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Sample records for integration host factor

  1. Integration host factor of Mycobacterium tuberculosis, mIHF, compacts DNA by a bending mechanism.

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    Arpit Mishra

    Full Text Available The bacterial chromosomal DNA is folded into a compact structure called as 'nucleoid' so that the bacterial genome can be accommodated inside the cell. The shape and size of the nucleoid are determined by several factors including DNA supercoiling, macromolecular crowding and nucleoid associated proteins (NAPs. NAPs bind to different sites of the genome in sequence specific or non-sequence specific manner and play an important role in DNA compaction as well as regulation. Until recently, few NAPs have been discovered in mycobacteria owing to poor sequence similarities with other histone-like proteins of eubacteria. Several putative NAPs have now been identified in Mycobacteria on the basis of enriched basic residues or histone-like "PAKK" motifs. Here, we investigate mycobacterial Integration Host Factor (mIHF for its architectural roles as a NAP using atomic force microscopy and DNA compaction experiments. We demonstrate that mIHF binds DNA in a non-sequence specific manner and compacts it by a DNA bending mechanism. AFM experiments also indicate a dual architectural role for mIHF in DNA compaction as well as relaxation. These results suggest a convergent evolution in the mechanism of E. coli and mycobacterial IHF in DNA compaction.

  2. Integration host factor is required for replication of pYGK-derived plasmids in Aggregatibacter actinomycetemcomitans.

    Science.gov (United States)

    Torres-Escobar, Ascención; Juárez-Rodríguez, María D; Demuth, Donald R

    2014-08-01

    In this study, we show that integration host factor protein (IHF) is required for replication of pYGK plasmids in Aggregatibacter actinomycetemcomitans. YGK plasmids were not replicated in A. actinomycetemcomitans strains lacking either the α- or β- subunit of IHF. However, the deletion mutants were complemented, and plasmid replication was restored when the promoter region and gene for either ihfA or ihfB was cloned into pYGK. We also identified two motifs that resemble the consensus IHF-binding site in a 813-bp fragment containing the pYGK origin of replication. Using electrophoretic mobility shift assays, purified IHFα-IHFβ protein complex was shown to bind to probes containing either of these motifs. To our knowledge, this is the first report showing that plasmid replication is IHF-dependent in the family Pasteurellaceae. In addition, using site-direct mutagenesis, the XbaI and KpnI restriction sites in the suicide vector pJT1 were modified to generate plasmid pJT10. The introduction of these new unique sites in pJT10 facilitates the transfer of transcriptional or translational lacZ fusion constructs for the generation of single-copy chromosomal insertion of the reporter construct. Plasmid pJT10 and its derivatives will be useful for genetic studies in Aggregatibacter (Actinobacillus) and probably other genera of Pasteurellaceae, including Haemophilus, Pasteurella, and Mannheimia.

  3. The Bacteroides thetaiotaomicron protein Bacteroides host factor A participates in integration of the integrative conjugative element CTnDOT into the chromosome.

    Science.gov (United States)

    Ringwald, Kenneth; Gardner, Jeffrey

    2015-04-01

    CTnDOT is a conjugative transposon found in Bacteroides species. It encodes multiple antibiotic resistances and is stimulated to transfer by exposure to tetracycline. CTnDOT integration into the host chromosome requires IntDOT and a previously unknown host factor. We have identified a protein, designated BHFa (Bacteroides host factor A), that participates in integrative recombination. BHFa is the first host factor identified for a site-specific recombination reaction in the CTnDOT family of integrative and conjugative elements. Based on the amino acid sequence of BHFa, the ability to bind specifically to 4 sites in the attDOT DNA, and its activity in the integration reaction, BHFa is a member of the IHF/HU family of nucleoid-associated proteins. Other DNA bending proteins that bind DNA nonspecifically can substitute for BHFa in the integration reaction. Bacteroides species are normal members of the human colonic microbiota. These species can harbor and spread self-transmissible genetic elements (integrative conjugative elements [ICEs]) that contain antibiotic resistance genes. This work describes the role of a protein, BHFa, and its importance in the integration reaction required for the element CTnDOT to persist in Bacteroides host cells. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. Host Integration Server 2004

    Institute of Scientific and Technical Information of China (English)

    PaulThurrott; 杨岩

    2005-01-01

    微软发布的Host Integration Server(HIS)2004,是IBM大型主机集成服务器的一个重要的更新,添加了一些重要的新特点和改进。与大多数微软公司协同工作的产品不同,HIS 2004的设计目的是为了移植,而不是纯粹的集成,事实上它将会帮助客户从现有的传统平台中得到更多的价值——在这种情况下,所指的产品就是IBM大型主机和iSeries(也就是以前的AS/400)系列机型。

  5. Specific Photocrosslinking of DNA-Protein Complexes: Identification of Contacts Between Integration Host Factor and Its Target DNA

    Science.gov (United States)

    Yang, Shu-Wei; Nash, Howard A.

    1994-12-01

    Azide moieties have been specifically placed in the backbone of DNA by chemical coupling between azidophenacyl bromide and uniquely positioned phosphorothioate residues. The derivatized DNA forms specific complexes with a DNA-binding protein and, following irradiation with 302-nm light, makes specific crosslinks to the protein. Isolation of this covalent complex, followed by tryptic digestion and Edman degradation of the resulting crosslinked peptide, identifies the portion of the protein that is near the derivatized segment of the target DNA. We use this method to probe the interaction between a specific DNA sequence and integration host factor (IHF) protein. A single IHF heterodimer is known to contact >25 bp of DNA and thereby introduce a sharp bend. Two segments of a typical IHF site were derivatized with aryl azide. Although the segments were separated by only 5 bp, they crosslinked to different subunits of IHF. The locations of the crosslinks support our current view for the way IHF protein binds to and bends its specific targets.

  6. SARS Pathogenesis: Host Factors

    NARCIS (Netherlands)

    A. de Lang (Anna)

    2012-01-01

    textabstractWhile it is hypothesized that Sever Acute Respiratory Syndrome (SARS) in humans is caused by a disproportional immune response illustrated by inappropriate induction of inflammatory cytokines, the exact nature of the host response to SARS coronavirus (CoV) infection causing severe

  7. Global analysis of ion dependence unveils hidden steps in DNA binding and bending by integration host factor

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    Vivas, Paula; Velmurugu, Yogambigai; Kuznetsov, Serguei V.; Rice, Phoebe A.; Ansari, Anjum

    2013-09-01

    Proteins that recognize and bind to specific sites on DNA often distort the DNA at these sites. The rates at which these DNA distortions occur are considered to be important in the ability of these proteins to discriminate between specific and nonspecific sites. These rates have proven difficult to measure for most protein-DNA complexes in part because of the difficulty in separating the kinetics of unimolecular conformational rearrangements (DNA bending and kinking) from the kinetics of bimolecular complex association and dissociation. A notable exception is the Integration Host Factor (IHF), a eubacterial architectural protein involved in chromosomal compaction and DNA recombination, which binds with subnanomolar affinity to specific DNA sites and bends them into sharp U-turns. The unimolecular DNA bending kinetics has been resolved using both stopped-flow and laser temperature-jump perturbation. Here we expand our investigation by presenting a global analysis of the ionic strength dependence of specific binding affinity and relaxation kinetics of an IHF-DNA complex. This analysis enables us to obtain each of the underlying elementary rates (DNA bending/unbending and protein-DNA association/dissociation), and their ionic strength dependence, even under conditions where the two processes are coupled. Our analysis indicates interesting differences in the ionic strength dependence of the bi- versus unimolecular steps. At moderate [KCl] (100-500 mM), nearly all the ionic strength dependence to the overall equilibrium binding affinity appears in the bimolecular association/dissociation of an initial, presumably weakly bent, encounter complex, with a slope SKbi ≈ 8 describing the loglog-dependence of the equilibrium constant to form this complex on [KCl]. In contrast, the unimolecular equilibrium constant to form the fully wrapped specific complex from the initial complex is nearly independent of [KCl], with SKuni water molecules, which is osmotically favored by

  8. Integration Host Factor (IHF binds to the promoter region of the phtD operon involved in phaseolotoxin synthesis in P. syringae pv. phaseolicola NPS3121

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    Álvarez-Morales Ariel

    2011-05-01

    Full Text Available Abstract Background Pseudomonas syringae pv. phaseolicola, the causal agent of halo blight disease in beans, produces a toxin known as phaseolotoxin, in whose synthesis participate a group of genes organized within the genome in a region known as the "Pht cluster". This region, which is thought to have been acquired by horizontal gene transfer, includes 5 transcriptional units, two monocistronic (argK, phtL and three polycistronic (phtA, phtD, phtM, whose expression is temperature dependent. So far, the regulatory mechanisms involved in phaseolotoxin synthesis have not been elucidated and the only well-established fact is the requirement of low temperatures for its synthesis. In this work, we searched for regulatory proteins that could be involved in phaseolotoxin synthesis, focusing on the regulation of the phtD operon. Results In this study we identified the global regulator IHF (Integration Host Factor, which binds to the promoter region of the phtD operon, exerting a negative effect on the expression of this operon. This is the first regulatory protein identified as part of the phaseolotoxin synthesis system. Our findings suggest that the Pht cluster was similarly regulated in the ancestral cluster by IHF or similar protein, and integrated into the global regulatory mechanism of P. syringae pv. phaseolicola, after the horizontal gene transfer event by using the host IHF protein. Conclusion This study identifies the IHF protein as one element involved in the regulation of phaseolotoxin synthesis in P. syringae pv. phaseolicola NPS3121 and provides new insights into the regulatory mechanisms involved in phaseolotoxin production.

  9. Host factors in nidovirus replication

    NARCIS (Netherlands)

    Wilde, Adriaan Hugo de

    2013-01-01

    The interplay between nidoviruses and the infected host cell was investigated. Arterivirus RNA-synthesising activity was shown to depend on intact membranes and on a cytosolic host protein which does not cosediment with the RTC. Furthermore, the immunosuppressant drug cyclosporin A (CsA) blocks repl

  10. A novel function of Streptomyces integration host factor (sIHF) in the control of antibiotic production and sporulation in Streptomyces coelicolor.

    Science.gov (United States)

    Yang, Yung-Hun; Song, Eunjung; Willemse, Joost; Park, Sung-Hee; Kim, Woo-Seong; Kim, Eun-jung; Lee, Bo-Rahm; Kim, Ji-Nu; van Wezel, Gilles P; Kim, Byung-Gee

    2012-03-01

    Bacterial integration host factors (IHFs) play important roles in site-specific recombination, DNA replication, transcription, genome organization and bacterial pathogenesis. In Streptomyces coelicolor, there are three putative IHFs: SCO1480, SCO2950 and SCO5556. SCO1480 or Streptomyces IHF (sIHF) was previously identified as a transcription factor that binds to the promoter region of redD, the pathway-specific regulatory gene for the undecylprodigiosin biosynthetic gene cluster. Here we show that production of the pigmented antibiotics actinorhodin and undecylprodigiosin is strongly enhanced in sihf null mutants, while sporulation was strongly inhibited, with an on average 25% increase in spore size. Furthermore, the sihf mutant spores showed strongly reduced viability, with high sensitivity to heat and live/dead staining revealing a high proportion of empty spores, while enhanced expression of sIHF increased viability. This suggests a major role for sIHF in controlling viability, perhaps via the control of DNA replication and/or segregation. Proteomic analysis of the sihf null mutant identified several differentially expressed transcriptional regulators, indicating that sIHF may have an extensive response regulon. These data surprisingly reveal that a basic architectural element conserved in many actinobacteria such as mycobacteria, corynebacteria, streptomycetes and rhodococci may act as a global regulator of secondary metabolism and cell development.

  11. Host factors influencing viral persistence

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Nansen, A; Ørding Andreasen, Susanne

    2000-01-01

    host were used. Our results reveal that very different outcomes may be observed depending on virus strain and immunocompetence of the host. Thus while CD4+ cells are not critical during the initial phase of virus control, infectious virus reappear in mice lacking CD4+ cells, B cells or CD40 ligand...... that these different outcomes may be explained in relatively simple mathematical terms. This suggests that modelling may be used as a means to predict critical host and virus parameters. Therefore, combining mathematical modelling with precise, quantitative, in vivo analyses looks to be a promising approach...

  12. Mlc is a transcriptional activator with a key role in integrating cyclic AMP receptor protein and integration host factor regulation of leukotoxin RNA synthesis in Aggregatibacter actinomycetemcomitans

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    Aggregatibacter actinomycetemcomitans, a periodontal pathogen, synthesizes leukotoxin (LtxA), a protein that helps the bacterium evade the host immune response. Transcription of the ltxA operon is induced during anaerobic growth. The cAMP receptor protein (CRP) indirectly increases ltxA expression...

  13. A dual binding site for integration host factor and the response regulator CtrA inside the Caulobacter crescentus replication origin.

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    Siam, Rania; Brassinga, Ann Karen C; Marczynski, Gregory T

    2003-09-01

    The response regulator CtrA controls chromosome replication by binding to five sites, a, b, c, d, and e, inside the Caulobacter crescentus replication origin (Cori). In this study, we demonstrate that integration host factor (IHF) binds Cori over the central CtrA binding site c. Surprisingly, IHF and CtrA share DNA recognition sequences. Rather than promoting cooperative binding, IHF binding hinders CtrA binding to site c and nearby site d. Unlike other CtrA binding sites, DNA mutations in the CtrA c/IHF site uniquely impair autonomous Cori plasmid replication. These mutations also alter transcription from distant promoters more than 100 bp away. When the CtrA c/IHF site was deleted from the chromosome, these cells grew slowly and became selectively intolerant to a CtrA phosphor-mimic allele (D51E). Since CtrA protein concentration decreases during the cell cycle as IHF protein concentration increases, we propose a model in which IHF displaces CtrA in order to bend Cori and promote efficient chromosome replication.

  14. Integration host factor assembly at the cohesive end site of the bacteriophage lambda genome: implications for viral DNA packaging and bacterial gene regulation.

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    Sanyal, Saurarshi J; Yang, Teng-Chieh; Catalano, Carlos Enrique

    2014-12-09

    Integration host factor (IHF) is an Escherichia coli protein involved in (i) condensation of the bacterial nucleoid and (ii) regulation of a variety of cellular functions. In its regulatory role, IHF binds to a specific sequence to introduce a strong bend into the DNA; this provides a duplex architecture conducive to the assembly of site-specific nucleoprotein complexes. Alternatively, the protein can bind in a sequence-independent manner that weakly bends and wraps the duplex to promote nucleoid formation. IHF is also required for the development of several viruses, including bacteriophage lambda, where it promotes site-specific assembly of a genome packaging motor required for lytic development. Multiple IHF consensus sequences have been identified within the packaging initiation site (cos), and we here interrogate IHF-cos binding interactions using complementary electrophoretic mobility shift (EMS) and analytical ultracentrifugation (AUC) approaches. IHF recognizes a single consensus sequence within cos (I1) to afford a strongly bent nucleoprotein complex. In contrast, IHF binds weakly but with positive cooperativity to nonspecific DNA to afford an ensemble of complexes with increasing masses and levels of condensation. Global analysis of the EMS and AUC data provides constrained thermodynamic binding constants and nearest neighbor cooperativity factors for binding of IHF to I1 and to nonspecific DNA substrates. At elevated IHF concentrations, the nucleoprotein complexes undergo a transition from a condensed to an extended rodlike conformation; specific binding of IHF to I1 imparts a significant energy barrier to the transition. The results provide insight into how IHF can assemble specific regulatory complexes in the background of extensive nonspecific DNA condensation.

  15. Function of IHF in lambda DNA packaging. I. Identification of the strong binding site for integration host factor and the locus for intrinsic bending in cosB.

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    Xin, W; Feiss, M

    1993-03-20

    Integration host factor (IHF) plays an accessory role in lambda DNA packaging. IHF affects the interaction of the lambda DNA packaging protein, terminase, with cos, the site on lambda DNA at which terminase binds and introduces staggered nicks to generate cohesive ends of mature lambda chromosomes. cos includes cosB, the terminase binding site and cosN, the adjacent nicking site. cosB includes multiple binding sites for gpNu1, the small subunit of terminase, and an IHF binding site, I1. I1 contains two overlapping sequences, called I1A and I1B, that closely match the consensus sequence for IHF binding sites. The I1A sequence was determined to be the site of IHF binding by hydroxyl radical footprinting experiments. Comparison of the pattern of IHF-induced enhancements and diminishments at I1 with published patterns for IHF binding sites at the lambda attachment site identifies I1A as the IHF binding site at I1. The conclusion that I1A is the IHF binding site was confirmed by studies with DNA mutant in I1A. The I1A- mutation, consisting of three adjacent base-pair changes in I1A, abolished IHF binding. In contrast to the I1A- mutation, a mutation in I1B, also consisting of three adjacent base-pair changes, caused a reduction in the affinity of IHF for I1A, and caused a reduction in the magnitude of the net intrinsic bending of cos lambda.

  16. Asymmetric positioning of Cas1–2 complex and Integration Host Factor induced DNA bending guide the unidirectional homing of protospacer in CRISPR-Cas type I-E system

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    Yoganand, K.N.R.; Sivathanu, R.; Nimkar, Siddharth; Anand, B.

