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1

FY2003 LDRD Final Annual Report Article: Pathogen Pathway Project  

SciTech Connect

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

Fitch, J P; McCutchen-Maloney, S L

2003-11-10

2

Intervention of Phytohormone Pathways by Pathogen Effectors[OPEN  

PubMed Central

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

Kazan, Kemal; Lyons, Rebecca

2014-01-01

3

The molecular pathways underlying host resistance and tolerance to pathogens  

PubMed Central

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

Glass, Elizabeth J.

2012-01-01

4

Versatile persistence pathways for pathogens of animals and plants.  

PubMed

The glyoxylate cycle and the glycine cleavage system are part of conserved metabolic pathways involved in the chronic persistence of microorganisms in animal hosts. In the chromosome of the plant pathogen Rhodococcus fascians, the vic locus has been identified as a region containing genes essential for persistence inside induced leafy galls. Sequence analysis showed that this 18-kb locus is syntenic with chromosomal regions of Mycobacterium species that encompass the 'persistence' loci of these mammalian pathogens. Hence, the ability to switch diet inside the host appears to be governed by 'persistence' enzymes that are conserved between pathogens of animals and plants. PMID:12419605

Vereecke, Danny; Cornelis, Karen; Temmerman, Wim; Holsters, Marcelle; Goethals, Koen

2002-11-01

5

PATHWAY: A Computer Model to Determine Sewage Sludge Pathogen Transport Through Environmental Pathways.  

National Technical Information Service (NTIS)

A computer program is presently being developed to model the transport of pathogens through environmental pathways as a result of the application of treated sewage sludge. Specific sludge application cases include the use of treated sludge as a cropland f...

R. E. Sheridan M. F. Abernathy J. G. Yeager

1979-01-01

6

Signal Transduction Pathways Regulating Differentiation and Pathogenicity of Cryptococcus neoformans  

Microsoft Academic Search

The basidiomycetous yeastCryptococcus neoformansis a human pathogen. Several phenotypes of this organism are defined as virulence traits including the polysaccharide capsule, melanin, and the ability to grow at 37°C. The signaling pathways regulating the expression of these phenotypes and other important cellular processes are being defined on a molecular level. For example, the highly conserved signaling molecule calcineurin regulates high

J. Andrew Alspaugh; John R. Perfect; Joseph Heitman

1998-01-01

7

Versatile persistence pathways for pathogens of animals and plants  

Microsoft Academic Search

The glyoxylate cycle and the glycine cleavage system are part of conserved metabolic pathways involved in the chronic persistence of microorganisms in animal hosts. In the chromosome of the plant pathogen Rhodococcus fascians, the vic locus has been identified as a region containing genes essential for persistence inside induced leafy galls. Sequence analysis showed that this 18-kb locus is syntenic

Danny Vereecke; Karen Cornelis; Wim Temmerman; Marcelle Holsters; Koen Goethals

2002-01-01

8

Stress Signaling Pathways for the Pathogenicity of Cryptococcus  

PubMed Central

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

Jung, Kwang-Woo

2013-01-01

9

ARTicle  

NSDL National Science Digital Library

ARTicle is yet another entry in the arena of museum blogs, this time from the Art Institute of Chicago (AIC). ARTicle is intended to cover all sorts of subjects related to the AIC, and its six staff writers ask readers to, "Think of it as a little peek behind the scenes." The blog dates back to October of 2009, and visitors will find recent entries that include a staff picks entry, an entry on saints and symbols, and a short video featuring Robby S., a media assistant in Communications. In the video, Robby discusses Chilean painter Matta's The Earth Is a Man, 1942, which he describes as looking like a bunch of things floating in soup. Another recent post by Sarah M. investigates a piece currently on view in the modern wing, Shade by London-based Dutch designer Simon Heijdens, taking a look at how the work was installed and the possible meaning behind the work. If a "little peek behind the scenes" means the opportunity to hear people talking about art in an accessible and straightforward fashion, then ARTicle certainly achieves its stated goal.

10

An inside job: subversion of the host secretory pathway by intestinal pathogens  

PubMed Central

Purpose of review The cellular secretory pathway, composed of the endoplasmic reticulum, Golgi apparatus, and cellular vesicles, mediates the intracellular trafficking of proteins and lipids. Gastrointestinal pathogens frequently affect the functions of enterocytes, the differentiated cells involved in secretion and absorption of extracellular molecules. Microbial pathogenesis can be enhanced by altering the trafficking of key molecules such as brush border enzymes, soluble immune mediators such as cytokines and chemokines, and MHC Class I molecules, all of which rely on the secretory pathway for their appropriate cellular localization. This review focuses on our current understanding of the distinct mechanisms employed by enteric pathogens to antagonize the secretory pathway. Recent findings Many pathogens encode individual or multiple proteins to antagonize the secretory pathway, including disrupting the trafficking of vesicles between the endoplasmic reticulum, Golgi, and plasma membrane. This antagonism allows for increased pathogenesis and can assist, directly or indirectly, in microbial replication. Virtually all arms of the secretory pathway are targeted by intestinal pathogens, supporting the pathogenic significance of shutting this pathway down. Summary This review summarizes the mechanisms utilized by gut pathogens to disrupt the cellular secretory pathway and addresses potential therapeutic targets to combat these highly prevalent and burdensome microbes.

Sharp, Tyler M.; Estes, Mary K.

2014-01-01

11

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

PubMed Central

Cryptococcus neoformans is a basidiomycete human fungal pathogen that causes meningoencephalitis in both immunocompromised and immunocompetent individuals. The ability to sense and respond to diverse extracellular signals is essential for the pathogen to infect and cause disease in the host. Four major stress-activated signaling (SAS) pathways have been characterized in C. neoformans, including the HOG (high osmolarity glycerol response), PKC/Mpk1 MAPK (mitogen-activated protein kinase), calcium-dependent calcineurin, and RAS signaling pathways. The HOG pathway in C. neoformans not only controls responses to diverse environmental stresses, including osmotic shock, UV irradiation, oxidative stress, heavy metal stress, antifungal drugs, toxic metabolites, and high temperature, but also regulates ergosterol biosynthesis. The PKC (Protein kinase C)/Mpk1 pathway in C. neoformans is involved in a variety of stress responses, including osmotic, oxidative, and nitrosative stresses and breaches of cell wall integrity. The Ca2+/calmodulin- and Ras-signaling pathways also play critical roles in adaptation to certain environmental stresses, such as high temperature and sexual differentiation. Perturbation of the SAS pathways not only impairs the ability of C. neoformans to resist a variety of environmental stresses during host infection, but also affects production of virulence factors, such as capsule and melanin. A drug(s) capable of targeting signaling components of the SAS pathway will be effective for treatment of cryptococcosis.

Jung, Kwang-Woo

2009-01-01

12

Pathogen evasion strategies for the major histocompatibility complex class I assembly pathway  

PubMed Central

Major histocompatibility complex (MHC) class I molecules bind and present short antigenic peptides from endogenously or exogenously derived sources to CD8+ cytotoxic T lymphocytes (CTL), with recognition of a foreign peptide normally targeting the cell for lysis. It is generally thought that the high level of MHC polymorphism, which is concentrated mostly within the peptide-binding groove, is driven by the ‘evolutionary arms race’ against pathogens. Many pathogens have developed novel and intriguing mechanisms for evading the continuous sampling of the intracellular and intercellular environments by MHC molecules, none more so than viruses. The characterization of immunoevasion mechanisms has improved our understanding of MHC biology. This review will highlight our current understanding of the MHC class I biosynthetic pathway and how it has been exploited by pathogens, especially viruses, to potentially evade CTL recognition.

Antoniou, Antony N; Powis, Simon J

2008-01-01

13

Degradation of aromatic compounds through the ?-ketoadipate pathway is required for pathogenicity of the tomato wilt pathogen Fusarium oxysporum f. sp. lycopersici.  

PubMed

Plant roots react to pathogen attack by the activation of general and systemic resistance, including the lignification of cell walls and increased release of phenolic compounds in root exudate. Some fungi have the capacity to degrade lignin using ligninolytic extracellular peroxidases and laccases. Aromatic lignin breakdown products are further catabolized via the ?-ketoadipate pathway. In this study, we investigated the role of 3-carboxy-cis,cis-muconate lactonizing enzyme (CMLE), an enzyme of the ?-ketoadipate pathway, in the pathogenicity of Fusarium oxysporum f. sp. lycopersici towards its host, tomato. As expected, the cmle deletion mutant cannot catabolize phenolic compounds known to be degraded via the ?-ketoadipate pathway. In addition, the mutant is impaired in root invasion and is nonpathogenic, even though it shows normal superficial root colonization. We hypothesize that the ?-ketoadipate pathway in plant-pathogenic, soil-borne fungi is necessary to degrade phenolic compounds in root exudate and/or inside roots in order to establish disease. PMID:22827542

Michielse, Caroline B; Reijnen, Linda; Olivain, Chantal; Alabouvette, Claude; Rep, Martijn

2012-12-01

14

Bi-cycling the furin pathway: from TGN localization to pathogen activation and embryogenesis  

Microsoft Academic Search

Furin is a secretory pathway endoprotease that catalyses the maturation of a strikingly diverse group of proprotein substrates, ranging from growth factors and receptors to pathogen proteins, in multiple compartments within the trans-Golgi network (TGN)\\/endosomal system. This review focuses on recent developments in the biochemistry and cell biology of the endoprotease, including the mechanism of TGN localization, phosphorylation-dependent regulation of

Sean S. Molloy; Eric D. Anderson; François Jean; Gary Thomas

1999-01-01

15

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

PubMed Central

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

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

2014-01-01

16

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

PubMed

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

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

2014-01-01

17

Transcriptome of Aphanomyces euteiches: New Oomycete Putative Pathogenicity Factors and Metabolic Pathways  

PubMed Central

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

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

2008-01-01

18

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

PubMed Central

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

2012-01-01

19

Article The bantam MicroRNA Is a Target of the Hippo Tumor-Suppressor Pathway  

Microsoft Academic Search

Summary Background: The Hippo tumor-suppressor pathway has emerged as a key signaling pathway that controls tissue size inDrosophila. Hippo signaling restricts tissue size by promoting apoptosis and cell-cycle arrest, and animals carrying clones of cells mutant for hippo de- velop severely overgrown adult structures. The Hippo pathway is thought to exert its effects by modulating gene expression through the phosphorylation

Riitta Nolo; Clayton M. Morrison; Chunyao Tao; Xinwei Zhang; Georg Halder

20

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

PubMed Central

Peroxisomes participate in various important metabolisms and are required in pathogenicity of fungal plant pathogens. Peroxisomal matrix proteins are imported from cytoplasm into peroxisomes through peroxisomal targeting signal 1 (PTS1) or peroxisomal targeting signal 2 (PTS2) import pathway. PEX5 and PEX7 genes participate in the two pathways respectively. The involvement of PEX7 mediated PTS2 import pathway in fungal pathogenicity has been documented, while that of PTS1 remains unclear. Through null mutant analysis of MoPEX5, the PEX5 homolog in Magnaporthe oryzae, we report the crucial roles of PTS1 pathway in the development and host infection in the rice blast fungus, and compared with those of PTS2. We found that MoPEX5 disruption specifically blocked the PTS1 pathway. ?mopex5 was unable to use lipids as sole carbon source and lost pathogenicity completely. Similar as ?mopex7, ?mopex5 exhibited significant reduction in lipid utilization and mobilization, appressorial turgor genesis and H2O2 resistance. Additionally, ?mopex5 presented some distinct defects which were undetected in ?mopex7 in vegetative growth, conidial morphogenesis, appressorial morphogenesis and melanization. The results indicated that the PTS1 peroxisomal import pathway, in addition to PTS2, is required for fungal development and pathogenicity of the rice blast fungus, and also, as a main peroxisomal import pathway, played a more predominant role than PTS2.

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

2013-01-01

21

Comprehensive database of Chorismate synthase enzyme from shikimate pathway in pathogenic bacteria  

PubMed Central

Background Infectious diseases are major public health problem. It is increasingly affecting more than 50 million people worldwide. Targeting shikimate pathway could be efficiently used for the development of broad spectrum antimicrobial compound against variety of infectious diseases. Chorismate synthase is an enzyme in shikimate pathway that catalyzes Phosphoenol pyruvate to chorismate in most of the prokaryotic bacteria. This step is crucial for its growth, since Chorismate acts as a precursor molecule for the synthesis of aromatic amino acids. Hence, we present a comprehensive database of Chorismate Synthase Database (CSDB) which is a manually curated database. It provides information on the sequence, structure and biological activity of chorismate synthase from shikimate pathway of pathogenic bacteria. Design of suitable inhibitors for this enzyme, hence could be a probable solution to destroy its proteomic machinery and thereby inhibit the bacterial growth. Description The aim of this study was to characterise chorismate synthase enzyme belonging to pathogenic bacteria to analysis the functional and structural characterization of chorismate synthase is very important for both structure-based and ligand based drug design. Conclusions The broad range of data easy to use user interface makes csdb.in a useful database for researchers in designing drugs.

2013-01-01

22

Pathogenic Role of the Wnt Signaling Pathway Activation In Laser-Induced Choroidal Neovascularization  

PubMed Central

Purpose. Choroidal neovascularization (CNV) is a severe complication of AMD. The Wnt signaling pathway has been shown to mediate angiogenesis. The purpose of this study was to investigate the pathogenic role of the Wnt pathway in CNV and explore the therapeutic potential of a novel Wnt signaling inhibitor in CNV. Methods. Adult rats and mice were photocoagulated using diode laser to induce CNV. On the same day, the animals were intravitreally injected with a monoclonal antibody (Mab2F1) blocking LRP6 or nonspecific mouse IgG. The Wnt signaling activation and target gene expression in the eyecup were determined by Western blot analysis. Fundus angiography was used to examine leakage from the laser lesion. CNV areas were measured on choroidal flatmount using FITC-dextran. Results. Levels of Wnt pathway components and Wnt target gene expression were elevated in both laser-induced CNV rat and mouse eyecups, suggesting activation of the Wnt pathway. Significant suppression of Wnt signaling was observed in the Mab2F1 treatment group. Mab2F1 decreased vascular leakage from CNV lesions and reduced the neovascular area in laser-induced CNV rats. Mab2F1 inhibited the hypoxia-induced activation of Wnt signaling in cultured RPE cells. Mab2F1 also ameliorated retinal inflammation and vascular leakage in the eyecups of very low-density lipoprotein receptor knockout mice, a model of subretinal neovascularization. Conclusions. The Wnt pathway is activated in the laser-induced CNV models and plays a pathogenic role in CNV. Blockade of Wnt signaling using an anti-LRP6 antibody has therapeutic potential in CNV.

Hu, Yang; Chen, Ying; Lin, Mingkai; Lee, Kyungwon; Mott, Robert A.; Ma, Jian-xing

2013-01-01

23

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

PubMed

Burkholderia glumae is a causal agent of rice grain and sheath rot. Similar to other phytopathogens, B. glumae adapts well to the host environment and controls its biology to induce diseases in the host plant; however, its molecular mechanisms are not yet fully understood. To gain a better understating of the actual physiological changes that occur in B. glumae during infection, we analyzed B. glumae transcriptome from infected rice tissues using an RNA-seq technique. To accomplish this, we analyzed differentially expressed genes (DEGs) and identified 2653 transcripts that were significantly altered. We then performed KEGG pathway and module enrichment of the DEGs. Interestingly, most genes involved bacterial chemotaxis-mediated motility, ascorbate and trehalose metabolisms, and sugar transporters including l-arabinose and d-xylose were found to be highly enriched. The in vivo transcriptional profiling of pathogenic B. glumae will facilitate elucidation of unknown plant-pathogenic bacteria interactions, as well as the overall infection processes. PMID:24949534

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

2014-08-15

24

GENIES: a natural-language processing system for the extraction of molecular pathways from journal articles  

Microsoft Academic Search

Systems that extract structured information from natural language passages have been highly successful in specialized domains. The time is opportune for devel- oping analogous applications for molecular biology and genomics. We present a system, GENIES, that extracts and structures information about cellular pathways from the biological literature in accordance with a knowledge model that we developed earlier. We implemented GENIES

Carol Friedman; Pauline Kra; Hong Yu; Michael Krauthammer; Andrey Rzhetsky

2001-01-01

25

A Model of an Integrated Immune System Pathway in Homo sapiens and Its Interaction with Superantigen Producing Expression Regulatory Pathway in Staphylococcus aureus: Comparing Behavior of Pathogen Perturbed and Unperturbed Pathway  

PubMed Central

Response of an immune system to a pathogen attack depends on the balance between the host immune defense and the virulence of the pathogen. Investigation of molecular interactions between the proteins of a host and a pathogen helps in identifying the pathogenic proteins. It is necessary to understand the dynamics of a normally behaved host system to evaluate the capacity of its immune system upon pathogen attack. In this study, we have compared the behavior of an unperturbed and pathogen perturbed host system. Moreover, we have developed a formalism under Flux Balance Analysis (FBA) for the optimization of conflicting objective functions. We have constructed an integrated pathway system, which includes Staphylococcal Superantigen (SAg) expression regulatory pathway and TCR signaling pathway of Homo sapiens. We have implemented the method on this pathway system and observed the behavior of host signaling molecules upon pathogen attack. The entire study has been divided into six different cases, based on the perturbed/unperturbed conditions. In other words, we have investigated unperturbed and pathogen perturbed human TCR signaling pathway, with different combinations of optimization of concentrations of regulatory and signaling molecules. One of these cases has aimed at finding out whether minimization of the toxin production in a pathogen leads to the change in the concentration levels of the proteins coded by TCR signaling pathway genes in the infected host. Based on the computed results, we have hypothesized that the balance between TCR signaling inhibitory and stimulatory molecules can keep TCR signaling system into resting/stimulating state, depending upon the perturbation. The proposed integrated host-pathogen interaction pathway model has accurately reflected the experimental evidences, which we have used for validation purpose. The significance of this kind of investigation lies in revealing the susceptible interaction points that can take back the Staphylococcal Enterotoxin (SE)-challenged system within the range of normal behavior.

Tomar, Namrata; De, Rajat K.

2013-01-01

26

Of truth and pathways: chasing bits of information through myriads of articles.  

PubMed

Knowledge on interactions between molecules in living cells is indispensable for theoretical analysis and practical applications in modern genomics and molecular biology. Building such networks relies on the assumption that the correct molecular interactions are known or can be identified by reading a few research articles. However, this assumption does not necessarily hold, as truth is rather an emerging property based on many potentially conflicting facts. This paper explores the processes of knowledge generation and publishing in the molecular biology literature using modelling and analysis of real molecular interaction data. The data analysed in this article were automatically extracted from 50000 research articles in molecular biology using a computer system called GeneWays containing a natural language processing module. The paper indicates that truthfulness of statements is associated in the minds of scientists with the relative importance (connectedness) of substances under study, revealing a potential selection bias in the reporting of research results. Aiming at understanding the statistical properties of the life cycle of biological facts reported in research articles, we formulate a stochastic model describing generation and propagation of knowledge about molecular interactions through scientific publications. We hope that in the future such a model can be useful for automatically producing consensus views of molecular interaction data. PMID:12169554

Krauthammer, Michael; Kra, Pauline; Iossifov, Ivan; Gomez, Shawn M; Hripcsak, George; Hatzivassiloglou, Vasileios; Friedman, Carol; Rzhetsky, Andrey

2002-01-01

27

A Single MAPKKK Regulates the Hog1 MAPK Pathway in the Pathogenic Fungus Candida albicans  

PubMed Central

The Hog1 mitogen-activated protein kinase (MAPK) plays a central role in stress responses in the human pathogen Candida albicans. Here, we have investigated the MAPK kinase kinase (MAPKKK)-dependent regulation of the pathway. In contrast to the Hog1 pathway in Saccharomyces cerevisiae, which is regulated by three MAPKKKs (Ssk2, Ssk22, and Ste11), our results demonstrate that Hog1 in C. albicans is regulated by a single MAPKKK Ssk2. Deletion of SSK2 results in comparable stress and morphological phenotypes exhibited by hog1? cells, and Ssk2 is required for the stress-induced phosphorylation and nuclear accumulation of Hog1, and for Hog1-dependent gene expression. Furthermore, phenotypes associated with deletion of SSK2 can be circumvented by expression of a phosphomimetic mutant of the MAPKK Pbs2, indicating that Ssk2 regulates Hog1 via activation of Pbs2. In S. cerevisiae, the Hog1 pathway is also regulated by the MAPKKK Ste11. However, we can find no connection between Ste11 and the regulation of Hog1 in C. albicans. Furthermore, expression of a chimeric Pbs2 protein containing the Ste11-dependent regulatory region of S. cerevisiae Pbs2, fails to stimulate Ste11-dependent stress signaling in C. albicans. Collectively, our data show that Ssk2 is the sole MAPKKK to relay stress signals to Hog1 in C. albicans and that the MAPK signaling network in C. albicans has diverged significantly from the corresponding network in S. cerevisiae.

Cheetham, Jill; Smith, Deborah A.; da Silva Dantas, Alessandra; Doris, Kathryn S.; Patterson, Miranda J.; Bruce, Catherine R.

2007-01-01

28

The endocytic adaptor proteins of pathogenic fungi: charting new and familiar pathways  

PubMed Central

Intracellular transport is an essential biological process that is highly conserved throughout the eukaryotic organisms. In fungi, adaptor proteins implicated in the endocytic cycle of endocytosis and exocytosis were found to be important for growth, differentiation, and/or virulence. For example, Saccharomyces cerevisiae Pan1 is an endocytic protein that regulates membrane trafficking, the actin cytoskeleton, and signaling. In Cryptococcus neoformans, a multi-modular endocytic protein, Cin1, was recently found to have pleiotropic functions in morphogenesis, endocytosis, exocytosis, and virulence. Interestingly, Cin1 is homologous to human intersectin ITSN1, but homologs of Cin1/ITSN1 were not found in ascomycetous S. cerevisiae and Candida albicans, or zygomycetous fungi. Moreover, an Eps15 protein homologous to S. cerevisiae Pan1/Ede1 and additional relevant protein homologs were identified in C. neoformans, suggesting the existence of either a distinct endocytic pathway mediated by Cin1 or pathways by either Cin1 or/and Pan1/Ede1 homologs. Whether and how the Cin1-mediated endocytic pathway represents a unique role in pathogenesis or reflects a redundancy of a transport apparatus remains an open and challenging question. This review discusses recent findings of endocytic adaptor proteins from pathogenic fungi and provides a perspective for novel endocytic machinery operating in C. neoformans. An understanding of intracellular trafficking mechanisms as they relate to pathogenesis will likely reveal the identity of novel antifungal targets.

WANG, PING; SHEN, GUI

2012-01-01

29

Genomics of iron acquisition in the plant pathogen Erwinia amylovora: insights in the biosynthetic pathway of the siderophore desferrioxamine E.  

PubMed

Genomics has clarified the biosynthetic pathway for desferrioxamine E critical for iron acquisition in the enterobacterial fire blight pathogen Erwinia amylovora. Evidence for each of the individual steps and the role of desferrioxamine E biosynthesis in pathogen virulence and cell protection from host defenses is presented. Using comparative genomics, it can be concluded that desferrioxamine biosynthesis is ancestral within the genera Erwinia and Pantoea. PMID:21814817

Smits, Theo H M; Duffy, Brion

2011-10-01

30

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

PubMed Central

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

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

2006-01-01

31

Biosynthetic pathway for mannopeptimycins, lipoglycopeptide antibiotics active against drug-resistant gram-positive pathogens.  

PubMed

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

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

2006-06-01

32

Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer.  

PubMed

Genetic and pharmacological studies of indoleamine 2,3-dioxygenase (IDO) have established this tryptophan catabolic enzyme as a central driver of malignant development and progression. IDO acts in tumor, stromal and immune cells to support pathogenic inflammatory processes that engender immune tolerance to tumor antigens. The multifaceted effects of IDO activation in cancer include the suppression of T and NK cells, the generation and activation of T regulatory cells and myeloid-derived suppressor cells, and the promotion of tumor angiogenesis. Mechanistic investigations have defined the aryl hydrocarbon receptor, the master metabolic regulator mTORC1 and the stress kinase Gcn2 as key effector signaling elements for IDO, which also exerts a non-catalytic role in TGF-? signaling. Small-molecule inhibitors of IDO exhibit anticancer activity and cooperate with immunotherapy, radiotherapy or chemotherapy to trigger rapid regression of aggressive tumors otherwise resistant to treatment. Notably, the dramatic antitumor activity of certain targeted therapeutics such as imatinib (Gleevec) in gastrointestinal stromal tumors has been traced in part to IDO downregulation. Further, antitumor responses to immune checkpoint inhibitors can be heightened safely by a clinical lead inhibitor of the IDO pathway that relieves IDO-mediated suppression of mTORC1 in T cells. In this personal perspective on IDO as a nodal mediator of pathogenic inflammation and immune escape in cancer, we provide a conceptual foundation for the clinical development of IDO inhibitors as a novel class of immunomodulators with broad application in the treatment of advanced human cancer. PMID:24711084

Prendergast, George C; Smith, Courtney; Thomas, Sunil; Mandik-Nayak, Laura; Laury-Kleintop, Lisa; Metz, Richard; Muller, Alexander J

2014-07-01

33

The Drosophila melanogaster Toll Pathway Participates in Resistance to Infection by the Gram-Negative Human Pathogen Pseudomonas aeruginosa  

Microsoft Academic Search

Pseudomonas aeruginosa is a gram-negative pathogen that infects immunocompromised and cystic fibrosis patients. The molecular basis of the host-P. aeruginosa interaction and the effect of specific P. aeruginosa virulence factors on various components of the innate immunity pathways are largely unknown. We examine interactions between P. aeruginosa virulence factors and components of innate immunity response in the Drosophila melanogaster model

Gee W. Lau; Boyan C. Goumnerov; Cynthia L. Walendziewicz; Jennifer Hewitson; Wenzhong Xiao; Shalina Mahajan-Miklos; Ronald G. Tompkins; Lizabeth A. Perkins; Laurence G. Rahme

2003-01-01

34

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

PubMed Central

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

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

2013-01-01

35

Relationships between calcium and sphingolipid-dependent signalling pathways during the early steps of plant-pathogen interactions.  

PubMed

An increase in cellular calcium ion (Ca(2+)) concentration is now acknowledged to be one of the earliest events occurring during the induction of plant defence responses to a wide variety of pathogens. Sphingoid long-chain bases (LCBs) have also been recently demonstrated to be important mediators of defence-related programmed cell death during pathogen attack. Here, we present recent data highlighting how Ca(2+) and LCBs may be interconnected to regulate cellular processes which lead either to plant susceptibility or to resistance mechanisms. This article is part of a Special Issue entitled: 12th European Symposium on Calcium. PMID:23219859

Thuleau, Patrice; Aldon, Didier; Cotelle, Valérie; Brière, Christian; Ranty, Benoit; Galaud, Jean-Philippe; Mazars, Christian

2013-07-01

36

Toward a molecular pathogenic pathway for Yersinia pestis YopM  

PubMed Central

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

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

2012-01-01

37

Activation of the Wnt Pathway Plays a Pathogenic Role in Diabetic Retinopathy in Humans and Animal Models  

PubMed Central

Although Wnt signaling is known to mediate multiple biological and pathological processes, its association with diabetic retinopathy (DR) has not been established. Here we show that retinal levels and nuclear translocation of ?-catenin, a key effector in the canonical Wnt pathway, were increased in humans with DR and in three DR models. Retinal levels of low-density lipoprotein receptor-related proteins 5 and 6, coreceptors of Wnts, were also elevated in the DR models. The high glucose-induced activation of ?-catenin was attenuated by aminoguanidine, suggesting that oxidative stress is a direct cause for the Wnt pathway activation in diabetes. Indeed, Dickkopf homolog 1, a specific inhibitor of the Wnt pathway, ameliorated retinal inflammation, vascular leakage, and retinal neovascularization in the DR models. Dickkopf homolog 1 also blocked the generation of reactive oxygen species induced by high glucose, suggesting that Wnt signaling contributes to the oxidative stress in diabetes. These observations indicate that the Wnt pathway plays a pathogenic role in DR and represents a novel therapeutic target.

Chen, Ying; Hu, Yang; Zhou, Ti; Zhou, Kevin K.; Mott, Robert; Wu, Mingyuan; Boulton, Michael; Lyons, Timothy J.; Gao, Guoquan; Ma, Jian-xing

2009-01-01

38

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

PubMed Central

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

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

2012-01-01

39

Gingipain-dependent degradation of mammalian target of rapamycin pathway proteins by the periodontal pathogen Porphyromonas gingivalis during invasion.  

PubMed

Porphyromonas gingivalis and Tannerella forsythia are gram-negative pathogens strongly associated with periodontitis. Their abilities to interact, invade and persist within host cells are considered crucial to their pathogenicity, but the mechanisms by which they subvert host defences are not well understood. In this study, we set out to investigate whether P. gingivalis and T. forsythia directly target key signalling molecules that may modulate the host cell phenotype to favour invasion and persistence. Our data identify, for the first time, that P. gingivalis, but not T. forsythia, reduces levels of intracellular mammalian target of rapamycin (mTOR) in oral epithelial cells following invasion over a 4-h time course, via the action of gingipains. The ability of cytochalasin D to abrogate P. gingivalis-mediated mTOR degradation suggests that this effect is dependent upon cellular invasion. We also show that levels of several other proteins in the mTOR signalling pathway are modulated by gingipains, either directly or as a consequence of mTOR degradation including p-4E-BP1. Taken together, our data suggest that P. gingivalis manipulates the mTOR pathway, providing evidence for a potentially novel mechanism by which P. gingivalis mediates its effects on host cell responses to infection. PMID:23714361

Stafford, P; Higham, J; Pinnock, A; Murdoch, C; Douglas, C W I; Stafford, G P; Lambert, D W

2013-10-01

40

A resealed-cell system for analyzing pathogenic intracellular events: perturbation of endocytic pathways under diabetic conditions.  

PubMed

Cell-based assay systems that can serve as cellular models of aberrant function in pathogenic organs would be novel and useful tools for screening drugs and clarifying the molecular mechanisms of various diseases. We constructed model cells that replicated the conditions in diabetic hepatocytes by using the cell resealing technique, which enables the exchange of cytosol. The plasma membrane of HeLa cells was permeabilized with the streptococcal toxin streptolysin O, and cytosol that had been prepared from wild-type or db/db diabetic mice was introduced into the resulting semi-intact cells. By resealing the plasma membrane by exposure to Ca(2+), we created WT or Db model cells, in which the cytosolic conditions replicated those of healthy or diabetic liver. Interestingly, phosphorylation of p38 MAPK was promoted, whereas the level of endosomal phosphatidylinositol-3-phosphate was decreased, in Db cells. We investigated several endocytic pathways in WT and Db cells, and found that retrograde endosome-to-Golgi transport was delayed in a p38 MAPK-dependent manner in Db cells. Furthermore, the degradation pathway of the EGF receptor from endosomes to lysosomes was enhanced in Db cells, and this did not depend on the activation of p38 MAPK. The disease model cell system should become a powerful tool for the detection of aberrant processes in cells under pathogenic conditions and for therapeutic applications. PMID:22952896

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

2012-01-01

41

Expression of callose synthase genes and its connection with Npr1 signaling pathway during pathogen infection.  

PubMed

Callose synthesis occurs at specific stages of plant cell wall development in all cell types, and in response to pathogen attack, wounding and physiological stresses. We determined the expression pattern of "upstream regulatory sequence" of 12 Arabidopsis callose synthase genes (CalS1-12) genes and demonstrated that different callose synthases are expressed specifically in different tissues during plant development. That multiple CalS genes are expressed in the same cell type suggests the possibility that CalS complex may be constituted by heteromeric subunits. Five CalS genes were induced by pathogen (Hyaloperonospora arabidopsis, previously known as Peronospora parasitica, the causal agent of downy mildew) or salicylic acid (SA), while the other seven CalS genes were not affected by these treatments. Among the genes that are induced, CalS1 and CalS12 showed the highest responses. In Arabidopsis npr1 mutant, impaired in response of pathogenesis related (PR) genes to SA, the induction of CalS1 and CalS12 genes by the SA or pathogen treatments was significantly reduced. The patterns of expression of the other three CalS genes were not changed significantly in the npr1 mutant. These results suggest that the high induction observed of CalS1 and CalS12 is Npr1 dependent while the weak induction of five CalS genes is Npr1 independent. In a T-DNA knockout mutant of CalS12, callose encasement around the haustoria on the infected leaves was reduced and the mutant was found to be more resistant to downy mildew as compared to the wild type plants. PMID:18807070

Dong, Xiaoyun; Hong, Zonglie; Chatterjee, Jayanta; Kim, Sunghan; Verma, Desh Pal S

2008-12-01

42

Possible pathogenic pathways in the adverse clinical events seen following ivermectin administration to onchocerciasis patients.  

PubMed Central

Background Reactions are commonly associated with the chemotherapy of onchocerciasis. However unmanageable reactions are uncommon when ivermectin (Mectizan®) is used for the treatment of this infection, and this drug has proved to be a great improvement over previously used agents. Serious adverse events (SAE) nevertheless have occurred, and there is considerable concern about the negative effect such events may have on mass drug administration programs. This paper reviews the basic pathogenic mechanisms that can be involved in the destruction of microfilaria by chemotherapeutic agents. A central challenge to filarial chemotherapy is the need to remove parasites from biologically sensitive tissues, a more difficult medical challenge than eliminating nematodes from the gastrointestinal tract. Explanations for the etiology of the serious adverse reactions occurring with ivermectin treatment in specific geographic areas where there is coincident heavy Loa loa infections are hampered by a lack of specific pathological case material. Ways to investigate these possibilities are reviewed. Possible pathogenic mechanisms include embolic vascular pathology accompanied by local inflammation, blood brain barrier mdr1 abnormalities, and genetic predisposition to excessive inflammatory responses. Conclusion It is important to keep ivermectin, and all its associated adverse clinical events, in perspective with the many other chemotherapeutic agents in general use – many of which produce serious adverse events even more frequently than does ivermectin. Currently available evidence indicates that the pathogenesis of the Loa-associated adverse reactions are probably related to inflammatory responses to microfilariae in specific tissues. However, the possibility of genetic predispositions to pathology should also be considered.

Mackenzie, Charles D; Geary, Timothy G; Gerlach, John A

2003-01-01

43

Characterization and Regulation of the Trehalose Synthesis Pathway and Its Importance in the Pathogenicity of Cryptococcus neoformans  

PubMed Central

The disaccharide trehalose has been found to play diverse roles, from energy source to stress protectant, and this sugar is found in organisms as diverse as bacteria, fungi, plants, and invertebrates but not in mammals. Recent studies in the pathobiology of Cryptococcus neoformans identified the presence of a functioning trehalose pathway during infection and suggested its importance for C. neoformans survival in the host. Therefore, in C. neoformans we created null mutants of the trehalose-6-phosphate (T6P) synthase (TPS1), trehalose-6-phophate phosphatase (TPS2), and neutral trehalase (NTH1) genes. We found that both TPS1 and TPS2 are required for high-temperature (37°C) growth and glycolysis but that the block at TPS2 results in the apparent toxic accumulation of T6P, which makes this enzyme a fungicidal target. Sorbitol suppresses the growth defect in the tps1 and tps2 mutants at 37°C, which supports the hypothesis that these sugars (trehalose and sorbitol) act primarily as stress protectants for proteins and membranes during exposure to high temperatures in C. neoformans. The essential nature of this pathway for disease was confirmed when a tps1 mutant strain was found to be avirulent in both rabbits and mice. Furthermore, in the system of the invertebrate C. elegans, in which high in vivo temperature is no longer an environmental factor, attenuation in virulence was still noted with the tps1 mutant, and this supports the hypothesis that the trehalose pathway in C. neoformans is involved in more host survival mechanisms than simply high-temperature stresses and glycolysis. These studies in C. neoformans and previous studies in other pathogenic fungi support the view of the trehalose pathway as a selective fungicidal target for use in antifungal development.

Petzold, Elizabeth Wills; Himmelreich, Uwe; Mylonakis, Eleftherios; Rude, Thomas; Toffaletti, Dena; Cox, Gary M.; Miller, Jackie L.; Perfect, John R.

