source of methyl salicylate in the rhizosphere is pathogen-infected plants. Methyl salicylate induced B. subtilis biosynthesis of the antibiotics bacilysin and fengycin, the latter of which exhibited inhibitory activity against the plant pathogenic fungus Fusarium oxysporum. We propose that B. subtilis may sense plants under pathogen attack via methyl salicylate, and express defense responses that protect both B. subtilis and host plants in the rhizosphere. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.
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Interferon induced IFIT family genes in host antiviral defense.
Zhou, Xiang; Michal, Jennifer J; Zhang, Lifan; Ding, Bo; Lunney, Joan K; Liu, Bang; Jiang, Zhihua
2013-01-01
Secretion of interferons (IFNs) from virus-infected cells is a hallmark of host antiviral immunity and in fact, IFNs exert their antiviral activities through the induction of antiviral proteins. The IFN-induced protein with tetratricopeptide repeats (IFITs) family is among hundreds of IFN-stimulated genes. This family contains a cluster of duplicated loci. Most mammals have IFIT1, IFIT2, IFIT3 and IFIT5; however, bird, marsupial, frog and fish have only IFIT5. Regardless of species, IFIT5 is always adjacent to SLC16A12. IFIT family genes are predominantly induced by type I and type III interferons and are regulated by the pattern recognition and the JAK-STAT signaling pathway. IFIT family proteins are involved in many processes in response to viral infection. However, some viruses can escape the antiviral functions of the IFIT family by suppressing IFIT family genes expression or methylation of 5' cap of viral molecules. In addition, the variants of IFIT family genes could significantly influence the outcome of hepatitis C virus (HCV) therapy. We believe that our current review provides a comprehensive picture for the community to understand the structure and function of IFIT family genes in response to pathogens in human, as well as in animals.
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de Jong, Hanna K.; Koh, Gavin C. K. W.; Achouiti, Ahmed; van der Meer, Anne J.; Bulder, Ingrid; Stephan, Femke; Roelofs, Joris J. T. H.; Day, Nick P. J.; Peacock, Sharon J.; Zeerleder, Sacha; Wiersinga, W. Joost
2014-01-01
Neutrophil extracellular traps (NETs) are a central player in the host response to bacteria: neutrophils release extracellular DNA (nucleosomes) and neutrophil elastase to entrap and kill bacteria. We studied the role of NETs in Burkholderia pseudomallei infection (melioidosis), an important cause