    2017-01-01

    CRISPR–Cas system epitomizes prokaryote-specific quintessential adaptive defense machinery that limits the genome invasion of mobile genetic elements. It confers adaptive immunity to bacteria by capturing a protospacer fragment from invading foreign DNA, which is later inserted into the leader proximal end of CRIPSR array and serves as immunological memory to recognize recurrent invasions. The universally conserved Cas1 and Cas2 form an integration complex that is known to mediate the protospacer invasion into the CRISPR array. However, the mechanism by which this protospacer fragment gets integrated in a directional fashion into the leader proximal end is elusive. Here, we employ CRISPR/dCas9 mediated immunoprecipitation and genetic analysis to identify Integration Host Factor (IHF) as an indispensable accessory factor for spacer acquisition in Escherichia coli. Further, we show that the leader region abutting the first CRISPR repeat localizes IHF and Cas1–2 complex. IHF binding to the leader region induces bending by about 120° that in turn engenders the regeneration of the cognate binding site for protospacer bound Cas1–2 complex and brings it in proximity with the first CRISPR repeat. This appears to guide Cas1–2 complex to orient the protospacer invasion towards the leader-repeat junction thus driving the integration in a polarized fashion. PMID:27899566

  17. Herpesvirus Genome Integration into Telomeric Repeats of Host Cell Chromosomes.

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    Osterrieder, Nikolaus; Wallaschek, Nina; Kaufer, Benedikt B

    2014-11-01

    It is well known that numerous viruses integrate their genetic material into host cell chromosomes. Human herpesvirus 6 (HHV-6) and oncogenic Marek's disease virus (MDV) have been shown to integrate their genomes into host telomeres of latently infected cells. This is unusual for herpesviruses as most maintain their genomes as circular episomes during the quiescent stage of infection. The genomic DNA of HHV-6, MDV, and several other herpesviruses harbors telomeric repeats (TMRs) that are identical to host telomere sequences (TTAGGG). At least in the case of MDV, viral TMRs facilitate integration into host telomeres. Integration of HHV-6 occurs not only in lymphocytes but also in the germline of some individuals, allowing vertical virus transmission. Although the molecular mechanism of telomere integration is poorly understood, the presence of TMRs in a number of herpesviruses suggests it is their default program for genome maintenance during latency and also allows efficient reactivation.

  18. Integration of plastids with their hosts: Lessons learned from dinoflagellates.

    Science.gov (United States)

    Dorrell, Richard G; Howe, Christopher J

    2015-08-18

    After their endosymbiotic acquisition, plastids become intimately connected with the biology of their host. For example, genes essential for plastid function may be relocated from the genomes of plastids to the host nucleus, and pathways may evolve within the host to support the plastid. In this review, we consider the different degrees of integration observed in dinoflagellates and their associated plastids, which have been acquired through multiple different endosymbiotic events. Most dinoflagellate species possess plastids that contain the pigment peridinin and show extreme reduction and integration with the host biology. In some species, these plastids have been replaced through serial endosymbiosis with plastids derived from a different phylogenetic derivation, of which some have become intimately connected with the biology of the host whereas others have not. We discuss in particular the evolution of the fucoxanthin-containing dinoflagellates, which have adapted pathways retained from the ancestral peridinin plastid symbiosis for transcript processing in their current, serially acquired plastids. Finally, we consider why such a diversity of different degrees of integration between host and plastid is observed in different dinoflagellates and how dinoflagellates may thus inform our broader understanding of plastid evolution and function.

  19. Data integration aids understanding of butterfly-host plant networks

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    Muto-Fujita, Ai; Takemoto, Kazuhiro; Kanaya, Shigehiko; Nakazato, Takeru; Tokimatsu, Toshiaki; Matsumoto, Natsushi; Kono, Mayo; Chubachi, Yuko; Ozaki, Katsuhisa; Kotera, Masaaki

    2017-03-01

    Although host-plant selection is a central topic in ecology, its general underpinnings are poorly understood. Here, we performed a case study focusing on the publicly available data on Japanese butterflies. A combined statistical analysis of plant-herbivore relationships and taxonomy revealed that some butterfly subfamilies in different families feed on the same plant families, and the occurrence of this phenomenon more than just by chance, thus indicating the independent acquisition of adaptive phenotypes to the same hosts. We consequently integrated plant-herbivore and plant-compound relationship data and conducted a statistical analysis to identify compounds unique to host plants of specific butterfly families. Some of the identified plant compounds are known to attract certain butterfly groups while repelling others. The additional incorporation of insect-compound relationship data revealed potential metabolic processes that are related to host plant selection. Our results demonstrate that data integration enables the computational detection of compounds putatively involved in particular interspecies interactions and that further data enrichment and integration of genomic and transcriptomic data facilitates the unveiling of the molecular mechanisms involved in host plant selection.

  20. Data integration aids understanding of butterfly–host plant networks

    Science.gov (United States)

    Muto-Fujita, Ai; Takemoto, Kazuhiro; Kanaya, Shigehiko; Nakazato, Takeru; Tokimatsu, Toshiaki; Matsumoto, Natsushi; Kono, Mayo; Chubachi, Yuko; Ozaki, Katsuhisa; Kotera, Masaaki

    2017-01-01

    Although host-plant selection is a central topic in ecology, its general underpinnings are poorly understood. Here, we performed a case study focusing on the publicly available data on Japanese butterflies. A combined statistical analysis of plant–herbivore relationships and taxonomy revealed that some butterfly subfamilies in different families feed on the same plant families, and the occurrence of this phenomenon more than just by chance, thus indicating the independent acquisition of adaptive phenotypes to the same hosts. We consequently integrated plant–herbivore and plant–compound relationship data and conducted a statistical analysis to identify compounds unique to host plants of specific butterfly families. Some of the identified plant compounds are known to attract certain butterfly groups while repelling others. The additional incorporation of insect–compound relationship data revealed potential metabolic processes that are related to host plant selection. Our results demonstrate that data integration enables the computational detection of compounds putatively involved in particular interspecies interactions and that further data enrichment and integration of genomic and transcriptomic data facilitates the unveiling of the molecular mechanisms involved in host plant selection. PMID:28262809

  1. Barrier to auto integration factor becomes dephosphorylated during HSV-1 Infection and Can Act as a host defense by impairing viral DNA replication and gene expression.

    Science.gov (United States)

    Jamin, Augusta; Thunuguntla, Prasanth; Wicklund, April; Jones, Clinton; Wiebe, Matthew S

    2014-01-01

    BAF (Barrier to Autointegration Factor) is a highly conserved DNA binding protein that senses poxviral DNA in the cytoplasm and tightly binds to the viral genome to interfere with DNA replication and transcription. To counteract BAF, a poxviral-encoded protein kinase phosphorylates BAF, which renders BAF unable to bind DNA and allows efficient viral replication to occur. Herein, we examined how BAF phosphorylation is affected by herpes simplex virus type 1 (HSV-1) infection and tested the ability of BAF to interfere with HSV-1 productive infection. Interestingly, we found that BAF phosphorylation decreases markedly following HSV-1 infection. To determine whether dephosphorylated BAF impacts HSV-1 productive infection, we employed cell lines stably expressing a constitutively unphosphorylated form of BAF (BAF-MAAAQ) and cells overexpressing wild type (wt) BAF for comparison. Although HSV-1 production in cells overexpressing wtBAF was similar to that in cells expressing no additional BAF, viral growth was reduced approximately 80% in the presence of BAF-MAAAQ. Experiments were also performed to determine the mechanism of the antiviral activity of BAF with the following results. BAF-MAAAQ was localized to the nucleus, whereas wtBAF was dispersed throughout cells prior to infection. Following infection, wtBAF becomes dephosphorylated and relocalized to the nucleus. Additionally, BAF was associated with the HSV-1 genome during infection, with BAF-MAAAQ associated to a greater extent than wtBAF. Importantly, unphosphorylated BAF inhibited both viral DNA replication and gene expression. For example, expression of two regulatory proteins, ICP0 and VP16, were substantially reduced in cells expressing BAF-MAAAQ. However, other viral genes were not dramatically affected suggesting that expression of certain viral genes can be differentially regulated by unphosphorylated BAF. Collectively, these results suggest that BAF can act in a phosphorylation-regulated manner to impair

  2. Factorization of Behavioral Integrity

    DEFF Research Database (Denmark)

    Li, Ximeng; Nielson, Flemming; Nielson, Hanne Riis

    2015-01-01

    We develop a bisimulation-based nonintereference property that describes the allowed dependencies between communication behaviors of different integrity levels. The property is able to capture all possible combinations of integrity levels for the “presence” and “content” of actual communications....... Channels of low presence integrity and high content integrity can be used to model the effect of Message Authentication Codes or the consequence of Denial of Service Attacks. In case the distinction between “presence” and “content” is deliberately blurred, the noninterference property specialises...

  3. Integrative functional genomics of hepatitis C virus infection identifies host dependencies in complete viral replication cycle.

    Science.gov (United States)

    Li, Qisheng; Zhang, Yong-Yuan; Chiu, Stephan; Hu, Zongyi; Lan, Keng-Hsin; Cha, Helen; Sodroski, Catherine; Zhang, Fang; Hsu, Ching-Sheng; Thomas, Emmanuel; Liang, T Jake

    2014-05-01

    Recent functional genomics studies including genome-wide small interfering RNA (siRNA) screens demonstrated that hepatitis C virus (HCV) exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from our previous infectious HCV (HCVcc) siRNA screen. Applying functional genomics approaches and various in vitro HCV model systems, including HCV pseudoparticles (HCVpp), single-cycle infectious particles (HCVsc), subgenomic replicons, and HCV cell culture systems (HCVcc), we identified and characterized novel host factors or pathways required for each individual step of the HCV replication cycle. Particularly, we uncovered multiple HCV entry factors, including E-cadherin, choline kinase α, NADPH oxidase CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39 other host factors are required for HCV RNA replication, while the deubiquitinating enzyme USP11 and multiple other cellular genes are specifically involved in HCV IRES-mediated translation. Families of antiviral factors that target HCV replication or translation were also identified. In addition, various virologic assays validated that 66 host factors are involved in HCV assembly or secretion. These genes included insulin-degrading enzyme (IDE), a proviral factor, and N-Myc down regulated Gene 1 (NDRG1), an antiviral factor. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allows the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. This comprehensive study of HCV host

  4. Integrative functional genomics of hepatitis C virus infection identifies host dependencies in complete viral replication cycle.

    Directory of Open Access Journals (Sweden)

    Qisheng Li

    2014-05-01

    Full Text Available Recent functional genomics studies including genome-wide small interfering RNA (siRNA screens demonstrated that hepatitis C virus (HCV exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from our previous infectious HCV (HCVcc siRNA screen. Applying functional genomics approaches and various in vitro HCV model systems, including HCV pseudoparticles (HCVpp, single-cycle infectious particles (HCVsc, subgenomic replicons, and HCV cell culture systems (HCVcc, we identified and characterized novel host factors or pathways required for each individual step of the HCV replication cycle. Particularly, we uncovered multiple HCV entry factors, including E-cadherin, choline kinase α, NADPH oxidase CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39 other host factors are required for HCV RNA replication, while the deubiquitinating enzyme USP11 and multiple other cellular genes are specifically involved in HCV IRES-mediated translation. Families of antiviral factors that target HCV replication or translation were also identified. In addition, various virologic assays validated that 66 host factors are involved in HCV assembly or secretion. These genes included insulin-degrading enzyme (IDE, a proviral factor, and N-Myc down regulated Gene 1 (NDRG1, an antiviral factor. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allows the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. This comprehensive study

  5. Integration Host Factor Is Required for RpoN-Dependent hrpL Gene Expression and Controls Motility by Positively Regulating rsmB sRNA in Erwinia amylovora.

    Science.gov (United States)

    Lee, Jae Hoon; Zhao, Youfu

    2016-01-01

    Erwinia amylovora requires an hrp-type III secretion system (T3SS) to cause disease. It has been reported that HrpL, the master regulator of T3SS, is transcriptionally regulated by sigma factor 54 (RpoN), YhbH, and HrpS. In this study, the role of integration host factor (IHF) in regulating hrpL and T3SS gene expression was investigated. IHF is a nucleoid-associated protein that regulates gene expression by influencing nucleoid structure and DNA bending. Our results showed that both ihfA and ihfB mutants of E. amylovora did not induce necrotic lesions on pear fruits. Growth of both mutants was greatly reduced, and expression of the hrpL and T3SS genes was significantly down-regulated as compared with those of the wild type. In addition, expression of the ihfA, but not the ihfB gene, was under auto-suppression by IHF. Furthermore, both ihfA and ihfB mutants were hypermotile, due to significantly reduced expression of small RNA (sRNA) rsmB. Electrophoresis mobility shift assay further confirmed that IHF binds to the promoters of the hrpL and ihfA genes, as well as the rsmB sRNA gene. These results indicate that IHF is required for RpoN-dependent hrpL gene expression and virulence, and controls motility by positively regulating the rsmB sRNA in E. amylovora.

  6. Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens.

    Directory of Open Access Journals (Sweden)

    Deborah Chasman

    2016-07-01

    Full Text Available Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.

  7. Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens.

    Science.gov (United States)

    Chasman, Deborah; Walters, Kevin B; Lopes, Tiago J S; Eisfeld, Amie J; Kawaoka, Yoshihiro; Roy, Sushmita

    2016-07-01

    Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.

  8. Integrating Factors and ODE Patterns

    CERN Document Server

    Cheb-Terrab, E S

    1997-01-01

    A systematic algorithm for building integrating factors of the form mu(x,y') or mu(y,y') for non-linear second order ODEs is presented. When such an integrating factor exists, the scheme returns the integrating factor itself, without solving any auxiliary differential equations. The scheme was implemented in Maple, in the framework of the ODEtools package and its ODE-solver. A comparison between this implementation and other computer algebra ODE-solvers in solving related non-linear examples from Kamke's book is shown.

  9. Discovery of insect and human dengue virus host factors.

    Science.gov (United States)

    Sessions, October M; Barrows, Nicholas J; Souza-Neto, Jayme A; Robinson, Timothy J; Hershey, Christine L; Rodgers, Mary A; Ramirez, Jose L; Dimopoulos, George; Yang, Priscilla L; Pearson, James L; Garcia-Blanco, Mariano A

    2009-04-23

    Dengue fever is the most frequent arthropod-borne viral disease of humans, with almost half of the world's population at risk of infection. The high prevalence, lack of an effective vaccine, and absence of specific treatment conspire to make dengue fever a global public health threat. Given their compact genomes, dengue viruses (DENV-1-4) and other flaviviruses probably require an extensive number of host factors; however, only a limited number of human, and an even smaller number of insect host factors, have been identified. Here we identify insect host factors required for DENV-2 propagation, by carrying out a genome-wide RNA interference screen in Drosophila melanogaster cells using a well-established 22,632 double-stranded RNA library. This screen identified 116 candidate dengue virus host factors (DVHFs). Although some were previously associated with flaviviruses (for example, V-ATPases and alpha-glucosidases), most of the DVHFs were newly implicated in dengue virus propagation. The dipteran DVHFs had 82 readily recognizable human homologues and, using a targeted short-interfering-RNA screen, we showed that 42 of these are human DVHFs. This indicates notable conservation of required factors between dipteran and human hosts. This work suggests new approaches to control infection in the insect vector and the mammalian host.

  10. Interaction between viral RNA silencing suppressors and host factors in plant immunity.

    Science.gov (United States)

    Nakahara, Kenji S; Masuta, Chikara

    2014-08-01

    To elucidate events in the molecular arms race between the host and pathogen in evaluating plant immunity, a zigzag model is useful for uncovering aspects common to different host-pathogen interactions. By analogy of the steps in virus-host interactions with the steps in the standard zigzag model outlined in recent papers, we may regard RNA silencing as pattern-triggered immunity (PTI) against viruses, RNA silencing suppressors (RSSs) as effectors to overcome host RNA silencing and resistance gene (R-gene)-mediated defense as effector-triggered immunity (ETI) recognizing RSSs as avirulence proteins. However, because the standard zigzag model does not fully apply to some unique aspects in the interactions between a plant host and virus, we here defined a model especially designed for viruses. Although we simplified the phenomena involved in the virus-host interactions in the model, certain specific interactive steps can be explained by integrating additional host factors into the model. These host factors are thought to play an important role in maintaining the efficacy of the various steps in the main pathway of defense against viruses in this model for virus-plant interactions. For example, we propose candidates that may interact with viral RSSs to induce the resistance response. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Studying Salmonellae and Yersiniae host-pathogen interactions using integrated 'omics and modeling.

    Science.gov (United States)

    Ansong, Charles; Deatherage, Brooke L; Hyduke, Daniel; Schmidt, Brian; McDermott, Jason E; Jones, Marcus B; Chauhan, Sadhana; Charusanti, Pep; Kim, Young-Mo; Nakayasu, Ernesto S; Li, Jie; Kidwai, Afshan; Niemann, George; Brown, Roslyn N; Metz, Thomas O; McAteer, Kathleen; Heffron, Fred; Peterson, Scott N; Motin, Vladimir; Palsson, Bernhard O; Smith, Richard D; Adkins, Joshua N

    2013-01-01

    Salmonella and Yersinia are two distantly related genera containing species with wide host-range specificity and pathogenic capacity. The metabolic complexity of these organisms facilitates robust lifestyles both outside of and within animal hosts. Using a pathogen-centric systems biology approach, we are combining a multi-omics (transcriptomics, proteomics, metabolomics) strategy to define properties of these pathogens under a variety of conditions including those that mimic the environments encountered during pathogenesis. These high-dimensional omics datasets are being integrated in selected ways to improve genome annotations, discover novel virulence-related factors, and model growth under infectious states. We will review the evolving technological approaches toward understanding complex microbial life through multi-omic measurements and integration, while highlighting some of our most recent successes in this area.