2006-01-01

44

AUTOANTIBODY PROFILING TO IDENTIFY BIOMARKERS OF KEY PATHOGENIC PATHWAYS IN MUCINOUS OVARIAN CANCER  

PubMed Central

Mucinous epithelial ovarian cancers are clinically and morphologically distinct from the other histopathologic subtypes of ovarian cancer. Unlike other ovarian subtypes, epidemiologic studies have indicated that tobacco exposure is a significant risk factor for developing mucinous ovarian cancer. Detection of autoantibody reactivity is useful in biomarker discovery and for explaining the role of important pathophysiologic pathways in disease. In order to study if there are specific antibody biomarkers in the plasma samples of mucinous ovarian cancer patients, we have initiated a screen by employing a “reverse capture antibody microarray” platform that uses native host antigens derived from mucinous ovarian tissues as “baits” for the capture of differentially labeled patient and control autoantibodies. 35 autoantibodies that were significantly elevated in the cancer plasma samples compared with healthy controls, and six autoantibodies that segregated smoking and nonsmoking patients were identified. Functional annotation of the antibody targets has identified nine target antigens involved in integrin and Wnt signaling pathways. Immunohistochemistry of archived ovarian specimens showed significant overexpression of eight of the nine target antigens in mucinous ovarian tumor tissues, suggesting that plasma autoantibodies from mucinous ovarian cancer patients might have heightened reactivities with epitopes presented by these overexpressed antigens. Autoantibody profiling may have an unexpected utility in uncovering key signaling pathways that are dysregulated in the system of interest.

Tang, Liangdan; Yang, Junzheng; Ng, Shu-Kay; Rodriguez, Noah; Choi, Pui-Wah; Vitonis, Allison; Wang, Kui; McLachlan, Geoffrey J.; Caiazzo, Robert J.; Liu, Brian C.-S.; Welch, William R.; Cramer, Daniel W.; Berkowitz, Ross S.; Ng, Shu-Wing

2009-01-01

45

Secrets of a Successful Pathogen: Legionella Resistance to Progression Along the Autophagic Pathway  

PubMed Central

To proliferate within phagocytes, Legionella pneumophila relies on Type IV secretion to modulate host cellular pathways. Autophagy is an evolutionarily conserved degradative pathway that captures and transfers a variety of microbes to lysosomes. Biogenesis of L. pneumophila-containing vacuoles and autophagosomes share several features, including endoplasmic reticulum (ER)-derived membranes, contributions by the host GTPases Rab1, Arf1 and Sar1, and a final destiny in lysosomes. We discuss morphological, molecular genetic, and immunological data that support the model that, although A/J mouse macrophages efficiently engulf L. pneumophila within autophagosomal membranes, the Type IV effector proteins DrrA/SidM, LidA, and RalF prolong association with the ER. By inhibiting immediately delivery to lysosomes, the bacteria persist in immature autophagosomal vacuoles for a period sufficient to differentiate into an acid-resistant, replicative form. Subsequent secretion of the Type IV effector LepB releases the block to autophagosome maturation, and the adapted progeny continue to replicate within autophagolysosomes. Accordingly, L. pneumophila can be exploited as a genetic tool to analyze the recruitment and function of the macrophage autophagy pathway.

Joshi, Amrita D.; Swanson, Michele S.

2011-01-01

46

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

PubMed Central

The encapsulated fungal pathogen Cryptococcus neoformans causes cryptococcosis in immunocompromised individuals. Although cell surface mannoproteins have been implicated in C. neoformans pathogenicity, the structure of N-linked glycans assembled on mannoproteins has not yet been elucidated. By analyzing oligosaccharide profiles combined with exoglycosidase treatment, we report here that C. neoformans has serotype-specific high mannose-type N-glycans with or without a ?1,2-xylose residue, which is attached to the trimannosyl core of N-glycans. Interestingly, the neutral N-glycans of serotypes A and D were shown to contain a xylose residue, whereas those of serotype B appeared to be much shorter and devoid of a xylose residue. Moreover, analysis of the C. neoformans uxs1? mutant demonstrated that UDP-xylose is utilized as a donor sugar in N-glycan biosynthesis. We also constructed and analyzed a set of C. neoformans mutant strains lacking genes putatively assigned to the reconstructed N-glycan biosynthesis pathway. It was shown that the outer chain of N-glycan is initiated by CnOch1p with addition of an ?1,6-mannose residue and then subsequently extended by CnMnn2p with multiple additions of ?1,2-mannose residues. Finally, comparative analysis of acidic N-glycans from wild-type, Cnoch1?, Cnmnn2?, and Cnuxs1? strains strongly indicated the presence of xylose phosphate attached to mannose residues in the core and outer region of N-glycans. Our data present the first report on the unique structure and biosynthesis pathway of N-glycans in C. neoformans.

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

2012-01-01

47

A key enzyme of the Leloir pathway is involved in pathogenicity of Leptosphaeria maculans toward oilseed rape.  

PubMed

Agrobacterium tumefaciens-mediated random insertional mutagenesis was used to investigate pathogenicity determinants in Leptosphaeria maculans. One tagged nonpathogenic mutant, termed m186, is analyzed in detail here. Microscopic analyses of infected plant tissues revealed that m186 is specifically blocked at the invasive growth phase after an unaffected initial penetration stage and is unable to switch to the necrotrophic lifestyle. In addition, m186 exhibits an altered cell wall and seems to be affected in its ability to produce cell-wall-degrading enzymes. The T-DNA insertion occurs in the intergenic region between two head-to-tail genes, leading to a constitutive upregulation of their expression. Complementation experiments showed that only one of these two genes, Lmepi, fully accounts for the mutant phenotype. Bioinformatics and expression analyses along with functional studies suggested that the Lmepi gene encodes for the highly conserved UDP-glucose-4-epimerase, a key enzyme of the Leloir pathway involved in galactose metabolism. For the third time, this study highlights the intimate connection between primary metabolism and pathogenicity in L. maculans. This finding, along with similar data obtained from the related species Stagonospora nodorum, indicates the importance of in planta nutrition for the success of infection of plants by fungi belonging to class Dothideomycete. PMID:19445597

Remy, E; Meyer, M; Blaise, F; Simon, U K; Kuhn, D; Balesdent, M H; Rouxel, T

2009-06-01

48

The cAMP pathway is important for controlling the morphological switch to the pathogenic yeast form of Paracoccidioides brasiliensis  

PubMed Central

Paracoccidioides brasiliensis is a human pathogenic fungus that switches from a saprobic mycelium to a pathogenic yeast. Consistent with the morphological transition being regulated by the cAMP-signalling pathway, there is an increase in cellular cAMP levels both transiently at the onset (< 24 h) and progressively in the later stages (> 120 h) of the transition to the yeast form, and this transition can be modulated by exogenous cAMP. We have cloned the cyr1 gene encoding adenylate cyclase (AC) and established that its transcript levels correlate with cAMP levels. In addition, we have cloned the genes encoding three G? (Gpa1–3), G? (Gpb1) and G? (Gpg1) G proteins. Gpa1 and Gpb1 interact with one another and the N-terminus of AC, but neither Gpa2 nor Gpa3 interacted with Gpb1 or AC. The interaction of Gpa1 with Gpb1 was blocked by GTP, but its interaction with AC was independent of bound nucleotide. The transcript levels for gpa1, gpb1 and gpg1 were similar in mycelium, but there was a transient excess of gpb1 during the transition, and an excess of gpa1 in yeast. We have interpreted our findings in terms of a novel signalling mechanism in which the activity of AC is differentially modulated by Gpa1 and Gpb1 to maintain the signal over the 10 days needed for the morphological switch.

Chen, Daliang; Janganan, Thamarai K; Chen, Gongyou; Marques, Everaldo R; Kress, Marcia R; Goldman, Gustavo H; Walmsley, Adrian R; Borges-Walmsley, M Ines

2007-01-01

49

Unfolded protein response in Fuchs Endothelial Corneal Dystrophy: a Unifying Pathogenic Pathway?  

PubMed Central

Purpose To assess for activation of the unfolded protein response in corneal endothelium of Fuchs endothelial corneal dystrophy patients. Design Retrospective comparative case series of laboratory specimens Methods Corneal specimens of patients with Fuchs dystrophy and controls with corneal pathologies other than Fuchs dystrophy were evaluated by transmission electron microscopy (TEM) to evaluate for structural changes of the rough endoplasmic reticulum in corneal endothelium. TEM images were evaluated for alterations of rough endoplasmic reticulum as sign of unfolded protein response. Normal autopsy eyes, Fuchs dystrophy, and keratoconus corneas were used for immunohistochemistry. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections of patient corneas for three unfolded protein response markers (GRP78, phospho-eIF2?, CHOP) and two apoptosis markers (Caspase 3 and 9). Immunohistochemistry signal quantitation of corneal endothelium for evaluation of marker expression was performed using automated software. Corneal sections were assessed quantitatively for levels of immunohistochemistry marker expression. Results TEM showed enlargement of rough endoplasmic reticulum in corneal endothelium of all Fuchs dystrophy specimens. Immunohistochemistry quantitation demonstrated a significant increase in mean signal in corneal endothelium from Fuchs dystrophy patients for markers GRP78, phospho-eIF2?, CHOP and caspase 9, compared with non- Fuchs dystrophy corneas (p < 0.05). Conclusions Results of both TEM and immunohistochemistry indicate activation of unfolded protein response in Fuchs dystrophy. Unfolded protein response activation leads to endothelial cell apoptosis in Fuchs dystrophy and may play a central pathogenic role in this disease.

Engler, Christoph; Kelliher, Clare; Spitze, Arielle R.; Speck, Caroline L.; Eberhart, Charles G.; Jun, Albert S.

2009-01-01

50

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

PubMed Central

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

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

2012-01-01

51

Trypanosoma cruzi Infection and Endothelin-1 Cooperatively Activate Pathogenic Inflammatory Pathways in Cardiomyocytes  

PubMed Central

Trypanosoma cruzi, the causative agent of Chagas' disease, induces multiple responses in the heart, a critical organ of infection and pathology in the host. Among diverse factors, eicosanoids and the vasoactive peptide endothelin-1 (ET-1) have been implicated in the pathogenesis of chronic chagasic cardiomyopathy. In the present study, we found that T. cruzi infection in mice induces myocardial gene expression of cyclooxygenase-2 (Cox2) and thromboxane synthase (Tbxas1) as well as endothelin-1 (Edn1) and atrial natriuretic peptide (Nppa). T. cruzi infection and ET-1 cooperatively activated the Ca2+/calcineurin (Cn)/nuclear factor of activated T cells (NFAT) signaling pathway in atrial myocytes, leading to COX-2 protein expression and increased eicosanoid (prostaglandins E2 and F2?, thromboxane A2) release. Moreover, T. cruzi infection of ET-1-stimulated cardiomyocytes resulted in significantly enhanced production of atrial natriuretic peptide (ANP), a prognostic marker for impairment in cardiac function of chagasic patients. Our findings support an important role for the Ca2+/Cn/NFAT cascade in T. cruzi-mediated myocardial production of inflammatory mediators and may help define novel therapeutic targets.

Corral, Ricardo S.; Guerrero, Nestor A.; Cuervo, Henar; Girones, Nuria; Fresno, Manuel

2013-01-01

52

Antioxidant susceptibility of pathogenic pathways in subjects with antiphospholipid antibodies: a pilot study.  

PubMed

The pathogenesis of antiphospholipid antibody (aPL) related thrombosis is multifactorial and includes, amongst others, enhanced coagulation activation measured as prothrombin fragment 1 + 2 (F1 + 2), elevated plasma levels of von Willebrand factor (vWF), plasminogen activator inhibitor (PAI) and endothelin-1 (ET-1) as well as heightened thromboxane generation and lipid peroxidation. To evaluate the antioxidant susceptibility of some of the above pathways, probucol (500 mg/d orally, a cholesterol lowering agent bearing antioxidant properties) was administered for a three week period to 14 subjects with aPL and to seven healthy controls. At baseline aPL participants showed higher plasma levels of vWF (P = 0.006), ET-1 (P = 0.0002) and enhanced urinary excretion of 11-dehydro-thromboxane-B2 (TXB2) (P = 0.0004), F2-isoprostanes (marker of lipid peroxidation) (P = 0.02) and albumin (P = 0.04) than controls. In the aPL group baseline IgG anticardiolipin (aCL) titre positively related with urinary TXB2 (r2 = 0.43, P = 0.01) and inversely with urinary NOx (r2 = -0.6, P = 0.005) whereas urinary NOx and TXB2 were negatively correlated (r2 = -0.42, P = 0.01). After the treatment period significant decreases from baseline values were noted for PAI (P = 0.01), ET-1 (P = 0.006), TXB2 (P = 0.02), F2-isoprostanes (P = 0.01) and albuminuria (P = 0.01) in aPL participants but not in controls. These pilot data support oxidative sensitive mechanisms and a potential role for antioxidant treatment in the pathogenesis of aPL induced vasculopathy. PMID:11199924

Ames, P R; Tommasino, C; Alves, J; Morrow, J D; Iannaccone, L; Fossati, G; Caruso, S; Caccavo, F; Brancaccio, V

2000-01-01

53

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

PubMed Central

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

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

2013-01-01

54

Pathogenic mechanisms of bradykinin mediated diseases: dysregulation of an innate inflammatory pathway.  

PubMed

Binding of negatively charged macromolecules to factor XII induces a conformational change such that it becomes a substrate for trace amounts of activated factor present in plasma (less than 0.01%). As activated factor XII (factor XIIa or factor XIIf) forms, it converts prekallikrein (PK) to kallikrein and kallikrein cleaves high molecular weight kininogen (HK) to release bradykinin. A far more rapid activation of the remaining unactivated factor XII occurs by enzymatic cleavage by kallikrein (kallikrein-feedback) and sequential cleavage yields two forms of activated factor XII; namely, factor XIIa followed by factor XII fragment (factor XIIf). PK circulates bound to HK and binding induces a conformational change in PK so that it acquires enzymatic activity and can stoichiometrically cleave HK to produce bradykinin. This reaction is prevented from occurring in plasma by the presence of C1 inhibitor (C1 INH). The same active site leads to autoactivation of the PK-HK complex to generate kallikrein if a phosphate containing buffer is used. Theoretically, formation of kallikrein by this factor XII-independent route can activate surface-bound factor XII to generate factor XIIa resulting in a marked increase in the rate of bradykinin formation as stoichiometric reactions are replaced by Michaelis-Menton, enzyme-substrate, kinetics. Zinc-dependent binding of the constituents of the bradykinin-forming cascade to the surface of endothelial cells is mediated by gC1qR and bimolecular complexes of gC1qR-cytokeratin 1 and cytokeratin 1-u-PAR (urokinase plasminogen activator receptor). Factor XII and HK compete for binding to free gC1qR (present in excess) while cytokeratin 1-u-PAR preferentially binds factor XII and gC1qR-cytokeratin 1 preferentially binds HK. Autoactivation of factor XII can be initiated as a result of binding to gC1qR but is prevented by C1 INH. Yet stoichiometric activation of PK-HK to yield kallikrein in the absence of factor XII can be initiated by heat shock protein 90 (HSP-90) which forms a zinc-dependent trimolecular complex by binding to HK. Thus, endothelial cell-dependent activation can be initiated by activation of factor XII or by activation of PK-HK. Hereditary angioedema (HAE), types I and II, are due to autosomal dominant mutations of the C1 INH gene. In type I disease, the level of C1 INH protein and function is proportionately low, while type II disease has a normal protein level but diminished function. There is trans-inhibition of the one normal gene so that functional levels are 30% or less and severe angioedema affecting peripheral structures, the gastrointestinal tract, and the larynx results. Prolonged incubation of plasma of HAE patients (but not normal controls) leads to bradykinin formation and conversion of PK to kallikrein which is reversed by reconstitution with C1 INH. The disorder can be treated by C1 INH replacement, inhibition of plasma kallikrein, or blockade at the bradykinin B-2 receptor. A recently described HAE with normal C1 INH (based on inhibition of activated C1s) presents similarly; the defect is not yet clear, however one-third of patients have a mutant factor XII gene. We have shown that this HAE has a defect in bradykinin overproduction whether the factor XII mutation is present or not, that patients' C1 INH is capable of inhibiting factor XIIa and kallikrein (and not just activated C1) but the functional level is approximately 40-60% of normal, and that ?2 macroglobulin protein levels are normal. In vitro abnormalities can be suppressed by raising C1 INH to twice normal levels. Finally, aggregated proteins have been shown to activate the bradykinin-forming pathway by catalyzing factor XII autoactivation. Those include the amyloid ? protein of Alzheimer's disease and cryoglobulins. This may represent a new avenue for kinin-dependent research in human disease. In allergy (anaphylaxis; perhaps other mast cell-dependent reactions), the oversulfated proteoglycan of mast cells, liberated along with histamine, also catalyze factor XII autoactivation. PMID:24388213

Kaplan, Allen P; Joseph, Kusumam

2014-01-01

55

Pathogen-pathogen interaction  

PubMed Central

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

2010-01-01

56

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

PubMed Central

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

Ivanov, Stanimir S.; Roy, Craig R.

2013-01-01

57

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

PubMed

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

Ivanov, Stanimir S; Roy, Craig R

2013-12-01

58

Ras links cellular morphogenesis to virulence by regulation of the MAP kinase and cAMP signalling pathways in the pathogenic fungus Candida albicans.  

PubMed

The pathogenic fungus Candida albicans is capable of responding to a wide variety of environmental cues with a morphological transition from a budding yeast to a polarized filamentous form. We demonstrate that the Ras homologue of C. albicans, CaRas1p, is required for this morphological transition and thereby contributes to the development of pathogenicity. However, CaRas1p is not required for cellular viability. Deletion of both alleles of the CaRAS1 gene caused in vitro defects in morphological transition that were reversed by either supplementing the growth media with cAMP or overexpressing components of the filament-inducing mitogen-activated protein (MAP) kinase cascade. The induction of filament-specific secreted aspartyl proteinases encoded by the SAP4-6 genes was blocked in the mutant cells. The defects in filament formation were also observed in situ after phagocytosis of C. albicans cells in a macrophage cell culture assay and, in vivo, after infection of kidneys in a mouse model for systemic candidiasis. In the macrophage assay, the mutant cells were less resistant to phagocytosis. Moreover, the defects in filament formation were associated with reduced virulence in the mouse model. These results indicate that, in response to environmental cues, CaRas1p is required for the regulation of both a MAP kinase signalling pathway and a cAMP signalling pathway. CaRas1p-dependent activation of these pathways contributes to the pathogenicity of C. albicans cells through the induction of polarized morphogenesis. These findings elucidate a new medically relevant role for Ras in cellular morphogenesis and virulence in an important human infectious disease. PMID:11722734

Leberer, E; Harcus, D; Dignard, D; Johnson, L; Ushinsky, S; Thomas, D Y; Schröppel, K

2001-11-01

59

Bioterrorism Articles  

NSDL National Science Digital Library

The Journal of the American Medical Association (JAMA) is offering free access to a large number of its previously published articles related to bioterrorism. Among the articles are five pieces by the Working Group on Civilian Biodefense, which are focused on Anthrax, Smallpox, Plague, Botulinum Toxin, and Tularemia. The remainder of the articles are sorted by subject, including these diseases plus Ebola and Brucella, as well as Clinical Articles, Epidemiologic Investigations, articles on Preparedness, and a section devoted to Policy, Historical, and Editorial Perspectives. Articles are available in HTML or .pdf formats.

1995-01-01

60

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

PubMed

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

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

2005-02-01

61

The Entner-Doudoroff pathway is obligatory for gluconate utilization and contributes to the pathogenicity of Vibrio cholerae.  

PubMed

The Entner-Doudoroff (ED) pathway has recently been shown to play an important role in sugar catabolism for many organisms although very little information is available on the functionality of this pathway in Vibrio cholerae, the causative agent of cholera. In this study, activation of the genes edd and eda, encoding 6-phosphogluconate dehydratase and 2-keto-3-deoxy-6-phosphogluconate aldolase, was used as a marker of a functional ED pathway in V. cholerae. Transcriptional activation analyses and gene silencing experiments with cells grown in sugar-supplemented M9 medium demonstrated that the ED pathway is functional in V. cholerae and is obligatory for gluconate catabolism. Importantly, selective activation of the ED pathway led to concurrent elevation of transcripts of prime virulence genes (ctxA and tcpA) and their regulator (toxT). Further, lowering of these transcript levels and cholera toxin production in vitro by an ED pathway-defective mutant (strain N16961 with a ?edd mutation [?edd(N16961) strain]) suggested the importance of this pathway in regulating V. cholerae virulence. The in vivo relevance of these data was established as the mutant failed to colonize in suckling mice intestine or to induce fluid accumulation in ligated rabbit ileal loops. Activation of the ED pathway in V. cholerae was shown to inhibit biofilm formation in vitro that could be reversed in the mutant. As further support for these results, comparative transcriptome analysis with cells grown in the presence of glucose or gluconate revealed that a functional ED pathway led to activation of a subset of previously reported in vivo expressed genes. All of these results suggest the importance of the ED pathway in V. cholerae pathogenesis. PMID:22544275

Patra, Tapas; Koley, Hemanta; Ramamurthy, Thandavarayan; Ghose, Asoke C; Nandy, Ranjan K

2012-07-01

62

The Ustilago maydis Clp1 protein orchestrates pheromone and b-dependent signaling pathways to coordinate the cell cycle and pathogenic development.  

PubMed

Regulation of the cell cycle and morphogenetic switching during pathogenic and sexual development in Ustilago maydis is orchestrated by a concerted action of the a and b mating-type loci. Activation of either mating-type locus triggers the G2 cell cycle arrest that is a prerequisite for the formation of the infectious dikaryon; this cell cycle arrest is released only after penetration of the host plant. Here, we show that bW, one of the two homeodomain transcription factors encoded by the b mating-type locus, and the zinc-finger transcription factor Rbf1, a master regulator for pathogenic development, interact with Clp1 (clampless 1), a protein required for the distribution of nuclei during cell division of the dikaryon. In addition, we identify Cib1, a previously undiscovered bZIP transcription factor required for pathogenic development, as a Clp1-interacting protein. Clp1 interaction with bW blocks b-dependent functions, such as the b-dependent G2 cell cycle arrest and dimorphic switching. The interaction of Clp1 with Rbf1 results in the repression of the a-dependent pheromone pathway, conjugation tube formation, and the a-induced G2 cell cycle arrest. The concerted interaction of Clp1 with Rbf1 and bW coordinates a- and b-dependent cell cycle control and ensures cell cycle release and progression at the onset of biotrophic development. PMID:20729384

Heimel, Kai; Scherer, Mario; Schuler, David; Kämper, Jörg

2010-08-01

63

The Ustilago maydis Clp1 Protein Orchestrates Pheromone and b-Dependent Signaling Pathways to Coordinate the Cell Cycle and Pathogenic Development[W  

PubMed Central

Regulation of the cell cycle and morphogenetic switching during pathogenic and sexual development in Ustilago maydis is orchestrated by a concerted action of the a and b mating-type loci. Activation of either mating-type locus triggers the G2 cell cycle arrest that is a prerequisite for the formation of the infectious dikaryon; this cell cycle arrest is released only after penetration of the host plant. Here, we show that bW, one of the two homeodomain transcription factors encoded by the b mating-type locus, and the zinc-finger transcription factor Rbf1, a master regulator for pathogenic development, interact with Clp1 (clampless 1), a protein required for the distribution of nuclei during cell division of the dikaryon. In addition, we identify Cib1, a previously undiscovered bZIP transcription factor required for pathogenic development, as a Clp1-interacting protein. Clp1 interaction with bW blocks b-dependent functions, such as the b-dependent G2 cell cycle arrest and dimorphic switching. The interaction of Clp1 with Rbf1 results in the repression of the a-dependent pheromone pathway, conjugation tube formation, and the a-induced G2 cell cycle arrest. The concerted interaction of Clp1 with Rbf1 and bW coordinates a- and b-dependent cell cycle control and ensures cell cycle release and progression at the onset of biotrophic development.

Heimel, Kai; Scherer, Mario; Schuler, David; Kamper, Jorg

2010-01-01

64

Cotton GhMPK2 is involved in multiple signaling pathways and mediates defense responses to pathogen infection and oxidative stress.  

PubMed

Mitogen-activated protein kinase (MAPK) cascades play important roles in mediating pathogen responses and reactive oxygen species signaling. In plants, MAPKs are classified into four major groups (A-D). Previous studies have mainly focused on groups A and B, but little is known about group C. In this study, we functionally characterized a stress-responsive group C MAPK gene (GhMPK2) from cotton. Northern blot analysis indicated that GhMPK2 was induced not only by signaling molecules, such as ethylene and methyl jasmonate, but also by methyl viologen-mediated oxidative stress. Transgenic tobacco (Nicotiana tabacum) plants that overexpress GhMPK2 displayed enhanced resistance to fungal and viral pathogens, and the expression of the pathogenesis-related (PR) genes, including PR1, PR2, PR4, and PR5, was significantly increased. Interestingly, the transcription of 1-aminocyclopropane-1-carboxylic acid synthase (ACS) and 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) was significantly upregulated in transgenic plants, suggesting that GhMPK2 positively regulates ethylene synthesis. Moreover, overexpression of GhMPK2 elevated the expression of several antioxidant enzymes, conferring on transgenic plants enhanced reactive oxygen species scavenging capability and oxidative stress tolerance. These results increased our understanding of the role of the group C GhMPK2 gene in multiple defense-signaling pathways, including those that are involved in responses to pathogen infection and oxidative stress. PMID:21338470

Zhang, Liang; Xi, Dongmei; Luo, Lu; Meng, Fei; Li, Yuzhen; Wu, Chang-ai; Guo, Xingqi

2011-04-01

65

Biosecurity and vector behaviour: evaluating the potential threat posed by anglers and canoeists as pathways for the spread of invasive non-native species and pathogens.  

PubMed

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

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

2014-01-01

66

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

PubMed Central

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

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

2014-01-01

67

ARTICLE WATCH  

PubMed Central

This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, Hartwell Center, St. Jude Children’s Research Hospital, 332 North Lauderdale St., Memphis TN 38105-2794. Tel: (901) 495-4844; Fax: (901) 495-2945; email: Clive.Slaughter@stjude.org or to any member of the editorial board. Article summaries reflect the reviewer’s opinions and not necessarily those of the Association.

2007-01-01

68

Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS  

PubMed Central

Many mutations confer upon copper/zinc superoxide dismutase-1 (SOD1) one or more toxic function(s) that impair motor neuron viability and cause familial amyotrophic lateral sclerosis (FALS). Using a conformation-specific antibody that detects misfolded SOD1 (C4F6), we demonstrate that oxidized WT-SOD1 and mutant-SOD1 share a conformational epitope that is not present in normal WT-SOD1. In a subset of human sporadic ALS (SALS) cases, motor neurons in the lumbosacral spinal cord displayed striking C4F6 immunoreactivity, denoting the presence of aberrant WT-SOD1 species. Recombinant, oxidized WT-SOD1 and WT-SOD1 immunopurified from SALS tissues inhibited kinesin-based fast axonal transport in a manner similar to FALS-linked mutant SOD1. Studies here suggest that WT-SOD1 can be pathogenic in SALS and identifies an SOD1-dependent pathogenic mechanism common to FALS and SALS.

Bosco, Daryl A.; Morfini, Gerardo; Karabacak, N. Murat; Song, Yuyu; Gros-Louis, Francois; Pasinelli, Piera; Goolsby, Holly; Fontaine, Benjamin A.; Lemay, Nathan; McKenna-Yasek, Diane; Frosch, Matthew P.; Agar, Jeffery N.; Julien, Jean-Pierre; Brady, Scott T.; Brown, Robert H.

2010-01-01

69

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

PubMed Central

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

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

2013-01-01

70

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

PubMed

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

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

2013-03-01

71

Pathogen Sensing Pathways in Human Embryonic Stem Cell Derived-Endothelial Cells: Role of NOD1 Receptors  

PubMed Central

Human embryonic stem cell-derived endothelial cells (hESC-EC), as well as other stem cell derived endothelial cells, have a range of applications in cardiovascular research and disease treatment. Endothelial cells sense Gram-negative bacteria via the pattern recognition receptors (PRR) Toll-like receptor (TLR)-4 and nucleotide-binding oligomerisation domain-containing protein (NOD)-1. These pathways are important in terms of sensing infection, but TLR4 is also associated with vascular inflammation and atherosclerosis. Here, we have compared TLR4 and NOD1 responses in hESC-EC with those of endothelial cells derived from other stem cells and with human umbilical vein endothelial cells (HUVEC). HUVEC, endothelial cells derived from blood progenitors (blood outgrowth endothelial cells; BOEC), and from induced pluripotent stem cells all displayed both a TLR4 and NOD1 response. However, hESC-EC had no TLR4 function, but did have functional NOD1 receptors. In vivo conditioning in nude rats did not confer TLR4 expression in hESC-EC. Despite having no TLR4 function, hESC-EC sensed Gram-negative bacteria, a response that was found to be mediated by NOD1 and the associated RIP2 signalling pathways. Thus, hESC-EC are TLR4 deficient but respond to bacteria via NOD1. This data suggests that hESC-EC may be protected from unwanted TLR4-mediated vascular inflammation, thus offering a potential therapeutic advantage.

Reed, Daniel M.; Foldes, Gabor; Gatheral, Timothy; Paschalaki, Koralia E.; Lendvai, Zsuzsanna; Bagyura, Zsolt; Nemeth, Tamas; Skopal, Judit; Merkely, Bela; Telcian, Aurica G.; Gogsadze, Leila; Edwards, Michael R.; Gough, Peter J.; Bertin, John; Johnston, Sebastian L.; Harding, Sian E.; Mitchell, Jane A.

2014-01-01

72

A CREB3-ARF4 signalling pathway mediates the response to Golgi stress and susceptibility to pathogens.  

PubMed

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

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

2013-12-01

73

Pathogen-associated molecular patterns initiate inflammation and perturb the endocrine function of bovine granulosa cells from ovarian dominant follicles via TLR2 and TLR4 pathways.  

PubMed

Bacterial infections of the uterus or mammary gland commonly cause disease and infertility by perturbing growth and steroidogenesis of the dominant follicle in the ovary of cattle. Cells of the innate immune system use Toll-like receptors TLR2, TLR4, and TLR5 to recognize pathogen-associated molecular patterns (PAMPs) expressed by bacteria, leading to activation of MAPK and nuclear factor-?B? pathways and production of inflammatory cytokines such as IL-1? and IL-6, and the chemokine IL-8. The present study tested whether granulosa cells from dominant follicles have functional TLR2, TLR4, and TLR5 pathways. Supernatants of primary bovine granulosa cells accumulated IL-1?, IL-6, and IL-8 when treated for 24 hours with Pam3CSK4 (PAM) that binds TLR2 or lipopolysaccharide (LPS) that binds TLR4 but not flagellin that binds TLR5. Granulosa cell responses to PAM or LPS were rapid, with increased phosphorylation of p38 and ERK1/2 within 30 minutes and increased abundance of IL6, IL1B, IL10, TNF, IL8, and CCL5 mRNA after 3 hours of treatment. Accumulation of IL-6 in response to PAM and LPS was attenuated using small interfering RNA targeting TLR2 and TLR4, respectively. Furthermore, treating granulosa cells with inhibitors targeting MAPK or nuclear factor-?B reduced the accumulation of IL-6 in response to LPS or PAM. Treatment with LPS or PAM reduced the accumulation of estradiol and progesterone, and the PAMPs reduced granulosa cell expression of CYP19A1 mRNA and protein. In conclusion, bacterial PAMPs initiate inflammation and perturb the endocrine function of bovine granulosa cells from dominant follicles via TLR2 and TLR4 pathways. PMID:23825132

Price, Jennifer C; Bromfield, John J; Sheldon, I Martin

2013-09-01

74

Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease  

PubMed Central

Hemoglobin is an important nutrient source for intraerythrocytic malaria organisms. Its catabolism occurs in an acidic digestive vacuole. Our previous studies suggested that an aspartic protease plays a key role in the degradative process. We have now isolated this enzyme and defined its role in the hemoglobinolytic pathway. Laser desorption mass spectrometry was used to analyze the proteolytic action of the purified protease. The enzyme has a remarkably stringent specificity towards native hemoglobin, making a single cleavage between alpha 33Phe and 34Leu. This scission is in the hemoglobin hinge region, unraveling the molecule and exposing other sites for proteolysis. The protease is inhibited by pepstatin and has NH2-terminal homology to mammalian aspartic proteases. Isolated digestive vacuoles make a pepstatin- inhibitable cleavage identical to that of the purified enzyme. The pivotal role of this aspartic hemoglobinase in initiating hemoglobin degradation in the malaria parasite digestive vacuoles is demonstrated.

1991-01-01

75

Reactive Oxygen Species Homeostasis and Virulence of the Fungal Pathogen Cryptococcus neoformans Requires an Intact Proline Catabolism Pathway  

PubMed Central

Degradation of the multifunctional amino acid proline is associated with mitochondrial oxidative respiration. The two-step oxidation of proline is catalyzed by proline oxidase and ?1-pyrroline-5-carboxylate (P5C) dehydrogenase, which produce P5C and glutamate, respectively. In animal and plant cells, impairment of P5C dehydrogenase activity results in P5C-proline cycling when exogenous proline is supplied via the actions of proline oxidase and P5C reductase (the enzyme that converts P5C to proline). This proline is oxidized by the proline oxidase-FAD complex that delivers electrons to the electron transport chain and to O2, leading to mitochondrial reactive oxygen species (ROS) overproduction. Coupled activity of proline oxidase and P5C dehydrogenase is therefore important for maintaining ROS homeostasis. In the genome of the fungal pathogen Cryptococcus neoformans, there are two paralogs (PUT1 and PUT5) that encode proline oxidases and a single ortholog (PUT2) that encodes P5C dehydrogenase. Transcription of all three catabolic genes is inducible by the presence of proline. However, through the creation of deletion mutants, only Put5 and Put2 were found to be required for proline utilization. The put2? mutant also generates excessive mitochondrial superoxide when exposed to proline. Intracellular accumulation of ROS is a critical feature of cell death; consistent with this fact, the put2? mutant exhibits a slight, general growth defect. Furthermore, Put2 is required for optimal production of the major cryptococcal virulence factors. During murine infection, the put2? mutant was discovered to be avirulent; this is the first report highlighting the importance of P5C dehydrogenase in enabling pathogenesis of a microorganism.

Lee, I. Russel; Lui, Edmund Y. L.; Chow, Eve W. L.; Arras, Samantha D. M.; Morrow, Carl A.; Fraser, James A.

2013-01-01

76

MICROBIOLOGY: A Bacterial Pathogen Sees the Light  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Photosensitive proteins abound in the bacterial kingdom, but their cellular functions often remain a mystery. In this Perspective Kennis and Crosson discuss how Swartz et al. identified a functional role for a new type of light sensor in bacteria--light, oxygen, or voltage (LOV) histidine kinase. In the notorious pathogen Brucella abortus, light increases the enzymatic activity of this kinase, which, remarkably, increases virulence of the bacterium. Related LOV histidine kinases are conserved across a range of bacterial taxa, suggesting that this virulence pathway could be one of many new photosensory pathways regulating bacterial physiology.

John T. M. Kennis (Faculty of Sciences, Vrije Universiteit;Biophysics Department); Sean Crosson (The University of Chicago;Department of Biochemistry and Molecular Biology)

2007-08-24

77

Silicon-induced changes in antifungal phenolic acids, flavonoids, and key phenylpropanoid pathway genes during the interaction between miniature roses and the biotrophic pathogen Podosphaera pannosa.  

PubMed

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

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

2011-12-01

78

Siderophore-Based Iron Acquisition and Pathogen Control  

PubMed Central

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

Miethke, Marcus; Marahiel, Mohamed A.

2007-01-01

79

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

PubMed Central

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

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

2013-01-01

80

Quinolones induce partial or total loss of pathogenicity islands in uropathogenic Escherichia coli by SOS-dependent or -independent pathways, respectively.  

PubMed

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

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

2006-02-01

81

Cauliflower mosaic virus, a Compatible Pathogen of Arabidopsis, Engages Three Distinct Defense-Signaling Pathways and Activates Rapid Systemic Generation of Reactive Oxygen Species1  

PubMed Central

We analyzed expression of marker genes for three defense pathways during infection by Cauliflower mosaic virus (CaMV), a compatible pathogen of Arabidopsis (Arabidopsis thaliana), using luciferase reporter transgenes and directly by measuring transcript abundance. Expression of PR-1, a marker for salicylic acid signaling, was very low until 8 d postinoculation and then rose sharply, coinciding with the rise in virus levels. In contrast, as early as 2 h postinoculation, transcriptional up-regulation of GST1—a marker for reactive oxygen species—and PDF1.2—a marker for jasmonic acid/ethylene defense signaling—was detectable in the virus-inoculated leaf and systemically. In parallel with the activation of GST1, H2O2 accumulated locally and systemically in virus- but not mock-inoculated plants. However, in plants inoculated with infectious CaMV DNA rather than virus particles, the onset of systemic luciferase activity was delayed by 24 to 48 h, suggesting that virion structural proteins act as the elicitor. This phenomenon, which we term the rapid systemic response, preceded virus movement from the inoculated leaf; therefore, the systemic signal is not viral. Systemic, but not local, H2O2 accumulation was abolished in rbohDF double mutants and in etr1-1 and ein2-1 mutants, implicating NADPH oxidase and ethylene signaling in the generation and transduction of the response. Ethylene, but not rbohDF mutants, also showed reduced susceptibility to CaMV, whereas in NahG transgenics, virus levels were similar to wild type. These findings implicate reactive oxygen species and ethylene in signaling in response to CaMV infection, but suggest that salicylic acid does not play an effective role.