  12. Host Cell Factors as Antiviral Targets in Arenavirus Infection

    Directory of Open Access Journals (Sweden)

    Elsa B. Damonte

    2012-09-01

    Full Text Available Among the members of the Arenaviridae family, Lassa virus and Junin virus generate periodic annual outbreaks of severe human hemorrhagic fever (HF in endemic areas of West Africa and Argentina, respectively. Given the human health threat that arenaviruses represent and the lack of a specific and safe chemotherapy, the search for effective antiviral compounds is a continuous demanding effort. Since diverse host cell pathways and enzymes are used by RNA viruses to fulfill their replicative cycle, the targeting of a host process has turned an attractive antiviral approach in the last years for many unrelated virus types. This strategy has the additional benefit to reduce the serious challenge for therapy of RNA viruses to escape from drug effects through selection of resistant variants triggered by their high mutation rate. This article focuses on novel strategies to identify inhibitors for arenavirus therapy, analyzing the potential for antiviral developments of diverse host factors essential for virus infection.

  13. Host cell factors as antiviral targets in arenavirus infection.

    Science.gov (United States)

    Linero, Florencia N; Sepúlveda, Claudia S; Giovannoni, Federico; Castilla, Viviana; García, Cybele C; Scolaro, Luis A; Damonte, Elsa B

    2012-09-01

    Among the members of the Arenaviridae family, Lassa virus and Junin virus generate periodic annual outbreaks of severe human hemorrhagic fever (HF) in endemic areas of West Africa and Argentina, respectively. Given the human health threat that arenaviruses represent and the lack of a specific and safe chemotherapy, the search for effective antiviral compounds is a continuous demanding effort. Since diverse host cell pathways and enzymes are used by RNA viruses to fulfill their replicative cycle, the targeting of a host process has turned an attractive antiviral approach in the last years for many unrelated virus types. This strategy has the additional benefit to reduce the serious challenge for therapy of RNA viruses to escape from drug effects through selection of resistant variants triggered by their high mutation rate. This article focuses on novel strategies to identify inhibitors for arenavirus therapy, analyzing the potential for antiviral developments of diverse host factors essential for virus infection.

  14. Host and Viral Factors in HIV-Mediated Bystander Apoptosis

    Science.gov (United States)

    Garg, Himanshu; Joshi, Anjali

    2017-01-01

    Human immunodeficiency virus (HIV) infections lead to a progressive loss of CD4 T cells primarily via the process of apoptosis. With a limited number of infected cells and vastly disproportionate apoptosis in HIV infected patients, it is believed that apoptosis of uninfected bystander cells plays a significant role in this process. Disease progression in HIV infected individuals is highly variable suggesting that both host and viral factors may influence HIV mediated apoptosis. Amongst the viral factors, the role of Envelope (Env) glycoprotein in bystander apoptosis is well documented. Recent evidence on the variability in apoptosis induction by primary patient derived Envs underscores the role of Env glycoprotein in HIV disease. Amongst the host factors, the role of C-C Chemokine Receptor type 5 (CCR5), a coreceptor for HIV Env, is also becoming increasingly evident. Polymorphisms in the CCR5 gene and promoter affect CCR5 cell surface expression and correlate with both apoptosis and CD4 loss. Finally, chronic immune activation in HIV infections induces multiple defects in the immune system and has recently been shown to accelerate HIV Env mediated CD4 apoptosis. Consequently, those factors that affect CCR5 expression and/or immune activation in turn indirectly regulate HIV mediated apoptosis making this phenomenon both complex and multifactorial. This review explores the complex role of various host and viral factors in determining HIV mediated bystander apoptosis. PMID:28829402

  15. Susceptibility to Phytophthora ramorum in a key infectious host: landscape variation in host genotype, host phenotype, and environmental factors.

    Science.gov (United States)

    Anacker, Brian L; Rank, Nathan E; Hüberli, Daniel; Garbelotto, Matteo; Gordon, Sarah; Harnik, Tami; Whitkus, Richard; Meentemeyer, Ross

    2008-01-01

    Sudden oak death is an emerging forest disease caused by the invasive pathogen Phytophthora ramorum. Genetic and environmental factors affecting susceptibility to P. ramorum in the key inoculum-producing host tree Umbellularia californica (bay laurel) were examined across a heterogeneous landscape in California, USA. Laboratory susceptibility trials were conducted on detached leaves and assessed field disease levels for 97 host trees from 12 225-m(2) plots. Genotype and phenotype characteristics were assessed for each tree. Effects of plot-level environmental conditions (understory microclimate, amount of solar radiation and topographic moisture potential) on disease expression were also evaluated. Susceptibility varied significantly among U. californica trees, with a fivefold difference in leaf lesion size. Lesion size was positively related to leaf area, but not to other phenotypic traits or to field disease level. Genetic diversity was structured at three spatial scales, but primarily among individuals within plots. Lesion size was significantly related to amplified fragment length polymorphism (AFLP) markers, but local environment explained most variation in field disease level. Thus, substantial genetic variation in susceptibility to P. ramorum occurs in its principal foliar host U. californica, but local environment mediates expression of susceptibility in nature.

  16. Herpesvirus telomeric repeats facilitate genomic integration into host telomeres and mobilization of viral DNA during reactivation.

    Science.gov (United States)

    Kaufer, Benedikt B; Jarosinski, Keith W; Osterrieder, Nikolaus

    2011-03-14

    Some herpesviruses, particularly lymphotropic viruses such as Marek's disease virus (MDV) and human herpesvirus 6 (HHV-6), integrate their DNA into host chromosomes. MDV and HHV-6, among other herpesviruses, harbor telomeric repeats (TMRs) identical to host telomeres at either end of their linear genomes. Using MDV as a natural virus-host model, we show that herpesvirus TMRs facilitate viral genome integration into host telomeres and that integration is important for establishment of latency and lymphoma formation. Integration into host telomeres also aids in reactivation from the quiescent state of infection. Our results and the presence of TMRs in many herpesviruses suggest that integration mediated by viral TMRs is a conserved mechanism, which ensures faithful virus genome maintenance in host cells during cell division and allows efficient mobilization of dormant viral genomes. This finding is of particular importance as reactivation is critical for virus spread between susceptible individuals and is necessary for continued herpesvirus evolution and survival.

  17. The Host Specificities of Baculovirus per os Infectivity Factors.

    Directory of Open Access Journals (Sweden)

    Jingjiao Song

    Full Text Available Baculoviruses are insect-specific pathogens with a generally narrow host ranges. Successful primary infection is initiated by the proper interaction of at least 8 conserved per os infectivity factors (PIFs with the host's midgut cells, a process that remains largely a mystery. In this study, we investigated the host specificities of the four core components of the PIF complex, P74, PIF1, PIF2 and PIF3 by using Helicoverpa armigera nucleopolyhedrovirus (HearNPV backbone. The four pifs of HearNPV were replaced by their counterparts from a group I Autographa californica multiple nucleopolyhedrovirus (AcMNPV or a group II Spodoptera litura nucleopolyhedrovirus (SpltNPV. Transfection and infection assays showed that all the recombinant viruses were able to produce infectious budded viruses (BVs and were lethal to H. armigera larvae via intrahaemocoelic injection. However, feeding experiments using very high concentration of occlusion bodies demonstrated that all the recombinant viruses completely lost oral infectivity except SpltNPV pif3 substituted pif3-null HearNPV (vHaBacΔpif3-Sppif3-ph. Furthermore, bioassay result showed that the median lethal concentration (LC50 value of vHaBacΔpif3-Sppif3-ph was 23-fold higher than that of the control virus vHaBacΔpif3-Hapif3-ph, indicating that SpltNPV pif3 can only partially substitute the function of HearNPV pif3. These results suggested that most of PIFs tested have strict host specificities, which may account, at least in part, for the limited host ranges of baculoviruses.

  18. Complement factor H in host defense and immune evasion.

    Science.gov (United States)

    Parente, Raffaella; Clark, Simon J; Inforzato, Antonio; Day, Anthony J

    2017-05-01

    Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer.

  19. Host genetics and environmental factors regulate ecological succession of the mouse colon tissue-associated microbiota.

    Directory of Open Access Journals (Sweden)

    Philip Smith

    Full Text Available BACKGROUND: The integration of host genetics, environmental triggers and the microbiota is a recognised factor in the pathogenesis of barrier function diseases such as IBD. In order to determine how these factors interact to regulate the host immune response and ecological succession of the colon tissue-associated microbiota, we investigated the temporal interaction between the microbiota and the host following disruption of the colonic epithelial barrier. METHODOLOGY/PRINCIPAL FINDINGS: Oral administration of DSS was applied as a mechanistic model of environmental damage of the colon and the resulting inflammation characterized for various parameters over time in WT and Nod2 KO mice. RESULTS: In WT mice, DSS damage exposed the host to the commensal flora and led to a migration of the tissue-associated bacteria from the epithelium to mucosal and submucosal layers correlating with changes in proinflammatory cytokine profiles and a progressive transition from acute to chronic inflammation of the colon. Tissue-associated bacteria levels peaked at day 21 post-DSS and declined thereafter, correlating with recruitment of innate immune cells and development of the adaptive immune response. Histological parameters, immune cell infiltration and cytokine biomarkers of inflammation were indistinguishable between Nod2 and WT littermates following DSS, however, Nod2 KO mice demonstrated significantly higher tissue-associated bacterial levels in the colon. DSS damage and Nod2 genotype independently regulated the community structure of the colon microbiota. CONCLUSIONS/SIGNIFICANCE: The results of these experiments demonstrate the integration of environmental and genetic factors in the ecological succession of the commensal flora in mammalian tissue. The association of Nod2 genotype (and other host polymorphisms and environmental factors likely combine to influence the ecological succession of the tissue-associated microflora accounting in part for their

  20. Microfluidic large scale integration of viral-host interaction analysis.

    Science.gov (United States)

    Ben-Ari, Ya'ara; Glick, Yair; Kipper, Sarit; Schwartz, Nika; Avrahami, Dorit; Barbiro-Michaely, Efrat; Gerber, Doron

    2013-06-21

    Viral-host interactions represent potential drug targets for novel antiviral strategies (Flisiak et al., Hepatology, 2008, 47, 817-26). Hence, it is important to establish an adequate platform for identifying and analyzing such interactions. In this review, we discuss bottlenecks in conventional protein-protein interaction methodologies and present the contribution of innovative microfluidic-based technologies towards a solution to these problems with respect to viral-host proteomics.

  1. BiologicalNetworks - tools enabling the integration of multi-scale data for the host-pathogen studies

    Directory of Open Access Journals (Sweden)

    Ponomarenko Julia

    2011-01-01

    Full Text Available Abstract Background Understanding of immune response mechanisms of pathogen-infected host requires multi-scale analysis of genome-wide data. Data integration methods have proved useful to the study of biological processes in model organisms, but their systematic application to the study of host immune system response to a pathogen and human disease is still in the initial stage. Results To study host-pathogen interaction on the systems biology level, an extension to the previously described BiologicalNetworks system is proposed. The developed methods and data integration and querying tools allow simplifying and streamlining the process of integration of diverse experimental data types, including molecular interactions and phylogenetic classifications, genomic sequences and protein structure information, gene expression and virulence data for pathogen-related studies. The data can be integrated from the databases and user's files for both public and private use. Conclusions The developed system can be used for the systems-level analysis of host-pathogen interactions, including host molecular pathways that are induced/repressed during the infections, co-expressed genes, and conserved transcription factor binding sites. Previously unknown to be associated with the influenza infection genes were identified and suggested for further investigation as potential drug targets. Developed methods and data are available through the Java application (from BiologicalNetworks program at http://www.biologicalnetworks.org and web interface (at http://flu.sdsc.edu.

  2. An integrating factor matrix method to find first integrals

    Energy Technology Data Exchange (ETDEWEB)

    Saputra, K V I [Faculty of Science and Mathematics, University Pelita Harapan, Jl. MH Thamrin Boulevard, Tangerang Banten, 15811 (Indonesia); Quispel, G R W [Department of Mathematics and Statistical Science, La Trobe University, Bundoora 3086 (Australia); Van Veen, L, E-mail: kie.saputra@staff.uph.ed [Faculty of Science, University of Ontario Institute of Technology, 2000 Simcoe St N., Oshawa, Ontario, L1H 7K4 (Canada)

    2010-06-04

    In this paper we develop an integrating factor matrix method to derive conditions for the existence of first integrals. We use this novel method to obtain first integrals, along with the conditions for their existence, for two- and three-dimensional Lotka-Volterra systems with constant terms. The results are compared to previous results obtained by other methods.

  3. An integrating factor matrix method to find first integrals

    CERN Document Server

    Saputra, K V I; van Veen, L

    2010-01-01

    In this paper we developed an integrating factor matrix method to derive conditions for the existence of first integrals. We use this novel method to obtain first integrals, along with the conditions for their existence, for two and three dimensional Lotka-Volterra systems with constant terms. The results are compared to previous results obtained by other methods.

  4. A computational tool integrating host immunity with antibiotic dynamics to study tuberculosis treatment.

    Science.gov (United States)

    Pienaar, Elsje; Cilfone, Nicholas A; Lin, Philana Ling; Dartois, Véronique; Mattila, Joshua T; Butler, J Russell; Flynn, JoAnne L; Kirschner, Denise E; Linderman, Jennifer J

    2015-02-21

    While active tuberculosis (TB) is a treatable disease, many complex factors prevent its global elimination. Part of the difficulty in developing optimal therapies is the large design space of antibiotic doses, regimens and combinations. Computational models that capture the spatial and temporal dynamics of antibiotics at the site of infection can aid in reducing the design space of costly and time-consuming animal pre-clinical and human clinical trials. The site of infection in TB is the granuloma, a collection of immune cells and bacteria that form in the lung, and new data suggest that penetration of drugs throughout granulomas is problematic. Here we integrate our computational model of granuloma formation and function with models for plasma pharmacokinetics, lung tissue pharmacokinetics and pharmacodynamics for two first line anti-TB antibiotics. The integrated model is calibrated to animal data. We make four predictions. First, antibiotics are frequently below effective concentrations inside granulomas, leading to bacterial growth between doses and contributing to the long treatment periods required for TB. Second, antibiotic concentration gradients form within granulomas, with lower concentrations toward their centers. Third, during antibiotic treatment, bacterial subpopulations are similar for INH and RIF treatment: mostly intracellular with extracellular bacteria located in areas non-permissive for replication (hypoxic areas), presenting a slowly increasing target population over time. Finally, we find that on an individual granuloma basis, pre-treatment infection severity (including bacterial burden, host cell activation and host cell death) is predictive of treatment outcome.

  5. Integrated Detection of Pathogens and Host Biomarkers for Wounds

    Energy Technology Data Exchange (ETDEWEB)

    Jaing, C

    2012-03-19

    The increasing incidence and complications arising from combat wounds has necessitated a reassessment of methods for effective treatment. Infection, excessive inflammation, and incidence of drug-resistant organisms all contribute toward negative outcomes for afflicted individuals. The organisms and host processes involved in wound progression, however, are incompletely understood. We therefore set out, using our unique technical resources, to construct a profile of combat wounds which did or did not successfully resolve. We employed the Lawrence Livermore Microbial Detection Array and identified a number of nosocomial pathogens present in wound samples. Some of these identities corresponded with bacterial isolates previously cultured, while others were not obtained via standard microbiology. Further, we optimized proteomics protocols for the identification of host biomarkers indicative of various stages in wound progression. In combination with our pathogen data, our biomarker discovery efforts will provide a profile corresponding to wound complications, and will assist significantly in treatment of these complex cases.

  6. Piecemeal versus precipitous factor market integration

    NARCIS (Netherlands)

    H. Dellas (Harris); C.G. de Vries (Casper)

    1995-01-01

    textabstractStudies the effects of speed of international factor markets integration within a general equilibrium, two country model. Variant of Diamond's overlapping generations model; Effects of an international factor market liberalization; Determination of the amount of capital needed to

  7. Development of an Integrated Human Factors Toolkit

    Science.gov (United States)

    Resnick, Marc L.

    2003-01-01

    An effective integration of human abilities and limitations is crucial to the success of all NASA missions. The Integrated Human Factors Toolkit facilitates this integration by assisting system designers and analysts to select the human factors tools that are most appropriate for the needs of each project. The HF Toolkit contains information about a broad variety of human factors tools addressing human requirements in the physical, information processing and human reliability domains. Analysis of each tool includes consideration of the most appropriate design stage, the amount of expertise in human factors that is required, the amount of experience with the tool and the target job tasks that are needed, and other factors that are critical for successful use of the tool. The benefits of the Toolkit include improved safety, reliability and effectiveness of NASA systems throughout the agency. This report outlines the initial stages of development for the Integrated Human Factors Toolkit.

  8. Integrative Functional Genomics of Hepatitis C Virus Infection Identifies Host Dependencies in Complete Viral Replication Cycle

    OpenAIRE

    Qisheng Li; Yong-Yuan Zhang; Stephan Chiu; Zongyi Hu; Keng-Hsin Lan; Helen Cha; Catherine Sodroski; Fang Zhang; Ching-Sheng Hsu; Emmanuel Thomas; T Jake Liang

    2014-01-01

    Recent functional genomics studies including genome-wide small interfering RNA (siRNA) screens demonstrated that hepatitis C virus (HCV) exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies unc...