Love, Andrew J.; Yun, Byung Wook; Laval, Valerie; Loake, Gary J.; Milner, Joel J.

2005-01-01

82

Pathogen Phytosensing: Plants to Report Plant Pathogens  

PubMed Central

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

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

2008-01-01

83

Transcriptional responses to pathogens in Caenorhabditis elegans  

PubMed Central

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

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

2008-01-01

84

Signaling During Pathogen Infection  

NSDL National Science Digital Library

Pathogens infect almost every living organism. In animals, including humans, the diversity of pathogens ranges from viruses, bacteria, and unicellular parasites to complex fungi, worms, and arthropods. Because pathogens have coevolved with their hosts and have sometimes been coopted as symbionts or commensals, each pathogen/host pair represents a striking success story of survival that reflects the biological complexity of both parties. All invading microorganisms face similar problems, such as gaining access to their host, achieving successful replication, and spreading to a similar or different host. It is therefore not surprising that many different pathogens target similar organs, cell types, and even molecules to achieve their goals. However, no two microbial parasites appear to be completely alike. Although they often target similar signaling networks, they do so in subtly different ways to achieve the desired outcome. This review has eight figures, three movies, and 139 citations and emphasizes two well-established signaling pathways that are often activated during the interaction of different pathogens with their host cells. It illustrates a small part of how the dissection of host/pathogen interactions can reveal, on a molecular scale, a nature shaped by evolutionary forces that can rival the great descriptions of our macroscopic world.

Sylvia Munter (University of Heidelberg Medical School;Department of Parasitology REV); Michael Way (London Research Institute;Cancer Research UK REV); Freddy Frischknecht (University of Heidelberg Medical School;Department of Parasitology REV)

2006-05-16

85

The Endless Race Between Plant and Pathogen  

NSDL National Science Digital Library

This article introduces a special issue on plant pathology, including new insights into the evolutionary forces driving plant-pathogen interactions, as well as the practical outcomes in terms of pathogen management.

Pamela Hines (AAAS;); Jean Marx (AAAS;)

2001-06-22

86

Antibiotic targeting of the bacterial secretory pathway.  

PubMed

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

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

2014-08-01

87

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

PubMed

It was previously reported that the amounts of lysophosphatidylcholines (lysoPCs), which are naturally occurring bioactive lipid molecules, significantly increase following pathogen inoculation, as determined using ultraperformance liquid chromatography-quadrupole-time of flight/mass spectrometry analyses. Here, real-time quantitative RT-PCR was performed for the phospholipase A2 (PLA2) genes, Nt1PLA2 and Nt2PLA2, which are responsible for LysoPCs generation. The transcription level of Nt2PLA2 in pathogen-infected tobacco plants transiently peaked at 1h and 36h, whereas induction of Nt1PLA2 transcription peaked at 36h. A prominent biphasic ROS accumulation in lysoPC (C18:1(9Z))-treated tobacco leaves was also observed. Transcription of NtRbohD, a gene member of NADPH oxidase, showed biphasic kinetics upon lysoPC 18:1 treatment, as evidenced by an early transient peak in phase I at 1h and a massive peak in phase II at 12h. Each increase in NtACS2 and NtACS4 transcription, gene members of the ACC synthase family, was followed by biphasic peaks of ethylene production after lysoPC 18:1 treatment. This suggested that lysoPC (C18:1)-induced ethylene production was regulated at the transcriptional level of time-dependent gene members. LysoPC 18:1 treatment also rapidly induced cell damage. LysoPC 18:1-induced cell death was almost completely abrogated in ROS generation-impaired transgenic plants (rbohD-as and rbohF-as), ethylene production-impaired transgenic plants (CAS-AS and CAO-AS), and ethylene signaling-impaired transgenic plants (Ein3-AS), respectively. Taken together, pathogen-induced lysoPCs enhance pathogen susceptibility accompanied by ROS and ethylene biosynthesis, resulting in chlorophyll degradation and cell death. Expression of PR genes (PR1-a, PR-3, and PR-4b) and LOX3 was strongly induced in lysoPC 18:1-treated leaves, indicating the involvement of lysoPC 18:1 in the defense response. However, lysoPC 18:1 treatment eventually resulted in cell death, as evidenced by metacaspase gene expression. Therefore, a hypothesis is proposed that the antipathogenic potential of lysoPC 18:1 is dependent on how quickly it is removed from cells for avoidance of lysoPC toxicity. PMID:24837357

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

2014-08-01

88

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

PubMed Central

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

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

2013-01-01

89

Up-regulation of intracellular signalling pathways may play a central pathogenic role in hypertension, atherogenesis, insulin resistance, and cancer program - the ‘PKC syndrome’  

Microsoft Academic Search

The modern diet is greatly different from that of our paleolithic forebears? in a number of respects. There is reason to believe that many of these dietary shifts can up-regulate intracellular signalling pathways mediated by free intracellular calcium and protein kinase C, particularly in vascular smooth muscle cells; this disorder of intracellular regulation is given the name ‘PKC syndrome#x02019;. PKC

M. F. McCarty

1996-01-01

90

The periodontal pathogen Porphyromonas gingivalis changes the gene expression in vascular smooth muscle cells involving the TGFbeta/Notch signalling pathway and increased cell proliferation  

PubMed Central

Background Porphyromonas gingivalis is a gram-negative bacterium that causes destructive chronic periodontitis. In addition, this bacterium is also involved in the development of cardiovascular disease. The aim of this study was to investigate the effects of P. gingivalis infection on gene and protein expression in human aortic smooth muscle cells (AoSMCs) and its relation to cellular function. Results AoSMCs were exposed to viable P. gingivalis for 24?h, whereafter confocal fluorescence microscopy was used to study P. gingivalis invasion of AoSMCs. AoSMCs proliferation was evaluated by neutral red assay. Human genome microarray, western blot and ELISA were used to investigate how P. gingivalis changes the gene and protein expression of AoSMCs. We found that viable P. gingivalis invades AoSMCs, disrupts stress fiber structures and significantly increases cell proliferation. Microarray results showed that, a total of 982 genes were identified as differentially expressed with the threshold log2 fold change?>?|1| (adjust p-value <0.05). Using bioinformatic data mining, we demonstrated that up-regulated genes are enriched in gene ontology function of positive control of cell proliferation and down-regulated genes are enriched in the function of negative control of cell proliferation. The results from pathway analysis revealed that all the genes belonging to these two categories induced by P. gingivalis were enriched in 25 pathways, including genes of Notch and TGF-beta pathways. Conclusions This study demonstrates that P. gingivalis is able to invade AoSMCs and stimulate their proliferation. The activation of TGF-beta and Notch signaling pathways may be involved in the bacteria-mediated proliferation of AoSMCs. These findings further support the association between periodontitis and cardiovascular diseases.

2013-01-01

91

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

PubMed

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

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

2012-11-01

92

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

PubMed

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

Dogi, C A; Weill, F; Perdigón, G

2010-01-01

93

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

PubMed Central

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

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

2013-01-01

94

Publishing International Counseling Articles  

ERIC Educational Resources Information Center

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

Hohenshil, Thomas H.; Amundson, Norman E.

2011-01-01

95

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

PubMed

The Arabidopsis NPR1 protein is an essential regulatory component of systemic acquired resistance (SAR). Mutations in the NPR1 gene completely block the induction of SAR by signals such as salicylic acid (SA). An Arabidopsis mutant, snc1 (suppressor of npr1-1, constitutive 1), was isolated in a screen for suppressors of npr1-1. In the npr1-1 background, the snc1 mutation resulted in constitutive resistance to Pseudomonas syringae maculicola ES4326 and Peronospora parasitica Noco2. High levels of SA were detected in the mutant and shown to be required for manifestation of the snc1 phenotype. The snc1 mutation was mapped to the RPP5 resistance (R) gene cluster and the eds1 mutation that blocks RPP5-mediated resistance suppressed snc1. These data suggest that a RPP5-related resistance pathway is activated constitutively in snc1. This pathway does not employ NPR1 but requires the signal molecule SA and the function of EDS1. Moreover, in snc1, constitutive resistance is conferred in the absence of cell death, which is often associated with R-gene mediated resistance. PMID:11605952

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

2001-10-01

96

Up-regulation of intracellular signalling pathways may play a central pathogenic role in hypertension, atherogenesis, insulin resistance, and cancer promotion--the 'PKC syndrome'.  

PubMed

The modern diet is greatly different from that of our paleolithic forebears' in a number of respects. There is reason to believe that many of these dietary shifts can up-regulate intracellular signalling pathways mediated by free intracellular calcium and protein kinase C, particularly in vascular smooth muscle cells; this disorder of intracellular regulation is given the name 'PKC syndrome'. PKC syndrome may entail either a constitutive activation of these pathways, or a sensitization to activation by various agonists. The modern dietary perturbations which tend to induce PKC syndrome may include increased dietary fat and sodium, and decreased intakes of omega-3 fats, potassium, calcium, magnesium and chromium. Insulin resistance may be both a cause and effect of PKC syndrome, and weight reduction and aerobic training should act to combat this disorder. PKC syndrome sensitizes vascular smooth muscle cells to both vasoconstrictors and growth factors, and thus promotes both hypertension and atherogenesis. In platelets, it induces hyperaggregability, while in the microvasculature it may be a mediator of diabetic microangiopathy. In vascular endothelium, intimal macrophages, and hepatocytes, increased protein kinase C activity can be expected to increase cardiovascular risk. Up-regulation of protein kinase C in stem cells may also play a role in the promotion of 'Western' fat-related cancers. Practical guidelines for combatting PKC syndrome are suggested. PMID:8676754

McCarty, M F

1996-03-01

97

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

PubMed

Enterohaemorrhagic Escherichia coli (EHEC) causes life-threatening infections in humans as a consequence of the production of Shiga-like toxins. Lack of a good animal model system currently hinders in vivo study of EHEC virulence by systematic genetic methods. Here we applied the genetically tractable animal, Caenorhabditis elegans, as a surrogate host to study the virulence of EHEC as well as the host immunity to this human pathogen. Our results show that E.?coli O157:H7, a serotype of EHEC, infects and kills C.?elegans. Bacterial colonization and induction of the characteristic attaching and effacing (A/E) lesions in the intact intestinal epithelium of C.?elegans by E.?coli O157:H7 were concomitantly demonstrated in vivo. Genetic analysis indicated that the Shiga-like toxin 1 (Stx1) of E.?coli O157:H7 is a virulence factor in C.?elegans and is required for full toxicity. Moreover, the C.?elegans p38 mitogen-activated protein kinase (MAPK) pathway, an evolutionarily conserved innate immune and stress response signalling pathway, is activated in the regulation of host susceptibility to EHEC infection in a Stx1-dependent manner. Our results validate the EHEC-C.?elegans interaction as suitable for future comprehensive genetic screens for both novel bacterial and host factors involved in the pathogenesis of EHEC infection. PMID:22985085

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

2013-01-01

98

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

PubMed Central

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

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

2013-01-01

99

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

PubMed Central

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

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

2014-01-01

100

Articles About Reflexology  

NSDL National Science Digital Library

This collection of articles, provided by Positive Health Magazine, provides information on reflexology for stroke; vertical reflexology; precision reflexology; reflexology for skin disorders; and integrating color with reflexology. The collection of articles also offers some case studies in reflexology. Most of the articles are lengthy and provide helpful color illustrations. The articles would be of interest to aspiring and practicing reflexologists, as well as massage therapists and other practitioners of therapeutic massage.

2007-04-22

101

Activation of Type I and III Interferon Signalling Pathways Occurs in Lung Epithelial Cells Infected with Low Pathogenic Avian Influenza Viruses  

PubMed Central

The host response to the low pathogenic avian influenza (LPAI) H5N2, H5N3 and H9N2 viruses were examined in A549, MDCK, and CEF cells using a systems-based approach. The H5N2 and H5N3 viruses replicated efficiently in A549 and MDCK cells, while the H9N2 virus replicated least efficiently in these cell types. However, all LPAI viruses exhibited similar and higher replication efficiencies in CEF cells. A comparison of the host responses of these viruses and the H1N1/WSN virus and low passage pH1N1 clinical isolates was performed in A549 cells. The H9N2 and H5N2 virus subtypes exhibited a robust induction of Type I and Type III interferon (IFN) expression, sustained STAT1 activation from between 3 and 6 hpi, which correlated with large increases in IFN-stimulated gene (ISG) expression by 10 hpi. In contrast, cells infected with the pH1N1 or H1N1/WSN virus showed only small increases in Type III IFN signalling, low levels of ISG expression, and down-regulated expression of the IFN type I receptor. JNK activation and increased expression of the pro-apoptotic XAF1 protein was observed in A549 cells infected with all viruses except the H1N1/WSN virus, while MAPK p38 activation was only observed in cells infected with the pH1N1 and the H5 virus subtypes. No IFN expression and low ISG expression levels were generally observed in CEF cells infected with either AIV, while increased IFN and ISG expression was observed in response to the H1N1/WSN infection. These data suggest differences in the replication characteristics and antivirus signalling responses both among the different LPAI viruses, and between these viruses and the H1N1 viruses examined. These virus-specific differences in host cell signalling highlight the importance of examining the host response to avian influenza viruses that have not been extensively adapted to mammalian tissue culture.

Sutejo, Richard; Yeo, Dawn S.; Myaing, Myint Zu; Hui, Chen; Xia, Jiajia; Ko, Debbie; Cheung, Peter C. F.; Tan, Boon-Huan; Sugrue, Richard J.

2012-01-01

102

Pathogen intelligence.  

PubMed

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

Steinert, Michael

2014-01-01

103

Method of drying articles  

DOEpatents

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

Janney, Mark A. (Knoxville, TN); Kiggans, Jr., James O. (Oak Ridge, TN)

1999-01-01

104

Method of drying articles  

DOEpatents

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

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

1999-03-23

105

ADS Article Service  

NSDL National Science Digital Library

The Astrophysics Data System, a database funded by the US National Aeronautics and Space Administration, provides access to scanned astronomical journal articles. The database currently contains sixteen journals, including Astronomy & Astrophysics and Meteoritics & Planetary Sciences, from which articles may be viewed. To find articles, specify volume number and page or plate number. The database is restricted to archived journals; most journals are available through 1996, with a few available through 1997. In addition, the articles can be accessed through separate table of contents and abstract services also provided by ADS.

106

Pathogenic agents in freshwater resources  

NASA Astrophysics Data System (ADS)

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

Geldreich, Edwin E.

1996-02-01

107

Metagenomic identification of viral pathogens.  

PubMed

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

Bibby, Kyle

2013-05-01

108

Permaculture Magazine Articles  

NSDL National Science Digital Library

This website from Permaculture Magazine offers a selection of gratis online articles. According to the site, this section "has sample articles from previous issues of Permaculture Magazine. These have been chosen primarily to give an idea of the broad range of subjects covered by the magazine" back to issue number nine. Topics include ecofarming, bird management, earthen huts, and pollution control.

2008-04-03

109

Nanotechnology Featured Articles  

NSDL National Science Digital Library

Three articles from each issue of the Institute of Physics Nanotechnology journal are freely available to all visitors. The selections from the journal are made based on the Editor's choice, or due to their topicality. As a result, the titles are subject to change. The articles are located at the bottom of the page.

110

Article Watch, December 2013  

PubMed Central

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

Slaughter, Clive A.

2013-01-01

111

Article Watch: July 2014  

PubMed Central

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

Slaughter, Clive A.

2014-01-01

112

Article Watch: April 2014  

PubMed Central

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

Slaughter, Clive A.

2014-01-01

113

Article Watch, April 2012  

PubMed Central

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

Slaughter, Clive

2012-01-01

114

Emerald Engineering Articles  

NSDL National Science Digital Library

This webpage from Emerald Publishing features a collection of recently published journals and articles pertaining to engineering technology, in particular, electronics, bio, chemical and medical. Of the 16 engineering journals published by Emerald, 14 are listed in ISI.

2010-11-15

115

Recompressed exfoliated graphite articles  

DOEpatents

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

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

2013-08-06

116

Bacterial pathogens.  

PubMed

Bacterial infections are frequent complications among patients treated for cancer. The type, severity, and treatment of bacterial infections vary and depend upon the specific malignancy, associated chemotherapies, and transplantation. This chapter discusses commonly encountered bacterial pathogens as well as Nocardia and mycobacteria in patients with cancer and addresses the clinical syndromes and management. Drug-resistant bacteria are becoming an increasingly recognized problem in patients with cancer. Antimicrobial resistance in select gram-positive and gram-negative bacteria are discussed along with the mechanisms of resistance and recommended therapies. PMID:24706222

Wilson, John W

2014-01-01

117

SEWAGE SLUDGE PATHOGEN TRANSPORT MODEL PROJECT  

EPA Science Inventory

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

118

Detection of enteric pathogens by the nodosome.  

PubMed

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

Keestra, A Marijke; Bäumler, Andreas J

2014-03-01

119

Avian Haematozoa: mortality and pathogenicity  

Microsoft Academic Search

A review of 5640 articles on avian blood parasites showed that 236 reported mortality or gross pathogenicity in birds, and 89% of them were concerned with mortality in domesticated birds and how to control the blood parasites involved. Only 6% of records concerned birds in zoological gardens; the remainder referred to mortality in wild birds.

G. F. Bennett; M. A. Peirce; R. W. Ashford

1993-01-01

120

"Alternative" Endocytic Mechanisms Exploited by Pathogens  

PubMed Central

Some pathogens utilize unique routes to enter cells that may evade the intracellular barriers encountered by the typical clathrin-mediated endocytic pathway. Retrograde transport and caveolar uptake are among the better characterized pathways, as alternatives to clathrin-mediated endocytosis, that are known to facilitate entry of pathogens and potential delivery agents. Recent characterization of the trafficking mechanisms of prion proteins and certain bacteria may present new paradigms for strategizing improvements in therapeutic spread and retention of therapy. This review will provide an overview of such endocytic pathways, and discuss current and future possibilities in using these routes as a means to improve therapeutic delivery.

Medina-Kauwe, Lali K.

2007-01-01

121

Waterborne pathogens in urban watersheds.  

PubMed

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

Arnone, Russell D; Walling, Joyce Perdek

2007-03-01

122

Molded Magnetic Article  

NASA Technical Reports Server (NTRS)

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

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

2000-01-01

123

An artificial immune system approach to news article recommendation  

Microsoft Academic Search

Artificial immune systems are solution finding techniques often used for classification and recommendation problems. Danger theory is one of new context dependant response theories of how an artificial immune system responds to pathogens. News articles recommendation systems solve problems of presenting articles with interesting topics to user honoring evolving user preferences and past choices. This paper describes how artificial immune

B. Mihaljevic; I. Cavrak; M. Zagar

2005-01-01

124

FindArticles.com  

NSDL National Science Digital Library

This new service is a partnership between LookSmart and the Gale Group, a publisher of research and reference materials for libraries, businesses, and information technologists. The site offers free access to the full-text of articles published in over 350 magazines and journals dating from 1998. Users can search the database by keyword and by one of the nine subject categories (Arts & Entertainment, Computers & Technology, Reference & Education, Sports, etc.). Search returns include article title, periodical, and short description, with a link to the full-text, which is conveniently and quickly displayed at the FindArticles site, though with numerous advertising banners. Visitors can also view a list of the publications indexed, alphabetically or by subject. Periodical listings include a one-sentence description and a link to their Website. Despite the banners and other commercial content (the bills must be paid, after all) this site is a very useful reference source, indexing many leading journals and magazines.

125

[Research progress in pathogenicity of Ureaplasma urealyticum].  

PubMed

Ureaplasma urealyticum (UU) is closely related to human diseases including non-gonococcal urethritis (NGU), infertility, premature membranes and neonatal bronchopulmonary dysplasia. Researches on the pathogenicity of UU have become a hot topic in recent years, and suggest that many potential pathogenicity genes or putative pathogenicity islands are involved in its virulence. Moreover, the biovar and serum types of UU, the infection concentration and the state of the host immune system are also important to determine whether UU can cause human disease or not. In this article the recent progress of researches in the pathogenicity of UU is reviewed. PMID:24022938

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

2013-07-01

126

Slime Mold Development: Article  

NSDL National Science Digital Library

This article describes a video composed of a sequence of time lapse films created by John Tyler Bonner in the 1940s to show the life cycle of the cellular slime mold, Dictyostelium discoideum. As only the second person to study slime molds, Bonner frequently encountered audiences who had never heard of, let alone seen, the unusual organism. He therefore decided to create a film to present at seminars in order to introduce his object of study. Bonner created the video for his senior thesis at Harvard University with the help of photographer Frank Smith. Bonner began to work at Princeton University in 1947, thus the mention of that university on the title screen of the film. It was digitized and narrated by developmental biologist Rachel Fink of Mount Holyoke College. Includes (approximate starting times given): Amoebae [00:02]; Aggregation [00:27]; Migrating Pseudoplasmodia [02:16]; Culmination [03:28]; Trisected Pseudoplasmodium [04:17].

Mary E. Sunderland (ASU Embryo Project Encyclopedia)

2011-11-28

127

Assembly Test Article (ATA)  

NASA Technical Reports Server (NTRS)

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

Ricks, Glen A.

1988-01-01

128

Oomycete pathogens encode RNA silencing suppressors  

PubMed Central

Effectors are essential virulence proteins produced by a broad range of parasites, including viruses, bacteria, fungi, oomycetes, protozoa, insects and nematodes. Upon entry into host cells, pathogen effectors manipulate specific physiological processes or signaling pathways to subvert host immunity. Most effectors, especially those of eukaryotic pathogens, remain functionally uncharacterized. Here, we show that two effectors from the oomycete plant pathogen Phytophthora sojae suppress RNA silencing in plants by inhibiting the biogenesis of small RNAs. Ectopic expression of these Phytophthora suppressors of RNA silencing enhances plant susceptibility to both a virus and Phytophthora, showing that some eukaryotic pathogens have evolved virulence proteins that target host RNA silencing processes to promote infection. These findings identify RNA silencing suppression as a common strategy used by pathogens across kingdoms to cause disease and are consistent with RNA silencing having key roles in host defense.

Qiao, Yongli; Liu, Lin; Xiong, Qin; Flores, Cristina; Wong, James; Shi, Jinxia; Wang, Xianbing; Liu, Xigang; Xiang, Qijun; Jiang, Shushu; Zhang, Fuchun; Wang, Yuanchao; Judelson, Howard S; Chen, Xuemei; Ma, Wenbo

2014-01-01

129

BIOSYNTHETIC PATHWAYS: Biosynthesis Meets Bioinformatics  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. In his Perspective, Cane discusses the increasing importance of the study of biosynthetic pathways in the discovery of biochemical reactions and pathways. Two recent papers (Rohdich et al. and Khaleeli et al.) highlight the increasing role of molecular biology and genomics in the study of biosynthetic pathways.

David E. Cane (Brown University;Department of Chemistry)

2000-02-04

130

Rickettsial pathogens and their arthropod vectors.  

PubMed Central

Rickettsial diseases, important causes of illness and death worldwide, exist primarily in endemic and enzootic foci that occasionally give rise to sporadic or seasonal outbreaks. Rickettsial pathogens are highly specialized for obligate intracellular survival in both the vertebrate host and the invertebrate vector. While studies often focus primarily on the vertebrate host, the arthropod vector is often more important in the natural maintenance of the pathogen. Consequently, coevolution of rickettsiae with arthropods is responsible for many features of the host-pathogen relationship that are unique among arthropod-borne diseases, including efficient pathogen replication, long-term maintenance of infection, and transstadial and transovarial transmission. This article examines the common features of the host-pathogen relationship and of the arthropod vectors of the typhus and spotted fever group rickettsiae.

Azad, A. F.; Beard, C. B.

1998-01-01

131

The cuticle and plant defense to pathogens  

PubMed Central

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

Serrano, Mario; Coluccia, Fania; Torres, Martha; L'Haridon, Floriane; Metraux, Jean-Pierre

2014-01-01

132

PATHOGENS: VIEWS OF EPA'S PATHOGEN EQUIVALENCY COMMITTEE  

EPA Science Inventory

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

133

Bankruptcy and Revised Article 9.  

National Technical Information Service (NTIS)

On July 1, 2001 revisions to Article 9 of the Uniform Commercial Code became effective in almost every state. David Lander Esq., moderates a discussion of the Article 9 changes and their ramifications for bankruptcy judges and practitioners. Nationally re...

2001-01-01

134

Article Omission across Child Languages  

ERIC Educational Resources Information Center

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

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

2008-01-01

135

Microwave sintering of multiple articles  

DOEpatents

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

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

1993-01-01

136

19 CFR of - Textile Articles  

Code of Federal Regulations, 2010 CFR

...2009-04-01 2009-04-01 false Textile Articles of Extension of ATPA Benefits to...SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED...Eradication Act Apparel and Other Textile Articles Under the Andean Trade Promotion...

2009-04-01

137

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

Microsoft Academic Search

Some of the most successful pathogens of human, such as Mycobacterium tuberculosis (Mtb), HIV, and Leishmania donovani not only establish chronic infections but also remain a grave global threat. These pathogens have developed innovative strategies to evade immune responses such as antigenic shift and drift, interference with antigen processing\\/presentation, subversion of phagocytosis, induction of immune regulatory pathways, and manipulation of

Nargis Khan; Uthaman Gowthaman; Susanta Pahari; Javed N. Agrewala

2012-01-01

138

Pathogen recognition and development of particulate vaccines: Does size matter?  

Microsoft Academic Search

The use of particulate carriers holds great promise for the development of effective and affordable recombinant vaccines. Rational development requires a detailed understanding of particle up-take and processing mechanisms to target cellular pathways capable of stimulating the required immune responses safely. These mechanisms are in turn based on how the host has evolved to recognize and process pathogens. Pathogens, as

Sue D. Xiang; Anja Scholzen; Gabriela Minigo; Cassandra David; Vasso Apostolopoulos; Patricia L. Mottram; Magdalena Plebanski

2006-01-01

139

Emerging Escherichia Pathogen  

PubMed Central

Escherichia hermannii was first identified as a new species in 1982. It has rarely been reported as a human pathogen. We report the first case of E. hermannii as the sole pathogen in a catheter-related bloodstream infection.

Permpalung, Nitipong; Sentochnik, Deborah E.

2013-01-01

140

Determinants of Microbial Pathogenicity.  

National Technical Information Service (NTIS)

The terms of pathogenicity and virulence are synonymous; they mean the capacity to produce disease. To be pathogenic a microorganism must be able to: (1) Infect the mucous surfaces of the respiratory, alimentary or urogenital tracts. Some microbes are int...

H. Smith

1984-01-01

141

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

Microsoft Academic Search

Arenaviruses are rodent-borne viruses, with five members of the family capable of causing severe hemor- rhagic fevers if transmitted to humans. To date, two distinct cellular receptors have been identified that are used by different pathogenic viruses, -dystroglycan by Lassa fever virus and transferrin receptor 1 (TfR1) by certain New World clade B viruses. Our previous studies have suggested that

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

2008-01-01

142

Surface treatment of ceramic articles  

DOEpatents

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

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

1998-12-22

143

Modulation of NF-?B signalling by microbial pathogens  

PubMed Central

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

Rahman, Masmudur M.; McFadden, Grant

2013-01-01

144

Insect Behavior: Student Review Articles  

NSDL National Science Digital Library

Colorado State University entomology professor Dr. Louis Bjostad provides this interesting resource of review articles on insect behavior. Each review article was written by a student as part of a graduate level course held in Spring 1999; review articles consist of a three to six paragraph summary of research, followed by a dozen or more recent references. Titles include "Communal Roosting in Insects" and "Behavioral Aspects of Biological Control of Spider Mites," among dozens of others. For those interested in reading summaries of (and finding references to) recent scientific articles on insect behavior, this is an excellent starting place.

145

Taxonomy of bacterial fish pathogens  

PubMed Central

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

2011-01-01

146

Molecular Pathways: The Hedgehog Signaling Pathway in Cancer  

PubMed Central

The Hedgehog (Hh) signaling pathway regulates embryonic development and may be aberrantly activated in a wide variety of human cancers. Efforts to target pathogenic Hh signaling have steadily progressed from the laboratory to the clinic, and the recent approval of the Hh pathway inhibitor vismodegib for patients with advanced basal cell carcinoma (BCC) represents an important milestone. On the other hand, Hh pathway antagonists have failed to demonstrate significant clinical activity in other solid tumors. The reasons for these negative results are not precisely understood, but it is possible that the impact of Hh pathway inhibition has not been adequately measured by the clinical endpoints used thus far or that aberrancies in Hh signal transduction limit the activity of currently available pathway antagonists. Further basic and correlative studies to better understand Hh signaling in human tumors and validate putative anti-tumor mechanisms in the clinical setting may ultimately improve the success of Hh pathway inhibition to other tumor types.

McMillan, Ross; Matsui, William

2012-01-01

147

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

PubMed Central

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

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

1968-01-01

148

Mobilizing Information in Journal Articles.  

ERIC Educational Resources Information Center

Explores the disaggregation (ability to access/manipulate individual components of a document) and reaggregation (compilation of article components into a new written work) of scientific and technical journal articles by students and faculty members. Results lead to a discussion of metadata, the role of context in constraining component use, and…

Bishop, Ann Peterson

1998-01-01

149

Une Pedagogie de l'article (Instruction in the Article).  

ERIC Educational Resources Information Center

A study of error patterns in Polish students' use of the French article provides the basis for an instructional approach that focuses on developing students' linguistic awareness rather than teaching rules of usage. (MSE)

Wilczinska, Veronica

1989-01-01

150

A nutritive view on the host–pathogen interplay  

Microsoft Academic Search

The interaction between pathogenic microbes and their host is determined by survival strategies on both sides, including competition for essential nutrients. During evolution, pathogenic microbes developed ways to access certain nutrients from the host, which, by contrast, can be exploited by the host for defence by restricting the availability of these nutrients. In this article, we review ecological aspects of

Ulrich E. Schaible; Stefan H. E. Kaufmann

2005-01-01

151

Coevolution of Plants and Their Pathogens in Natural Habitats  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Understanding of plant-pathogen coevolution in natural systems continues to develop as new theories at the population and species level are increasingly informed by studies unraveling the molecular basis of interactions between individual plants and their pathogens.

Jeremy J. Burdon (Commonwealth Scientific and Industrial Research Organization (CSIRO)âÂÂPlant Industry;); Peter H. Thrall (Commonwealth Scientific and Industrial Research Organization (CSIRO)âÂÂPlant Industry;)

2009-05-08

152

Pathogenic Microorganisms in Water  

NSDL National Science Digital Library

Pathogenic Microorganisms in Water: Traditionally, groundwater has been used without treatment because the soil acts as a filter, removing pathogenic microorganisms. Some potential sources of pathogens (or disease causing organisms) in groundwater include septic tanks, leaking sewer lines, sewage sludge, intentional groundwater recharge with sewage, irrigation with sewage, direct injection of sewage, domestic solid waste disposal (landfills) and sewage oxidation ponds. The objective of the session is to introduce hydrogeologist to the types of microorganisms, sources of pathogens, and a simple exercise that can be incorporated into a hydrogeology class.

Lenczewski, Melissa

153

Autophagy vitalizes the pathogenicity of pathogenic fungi.  

PubMed

Plant pathogenic fungi utilize a series of complex infection structures, in particular the appressorium, to gain entry to and colonize plant tissue. As a consequence of the accumulation of huge quantities of glycerol in the cell the appressorium generates immense intracellular turgor pressure allowing the penetration peg of the appressorium to penetrate the leaf cuticle. Autophagic processes are ubiquitous in eukaryotic cells and facilitate the bulk degradation of macromolecules and organelles. The study of autophagic processes has been extended from the model yeast Saccharomyces cerevisiae to pathogenic fungi such as the rice blast fungus Magnaporthe oryzae. Significantly, null mutants for the expression of M. oryzae autophagy gene homologs lose their pathogenicity for infection of host plants. Clarification of the functions and network of interactions between the proteins expressed by M. oryzae autophagy genes will lead to a better understanding of the role of autophagy in fungal pathogenesis and help in the development of new strategies for disease control. PMID:22935638

Liu, Xiao-Hong; Gao, Hui-Min; Xu, Fei; Lu, Jian-Ping; Devenish, Rodney J; Lin, Fu-Cheng

2012-10-01

154

Src-family and Syk kinases in activating and inhibitory pathways in innate immune cells: signaling cross talk.  

PubMed

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

Lowell, Clifford A

2011-03-01

155

Professional Communication through Journal Articles.  

ERIC Educational Resources Information Center

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

Rochester, Maxine K.

1996-01-01

156

Computational Science Software and Articles  

NSDL National Science Digital Library

This site introduces computational science with a brief overview which distinguishes computational science ("use primarily of computation, rather than of theorizing or experimentation, to attain scientific knowledge") from computer science ("the invention of efficient search and sort algorithms, techniques of parallel processing, etc."). There are a number of links to software and articles that help the visitor understand. This page is from a larger site that contains even more software and articles on topics including calendars, date conversion, and encryption.

2009-09-01

157

Parallel independent evolution of pathogenicity within the genus Yersinia.  

PubMed

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

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

2014-05-01

158

Parallel independent evolution of pathogenicity within the genus Yersinia  

PubMed Central

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

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

2014-01-01

159

Emerging foodborne pathogens  

Microsoft Academic Search

The broad spectrum of foodborne infections has changed dramatically over time, as well-established pathogens have been controlled or eliminated, and new ones have emerged. The burden of foodborne disease remains substantial: one in four Americans is estimated to have a significant foodborne illness each year. The majority of these illnesses are not accounted for by known pathogens, so more must

Robert V. Tauxe

2002-01-01

160

BACTERIAL WATERBORNE PATHOGENS  

EPA Science Inventory

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

161

Microsporidia: emerging pathogenic protists  

Microsoft Academic Search

Microsporidia are eukaryotic spore forming obligate intracellular protozoan parasites first recognized over 100 years ago. These organisms infect all of the major animal groups and are now recognized as opportunistic pathogens of humans. Microsporidian spores are common in the environment and microsporidia pathogenic to humans have been found in water supplies. The genera Nosema, Vittaforma, Brachiola, Pleistophora, Encephalitozoon, Enterocytozoon, Septata

Louis M. Weiss

2001-01-01

162

Plant pathogen resistance  

DOEpatents

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

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

2012-11-27

163

Plant pathogenic Pseudomonas species  

Microsoft Academic Search

In the current taxonomy, plant pathogenic Pseudomonas species are restricted to rRNA group I organisms belonging to the Gamma subclass of Proteobacteria. Currently, about 21 validly described plant pathogenic Pseudomonas species are known. The most important species is P. syringae with more than 50 described pathovars. The pathovar concept is confusing and the taxonomy of P. syringae needs revision. P.

Monica Höfte; PAUL DE VOS

164

Identifying dysregulated pathways in cancers from pathway interaction networks  

PubMed Central

Background Cancers, a group of multifactorial complex diseases, are generally caused by mutation of multiple genes or dysregulation of pathways. Identifying biomarkers that can characterize cancers would help to understand and diagnose cancers. Traditional computational methods that detect genes differentially expressed between cancer and normal samples fail to work due to small sample size and independent assumption among genes. On the other hand, genes work in concert to perform their functions. Therefore, it is expected that dysregulated pathways will serve as better biomarkers compared with single genes. Results In this paper, we propose a novel approach to identify dysregulated pathways in cancer based on a pathway interaction network. Our contribution is three-fold. Firstly, we present a new method to construct pathway interaction network based on gene expression, protein-protein interactions and cellular pathways. Secondly, the identification of dysregulated pathways in cancer is treated as a feature selection problem, which is biologically reasonable and easy to interpret. Thirdly, the dysregulated pathways are identified as subnetworks from the pathway interaction networks, where the subnetworks characterize very well the functional dependency or crosstalk between pathways. The benchmarking results on several distinct cancer datasets demonstrate that our method can obtain more reliable and accurate results compared with existing state of the art methods. Further functional analysis and independent literature evidence also confirm that our identified potential pathogenic pathways are biologically reasonable, indicating the effectiveness of our method. Conclusions Dysregulated pathways can serve as better biomarkers compared with single genes. In this work, by utilizing pathway interaction networks and gene expression data, we propose a novel approach that effectively identifies dysregulated pathways, which can not only be used as biomarkers to diagnose cancers but also serve as potential drug targets in the future.

2012-01-01

165

Pathogen inactivation techniques.  

PubMed

The desire to rid the blood supply of pathogens of all types has led to the development of many technologies aimed at the same goal--eradication of the pathogen(s) without harming the blood cells or generating toxic chemical agents. This is a very ambitious goal, and one that has yet to be achieved. One approach is to shun the 'one size fits all' concept and to target pathogen-reduction agents at the Individual component types. This permits the development of technologies that might be compatible with, for example, plasma products but that would be cytocidal and thus incompatible with platelet concentrates or red blood cell units. The technologies to be discussed include solvent detergent and methylene blue treatments--designed to inactivate plasma components and derivatives; psoralens (S-59--amotosalen) designed to pathogen-reduce units of platelets; and two products aimed at red blood cells, S-303 (a Frale--frangible anchor-linker effector compound) and Inactine (a binary ethyleneimine). A final pathogen-reduction material that might actually allow one material to inactivate all three blood components--riboflavin (vitamin B2)--is also under development. The sites of action of the amotosalen (S-59), the S-303 Frale, Inactine, and riboflavin are all localized in the nucleic acid part of the pathogen. Solvent detergent materials act by dissolving the plasma envelope, thus compromising the integrity of the pathogen membrane and rendering it non-infectious. By disrupting the pathogen's ability to replicate or survive, its infectivity is removed. The degree to which bacteria and viruses are affected by a particular pathogen-reducing technology relates to its Gram-positive or Gram-negative status, to the sporulation characteristics for bacteria, and the presence of lipid or protein envelopes for viruses. Concerns related to photoproducts and other breakdown products of these technologies remain, and the toxicology of pathogen-reduction treatments is a major ongoing area of investigation. Clearly, regulatory agencies have a major role to play in the evaluation of these new technologies. This chapter will cover the several types of pathogen-reduction systems, mechanisms of action, the inactivation efficacy for specific types of pathogens, toxicology of the various systems and the published research and clinical trial data supporting their potential usefulness. Due to the nature of the field, pathogen reduction is a work in progress and this review should be considered as a snapshot in time rather than a clear picture of what the future will bring. PMID:16377551

Pelletier, J P R; Transue, S; Snyder, E L

2006-01-01

166

Processes for managing pathogens.  

PubMed

Wastewater contains human, animal, and plant pathogens capable of causing viral, bacterial, or parasitic infections. There are several routes whereby sewage pathogens may affect human health, including direct contact, contamination of food crops, zoonoses, and vectors. The range and numbers of pathogens in municipal wastewater vary with the level of endemic disease in the community, discharges from commercial activities, and seasonal factors. Regulations to control pathogen risk in the United States and Europe arising from land application of biosolids are based on the concept of multiple barriers to the prevention of transmission. The barriers are (i) treatment to reduce pathogen content and vector attraction, (ii) restrictions on crops grown on land to which biosolids have been applied, and (iii) minimum intervals following application and grazing or harvesting. Wastewater treatment reduces number of pathogens in the wastewater by concentrating them with the solids in the sludge. Although some treatment processes are designed specifically to inactivate pathogens, many are not, and the actual mechanisms of microbial inactivation are not fully understood for all processes. Vector attraction is reduced by stabilization (reduction of readily biodegradable material) and/or incorporation immediately following application. Concerns about health risks have renewed interest in the effects of treatment (on pathogens) and advanced treatment methods, and work performed in the United States suggests that Class A pathogen reduction can be achieved less expensively than previously thought. Effective pathogen risk management requires control to the complete chain of sludge treatment, biosolids handling and application, and post-application activities. This may be achieved by adherence to quality management systems based on hazard analysis critical control point (HACCP) principles. PMID:15647539

Godfree, Alan; Farrell, Joseph

2005-01-01

167

Neuroprotective effect of Fn14 deficiency is associated with induction of the granulocyte-colony stimulating factor (G-CSF) pathway in experimental stroke and enhanced by a pathogenic human antiphospholipid antibody.  

PubMed

Using a transgenic mouse model of ischemic stroke we checked for a possible interaction of antiphospholipid antibodies (aPL) which often cause thromboses as well as central nervous system (CNS) involvement under non-thrombotic conditions and the TWEAK/Fn14 pathway known to be adversely involved in inflammatory and ischemic brain disease. After 7 days, infarct volumes were reduced in Fn14 deficient mice and were further decreased by aPL treatment. This was associated with strongest increase of the endogenous neuroprotective G-CSF/G-CSF receptor system. This unexpected beneficial action of aPL is an example for a non-thrombogenic action and the double-edged nature of aPL. PMID:20557950

Frauenknecht, Katrin; Bargiotas, Panagiotis; Bauer, Henrike; von Landenberg, Philipp; Schwaninger, Markus; Sommer, Clemens

2010-10-01

168

REVIEW ARTICLE: Fibre optic gyroscopes  

Microsoft Academic Search

The fibre optic gyroscope (FOG) offers the potential of a low cost, high performance strap down inertial navigational instrument. In this article, the principles of the FOG are reviewed and the factors which limit the performance of the system are discussed. The basic Sagnac interferometer is shown to be susceptible to polarisation effects, optically induced nonlinearities and both spatial and

B. Culshaw; I. P. Giles

1983-01-01

169

Journal Articles as Case Studies  

NSDL National Science Digital Library

Students use as the basis for a case study a journal article investigating whether people who claimed to have severe lactose intolerance really were unable to digest lactose. This type of case is referred to as an "issues" or "analysis" type of case in wh

Cornely, Kathleen

1999-11-01

170

Incremental Clustering of Newsgroup Articles  

Microsoft Academic Search

Clustering text documents is a basic enabling technique in a wide variety of Information and Knowledge Management applications. This paper presents an incremental clustering system to organize and manage Newsgroup articles. It serves administrators and readers of a Newsgroup to archive important postings and to get a structured overview on current developments and topics. To be practically applicable, such a

Sascha Hennig; Michael Wurst

2006-01-01

171

Bibliography of Open Classroom Articles.  

ERIC Educational Resources Information Center

Selected periodicals dealing with the open classroom concept are reviewed and evaluated in this annotated bibliography, which is intended as an introduction to open education for parents and concerned citizens. Technical journals are avoided. Some articles are singled out and rated as good, very good, or excellent. The majority deal with the open…

Sibly, Nancy, Comp.

172

GEOGRAPHIC INDEX OF ENVIRONMENTAL ARTICLES  

EPA Science Inventory

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

173

Ophthalmic Parasitosis: A Review Article  

PubMed Central

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

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

2012-01-01

174

Distinct mechanisms of DNA repair in mycobacteria and their implications in attenuation of the pathogen growth.  

PubMed

About a third of the human population is estimated to be infected with Mycobacterium tuberculosis. Emergence of drug resistant strains and the protracted treatment strategies have compelled the scientific community to identify newer drug targets, and to develop newer vaccines. In the host macrophages, the bacterium survives within an environment rich in reactive nitrogen and oxygen species capable of damaging its genome. Therefore, for its successful persistence in the host, the pathogen must need robust DNA repair mechanisms. Analysis of M. tuberculosis genome sequence revealed that it lacks mismatch repair pathway suggesting a greater role for other DNA repair pathways such as the nucleotide excision repair, and base excision repair pathways. In this article, we summarize the outcome of research involving these two repair pathways in mycobacteria focusing primarily on our own efforts. Our findings, using Mycobacterium smegmatis model, suggest that deficiency of various DNA repair functions in single or in combinations severely compromises their DNA repair capacity and attenuates their growth under conditions typically encountered in macrophages. PMID:21982925

Kurthkoti, Krishna; Varshney, Umesh

2012-04-01

175

The Arabidopsis cyclic nucleotide-gated ion channels AtCNGC2 and AtCNGC4 work in the same signaling pathway to regulate pathogen defense and floral transition.  

PubMed

Arabidopsis (Arabidopsis thaliana) cyclic nucleotide-gated ion channels (CNGCs) form a large family consisting of 20 members and have been implicated in Ca(2+) signaling related to various physiological processes, such as pathogen defense, development, and thermotolerance. The null mutant of AtCNGC2, defense, no death (dnd1), exhibits autoimmune phenotypes, while it is impaired in mounting the hypersensitive response, which is a hallmark of effector-triggered (i.e. RESISTANCE-gene mediated) resistance. It has been suggested that AtCNGC2 is involved in defense responses and likely other aspects of physiology through its role as a Ca(2+)-conducting channel. However, the downstream signaling components and its relation with AtCNGC4, which is the closest paralog of AtCNGC2, remain elusive. Despite the fact that cngc4 mutants display almost identical phenotypes to those seen in cngc2 mutants, not much is known about their relationship. Here, we report the identification and characterization of the Arabidopsis mutant repressor of defense no death1 (rdd1), obtained from a suppressor screen of a transfer DNA insertion knockout mutant of AtCNGC2 in order to identify downstream components of dnd1-mediated signal transduction. rdd1 suppressed the majority of dnd1-mediated phenotypes except Ca(2+) hypersensitivity. In addition, rdd1 also suppressed the dnd1-mediated late-flowering phenotype that was discovered in this study. Our genetic analysis conducted to elucidate the relationship between AtCNGC2 and AtCNGC4 indicates that RDD1 is also involved in AtCNGC4-mediated signal transduction. Lastly, bimolecular fluorescence complementation analysis suggests that AtCNGC2 and AtCNGC4 are likely part of the same channel complex. PMID:24027242

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

2013-10-01

176

Host-Pathogen Interactions  

PubMed Central

The results presented demonstrate that microbial pathogens of plants have the ability to secrete proteins which effectively inhibit an enzyme synthesized by the host; an enzyme whose substrate is a constituent of the cell wall of the pathogen. The system in which this was discovered is the anthracnose-causing fungal pathogen (Colletotrichum lindemuthianum) and its host, the French bean (Phaseolus vulgaris). An endo-?-1, 3-glucanase present in the bean leaves is specifically inhibited by a protein secreted by C. lindemuthianum. The cell walls of C. lindemuthianum are shown to be composed largely of a 1, 3-glucan.

Albersheim, Peter; Valent, Barbara S.

1974-01-01

177

Pathogenic Mutations Associated with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Differently Affect Jagged1 Binding and Notch3 Activity via the RBP/JK Signaling Pathway  

PubMed Central

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited vascular dementia characterized by the degeneration of smooth-muscle cells in small cerebral arteries. CADASIL is caused by mutations in NOTCH3, one of the four mammalian homologs to the Drosophila melanogaster NOTCH gene. Disease-associated mutations are distributed throughout the 34 epidermal growth factor–like repeats (EGFRs) that compose the extracellular domain of the Notch3 receptor and result in a loss or a gain of a cysteine residue in one of these EGFRs. In human adults, Notch3 expression is highly restricted to vascular smooth-muscle cells. In patients with CADASIL, there is an abnormal accumulation of Notch3 in the vessel. Molecular pathways linking NOTCH3 mutations to degeneration of vascular smooth-muscle cells are as yet poorly understood. In this study, we investigated the effect of CADASIL mutations on Notch3 activity. We studied five naturally occurring mutations: R90C and C212S, located in the previously identified mutational hotspot EGFR2–5; C428S, shown in this study to be located in the ligand-binding domain EGFR10–11; and C542Y and R1006C, located in EGFR13 and EGFR26, respectively. All five mutant proteins were correctly processed. The C428S and C542Y mutant receptors exhibited a significant reduction in Jagged1-induced transcriptional activity of a RBP/JK responsive luciferase reporter, relative to wild-type Notch3. Impaired signaling activity of these two mutants arose through different mechanisms; the C428S mutant lost its Jagged1-binding ability, whereas C542Y retained it but exhibited an impaired presentation to the cell surface. In contrast, the R90C, C212S, and R1006C mutants retained the ability to bind Jagged1 and were associated with apparently normal levels of signaling activity. We conclude that mutations in Notch3 differently affect Jagged1 binding and Notch3 signaling via the RBP/JK pathway.

Joutel, Anne; Monet, Marie; Domenga, Valerie; Riant, Florence; Tournier-Lasserve, Elisabeth

2004-01-01

178

Main Propulsion Test Article (MPTA)  

NASA Technical Reports Server (NTRS)

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

Snoddy, Cynthia

2010-01-01

179

Fabrication of Molded Magnetic Article  

NASA Technical Reports Server (NTRS)

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

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

2001-01-01

180

Potential drug targets in Mycobacterium tuberculosis through metabolic pathway analysis  

Microsoft Academic Search

The emergence of multidrug resistant varieties of Mycobacterium tuberculosis has led to a search for novel drug targets. We have performed an insilico comparative analysis of metabolic pathways of the host Homo sapiens and the pathogen M. tuberculosis. Enzymes from the biochemical pathways of M. tuberculosis from the KEGG metabolic pathway database were compared with proteins from the hostH. sapiens,

Sharmila Anishetty; Mrudula Pulimi; Pennathur Gautam

2005-01-01

181

Modulation of NF-?B signalling by microbial pathogens  

Microsoft Academic Search

The nuclear factor-?B (NF-?B) family of transcription factors plays a central part in the host response to infection by microbial pathogens, by orchestrating the innate and acquired host immune responses. The NF-?B proteins are activated by diverse signalling pathways that originate from many different cellular receptors and sensors. Many successful pathogens have acquired sophisticated mechanisms to regulate the NF-?B signalling

Masmudur M. Rahman; Grant McFadden

2011-01-01

182

42 CFR 35.35 - Unsalable articles.  

Code of Federal Regulations, 2013 CFR

...2013-10-01 2013-10-01 false Unsalable articles. 35.35 Section 35.35 Public...AND STATION MANAGEMENT Disposition of Articles Produced by Patients § 35.35 Unsalable articles. Articles having no commercial...

2013-10-01

183

[Major pathogenic links of atherosclerosis].  

PubMed

The experimental and clinical data concerning pathogenesis of the atherosclerosis are summarized and analyzed in this article. Major concepts that explain initiation and progressive growth of atherosclerosis such as lipid infiltrations, response to disturbing factors, "response on the keeping of particles" and inflammatory processes are discussed. These concepts are considered as base for integral theory of atherosclerosis according which the inflammatory process in atherosclerosis are the result of the universal response reaction of endothelium to the various disturbing risk factors. Chronic inflammation leads to complex cellular and molecular interactions among cells derived from the endothelium, smooth muscle and several blood cell components and causes oxidative stress, proliferation of smooth muscle cells, oxidative modification of LDL, uptake and macrophage foam cell formation, endothelium dysfunction. Major pathogenic links of atherosclerosis, such as inflammation, oxidative stress, oxidative modification of LDL, lipid infiltration, endothelial dysfunction closely interact, forming close vicious circles which leads to metabolic and morphological disturbances, re-modulation of blood vessels, cardiovascular diseases and such complication as cardiac infarction and stroke. Pathogenic peculiarities of atherosclerosis are the theoretic base to the elaboration of therapeutic strategy. Endothelium may be discussed as a new therapeutic target in atherosclerosis. So far as the leukotrienes play an important role in inflammatory processes, it is suggested that the leukotrienes may be as a potential therapeutic target in cardiovascular diseases. PMID:16369071

Antelava, N A; Pachkoriia, K Z; Kezeli, T D; Nikuradze, N S; Shamkulashvili, G G

2005-11-01

184

Publishing Scientific Articles in XML.  

NASA Astrophysics Data System (ADS)

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

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

2001-12-01

185

DDTRP: Database of Drug Targets for Resistant Pathogens  

PubMed Central

Emergence of drug resistance is a major threat to public health. Many pathogens have developed resistance to most of the existing antibiotics, and multidrug-resistant and extensively drug resistant strains are extremely difficult to treat. This has resulted in an urgent need for novel drugs. We describe a database called ‘Database of Drug Targets for Resistant Pathogens’ (DDTRP). The database contains information on drugs with reported resistance, their respective targets, metabolic pathways involving these targets, and a list of potential alternate targets for seven pathogens. The database can be accessed freely at http://bmi.icmr.org.in/DDTRP.

Sundaramurthi, Jagadish Chandrabose; Ramanandan, Prabhakaran; Brindha, Sridharan; Subhasree, Chelladurai Ramarathnam; Prasad, Abhimanyu; Kumaraswami, Vasanthapuram; Hanna, Luke Elizabeth

2011-01-01

186

Pathogens and gene product normalization in the biomedical literature.  

PubMed

We present a new approach for pathogens and gene product normalization in the biomedical literature. The idea of this approach was motivated by needs such as literature curation, in particular applied to the field of infectious diseases thus, variants of bacterial species (S. aureus, Staphyloccocus aureus, ...) and their gene products (protein ArsC, Arsenical pump modifier, Arsenate reductase, ...). Our approach is based on the use of an Ontology Look-up Service, a Gene Ontology Categorizer (GOCat) and Gene Normalization methods. In the pathogen detection task the use of OLS disambiguates found pathogen names. GOCat results are incorporated into overall score system to support and to confirm the decisionmaking in normalization process of pathogens and their genomes. The evaluation was done on two test sets of BioCreativeIII benchmark: gold standard of manual curation (50 articles) and silver standard (507 articles) curated by collective results of BCIII participants. For the cross-species GN we achieved the precision of 46% for silver and 27% for gold sets. Pathogen normalization results showed 95% of precision and 93% of recall. The impact of GOCat explicitly improves results of pathogen and gene normalization, basically confirming identified pathogens and boosting correct gene identifiers on the top of the results' list ranked by confidence. A correct identification of the pathogen is able to improve significantly normalization effectiveness and to solve the disambiguation problem of genes. PMID:22491118

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

2012-01-01

187

Neopolyploidy and pathogen resistance  

PubMed Central

Despite the well-documented historical importance of polyploidy, the mechanisms responsible for the establishment and evolutionary success of novel polyploid lineages remain unresolved. One possibility, which has not been previously evaluated theoretically, is that novel polyploid lineages are initially more resistant to pathogens than the diploid progenitor species. Here, we explore this possibility by developing and analysing mathematical models of interactions between newly formed polyploid lineages and their pathogens. We find that for the genetic mechanisms of pathogen resistance with the best empirical support, newly formed polyploid populations of hosts are expected to be more resistant than their diploid progenitors. This effect can be quite strong and, in the case of perennial species with recurrent polyploid formation, may last indefinitely, potentially providing a general explanation for the successful establishment of novel polyploid lineages.

Oswald, Benjamin P; Nuismer, Scott L

2007-01-01

188

Emerging and reemerging pathogens.  

PubMed

From 1973 to 1995, 29 new and reemerging pathogenic microbes were recognized. However, in discussions about emerging infectious diseases, the focus is often on the clinical effects of the host-parasite relationship, rather than the examination of the biology of the pathogen. Many of what we refer to as emerging diseases are characterized better as 'diseases of human progress'. Thus, the aerosolization of water has played an important role in the emergence of Legionella pneumophila infections. New diseases are superimposed on endemic diseases such as diarrhoeal diseases, malaria and tuberculosis. In addition, many pathogens are becoming increasingly resistant to standard antimicrobial drugs, making treatment difficult and in some cases impossible. We summarize our experience on emerging parasitic diseases (primary amoebic meningoencephalitis, respiratory cryptosporidiosis, and diplogonoporiasis), and selected problems of bacterial resistance (MDR tuberculosis caused by Mycobacterium bovis and macrolide-resistance mechanisms of Streptococcus pneumoniae and S. pyogenes). PMID:11091058

Gomez-Lus, R; Clavel, A; Castillo, J; Seral, C; Rubio, C

2000-11-01

189

Herpesvirus Exploitation of Host Immune Inhibitory Pathways  

PubMed Central

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

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

2012-01-01

190

Signaling pathways in rheumatoid arthritis  

Microsoft Academic Search

Signaling pathways orchestrate the inflammatory response by regulating various cellular functions such as programmed cell\\u000a death, cell differentiation and proliferation or secretion of signaling molecules. They are classically activated by ligand\\u000a engagement of surface receptors but increasing evidence suggests that intracellular proteins can also detect danger signals.\\u000a Protection from pathogens, chemical or physical injury, or neoplasia relies on a tightly

Jean-Marc Waldburger; Gary S. Firestein

191

The Keystone Pathogen Hypothesis  

PubMed Central

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

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

2012-01-01

192

Bloodborne Pathogens Program  

NASA Technical Reports Server (NTRS)

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

Blasdell, Sharon

1993-01-01

193

Botrytis cinerea manipulates the antagonistic effects between immune pathways to promote disease development in tomato.  

PubMed

Plants have evolved sophisticated mechanisms to sense and respond to pathogen attacks. Resistance against necrotrophic pathogens generally requires the activation of the jasmonic acid (JA) signaling pathway, whereas the salicylic acid (SA) signaling pathway is mainly activated against biotrophic pathogens. SA can antagonize JA signaling and vice versa. Here, we report that the necrotrophic pathogen Botrytis cinerea exploits this antagonism as a strategy to cause disease development. We show that B. cinerea produces an exopolysaccharide, which acts as an elicitor of the SA pathway. In turn, the SA pathway antagonizes the JA signaling pathway, thereby allowing the fungus to develop its disease in tomato (Solanum lycopersicum). SA-promoted disease development occurs through Nonexpressed Pathogen Related1. We also show that the JA signaling pathway required for tomato resistance against B. cinerea is mediated by the systemin elicitor. These data highlight a new strategy used by B. cinerea to overcome the plant's defense system and to spread within the host. PMID:21665999

El Oirdi, Mohamed; El Rahman, Taha Abd; Rigano, Luciano; El Hadrami, Abdelbasset; Rodriguez, María Cecilia; Daayf, Fouad; Vojnov, Adrian; Bouarab, Kamal

2011-06-01

194

The RAM Network in Pathogenic Fungi  

PubMed Central

The regulation of Ace2 and morphogenesis (RAM) network is a protein kinase signaling pathway conserved among eukaryotes from yeasts to humans. Among fungi, the RAM network has been most extensively studied in the model yeast Saccharomyces cerevisiae and has been shown to regulate a range of cellular processes, including daughter cell-specific gene expression, cell cycle regulation, cell separation, mating, polarized growth, maintenance of cell wall integrity, and stress signaling. Increasing numbers of recent studies on the role of the RAM network in pathogenic fungal species have revealed that this network also plays an important role in the biology and pathogenesis of these organisms. In addition to providing a brief overview of the RAM network in S. cerevisiae, we summarize recent developments in the understanding of RAM network function in the human fungal pathogens Candida albicans, Candida glabrata, Cryptococcus neoformans, Aspergillus fumigatus, and Pneumocystis spp.

Saputo, Sarah; Chabrier-Rosello, Yeissa; Luca, Francis C.; Kumar, Anuj

2012-01-01

195

Circadian regulation of plant immunity to pathogens.  

PubMed

The plant circadian clock primes the immune response of Arabidopsis thaliana to infection with the bacterial pathogen Pseudomonas syringae pv tomato DC3000 (Pst DC3000) such that there is a more robust response during the subjective day than subjective night. Thus Pst DC3000 growth in plants infected with the same initial titre of bacteria varies depending on the time of day of infection (Bhardwaj et al., PLoS One 6: e26968, 2011; Zhang et al., PLoS Pathog 9:e1003370, 2013). We describe here a protocol for assaying bacterial leaf titres following pressure infiltration or spray inoculation of Arabidopsis thaliana with Pst DC3000. We also describe a method for assaying plant susceptibility to infection with the necrotrophic fungal pathogen Botrytis cinerea. These methods can be used in studying the circadian clock regulation of signal transduction pathways controlling plant defense responses. PMID:24792058

Ingle, Robert A; Roden, Laura C

2014-01-01

196

DISINFECTION OF EMERGING PATHOGENS  

EPA Science Inventory

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

197

Actinomycetes as plant pathogens  

Microsoft Academic Search

Biology, taxonomy, pathogenicity and control of plant disease inducing actinomycetes are reviewed. Recent progress in the study of potato, sweet potato, blueberry and fruit and forest tree diseases is illustrated. The role in potato scab pathogenesis of the newly discovered phytotoxins, thaxtomins, is discussed.

Romano Locci

1994-01-01

198

42 CFR 35.35 - Unsalable articles.  

Code of Federal Regulations, 2012 CFR

...Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT Disposition of Articles Produced by Patients § 35.35 Unsalable articles. Articles having no commercial value...

2012-10-01

199

Articles on Education from Mercury Magazine  

NSDL National Science Digital Library

This site features an archive of educational articles that have been featured in Mercury Magazine. Each article features resources and news for astronomy educators. The articles discuss a variety of topics, but all are related to teaching astronomy.

2011-02-03

200

Stress adaptation in a pathogenic fungus  

PubMed Central

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

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

2014-01-01

201

Finding and Recommending Scholarly Articles  

NASA Astrophysics Data System (ADS)

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

Kurtz, Michael J.; Henneken, Edwin A.

2014-05-01

202

Bacterial inhibition of eukaryotic pro-inflammatory pathways  

Microsoft Academic Search

Eukaryotic cells perceive and respond to microbes, both pathogenic and commensal, by activation of signaling cascades such\\u000a as the NF-K B pathway. Induction of such pathways leads to the upregulation of a program of gene expression that mediates pro-inflammatory\\u000a and anti-apoptotic effector proteins. This host response is usually effective in clearing or controlling an infection. For\\u000a pathogens (and potentially, symbionts)

Andrew S. Neish

2004-01-01

203

Draft Genome Sequence of the Sexually Transmitted Pathogen Trichomonas vaginalis  

Microsoft Academic Search

We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the ~160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated

J. M. Carlton; R. P. Hirt; J. C. Silva; A. L. Delcher; Michael Schatz; Qi Zhao; J. R. Wortman; S. L. Bidwell; U. C. M. Alsmark; Sébastien Besteiro; Thomas Sicheritz-Ponten; C. J. Noel; J. B. Dacks; P. G. Foster; Cedric Simillion; Y. Van de Peer; Diego Miranda-Saavedra; G. J. Barton; G. D. Westrop; S. Muller; Daniele Dessi; P. L. Fiori; Qinghu Ren; Ian Paulsen; Hanbang Zhang; F. D. Bastida-Corcuera; Augusto Simoes-Barbosa; M. T. Brown; R. D. Hayes; Mandira Mukherjee; C. Y. Okumura; Rachel Schneider; A. J. Smith; Stepanka Vanacova; Maria Villalvazo; B. J. Haas; Mihaela Pertea; Tamara V. Feldblyum; T. R. Utterback; Chung-Li Shu; Kazutoyo Osoegawa; P. J. de Jong; Ivan Hrdy; Lenka Horvathova; Zuzana Zubacova; Pavel Dolezal; Shehre-Banoo Malik; J. M. Logsdon; Katrin Henze; Arti Gupta; Ching C. Wang; R. L. Dunne; J. A. Upcroft; Peter Upcroft; Owen White; S. L. Salzberg; Petrus Tang; Cheng-Hsun Chiu; Ying-Shiung Lee; T. M. Embley; G. H. Coombs; J. C. Mottram; Jan Tachezy; C. M. Fraser-Liggett; P. J. Johnson

2007-01-01

204

Induced pathogen and insect resistance in Arabidopsis: transcriptomics and specificity of defense  

Microsoft Academic Search

An important question in plant defense signaling research is: how are plants capable of integrating signals induced by pathogenic micro-organisms and herbivorous insects into defenses that are specifically active against the attacker encountered? Plant defenses against pathogens and insects are differentially regulated by cross-communicating signaling pathways in which salicylic acid (SA), jasmonic acid (JA) and ethylene (ET) play key roles.

Oosten van V. R

2007-01-01

205

Carbon Metabolism of Enterobacterial Human Pathogens Growing in Epithelial Colorectal Adenocarcinoma (Caco-2) Cells  

Microsoft Academic Search

Analysis of the genome sequences of the major human bacterial pathogens has provided a large amount of information concerning their metabolic potential. However, our knowledge of the actual metabolic pathways and metabolite fluxes occurring in these pathogens under infection conditions is still limited. In this study, we analysed the intracellular carbon metabolism of enteroinvasive Escherichia coli (EIEC HN280 and EIEC

Andreas Götz; Eva Eylert; Wolfgang Eisenreich; Werner Goebel; Holger Bruggemann

2010-01-01

206

Serous ovarian cancer signaling pathways.  

PubMed

Ovarian cancer is the most lethal malignancy of the female genital tract, mainly due to the failure of early diagnosis and the limitations posed by the conventional chemotherapies. Current research has focused in the study of cascades of various cellular molecular reactions, known as signaling pathways. In this review article, authors try to describe the current knowledge regarding the signaling pathways that influence multiple cellular processes in serous ovarian cancer and especially the pathogenesis. Thorough understanding of the precise role of these pathways can lead to the development of new and more effective targeted therapies as well as novel biomarkers in ovarian cancer. PMID:24476895

Kotsopoulos, Ioannis C; Papanikolaou, Alexios; Lambropoulos, Alexandros F; Papazisis, Konstantinos T; Tsolakidis, Dimitrios; Touplikioti, Panagiota; Tarlatzis, Basil C

2014-03-01

207

Clerkship pathway  

PubMed Central

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

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

2012-01-01

208

In silico Identification of Putative Drug Targets in Pseudomonas aeruginosa Through Metabolic Pathway Analysis  

Microsoft Academic Search

Comparative genomic analysis between pathogens and the host Homo sapiens has led to identification of novel drug targets. Microbial drug target identification and validation has been the latest\\u000a trend in pharmacoinformatics. In order to identify a suitable drug target for the pathogen Pseudomonas aeruginosa an in silico comparative analysis of the metabolic pathways between the pathogen and the host Homo

Deepak Perumal; Chu Sing Lim; Meena K. Sakharkar

2007-01-01

209

Arachidonic acid metabolites in pathogenic yeasts  

PubMed Central

Although most of what is known about the biology and function of arachidonic acid metabolites comes from the study of mammalian biology, these compounds can also be produced by lower eukaryotes, including yeasts and other fungi. It is also in this group of organisms that the least is known about the metabolic pathways leading to the production of these compounds as well as the functions of these compounds in the biology of fungi and yeasts. This review will deal with the discovery of oxylipins from polyunsaturated fatty acids, and more specifically the arachidonic acid derived eicosanoids, such as 3-hydroxy eicosatetraenoic acid, prostaglandin F2? and prostaglandin E2, in yeasts starting in the early 1990s. This review will also focus on what is known about the metabolic pathways and/or proteins involved in the production of these compounds in pathogenic yeasts. The possible roles of these compounds in the biology, including the pathology, of these organisms will be discussed.

2012-01-01

210

A guide to in silico vaccine discovery for eukaryotic pathogens.  

PubMed

In this article, a framework for an in silico pipeline is presented as a guide to high-throughput vaccine candidate discovery for eukaryotic pathogens, such as helminths and protozoa. Eukaryotic pathogens are mostly parasitic and cause some of the most damaging and difficult to treat diseases in humans and livestock. Consequently, these parasitic pathogens have a significant impact on economy and human health. The pipeline is based on the principle of reverse vaccinology and is constructed from freely available bioinformatics programs. There are several successful applications of reverse vaccinology to the discovery of subunit vaccines against prokaryotic pathogens but not yet against eukaryotic pathogens. The overriding aim of the pipeline, which focuses on eukaryotic pathogens, is to generate through computational processes of elimination and evidence gathering a ranked list of proteins based on a scoring system. These proteins are either surface components of the target pathogen or are secreted by the pathogen and are of a type known to be antigenic. No perfect predictive method is yet available; therefore, the highest-scoring proteins from the list require laboratory validation. PMID:23097412

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

2013-11-01

211

Agent-Based Personal Article Citation Assistant  

Microsoft Academic Search

Scientific researchers usually need to deal with a large number of scientific and technical articles. A handy toolkit to facilitate retrieval and identification of these articles is vital. This paper presents an agent-based personal article citation assistant (APACA). As an autonomous agent, it provides extensive and efficient assistance for users to identify most related citations in a local article repository

C. Ma; J. Q. Feng; Q. H. Wu

2005-01-01

212

Microbiota-mediated colonization resistance against intestinal pathogens.  

PubMed

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

Buffie, Charlie G; Pamer, Eric G

2013-11-01

213

MagPortal: Magazine Articles on Business  

NSDL National Science Digital Library

MagPortal has compiled this online collection of business articles on a variety of subjects. The sixteen subcategories include Diversity, Future Trends, Industries, Small Business, and Strategies and Management. The articles are current to the month and annotated, including date of article, author, title, and a brief description. Small yellow and orange icons allow users to mark articles and to retrieve related articles in other categories. Clicking on the article title takes users to the original publication. Articles from previous months may be accessed through the MagPortal archive linked at the bottom of each section.

214

Use of critical pathways to improve the care of patients with acute myocardial infarction 1 1 Dr. Krumholz is a Paul Beeson Faculty Scholar. This article was written by CDR Eric S. Holmboe while a fellow in the Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine. The views expressed in this article are those of the author and do not reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government  

Microsoft Academic Search

Purpose: While critical pathways have become a popular strategy to improve the quality of care, their effectiveness is not well defined. The objective of this study was to investigate the effect of a critical pathway on processes of care and outcomes for Medicare patients admitted with acute myocardial infarction.Subjects and Methods: A retrospective cross-sectional and longitudinal cohort study was made

Eric S Holmboe; Thomas P Meehan; Martha J Radford; Yun Wang; Thomas A Marciniak; Harlan M Krumholz

1999-01-01

215

Microtubules and Pathogen Defence  

Microsoft Academic Search

The cytoskeletal network of plant cells represents a dynamic structure that responds to external\\u000a stimuli by changes of organization. An attack of pathogenic microbes represents an external stress that\\u000a seriously threatens plant survival. Growing evidence from recent research indicates that cytoskeletal elements,\\u000a such as microtubules and microfilaments, are central players in plant defence responses. Tubulin and actin\\u000a inhibitors suppress the polarization

Issei Kobayashi; Yuhko Kobayashi

216

Pathways of Antigen Processing  

PubMed Central

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

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

2014-01-01

217

Microbial Pathogens in the Fungal Kingdom.  

PubMed

The fungal kingdom is vast, spanning ~1.5 to as many as 5 million species diverse as unicellular yeasts, filamentous fungi, mushrooms, lichens, and both plant and animal pathogens. The fungi are closely aligned with animals in one of the six to eight supergroups of eukaryotes, the opisthokonts. The animal and fungal kingdoms last shared a common ancestor ~1 billion years ago, more recently than other groups of eukaryotes. As a consequence of their close evolutionary history and shared cellular machinery with metazoans, fungi are exceptional models for mammalian biology, but prove more difficult to treat in infected animals. The last common ancestor to the fungal/metazoan lineages is thought to have been unicellular, aquatic, and motile with a posterior flagellum, and certain extant species closely resemble this hypothesized ancestor. Species within the fungal kingdom were traditionally assigned to four phyla, including the basal fungi (Chytridiomycota, Zygomycota) and the more recently derived monophyletic lineage, the dikarya (Ascomycota, Basidiomycota). The fungal tree of life project has revealed that the basal lineages are polyphyletic, and thus there are as many as eight to ten fungal phyla. Fungi that infect vertebrates are found in all of the major lineages, and virulence arose multiple times independently. A sobering recent development involves the species Batrachochytrium dendrobatidis from the basal fungal phylum, the Chytridiomycota, which has emerged to cause global amphibian declines and extinctions. Genomics is revolutionizing our view of the fungal kingdom, and genome sequences for zygomycete pathogens (Rhizopus, Mucor), skin-associated fungi (dermatophytes, Malassezia), and the Candida pathogenic species clade promise to provide insights into the origins of virulence. Here we survey the diversity of fungal pathogens and illustrate key principles revealed by genomics involving sexual reproduction and sex determination, loss of conserved pathways in derived fungal lineages that are retained in basal fungi, and shared and divergent virulence strategies of successful human pathogens, including dimorphic and trimorphic transitions in form. The overarching conclusion is that fungal pathogens of animals have arisen repeatedly and independently throughout the fungal tree of life, and while they share general properties, there are also unique features to the virulence strategies of each successful microbial pathogen. PMID:21528015

Heitman, Joseph

2011-03-01

218

PIPS: Pathogenicity Island Prediction Software  

PubMed Central

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

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

2012-01-01

219

Pathway 1.0.3  

NSDL National Science Digital Library

Sometimes wandering through the wilds of Wikipedia can result in confusion. For Dennis Lorson, his wandering led him to create this handy application. With Pathway 1.0.3 visitors can retrace their own steps through Wikipedia by creating a graphical network representation of article pages. It's worth a try, and it will work with all computers running Mac OS X 10.4.

Lorson, Dennis

2007-01-01

220

Arabidopsis Jasmonate Signaling Pathway  

NSDL National Science Digital Library

Jasmonates control defense gene expression and male fertility in the model plant Arabidopsis thaliana. In both cases, the involvement of the jasmonate pathway is complex, involving large-scale transcriptional reprogramming. Additionally, jasmonate signaling is hard-wired into the auxin, ethylene, and salicylate signal networks, all of which are under intense investigation in Arabidopsis. In male fertility, jasmonic acid (JA) is the essential signal intervening both at the level of anther elongation and in pollen dehiscense. A number of genes potentially involved in jasmonate-dependent anther elongation have recently been discovered. In the case of defense, at least two jasmonates, JA and its precursor 12-oxo-phytodienoic acid (OPDA), are necessary for the fine-tuning of defense gene expression in response to various microbial pathogens and arthropod herbivores. However, only OPDA is required for full resistance to some insects and fungi. Other jasmonates probably affect yet more physiological responses. A series of breakthroughs have identified the SKP/CULLIN/F-BOX (SCF), CORONATINE INSENSITIVE (COI1) complex, acting together with the CONSTITUTIVE PHOTOMORPHOGENIC 9 (COP9) signalosome, as central regulatory components of jasmonate signaling in Arabidopsis. The studies, mostly involving mutational approaches, have paved the way for suppressor screens that are expected to further extend our knowledge of jasmonate signaling. When these and other new mutants affecting jasmonate signaling are characterized, new nodes will be added to the Arabidopsis Jasmonate Signaling Pathway Connections Map, and the lists of target genes regulated by jasmonates in Arabidopsis will be expanded.