  9. Cancer immunology--analysis of host and tumor factors for personalized medicine.

    Science.gov (United States)

    Ogino, Shuji; Galon, Jérôme; Fuchs, Charles S; Dranoff, Glenn

    2011-08-09

    Immune cells in the tumor microenvironment have an important role in regulating tumor progression. Therefore, stimulating immune reactions to tumors can be an attractive therapeutic and prevention strategy. Cancer cells and host cells constantly interact with each other in the tumor microenvironment; thus, cancer immunology is an interdisciplinary area where integrated analysis of both host and tumor factors is needed. Cancer represents a heterogeneous group of diseases with different genetic and epigenetic alterations; therefore, molecular classification of cancer (for example lung, prostate and breast cancers) is an important component in clinical decision making. However, most studies on antitumor immunity and clinical outcome lack analysis of tumor molecular biomarkers. In this Review, we discuss colorectal cancer as a prototypical example of cancer. Common molecular classifiers of colon cancer include KRAS, BRAF and PIK3CA mutations, microsatellite instability, LINE-1 methylation, and CpG island methylator phenotype. Since tumor molecular features and immune reactions are inter-related, a comprehensive assessment of these factors is critical. Examining the effects of tumor-host interactions on clinical outcome and prognosis represents an evolving interdisciplinary field of molecular pathological epidemiology. Pathological immunity evaluation may provide information on prognosis and help identify patients who are more likely to benefit from immunotherapy.

  10. Fundamental factors determining the nature of parasite aggregation in hosts.

    Directory of Open Access Journals (Sweden)

    Sébastien Gourbière

    Full Text Available The distribution of parasites in hosts is typically aggregated: a few hosts harbour many parasites, while the remainder of hosts are virtually parasite free. The origin of this almost universal pattern is central to our understanding of host-parasite interactions; it affects many facets of their ecology and evolution. Despite this, the standard statistical framework used to characterize parasite aggregation does not describe the processes generating such a pattern. In this work, we have developed a mathematical framework for the distribution of parasites in hosts, starting from a simple statistical description in terms of two fundamental processes: the exposure of hosts to parasites and the infection success of parasites. This description allows the level of aggregation of parasites in hosts to be related to the random variation in these two processes and to true host heterogeneity. We show that random variation can generate an aggregated distribution and that the common view, that encounters and success are two equivalent filters, applies to the average parasite burden under neutral assumptions but it does not apply to the variance of the parasite burden, and it is not true when heterogeneity between hosts is incorporated in the model. We find that aggregation decreases linearly with the number of encounters, but it depends non-linearly on parasite success. We also find additional terms in the variance of the parasite burden which contribute to the actual level of aggregation in specific biological systems. We have derived the formal expressions of these contributions, and these provide new opportunities to analyse empirical data and tackle the complexity of the origin of aggregation in various host-parasite associations.

  11. The chemical basis of host nest detection and chemical integration in a cuckoo paper wasp.

    Science.gov (United States)

    Cini, Alessandro; Bruschini, Claudia; Signorotti, Lisa; Pontieri, Luigi; Turillazzi, Stefano; Cervo, Rita

    2011-11-01

    Insect social life is governed by chemicals. A great number of studies have demonstrated that the blend of hydrocarbons present on the cuticle (CHCs) plays a pivotal role in intra- and inter-specific communication. It is not surprising, therefore, that social parasites, specialized in exploiting the costly parental care provided by host workers, exploit the host chemical communication system too. Throughout their life cycle, social parasites intercept and break this CHC-based code. Recently, however, several polar compounds (mainly peptides) have been found in addition to CHCs both on the cuticle and on the comb surface of social insects, and their semiochemical role has been demonstrated in some circumstances. In the present study, we used the paper wasp social parasite-host system Polistes sulcifer (Zimmerman)-Polistes dominulus (Christ) to evaluate the relative importance of the CHCs and polar compounds in two different steps of the host exploitation process: host nest detection by the pre-usurping parasite and parasite chemical integration into the host colony. After separating the polar and apolar fractions of the host nest as well as those of pre- and post-usurpation parasites, we carried out laboratory assays based on the binary choice model. Our results show that nest polar compounds neither are used by the parasite to detect the host's nest nor play a role in parasite chemical integration into the host colony. In contrast, we demonstrate that CHCs are fundamental in both steps, thus confirming their primary role in social insect life and consequently in social parasite-host interactions.

  12. Multiple attractors of host-parasitoid models with integrated pest management strategies: eradication, persistence and outbreak.

    Science.gov (United States)

    Tang, Sanyi; Xiao, Yanni; Cheke, Robert A

    2008-03-01

    Host-parasitoid models including integrated pest management (IPM) interventions with impulsive effects at both fixed and unfixed times were analyzed with regard to host-eradication, host-parasitoid persistence and host-outbreak solutions. The host-eradication periodic solution with fixed moments is globally stable if the host's intrinsic growth rate is less than the summation of the mean host-killing rate and the mean parasitization rate during the impulsive period. Solutions for all three categories can coexist, with switch-like transitions among their attractors showing that varying dosages and frequencies of insecticide applications and the numbers of parasitoids released are crucial. Periodic solutions also exist for models with unfixed moments for which the maximum amplitude of the host is less than the economic threshold. The dosages and frequencies of IPM interventions for these solutions are much reduced in comparison with the pest-eradication periodic solution. Our results, which are robust to inclusion of stochastic effects and with a wide range of parameter values, confirm that IPM is more effective than any single control tactic.

  13. The herbaceous landlord: integrating the effects of symbiont consortia within a single host.

    Science.gov (United States)

    Vandegrift, Roo; Roy, Bitty A; Pfeifer-Meister, Laurel; Johnson, Bart R; Bridgham, Scott D

    2015-01-01

    Plants are typically infected by a consortium of internal fungal associates, including endophytes in their leaves, as well as arbuscular mycorrhizal fungi (AMF) and dark septate endophytes (DSE) in their roots. It is logical that these organisms will interact with each other and the abiotic environment in addition to their host, but there has been little work to date examining the interactions of multiple symbionts within single plant hosts, or how the relationships among symbionts and their host change across environmental conditions. We examined the grass Agrostis capillaris in the context of a climate manipulation experiment in prairies in the Pacific Northwest, USA. Each plant was tested for presence of foliar endophytes in the genus Epichloë, and we measured percent root length colonized (PRLC) by AMF and DSE. We hypothesized that the symbionts in our system would be in competition for host resources, that the outcome of that competition could be driven by the benefit to the host, and that the host plants would be able to allocate carbon to the symbionts in such a way as to maximize fitness benefit within a particular environmental context. We found a correlation between DSE and AMF PRLC across climatic conditions; we also found a fitness cost to increasing DSE colonization, which was negated by presence of Epichloë endophytes. These results suggest that selective pressure on the host is likely to favor host/symbiont relationships that structure the community of symbionts in the most beneficial way possible for the host, not necessarily favoring the individual symbiont that is most beneficial to the host in isolation. These results highlight the need for a more integrative, systems approach to the study of host/symbiont consortia.

  14. The herbaceous landlord: integrating the effects of symbiont consortia within a single host

    Directory of Open Access Journals (Sweden)

    Roo Vandegrift

    2015-11-01

    Full Text Available Plants are typically infected by a consortium of internal fungal associates, including endophytes in their leaves, as well as arbuscular mycorrhizal fungi (AMF and dark septate endophytes (DSE in their roots. It is logical that these organisms will interact with each other and the abiotic environment in addition to their host, but there has been little work to date examining the interactions of multiple symbionts within single plant hosts, or how the relationships among symbionts and their host change across environmental conditions. We examined the grass Agrostis capillaris in the context of a climate manipulation experiment in prairies in the Pacific Northwest, USA. Each plant was tested for presence of foliar endophytes in the genus Epichloë, and we measured percent root length colonized (PRLC by AMF and DSE. We hypothesized that the symbionts in our system would be in competition for host resources, that the outcome of that competition could be driven by the benefit to the host, and that the host plants would be able to allocate carbon to the symbionts in such a way as to maximize fitness benefit within a particular environmental context. We found a correlation between DSE and AMF PRLC across climatic conditions; we also found a fitness cost to increasing DSE colonization, which was negated by presence of Epichloë endophytes. These results suggest that selective pressure on the host is likely to favor host/symbiont relationships that structure the community of symbionts in the most beneficial way possible for the host, not necessarily favoring the individual symbiont that is most beneficial to the host in isolation. These results highlight the need for a more integrative, systems approach to the study of host/symbiont consortia.

  15. Emerging functions as host cell factors - an encyclopedia of annexin-pathogen interactions.

    Science.gov (United States)

    Kuehnl, Alexander; Musiol, Agnes; Raabe, Carsten A; Rescher, Ursula

    2016-10-01

    Emerging infectious diseases and drug-resistant infectious agents call for the development of innovative antimicrobial strategies. With pathogenicity now considered to arise from the complex and bi-directional interplay between a microbe and the host, host cell factor targeting has emerged as a promising approach that might overcome the limitations of classical antimicrobial drug development and could open up novel and efficient therapeutic strategies. Interaction with and modulation of host cell membranes is a recurrent theme in the host-microbe relationship. In this review, we provide an overview of what is currently known about the role of the Ca2+ dependent, membrane-binding annexin protein family in pathogen-host interactions, and discuss their emerging functions as host cell derived auxiliary proteins in microbe-host interactions and host cell targets.

  16. DMPD: Macrophage migration inhibitory factor and host innate immune responses tomicrobes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14620137 Macrophage migration inhibitory factor and host innate immune responses to...microbes. Calandra T. Scand J Infect Dis. 2003;35(9):573-6. (.png) (.svg) (.html) (.csml) Show Macrophage migration... inhibitory factor and host innate immune responses tomicrobes. PubmedID 14620137 Title Macrophage migration

  17. Marek’s disease herpesvirus vaccines integrate into chicken host chromosomes yet lack a virus-host phenotype associated with oncogenic transformation

    Science.gov (United States)

    Marek's disease (MD) is a lymphotrophic and oncogenic disease of chickens that can lead to death in susceptible and unimmunized host birds. The causative pathogen, Marek's disease virus (MDV), a highly oncogenic alphaherpesvirus, integrates into host genome near the telomeres during viral latency an...

  18. Determining host metabolic limitations on viral replication via integrated modeling and experimental perturbation.

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    Elsa W Birch

    Full Text Available Viral replication relies on host metabolic machinery and precursors to produce large numbers of progeny - often very rapidly. A fundamental example is the infection of Escherichia coli by bacteriophage T7. The resource draw imposed by viral replication represents a significant and complex perturbation to the extensive and interconnected network of host metabolic pathways. To better understand this system, we have integrated a set of structured ordinary differential equations quantifying T7 replication and an E. coli flux balance analysis metabolic model. Further, we present here an integrated simulation algorithm enforcing mutual constraint by the models across the entire duration of phage replication. This method enables quantitative dynamic prediction of virion production given only specification of host nutritional environment, and predictions compare favorably to experimental measurements of phage replication in multiple environments. The level of detail of our computational predictions facilitates exploration of the dynamic changes in host metabolic fluxes that result from viral resource consumption, as well as analysis of the limiting processes dictating maximum viral progeny production. For example, although it is commonly assumed that viral infection dynamics are predominantly limited by the amount of protein synthesis machinery in the host, our results suggest that in many cases metabolic limitation is at least as strict. Taken together, these results emphasize the importance of considering viral infections in the context of host metabolism.

  19. Integrating refugee and host health services in West Nile districts, Uganda.

    Science.gov (United States)

    Orach, Christopher Garimoi; De Brouwere, Vincent

    2006-01-01

    Refugees are a common feature in Africa and Uganda is no exception. However, Uganda does not have the resources to provide health care to all its own citizens, let alone to refugees. Refugee health services are therefore usually set up and provided separately by international organizations such as the United Nations High Commissioner for Refugees (UNHCR). However, such services often end up being the only available or reliable services in a particular location for both host and refugee populations. Yet the host populations are often denied access to these services because, in theory, other services are being provided by their government. The case study in the West Nile region of Uganda describes how host and refugee services were integrated in an attempt to address the concerns of inequity of access to care for host populations, when reasonably good health services were available to nearby refugee populations. The paper identifies and discusses the challenges encountered and those remaining.

  20. Structural basis for antagonizing a host restriction factor by C7 family of poxvirus host-range proteins.

    Science.gov (United States)

    Meng, Xiangzhi; Krumm, Brian; Li, Yongchao; Deng, Junpeng; Xiang, Yan

    2015-12-01

    Human sterile alpha motif domain-containing 9 (SAMD9) protein is a host restriction factor for poxviruses, but it can be overcome by some poxvirus host-range proteins that share homology with vaccinia virus C7 protein. To understand the mechanism of action for this important family of host-range factors, we determined the crystal structures of C7 and myxoma virus M64, a C7 family member that is unable to antagonize SAMD9. Despite their different functions and only 23% sequence identity, the two proteins have very similar overall structures, displaying a previously unidentified fold comprised of a compact 12-stranded antiparallel β-sandwich wrapped in two short α helices. Extensive structure-guided mutagenesis of C7 identified three loops clustered on one edge of the β sandwich as critical for viral replication and binding with SAMD9. The loops are characterized with functionally important negatively charged, positively charged, and hydrophobic residues, respectively, together forming a unique "three-fingered molecular claw." The key residues of the claw are not conserved in two C7 family members that do not antagonize SAMD9 but are conserved in distantly related C7 family members from four poxvirus genera that infect diverse mammalian species. Indeed, we found that all in the latter group of proteins bind SAMD9. Taken together, our data indicate that diverse mammalian poxviruses use a conserved molecular claw in a C7-like protein to target SAMD9 and overcome host restriction.

  1. Viral Carcinogenesis: Factors Inducing DNA Damage and Virus Integration

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    Yan Chen

    2014-10-01

    Full Text Available Viruses are the causative agents of 10%–15% of human cancers worldwide. The most common outcome for virus-induced reprogramming is genomic instability, including accumulation of mutations, aberrations and DNA damage. Although each virus has its own specific mechanism for promoting carcinogenesis, the majority of DNA oncogenic viruses encode oncogenes that transform infected cells, frequently by targeting p53 and pRB. In addition, integration of viral DNA into the human genome can also play an important role in promoting tumor development for several viruses, including HBV and HPV. Because viral integration requires the breakage of both the viral and the host DNA, the integration rate is believed to be linked to the levels of DNA damage. DNA damage can be caused by both endogenous and exogenous factors, including inflammation induced by either the virus itself or by co-infections with other agents, environmental agents and other factors. Typically, cancer develops years to decades following the initial infection. A better understanding of virus-mediated carcinogenesis, the networking of pathways involved in transformation and the relevant risk factors, particularly in those cases where tumorigenesis proceeds by way of virus integration, will help to suggest prophylactic and therapeutic strategies to reduce the risk of virus-mediated cancer.

  2. Towards an Integrative Understanding of Diet-Host-Gut Microbiome Interactions.

    Science.gov (United States)

    Read, Mark N; Holmes, Andrew J

    2017-01-01

    Over the last 20 years, a sizeable body of research has linked the microbiome and host diet to a remarkable diversity of diseases. Yet, unifying principles of microbiome assembly or function, at levels required to rationally manipulate a specific individual's microbiome to their benefit, have not emerged. A key driver of both community composition and activity is the host diet, but diet-microbiome interactions cannot be characterized without consideration of host-diet interactions such as appetite and digestion. This becomes even more complex if health outcomes are to be explored, as microbes engage in multiple interactions and feedback pathways with the host. Here, we review these interactions and set forth the need to build conceptual models of the diet-microbiome-host axes that draw out the key principles governing this system's dynamics. We highlight how "units of response," characterizations of similarly behaving microbes, do not correlate consistently with microbial sequence relatedness, raising a challenge for relating high-throughput data sets to conceptual models. Furthermore, they are question-specific; responses to resource environment may be captured at higher taxonomic levels, but capturing microbial products that depend on networks of different interacting populations, such as short-chain fatty acid production through anaerobic fermentation, can require consideration of the entire community. We posit that integrative approaches to teasing apart diet-microbe-host interactions will help bridge between experimental data sets and conceptual models and will be of value in formulating predictive models.

  3. Virus and host factors affecting the clinical outcome of Bluetongue Virus infection

    NARCIS (Netherlands)

    Caporale, M.; Gialleonorado, L.; Janowicz, A.; Wilkie, G.; Shaw, A.; Savini, G.; Rijn, van P.A.; Mertens, P.; Ventura, M.; Palmarini, M.

    2014-01-01

    Bluetongue is a major infectious disease of ruminants caused by bluetongue virus (BTV), an arbovirus transmitted by Culicoides. Here, we assessed virus and host factors influencing the clinical outcome of BTV infection using a single experimental framework. We investigated how mammalian host species

  4. Targeting Host Factors to Treat West Nile and Dengue Viral Infections

    Directory of Open Access Journals (Sweden)

    Manoj N. Krishnan

    2014-02-01

    Full Text Available West Nile (WNV and Dengue (DENV viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

  5. The Golgi associated ERI3 is a Flavivirus host factor

    Science.gov (United States)

    Ward, Alex Michael; Calvert, Meredith E. K.; Read, Leah R.; Kang, Seokyoung; Levitt, Brandt E.; Dimopoulos, George; Bradrick, Shelton S.; Gunaratne, Jayantha; Garcia-Blanco, Mariano A.

    2016-01-01

    Dengue virus (DENV) is a mosquito-borne Flavivirus classified into four serotypes (DENV-1-4) that causes Dengue fever (DF), Dengue hemorrhagic Fever (DHF) or Dengue shock syndrome (DSS). An estimated 390 million people are at risk for infection with DENV and there are no effective vaccines or therapeutics. We utilized RNA chromatography coupled with quantitative mass spectrometry (qMS) to identify host RNA binding proteins (RBPs) that interact with DENV-2 RNA. We identified ERI3 (also PRNPIP and PINT1), a putative 3′–5′ RNA exonuclease, which preferentially associates with DENV-2 genomic RNA via interactions with dumbbell structures in the 3′ UTR. ERI3 is required for accumulation of DENV-2 genomic RNA and production of infectious particles. Furthermore, the mosquito homologue of ERI3 is required for DENV-2 replication in adult Aedes aegypti mosquitos implying that the requirement for ERI3 is conserved in both DENV hosts. In human cells ERI3 localizes to the Golgi in uninfected cells, but relocalizes near sites of DENV-2 replication in infected cells. ERI3 is not required for maintaining DENV-2 RNA stability or translation of the viral polyprotein, but is required for viral RNA synthesis. Our results define a specific role for ERI3 and highlight the importance of Golgi proteins in DENV-2 replication. PMID:27682269

  6. A Trematode Parasite Derived Growth Factor Binds and Exerts Influences on Host Immune Functions via Host Cytokine Receptor Complexes

    Science.gov (United States)

    Sulaiman, Azad A.; Zolnierczyk, Katarzyna; Japa, Ornampai; Owen, Jonathan P.; Maddison, Ben C.; Hodgkinson, Jane E.; Gough, Kevin C.

    2016-01-01

    The trematode Fasciola hepatica is responsible for chronic zoonotic infection globally. Despite causing a potent T-helper 2 response, it is believed that potent immunomodulation is responsible for rendering this host reactive non-protective host response thereby allowing the parasite to remain long-lived. We have previously identified a growth factor, FhTLM, belonging to the TGF superfamily can have developmental effects on the parasite. Herein we demonstrate that FhTLM can exert influence over host immune functions in a host receptor specific fashion. FhTLM can bind to receptor members of the Transforming Growth Factor (TGF) superfamily, with a greater affinity for TGF-β RII. Upon ligation FhTLM initiates the Smad2/3 pathway resulting in phenotypic changes in both fibroblasts and macrophages. The formation of fibroblast CFUs is reduced when cells are cultured with FhTLM, as a result of TGF-β RI kinase activity. In parallel the wound closure response of fibroblasts is also delayed in the presence of FhTLM. When stimulated with FhTLM blood monocyte derived macrophages adopt an alternative or regulatory phenotype. They express high levels interleukin (IL)-10 and arginase-1 while displaying low levels of IL-12 and nitric oxide. Moreover they also undergo significant upregulation of the inhibitory receptor PD-L1 and the mannose receptor. Use of RNAi demonstrates that this effect is dependent on TGF-β RII and mRNA knock-down leads to a loss of IL-10 and PD-L1. Finally, we demonstrate that FhTLM aids newly excysted juveniles (NEJs) in their evasion of antibody-dependent cell cytotoxicity (ADCC) by reducing the NO response of macrophages—again dependent on TGF-β RI kinase. FhTLM displays restricted expression to the F. hepatica gut resident NEJ stages. The altered fibroblast responses would suggest a role for dampened tissue repair responses in facilitating parasite migration. Furthermore, the adoption of a regulatory macrophage phenotype would allow for a reduced

  7. A Trematode Parasite Derived Growth Factor Binds and Exerts Influences on Host Immune Functions via Host Cytokine Receptor Complexes.

    Directory of Open Access Journals (Sweden)

    Azad A Sulaiman

    2016-11-01

    Full Text Available The trematode Fasciola hepatica is responsible for chronic zoonotic infection globally. Despite causing a potent T-helper 2 response, it is believed that potent immunomodulation is responsible for rendering this host reactive non-protective host response thereby allowing the parasite to remain long-lived. We have previously identified a growth factor, FhTLM, belonging to the TGF superfamily can have developmental effects on the parasite. Herein we demonstrate that FhTLM can exert influence over host immune functions in a host receptor specific fashion. FhTLM can bind to receptor members of the Transforming Growth Factor (TGF superfamily, with a greater affinity for TGF-β RII. Upon ligation FhTLM initiates the Smad2/3 pathway resulting in phenotypic changes in both fibroblasts and macrophages. The formation of fibroblast CFUs is reduced when cells are cultured with FhTLM, as a result of TGF-β RI kinase activity. In parallel the wound closure response of fibroblasts is also delayed in the presence of FhTLM. When stimulated with FhTLM blood monocyte derived macrophages adopt an alternative or regulatory phenotype. They express high levels interleukin (IL-10 and arginase-1 while displaying low levels of IL-12 and nitric oxide. Moreover they also undergo significant upregulation of the inhibitory receptor PD-L1 and the mannose receptor. Use of RNAi demonstrates that this effect is dependent on TGF-β RII and mRNA knock-down leads to a loss of IL-10 and PD-L1. Finally, we demonstrate that FhTLM aids newly excysted juveniles (NEJs in their evasion of antibody-dependent cell cytotoxicity (ADCC by reducing the NO response of macrophages-again dependent on TGF-β RI kinase. FhTLM displays restricted expression to the F. hepatica gut resident NEJ stages. The altered fibroblast responses would suggest a role for dampened tissue repair responses in facilitating parasite migration. Furthermore, the adoption of a regulatory macrophage phenotype would allow

  8. Virulence Factors and Strategies of Leptopilina spp.: Selective Responses in Drosophila Hosts

    Science.gov (United States)

    Lee, Mark J.; Kalamarz, Marta E.; Paddibhatla, Indira; Small, Chiyedza; Rajwani, Roma; Govind, Shubha

    2010-01-01

    To ensure survival, parasitic wasps of Drosophila have evolved strategies to optimize host development to their advantage. They also produce virulence factors that allow them to overcome or evade host defense. Wasp infection provokes cellular and humoral defense reactions, resulting in alteration in gene expression of the host. The activation of these reactions is controlled by conserved mechanisms shared by other invertebrate and vertebrate animals. Application of genomics and bioinformatics approaches is beginning to reveal comparative host gene expression changes after infection by different parasitic wasps. We analyze this comparison in the context of host physiology and immune cells, as well as the biology of the venom factors that wasps introduce into their hosts during oviposition. We compare virulence strategies of Leptopilina boulardi and L. heterotoma, in relation to genome-wide changes in gene expression in the fly hosts after infection. This analysis highlights fundamental differences in the changes that the host undergoes in its immune and general physiology in response to the two parasitic wasps. Such a comparative approach has the potential of revealing mechanisms governing the evolution of pathogenicity and how it impacts host range. PMID:19773069

  9. Yersinia virulence factors - a sophisticated arsenal for combating host defences.

    Science.gov (United States)

    Atkinson, Steve; Williams, Paul

    2016-01-01

    The human pathogens Yersinia pseudotuberculosis and Yersinia enterocolitica cause enterocolitis, while Yersinia pestis is responsible for pneumonic, bubonic, and septicaemic plague. All three share an infection strategy that relies on a virulence factor arsenal to enable them to enter, adhere to, and colonise the host while evading host defences to avoid untimely clearance. Their arsenal includes a number of adhesins that allow the invading pathogens to establish a foothold in the host and to adhere to specific tissues later during infection. When the host innate immune system has been activated, all three pathogens produce a structure analogous to a hypodermic needle. In conjunction with the translocon, which forms a pore in the host membrane, the channel that is formed enables the transfer of six 'effector' proteins into the host cell cytoplasm. These proteins mimic host cell proteins but are more efficient than their native counterparts at modifying the host cell cytoskeleton, triggering the host cell suicide response. Such a sophisticated arsenal ensures that yersiniae maintain the upper hand despite the best efforts of the host to counteract the infecting pathogen.

  10. Yersinia virulence factors - a sophisticated arsenal for combating host defences

    Science.gov (United States)

    Atkinson, Steve; Williams, Paul

    2016-01-01

    The human pathogens Yersinia pseudotuberculosis and Yersinia enterocolitica cause enterocolitis, while Yersinia pestis is responsible for pneumonic, bubonic, and septicaemic plague. All three share an infection strategy that relies on a virulence factor arsenal to enable them to enter, adhere to, and colonise the host while evading host defences to avoid untimely clearance. Their arsenal includes a number of adhesins that allow the invading pathogens to establish a foothold in the host and to adhere to specific tissues later during infection. When the host innate immune system has been activated, all three pathogens produce a structure analogous to a hypodermic needle. In conjunction with the translocon, which forms a pore in the host membrane, the channel that is formed enables the transfer of six ‘effector’ proteins into the host cell cytoplasm. These proteins mimic host cell proteins but are more efficient than their native counterparts at modifying the host cell cytoskeleton, triggering the host cell suicide response. Such a sophisticated arsenal ensures that yersiniae maintain the upper hand despite the best efforts of the host to counteract the infecting pathogen. PMID:27347390

  11. The integrative taxonomic approach reveals host specific species in an encyrtid parasitoid species complex.

    Directory of Open Access Journals (Sweden)

    Douglas Chesters

    Full Text Available Integrated taxonomy uses evidence from a number of different character types to delimit species and other natural groupings. While this approach has been advocated recently, and should be of particular utility in the case of diminutive insect parasitoids, there are relatively few examples of its application in these taxa. Here, we use an integrated framework to delimit independent lineages in Encyrtus sasakii (Hymenoptera: Chalcidoidea: Encyrtidae, a parasitoid morphospecies previously considered a host generalist. Sequence variation at the DNA barcode (cytochrome c oxidase I, COI and nuclear 28S rDNA loci were compared to morphometric recordings and mating compatibility tests, among samples of this species complex collected from its four scale insect hosts, covering a broad geographic range of northern and central China. Our results reveal that Encyrtus sasakii comprises three lineages that, while sharing a similar morphology, are highly divergent at the molecular level. At the barcode locus, the median K2P molecular distance between individuals from three primary populations was found to be 11.3%, well outside the divergence usually observed between Chalcidoidea conspecifics (0.5%. Corroborative evidence that the genetic lineages represent independent species was found from mating tests, where compatibility was observed only within populations, and morphometric analysis, which found that despite apparent morphological homogeneity, populations clustered according to forewing shape. The independent lineages defined by the integrated analysis correspond to the three scale insect hosts, suggesting the presence of host specific cryptic species. The finding of hidden host specificity in this species complex demonstrates the critical role that DNA barcoding will increasingly play in revealing hidden biodiversity in taxa that present difficulties for traditional taxonomic approaches.

  12. Host-derived, pore-forming toxin-like protein and trefoil factor complex protects the host against microbial infection.

    Science.gov (United States)

    Xiang, Yang; Yan, Chao; Guo, Xiaolong; Zhou, Kaifeng; Li, Sheng'an; Gao, Qian; Wang, Xuan; Zhao, Feng; Liu, Jie; Lee, Wen-Hui; Zhang, Yun

    2014-05-06

    Aerolysins are virulence factors belonging to the bacterial β-pore-forming toxin superfamily. Surprisingly, numerous aerolysin-like proteins exist in vertebrates, but their biological functions are unknown. βγ-CAT, a complex of an aerolysin-like protein subunit (two βγ-crystallin domains followed by an aerolysin pore-forming domain) and two trefoil factor subunits, has been identified in frogs (Bombina maxima) skin secretions. Here, we report the rich expression of this protein, in the frog blood and immune-related tissues, and the induction of its presence in peritoneal lavage by bacterial challenge. This phenomena raises the possibility of its involvement in antimicrobial infection. When βγ-CAT was administrated in a peritoneal infection model, it greatly accelerated bacterial clearance and increased the survival rate of both frogs and mice. Meanwhile, accelerated Interleukin-1β release and enhanced local leukocyte recruitments were determined, which may partially explain the robust and effective antimicrobial responses observed. The release of interleukin-1β was potently triggered by βγ-CAT from the frog peritoneal cells and murine macrophages in vitro. βγ-CAT was rapidly endocytosed and translocated to lysosomes, where it formed high molecular mass SDS-stable oligomers (>170 kDa). Lysosomal destabilization and cathepsin B release were detected, which may explain the activation of caspase-1 inflammasome and subsequent interleukin-1β maturation and release. To our knowledge, these results provide the first functional evidence of the ability of a host-derived aerolysin-like protein to counter microbial infection by eliciting rapid and effective host innate immune responses. The findings will also largely help to elucidate the possible involvement and action mechanisms of aerolysin-like proteins and/or trefoil factors widely existing in vertebrates in the host defense against pathogens.

  13. Wolbachia as an infectious extrinsic factor manipulating host signalling pathways

    Directory of Open Access Journals (Sweden)

    Ilaria eNegri

    2012-01-01

    Full Text Available Wolbachia pipientis is a widespread endosymbiont of filarial nematodes and arthropods. While in worms the symbiosis is obligate, in arthropods Wolbachia induces several reproductive manipulations (i.e. cytoplasmic incompatibility, parthenogenesis, feminization of genetic males and male-killing in order to increase the number of infected females. These various phenotypic effects may be linked to differences in host physiology, and in particular to endocrine-related processes governing growth, development and reproduction. Indeed, a number of evidences links Wolbachia symbiosis to insulin and ecdysteroid signalling, two multilayered pathways known to work antagonistically, jointly or even independently for the regulation of different molecular networks. At present it is not clear whether Wolbachia manipulates one pathway, thus affecting other related metabolic networks, or if it targets both pathways, even interacting at several points in each of them. Interestingly, in view of the interplay between hormone signalling and epigenetic machinery, a direct influence of the infection on hormonal signalling involving ecdysteroids might be achievable through the manipulation of the host’s epigenetic pathways.

  14. DMPD: The interferon regulatory factor family in host defense: mechanism of action. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17502370 The interferon regulatory factor family in host defense: mechanism of acti....html) (.csml) Show The interferon regulatory factor family in host defense: mechanism of action. PubmedID 1...7502370 Title The interferon regulatory factor family in host defense: mechanism

  15. Host susceptibility factors in mycobacterial infection. Genetics and body morphotype.

    Science.gov (United States)

    Guide, Shireen V; Holland, Steven M

    2002-03-01

    Through identification and evaluation of mutations and polymorphisms in components of the IFN gamma response pathways, a better understanding of the mechanisms and risk factors influencing the development of mycobacterial disease is gained. This may lead the way for development of therapeutic and preventative strategies. Although conventional science has focused on identifying discrete mutations, greater awareness of the impact of subtle changes, both at the genetic (polymorphisms) and physical levels (body morphotype), may prove critical in the investigative process. There has been extraordinary progress in the understanding of mycobacterial susceptibility factors over the last few years. The recognition of characteristic phenotypes will lead to the identification of new genetic bases for disease.

  16. IMSA: integrated metagenomic sequence analysis for identification of exogenous reads in a host genomic background.

    Directory of Open Access Journals (Sweden)

    Michelle T Dimon

    Full Text Available Metagenomics, the study of microbial genomes within diverse environments, is a rapidly developing field. The identification of microbial sequences within a host organism enables the study of human intestinal, respiratory, and skin microbiota, and has allowed the identification of novel viruses in diseases such as Merkel cell carcinoma. There are few publicly available tools for metagenomic high throughput sequence analysis. We present Integrated Metagenomic Sequence Analysis (IMSA, a flexible, fast, and robust computational analysis pipeline that is available for public use. IMSA takes input sequence from high throughput datasets and uses a user-defined host database to filter out host sequence. IMSA then aligns the filtered reads to a user-defined universal database to characterize exogenous reads within the host background. IMSA assigns a score to each node of the taxonomy based on read frequency, and can output this as a taxonomy report suitable for cluster analysis or as a taxonomy map (TaxMap. IMSA also outputs the specific sequence reads assigned to a taxon of interest for downstream analysis. We demonstrate the use of IMSA to detect pathogens and normal flora within sequence data from a primary human cervical cancer carrying HPV16, a primary human cutaneous squamous cell carcinoma carrying HPV 16, the CaSki cell line carrying HPV16, and the HeLa cell line carrying HPV18.

  17. Integrated metagenomics/metaproteomics reveals human host-microbiota signatures of Crohn's disease.

    Directory of Open Access Journals (Sweden)

    Alison R Erickson

    Full Text Available Crohn's disease (CD is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD or colon (CCD. Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers.

  18. Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn's Disease

    Science.gov (United States)

    Darzi, Youssef; Mongodin, Emmanuel F.; Pan, Chongle; Shah, Manesh; Halfvarson, Jonas; Tysk, Curt; Henrissat, Bernard; Raes, Jeroen; Verberkmoes, Nathan C.; Jansson, Janet K.