Aurelie Gfeller (University of Lausanne;Gene Expression Laboratory and Faculty of Biology and Medicine REV); Robin Liechti (University of Lausanne;Gene Expression Laboratory and Faculty of Biology and Medicine REV); Edward E. Farmer (University of Lausanne;Gene Expression Laboratory and Faculty of Biology and Medicine REV)

2006-02-14

221

Method of nitriding refractory metal articles  

DOEpatents

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

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

1994-03-15

222

Method of nitriding refractory metal articles  

DOEpatents

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

Tiegs, Terry N. (Lenoir City, TN); Holcombe, Cressie E. (Knoxville, TN); Dykes, Norman L. (Oak Ridge, TN); Omatete, Ogbemi O. (Lagos, NG); Young, Albert C. (Flushing, NY)

1994-01-01

223

48 CFR 425.104 - Nonavailable articles.  

Code of Federal Regulations, 2013 CFR

...2013-10-01 false Nonavailable articles. 425.104 Section 425.104 ...Act-Supplies 425.104 Nonavailable articles. Information required by FAR 25.104(b) shall be submitted to the SPE for submission to the...

2013-10-01

224

48 CFR 825.104 - Nonavailable articles.  

Code of Federal Regulations, 2013 CFR

...PROGRAMS FOREIGN ACQUISITION Buy American Act-Supplies 825.104 Nonavailable articles. The following items are added to the list of nonavailable articles contained in FAR 25.104: Glass, lead Insulin,...

2013-10-01

225

MICROBIOLOGY: Enhanced: A Furtive Pathogen Revealed  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required: The pathogenic bacterium Neisseria meningitidis is the cause of meningococcal meningitis. Although a vaccine is available for Neisseria of serogroups A and C, there is no vaccine available for serogroup B. In a Perspective, Nassif reports on the sequencing of the complete genome of N. meningitidis type B strain MC58 (Tettelin et al.) and the mining of this genome to identify highly conserved surface proteins that may be valuable as vaccine antigens (Pizza et al.).

Xavier Nassif (Faculté de Médecine Necker-Enfants Malades;INSERM Unit 411)

2000-03-10

226

MICROBIOLOGY: Enhanced: Pathogenic Bacteria Prefer Heme  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Bloodletting by physicians before the era of antibiotics may seem like a barbaric practice, but it may have been of some benefit to patients suffering from bacterial infections. In her Perspective, Rouault explains that most bacteria depend on a source of iron to grow and survive inside their animal hosts. A new study (Skaar et al.) shows that the pathogenic bacterium Staphylococcus aureus uses several ingenious strategies to obtain iron from heme stored as hemoglobin in the red blood cells of its mammalian hosts.

Tracey A. Rouault (National Institute of Child Health and Human Development;Human Iron Metabolism, Cell Biology and Metabolism Branch)

2004-09-10

227

Stress Response and Pathogenicity of the Necrotrophic Fungal Pathogen Alternaria alternata  

PubMed Central

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

Chung, Kuang-Ren

2012-01-01

228

Method for fabricating boron carbide articles  

Microsoft Academic Search

Described is a method for fabricating an essentially uniformly dense boron carbide article of a length-to-diameter or width ratio greater than 2 to 1 comprising the steps of providing a plurality of article segments to be joined together to form the article with each of said article segments having a length-to-diameter or width ratio less than 1.5 to 1. Each

Z. Ardary; C. Reynolds

1980-01-01

229

Do plant and human pathogens have a common pathogenicity strategy?  

Microsoft Academic Search

Recently, a novel ‘two-step’ model of pathogenicity has been described that suggests host-cell-derived vasculoproliferative factors play a crucial role in the pathogenesis of bacillary angiomatosis, a disease caused by the human pathogenic bacterium Bartonella henselae. The resulting proliferation of endothelial cells could be interpreted as bacterial pathogens triggering the promotion of their own habitat: the host cell. Similar disease mechanisms

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

2002-01-01

230

Immune cells have sex and so should journal articles.  

PubMed

Males and females have the same immunological cells, proteins, and pathways in place to protect against the development of disease. The kinetics, magnitude, and skewing of the responses mounted against pathogens, allergens, toxins, or self-antigens, however, can differ dramatically between the sexes. Generally, females mount higher innate and adaptive immune responses than males, which can result in faster clearance of pathogens but also contributes to increased susceptibility to inflammatory and autoimmune diseases in females compared with males. Hormonal and genetic factors contribute significantly to sex differences in immune function and disease pathogenesis. In particular, the expression of X-linked genes and microRNA as well as sex steroid hormones signaling through hormone receptors in immune cells can affect responses to immunological stimuli differently in males and females. Despite data illustrating profound differences between the sexes in immune function, sex differences in the pathogenesis of disease are often overlooked in biomedical research. Establishing journal policies that require authors to report the sex of their cells, animals, and subjects will improve our understanding of the pathogenesis of diseases, with the long-term goal of personalizing treatments for immune-mediated diseases differently for males and females in an effort to protect us equally. PMID:22434079

Klein, Sabra L

2012-06-01

231

The Pathway Tools Software in 2009  

Microsoft Academic Search

Abstract Pathway Tools is a production-quality software environment for creating a type of model- organism database (MOD) called a Pathway\\/Genome Database (PGDB). A PGDB such as EcoCyc integrates the evolving understanding of the genes, proteins, metabolic network, and regulatory network of an organism. This article provides an overview of Pathway Tools capabilities. The software performs multiple computational inferences including prediction

Peter D. Karp; Suzanne M. Paley; Markus Krummenacker; Mario Latendresse; Joseph M. Dale; Tom Lee; Pallavi Kaipa; Fred Gilham; Aaron Spaulding; Liviu Popescu; Tomer Altman; Ian Paulsen; Ingrid M. Keseler; Ron Caspi

2009-01-01

232

Referent Salience Affects Second Language Article Use  

ERIC Educational Resources Information Center

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

Trenkic, Danijela; Pongpairoj, Nattama

2013-01-01

233

Authoring Newspaper Science Articles: A Rewarding Experience  

ERIC Educational Resources Information Center

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

Gonzalez-Espada, Wilson J.

2009-01-01

234

Measuring the Interestingness of News Articles  

SciTech Connect

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

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

2007-09-24

235

Measuring the Interestingness of News Articles.  

National Technical Information Service (NTIS)

An explosive growth of online news has taken place. Users are inundated with thousands of news articles, only some of which are interesting. A system to filter out uninteresting articles would aid users that need to read and analyze many articles daily, s...

A. F. Cardenas D. J. Buttler R. K. Pon

2007-01-01

236

Cryptosporidium Pathogenicity and Virulence  

PubMed Central

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

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

2013-01-01

237

Host-pathogen interactions: can micronutrients tip the balance?  

PubMed

Nutrients are essential to the human host and to its invading pathogens. The purpose of this International Nutrition Council symposium on Micronutrient Regulation of Host-Pathogen Interactions held at Experimental Biology 2006 was to examine new knowledge about the mechanisms by which certain limiting micronutrients can mediate the balance of power between the human host and its numerous potential pathogens. In this introductory article, we briefly review how competition for nutrients is critical to the survival of both host and pathogen and describe some of the evolved mechanisms by which each attempts to gain supremacy over the other. We provide examples of how the presence or absence of certain mechanisms for nutrient acquisition can govern the niche specificity of organisms. We then describe some of the extensive evidence suggesting that, of all the nutrients, iron plays an especially crucial role in host-pathogen interactions. To this end, we provide a reminder of early studies suggesting that universal iron administration under conditions of high pathogen exposure may lead to adverse consequences. Finally, we provide some cautionary tales in the form of intervention studies in which the administration of other micronutrients yielded unpredicted adverse effects. These lessons emphasize the need to step back from an unbalanced concentration of research funds on empirical trials (often built on an inadequate theoretical basis) and toward a greater concentration on integrated clinical research into nutrient effects on host defenses and pathogen virulence. PMID:17449601

Prentice, Andrew M; Ghattas, Hala; Cox, Sharon E

2007-05-01

238

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

PubMed

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

Pareja, Maria Eugenia Mansilla; Colombo, Maria I

2013-01-01

239

Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms  

PubMed Central

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

Mansilla Pareja, Maria Eugenia; Colombo, Maria I.

2013-01-01

240

Science and Technology Review Mapping Pathogens for Biodefense.  

National Technical Information Service (NTIS)

This months issue has the following articles: (1)'Computing Science: One Arrow in the Quiver for Homeland Security'--Commentary by Wayne Shotts; (2) 'On the Front Lines of Biodefense'--The Laboratory's pathogen bioinformatics group is developing ways to r...

2004-01-01

241

Endophytic actinobacteria induce defense pathways in Arabidopsis thaliana.  

PubMed

Endophytic actinobacteria, isolated from healthy wheat tissue, which are capable of suppressing a number wheat fungal pathogens both in vitro and in planta, were investigated for the ability to activate key genes in the systemic acquired resistance (SAR) or the jasmonate/ethylene (JA/ET) pathways in Arabidopsis thaliana. Inoculation of A. thaliana (Col-0) with selected endophytic strains induced a low level of SAR and JA/ET gene expression, measured using quantitative polymerase chain reaction. Upon pathogen challenge, endophyte-treated plants demonstrated a higher abundance of defense gene expression compared with the non-endophyte-treated controls. Resistance to the bacterial pathogen Erwinia carotovora subsp. carotovora required the JA/ET pathway. On the other hand, resistance to the fungal pathogen Fusarium oxysporum involved primarily the SAR pathway. The endophytic actinobacteria appear to be able to "prime" both the SAR and JA/ET pathways, upregulating genes in either pathway depending on the infecting pathogen. Culture filtrates of the endophytic actinobacteria were investigated for the ability to also activate defense pathways. The culture filtrate of Micromonospora sp. strain EN43 grown in a minimal medium resulted in the induction of the SAR pathway; however, when grown in a complex medium, the JA/ET pathway was activated. Further analysis using Streptomyces sp. strain EN27 and defense-compromised mutants of A. thaliana indicated that resistance to E. carotovora subsp. carotovora occurred via an NPR1-independent pathway and required salicylic acid whereas the JA/ET signaling molecules were not essential. In contrast, resistance to F. oxysporum mediated by Streptomyces sp. strain EN27 occurred via an NPR1-dependent pathway but also required salicylic acid and was JA/ET independent. PMID:18184065

Conn, V M; Walker, A R; Franco, C M M

2008-02-01

242

PI3K-? inhibitors in the therapeutic intervention of diseases caused by obligate intracellular pathogens  

PubMed Central

Our increased understanding of host pathogen interactions shows that pathogens could capitalize on host cell pathways to favor entry and disease establishment. One such pathway used by Leishmania mexicana to enter into neutrophils and macrophages is the PI3K? signaling pathway. We recently showed that the use of the PI3K? inhibitor AS-605240 for the treatment of experimental L. mexicana infection in mice resulted in significantly lower parasite burdens and lesion sizes than WT untreated mice. Further, AS-605240 was found to be as effective as Sodium Stibogluconate, the drug of choice for treatment of L. mexicana infection, in reducing parasite burdens in mice. Here, we provide potential mechanisms of PI3K? blockade in promoting resistance to L. mexicana infection in mice. As a proof of principle, we propose that targeting host cell signaling pathways used in the establishment of infection could be a possible therapeutic option in the management of obligate intracellular pathogens.

Oghumu, Steve; Satoskar, Abhay R.

2013-01-01

243

Protein Disulfide Isomerase and Host-Pathogen Interaction  

PubMed Central

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

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

2011-01-01

244

27 CFR 26.51 - Formulas for articles, eligible articles and products manufactured with denatured spirits.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Formulas for articles, eligible articles and products manufactured with denatured spirits...DEPARTMENT OF THE TREASURY ALCOHOL LIQUORS AND ARTICLES FROM PUERTO RICO AND THE VIRGIN ISLANDS...

2013-04-01

245

27 CFR 26.221 - Formulas for articles, eligible articles and products manufactured with denatured spirits.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Formulas for articles, eligible articles and products manufactured with denatured spirits...DEPARTMENT OF THE TREASURY ALCOHOL LIQUORS AND ARTICLES FROM PUERTO RICO AND THE VIRGIN ISLANDS...

2013-04-01

246

Fungal pathogens of Proteaceae.  

PubMed

Species of Leucadendron, Leucospermum and Protea (Proteaceae) are in high demand for the international floriculture market due to their brightly coloured and textured flowers or bracts. Fungal pathogens, however, create a serious problem in cultivating flawless blooms. The aim of the present study was to characterise several of these pathogens using morphology, culture characteristics, and DNA sequence data of the rRNA-ITS and LSU genes. In some cases additional genes such as TEF 1-? and CHS were also sequenced. Based on the results of this study, several novel species and genera are described. Brunneosphaerella leaf blight is shown to be caused by three species, namely B. jonkershoekensis on Protea repens, B. nitidae sp. nov. on Protea nitida and B. protearum on a wide host range of Protea spp. (South Africa). Coniothyrium-like species associated with Coniothyrium leaf spot are allocated to other genera, namely Curreya grandicipis on Protea grandiceps, and Microsphaeropsis proteae on P. nitida (South Africa). Diaporthe leucospermi is described on Leucospermum sp. (Australia), and Diplodina microsperma newly reported on Protea sp. (New Zealand). Pyrenophora blight is caused by a novel species, Pyrenophora leucospermi, and not Drechslera biseptata or D. dematoidea as previously reported. Fusicladium proteae is described on Protea sp. (South Africa), Pestalotiopsis protearum on Leucospermum cuneiforme (Zimbabwe), Ramularia vizellae and R. stellenboschensis on Protea spp. (South Africa), and Teratosphaeria capensis on Protea spp. (Portugal, South Africa). Aureobasidium leaf spot is shown to be caused by two species, namely A. proteae comb. nov. on Protea spp. (South Africa), and A. leucospermi sp. nov. on Leucospermum spp. (Indonesia, Portugal, South Africa). Novel genera and species elucidated in this study include Gordonomyces mucovaginatus and Pseudopassalora gouriqua (hyphomycetes), and Xenoconiothyrium catenata (coelomycete), all on Protea spp. (South Africa). PMID:22403475

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

2011-12-01

247

Mining biological networks from full-text articles.  

PubMed

The study of biological networks is playing an increasingly important role in the life sciences. Many different kinds of biological system can be modelled as networks; perhaps the most important examples are protein-protein interaction (PPI) networks, metabolic pathways, gene regulatory networks, and signalling networks. Although much useful information is easily accessible in publicly databases, a lot of extra relevant data lies scattered in numerous published papers. Hence there is a pressing need for automated text-mining methods capable of extracting such information from full-text articles. Here we present practical guidelines for constructing a text-mining pipeline from existing code and software components capable of extracting PPI networks from full-text articles. This approach can be adapted to tackle other types of biological network. PMID:24788265

Czarnecki, Jan; Shepherd, Adrian J

2014-01-01

248

Pathway-Pondering: Metabolic Engineering Problem Space  

NSDL National Science Digital Library

This problem space can be used to explore concepts related to metabolism. It is based on an article by Causey et al. (2004), entitled "Engineering Escherichia coli for Efficient Conversion of Glucose to Pyruvate". Students can use the original data from the article and various tools to visualize metabolic pathways to explore questions about bioengineering.

Sebrenka Robic (Agnes Scott College;); Kam Dahlquist (Loyola Marymount University;)

2007-06-17

249

When does pathogen evolution maximize the basic reproductive number in well-mixed host-pathogen systems?  

PubMed

Pathogen evolution towards the largest basic reproductive number, R0, has been observed in many theoretical models, but this conclusion does not hold universally. Previous studies of host-pathogen systems have defined general conditions under which R0 maximization occurs in terms of R0 itself. However, it is unclear what constraints these conditions impose on the functional forms of pathogen related processes (e.g. transmission, recover, or mortality) and how those constraints relate to the characteristics of natural systems. Here we focus on well-mixed SIR-type host-pathogen systems and, via a synthesis of results from the literature, we present a set of sufficient mathematical conditions under which evolution maximizes R0. Our conditions are in terms of the functional responses of the system and yield three general biological constraints on when R0 maximization will occur. First, there are no genotype-by-environment interactions. Second, the pathogen utilizes a single transmission pathway (i.e. either horizontal, vertical, or vector transmission). Third, when mortality is density dependent: (i) there is a single infectious class that individuals cannot recover from, (ii) mortality in the infectious class is entirely density dependent, and (iii) the rates of recovery, infection progression, and mortality in the exposed classes are independent of the pathogen trait. We discuss how this approach identifies the biological mechanisms that increase the dimension of the environmental feedback and prevent R0 maximization. PMID:23070214

Cortez, Michael H

2013-12-01

250

Method of producing silicon carbide articles  

DOEpatents

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

Milewski, John V. (Los Alamos, NM)

1985-01-01

251

Reporting ethical practices in journal articles.  

PubMed

Little attention has focused on the reporting of ethical research practices in journal articles. In Study 1, published articles in 2 psychopathology journals were reviewed to ascertain the types of ethical research information that were reported. In Study 2, a survey was sent to authors in Study 1 to determine which ethical practices they engaged in, if they reported this information, and reasons for not including this information in their article. In general, there is a great variability regarding the types of ethical research practices reported in journal articles. Commonly cited reasons for not including ethical research practice information in the articles included the need for brevity, belief that it was common practice, and lack of relevance for the project. These results suggest that there is no standard practice for reporting research practices in journal articles and great variability in the implementation of procedures that are generally considered standard. PMID:12656070

Sigmon, Sandra T; Boulard, Nina E; Whitcomb-Smith, Stacy

2002-01-01

252

Biaxially textured articles formed by powder metallurgy  

DOEpatents

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

Goyal, Amit (Knoxville, TN); Williams, Robert K. (Knoxville, TN)

2001-01-01

253

Signaling Pathways in Cartilage Repair  

PubMed Central

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

Mariani, Erminia; Pulsatelli, Lia; Facchini, Andrea

2014-01-01

254

Bacteria: More Than Pathogens  

NSDL National Science Digital Library

This ActionBioscience lesson plan has students explore the many roles of bacteria, harmful and beneficial. A detailed article written for ActionBioscience by a microbiologist provides background information, which is followed by discussion questions and educational activities designed for middle school to undergraduate biology courses. The Web site also provides carefully selected links for further exploring the topic, including useful sites for student research projects.

Wassenaar, Trudy M.

255

New trends in emerging pathogens  

Microsoft Academic Search

The emergence of pathogens is the result of a number of impact in all parts of the food chain.The emerging technologies in food production explain how new pathogens can establish themselves in the food chain and compromise food safety. The impact of the food technology is analysed for several bacteria, such as Yersinia, Campylobacter, Arcobacter, Helicobacter pullorum, Enterobacter sakazakii, Mycobacterium

Niels Skovgaard

2007-01-01

256

Common themes in microbial pathogenicity.  

PubMed Central

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

Finlay, B B; Falkow, S

1989-01-01

257

Common and Uncommon Pathogenic Cascades in Lysosomal Storage Diseases*  

PubMed Central

Lysosomal storage diseases (LSDs), of which about 50 are known, are caused by the defective activity of lysosomal proteins, resulting in accumulation of unmetabolized substrates. As a result, a variety of pathogenic cascades are activated such as altered calcium homeostasis, oxidative stress, inflammation, altered lipid trafficking, autophagy, endoplasmic reticulum stress, and autoimmune responses. Some of these pathways are common to many LSDs, whereas others are only altered in a subset of LSDs. We now review how these cascades impact upon LSD pathology and suggest how intervention in the pathways may lead to novel therapeutic approaches.

Vitner, Einat B.; Platt, Frances M.; Futerman, Anthony H.

2010-01-01

258

Red card for pathogens: phytoalexins in sorghum and maize.  

PubMed

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

Poloni, Alana; Schirawski, Jan

2014-01-01

259

Pathogen Specific, IRF3-Dependent Signaling and Innate Resistance to Human Kidney Infection  

PubMed Central

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

Fischer, Hans; Lutay, Nataliya; Ragnarsdottir, Bryndis; Yadav, Manisha; Jonsson, Klas; Urbano, Alexander; Al Hadad, Ahmed; Ramisch, Sebastian; Storm, Petter; Dobrindt, Ulrich; Salvador, Ellaine; Karpman, Diana; Jodal, Ulf; Svanborg, Catharina

2010-01-01

260

Qualitative Research Articles: Guidelines, Suggestions and Needs  

ERIC Educational Resources Information Center

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

Crescentini, Alberto; Mainardi, Giuditta

2009-01-01

261

Automatic Paraphrase Acquisition from News Articles  

Microsoft Academic Search

Paraphrases play an important role in the variety and complexity of natural language documents. However they adds to the difficulty of natural language processing. Here we describe a procedure for ob- taining paraphrases from news article. A set of paraphrases can be useful for various kinds of applications. Articles derived from dif- ferent newspapers can contain paraphrases if they report

Yusuke Shinyama; Satoshi Sekine; Kiyoshi Sudo

2002-01-01

262

Citation Advantage of Open Access Articles  

Microsoft Academic Search

Open access (OA) to the research literature has the potential to accelerate recognition and dissemination of research findings, but its actual effects are controversial. This was a longitudinal bibliometric analysis of a cohort of OA and non-OA articles published between June 8, 2004, and December 20, 2004, in the same journal (PNAS: Proceedings of the National Academy of Sciences). Article

Gunther Eysenbach

2006-01-01

263

Teaching Critical Appraisal of Articles on Psychopharmacology  

ERIC Educational Resources Information Center

Objective: Psychiatrists and other physicians sometimes read publications superficially, relying excessively on abstracts. The authors addressed this problem by teaching critical appraisal of individual articles. Method: The authors developed a 23-item appraisal instrument to assess articles in the area of psychopharmacology. The results were…

Mohr, Pavel; Hoschl, Cyril; Volavka, Jan

2012-01-01

264

How Teachers and Researchers Read Academic Articles  

ERIC Educational Resources Information Center

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

Bartels, Nat

2003-01-01

265

Qualitative research articles: guidelines, suggestions and needs  

Microsoft Academic Search

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

Alberto Crescentini; Giuditta Mainardi

2009-01-01

266

Articles on American Literature, 1968-1975.  

ERIC Educational Resources Information Center

This is the third volume in a series giving bibliographic references for articles written about many phases of American literature. It has an extensive section listing articles about the works of specific American authors. Other sections included are: American literature (aims and methods, bibliography, biography and autobiography, and ethnic…

Leary, Lewis, Comp.; Auchard, John, Comp.

267

Gymnastics. Selected Coaching Articles. Officiating Techniques.  

ERIC Educational Resources Information Center

This publication is a compilation of articles directed toward providing a better understanding of the various aspects of gymnastics and to promote a greater proficiency among educators, coaches, judges, leaders, and participants of sport programs for girls and women. Articles in the first section cover the technical aspects of gymnastics: (1)…

Niccollai, Rene, Ed.

268

Periodical Articles of School Historical Interest.  

ERIC Educational Resources Information Center

This translation from the "Yearbook of Danish School History" summarizes nine articles from Danish educational journals. Six describe past changes in primary education, teacher training and salaries, the Greenland schools, and the definitions of deviant behavior. The remaining three articles present background information on current problems. (AM)

Norgaard, Ellen

1981-01-01

269

Online medical journal article layout analysis  

Microsoft Academic Search

We describe a physical and logical layout analysis algorithm, which is applied to segment and label online medical journal articles (regular HTML and PDF-Converted-HTML files). For these articles, the geometric layout of the Web page is the most important cue for physical layout analysis. The key to physical layout analysis is then to render the HTML file in a Web

Jie Zou; Daniel Le; George R. Thoma

2007-01-01

270

Method of manufacturing ceramic shaped articles  

NASA Technical Reports Server (NTRS)

A method of manufacturing ceramic shaped articles, wherein tapes of ceramic powder material in mixture with a binder material and special additives are shaped and then articles are stamped out from said tapes and sintered in a sintering furnace is described.

Inoue, K.

1983-01-01

271

The Type I Interferon Pathway  

NSDL National Science Digital Library

The type I interferon (IFN-α/β) signal transduction pathway is not only the first-characterized Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, but one of the best studied in molecular detail. IFN-α-stimulated gene factor 3 (ISGF3) is atypical for STAT-containing complexes, because it requires interaction with an additional factor, IFN regulatory factor 9 (IRF9), to provide specific DNA binding. Type I IFN is the main innate antiviral cytokine, and the outcome of ISGF3 activation is establishment of the cellular antiviral state, in which cells are able to inhibit the replication of a broad range of virus types providing a general resistance to infection. It is increasingly evident that other branches of the innate and adaptive immune systems activate IFN-α/β signaling, indicating its importance in various stress responses. The Connections Map provides an overview of this canonical pathway, with an interpathway relation to the Toll-like Receptor Pathway, which stimulates the production of type I interferons in response to microbial pathogens. Science Viewpoint D. S. Aaronson, C. M. Horvath, A road map for those who don't know JAK-STAT. Science 296, 1653-1655 (2002). [Abstract] [Full Text

David S. Aaronson (Mount Sinai School of Medicine;Immunobiology Center REV); Curt M. Horvath (Mount Sinai School of Medicine;Immunobiology Center REV)

2003-08-26

272

The Oxylipin Pathway in Arabidopsis  

PubMed Central

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

Creelman, Robert A.; Mulpuri, Rao

2002-01-01

273

Manned remote work station development article  

NASA Technical Reports Server (NTRS)

The two prime objectives of the Manned Remote Work Station (MRWS) Development Article Study are to first, evaluate the MRWS flight article roles and associated design concepts for fundamental requirements and embody key technology developments into a simulation program; and to provide detail manufacturing drawings and schedules for a simulator development test article. An approach is outlined which establishes flight article requirements based on past studies of Solar Power Satellite, orbital construction support equipments, construction bases and near term shuttle operations. Simulation objectives are established for those technology issues that can best be addressed on a simulator. Concepts for full-scale and sub-scale simulators are then studied to establish an overall approach to studying MRWS requirements. Emphasis then shifts to design and specification of a full-scale development test article.

1978-01-01

274

Utilization survey of prototype structural test article  

NASA Technical Reports Server (NTRS)

A survey was conducted of six aerospace companies and two NASA agencies to determine how prototype structural test articles are used in flight operations. The prototype structures are airframes and similar devices which are used for testing and generally are not flown. The survey indicated the following: (1) prototype test articles are not being discarded after development testing is complete, but are used for other purposes, (2) only two cases of prototypes being refurbished and flown were identified, (3) protective devices and inspection techniques are available to prevent or minimize test article damage, (4) substitute programs from design verification are availabel in lieu of using prototype structural articles, and (5) there is a trend away from dedicated test articles. Four options based on these study results were identified to reduce test and hardware costs without compromising reliability of the flight program.

Baber, S.; Mcdaniel, H. M.; Berry, M. J.

1974-01-01

275

Adhesion by pathogenic corynebacteria.  

PubMed

Pathogenic members of the genus Corynebacterium cause a wide range of serious infections in humans including diphtheria. Adhesion to host cells is a crucial step during infection. In Corynebacterium diphtheriae, adhesion is mediated primarily by filamentous structures called pili or fimbriae that are covalently attached to the bacterial cell wall. C. diphtheriae produces three distinct pilus structures, SpaA-, SpaD- and SpaH-type pili. Similar to other types, the prototype SpaA pilus consists of SpaA forming the pilus shaft and two minor pilins SpaB and SpaC located at the base and at the tip, respectively. The minor pilins SpaB/SpaC are critical for bacterial binding to human pharyngeal cells, and thus represent the major adhesins of corynebacteria. Like pili of many other gram-positive microbes, the assembly of corynebacterial pili occurs by a two-step mechanism, whereby pilins are covalently polymerized by a transpeptidase enzyme named pilin-specific sortase and the generated pilus polymer is subsequently anchored to the cell wall peptidoglycan via the base pilin by the housekeeping sortase or a non-polymerizing sortase. This chapter reviews the current knowledge of corynebacterial adhesion, with a specific focus on pilus structures, their assembly, and the mechanism of adhesion mediated by pili. PMID:21557059

Rogers, Elizabeth A; Das, Asis; Ton-That, Hung

2011-01-01

276

Host-Pathogen Interactions  

PubMed Central

A ?-glucan isolated from the mycelial walls of Phytophthora megasperma var. sojae and a glucan purified from yeast extract stimulate the accumulation of phytoalexins in red kidney bean, Phaseolus vulgaris, and stimulate the accumulation of the phytoalexin, rishitin, in potato tubers, Solanum tuberosum. These glucans have previously been shown to be potent elicitors of glyceollin accumulation in soybean, Glycine max. Treatment of kidney bean cotyledons with the glucan elicitors resulted in the accumulation of at least five fungistatic compounds. These compounds migrate during thin layer chromatography identically to the fungistatic compounds which accumulate in kidney beans which have been inoculated with Colletotrichum lindemuthianum, a fungal pathogen of kidney beans. Potatoes accumulate as much as 29 micrograms of rishitin per gram fresh weight following exposure to the glucan from Phytophthora megasperma var. sojae and as much as 19.5 micrograms of rishitin per gram fresh weight following exposure to yeast glucan. Potatoes accumulated 28 micrograms of rishitin per gram fresh weight following inoculation with live Phytophthora megasperma var. sojae. ImagesFig. 1

Cline, Kenneth; Wade, Mark; Albersheim, Peter

1978-01-01

277

Infection strategies of enteric pathogenic Escherichia coli  

PubMed Central

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

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

2012-01-01

278

Directionally solidified article with weld repair  

NASA Technical Reports Server (NTRS)

A directionally solidified nickel-base superalloy article has a defect therein extending parallel to the solidification direction. The article is repaired by removing any foreign matter present in the defect, and then heating the article to a repair temperature of from about 60 to about 98 percent of the solidus temperature of the base material in a chamber containing a protective gas that inhibits oxidation of the base material. The defect is filled with a filler metal while maintaining the article at the repair temperature. The filling is accomplished by providing a source of the filler metal of substantially the same composition as the base material of the directionally solidified article, and melting the filler metal into the defect progressively while moving the source of the filler metal relative to the article in a direction parallel to the solidification direction. Optionally, additional artificial heat extraction is accomplished in a heat-flow direction that is within about 45 degrees of the solidification direction, as the filler metal solidifies within the defect. The article may thereafter be heat treated.

Smashey, Russell W. (Inventor); Snyder, John H. (Inventor); Borne, Bruce L. (Inventor)

2003-01-01

279

Weld repair of directionally solidified articles  

NASA Technical Reports Server (NTRS)

A directionally solidified nickel-base superalloy article has a defect therein extending parallel to the solidification direction. The article is repaired by removing any foreign matter present in the defect, and then heating the article to a repair temperature of from about 60 to about 98 percent of the solidus temperature of the base material in a chamber containing a protective gas that inhibits oxidation of the base material. The defect is filled with a filler metal while maintaining the article at the repair temperature. The filling is accomplished by providing a source of the filler metal of substantially the same composition as the base material of the directionally solidified article, and melting the filler metal into the defect progressively while moving the source of the filler metal relative to the article in a direction parallel to the solidification direction. Optionally, additional artificial heat extraction is accomplished in a heat-flow direction that is within about 45 degrees of the solidification direction, as the filler metal solidifies within the defect. The article may thereafter be heat treated.

Smashey, Russell W. (Inventor); Snyder, John H. (Inventor); Borne, Bruce L. (Inventor)

2002-01-01

280

Environmental Pathogens, Emerging Pathogens and Biofilms in Microgravity.  

National Technical Information Service (NTIS)

Over the last couple of decades, those of us interested in drinking water microbiology have been intrigued by the environmental pathogens that not only survive, but are often thought to proliferate in drinking water, often associated with biofilms. These ...

T. E. Ford

2012-01-01

281

Coated article and method of making  

NASA Technical Reports Server (NTRS)

An article includes a silicon-containing substrate and a modified mullite coating. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating. The article can further comprise a thermal barrier coating applied to the modified mullite coating. The modified mullite coating functions as a bond coating between the external environmental/thermal barrier coating and the silicon-containing substrate. In a method of forming an article, a silicon-containing substrate is formed and a modified mullite coating is applied. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating.

Wang, Hongyu (Inventor); Lee, Kang Neung (Inventor)

2002-01-01

282

Coated article and method of making  

NASA Technical Reports Server (NTRS)

An article includes a silicon-containing substrate and a modified mullite coating. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating. The article can further comprise a thermal barrier coating applied to the modified mullite coating. The modified mullite coating functions as a bond coating between the external environmental/thermal barrier coating and the silicon-containing substrate. In a method of forming an article, a silicon-containing substrate is formed and a modified mullite coating is applied. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating.

Wang, Hongyu (Inventor); Lee, Kang Neung (Inventor)

2003-01-01

283

Torsional texturing of superconducting oxide composite articles  

DOEpatents

A method of texturing a multifilamentary article having filaments comprising a desired oxide superconductor or its precursors by torsionally deforming the article is provided. The texturing is induced by applying a torsional strain which is at least about 0.3 and preferably at least about 0.6 at the surface of the article, but less than the strain which would cause failure of the composite. High performance multifilamentary superconducting composite articles having a plurality of low aspect ratio, twisted filaments with substantially uniform twist pitches in the range of about 1.00 inch to 0.01 inch (25 to 0.25 mm), each comprising a textured desired superconducting oxide material, may be obtained using this texturing method. If tighter twist pitches are desired, the article may be heat treated or annealed and the strain repeated as many times as necessary to obtain the desired twist pitch. It is preferred that the total strain applied per step should be sufficient to provide a twist pitch tighter than 5 times the diameter of the article, and twist pitches in the range of 1 to 5 times the diameter of the article are most preferred. The process may be used to make a high performance multifilamentary superconducting article, having a plurality of twisted filaments, wherein the degree of texturing varies substantially in proportion to the radial distance from the center of the article cross-section, and is substantially radially homogeneous at any given cross-section of the article. Round wires and other low aspect ratio multifilamentary articles are preferred forms. The invention is not dependent on the melting characteristics of the desired superconducting oxide. Desired oxide superconductors or precursors with micaceous or semi-micaceous structures are preferred. When used in connection with desired superconducting oxides which melt irreversibly, it provides multifilamentary articles that exhibit high DC performance characteristics and AC performance markedly superior to any currently available for these materials. In a preferred embodiment, the desired superconducting oxide material is BSCCO 2223.

Christopherson, Craig John (Grafton, MA); Riley, Jr., Gilbert N. (Marlborough, MA); Scudiere, John (Bolton, MA)

2002-01-01

284

Production of super-smooth articles  

DOEpatents

Super-smooth rounded or formed articles made of thermoplastic materials including various poly(methyl methacrylate) or acrylonitrile-butadiene-styrene copolymers are produced by immersing the articles into a bath, the composition of which is slowly changed with time. The starting composition of the bath is made up of at least one solvent for the polymer and a diluent made up of at least one nonsolvent for the polymer and optional materials which are soluble in the bath. The resulting extremely smooth articles are useful as mandrels for laser fusion and should be useful for a wide variety of other purposes, for example lenses.

Duchane, David V. (Los Alamos, NM)

1983-01-01

285

Production of super-smooth articles  

SciTech Connect

Super-smooth rounded or formed articles made of thermoplastic materials including various poly(Methyl methacrylate) or acrylonitrile-butadiene-styrene copolymers are produced by immersing the articles into a bath, the composition of which is slowly changed with time. The starting composition of the bath is made up of at least one solvent for the polymer and a diluent made up of at least one nonsolvent for the polymer and optional materials which are soluble in the bath. The resulting extremely smooth articles are useful as mandrels for laser fusion and should be useful for a wide variety of other purposes, for example lenses.

Duchane, D.V.

1983-03-15

286

Production of super-smooth articles  

SciTech Connect

Super-smooth rounded or formed articles made of thermoplastic materials including various poly(methyl methacrylate) or acrylonitrile-butadiene-styrene copolymers are produced by immersing the articles into a bath, the composition of which is slowly changed with time. The starting composition of the bath is made up of at least one solvent for the polymer and a diluent made up of at least one nonsolvent for the polymer and optional materials which are soluble in the bath. The resulting extremely smooth articles are useful as mandrels for laser fusion and should be useful for a wide variety of other purposes, for example lenses.

Duchane, D.V.