    2012-01-01

    Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers. PMID:23209564

  19. Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn's Disease

    Energy Technology Data Exchange (ETDEWEB)

    Erickson, Alison L [ORNL; Cantarel, Brandi [University of Maryland School of Medicine, The, Baltimore, MD; Lamendella, Regina [Lawrence Berkeley National Laboratory (LBNL); Darzi, Youssef [Vrije Universiteit Brussel, Brussels, Belgium; Mongodin, Emmanuel [University of Maryland School of Medicine, The, Baltimore, MD; Pan, Chongle [ORNL; Shah, Manesh B [ORNL; Halfvarsson, J [Orebro University Hospital, Orebro, Sweden; Tysk, C [Orebro University Hospital, Orebro, Sweden; Henrissat, Bernard [Universite d' Aix-Marseille I & II; Raes, Jeroen [Vrije Universiteit Brussel, Brussels, Belgium; Verberkmoes, Nathan C [ORNL; Fraser-Liggett, C [University of Maryland; Hettich, Robert {Bob} L [ORNL; Jansson, Janet [Lawrence Berkeley National Laboratory (LBNL)

    2012-01-01

    Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers.

  20. Human Genome-Wide RNAi Screen for Host Factors That Modulate Intracellular Salmonella Growth

    OpenAIRE

    Thornbrough, Joshua M.; Tom Hundley; Raphael Valdivia; Worley, Micah J.

    2012-01-01

    Salmonella enterica is a bacterial pathogen of humans that can proliferate within epithelial cells as well as professional phagocytes of the immune system. While much has been learned about the microbial genes that influence the infectious process through decades of intensive research, relatively little is known about the host factors that affect infection. We performed a genome-wide siRNA screen to identify host genes that Salmonella enterica serovar Typhimurium (S. typhimurium) utilizes to ...

  1. Functional analysis of host factors that mediate the intracellular lifestyle of Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Qing-Ming Qin

    2011-06-01

    Full Text Available Cryptococcus neoformans (Cn, the major causative agent of human fungal meningoencephalitis, replicates within phagolysosomes of infected host cells. Despite more than a half-century of investigation into host-Cn interactions, host factors that mediate infection by this fungal pathogen remain obscure. Here, we describe the development of a system that employs Drosophila S2 cells and RNA interference (RNAi to define and characterize Cn host factors. The system recapitulated salient aspects of fungal interactions with mammalian cells, including phagocytosis, intracellular trafficking, replication, cell-to-cell spread and escape of the pathogen from host cells. Fifty-seven evolutionarily conserved host factors were identified using this system, including 29 factors that had not been previously implicated in mediating fungal pathogenesis. Subsequent analysis indicated that Cn exploits host actin cytoskeletal elements, cell surface signaling molecules, and vesicle-mediated transport proteins to establish a replicative niche. Several host molecules known to be associated with autophagy (Atg, including Atg2, Atg5, Atg9 and Pi3K59F (a class III PI3-kinase were also uncovered in our screen. Small interfering RNA (siRNA mediated depletion of these autophagy proteins in murine RAW264.7 macrophages demonstrated their requirement during Cn infection, thereby validating findings obtained using the Drosophila S2 cell system. Immunofluorescence confocal microscopy analyses demonstrated that Atg5, LC3, Atg9a were recruited to the vicinity of Cn containing vacuoles (CnCvs in the early stages of Cn infection. Pharmacological inhibition of autophagy and/or PI3-kinase activity further demonstrated a requirement for autophagy associated host proteins in supporting infection of mammalian cells by Cn. Finally, systematic trafficking studies indicated that CnCVs associated with Atg proteins, including Atg5, Atg9a and LC3, during trafficking to a terminal intracellular

  2. Obesity and endocrine therapy: host factors and breast cancer outcome.

    Science.gov (United States)

    Goodwin, Pamela J

    2013-08-01

    Obesity is becoming increasingly prevalent and it has been linked to poor breast cancer outcomes. Because obesity is associated with increased adipose tissue mass and aromatase activity [the target of aromatase inhibitors (AIs)], there is concern that these agents may be less effective in women who are overweight or obese. Four of the randomized trials of AIs vs. tamoxifen conducted in the adjuvant breast cancer setting (ATAC, BIG 1-98 and TEAM in the postmenopausal setting and ABCSG-12 in the premenopausal setting) have reported effects of body mass index (BMI) on the relative effectiveness of an AI vs. tamoxifen. Obesity was confirmed as an adverse prognostic factor in ATAC and BIG 1-98 but not the TEAM study; in ABSCG-12, obesity was associated with poor outcomes in the anastrozole arm only. In the three postmenopausal trials, the use of an AI vs. tamoxifen was associated with better outcomes at all levels of BMI [all hazard ratios for recurrence breast cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Microbial Hub Taxa Link Host and Abiotic Factors to Plant Microbiome Variation.

    Directory of Open Access Journals (Sweden)

    Matthew T Agler

    2016-01-01

    Full Text Available Plant-associated microorganisms have been shown to critically affect host physiology and performance, suggesting that evolution and ecology of plants and animals can only be understood in a holobiont (host and its associated organisms context. Host-associated microbial community structures are affected by abiotic and host factors, and increased attention is given to the role of the microbiome in interactions such as pathogen inhibition. However, little is known about how these factors act on the microbial community, and especially what role microbe-microbe interaction dynamics play. We have begun to address this knowledge gap for phyllosphere microbiomes of plants by simultaneously studying three major groups of Arabidopsis thaliana symbionts (bacteria, fungi and oomycetes using a systems biology approach. We evaluated multiple potential factors of microbial community control: we sampled various wild A. thaliana populations at different times, performed field plantings with different host genotypes, and implemented successive host colonization experiments under lab conditions where abiotic factors, host genotype, and pathogen colonization was manipulated. Our results indicate that both abiotic factors and host genotype interact to affect plant colonization by all three groups of microbes. Considering microbe-microbe interactions, however, uncovered a network of interkingdom interactions with significant contributions to community structure. As in other scale-free networks, a small number of taxa, which we call microbial "hubs," are strongly interconnected and have a severe effect on communities. By documenting these microbe-microbe interactions, we uncover an important mechanism explaining how abiotic factors and host genotypic signatures control microbial communities. In short, they act directly on "hub" microbes, which, via microbe-microbe interactions, transmit the effects to the microbial community. We analyzed two "hub" microbes (the

  4. Citizen science data reveal ecological, historical and evolutionary factors shaping interactions between woody hosts and wood-inhabiting fungi.

    Science.gov (United States)

    Heilmann-Clausen, Jacob; Maruyama, Pietro K; Bruun, Hans Henrik; Dimitrov, Dimitar; Laessøe, Thomas; Frøslev, Tobias Guldberg; Dalsgaard, Bo

    2016-12-01

    Woody plants host diverse communities of associated organisms, including wood-inhabiting fungi. In this group, host effects on species richness and interaction network structure are not well understood, especially not at large geographical scales. We investigated ecological, historical and evolutionary determinants of fungal species richness and network modularity, that is, subcommunity structure, across woody hosts in Denmark, using a citizen science data set comprising > 80 000 records of > 1000 fungal species on 91 genera of woody plants. Fungal species richness was positively related to host size, wood pH, and the number of species in the host genus, with limited influence of host frequency and host history, that is, time since host establishment in the area. Modularity patterns were unaffected by host history, but largely reflected host phylogeny. Notably, fungal communities differed substantially between angiosperm and gymnosperm hosts. Host traits and evolutionary history appear to be more important than host frequency and recent history in structuring interactions between hosts and wood-inhabiting fungi. High wood acidity appears to act as a stress factor reducing fungal species richness, while large host size, providing increased niche diversity, enhances it. In some fungal groups that are known to interact with live host cells in the establishment phase, host selectivity is common, causing a modular community structure. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  5. Integration of Visual and Olfactory Cues in Host Plant Identification by the Asian Longhorned Beetle, Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae).

    Science.gov (United States)

    Yv, Fei L; Hai, Xiaoxia; Wang, Zhigang; Yan, Aihua; Liu, Bingxiang; Bi, Yongguo

    2015-01-01

    Some insects use host and mate cues, including odor, color, and shape, to locate and recognize their preferred hosts and mates. Previous research has shown that the Asian longicorn beetle, Anoplophora glabripennis (Motschulsky), uses olfactory cues to locate host plants and differentiate them from non-host plants. However, whether A. glabripennis adults use visual cues or a combination of visual and olfactory cues remains unclear. In this study, we tested the host location and recognition behavior in A. glabripennis, which infests a number of hardwood species and causes considerable economic losses in North America, Europe and Asia. We determined the relative importance of visual and olfactory cues from Acer negundo in host plant location and recognition, as well as in the discrimination of non-host plants (Sabina chinensis and Pinus bungeana), by female and male A. glabripennis. Visual and olfactory cues from the host plants (A. negundo), alone and combined, attracted significantly more females and males than equivalent cues from non-host plants (S. chinensis and P. bungeana). Furthermore, the combination of visual and olfactory cues of host plants attracted more adults than either cue alone, and visual cues alone attracted significantly more adults than olfactory cues alone. This finding suggests that adult A. glabripennis has an innate preference for the visual and/or olfactory cues of its host plants (A. negundo) over those of the non-host plant and visual cues are initially more important than olfactory cues for orientation; furthermore, this finding also suggests that adults integrate visual and olfactory cues to find their host plants. Our results indicate that different modalities of host plant cues should be considered together to understand fully the communication between host plants and Asian longhorned beetles.

  6. Cycle Inhibiting Factors (Cifs): Cyclomodulins That Usurp the Ubiquitin-Dependent Degradation Pathway of Host Cells

    Science.gov (United States)

    Taieb, Frédéric; Nougayrède, Jean-Philippe; Oswald, Eric

    2011-01-01

    Cycle inhibiting factors (Cifs) are type III secreted effectors produced by diverse pathogenic bacteria. Cifs are “cyclomodulins” that inhibit the eukaryotic host cell cycle and also hijack other key cellular processes such as those controlling the actin network and apoptosis. This review summarizes current knowledge on Cif since its first characterization in enteropathogenic Escherichia coli, the identification of several xenologues in distant pathogenic bacteria, to its structure elucidation and the recent deciphering of its mode of action. Cif impairs the host ubiquitin proteasome system through deamidation of ubiquitin or the ubiquitin-like protein NEDD8 that regulates Cullin-Ring-ubiquitin Ligase (CRL) complexes. The hijacking of the ubiquitin-dependent degradation pathway of host cells results in the modulation of various cellular functions such as epithelium renewal, apoptosis and immune response. Cif is therefore a powerful weapon in the continuous arm race that characterizes host-bacteria interactions. PMID:22069713

  7. Cycle inhibiting factors (cifs): cyclomodulins that usurp the ubiquitin-dependent degradation pathway of host cells.

    Science.gov (United States)

    Taieb, Frédéric; Nougayrède, Jean-Philippe; Oswald, Eric

    2011-04-01

    Cycle inhibiting factors (Cifs) are type III secreted effectors produced by diverse pathogenic bacteria. Cifs are "cyclomodulins" that inhibit the eukaryotic host cell cycle and also hijack other key cellular processes such as those controlling the actin network and apoptosis. This review summarizes current knowledge on Cif since its first characterization in enteropathogenic Escherichia coli, the identification of several xenologues in distant pathogenic bacteria, to its structure elucidation and the recent deciphering of its mode of action. Cif impairs the host ubiquitin proteasome system through deamidation of ubiquitin or the ubiquitin-like protein NEDD8 that regulates Cullin-Ring-ubiquitin Ligase (CRL) complexes. The hijacking of the ubiquitin-dependent degradation pathway of host cells results in the modulation of various cellular functions such as epithelium renewal, apoptosis and immune response. Cif is therefore a powerful weapon in the continuous arm race that characterizes host-bacteria interactions.

  8. Cycle Inhibiting Factors (Cifs: Cyclomodulins That Usurp the Ubiquitin-Dependent Degradation Pathway of Host Cells

    Directory of Open Access Journals (Sweden)

    Eric Oswald

    2011-03-01

    Full Text Available Cycle inhibiting factors (Cifs are type III secreted effectors produced by diverse pathogenic bacteria. Cifs are “cyclomodulins” that inhibit the eukaryotic host cell cycle and also hijack other key cellular processes such as those controlling the actin network and apoptosis. This review summarizes current knowledge on Cif since its first characterization in enteropathogenic Escherichia coli, the identification of several xenologues in distant pathogenic bacteria, to its structure elucidation and the recent deciphering of its mode of action. Cif impairs the host ubiquitin proteasome system through deamidation of ubiquitin or the ubiquitin-like protein NEDD8 that regulates Cullin-Ring-ubiquitin Ligase (CRL complexes. The hijacking of the ubiquitin-dependent degradation pathway of host cells results in the modulation of various cellular functions such as epithelium renewal, apoptosis and immune response. Cif is therefore a powerful weapon in the continuous arm race that characterizes host-bacteria interactions.

  9. Host genetic factors in susceptibility to HIV-1 infection and progression to AIDS

    Indian Academy of Sciences (India)

    Koushik Chatterjee

    2010-04-01

    HIV-1 infection has rapidly spread worldwide and has become the leading cause of mortality in infectious diseases. The duration for development of AIDS (AIDS progression) is highly variable among HIV–1 infected individuals, ranging from 2–3 years to no signs of AIDS development in the entire lifetime. Several factors regulate the rate at which HIV-1 infection progresses to AIDS. Host genetic factors play an important role in the outcome of such complex or multifactor diseases as AIDS and are also known to regulate the rate of disease progression. This review focuses on the major host genes reported to affect the progression to AIDS in HIV-1 infected individuals.

  10. Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.

    Directory of Open Access Journals (Sweden)

    Debrah A Fine

    Full Text Available The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT.

  11. A Supramolecular Host-Guest Carrier System for Growth Factors Employing VHH Fragments

    NARCIS (Netherlands)

    Cabanas-Danés, J.; Rodrigues, E.D.; Landman, Ellie B.M.; Weerd, van J.; Blitterswijk, van C.A.; Verrips, T.; Huskens, J.; Karperien, H.B.J.; Jonkheijm, Pascal

    2014-01-01

    A supramolecular strategy is presented for the assembly of growth factors employing His6-tagged single-domain antibodies (VHH). A combination of orthogonal supramolecular interactions of β-cyclodextrin (βCD)-adamantyl (Ad) host-guest and N-nitrilotriacetic acid (NTA)-histidine (His) interactions was

  12. Host-related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans

    NARCIS (Netherlands)

    Bohn, Torsten; Desmarchelier, Charles; Dragsted, Lars O.; Nielsen, Charlotte S.; Stahl, Wilhelm; Rühl, Ralph; Keijer, Jaap; Borel, Patrick

    2017-01-01

    Carotenoid dietary intake and their endogenous levels have been associated with a decreased risk of several chronic diseases. There are indications that carotenoid bioavailability depends, in addition to the food matrix, on host factors. These include diseases (e.g. colitis), life-style habits (e

  13. Distinct immunoregulatory properties of macrophage migration inhibitory factors encoded by Eimeria parasites and their chicken host

    Science.gov (United States)

    Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays an important role in host defense against a variety of microorganisms including protozoan parasites. Interestingly, some microbial pathogens also express a MIF-like protein, although its role in disease pathogenesi...

  14. The clinical implications of integrating additional prognostic factors into the TNM.

    Science.gov (United States)

    Henson, Donald Earl; Schwartz, Arnold M; Chen, Dechang; Wu, Dengyuan

    2014-04-01

    The management of solid tumors is governed by host and tumor factors that traditionally have incorporated TNM staging with additional pathologic, biologic, and clinical host factors. Beyond the anatomic-based TNM, increasingly new prognostic and predictive factors are being discovered that have important survival and treatment implications. However, because the TNM is based on a "bin" model, additional prognostic factors would rapidly overwhelm the current system. This communication demonstrates the clinical implications and improved patient prognosis derived from a new algorithmic model based on clustering analysis. A new algorithm is described that integrates additional factors into the TNM and calculates survival. The results indicate that additional factors can be integrated into the TNM staging system providing additional patient stratification without changing the TNM definitions. Adding prognostic factors to traditional TNM staging increases substratification of given stages and identifies and separates favorable and unfavorable clinical outcomes for specific TNM stages. Integration of additional prognostic factors into the TNM by a clustering algorithm can change the stratification of patient outcome. This may guide the clinician to select a more rational management program based on the additional factors and improve cohort selection for clinical trials. © 2013 Wiley Periodicals, Inc.

  15. Structural determinants of host specificity of complement Factor H recruitment by Streptococcus pneumoniae.

    Science.gov (United States)

    Achila, David; Liu, Aizhuo; Banerjee, Rahul; Li, Yue; Martinez-Hackert, Erik; Zhang, Jing-Ren; Yan, Honggao

    2015-01-15

    Many human pathogens have strict host specificity, which affects not only their epidemiology but also the development of animal models and vaccines. Complement Factor H (FH) is recruited to pneumococcal cell surface in a human-specific manner via the N-terminal domain of the pneumococcal protein virulence factor choline-binding protein A (CbpAN). FH recruitment enables Streptococcus pneumoniae to evade surveillance by human complement system and contributes to pneumococcal host specificity. The molecular determinants of host specificity of complement evasion are unknown. In the present study, we show that a single human FH (hFH) domain is sufficient for tight binding of CbpAN, present the crystal structure of the complex and identify the critical structural determinants for host-specific FH recruitment. The results offer new approaches to the development of better animal models for pneumococcal infection and redesign of the virulence factor for pneumococcal vaccine development and reveal how FH recruitment can serve as a mechanism for both pneumococcal complement evasion and adherence.

  16. Novel Burkholderia mallei Virulence Factors Linked to Specific Host-Pathogen Protein Interactions*

    Science.gov (United States)

    Memišević, Vesna; Zavaljevski, Nela; Pieper, Rembert; Rajagopala, Seesandra V.; Kwon, Keehwan; Townsend, Katherine; Yu, Chenggang; Yu, Xueping; DeShazer, David; Reifman, Jaques; Wallqvist, Anders

    2013-01-01

    Burkholderia mallei is an infectious intracellular pathogen whose virulence and resistance to antibiotics makes it a potential bioterrorism agent. Given its genetic origin as a commensal soil organism, it is equipped with an extensive and varied set of adapted mechanisms to cope with and modulate host-cell environments. One essential virulence mechanism constitutes the specialized secretion systems that are designed to penetrate host-cell membranes and insert pathogen proteins directly into the host cell's cytosol. However, the secretion systems' proteins and, in particular, their host targets are largely uncharacterized. Here, we used a combined in silico, in vitro, and in vivo approach to identify B. mallei proteins required for pathogenicity. We used bioinformatics tools, including orthology detection and ab initio predictions of secretion system proteins, as well as published experimental Burkholderia data to initially select a small number of proteins as putative virulence factors. We then used yeast two-hybrid assays against normalized whole human and whole murine proteome libraries to detect and identify interactions among each of these bacterial proteins and host proteins. Analysis of such interactions provided both verification of known virulence factors and identification of three new putative virulence proteins. We successfully created insertion mutants for each of these three proteins using the virulent B. mallei ATCC 23344 strain. We exposed BALB/c mice to mutant strains and the wild-type strain in an aerosol challenge model using lethal B. mallei doses. In each set of experiments, mice exposed to mutant strains survived for the 21-day duration of the experiment, whereas mice exposed to the wild-type strain rapidly died. Given their in vivo role in pathogenicity, and based on the yeast two-hybrid interaction data, these results point to the importance of these pathogen proteins in modulating host ubiquitination pathways, phagosomal escape, and actin

  17. Structural integration in hypoxia-inducible factors

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Dalei; Potluri, Nalini; Lu, Jingping; Kim, Youngchang; Rastinejad, Fraydoon

    2015-08-20

    The hypoxia-inducible factors (HIFs) coordinate cellular adaptations to low oxygen stress by regulating transcriptional programs in erythropoiesis, angiogenesis and metabolism. These programs promote the growth and progression of many tumours, making HIFs attractive anticancer targets. Transcriptionally active HIFs consist of HIF-alpha and ARNT (also called HIF-1 beta) subunits. Here we describe crystal structures for each of mouse HIF-2 alpha-ARNT and HIF-1 alpha-ARNT heterodimers in states that include bound small molecules and their hypoxia response element. A highly integrated quaternary architecture is shared by HIF-2 alpha-ARNT and HIF-1 alpha-ARNT, wherein ARNT spirals around the outside of each HIF-alpha subunit. Five distinct pockets are observed that permit small-molecule binding, including PAS domain encapsulated sites and an interfacial cavity formed through subunit heterodimerization. The DNA-reading head rotates, extends and cooperates with a distal PAS domain to bind hypoxia response elements. HIF-alpha mutations linked to human cancers map to sensitive sites that establish DNA binding and the stability of PAS domains and pockets.

  18. Effects of Host Plant Factors on the Bacterial Communities Associated with Two Whitefly Sibling Species.

    Science.gov (United States)

    Su, Ming-Ming; Guo, Lei; Tao, Yun-Li; Zhang, You-Jun; Wan, Fang-Hao; Chu, Dong

    2016-01-01

    Although discrepancy in the specific traits and ecological characteristics of Bemisia tabaci between species are partially attributed to the B. tabaci-associated bacteria, the factors that affect the diversity of B. tabaci-associated bacteria are not well-understood. We used the metagenomic approach to characterize the B. tabaci-associated bacterial community because the approach is an effective tool to identify the bacteria. To investigate the effects of the host plant and a virus, tomato yellow leaf curl virus (TYLCV), on the bacterial communities of B. tabaci sibling species B and Q, we analyzed the bacterial communities associated with whitefly B and Q collected from healthy cotton, healthy tomato, and TYLCV-infected tomato. The analysis used miseq-based sequencing of a variable region of the bacterial 16S rDNA gene. For the bacteria associated with B. tabaci, we found that the influence of the host plant species was greater than that of the whitefly cryptic species. With further analysis of host plants infected with the TYLCV, the virus had no significant effects on the B. tabaci-associated bacterial community. The effects of different plant hosts and TYLCV-infection on the diversity of B. tabaci-associated bacterial communities were successfully analyzed in this study. To explain why B. tabaci sibling species with different host ranges differ in performance, the analysis of the bacterial community may be essential to the explanation.

  19. Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a Host Factor for Hepatitis C Virus Entry

    Directory of Open Access Journals (Sweden)

    Gisa Gerold

    2015-08-01

    Full Text Available Hepatitis C virus (HCV enters human hepatocytes through a multistep mechanism involving, among other host proteins, the virus receptor CD81. How CD81 governs HCV entry is poorly characterized, and CD81 protein interactions after virus binding remain elusive. We have developed a quantitative proteomics protocol to identify HCV-triggered CD81 interactions and found 26 dynamic binding partners. At least six of these proteins promote HCV infection, as indicated by RNAi. We further characterized serum response factor binding protein 1 (SRFBP1, which is recruited to CD81 during HCV uptake and supports HCV infection in hepatoma cells and primary human hepatocytes. SRFBP1 facilitates host cell penetration by all seven HCV genotypes, but not of vesicular stomatitis virus and human coronavirus. Thus, SRFBP1 is an HCV-specific, pan-genotypic host entry factor. These results demonstrate the use of quantitative proteomics to elucidate pathogen entry and underscore the importance of host protein-protein interactions during HCV invasion.

  20. Visual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infection

    Science.gov (United States)

    de Macedo Dossin, Fernando; Choi, Seo Yeon; Kim, Nam Youl; Kim, Hi Chul; Jung, Sung Yong; Schenkman, Sergio; Almeida, Igor C.; Emans, Neil; Freitas-Junior, Lucio H.

    2011-01-01

    The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical infection that affects millions of people in the Americas. Current chemotherapy relies on only two drugs that have limited efficacy and considerable side effects. Therefore, the development of new and more effective drugs is of paramount importance. Although some host cellular factors that play a role in T. cruzi infection have been uncovered, the molecular requirements for intracellular parasite growth and persistence are still not well understood. To further study these host-parasite interactions and identify human host factors required for T. cruzi infection, we performed a genome-wide RNAi screen using cellular microarrays of a printed siRNA library that spanned the whole human genome. The screening was reproduced 6 times and a customized algorithm was used to select as hits those genes whose silencing visually impaired parasite infection. The 162 strongest hits were subjected to a secondary screening and subsequently validated in two different cell lines. Among the fourteen hits confirmed, we recognized some cellular membrane proteins that might function as cell receptors for parasite entry and others that may be related to calcium release triggered by parasites during cell invasion. In addition, two of the hits are related to the TGF-beta signaling pathway, whose inhibition is already known to diminish levels of T. cruzi infection. This study represents a significant step toward unveiling the key molecular requirements for host cell invasion and revealing new potential targets for antiparasitic therapy. PMID:21625474

  1. Visual genome-wide RNAi screening to identify human host factors required for Trypanosoma cruzi infection.

    Directory of Open Access Journals (Sweden)

    Auguste Genovesio

    Full Text Available The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical infection that affects millions of people in the Americas. Current chemotherapy relies on only two drugs that have limited efficacy and considerable side effects. Therefore, the development of new and more effective drugs is of paramount importance. Although some host cellular factors that play a role in T. cruzi infection have been uncovered, the molecular requirements for intracellular parasite growth and persistence are still not well understood. To further study these host-parasite interactions and identify human host factors required for T. cruzi infection, we performed a genome-wide RNAi screen using cellular microarrays of a printed siRNA library that spanned the whole human genome. The screening was reproduced 6 times and a customized algorithm was used to select as hits those genes whose silencing visually impaired parasite infection. The 162 strongest hits were subjected to a secondary screening and subsequently validated in two different cell lines. Among the fourteen hits confirmed, we recognized some cellular membrane proteins that might function as cell receptors for parasite entry and others that may be related to calcium release triggered by parasites during cell invasion. In addition, two of the hits are related to the TGF-beta signaling pathway, whose inhibition is already known to diminish levels of T. cruzi infection. This study represents a significant step toward unveiling the key molecular requirements for host cell invasion and revealing new potential targets for antiparasitic therapy.

  2. Host Cell Factors in Filovirus Entry: Novel Players, New Insights

    Directory of Open Access Journals (Sweden)

    Stefan Pöhlmann

    2012-11-01

    Full Text Available Filoviruses cause severe hemorrhagic fever in humans with high case-fatality rates. The cellular factors exploited by filoviruses for their spread constitute potential targets for intervention, but are incompletely defined. The viral glycoprotein (GP mediates filovirus entry into host cells. Recent studies revealed important insights into the host cell molecules engaged by GP for cellular entry. The binding of GP to cellular lectins was found to concentrate virions onto susceptible cells and might contribute to the early and sustained infection of macrophages and dendritic cells, important viral targets. Tyrosine kinase receptors were shown to promote macropinocytic uptake of filoviruses into a subset of susceptible cells without binding to GP, while interactions between GP and human T cell Ig mucin 1 (TIM-1 might contribute to filovirus infection of mucosal epithelial cells. Moreover, GP engagement of the cholesterol transporter Niemann-Pick C1 was demonstrated to be essential for GP-mediated fusion of the viral envelope with a host cell membrane. Finally, mutagenic and structural analyses defined GP domains which interact with these host cell factors. Here, we will review the recent progress in elucidating the molecular interactions underlying filovirus entry and discuss their implications for our understanding of the viral cell tropism.

  3. Host factors and HIV-1 replication: clinical evidence and potential therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Mariana eSanta-Marta

    2013-10-01

    Full Text Available HIV and human defense mechanisms have co-evolved to counteract each other. In the process of infection, HIV takes advantage of cellular machinery and blocks the action of the host restriction factors. A small subset of HIV+ individuals control HIV infection and progression to AIDS in the absence of treatment. These individuals known, as long-term non-progressors (LNTPs exhibit genetic and immunological characteristics that confer upon them an efficient resistance to infection and/or disease progression. The identification of some of these host factors led to the development of therapeutic approaches that attempted to mimic the natural control of HIV infection. Some of these approaches are currently being tested in clinical trials. While there are many genes which carry mutations and polymorphisms associated with non-progression, this review will be specifically focused on HIV host restriction factors (RF including both the main chemokine receptors and chemokines as well as intracellular restriction factors including, APOBEC, TRIM, tetherin and SAMHD1. The understanding of molecular profiles and mechanisms present in LTNPs should provide new insights to control HIV infection and contribute to the development of novel therapies against AIDS.

  4. Identifying influential factors on integrated marketing planning using information technology

    Directory of Open Access Journals (Sweden)

    Karim Hamdi

    2014-07-01

    Full Text Available This paper presents an empirical investigation to identify important factors influencing integrated marketing planning using information technology. The proposed study designs a questionnaire for measuring integrated marketing planning, which consists of three categories of structural factors, behavioral factors and background factors. There are 40 questions associated with the proposed study in Likert scale. Cronbach alphas have been calculated for structural factors, behavioral factors and background factors as 0.89, 0.86 and 0.83, respectively. Using some statistical test, the study has confirmed the effects of three factors on integrated marketing. In addition, the implementation of Freedman test has revealed that structural factors were the most important factor followed by background factors and behavioral factors.

  5. Human genome-wide RNAi screen for host factors that modulate intracellular Salmonella growth.

    Science.gov (United States)

    Thornbrough, Joshua M; Hundley, Tom; Valdivia, Raphael; Worley, Micah J

    2012-01-01

    Salmonella enterica is a bacterial pathogen of humans that can proliferate within epithelial cells as well as professional phagocytes of the immune system. While much has been learned about the microbial genes that influence the infectious process through decades of intensive research, relatively little is known about the host factors that affect infection. We performed a genome-wide siRNA screen to identify host genes that Salmonella enterica serovar Typhimurium (S. typhimurium) utilizes to facilitate growth within human epithelial cells. In this screen, with siRNAs targeting every predicted gene in the human genome, we identified 252 new human-host-susceptibility factors (HSFs) for S. typhimurium. We also identified 39 genes whose silencing results in increased intracellular growth of S. typhimurium. The HSFs identified are regulated most centrally by NFκB and associate with each other through an extremely dense network of interactions that center around a group of kinases. Most genes identified were not previously appreciated as playing roles in the intracellular lifecycle of S. enterica. Numerous HSFs identified with interesting characteristics that could play plausible roles in mediating intracellular microbial growth are discussed. Importantly, this study reveals significant overlap between the host network that supports S. typhimurium growth within human epithelial cells and the one that promotes the growth of Mycobacterium tuberculosis within human macrophages. In addition to providing much new information about the molecular mechanisms underlying S. enterica-host cell interplay, all 252 HSFs identified are candidates for new anti-microbial targets for controlling S. enterica infections, and some may provide broad-spectrum anti-microbial activity.

  6. Genome-wide RNAi screen identifies broadly-acting host factors that inhibit arbovirus infection.

    Directory of Open Access Journals (Sweden)

    Ari Yasunaga

    2014-02-01

    Full Text Available Vector-borne viruses are an important class of emerging and re-emerging pathogens; thus, an improved understanding of the cellular factors that modulate infection in their respective vertebrate and insect hosts may aid control efforts. In particular, cell-intrinsic antiviral pathways restrict vector-borne viruses including the type I interferon response in vertebrates and the RNA interference (RNAi pathway in insects. However, it is likely that additional cell-intrinsic mechanisms exist to limit these viruses. Since insects rely on innate immune mechanisms to inhibit virus infections, we used Drosophila as a model insect to identify cellular factors that restrict West Nile virus (WNV, a flavivirus with a broad and expanding geographical host range. Our genome-wide RNAi screen identified 50 genes that inhibited WNV infection. Further screening revealed that 17 of these genes were antiviral against additional flaviviruses, and seven of these were antiviral against other vector-borne viruses, expanding our knowledge of invertebrate cell-intrinsic immunity. Investigation of two newly identified factors that restrict diverse viruses, dXPO1 and dRUVBL1, in the Tip60 complex, demonstrated they contributed to antiviral defense at the organismal level in adult flies, in mosquito cells, and in mammalian cells. These data suggest the existence of broadly acting and functionally conserved antiviral genes and pathways that restrict virus infections in evolutionarily divergent hosts.

  7. A System to Integrate Unmanned Undersea Vehicles with a Submarine Host Platform

    Science.gov (United States)

    2011-06-06

    UUV/HostSub X X F.3.2 Transfer data from/to UUV X F.3.3 Transfer data from/to HostSub X F.3.4 Repower UUV X F.3.5 Release connection with UUV/HostSub X...HostSub, along with repowering of the UUV. These events may occur in parallel. Once the system has determined that the UUV is repowered and all

  8. Host Factors and Biomarkers Associated with Poor Outcomes in Adults with Invasive Pneumococcal Disease.

    Directory of Open Access Journals (Sweden)

    Shigeo Hanada

    Full Text Available Invasive pneumococcal disease (IPD causes considerable morbidity and mortality. We aimed to identify host factors and biomarkers associated with poor outcomes in adult patients with IPD in Japan, which has a rapidly-aging population.In a large-scale surveillance study of 506 Japanese adults with IPD, we investigated the role of host factors, disease severity, biomarkers based on clinical laboratory data, treatment regimens, and bacterial factors on 28-day mortality.Overall mortality was 24.1%, and the mortality rate increased from 10.0% in patients aged ˂50 years to 33.1% in patients aged ≥80 years. Disease severity also increased 28-day mortality, from 12.5% among patients with bacteraemia without sepsis to 35.0% in patients with severe sepsis and 56.9% with septic shock. The death rate within 48 hours after admission was high at 54.9%. Risk factors for mortality identified by multivariate analysis were as follows: white blood cell (WBC count <4000 cells/μL (odds ratio [OR], 6.9; 95% confidence interval [CI], 3.7-12.8, p < .001; age ≥80 years (OR, 6.5; 95% CI, 2.0-21.6, p = .002; serum creatinine ≥2.0 mg/dL (OR, 4.5; 95% CI, 2.5-8.1, p < .001; underlying liver disease (OR, 3.5; 95% CI, 1.6-7.8, p = .002; mechanical ventilation (OR, 3.0; 95% CI, 1.7-5.6, p < .001; and lactate dehydrogenase ≥300 IU/L (OR, 2.4; 95% CI, 1.4-4.0, p = .001. Pneumococcal serotype and drug resistance were not associated with poor outcomes.Host factors, disease severity, and biomarkers, especially WBC counts and serum creatinine, were more important determinants of mortality than bacterial factors.

  9. Gut Microbiome and Infant Health: Brain-Gut-Microbiota Axis and Host Genetic Factors

    Science.gov (United States)

    Cong, Xiaomei; Xu, Wanli; Romisher, Rachael; Poveda, Samantha; Forte, Shaina; Starkweather, Angela; Henderson, Wendy A.

    2016-01-01

    The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gut microbiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns.