1981-05-29

287

Lipolytic Enzymes Involved in the Virulence of Human Pathogenic Fungi  

PubMed Central

Pathogenic microbes secrete various enzymes with lipolytic activities to facilitate their survival within the host. Lipolytic enzymes include extracellular lipases and phospholipases, and several lines of evidence have suggested that these enzymes contribute to the virulence of pathogenic fungi. Candida albicans and Cryptococcus neoformans are the most commonly isolated human fungal pathogens, and several biochemical and molecular approaches have identified their extracellular lipolytic enzymes. The role of lipases and phospholipases in the virulence of C. albicans has been extensively studied, and these enzymes have been shown to contribute to C. albicans morphological transition, colonization, cytotoxicity, and penetration to the host. While not much is known about the lipases in C. neoformans, the roles of phospholipases in the dissemination of fungal cells in the host and in signaling pathways have been described. Lipolytic enzymes may also influence the survival of the lipophilic cutaneous pathogenic yeast Malassezia species within the host, and an unusually high number of lipase-coding genes may complement the lipid dependency of this fungus. This review briefly describes the current understanding of the lipolytic enzymes in major human fungal pathogens, namely C. albicans, C. neoformans, and Malassezia spp.

Park, Minji; Do, Eunsoo

2013-01-01

288

Pathogen virulence of Phytophthora infestans: from gene to functional genomics.  

PubMed

The oomycete, Phytophthora infestans, is one of the most important plant pathogens worldwide. Much of the pathogenic success of P. infestans, the potato late blight agent, relies on its ability to generate large amounts of sporangia from mycelia, which release zoospores that encyst and form infection structures. Until recently, little was known about the molecular basis of oomycete pathogenicity by the avirulence molecules that are perceived by host defenses. To understand the molecular mechanisms interplay in the pathogen and host interactions, knowledge of the genome structure was most important, which is available now after genome sequencing. The mechanism of biotrophic interaction between potato and P. infestans could be determined by understanding the effector biology of the pathogen, which is until now poorly understood. The recent availability of oomycete genome will help in understanding of the signal transduction pathways followed by apoplastic and cytoplasmic effectors for translocation into host cell. Finally based on genomics, novel strategies could be developed for effective management of the crop losses due to the late blight disease. PMID:24431484

Sanju, Suman; Thakur, Aditi; Siddappa, Sundresha; Sreevathsa, Rohini; Srivastava, Nidhi; Shukla, Pradeep; Singh, B P

2013-04-01

289

Immune evasion by pathogenic leptospira strains: the secretion of proteases that directly cleave complement proteins.  

PubMed

Leptospirosis is an infectious disease of public health importance. To successfully colonize the host, pathogens have evolved multiple strategies to escape the complement system. Here we demonstrate that the culture supernatant of pathogenic but not saprophytic Leptospira inhibit the three complement pathways. We showed that the proteolytic activity in the supernatants of pathogenic strains targets the central complement molecule C3 and specific proteins from each pathway, such as factor B, C2, and C4b. The proteases cleaved ? and ? chains of C3 and work in synergy with host regulators to inactivate C3b. Proteolytic activity was inhibited by 1,10-phenanthroline, suggesting the participation of metalloproteases. A recombinant leptospiral metalloprotease from the thermolysin family cleaved C3 in serum and could be one of the proteases responsible for the supernatant activity. We conclude that pathogenic leptospiral proteases can deactivate immune effector molecules and represent potential targets to the development of new therapies in leptospirosis. PMID:24163418

Fraga, Tatiana Rodrigues; Courrol, Daniella Dos Santos; Castiblanco-Valencia, Mónica Marcela; Hirata, Izaura Yoshico; Vasconcellos, Sílvio Arruda; Juliano, Luiz; Barbosa, Angela Silva; Isaac, Lourdes

2014-03-01

290

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

SciTech Connect

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

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

2008-12-19

291

Chinese Space Science and Technology (Selected Articles).  

National Technical Information Service (NTIS)

This article carries out a technical summary for communication satellites. It describes limiting conditions in the process of designing communications satellites, and it details primary technical design characteristics of sub-systems on satellites, for ex...

1991-01-01

292

Chinese Space Science and Technology (Selected Articles).  

National Technical Information Service (NTIS)

This Chinese translation consists of two articles: Control of solid-apogee motor during orbit transfer maneuver; and Application of split-phase code PSK signal in data transmission of meteorological satellite remote sensing image.

1991-01-01

293

Shapers of Published NNS Research Articles.  

ERIC Educational Resources Information Center

Presents a comprehensive picture of the shapers of a published nonnative speaker research article by including the language professionals and indicating how they fit into the pre-publication processing of a text. (Author/VWL)

Burrough-Boenisch, Joy

2003-01-01

294

Polycarbonate Article with Chemical Resistant Coating.  

National Technical Information Service (NTIS)

An article of laminate construction is disclosed which is comprised of an underlayer of polycarbonate polymer material to which is applied a chemically resistant outer layer of polysulfone. The layers which are joined by compression-heat molding, are mold...

J. J. Kosmo F. S. Dawn

1989-01-01

295

The Definite Article in Bulgarian and Macedonian  

ERIC Educational Resources Information Center

The enclitic status of the article in Contemporary Standard Bulgarian and Contemporary Standard Macedonian is investigated by comparing its junctural and accentual properties with those of undisputed enclitics in each language. (Author/RM)

Elson, Mark J.

1976-01-01

296

Pyrimidine salvage pathway in Mycobacterium tuberculosis.  

PubMed

The causative agent of tuberculosis (TB), Mycobacterium tuberculosis, infects one-third of the world population. TB remains the leading cause of mortality due to a single bacterial pathogen. The worldwide increase in incidence of M. tuberculosis has been attributed to the high proliferation rates of multi and extensively drug-resistant strains, and to co-infection with the human immunodeficiency virus. There is thus a continuous requirement for studies on mycobacterial metabolism to identify promising targets for the development of new agents to combat TB. Singular characteristics of this pathogen, such as functional and structural features of enzymes involved in fundamental metabolic pathways, can be evaluated to identify possible targets for drug development. Enzymes involved in the pyrimidine salvage pathway might be attractive targets for rational drug design against TB, since this pathway is vital for all bacterial cells, and is composed of enzymes considerably different from those present in humans. Moreover, the enzymes of the pyrimidine salvage pathway might have an important role in the mycobacterial latent state, since M. tuberculosis has to recycle bases and/or nucleosides to survive in the hostile environment imposed by the host. The present review describes the enzymes of M. tuberculosis pyrimidine salvage pathway as attractive targets for the development of new antimycobacterial agents. Enzyme functional and structural data have been included to provide a broader knowledge on which to base the search for compounds with selective biological activity. PMID:21366534

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

2011-01-01

297

A Rejoinder to Hales’s Article  

Microsoft Academic Search

Conclusion  This then is an item-by-item reality check on the mathematical content of their objections to my article [2], on which they\\u000a have based their assessment on the status of the Kepler conjecture. It should now be clear from the responses that their objections\\u000a are without any mathematical foundations.\\u000a \\u000a Let me conclude this article with a few remarks on the proof

Wu-Yi Hsiang

1995-01-01

298

Biaxially textured articles formed by plastic deformation  

DOEpatents

A method of preparing a biaxially textured article comprises the steps of providing a metal preform, coating or laminating the preform with a metal layer, deforming the layer to a sufficient degree, and rapidly recrystallizing the layer to produce a biaxial texture. A superconducting epitaxial layer may then be deposited on the biaxial texture. In some embodiments the article further comprises buffer layers, electromagnetic devices or electro-optical devices.

Goyal, Amit (Knoxville, TN)

2001-01-01

299

Predicting clicks of PubMed articles  

PubMed Central

Predicting the popularity or access usage of an article has the potential to improve the quality of PubMed searches. We can model the click trend of each article as its access changes over time by mining the PubMed query logs, which contain the previous access history for all articles. In this article, we examine the access patterns produced by PubMed users in two years (July 2009 to July 2011). We explore the time series of accesses for each article in the query logs, model the trends with regression approaches, and subsequently use the models for prediction. We show that the click trends of PubMed articles are best fitted with a log-normal regression model. This model allows the number of accesses an article receives and the time since it first becomes available in PubMed to be related via quadratic and logistic functions, with the model parameters to be estimated via maximum likelihood. Our experiments predicting the number of accesses for an article based on its past usage demonstrate that the mean absolute error and mean absolute percentage error of our model are 4.0% and 8.1% lower than the power-law regression model, respectively. The log-normal distribution is also shown to perform significantly better than a previous prediction method based on a human memory theory in cognitive science. This work warrants further investigation on the utility of such a log-normal regression approach towards improving information access in PubMed.

Mao, Yuqing; Lu, Zhiyong

2013-01-01

300

Method for fabricating boron carbide articles  

Microsoft Academic Search

The fabrication of boron carbide articles having length-to-diameter or width ratios greater than 2 to 1 is described. The process consists of hot pressing boron carbide powder into article segments or portions in which the segments have a length-to-diameter or width ratio less than 1.5, aligning a plurality of the initially hot-pressed segments in a hot-pressing die with the end

Ardary

1978-01-01

301

Method for fabricating boron carbide articles  

Microsoft Academic Search

The present invention is directed to the fabrication of boron carbide articles having length-to-diameter or width ratios greater than 2 to 1. The process of the present invention is practiced by the steps comprising hot pressing boron carbide powder into article segments or portions in which the segments have a length-to-diameter or width ratio less than 1.5, aligning a plurality

Zane L. Ardary; Carl D. Reynolds

1980-01-01

302

Tracking multiple topics for finding interesting articles  

Microsoft Academic Search

We introduce multiple topic tracking (MTT) for iScore to better recommend news articles for users with multiple interests and to address changes in user interests over time. As an extension of the basic Rocchio algorithm, traditional topic detection and tracking, and single-pass clustering, MTT maintains multiple interest profiles to identify interesting articles for a specific user given user-feedback. Focusing on

Raymond K. Pon; Alfonso F. Cardenas; David Buttler; Terence Critchlow

2007-01-01

303

Tracking Multiple Topics for Finding Interesting Articles  

SciTech Connect

We introduce multiple topic tracking (MTT) for iScore to better recommend news articles for users with multiple interests and to address changes in user interests over time. As an extension of the basic Rocchio algorithm, traditional topic detection and tracking, and single-pass clustering, MTT maintains multiple interest profiles to identify interesting articles for a specific user given user-feedback. Focusing on only interesting topics enables iScore to discard useless profiles to address changes in user interests and to achieve a balance between resource consumption and classification accuracy. Also by relating a topic's interestingness to an article's interestingness, iScore is able to achieve higher quality results than traditional methods such as the Rocchio algorithm. We identify several operating parameters that work well for MTT. Using the same parameters, we show that MTT alone yields high quality results for recommending interesting articles from several corpora. The inclusion of MTT improves iScore's performance by 9% to 14% in recommending news articles from the Yahoo! News RSS feeds and the TREC11 adaptive filter article collection. And through a small user study, we show that iScore can still perform well when only provided with little user feedback.

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

2007-02-15

304

Database Citation in Full Text Biomedical Articles  

PubMed Central

Molecular biology and literature databases represent essential infrastructure for life science research. Effective integration of these data resources requires that there are structured cross-references at the level of individual articles and biological records. Here, we describe the current patterns of how database entries are cited in research articles, based on analysis of the full text Open Access articles available from Europe PMC. Focusing on citation of entries in the European Nucleotide Archive (ENA), UniProt and Protein Data Bank, Europe (PDBe), we demonstrate that text mining doubles the number of structured annotations of database record citations supplied in journal articles by publishers. Many thousands of new literature-database relationships are found by text mining, since these relationships are also not present in the set of articles cited by database records. We recommend that structured annotation of database records in articles is extended to other databases, such as ArrayExpress and Pfam, entries from which are also cited widely in the literature. The very high precision and high-throughput of this text-mining pipeline makes this activity possible both accurately and at low cost, which will allow the development of new integrated data services.

Kafkas, Senay; Kim, Jee-Hyub; McEntyre, Johanna R.

2013-01-01

305

Biosignatures of Pathogen and Host.  

National Technical Information Service (NTIS)

In information theory, a signature is characterized by the information content as well as noise statistics of the communication channel. Biosignatures have analogous properties. A biosignature can be associated with a particular attribute of a pathogen or...

J. P. Fitch

2002-01-01

306

Pathogenic 'Naegleria': Distribution in Nature.  

National Technical Information Service (NTIS)

Infection in man with pathogenic Naegleria, a free-living soil amoeba, results in a usually fatal disease entity known as primary amoebic meningoencephalitis. Epidemiological data usually included exposure to freshwater lakes or streams within the week pr...

F. M. Wellings P. T. Amuso A. L. Lewis M. J. Farmelo D. J. Moody

1979-01-01

307

NLR functions beyond pathogen recognition  

Microsoft Academic Search

The last 10 years have witnessed the identification of a new class of intracellular pattern-recognition molecules—the nucleotide-binding domain and leucine-rich repeat–containing family (NLR). Members of this family garnered interest as pattern-recognition receptors able to trigger inflammatory responses against pathogens. Many studies support a pathogen-recognition function for human NLR proteins and shed light on their role in the broader control of

Thomas A Kufer; Philippe J Sansonetti

2011-01-01

308

Principles of the Atmospheric Pathway for Invasive Species Applied to Soybean Rust  

NSDL National Science Digital Library

This peer reviewed article from BioScience is about disease in soybeans. Aerial transport alone is seldom responsible for the introduction of nonindigenous species into distant regions; however, the capacity to use the atmospheric pathway for rapid spread in large part determines the invasive potential of organisms once they are introduced. Because physical and biological features of Earth's surface influence the routes and timing of organisms that use the atmospheric pathway, long-distance movement of aerobiota is largely regular and thus predictable. Soybean rust (Phakopsora pachyrhizi), potentially the most destructive foliar disease of soybean, recently invaded North America. The concepts presented in this article form the basis of the soybean rust aerobiology prediction system (SRAPS) that was developed to assess potential pathogen movement from South America to the United States. Output from SRAPS guided the scouting operations after the initial discovery of soybean rust in Louisiana. Subsequent observations of P. pachyrhizi in the southeastern United States provide validation of the modeling effort.

SCOTT A. ISARD, STUART H. GAGE, PAUL COMTOIS, and JOSEPH M. RUSSO (;)

2005-10-01

309

Pathogenic Mechanisms of Pulmonary Arterial Hypertension  

PubMed Central

Pulmonary arterial hypertension (PAH)1 is a complex disease that causes significant morbidity and mortality and is clinically characterized by an increase in pulmonary vascular resistance. The histopathology is marked by vascular proliferation/fibrosis, remodeling, and vessel obstruction. Development of PAH involves the complex interaction of multiple vascular effectors at all anatomic levels of the arterial wall. Subsequent vasoconstriction, thrombosis, and inflammation ensue, leading to vessel wall remodeling and cellular hyperproliferation as the hallmarks of severe disease. These processes are influenced by genetic predisposition as well as diverse endogenous and exogenous stimuli. Recent studies have provided a glimpse at certain molecular pathways that contribute to pathogenesis; these have led to the identification of attractive targets for therapeutic intervention. We will review our current understanding of the mechanistic underpinnings of the genetic and exogenous/acquired triggers of PAH. The resulting imbalance of vascular effectors provoking pathogenic vascular changes will also be discussed, with an emphasis on common and overarching regulatory pathways that may relate to the primary triggers of disease. The current conceptual framework should allow for future studies to refine our understanding of the molecular pathogenesis of PAH and improve the therapeutic regimen for this disease.

Chan, Stephen Y.; Loscalzo, Joseph

2008-01-01

310

Suppression of fungal and nematode plant pathogens through arbuscular mycorrhizal fungi  

PubMed Central

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

Veresoglou, Stavros D.; Rillig, Matthias C.

2012-01-01

311

PURE: a PubMed article recommendation system based on content-based filtering.  

PubMed

We have developed a PubMed article recommendation system, PURE, which is based on content-based filtering. PURE has a web interface by which users can add/delete their preferred articles. Once articles are registered, PURE then performs model-based clustering of the preferred articles and recommends the highly-rated articles by the prediction using the trained model. PURE updates the PubMed articles and reports the recommendation by email on daily-base. This system will be helpful for biologists to reduce the time required for gathering information from PubMed. PURE is downloadable under GPL license, via www.bic.kyoto-u.ac.jp/pathway/mami/out/PURE.tar.gz. PMID:18546494

Yoneya, Takashi; Mamitsuka, Hiroshi

2007-01-01

312

Tracking Multiple Topics for Finding Interesting Articles  

SciTech Connect

We introduce multiple topic tracking (MTT) for iScore to better recommend news articles for users with multiple interests and to address changes in user interests over time. As an extension of the basic Rocchio algorithm, traditional topic detection and tracking, and single-pass clustering, MTT maintains multiple interest profiles to identify interesting articles for a specific user given user-feedback. Focusing on only interesting topics enables iScore to discard useless profiles to address changes in user interests and to achieve a balance between resource consumption and classification accuracy. iScore is able to achieve higher quality results than traditional methods such as the Rocchio algorithm. We identify several operating parameters that work well for MTT. Using the same parameters, we show that MTT alone yields high quality results for recommending interesting articles from several corpora. The inclusion of MTT improves iScore's performance by 25% in recommending news articles from the Yahoo! News RSS feeds and the TREC11 adaptive filter article collection. And through a small user study, we show that iScore can still perform well when only provided with little user feedback.

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

2008-01-03

313

Complement resistance of pathogenic Entamoeba histolytica mediated by trypsin-sensitive surface component(s).  

PubMed

Pathogenic forms of the protozoan parasite Entamoeba histolytica were reported previously to resist the cytolytic effect of the alternative complement pathway (AP) only temporarily during exposure to complement. In contrast, nonpathogenic forms of E. histolytica had been found to show AP resistance as a stable property. We studied the mechanisms of AP resistance of the two forms. Upon exposure to AP activity, resistant pathogenic or nonpathogenic forms bound significantly less C3 products than complement-sensitive pathogenic amebae, indicating that the two resistant forms both inhibited AP amplification. Various enzymatic treatments and inhibition of membrane mobility by cytochalasin B and glutaraldehyde fixation showed that the mechanisms of AP inhibition differed between pathogenic and nonpathogenic forms; in contrast to nonpathogenic forms, pathogenic amebae required intact membrane mobility and a trypsin-sensitive surface component(s) to inhibit AP activation. PMID:8478051

Hamelmann, C; Urban, B; Foerster, B; Horstmann, R D

1993-05-01

314

Waterborne protozoan pathogens.  

PubMed Central

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

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

1997-01-01

315

A clinical pathway for pediatric gastroenteritis.  

PubMed

Gastroenteritis is one of the most common reasons for hospitalization in the United States for children under the age of 5 years. Second only to respiratory problems, the cost of providing care for these children is estimated to exceed $2 billion dollars annually ( Burkhart, 1999; Prescilla, 2002). This article reviews the causes of gastroenteritis as well as the 1996 American Academy of Pediatrics Guidelines for treatment of gastroenteritis. These guidelines and more recently published literature were used to develop a clinical pathway to improve the care of pediatric patients admitted to the hospital with gastroenteritis. The article discusses the importance of clinical pathways and the process of implementation of a pathway for pediatric gastroenteritis. Additionally, the article provides a parent teaching tool to address recurrent questions parents have related to home management of a child with gastroenteritis. Useful web sites for resource information related to gastroenteritis are provided as well. PMID:12582292

Jones, Susan

2003-01-01

316

Update on the proteomics of major arthropod vectors of human and animal pathogens.  

PubMed

Vector-borne diseases (VBDs) are defined as infectious diseases of humans and animals caused by pathogenic agents such as viruses, protists, bacteria, and helminths transmitted by the bite of blood-feeding arthropod (BFA) vectors. VBDs represent a major public health threat in endemic areas, generally subtropical zones, and many are considered to be neglected diseases. Genome sequencing of some arthropod vectors as well as modern proteomic and genomic technologies are expanding our knowledge of arthropod-pathogen interactions. This review describes the proteomic approaches that have been used to investigate diverse biological questions about arthropod vectors, including the interplay between vectors and pathogens. Proteomic studies have identified proteins and biochemical pathways that may be involved in molecular crosstalk in BFA-pathogen associations. Future work can build upon this promising start and functional analyses coupled with interactome bioassays will be carried out to investigate the role of candidate peptides and proteins in BFA-human pathogen associations. Dissection of the host-pathogen interactome will be key to understanding the strategies and biochemical pathways used by BFAs to cope with pathogens. PMID:23077092

Patramool, Sirilaksana; Choumet, Valérie; Surasombatpattana, Pornapat; Sabatier, Laurence; Thomas, Frédéric; Thongrungkiat, Supatra; Rabilloud, Thierry; Boulanger, Nathalie; Biron, David G; Missé, Dorothée

2012-12-01

317

Food Microbial Pathogen Detection and Analysis Using DNA Microarray Technologies  

PubMed Central

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

Herold, Keith E.

2008-01-01

318

Laser production of articles from powders  

DOEpatents

Method and apparatus for forming articles from materials in particulate form in which the materials are melted by a laser beam and deposited at points along a tool path to form an article of the desired shape and dimensions. Preferably the tool path and other parameters of the deposition process are established using computer-aided design and manufacturing techniques. A controller comprised of a digital computer directs movement of a deposition zone along the tool path and provides control signals to adjust apparatus functions, such as the speed at which a deposition head which delivers the laser beam and powder to the deposition zone moves along the tool path.

Lewis, Gary K. (Los Alamos, NM); Milewski, John O. (Santa Fe, NM); Cremers, David A. (Los Alamos, NM); Nemec, Ronald B. (White Rock, NM); Barbe, Michael R. (White Rock, NM)

1998-01-01

319

Fluid casting of particle-based articles  

DOEpatents

A method for the production of articles made of a particle-based material; e.g., ceramics and sintered metals. In accordance with one aspect of the invention, a thermally settable slurry containing a relatively high concentration of the particles is introduced into an immiscible, heated fluid. The slurry sets or hardens into a shape determined by the physical characteristics of the fluid and the manner of introduction of the slurry into the fluid. For example, the slurry is pulse injected into the fluid to provide spherical articles. The hardened spheres may then be sintered to consolidate the particles and provide a high density product.

Menchhofer, Paul (Oak Ridge, TN)

1995-01-01

320

Fluid casting of particle-based articles  

DOEpatents

A method is disclosed for the production of articles made of a particle-based material; e.g., ceramics and sintered metals. In accordance with one aspect of the invention, a thermally settable slurry containing a relatively high concentration of the particles is introduced into an immiscible, heated fluid. The slurry sets hardens into a shape determined by the physical characteristics of the fluid and the manner of introduction of the slurry into the fluid. For example, the slurry is pulse injected into the fluid to provide spherical articles. The hardened spheres may then be sintered to consolidate the particles and provide a high density product. 1 figure.

Menchhofer, P.

1995-03-28

321

Low density, microcellular foams, preparation, and articles  

DOEpatents

A microcellular low-density foam of poly(4-methyl-1-pentene) particularly useful for forming targets for inertial confinement fusion has been developed. Articles made from the foam have been machined to tolerances of 0.0001 inch, although the densities of the fragile foam are low (about 10 to about 100 mg/cc) and the cell sizes are small (about 10 to about 30 ..mu..m). Methods for forming the foam and articles are given. The yield strength of the foam of the invention is higher than was obtained in other structures of this same material.

Young, A.T.

1982-03-03

322

The logic of the medical research article.  

PubMed

As do all forms of science, medical theories have a factual as well as a logical basis. New information is presented in medical research articles. These papers have three separate arguments: the argument of the hypothesis, the argument of the experimental protocol, and the argument of the hypothesis's judgement. These arguments may be examples of the hypothetico-deductive or confirmational model of scientific interference. The logical form of these arguments are informal and inductive rather than formal and deductive. Understanding the nature of the logic of the medical research article may help avoid erroneous conclusions. PMID:8259532

Velanovich, V

1993-09-01

323

Low density, microcellular foams, preparation, and articles  

DOEpatents

A microcellular low density foam of poly(4-methyl-1-pentene) which is particularly useful for forming targets for inertial confinement fusion has been developed. Articles made from the foam have been machined to tolerances of 0.0001 inch, although the densities of the fragile foam are low (about 10 to about 100 mg/cc) and the cell sizes are small (about 10 to about 30 .mu.m). Methods for forming the foam and articles are given; and the yield strength of the foam of the invention is higher than was obtained in other structures of this same material.

Young, Ainslie T. (Los Alamos, NM); Marsters, Robert G. (Jemez Springs, NM); Moreno, Dawn K. (Espanola, NM)

1984-01-01

324

Laser production of articles from powders  

DOEpatents

Method and apparatus for forming articles from materials in particulate form in which the materials are melted by a laser beam and deposited at points along a tool path to form an article of the desired shape and dimensions. Preferably the tool path and other parameters of the deposition process are established using computer-aided design and manufacturing techniques. A controller comprised of a digital computer directs movement of a deposition zone along the tool path and provides control signals to adjust apparatus functions, such as the speed at which a deposition head which delivers the laser beam and powder to the deposition zone moves along the tool path. 20 figs.

Lewis, G.K.; Milewski, J.O.; Cremers, D.A.; Nemec, R.B.; Barbe, M.R.

1998-11-17

325

Encyclopedia of Analytical Chemistry Free Sample Articles  

NSDL National Science Digital Library

From publishers John Wiley and Sons, Ltd., the Encyclopedia of Analytical Chemistry, considered the "most comprehensive analytical chemistry reference available," is due for publication in October 2000. In anticipation of the release of this fifteen-volume set, the publisher has posted a teaser: seventeen articles are freely available on the encyclopedia's Website. By completing a simple form, users may access representative articles (in .pdf format) from encyclopedia sections such as Peptides and Proteins; Electroanalytic Methods; Infrared, X-ray, and Mass Spectroscopy; Remote Sensing; and more. Libraries or wealthy individuals interested in ordering the Encyclopedia of Analytical Chemistry ($4,800) may do so at the site.

326

Microbial Exposure Assessment of Waterborne Pathogens  

Microsoft Academic Search

The large number of waterborne illnesses in Ireland and worldwide has highlighted the need to enhance strategies that minimize human exposure to pathogens in drinking water supplies. Waterborne pathogens of public concern together with relevant national and international legislation are reviewed in this study. Cryptosporidium species and pathogenic Escherichia coli are among pathogens of primary concern. The organisms originate from

Rory Coffey; Enda Cummins; Martin Cormican; Vincent O Flaherty; Stephen Kelly

2007-01-01

327

Pathogen evolution and the immunological niche.  

PubMed

Host immunity is a major driver of pathogen evolution and thus a major determinant of pathogen diversity. Explanations for pathogen diversity traditionally assume simple interactions between pathogens and the immune system, a view encapsulated by the susceptible-infected-recovered (SIR) model. However, there is growing evidence that the complexity of many host-pathogen interactions is dynamically important. This revised perspective requires broadening the definition of a pathogen's immunological phenotype, or what can be thought of as its immunological niche. After reviewing evidence that interactions between pathogens and host immunity drive much of pathogen evolution, I introduce the concept of a pathogen's immunological phenotype. Models that depart from the SIR paradigm demonstrate the utility of this perspective and show that it is particularly useful in understanding vaccine-induced evolution. This paper highlights questions in immunology, evolution, and ecology that must be answered to advance theories of pathogen diversity. PMID:25040161

Cobey, Sarah

2014-07-01

328

Chinese Space Science and Technology (selected articles)  

NASA Astrophysics Data System (ADS)

This article carries out a technical summary for communication satellites. It describes limiting conditions in the process of designing communications satellites, and it details primary technical design characteristics of sub-systems on satellites, for example, effective loading, attitudes, and orbit controls, as well as power sources, measurement control, structures, and heat control, along with other similar items.

1991-12-01

329

The Gifted Enigma: A Collection of Articles.  

ERIC Educational Resources Information Center

Twenty-one research articles originally published in the "Australasian Journal of Gifted Education" over the past decade are collected in this book and address aspects of gifted education including pedagogy and curriculum, policy and practice, social and emotional needs, school and family, neuropsychology and cognition, and special populations.…

Vialle, Wilma, Ed.; Geake, John, Ed.

330

Review article: thiopurines in inflammatory bowel disease  

Microsoft Academic Search

In the past 10-20 years, knowledge of both thiopurine pharmacology and -pharmacogenetics has been extended dramatically and used to develop new strategies to improve efficacy and reduce toxicity. To review thiopurine efficacy, toxicity, pharmacology, pharmacogenetics, interactions in patients with inflammatory bowel disease. Special attention was paid to new strategies for optimization of pharmacotherapy. To collect relevant scientific articles, a Pubmed

L. J. J. Derijks; L. P. L. Gilissen; P. M. Hooymans; D. W. Hommes

2006-01-01

331

Introductions in Research Articles: Variation across Disciplines.  

ERIC Educational Resources Information Center

Reports on an analysis of research article introductions from two related fields, Wildlife Behavior and Conservation Biology, using Swales' (1990), "Genre Analysis. English in Academic and Research Settings." Results of the analysis reveal disciplinary variation in the structure of this genre, which has important pedagogical implications.…

Samraj, B.

2002-01-01

332

Rhetorical Structure of Biochemistry Research Articles  

ERIC Educational Resources Information Center

This paper reports on the results of a move analysis [Swales, J. (1990). "Genre analysis." Cambridge: Cambridge University Press] of 60 biochemistry research articles. First, a corpus was systematically compiled to ensure that it represents core journals in the focused discipline. Then, coding reliability analysis was conducted to demonstrate…

Kanoksilapatham, Budsaba

2005-01-01

333

Writing Feature Articles with Intermediate Students  

ERIC Educational Resources Information Center

Students need regular opportunities to write expository text. However, focusing on report writing often leaves students without strong examples to study or analyze to guide and grow their own writing. Writing and studying feature articles, meant to inform and explain, can become an alternative to report writing, as they can easily be located in…

Morgan, Denise N.

2010-01-01

334

Review Article: Instructed Second Language Vocabulary Learning  

ERIC Educational Resources Information Center

This article overviews current research on second language vocabulary learning. It concludes that a large vocabulary is necessary to function in English: 8000-9000 word families for reading, and perhaps as many as 5000-7000 families for oral discourse. In addition, a number of word knowledge aspects need to be learned about each lexical item.…

Schmitt, Norbert

2008-01-01

335

Effect Size Reporting Practices in Published Articles  

ERIC Educational Resources Information Center

Effect size (ES) reporting practices in a sample of 10 educational research journals are examined in this study. Five of these journals explicitly require reporting ES and the other 5 have no such policy. Data were obtained from 99 articles published in the years 2003 and 2004, in which 183 statistical analyses were conducted. Findings indicate no…

Alhija, Fadia Nasser-Abu; Levy, Adi

2009-01-01

336

Generating summaries of multiple news articles  

Microsoft Academic Search

We present a natural language system which summarizes a series of news articles on the same event. It uses sum- marization operators, identified through empirical analysis of a corpus of news summaries, to group together templates from the output of the systems developed for ARPA's Mes- sage Understanding Conferences. Depending on the avail- able resources (e.g., space), summaries of different

Kathleen McKeown; Dragomir R. Radev

1995-01-01

337

Definite Article Usage across Varieties of English  

ERIC Educational Resources Information Center

This paper seeks to explore the extent of definite article usage variation in several varieties of English based on a classification of its usage types. An annotation scheme based on Hawkins and Prince was developed for this purpose. Using matching corpus data representing Inner Circle varieties and Outer Circle varieties, analysis was made on…

Wahid, Ridwan

2013-01-01

338

Interactional Metadiscourse in Research Article Abstracts  

ERIC Educational Resources Information Center

This paper deals with interpersonality in research article abstracts analysed in terms of interactional metadiscourse. The evolution in the distribution of three prominent interactional markers comprised in Hyland's (2005a) model, viz. hedges, boosters and attitude markers, is investigated in three decades of abstract writing in the field of…

Gillaerts, Paul; Van de Velde, Freek

2010-01-01

339

Education, Cyberspace, and Change [Serial Article Online].  

ERIC Educational Resources Information Center

This article was originally written on the internet in Australia to provide a starting point for discussions of new perspectives on education made possible by advanced technologies. Ecosocial changes in the practices and institutions called education are discussed in the context of changes in the practices and institutions called information…

Lemke, J. L.

1993-01-01

340

The Writing of Research Article Introductions.  

ERIC Educational Resources Information Center

Examines two leading journals from both physics and educational psychology to see whether the research article introductions typically include statements of principal findings. Indicates (1) a mismatch between descriptive practice and prescriptive advice and (2) a diversity in this rhetorical feature between the two fields. (JD)

Swales, John; Najjar, Hazem

1987-01-01

341

Remarks on Dr. Morton Prince's article: \\  

Microsoft Academic Search

Comments on M. Prince's article on the mechanism and interpretation of dreams (see Journal of Abnormal Psychology, Vol 5, 139-195, PA: 52638). There is a lack of quality and quantity in the material used by him in confirming Freud's results. There was inaccurate interpretation in his work, in addition to lack of depth in his methods. What he regards as

Ernest Jones

1911-01-01

342

REVIEW ARTICLE: Recent Advances in Nanomaterial Fabrication  

NASA Astrophysics Data System (ADS)

As nanostructures with well-controlled dimension, composition, and crystallinity are expected to be a new class of intriguing system for investigating structure-property relations, this review article provides a comprehensive review of researches of these materials and related applications.

Locharoenrat, Kitsakorn

2014-04-01

343

Student Portfolios: A Collection of Articles.  

ERIC Educational Resources Information Center

More and more, schools are looking to student portfolios as a valid, reliable, and authentic form of assessment. This collection offers practical, well-researched answers to a variety of philosophical, organizational, and implementational questions surrounding portfolio assessment. Articles in the first section provide a rationale for student…

Fogarty, Robin, Ed.

344

Informational Dynamics of Journal Article Titles.  

ERIC Educational Resources Information Center

Analyzes changing information values of journal article titles (measured by counting total number of words, number of keywords, and computing proportion of substantive words). Use of linear regression to determine change patterns for sample of titles from four selected journals, six library journals, and six miscellaneous journals (1951-1980) is…

Diener, Richard A. V.

1984-01-01

345

Metal articles having ultrafine particles dispersed therein  

SciTech Connect

This patent describes a metal article of manufacture. It comprises: a metal selected from the group consisting of copper, silver, gold, lead, tin, nickel, zinc, cobalt, antimony, bismuth, iron, cadmium, chromium, germanium, gallium, selenium, tellurium, mercury, tungsten arsenic, manganese, iridium, indium, ruthenium, rhenium, rhodium, molybdenum, palladium, osmium and platinum; and a plurality of ultrafine particles.

Alexander, G.B.; Nadkarni, R.A.

1992-07-28

346

Tracking Multiple Topics for Finding Interesting Articles.  

National Technical Information Service (NTIS)

We introduce multiple topic tracking (MTT) for iScore to better recommend news articles for users with multiple interests and to address changes in user interests over time. As an extension of the basic Rocchio algorithm, traditional topic detection and t...

A. F. Cardenas D. J. Buttler R. K. Pon T. J. Critchlow

2007-01-01

347

Article of Footwear with Temperature Regulation Means.  

National Technical Information Service (NTIS)

Article of footwear includes a sole, an insole overlying the sole, the insole having in a surface thereof a groove having an inlet and outlet in an edge of the insole, the groove winding substantially throughout the length and width of the insole upper su...

S. Szczesull M. J. Holthe

2005-01-01

348

Manned remote work station development article  

NASA Technical Reports Server (NTRS)

Flight article and associated design concepts are evaluated to meet fundamental requirements of a universal crew cabin to be used as a construction cherrypicker, a space crane turret, a railed work station, or a free flyer. Key technology developments are embodied into a simulation program. A schedule and simulation test plan matrix is given for the open cabin cherry picker.

1978-01-01

349

Topical Articles: Teaching Psychological Science through Writing  

ERIC Educational Resources Information Center

The teaching of psychological science occurs face-to-face in classrooms and also through writing via op-ed essays, magazine articles, trade books, Web sites, and textbooks. I discuss the teaching of psychological science through such outlets, offer some practical suggestions for writing, and reflect on what I have found motivating, helpful, and…

Myers, David G.

2007-01-01

350

Method for welding an article and terminating the weldment within the perimeter of the article  

NASA Technical Reports Server (NTRS)

An article is welded, as in weld repair of a defect, by positioning a weld lift-off block at a location on the surface of the article adjacent to the intended location of the end of the weldment on the surface of the article. The weld lift-off block has a wedge shape including a base contacting the surface of the article, and an upper face angled upwardly from the base from a base leading edge. A weld pool is formed on the surface of the article by directly heating the surface of the article using a heat source. The heat source is moved relative to the surface of the article and onto the upper surface of the weld lift-off block by crossing the leading edge of the wedge, without discontinuing the direct heating of the article by the heat source. The heating of the article with the heat source is discontinued only after the heat source is directly heating the upper face of the weld lift-off block, and not the article.

Smashey, Russell W. (Inventor); Snyder, John H. (Inventor); Boerger, Eric J. (Inventor); Borne, Bruce L. (Inventor)

2000-01-01

351

Plants, plant pathogens, and microgravity--a deadly trio.  

PubMed

Plants grown in spaceflight conditions are more susceptible to colonization by plant pathogens. The underlying causes for this enhanced susceptibility are not known. Possibly the formation of structural barriers and the activation of plant defense response components are impaired in spaceflight conditions. Either condition would result from altered gene expression of the plant. Because of the tools available, past studies focused on a few physiological responses or biochemical pathways. With recent advances in genomics research, new tools, including microarray technologies, are available to examine the global impact of growth in the spacecraft on the plant's gene expression profile. In ground-based studies, we have developed cDNA subtraction libraries of rice that are enriched for genes induced during pathogen infection and the defense response. Arrays of these genes are being used to dissect plant defense response pathways in a model system involving wild-type rice plants and lesion mimic mutants. The lesion mimic mutants are ideal experimental tools because they erratically develop defense response-like lesions in the absence of pathogens. The gene expression profiles from these ground-based studies will provide the molecular basis for understanding the biochemical and physiological impacts of spaceflight on plant growth, development and disease defense responses. This, in turn, will allow the development of strategies to manage plant disease for life in the space environment. PMID:11865865

Leach, J E; Ryba-White, M; Sun, Q; Wu, C J; Hilaire, E; Gartner, C; Nedukha, O; Kordyum, E; Keck, M; Leung, H; Guikema, J A

2001-06-01

352

Transient Pressure Test Article Test Program  

NASA Technical Reports Server (NTRS)

The Transient Pressure Test Article (TPTA) test program is being conducted at a new test facility located in the East Test Area at the National Aeronautics and Space Administration's (NASA's) Marshall Space Flight Center (MSFC) in Huntsville, Alabama. This facility, along with the special test equipment (STE) required for facility support, was constructed specifically to test and verify the sealing capability of the Redesigned Solid Rocket Motor (RSRM) field, igniter, and nozzle joints. The test article consists of full scale RSRM hardware loaded with inert propellant and assembled in a short stack configuration. The TPTA is pressurized by igniting a propellant cartridge capable of inducing a pressure rise rate which stimulates the ignition transient that occurs during launch. Dynamic loads are applied during the pressure cycle to simulate external tank attach (ETA) strut loads present on the ETA ring. Sealing ability of the redesigned joints is evaluated under joint movement conditions produced by these combined loads since joint sealing ability depends on seal resilience velocity being greater than gap opening velocity. Also, maximum flight dynamic loads are applied to the test article which is either pressurized to 600 psia using gaseous nitrogen (GN2) or applied to the test article as the pressure decays inside the test article on the down cycle after the ignition transient cycle. This new test facility is examined with respect to its capabilities. In addition, both the topic of test effectiveness versus space vehicle flight performance and new aerospace test techniques, as well as a comparison between the old SRM design and the RSRM are presented.

Vibbart, Charles M.

1989-01-01

353

Relevance of the lectin pathway of complement in rheumatic diseases.  

PubMed

Due to its importance both in the clearance of pathogens that contribute as rheumatic etiological agents and in the disposal of apoptotic bodies and potential autoimmune initiators, deficiencies of the components of the lectin pathway of complement have been found to increase susceptibility and modulate the severity of most rheumatic disorders. This chapter introduces the general aspects of the structure, function, and genetics of lectin pathway components and summarizes current knowledge of the field regarding rheumatic diseases predisposition and modulation. PMID:22397030

Boldt, Angelica B W; Goeldner, Isabela; de Messias-Reason, Iara J T

2012-01-01

354

The Evolution of the Wnt Pathway  

PubMed Central

Wnt genes are important regulators of embryogenesis and cell differentiation in vertebrates and insects. New data revealed by comparative genomics have now shown that members of the Wnt signaling pathway can be found in all clades of metazoans, but not in fungi, plants, or unicellular eukaryotes. This article focuses on new data from recent genomic analyses of several basal metazoan organisms, providing evidence that the Wnt pathway was a primordial signaling pathway during evolution. The formation of a Wnt signaling center at the site of gastrulation was instrumental for the formation of a primary, anterior–posterior body axis, which can be traced throughout animal evolution.

Holstein, Thomas W.

2012-01-01

355

The Main Aeromonas Pathogenic Factors  

PubMed Central

The members of the Aeromonas genus are ubiquitous, water-borne bacteria. They have been isolated from marine waters, rivers, lakes, swamps, sediments, chlorine water, water distribution systems, drinking water and residual waters; different types of food, such as meat, fish, seafood, vegetables, and processed foods. Aeromonas strains are predominantly pathogenic to poikilothermic animals, and the mesophilic strains are emerging as important pathogens in humans, causing a variety of extraintestinal and systemic infections as well as gastrointestinal infections. The most commonly described disease caused by Aeromonas is the gastroenteritis; however, no adequate animal model is available to reproduce this illness caused by Aeromonas. The main pathogenic factors associated with Aeromonas are: surface polysaccharides (capsule, lipopolysaccharide, and glucan), S-layers, iron-binding systems, exotoxins and extracellular enzymes, secretion systems, fimbriae and other nonfilamentous adhesins, motility and flagella.

Tomas, J. M.

2012-01-01

356

Proteomics of Plant Pathogenic Fungi  

PubMed Central

Plant pathogenic fungi cause important yield losses in crops. In order to develop efficient and environmental friendly crop protection strategies, molecular studies of the fungal biological cycle, virulence factors, and interaction with its host are necessary. For that reason, several approaches have been performed using both classical genetic, cell biology, and biochemistry and the modern, holistic, and high-throughput, omic techniques. This work briefly overviews the tools available for studying Plant Pathogenic Fungi and is amply focused on MS-based Proteomics analysis, based on original papers published up to December 2009. At a methodological level, different steps in a proteomic workflow experiment are discussed. Separate sections are devoted to fungal descriptive (intracellular, subcellular, extracellular) and differential expression proteomics and interactomics. From the work published we can conclude that Proteomics, in combination with other techniques, constitutes a powerful tool for providing important information about pathogenicity and virulence factors, thus opening up new possibilities for crop disease diagnosis and crop protection.

Gonzalez-Fernandez, Raquel; Prats, Elena; Jorrin-Novo, Jesus V.

2010-01-01

357

Infectious pathogens and bronchiolitis outcomes.  

PubMed

Bronchiolitis is a common early childhood illness and an important cause of morbidity, it is the number one cause of hospitalization among US infants. Bronchiolitis is also an active area of research, and recent studies have advanced our understanding of this illness. Although it has long been the conventional wisdom that the infectious etiology of bronchiolitis does not affect outcomes, a growing number of studies have linked specific pathogens of bronchiolitis (e.g., rhinovirus) to short- and long-term outcomes, such as future risk of developing asthma. The authors review the advent of molecular diagnostic techniques that have demonstrated diverse pathogens in bronchiolitis, and they review recent studies on the complex link between infectious pathogens of bronchiolitis and the development of childhood asthma. PMID:24702592

Hasegawa, Kohei; Mansbach, Jonathan M; Camargo, Carlos A

2014-07-01

358

Adverse Outcome Pathways and Ecological Risk Assessment: Bridging to Population Level Effects, Journal Article  

EPA Science Inventory

The viability of populations of plants and animals is a key focus for environmental regulation. Population-level responses integrate the cumulative effects of chemical stressors on individuals as those individuals interact with and are affected by their con-specifics, competitor...

359

Brain damage in preterm infants: etiological pathways.  

PubMed

Preterm newborns represent a high-risk population for brain damage, primarily affecting the white matter, and for related neurodevelopmental disabilities. Determinants of brain damage have been extensively investigated, but there are still many controversies on how these factors can influence the developing brain and provoke damage. The concept of etiological pathway, instead of a single determinant, appears to better explain pathogenetic mechanisms: the brain damage may represent the final outcome of exposure to several combinations of risk factors in the same pathway or in different pathways and can change according to the gestational age. The aim of this article is to review the current knowledge on the pathogenesis of brain damage in preterm infants, within the frame of two main theoretical models, the ischemic and the inflammatory pathway. The relationship between the two pathways and the contribution of genetic susceptibility to ischemic and/or inflammatory insult, in modulating the extent and severity of brain damage, is also discussed. PMID:16244398

Arpino, Carla; D'Argenzio, Luigi; Ticconi, Carlo; Di Paolo, Ambrogio; Stellin, Vincenzo; Lopez, Luisa; Curatolo, Paolo

2005-01-01

360

Interactive Fly: Developmental Pathways  

NSDL National Science Digital Library

this site describes evolutionarily conserved developmental pathways. The pathways are named according to the processes they govern, and not by the names of the genes involved: for example, "lateral inhibition" rather than "the Notch pathway." Inevitably, there will be cases where the function is less well understood: hence, "the Wingless pathway."

PhD Thomas B Brody (NIH Laboratory of Neurochemistry)

2006-12-11

361

Comparative Metabolic Systems Analysis of Pathogenic Burkholderia  

PubMed Central

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

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

2014-01-01

362

Calcium signaling in pathogenic and beneficial plant microbe interactions  

PubMed Central

Elevation of intracellular calcium levels in a plant cell is an early signaling event in many mutualistic and pathogenic plant/microbe interactions. In pathogenic plant/fungus interactions, receptor-mediated cytoplasmic calcium elevations induce defense genes via the activation of ion fluxes at the plasma membrane, an oxidative burst and MAPK activation. Mycorrhizal and beneficial endophytic plant/fungus interactions result in a better plant performance through sequencial cytoplasmic and nuclear calcium elevations. The specificity of the calcium responses depends on the calcium signature, its amplitude, duration, frequency and location, a selective activation of calcium channels in the diverse cellular membranes and the stimulation of calcium-dependent signaling components. Arabidopsis contains more than 100 genes for calcium-binding proteins and channels and the response to pathogens and beneficial fungi relies on a highly specific activation of individual members of these protein families. Genetic tools are required to understand this complex response patterns and the cross talks between the individual calcium-dependent signaling pathways. The beneficial interaction of Arabidopsis with the growth-promoting endophyte Piriformospora indica provides a nice model system to unravel signaling events leading to mutualistic or pathogenic plant/fungus interactions.

Vadassery, Jyothilakshmi

2009-01-01

363

Iron and copper as virulence modulators in human fungal pathogens.  

PubMed

Fungal pathogens have evolved sophisticated machinery to precisely balance the fine line between acquiring essential metals and defending against metal toxicity. Iron and copper are essential metals for many processes in both fungal pathogens and their mammalian hosts, but reduce viability when present in excess. However, during infection, the host uses these two metals differently. Fe has a long-standing history of influencing virulence in pathogenic fungi, mostly in regards to Fe acquisition. Numerous studies demonstrate the requirement of the Fe acquisition pathway of Candida, Cryptococcus and Aspergillus for successful systemic infection. Fe is not free in the host, but is associated with Fe-binding proteins, leading fungi to develop mechanisms to interact with and to acquire Fe from these Fe-bound proteins. Cu is also essential for cell growth and development. Essential Cu-binding proteins include Fe transporters, superoxide dismutase (SOD) and cytochrome c oxidase. Although Cu acquisition plays critical roles in fungal survival in the host, recent work has revealed that Cu detoxification is extremely important. Here, we review fungal responses to altered metal conditions presented by the host, contrast the roles of Fe and Cu during infection, and outline the critical roles of fungal metal homeostasis machinery at the host-pathogen axis. PMID:24851950

Ding, Chen; Festa, Richard A; Sun, Tian-Shu; Wang, Zhan-You

2014-07-01

364

Modifying lignin to improve bioenergy feedstocks: strengthening the barrier against pathogens?†  

PubMed Central

Lignin is a ubiquitous polymer present in cell walls of all vascular plants, where it rigidifies and strengthens the cell wall structure through covalent cross-linkages to cell wall polysaccharides. The presence of lignin makes the cell wall recalcitrant to conversion into fermentable sugars for bioenergy uses. Therefore, reducing lignin content and modifying its linkages have become major targets for bioenergy feedstock development through either biotechnology or traditional plant breeding. In addition, lignin synthesis has long been implicated as an important plant defense mechanism against pathogens, because lignin synthesis is often induced at the site of pathogen attack. This article explores the impact of lignin modifications on the susceptibility of a range of plant species to their associated pathogens, and the implications for development of feedstocks for the second-generation biofuels industry. Surprisingly, there are some instances where plants modified in lignin synthesis may display increased resistance to associated pathogens, which is explored in this article.

Sattler, Scott E.; Funnell-Harris, Deanna L.

2013-01-01

365

Solid Propellant Test Article (SPTA) Test Stand  

NASA Technical Reports Server (NTRS)

This photograph shows the Solid Propellant Test Article (SPTA) test stand with the Modified Nasa Motor (M-NASA) test article at the Marshall Space Flight Center (MSFC). The SPTA test stand, 12-feet wide by 12-feet long by 24-feet high, was built in 1989 to provide comparative performance data on nozzle and case insulation material and to verify thermostructural analysis models. A modified NASA 48-inch solid motor (M-NASA motor) with a 12-foot blast tube and 10-inch throat makes up the SPTA. The M-NASA motor is being used to evaluate solid rocket motor internal non-asbestos insulation materials, nozzle designs, materials, and new inspection techniques. New internal motor case instrumentation techniques are also being evaluated.

1991-01-01

366

Two-dimensional ranking of Wikipedia articles  

NASA Astrophysics Data System (ADS)

The Library of Babel, described by Jorge Luis Borges, stores an enormous amount of information. The Library exists ab aeterno. Wikipedia, a free online encyclopaedia, becomes a modern analogue of such a Library. Information retrieval and ranking of Wikipedia articles become the challenge of modern society. While PageRank highlights very well known nodes with many ingoing links, CheiRank highlights very communicative nodes with many outgoing links. In this way the ranking becomes two-dimensional. Using CheiRank and PageRank we analyze the properties of two-dimensional ranking of all Wikipedia English articles and show that it gives their reliable classification with rich and nontrivial features. Detailed studies are done for countries, universities, personalities, physicists, chess players, Dow-Jones companies and other categories.

Zhirov, A. O.; Zhirov, O. V.; Shepelyansky, D. L.

2010-10-01

367

Siemens SOFC Test Article and Module Design  

SciTech Connect

Preliminary design studies of the 95 kWe-class SOFC test article continue resulting in a stack architecture of that is 1/3 of 250 kWe-class SOFC advanced module. The 95 kWeclass test article is envisioned to house 20 bundles (eight cells per bundle) of Delta8 cells with an active length of 100 cm. Significant progress was made in the conceptual design of the internal recirculation loop. Flow analyses were initiated in order to optimize the bundle row length for the 250 kWeclass advanced module. A preferred stack configuration based on acceptable flow and thermal distributions was identified. Potential module design and analysis issues associated with pressurized operation were identified.

None

2011-03-31

368

Online medical journal article layout analysis  

NASA Astrophysics Data System (ADS)

We describe a physical and logical layout analysis algorithm, which is applied to segment and label online medical journal articles (regular HTML and PDF-Converted-HTML files). For these articles, the geometric layout of the Web page is the most important cue for physical layout analysis. The key to physical layout analysis is then to render the HTML file in a Web browser, so that the visual information in zones (composed of one or a set of HTML DOM nodes), especially their relative position, can be utilized. The recursive X-Y cut algorithm is adopted to construct a hierarchical zone tree structure. In logical layout analysis, both geometric and linguistic features are used. The HTML documents are modeled by a Hidden Markov Model with 16 states, and the Viterbi algorithm is then used to find the optimal label sequence, concluding the logical layout analysis.

Zou, Jie; Le, Daniel; Thoma, George R.

2007-01-01

369

On improving wikipedia search using article quality  

Microsoft Academic Search

Wikipedia is presently the largest free-and-open online en- cyclopedia collaboratively edited and maintained by volun- teers. While Wikipedia offers full-text search to its users, the accuracy of its relevance-based search can be compromised by poor quality articles edited by non-experts and inexpe- rienced contributors. In this paper, we propose a frame- work that re-ranks Wikipedia search results considering ar- ticle

Meiqun Hu; Ee-peng Lim; Aixin Sun; Hady Wirawan Lauw; Ba-quy Vuong

2007-01-01

370

Design manual: Oxygen Thermal Test Article (OTTA)  

NASA Technical Reports Server (NTRS)

The characteristics of a cryogenic tank for storing liquid hydrogen, nitrogen, oxygen, methane, or helium for an extended period of time with minimum losses are discussed. A description of the tank and control module, assembly drawings and details of major subassemblies, specific requirements controlling development of the system, thermal concept considerations, thermal analysis methods, and a record of test results are provided. The oxygen thermal test article thermal protection system has proven that the insulation system for cryogenic vessels is effective.

Chronic, W. L.; Baese, C. L.; Conder, R. L.

1974-01-01

371

Evolution of pathogenicity and sexual reproduction in eight Candida genomes  

PubMed Central

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

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

2009-01-01

372

MANAGING URBAN WATERSHED PATHOGEN CONTAMINATION  

EPA Science Inventory

This presentation is a summary of the EPA National Risk Management Research Laboratory (NRMRL) publication entitled Managing Urban Watershed Pathogen Contamination, EPA/600/R-03/111 (September 2003). It is available on the internet at http://www.epa.gov/ednnrmrl/repository/water...

373

MANAGING URBAN WATERSHED PATHOGEN CONTAMINATION  

EPA Science Inventory

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

374

Pathogenicity of Shigella in Chickens  

PubMed Central

Shigellosis in chickens was first reported in 2004. This study aimed to determine the pathogenicity of Shigella in chickens and the possibility of cross-infection between humans and chickens. The pathogenicity of Shigella in chickens was examined via infection of three-day-old SPF chickens with Shigella strain ZD02 isolated from a human patient. The virulence and invasiveness were examined by infection of the chicken intestines and primary chicken intestinal epithelial cells. The results showed Shigella can cause death via intraperitoneal injection in SPF chickens, but only induce depression via crop injection. Immunohistochemistry and transmission electron microscopy revealed the Shigella can invade the intestinal epithelia. Immunohistochemistry of the primary chicken intestinal epithelial cells infected with Shigella showed the bacteria were internalized into the epithelial cells. Electron microscopy also confirmed that Shigella invaded primary chicken intestinal epithelia and was encapsulated by phagosome-like membranes. Our data demonstrate that Shigella can invade primary chicken intestinal epithelial cells in vitro and chicken intestinal mucosa in vivo, resulting in pathogenicity and even death. The findings suggest Shigella isolated from human or chicken share similar pathogenicity as well as the possibility of human-poultry cross-infection, which is of public health significance.

Chen, Lu; Chang, Hong-tao; Liu, Hong-ying; Zhao, Jun; Wang, Xin-wei; Wang, Chuan-qing

2014-01-01

375

The Evolution of Foodborne Pathogens  

NASA Astrophysics Data System (ADS)

Despite continuous advances in food safety and disease surveillance, control, and prevention, foodborne bacterial infections remain a major public health concern. Because foodborne pathogens are commonly exposed to multiple environmental stressors, such as low pH and antibiotics, most have evolved specific mechanisms to facilitate survival in adverse environments.

Abu-Ali, Galeb S.; Manning, Shannon D.

376

Receptor use by pathogenic arenaviruses  

Microsoft Academic Search

The arenavirus family contains several important human pathogens including Lassa fever virus (LASV), lymphocytic choriomeningitis virus (LCMV) and the New World clade B viruses Junin (JUNV) and Machupo (MACV). Previously, ?-dystroglycan (?-DG) was identified as a receptor recognized by LASV and certain strains of LCMV. However, other studies have suggested that ?-DG is probably not used by the clade B

Therese Reignier; Jill Oldenburg; Beth Noble; Erika Lamb; Victor Romanowski; Michael J. Buchmeier; Paula M. Cannon

2006-01-01

377

Pathogenic: light or dark skin?  

PubMed

Currently, we use the term "pathogenicity" to indicate whether a variant in a gene has an influence on the phenotype or not. As this term is confusing, not neutral, and incorrectly refers to a disease state, it seems better to use a more neutral term. The suggestion is to use "affects function." PMID:24610774

den Dunnen, Johan T

2014-05-01

378

Pathogenicity of Aseptic Bursaphelenchus xylophilus  

PubMed Central

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

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

2012-01-01

379

Biosignatures of Pathogen and Host  

Microsoft Academic Search

In information theory, a signature is characterized by the information content as well as noise statistics of the communication channel. Biosignatures have analogous properties. A biosignature can be associated with a particular attribute of a pathogen or a host. However, the signature may be lost in backgrounds of similar or even identical signals from other sources. In this paper, we

J. P. Fitch; B. A. Chromy; C. E. Forde; E. Garcia; S. N. Gardner; P. P. Gu; T. A. Kuczmarksi; C. F. Melius; S L McCutchen-Maloney; F P Milanovich; V L Motin; L L Ott; A A Quong; J N Quong; J M Rocco; T R Slezak; B A Sokhansanj; E A Vitalis; A T Zemla; P M McCready

2002-01-01

380

Biosignatures of Pathogen and Host  

SciTech Connect

In information theory, a signature is characterized by the information content as well as noise statistics of the communication channel. Biosignatures have analogous properties. A biosignature can be associated with a particular attribute of a pathogen or a host. However, the signature may be lost in backgrounds of similar or even identical signals from other sources. In this paper, we highlight statistical and signal processing challenges associated with identifying good biosignatures for pathogens in host and other environments. In some cases it may be possible to identify useful signatures of pathogens through indirect but amplified signals from the host. Discovery of these signatures requires new approaches to modeling and data interpretation. For environmental biosignal collections, it is possible to use signal processing techniques from other applications (e.g., synthetic aperture radar) to track the natural progression of microbes over large areas. We also present a computer-assisted approach to identify unique nucleic-acid based microbial signatures. Finally, an understanding of host-pathogen interactions will result in better detectors as well as opportunities in vaccines and therapeutics.

Fitch, J P; Chromy, B A; Forde, C E; Garcia, E; Gardner, S N; Gu, P P; Kuczmarksi, T A; Melius, C F; McCutchen-Maloney, S L; Milanovich, F P; Motin, V L; Ott, L L; Quong, A A; Quong, J N; Rocco, J M; Slezak, T R; Sokhansanj, B A; Vitalis, E A; Zemla, A T; McCready, P M

2002-08-27

381

PATHOGEN RISK ASSESSMENT FEASIBILITY STUDY  

EPA Science Inventory

The report evaluates the practicality of formulating guidelines to assess the risk associated with exposure to pathogens in sludge. Risk assessment may be used to determine the likelihood that an environmental agent may cause human disease (that is, potential to cause human cance...

382

Pathogenicity of aseptic Bursaphelenchus xylophilus.  

PubMed

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

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

2012-01-01

383

PATHOGENIC 'NAEGLERIA': DISTRIBUTION IN NATURE  

EPA Science Inventory

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

384

Potentiation of pathogen-specific defense mechanisms in Arabidopsis by beta -aminobutyric acid.  

PubMed

The nonprotein amino acids gamma-aminobutyric acid (GABA) and beta-aminobutyric acid (BABA) have known biological effects in animals and plants. Their mode of action has been the object of thorough research in animals but remains unclear in plants. Our objective was to study the mode of action of BABA in the protection of Arabidopis plants against virulent pathogens. BABA protected Arabidopsis against the oomycete pathogen Peronospora parasitica through activation of natural defense mechanisms of the plant such as callose deposition, the hypersensitive response, and the formation of trailing necroses. BABA was still fully protective against P. parasitica in transgenic plants or mutants impaired in the salicylic acid, jasmonic acid, and ethylene signaling pathways. Treatment with BABA did not induce the accumulation of mRNA of the systemic acquired resistance (SAR)-associated PR-1 and the ethylene- and jasmonic acid-dependent PDF1.2 genes. However, BABA potentiated the accumulation of PR-1 mRNA after attack by virulent pathogenic bacteria. As a result, BABA-treated Arabidopsis plants were less diseased compared with the untreated control. In the case of bacteria, BABA protected mutants insensitive to jasmonic acid and ethylene but was not active in plants impaired in the SAR transduction pathway. Thus, BABA protects Arabidopsis against different virulent pathogens by potentiating pathogen-specific plant resistance mechanisms. In addition, we provide evidence that BABA-mediated papilla formation after P. parasitica infection is independent of the SAR signaling pathway. PMID:11058166

Zimmerli, L; Jakab, G; Metraux, J P; Mauch-Mani, B

2000-11-01

385

27 CFR 26.110 - Release of articles or liquors.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 false Release of articles or liquors. 26.110 Section...THE TREASURY ALCOHOL LIQUORS AND ARTICLES FROM PUERTO RICO AND THE VIRGIN ISLANDS Taxpayment of Liquors and Articles in Puerto Rico Articles §...

2013-04-01

386

The Aedes aegypti Toll Pathway Controls Dengue Virus Infection  

Microsoft Academic Search

Aedes aegypti, the mosquito vector of dengue viruses, utilizes its innate immune system to ward off a variety of pathogens, some of which can cause disease in humans. To date, the features of insects' innate immune defenses against viruses have mainly been studied in the fruit fly Drosophila melanogaster, which appears to utilize different immune pathways against different types of

Zhiyong Xi; Jose L. Ramirez; George Dimopoulos

2008-01-01

387

Toll-like receptors (TLRs) in aquatic animals: signaling pathways, expressions and immune responses.  

PubMed

The innate system's recognition of non-self and danger signals is mediated by a limited number of germ-line encoded pattern recognition receptors (PRRs) that recognize pathogen associated molecular patterns (PAMPs). Toll-like receptors (TLRs) are single, non-catalytic, membrane-spanning PRRs present in invertebrates and vertebrates. They act by specifically recognizing PAMPs of a variety of microbes and activate signaling cascades to induce innate immunity. A large number of TLRs have been identified in various aquatic animals of phyla Cnidaria, Annelida, Mollusca, Arthropoda, Echinodermata and Chordata. TLRs of aquatic and warm-blooded higher animals exhibit some distinctive features due to their diverse evolutionary lineages. However, majority of them share conserve signaling pathways in pathogen recognition and innate immunity. Functional analysis of novel TLRs in aquatic animals is very important in understanding the comparative immunology between warm-blooded and aquatic animals. In additions to innate immunity, recent reports have highlighted the additional roles of TLRs in adaptive immunity. Therefore, vaccines against many critical diseases of aquatic animals may be made more effective by supplementing TLR activators which will stimulate dendritic cells. This article describes updated information of TLRs in aquatic animals and their structural and functional relationship with warm-blooded animals. PMID:24291116

Rauta, Pradipta R; Samanta, Mrinal; Dash, Hirak R; Nayak, Bismita; Das, Surajit

2014-01-01

388

Cellular defense processes regulated by pathogen-elicited receptor signaling  

NASA Astrophysics Data System (ADS)

Vertebrates are constantly threatened by the invasion of microorganisms and have evolved systems of immunity to eliminate infectious pathogens in the body. Initial sensing of microbial agents is mediated by the recognition of pathogens by means of molecular structures expressed uniquely by microbes of a given type. So-called 'Toll-like receptors' are expressed on host epithelial barrier cells play an essential role in the host defense against microbial pathogens by inducing cell responses (e.g., proliferation, death, cytokine secretion) via activation of intracellular signaling networks. As these networks, comprising multiple interconnecting dynamic pathways, represent highly complex multi-variate "information processing" systems, the signaling activities particularly critical for governing the host cell responses are poorly understood and not easily ascertained by a priori theoretical notions. We have developed over the past half-decade a "data-driven" computational modeling approach, on a 'cue-signal-response' combined experiment/computation paradigm, to elucidate key multi-variate signaling relationships governing the cell responses. In an example presented here, we study how a canonical set of six kinase pathways combine to effect microbial agent-induced apoptotic death of a macrophage cell line. One modeling technique, partial least-squares regression, yielded the following key insights: {a} signal combinations most strongly correlated to apoptotic death are orthogonal to those most strongly correlated with release of inflammatory cytokines; {b} the ratio of two key pathway activities is the most powerful predictor of microbe-induced macrophage apoptotic death; {c} the most influential time-window of this signaling activity ratio is surprisingly fast: less than one hour after microbe stimulation.

Wu, Rongcong; Goldsipe, Arthur; Schauer, David B.; Lauffenburger, Douglas A.

2011-05-01

389

Crosstalk between plant responses to pathogens and herbivores: a view from the outside in  

Microsoft Academic Search

Plants encounter numerous pests and pathogens in the natural environment. An appropriate response to attack by such organisms can lead to tolerance or resistance mechanisms that enable the plant to sur- vive. Many studies concentrate on the signalling pathways that enable plants to recognize and respond to attack, and measure the downstream effect in either biochemical or molecular terms. At

Jane E. Taylor; Paul E. Hatcher; Nigel D. Paul

2010-01-01

390

Manipulation of small Rho GTPases is a pathogen-induced process detected by Nod1  

PubMed Central

Our innate immune system distinguishes microbes from self by detecting conserved pathogen-associated molecular patterns (PAMPs) 1. However, all microbes produce PAMPs, regardless of their pathogenic potential. To distinguish virulent microbes from ones with lower disease-causing potential the innate immune system detects conserved pathogen-induced processes 2, such as the presence of microbial products in the host cytosol, by mechanisms that are not fully resolved. Here we show that Nod1 senses cytosolic microbial products by monitoring the activation state of small Rho GTPases. Activation of Rac1 and Cdc42 by bacterial delivery or ectopic expression of a Salmonella virulence factor, SopE, triggered the Nod1 signaling pathway with consequent Rip2-mediated induction of NF-?B-dependent inflammatory responses. Similarly, activation of the Nod1 signaling pathway by peptidoglycan required Rac1 activity. Furthermore, constitutively active forms of Rac1, Cdc42 and RhoA activated the Nod1 signaling pathway. Our data identify activation of small Rho GTPases as a pathogen-induced process sensed through the Nod1 signaling pathway (Fig. S1).

Keestra, A. Marijke; Winter, Maria G.; Auburger, Josef J.; Frassle, Simon P.; Xavier, Mariana N.; Winter, Sebastian E.; Kim, Anita; Poon, Victor; Ravesloot, Marietta M.; Waldenmaier, Julian; Tsolis, Renee M.; Eigenheer, Richard A.; Baumler, Andreas J.

2013-01-01

391

Isocitrate lyase is essential for pathogenicity of the fungus Leptosphaeria maculans to canola (Brassica napus).  

PubMed

A pathogenicity gene has been identified in Leptosphaeria maculans, the ascomycetous fungus that causes blackleg disease of canola (Brassica napus). This gene encodes isocitrate lyase, a component of the glyoxylate cycle, and is essential for the successful colonization of B. napus. It was identified by a reverse genetics approach whereby a plasmid conferring hygromycin resistance was inserted randomly into the L. maculans genome. Twelve of 516 transformants tested had reduced pathogenicity on cotyledons of B. juncea and B. napus, and 1 of these 12 had a deletion of the isocitrate lyase gene, as well as an insertion of the hygromycin resistance gene. This mutant was unable to grow on fatty acids, including monolaurate, and the isocitrate lyase transcript was not detected. When the wild-type gene was reintroduced into the mutant, growth on monolaurate was restored and pathogenicity was partially restored. L. maculans isocitrate lyase is produced during infection of B. napus cotyledons, while the plant homologue is not. When 2.5% glucose was added to the inoculum of the isocitrate lyase mutant, lesions of sizes similar to those caused by wild-type isolate M1 developed on B. napus cotyledons. These findings suggest that the glyoxylate pathway is essential for disease development by this plant-pathogenic fungus, as has been shown recently for a fungal and bacterial pathogen of animals and a bacterial pathogen of plants. Involvement of the glyoxylate pathway in pathogenesis in animals and plants presents potential drug targets for control of diseases. PMID:12455691

Idnurm, Alexander; Howlett, Barbara J

2002-10-01

392

Isocitrate Lyase Is Essential for Pathogenicity of the Fungus Leptosphaeria maculans to Canola (Brassica napus)  

PubMed Central

A pathogenicity gene has been identified in Leptosphaeria maculans, the ascomycetous fungus that causes blackleg disease of canola (Brassica napus). This gene encodes isocitrate lyase, a component of the glyoxylate cycle, and is essential for the successful colonization of B. napus. It was identified by a reverse genetics approach whereby a plasmid conferring hygromycin resistance was inserted randomly into the L. maculans genome. Twelve of 516 transformants tested had reduced pathogenicity on cotyledons of B. juncea and B. napus, and 1 of these 12 had a deletion of the isocitrate lyase gene, as well as an insertion of the hygromycin resistance gene. This mutant was unable to grow on fatty acids, including monolaurate, and the isocitrate lyase transcript was not detected. When the wild-type gene was reintroduced into the mutant, growth on monolaurate was restored and pathogenicity was partially restored. L. maculans isocitrate lyase is produced during infection of B. napus cotyledons, while the plant homologue is not. When 2.5% glucose was added to the inoculum of the isocitrate lyase mutant, lesions of sizes similar to those caused by wild-type isolate M1 developed on B. napus cotyledons. These findings suggest that the glyoxylate pathway is essential for disease development by this plant-pathogenic fungus, as has been shown recently for a fungal and bacterial pathogen of animals and a bacterial pathogen of plants. Involvement of the glyoxylate pathway in pathogenesis in animals and plants presents potential drug targets for control of diseases.

Idnurm, Alexander; Howlett, Barbara J.

2002-01-01

393

Dispenser for deploying elongated flexible articles  

NASA Astrophysics Data System (ADS)

This document discloses a dispenser for storing an elongated flexible article in a coil coaxially about a deployment axis. The dispenser includes a receptacle with a storage volume about the deployment axis. A partitioning structure in the storage volume includes circumferentially spaced sets of axially extending, deflectable fingers that define portions of storage channels for each turn in a coil. Flexible restraining bands attached to the receptacle overlie the storage volume to retain the turns axially within the storage channels. The structure prevents random turn positioning of individual turns of the coil. Deployment from the dispenser occurs without tangles, kinks or knots and proceeds smoothly and quietly.

Hrycin, Frank M.; Abdow, David A.; Babb, John D.

1995-01-01

394

William H. Calvin Books and Articles  

NSDL National Science Digital Library

The full-text of several books authored by University of Washington professor William H. Calvin are available online. His newest book A Brain for All Seasons (A Scientific American book of the month) is about "what sudden climate flips did to human evolution over the last 2.5 million years." Most of his other books also focus on the subjects of the brain and human evolution. The hyperlinked table of contents makes browsing these texts more manageable. This Web page also includes other information about Calvin, including research, lectures, and shorter articles.

2002-01-01

395

Kids in the Hall of Biodiversity: Articles  

NSDL National Science Digital Library

This two-part article is part of the museum's Kids in Our Halls program, which was created by high school interns at the Museum. "Why are coral reefs important to all life?" is an overview of these "rain forests of the sea," examining how they are home to millions of aquatic species, why they are at risk, and what can be done to help preserve them. "Ever wonder where chocolate comes from?" takes a look at where chocolate comes from, how cacao beans are prepared using a 300-year-old process invented by the Aztecs, and the reasons why cacao trees are potentially endangered.

396

C. elegans detects pathogen-induced translational inhibition to activate immune signaling.  

PubMed

Pathogens commonly disrupt host cell processes or cause damage, but the surveillance mechanisms used by animals to monitor these attacks are poorly understood. Upon infection with pathogenic Pseudomonas aeruginosa, the nematode C. elegans upregulates infection response gene irg-1 using the zip-2 bZIP transcription factor. Here we show that P. aeruginosa infection inhibits mRNA translation in the intestine via the endocytosed translation inhibitor Exotoxin A, which leads to an increase in ZIP-2 protein levels. In the absence of infection we find that the zip-2/irg-1 pathway is upregulated following disruption of several core host processes, including inhibition of mRNA translation. ZIP-2 induction is conferred by a conserved upstream open reading frame in zip-2 that could derepress ZIP-2 translation upon infection. Thus, translational inhibition, a common pathogenic strategy, can trigger activation of an immune surveillance pathway to provide host defense. PMID:22520465

Dunbar, Tiffany L; Yan, Zhi; Balla, Keir M; Smelkinson, Margery G; Troemel, Emily R

2012-04-19

397

Alternative Certification Pathways: Filling a Gap?  

ERIC Educational Resources Information Center

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

Ludlow, Carlyn

2013-01-01

398

Knowledge representation of signal transduction pathways  

Microsoft Academic Search

Motivations: Signal transduction is the common term used to define a diverse topic that encompasses a large body of knowledge about the biochemical mechanisms. Since most of the knowledge of signal transduction resides in scientific articles and is represented by texts in natural language or by diagrams, there is the need of a knowledge representation model for signal transduction pathways

Ken-ichiro Fukuda; Toshihisa Takagi

2001-01-01

399

Autophagy in the regulation of pathogen replication and adaptive immunity  

PubMed Central

Autophagy is an evolutionary conserved homeostatic process by which cells deliver cytoplasmic material for degradation into lysosomes. Autophagy may have evolved as a nutrient-providing homeostatic pathway induced upon starvation, but with the acquisition of cargo-receptors autophagy has become an important cellular defence mechanism as well as a generator of antigenic peptides for MHC presentation. We propose that autophagy efficiently protects against microbes encountering the cytosolic environment accidentally, for example upon phagosomal damage, while pathogens routinely accessing the host cytosol have evolved to avoid or even benefit from autophagy.

Randow, Felix; Munz, Christian

2012-01-01

400

Pharmacology of intracellular signalling pathways  

PubMed Central

This article provides a brief and somewhat personalized review of the dramatic developments that have occurred over the last 45 years in our understanding of intracellular signalling pathways associated with G-protein-coupled receptor activation. Signalling via cyclic AMP, the phosphoinositides and Ca2+ is emphasized and these systems have already been revealed as new pharmacological targets. The therapeutic benefits of most of such targets are, however, yet to be realized, but it is certain that the discipline of pharmacology needs to widen its boundaries to meet these challenges in the future.

Nahorski, Stefan R

2006-01-01

401

19 CFR 134.25 - Containers or holders for repacked J-list articles and articles incapable of being marked.  

Code of Federal Regulations, 2013 CFR

...false Containers or holders for repacked J-list articles and articles incapable of being marked. 134.25 Section...25 Containers or holders for repacked J-list articles and articles incapable of being marked....

2013-04-01

402

Downstream Divergence of the Ethylene Signaling Pathway for Harpin-Stimulated Arabidopsis Growth and Insect Defense  

Microsoft Academic Search

Ethylene (ET) signal transduction may regulate plant growth and defense, depending on which components are recruited into the pathway in response to different stimuli. We report here that the ET pathway controls both insect resistance (IR) and plant growth enhancement (PGE) in Arabidopsis (Arabidopsis thaliana) plants responding to harpin, a protein produced by a plant pathogenic bacterium. PGE may result

Hong-Ping Dong; Jianling Peng; Zhilong Bao; Xiangdong Meng; Jean M. Bonasera

2004-01-01

403

Articles including thin film monolayers and multilayers  

DOEpatents

Articles of manufacture including: (a) a base substrate having an oxide surface layer, and a multidentate ligand, capable of binding a metal ion, attached to the oxide surface layer of the base substrate, (b) a base substrate having an oxide surface layer, a multidentate ligand, capable of binding a metal ion, attached to the oxide surface layer of the base substrate, and a metal species attached to the multidentate ligand, (c) a base substrate having an oxide surface layer, a multidentate ligand, capable of binding a metal ion, attached to the oxide surface layer of the base substrate, a metal species attached to the multidentate ligand, and a multifunctional organic ligand attached to the metal species, and (d) a base substrate having an oxide surface layer, a multidentate ligand, capable of binding a metal ion, attached to the oxide surface layer of the base substrate, a metal species attached to the multidentate ligand, a multifunctional organic ligand attached to the metal species, and a second metal species attached to the multifunctional organic ligand, are provided, such articles useful in detecting the presence of a selected target species, as nonliear optical materials, or as scavengers for selected target species.

Li, DeQuan (Los Alamos, NM); Swanson, Basil I. (Los Alamos, NM)

1995-01-01

404

Aluminum Alloy and Article Cast Therefrom  

NASA Technical Reports Server (NTRS)

A cast article from an aluminum alloy, which has improved mechanical properties at elevated temperatures, has the following composition in weight percent: Silicon 14 - 25.0, Copper 5.5 - 8.0, Iron 0.05 - 1.2, Magnesium 0.5 - 1.5, Nickel 0.05 - 0.9, Manganese 0.05 - 1.0, Titanium 0.05 - 1.2, Zirconium 0.05 - 1.2, Vanadium 0.05 - 1.2, Zinc 0.05 - 0.9, Phosphorus 0.001 - 0.1, and the balance is Aluminum, wherein the silicon-to-magnesium ratio is 10 - 25, and the copper-to-magnesium ratio is 4 - 15. The aluminum alloy contains a simultaneous dispersion of three types of Al3X compound particles (X=Ti, V, Zr) having a LI2, crystal structure, and their lattice parameters are coherent to the aluminum matrix lattice. A process for producing this cast article is also disclosed, as well as a metal matrix composite, which includes the aluminum alloy serving as a matrix and containing up to about 60% by volume of a secondary filler material.

Lee, Jonathan A. (Inventor); Chen, Po-Shou (Inventor)

2003-01-01

405

Article 19: Global Campaign for Free Expression  

NSDL National Science Digital Library

Along with other global campaigns to affect social and political transformation (such as Amnesty International), Article 19 is an organization designed "to combat censorship by promoting freedom of expression and access to official information." With offices in London and South Africa, the organization has partners in over 30 countries, and monitors, researches, publishes, and litigates on behalf of freedom of expression around the world. Certainly one of the first stops on the site should be the Virtual Handbook of Expression, which contains a number of briefs of freedom of expression cases from the UN Human Rights Committee, the Inter-American Commission and Court on Human Rights, the African Commission on Human and Peoples' Rights and the European Commission and Court of Human Rights. In addition, the Virtual Handbook contains a number of key documents, organized around themes that include such timely topics as defamation, national security, print regulation, and privacy. Of course, visitors will also find a great deal of additional material here, including information on Article 19's work in Africa, Asia, the Middle East, and a publication archive as well.

406

Pathogen reduction of blood components.  

PubMed

Thanks to many blood safety interventions introduced in developed countries the risk of transfusion transmitted infections has become exceedingly small in these countries. However, emerging pathogens still represent a serious challenge, as demonstrated by West Nile virus in the US and more recently by Chikungunya virus in the Indian Ocean. In addition bacterial contamination, particularly in platelets, and protozoa transmitted by blood components still represent sizeable risks in developed countries. In developing countries the risk of all transfusion transmitted infections is still high due to insufficient funding and organisation of the health service. Pathogen reduction of pooled plasma products has virtually eliminated the risk of transfusion transmitted infections, without compromising the quality of the products significantly. Pathogen reduction of blood components has been much more challenging. Solvent detergent treatment which has been so successfully applied for plasma products dissolves cell membranes, and can, therefore, only be applied for plasma and not for cellular blood components. Targeting of nucleic acids has been another method for pathogen inactivation of plasma and the only approach possible for cellular blood products. As documented in more than 15 year's track record, solvent detergent treatment of pooled plasma can yield high quality plasma. The increased risk for contamination by unknown viruses due to pooling is out weighed by elimination of TRALI, significant reduction in allergic reactions and standardisation of the product. Recently, a promising method for solvent detergent treatment of single donor plasma units has been published. Methylene blue light treatment of single donor plasma units has a similar long track record as pooled solvent detergent treated plasma; but the method is less well documented and affects coagulation factor activity more. Psoralen light treated plasma has only recently been introduced (CE marked in Europe, but not licensed by the FDA), while the method of Riboflavin light treatment of plasma still is under development. In addition to pathogen reduction the methods, however, result in some reduction of coagulation factor activity. For platelets only Psoralen and Riboflavin light treatment have been implemented. Both are CE marked products in Europe but only approved for clinical trials in the USA. The methods affect platelet activity, but result in clinically acceptable platelets with only slightly reduced CCI and increased demand for platelet transfusions. Pathogen reduction of red blood cells with FRALE (S-303) or INACTINE (PEN110) has so far resulted in the formation of antibodies against neo-epitopes on red blood cells. A promising method for Riboflavin treatment of red blood cells is under development. This manuscript reviews the current experience and discusses future trends. PMID:18602343

Solheim, Bjarte G

2008-08-01

407

Top 10 plant pathogenic bacteria in molecular plant pathology.  

PubMed

Many plant bacteriologists, if not all, feel that their particular microbe should appear in any list of the most important bacterial plant pathogens. However, to our knowledge, no such list exists. The aim of this review was to survey all bacterial pathologists with an association with the journal Molecular Plant Pathology and ask them to nominate the bacterial pathogens they would place in a 'Top 10' based on scientific/economic importance. The survey generated 458 votes from the international community, and allowed the construction of a Top 10 bacterial plant pathogen list. The list includes, in rank order: (1) Pseudomonas syringae pathovars; (2) Ralstonia solanacearum; (3) Agrobacterium tumefaciens; (4) Xanthomonas oryzae pv. oryzae; (5) Xanthomonas campestris pathovars; (6) Xanthomonas axonopodis pathovars; (7) Erwinia amylovora; (8) Xylella fastidiosa; (9) Dickeya (dadantii and solani); (10) Pectobacterium carotovorum (and Pectobacterium atrosepticum). Bacteria garnering honourable mentions for just missing out on the Top 10 include Clavibacter michiganensis (michiganensis and sepedonicus), Pseudomonas savastanoi and Candidatus Liberibacter asiaticus. This review article presents a short section on each bacterium in the Top 10 list and its importance, with the intention of initiating discussion and debate amongst the plant bacteriology community, as well as laying down a benchmark. It will be interesting to see, in future years, how perceptions change and which bacterial pathogens enter and leave the Top 10. PMID:22672649

Mansfield, John; Genin, Stephane; Magori, Shimpei; Citovsky, Vitaly; Sriariyanum, Malinee; Ronald, Pamela; Dow, Max; Verdier, Valérie; Beer, Steven V; Machado, Marcos A; Toth, Ian; Salmond, George; Foster, Gary D

2012-08-01

408

Laribacter hongkongensis: an emerging pathogen of infectious diarrhea.  

PubMed

Laribacter hongkongensis is relatively a new name in the list of bacterial pathogens for gastroenteritis and travelers' diarrhea. Addition of another name increases burden on the enteric infections as a whole. L. hongkongensis belongs to Neisseriaceae family of ? subclass Proteobacteria. L. hongkongensis was initially isolated in Hong Kong from blood and empyema of an alcoholic cirrhotic patient in 2001, followed by reports from Korea and China, representing a total of 38 articles in PubMed until April 2013. As of now, there is no report from Indian subcontinent where infectious diarrhea is very much prevalent and a major burden. This review provides information about the microbiological characteristics, consideration of an emerging pathogen, relative pathogenicity, genome and proteome content, resistance toward multiple antibiotics, adaptability to different stress, and other features since its time of discovery. Investigation for this bacterium may avoid misidentification as other microbial flora. Further studies like the geographical distribution, type of infection, disease burden, pathogenicity, or genomic exploration of this bacterium will be useful in characterizing them properly. This bacterium may possibly be the emerging threat to public health. PMID:24481985

Raja, M Krishna; Ghosh, Asit Ranjan

2014-07-01

409

Uniform fluorescent nanobioprobes for pathogen detection.  

PubMed

Manipulating biochemical reactions in living cells to synthesize nanomaterials is an attractive strategy to realize their synthesis that cannot take place in nature. Yeast cells have been skillfully utilized to produce desired nanoparticles through spatiotemporal coupling of intracellular nonrelated biochemical reaction pathways for formation of fluorescent CdSe quantum dots. Here, we have successfully transformed Staphylococcus aureus cells into cellular beacons (fluorescing cells), all of which are highly fluorescent and photostable with perfect uniformity. Importantly, on the basis of such cells, we efficiently fabricated fluorescent nanobioprobes by a specific interaction between the protein A expressed on the S. aureus surface and the Fc fragment domain of antibodies, avoiding the use of other common methods for cell surface modifications, such as molecular covalent connection or more difficult genetic and metabolic engineering. Coupled with immunomagnetic beads, the resulting fluorescent-biotargeting bifunctional cells, i.e., biotargeting cellular beacons, can be employed as nanobioprobes for detection of viruses, bacteria, and tumor cells. With this method, H9N2 AIV can be detected specifically with a limit of 8.94 ng/mL (based on protein content). Furthermore, diverse probes for detection of different pathogens or for other biomedical applications can be easily obtained by simply changing the antibody conjugated to the cell surface. PMID:24779675

Xiong, Ling-Hong; Cui, Ran; Zhang, Zhi-Ling; Yu, Xu; Xie, Zhixiong; Shi, Yun-Bo; Pang, Dai-Wen

2014-05-27

410

Effectiveness of Irradiation in Killing Pathogens.  

National Technical Information Service (NTIS)

United States Environmental Protection Agency regulations include gamma ray irradiation of sludge as an approved Process to Further Reduce Pathogens (PFRP) prior to land application. Research at Sandia National Laboratories on pathogen inactivation in slu...

J. G. Yeager, R. L. Ward

1980-01-01

411

Process of producing a ceramic matrix composite article and article formed thereby  

DOEpatents

A CMC article and process for producing the article to have a layer on its surface that protects a reinforcement material within the article from damage. The method entails providing a body containing a ceramic reinforcement material in a matrix material that contains a precursor of a ceramic matrix material. A fraction of the reinforcement material is present and possibly exposed at a surface of the body. The body surface is then provided with a surface layer formed of a slurry containing a particulate material but lacking the reinforcement material of the body. The body and surface layer are heated to form the article by converting the precursor within the body to form the ceramic matrix material in which the reinforcement material is contained, and by converting the surface layer to form the protective layer that covers any fraction of the reinforcement material exposed at the body surface.

Corman, Gregory Scot (Ballston Lake, NY); McGuigan, Henry Charles (Duanesburg, NY); Brun, Milivoj Konstantin (Ballston Lake, NY)

2011-10-25

412

Catalysis of protein folding by chaperones in pathogenic bacteria  

PubMed Central

Molecular chaperones are thought to inhibit off-pathway interactions such as aggregation from occurring without influencing the on-pathway formation of native structure. Here, we present a mechanism whereby the family of PapD-like chaperones, which are involved in the formation of adhesive pili in pathogenic bacteria, function by suppressing aggregation while simultaneously catalyzing the folding of subunits that make up the pilus. We also show that the Arg-8 residue, invariant in the cleft of all known PapD-like chaperones, makes up part of the active site of the chaperone. The data argue for a temporal mechanism of catalyzed folding. The terminal carboxylate group of a pilus subunit anchors to the active site of the chaperone by hydrogen bonding. This bonding spatially fixes the COOH terminus of the subunit in the correct context for ?-sheet formation, using the edge of the NH2-terminal domain of the chaperone as a nucleation site.

Bann, James G.; Pinkner, Jerome S.; Frieden, Carl; Hultgren, Scott J.

2004-01-01

413

Integrated patient pathways: “mipp” – a tool for quality improvement and cost management in health care. Pilot study on the pathway “Acute Myocardial Infarction”  

Microsoft Academic Search

This article describes the fundamentals of the “model of integrated patient pathways” (“mipp”) and its mode of action as a tool for quality improvement and cost management in health care. The model is based on three pillars: construction, implementation and benchmarking. Transparency of processes and costs become available from interdisciplinary construction of care pathways via an Access database. The article

Katharina Schmid; Dieter Conen

2000-01-01

414

Constraint-Based Modeling and Scheduling of Clinical Pathways  

NASA Astrophysics Data System (ADS)

In this article a constraint-based modeling of clinical pathways, in particular of surgical pathways, is introduced and used for an optimized scheduling of their tasks. The addressed optimization criteria are based on practical experiences in the area of Constraint Programming applications in medical work flow management. Objective functions having empirical evidence for their adequacy in the considered use cases are formally presented. It is shown how they are respected while scheduling clinical pathways.

Wolf, Armin

415

Pathogenicity of Mycobacterium tuberculosis Is Expressed by Regulating Metabolic Thresholds of the Host Macrophage  

PubMed Central

The success of Mycobacterium tuberculosis as a pathogen derives from its facile adaptation to the intracellular milieu of human macrophages. To explore this process, we asked whether adaptation also required interference with the metabolic machinery of the host cell. Temporal profiling of the metabolic flux, in cells infected with differently virulent mycobacterial strains, confirmed that this was indeed the case. Subsequent analysis identified the core subset of host reactions that were targeted. It also elucidated that the goal of regulation was to integrate pathways facilitating macrophage survival, with those promoting mycobacterial sustenance. Intriguingly, this synthesis then provided an axis where both host- and pathogen-derived factors converged to define determinants of pathogenicity. Consequently, whereas the requirement for macrophage survival sensitized TB susceptibility to the glycemic status of the individual, mediation by pathogen ensured that the virulence properties of the infecting strain also contributed towards the resulting pathology.

Saquib, Najmuddin; Sinha, Neeraj; Siddiqui, Zaved; Manivel, Venkatasamy; Chatterjee, Samrat; Rao, Kanury V. S.

2014-01-01

416

NCI DTP Pathways Services  

Cancer.gov

Pathways to Development Services Home Discovery Development Pathways Grants/Contracts Books/Publications Site Search Data Search What's New Section under development. Please direct inquiries to NCIDTPINFO@mail.nih.gov

417

Interactions of Bacterial Proteins with Host Eukaryotic Ubiquitin Pathways  

PubMed Central

Ubiquitination is a post-translational modification in which one or more 76 amino acid polypeptide ubiquitin molecules are covalently linked to the lysine residues of target proteins. Ubiquitination is the main pathway for protein degradation that governs a variety of eukaryotic cellular processes, including the cell-cycle, vesicle trafficking, antigen presentation, and signal transduction. Not surprisingly, aberrations in the system have been implicated in the pathogenesis of many diseases including inflammatory and neurodegenerative disorders. Recent studies have revealed that viruses and bacterial pathogens exploit the host ubiquitination pathways to gain entry and to aid their survival/replication inside host cells. This review will summarize recent developments in understanding the biochemical and structural mechanisms utilized by bacterial pathogens to interact with the host ubiquitination pathways.

Perrett, Charlotte Averil; Lin, David Yin-Wei; Zhou, Daoguo

2011-01-01

418

77 FR 34783 - Highly Pathogenic Avian Influenza  

Federal Register 2010, 2011, 2012, 2013

...RIN 0579-AC36 Highly Pathogenic Avian Influenza AGENCY: Animal and Plant Health Inspection...any subtype of highly pathogenic avian influenza (HPAI) is considered to exist. The...Newcastle disease and highly pathogenic avian influenza (HPAI). On January 24, 2011,...

2012-06-12

419

Awareness of foodborne pathogens among US consumers  

Microsoft Academic Search

Each year in the United States, microbial pathogens cause millions of cases of foodborne disease and result in many hospitalizations and deaths. Effective consumer education programs to promote safer food handling practices and other averting behaviors may benefit from consumer awareness of microbial pathogens. This paper investigates US consumers’ awareness of four major microbial pathogens (Salmonella, Campylobacter, Listeria and Escherichia

Chung-Tung Jordan Lin; Kimberly L. Jensen; Steven T. Yen

2005-01-01

420

DETERMINANTS OF CONSUMER AWARENESS OF FOODBORNE PATHOGENS  

Microsoft Academic Search

Each year, microbial pathogens cause millions of cases of foodborne disease and result in many hospitalizations and deaths. Effective consumer education programs to promote safer food handling practices and other averting behaviors may benefit from consumer awareness of microbial pathogens. This paper investigates U.S. consumers?' awareness of four major microbial pathogens (Salmonella, Campylobacter, Listeria and E. coli) as food safety

Chung-Tung Jordan Lin; Kimberly L. Jensen; Steven T. Yen

2004-01-01

421

The effect of treatment on pathogen virulence  

Microsoft Academic Search

The optimal virulence of a pathogen is determined by a trade-off between maximizing the rate of transmission and maximizing the duration of infectivity. Treatment measures such as curative therapy and case isolation exert selective pressure by reducing the duration of infectivity, reducing the value of duration-increasing strategies to the pathogen and favoring pathogen strategies that maximize the rate of transmission.

Travis C. Porco; James O. Lloyd-Smith; Kimber L. Gross; Alison P. Galvani

2005-01-01

422

Genomic islands in pathogenic and environmental microorganisms  

Microsoft Academic Search

Horizontal gene transfer is an important mechanism for the evolution of microbial genomes. Pathogenicity islands — mobile genetic elements that contribute to rapid changes in virulence potential — are known to have contributed to genome evolution by horizontal gene transfer in many bacterial pathogens. Increasing evidence indicates that equivalent elements in non-pathogenic species — genomic islands — are important in

Ulrich Dobrindt; Bianca Hochhut; Ute Hentschel; Jörg Hacker

2004-01-01

423

Method of molding fiber reinforced articles  

US Patent & Trademark Office Database

A method of molding fiber-reinforced thermoset resin articles having improved mechanical properties. A thermosettable organic material is injected into a mold containing a fiber web. The molding composition includes (a) a thermosettable organic material containing two or more polymerizable carbon-carbon double bonds, (b) an ethylenically unsaturated monomer which forms a liquid homogeneous mixture with and is copolymerizable with (a) and is different from (a), and (c) an effective amount of an initiator or a mixture of initiators characterized by a ten-hour half life temperature, or in the case of a mixture of initiators, and average ten-hour half life temperature, of greater than about 50.degree. C. and less than 105.degree. C., which produces on decomposition less than 1.0 milliliter of gas per gram of resin as measured at a temperature of 25.degree. C. and a pressure of one atmosphere.

1989-05-30

424

Coated foams, preparation, uses and articles  

DOEpatents

Hydrophobic cellular material is coated with a thin hydrophilic polymer skin which stretches tightly over the foam but which does not fill the cells of the foam, thus resulting in a polymer-coated foam structure having a smoothness which was not possible in the prior art. In particular, when the hydrophobic cellular material is a specially chosen hydrophobic polymer foam and is formed into arbitrarily chosen shapes prior to the coating with hydrophilic polymer, inertial confinement fusion (ICF) targets of arbitrary shapes can be produced by subsequently coating the shapes with metal or with any other suitable material. New articles of manufacture are produced, including improved ICF targets, improved integrated circuits, and improved solar reflectors and solar collectors. In the coating method, the cell size of the hydrophobic cellular material, the viscosity of the polymer solution used to coat, and the surface tension of the polymer solution used to coat are all very important to the coating.

Duchane, D.V.; Barthell, B.L.

1982-10-21

425

Article coated with flash bonded superhydrophobic particles  

DOEpatents

A method of making article having a superhydrophobic surface includes: providing a solid body defining at least one surface; applying to the surface a plurality of diatomaceous earth particles and/or particles characterized by particle sizes ranging from at least 100 nm to about 10 .mu.m, the particles being further characterized by a plurality of nanopores, wherein at least some of the nanopores provide flow through porosity, the particles being further characterized by a plurality of spaced apart nanostructured features that include a contiguous, protrusive material; flash bonding the particles to the surface so that the particles are adherently bonded to the surface; and applying a hydrophobic coating layer to the surface and the particles so that the hydrophobic coating layer conforms to the nanostructured features.

Simpson, John T (Clinton, TN) [Clinton, TN; Blue, Craig A (Knoxville, TN) [Knoxville, TN; Kiggans, Jr., James O [Oak Ridge, TN

2010-07-13

426

Gating by Cyclic AMP: Expanded Role for an Old Signaling Pathway  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. The intracellular signal transduction pathway that utilizes cyclic AMP as a key messenger was the first such pathway to be described and has served as a model for many other transducing systems. Now Iyengar illustrates how this classic pathway has yet another function--in a number of different biological systems, the cyclic AMP pathway appears to gate (either negatively or positively) other signal transduction pathways.

Ravi Iyengar (City University of New York;Department of Pharmacology, Mount Sinai School of Medicine)

1996-01-26

427

Pathogens in septage in Vietnam.  

PubMed

Septage is widely acknowledged as a major source of infectious pathogens while disposal of septage, and the operation and maintenance of septic tanks, is not regulated in many developing countries. Twenty untreated septage and septage sludge samples were taken from Can Tho City, Vietnam to examine their pathogen content, and indicator micro-organisms. Escherichia coli and Enterococcus spp. were detected in all samples, regardless of sludge storage time. Phages were detected in 80% of samples. Salmonella spp. were detected in 70% of the untreated septage and 60% of septage sludge samples. Concentrations of phages and bacteria tested in septage sludge after many years of tank storage were much higher than the expected levels. Helminth ova were present in 95% of untreated septage samples with an average of 450 oval(-1), and were detected in all septage sludge samples with an average of 16,000 oval(-1). Twelve varieties of helminth ova were identified. More helminth ova varieties in higher concentrations were found in septage than those reported from stool samples. The varieties' frequency ranged from 10% to 50% and Ascaris lumbricoides predominated. Results show that pathogens and indicator micro-organisms, especially helminth ova, accumulate in sludge. Thus helminth ova should be considered when septage sludge is treated and used for agriculture. Proper health protection measures must be applied for people handling septage. PMID:20138647

Yen-Phi, Vo Thi; Rechenburg, Andrea; Vinneras, Björn; Clemens, Joachim; Kistemann, Thomas

2010-04-01

428

Identifying pathogenic processes by integrating microarray data with prior knowledge  

PubMed Central

Background It is of great importance to identify molecular processes and pathways that are involved in disease etiology. Although there has been an extensive use of various high-throughput methods for this task, pathogenic pathways are still not completely understood. Often the set of genes or proteins identified as altered in genome-wide screens show a poor overlap with canonical disease pathways. These findings are difficult to interpret, yet crucial in order to improve the understanding of the molecular processes underlying the disease progression. We present a novel method for identifying groups of connected molecules from a set of differentially expressed genes. These groups represent functional modules sharing common cellular function and involve signaling and regulatory events. Specifically, our method makes use of Bayesian statistics to identify groups of co-regulated genes based on the microarray data, where external information about molecular interactions and connections are used as priors in the group assignments. Markov chain Monte Carlo sampling is used to search for the most reliable grouping. Results Simulation results showed that the method improved the ability of identifying correct groups compared to traditional clustering, especially for small sample sizes. Applied to a microarray heart failure dataset the method found one large cluster with several genes important for the structure of the extracellular matrix and a smaller group with many genes involved in carbohydrate metabolism. The method was also applied to a microarray dataset on melanoma cancer patients with or without metastasis, where the main cluster was dominated by genes related to keratinocyte differentiation. Conclusion Our method found clusters overlapping with known pathogenic processes, but also pointed to new connections extending beyond the classical pathways.

2014-01-01

429

Metabolic Profiling Reveals PAFAH1B3 as a Critical Driver of Breast Cancer Pathogenicity.  

PubMed

Many studies have identified metabolic pathways that underlie cellular transformation, but the metabolic drivers of cancer progression remain less well understood. The Hippo transducer pathway has been shown to confer malignant traits on breast cancer cells. In this study, we used metabolic mapping platforms to identify biochemical drivers of cellular transformation and malignant progression driven through RAS and the Hippo pathway in breast cancer and identified platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3) as a key metabolic driver of breast cancer pathogenicity that is upregulated in primary human breast tumors and correlated with poor prognosis. Metabolomic profiling suggests that PAFAH1B3 inactivation attenuates cancer pathogenicity through enhancing tumor-suppressing signaling lipids. Our studies provide a map of altered metabolism that underlies breast cancer progression and put forth PAFAH1B3 as a critical metabolic node in breast cancer. PMID:24954006

Mulvihill, Melinda M; Benjamin, Daniel I; Ji, Xiaodan; Le Scolan, Erwan; Louie, Sharon M; Shieh, Alice; Green, McKenna; Narasimhalu, Tara; Morris, Patrick J; Luo, Kunxin; Nomura, Daniel K

2014-07-17

430

Hedgehog Signaling Pathway  

NSDL National Science Digital Library

The Hedgehog (Hh) signaling pathway is essential for development and tissue homeostasis in metazoans. Probably as a result of its potent influence on cell-fate outcomes, the Hh pathway when corrupted results in malformations and diseases such as cancer. Many of the pathway components that contribute to Hh-mediated signal transduction are presented.

Leni Jacob (University of Texas Southwestern Medical Center;Department of Cell Biology REV); Lawrence Lum (University of Texas Southwestern Medical Center;Department of Cell Biology REV)

2007-10-09

431

Large scale comparison of innate responses to viral and bacterial pathogens in mouse and macaque.  

PubMed

Viral and bacterial infections of the lower respiratory tract are major causes of morbidity and mortality worldwide. Alveolar macrophages line the alveolar spaces and are the first cells of the immune system to respond to invading pathogens. To determine the similarities and differences between the responses of mice and macaques to invading pathogens we profiled alveolar macrophages from these species following infection with two viral (PR8 and Fuj/02 influenza A) and two bacterial (Mycobacterium tuberculosis and Francisella tularensis Schu S4) pathogens. Cells were collected at 6 time points following each infection and expression profiles were compared across and between species. Our analyses identified a core set of genes, activated in both species and across all pathogens that were predominantly part of the interferon response pathway. In addition, we identified similarities across species in the way innate immune cells respond to lethal versus non-lethal pathogens. On the other hand we also found several species and pathogen specific response patterns. These results provide new insights into mechanisms by which the innate immune system responds to, and interacts with, invading pathogens. PMID:21789257

Zinman, Guy; Brower-Sinning, Rachel; Emeche, Chineye H; Ernst, Jason; Huang, Grace Tzu-Wei; Mahony, Shaun; Myers, Amy J; O'Dee, Dawn M; Flynn, JoAnne L; Nau, Gerard J; Ross, Ted M; Salter, Russell D; Benos, Panayiotis V; Bar Joseph, Ziv; Morel, Penelope A

2011-01-01

432

Large Scale Comparison of Innate Responses to Viral and Bacterial Pathogens in Mouse and Macaque  

PubMed Central

Viral and bacterial infections of the lower respiratory tract are major causes of morbidity and mortality worldwide. Alveolar macrophages line the alveolar spaces and are the first cells of the immune system to respond to invading pathogens. To determine the similarities and differences between the responses of mice and macaques to invading pathogens we profiled alveolar macrophages from these species following infection with two viral (PR8 and Fuj/02 influenza A) and two bacterial (Mycobacterium tuberculosis and Francisella tularensis Schu S4) pathogens. Cells were collected at 6 time points following each infection and expression profiles were compared across and between species. Our analyses identified a core set of genes, activated in both species and across all pathogens that were predominantly part of the interferon response pathway. In addition, we identified similarities across species in the way innate immune cells respond to lethal versus non-lethal pathogens. On the other hand we also found several species and pathogen specific response patterns. These results provide new insights into mechanisms by which the innate immune system responds to, and interacts with, invading pathogens.

Zinman, Guy; Brower-Sinning, Rachel; Emeche, Chineye H.; Ernst, Jason; Huang, Grace Tzu-Wei; Mahony, Shaun; Myers, Amy J.; O'Dee, Dawn M.; Flynn, JoAnne L.; Nau, Gerard J.; Ross, Ted M.; Salter, Russell D.; Benos, Panayiotis V.; Bar Joseph, Ziv; Morel, Penelope A.

2011-01-01

433

Identifying pathogenicity genes in the rubber tree anthracnose fungus Colletotrichum gloeosporioides through random insertional mutagenesis.  

PubMed

To gain more insight into the molecular mechanisms of Colletotrichum gloeosporioides pathogenesis, Agrobacterium tumefaciens-mediated transformation (ATMT) was used to identify mutants of C. gloeosporioides impaired in pathogenicity. An ATMT library of 4128 C. gloeosporioides transformants was generated. Transformants were screened for defects in pathogenicity with a detached copper brown leaf assay. 32 mutants showing reproducible pathogenicity defects were obtained. Southern blot analysis showed 60.4% of the transformants had single-site T-DNA integrations. 16 Genomic sequences flanking T-DNA were recovered from mutants by thermal asymmetric interlaced PCR, and were used to isolate the tagged genes from the genome sequence of wild-type C. gloeosporioides by Basic Local Alignment Search Tool searches against the local genome database of the wild-type C. gloeosporioides. One potential pathogenicity genes encoded calcium-translocating P-type ATPase. Six potential pathogenicity genes had no known homologs in filamentous fungi and were likely to be novel fungal virulence factors. Two putative genes encoded Glycosyltransferase family 28 domain-containing protein and Mov34/MPN/PAD-1 family protein, respectively. Five potential pathogenicity genes had putative function matched with putative protein of other Colletotrichum species. Two known C. gloeosporioides pathogenicity genes were also identified, the encoding Glomerella cingulata hard-surface induced protein and C. gloeosporioides regulatory subunit of protein kinase A gene involved in cAMP-dependent PKA signal transduction pathway. PMID:23602122

Cai, Zhiying; Li, Guohua; Lin, Chunhua; Shi, Tao; Zhai, Ligang; Chen, Yipeng; Huang, Guixiu

2013-07-19

434

Distinctive Expansion of Potential Virulence Genes in the Genome of the Oomycete Fish Pathogen Saprolegnia parasitica  

PubMed Central

Oomycetes in the class Saprolegniomycetidae of the Eukaryotic kingdom Stramenopila have evolved as severe pathogens of amphibians, crustaceans, fish and insects, resulting in major losses in aquaculture and damage to aquatic ecosystems. We have sequenced the 63 Mb genome of the fresh water fish pathogen, Saprolegnia parasitica. Approximately 1/3 of the assembled genome exhibits loss of heterozygosity, indicating an efficient mechanism for revealing new variation. Comparison of S. parasitica with plant pathogenic oomycetes suggests that during evolution the host cellular environment has driven distinct patterns of gene expansion and loss in the genomes of plant and animal pathogens. S. parasitica possesses one of the largest repertoires of proteases (270) among eukaryotes that are deployed in waves at different points during infection as determined from RNA-Seq data. In contrast, despite being capable of living saprotrophically, parasitism has led to loss of inorganic nitrogen and sulfur assimilation pathways, strikingly similar to losses in obligate plant pathogenic oomycetes and fungi. The large gene families that are hallmarks of plant pathogenic oomycetes such as Phytophthora appear to be lacking in S. parasitica, including those encoding RXLR effectors, Crinkler's, and Necrosis Inducing-Like Proteins (NLP). S. parasitica also has a very large kinome of 543 kinases, 10% of which is induced upon infection. Moreover, S. parasitica encodes several genes typical of animals or animal-pathogens and lacking from other oomycetes, including disintegrins and galactose-binding lectins, whose expression and evolutionary origins implicate horizontal gene transfer in the evolution of animal pathogenesis in S. parasitica.

Belmonte, Rodrigo; Lobach, Lars; Christie, James; van den Ackerveken, Guido; Bottin, Arnaud; Bulone, Vincent; Diaz-Moreno, Sara M.; Dumas, Bernard; Fan, Lin; Gaulin, Elodie; Govers, Francine; Grenville-Briggs, Laura J.; Horner, Neil R.; Levin, Joshua Z.; Mammella, Marco; Meijer, Harold J. G.; Morris, Paul; Nusbaum, Chad; Oome, Stan; Phillips, Andrew J.; van Rooyen, David; Rzeszutek, Elzbieta; Saraiva, Marcia; Secombes, Chris J.; Seidl, Michael F.; Snel, Berend; Stassen, Joost H. M.; Sykes, Sean; Tripathy, Sucheta; van den Berg, Herbert; Vega-Arreguin, Julio C.; Wawra, Stephan; Young, Sarah K.; Zeng, Qiandong; Dieguez-Uribeondo, Javier; Russ, Carsten; Tyler, Brett M.; van West, Pieter

2013-01-01

435

Benfang Lei's research on heme acquisition in Gram-positive pathogens and bacterial pathogenesis  

PubMed Central

Benfang Lei’s laboratory conducts research on pathogenesis of human pathogen Group A Streptococcus (GAS) and horse pathogen Streptococcus equi (S. equi). His current research focuses on heme acquisition in Gram-positive pathogens and molecular mechanism of GAS and S. equi pathogenesis. Heme is an important source of essential iron for bacterial pathogens. Benfang Lei and colleagues identified the first cell surface heme-binding protein in Gram-positive pathogens and the heme acquisition system in GAS, demonstrated direct heme transfer from one protein to another, demonstrated an experimental pathway of heme acquisition by the Staphylococcus aureus Isd system, elucidated the activated heme transfer mechanism, and obtained evidence for a chemical mechanism of direct axial ligand displacement during the Shp-to-HtsA heme transfer reaction. These findings have considerably contributed to the progress that has been made over recent years in understanding the heme acquisition process in Gram-positive pathogens. Pathogenesis of GAS is mediated by an abundance of extracellular proteins, and pathogenic role and functional mechanism are not known for many of these virulence factors. Lei laboratory identified a secreted protein of GAS as a CovRS-regulated virulence factor that is a protective antigen and is critical for GAS spreading in the skin and systemic dissemination. These studies may lead to development of novel strategies to prevent and treat GAS infections.

Lei, Benfang

2010-01-01

436

The use of popular science articles in teaching scientific literacy  

Microsoft Academic Search

This article considers the use of popular science articles in teaching scientific literacy. Comparing the discourse features of popular science with research article and textbook science – the last two being target forms for students – it argues that popular science articles cannot serve as models for scientific writing. It does, however, suggest that popular articles can make science more

Jean Parkinson; Ralph Adendorff

2004-01-01

437

Organomercury Pathway Map  

NSDL National Science Digital Library

The University of Minnesota Biocatalysis/Biodegradation Database (UM/BBD) contains "microbial biocatalytic reactions and biodegradation pathways primarily for xenobiotic, chemical compounds." A new microbial enzyme-catalyzed reactions has been posted for Organomercury. The Organomercury pathway map highlights mercury, a highly toxic heavy metal used "as a pesticide, herbicide, fungicide, disinfectant and a preservative in cosmetics." The organomercury pathway map includes organisms which can initiate the pathway. The pathway map provides detailed information on each hyperlinked step, including graphics, product/substrate reactions, and external links to further information.</