  10. Gut Microbiome and Infant Health: Brain-Gut-Microbiota Axis and Host Genetic Factors.

    Science.gov (United States)

    Cong, Xiaomei; Xu, Wanli; Romisher, Rachael; Poveda, Samantha; Forte, Shaina; Starkweather, Angela; Henderson, Wendy A

    2016-09-01

    The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gut microbiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns.

  11. The Integrative Human Microbiome Project: dynamic analysis of microbiome-host omics profiles during periods of human health and disease.

    Science.gov (United States)

    2014-09-10

    Much has been learned about the diversity and distribution of human-associated microbial communities, but we still know little about the biology of the microbiome, how it interacts with the host, and how the host responds to its resident microbiota. The Integrative Human Microbiome Project (iHMP, http://hmp2.org), the second phase of the NIH Human Microbiome Project, will study these interactions by analyzing microbiome and host activities in longitudinal studies of disease-specific cohorts and by creating integrated data sets of microbiome and host functional properties. These data sets will serve as experimental test beds to evaluate new models, methods, and analyses on the interactions of host and microbiome. Here we describe the three models of microbiome-associated human conditions, on the dynamics of preterm birth, inflammatory bowel disease, and type 2 diabetes, and their underlying hypotheses, as well as the multi-omic data types to be collected, integrated, and distributed through public repositories as a community resource. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Salidroside exhibits anti-dengue virus activity by upregulating host innate immune factors.

    Science.gov (United States)

    Sharma, Navita; Mishra, K P; Ganju, Lilly

    2016-12-01

    Dengue is an arboviral disease with no effective therapy available. Therefore, there is an urgent need to find a potent antiviral agent against dengue virus (DENV). In the present study, salidroside, a main bioactive compound of Rhodiola rosea, was evaluated for its antiviral potential against DENV serotype-2 infection and its effect on host innate immune factors. Antiviral effects of salidroside were examined in DENV-infected cells by western blotting, flow cytometry and real-time PCR. Its underlying mechanism involved in antiviral action was determined by evaluating expression of host innate immune factors including RIG-I, IRF-3, IRF-7, PKR, P-eIF2α and NF-κB. Salidroside potently inhibited DENV infection by decreasing DENV envelope protein expression more than tenfold. Salidroside exerts its antiviral activity by increasing expression of RNA helicases such as RIG-I, thereby initiating a downstream signaling cascade that induces upregulation of IRF-3 and IRF-7. It prevents viral protein synthesis by increasing the expression of PKR and P-eIF2α while decreasing NF-κB expression. It was also found to induce the expression of IFN-α. In addition, the number of NK cells and CD8(+) T cells were also found to be increased by salidroside treatment in human PBMCs, which are important in limiting DENV replication during early stages of infection. The findings presented here suggest that salidroside exhibits antiviral activity against DENV by inhibiting viral protein synthesis and boosting host immunity by increasing the expression of host innate immune factors and hence could be considered for the development of an effective therapeutic agent against DENV infection.

  13. Social Hackers: Integration in the Host Chemical Recognition System by a Paper Wasp Social Parasite

    Science.gov (United States)

    Turillazzi, S.; Sledge, M. F.; Dani, F. R.; Cervo, R.; Massolo, A.; Fondelli, L.

    Obligate social parasites in the social insects have lost the worker caste and the ability to establish nests. As a result, parasites must usurp a host nest, overcome the host recognition system, and depend on the host workers to rear their offspring. We analysed cuticular hydrocarbon profiles of live parasite females of the paper wasp social parasite Polistes sulcifer before and after usurpation of host nests, using the non-destructive technique of solid-phase micro-extraction. Our results reveal that hydrocarbon profiles of parasites change after usurpation of host nests to match the cuticular profile of the host species. Chemical evidence further shows that the parasite queen changes the odour of the nest by the addition of a parasite-specific hydrocarbon. We discuss the possible role of this in the recognition and acceptance of the parasite and its offspring in the host colony.

  14. Transcription factor ATF3 links host adaptive response to breast cancer metastasis

    Science.gov (United States)

    Wolford, Chris C.; McConoughey, Stephen J.; Jalgaonkar, Swati P.; Leon, Marino; Merchant, Anand S.; Dominick, Johnna L.; Yin, Xin; Chang, Yiseok; Zmuda, Erik J.; O’Toole, Sandra A.; Millar, Ewan K.A.; Roller, Stephanie L.; Shapiro, Charles L.; Ostrowski, Michael C.; Sutherland, Robert L.; Hai, Tsonwin

    2013-01-01

    Host response to cancer signals has emerged as a key factor in cancer development; however, the underlying molecular mechanism is not well understood. In this report, we demonstrate that activating transcription factor 3 (ATF3), a hub of the cellular adaptive response network, plays an important role in host cells to enhance breast cancer metastasis. Immunohistochemical analysis of patient tumor samples revealed that expression of ATF3 in stromal mononuclear cells, but not cancer epithelial cells, is correlated with worse clinical outcomes and is an independent predictor for breast cancer death. This finding was corroborated by data from mouse models showing less efficient breast cancer metastasis in Atf3-deficient mice than in WT mice. Further, mice with myeloid cell–selective KO of Atf3 showed fewer lung metastases, indicating that host ATF3 facilitates metastasis, at least in part, by its function in macrophage/myeloid cells. Gene profiling analyses of macrophages from mouse tumors identified an ATF3-regulated gene signature that could distinguish human tumor stroma from distant stroma and could predict clinical outcomes, lending credence to our mouse models. In conclusion, we identified ATF3 as a regulator in myeloid cells that enhances breast cancer metastasis and has predictive value for clinical outcomes. PMID:23921126

  15. Clinical heterogeneity of human neurocysticercosis results from complex interactions among parasite, host and environmental factors.

    Science.gov (United States)

    Fleury, Agnès; Escobar, Alfonso; Fragoso, Gladis; Sciutto, Edda; Larralde, Carlos

    2010-04-01

    Human neurocysticercosis (NC) is endemic in most countries of Latin America, Asia and Africa and is re-emerging in some industrialized nations. Both within and among endemic countries, NC is very variable in its clinical and radiological features, as well as in the intensity of the immuno-inflammatory reactions of the hosts. This review, focusing on the Mexican experience, describes and interprets the heterogeneity of NC as the result of different combinations among factors associated with the parasite, host and environment. The review may serve to foster similar descriptive efforts in other endemic areas of the world in order to facilitate the identification of the distinct factors that participate in the complex pathogenesis and diverse clinical outcomes of NC. In particular, it is necessary to understand the precise physiopathology of the inflammatory reaction associated with NC, as inflammation is one of the characteristics of those NC cases that are clinically more severe and less responsive to current treatments. Devising new medical interventions through the use of molecular regulators of the innate and adaptive immune responses of the host is a largely unexplored approach that could improve the existing forms of treatment. Copyright 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

  16. Helicobacter pylori virulence genes and host genetic polymorphisms as risk factors for peptic ulcer disease.

    Science.gov (United States)

    Miftahussurur, Muhammad; Yamaoka, Yoshio

    2015-01-01

    Helicobacter pylori infection plays an important role in the pathogenesis of peptic ulcer disease (PUD). Several factors have been proposed as possible H. pylori virulence determinants; for example, bacterial adhesins and gastric inflammation factors are associated with an increased risk of PUD. However, differences in bacterial virulence factors alone cannot explain the opposite ends of the PUD disease spectrum, that is duodenal and gastric ulcers; presumably, both bacterial and host factors contribute to the differential response. Carriers of the high-producer alleles of the pro-inflammatory cytokines IL-1B, IL-6, IL-8, IL-10, and TNF-α who also carry low-producer allele of anti-inflammatory cytokines have severe gastric mucosal inflammation, whereas carriers of the alternative alleles have mild inflammation. Recent reports have suggested that the PSCA and CYP2C19 ultra-rapid metabolizer genotypes are also associated with PUD.

  17. Integrative analyses unveil speciation linked to host plant shift in Spialia butterflies.

    Science.gov (United States)

    Hernández-Roldán, Juan L; Dapporto, Leonardo; Dincă, Vlad; Vicente, Juan C; Hornett, Emily A; Šíchová, Jindra; Lukhtanov, Vladimir A; Talavera, Gerard; Vila, Roger

    2016-09-01

    Discovering cryptic species in well-studied areas and taxonomic groups can have profound implications in understanding eco-evolutionary processes and in nature conservation because such groups often involve research models and act as flagship taxa for nature management. In this study, we use an array of techniques to study the butterflies in the Spialia sertorius species group (Lepidoptera, Hesperiidae). The integration of genetic, chemical, cytogenetic, morphological, ecological and microbiological data indicates that the sertorius species complex includes at least five species that differentiated during the last three million years. As a result, we propose the restitution of the species status for two taxa often treated as subspecies, Spialia ali (Oberthür, 1881) stat. rest. and Spialia therapne (Rambur, 1832) stat. rest., and describe a new cryptic species Spialia rosae Hernández-Roldán, Dapporto, Dincă, Vicente & Vila sp. nov. Spialia sertorius (Hoffmannsegg, 1804) and S. rosae are sympatric and synmorphic, but show constant differences in mitochondrial DNA, chemical profiles and ecology, suggesting that S. rosae represents a case of ecological speciation involving larval host plant and altitudinal shift, and apparently associated with Wolbachia infection. This study exemplifies how a multidisciplinary approach can reveal elusive cases of hidden diversity.

  18. Role of Host Genetic Factors in the Outcome of Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Hubert E. Blum

    2009-08-01

    Full Text Available The natural history of hepatitis C virus (HCV infection is determined by a complex interplay between host genetic, immunological and viral factors. This review highlights genes involved in innate and adaptive immune responses associated with different outcomes of HCV infection. For example, an association of HCV clearance with certain HLA alleles has been demonstrated. The mechanisms responsible for these associations have been linked to specific T cell responses for some particular alleles (e.g., HLA-B27. Genetic associations involved in T cell regulation and function further underline the role of the adaptive immune response in the natural history of HCV infection. In addition, some genes involved in innate NK cell responses demonstrate the complex interplay between components of the immune system necessary for a successful host response to HCV infection.

  19. Factors affecting patterns of Amblyomma triste (Acari: Ixodidae) parasitism in a rodent host.

    Science.gov (United States)

    Colombo, Valeria C; Nava, Santiago; Antoniazzi, Leandro R; Monje, Lucas D; Racca, Andrea L; Guglielmone, Alberto A; Beldomenico, Pablo M

    2015-07-30

    Here we offer a multivariable analysis that explores associations of different factors (i.e., environmental, host parameters, presence of other ectoparasites) with the interaction of Amblyomma triste immature stages and one of its main hosts in Argentina, the rodent Akodon azarae. Monthly and for two years, we captured and sampled rodents at 16 points located at 4 different sites in the Parana River Delta region. The analyses were conducted with Generalized Linear Mixed Models with a negative binomial response (counts of larvae or nymphs). The independent variables assessed were: (a) environmental: trapping year, season, presence of cattle; type of vegetation (natural grassland or implanted forest); rodent abundance; (b) host parameters: body length; sex; body condition; blood cell counts; natural antibody titres; and (c) co-infestation with other ectoparasites: other stage of A. triste; Ixodes loricatus; lice; mites; and fleas. Two-way interaction terms deemed a priori as relevant were also included in the analysis. Larvae were affected by all environmental variables assessed and by the presence of other ectoparasites (lice, fleas and other tick species). Host factors significantly associated with larval count were sex and levels of natural antibodies. Nymphs were associated with season, presence of cattle, body condition, body length and with burdens of I. loricatus. In most cases, the direction and magnitude of the associations were context-dependent (many interaction terms were significant). The findings of greater significance and implications of our study are two. Firstly, as burdens of A. triste larvae and nymphs were greater where cattle were present, and larval tick burdens were higher in implanted forests, silvopastoral practices developing in the region may affect the population dynamics of A. triste, and consequently the eco-epidemiology of Rickettsia parkeri. Secondly, strong associations and numerous interactions with other ectoparasites suggest that

  20. Interactions of Prototype Foamy Virus Capsids with Host Cell Polo-Like Kinases Are Important for Efficient Viral DNA Integration.

    Directory of Open Access Journals (Sweden)

    Irena Zurnic

    2016-08-01

    Full Text Available Unlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H screen with prototype FV (PFV Gag protein as bait we identified human polo-like kinase 2 (hPLK2, a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs. In the case of rat PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes in a Gag STP motif-dependent manner, confirming a specific and dominant nature of the Gag-PLK interaction in mammalian cells. The functional relevance of the Gag-PLK interaction was examined in the context of replication-competent FVs and single-round PFV vectors. Although STP motif mutated viruses displayed wild type (wt particle release, RNA packaging and intra-particle reverse transcription, their replication capacity was decreased 3-fold in single-cycle infections, and up to 20-fold in spreading infections over an extended time period. Strikingly similar defects were observed when cells infected with single-round wt Gag PFV vectors were treated with a pan PLK inhibitor. Analysis of entry kinetics of the mutant viruses indicated a post-fusion defect resulting in delayed and reduced integration, which was accompanied with an enhanced preference to integrate into heterochromatin. We conclude that interaction between PFV Gag and cellular PLK proteins is important for early replication steps of PFV within host cells.

  1. Interactions of Prototype Foamy Virus Capsids with Host Cell Polo-Like Kinases Are Important for Efficient Viral DNA Integration

    Science.gov (United States)

    Zurnic, Irena; Hütter, Sylvia; Rzeha, Ute; Stanke, Nicole; Reh, Juliane; Müllers, Erik; Hamann, Martin V.; Kern, Tobias; Gerresheim, Gesche K.; Serrao, Erik; Lesbats, Paul; Engelman, Alan N.; Cherepanov, Peter; Lindemann, Dirk

    2016-01-01

    Unlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs) via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H) screen with prototype FV (PFV) Gag protein as bait we identified human polo-like kinase 2 (hPLK2), a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P) motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs. In the case of rat PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes in a Gag STP motif-dependent manner, confirming a specific and dominant nature of the Gag-PLK interaction in mammalian cells. The functional relevance of the Gag-PLK interaction was examined in the context of replication-competent FVs and single-round PFV vectors. Although STP motif mutated viruses displayed wild type (wt) particle release, RNA packaging and intra-particle reverse transcription, their replication capacity was decreased 3-fold in single-cycle infections, and up to 20-fold in spreading infections over an extended time period. Strikingly similar defects were observed when cells infected with single-round wt Gag PFV vectors were treated with a pan PLK inhibitor. Analysis of entry kinetics of the mutant viruses indicated a post-fusion defect resulting in delayed and reduced integration, which was accompanied with an enhanced preference to integrate into heterochromatin. We conclude that interaction between PFV Gag and cellular PLK proteins is important for early replication steps of PFV within host cells. PMID:27579920

  2. Human host defense peptide LL-37 stimulates virulence factor production and adaptive resistance in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Nikola Strempel

    Full Text Available A multitude of different virulence factors as well as the ability to rapidly adapt to adverse environmental conditions are important features for the high pathogenicity of Pseudomonas aeruginosa. Both virulence and adaptive resistance are tightly controlled by a complex regulatory network and respond to external stimuli, such as host signals or antibiotic stress, in a highly specific manner. Here, we demonstrate that physiological concentrations of the human host defense peptide LL-37 promote virulence factor production as well as an adaptive resistance against fluoroquinolone and aminoglycoside antibiotics in P. aeruginosa PAO1. Microarray analyses of P. aeruginosa cells exposed to LL-37 revealed an upregulation of gene clusters involved in the production of quorum sensing molecules and secreted virulence factors (PQS, phenazine, hydrogen cyanide (HCN, elastase and rhamnolipids and in lipopolysaccharide (LPS modification as well as an induction of genes encoding multidrug efflux pumps MexCD-OprJ and MexGHI-OpmD. Accordingly, we detected significantly elevated levels of toxic metabolites and proteases in bacterial supernatants after LL-37 treatment. Pre-incubation of bacteria with LL-37 for 2 h led to a decreased susceptibility towards gentamicin and ciprofloxacin. Quantitative Realtime PCR results using a PAO1-pqsE mutant strain present evidence that the quinolone response protein and virulence regulator PqsE may be implicated in the regulation of the observed phenotype in response to LL-37. Further experiments with synthetic cationic antimicrobial peptides IDR-1018, 1037 and HHC-36 showed no induction of pqsE expression, suggesting a new role of PqsE as highly specific host stress sensor.

  3. Targeting host factors: A novel rationale for the management of hepatitis C virus

    Institute of Scientific and Technical Information of China (English)

    Mahmoud Aboelneen Khattab

    2009-01-01

    Hepatitis C is recognized as a major threat to global public health. The current treatment of patients with chronic hepatitis C is the addition of ribavirin to interferon-based therapy which has limited efficacy, poor tolerability, and significant expense. New treatment options that are more potent and less toxic are much needed. Moreover, more effective treatment is an urgent priority for those who relapse or do not respond to current regimens. A major obstacle in combating hepatitis C virus (HCV) infection is that the fidelity of the viral replication machinery is notoriously low, thus enabling the virus to quickly develop mutations that resist compounds targeting viral enzymes. Therefore, an approach targeting the host cofactors, which are indispensable for the propagation of viruses, may be an ideal target for the development of antiviral agents because they have a lower rate of mutation than that of the viral genome, as long as they have no side effects to patients. Drugs targeting, for example, receptors of viral entry, host metabolism or nuclear receptors, which are factors required to complete the HCV life cycle, may be more effective in combating the viral infection. Targeting host cofactors of the HCV life cycle is an attractive concept because it imposes a higher genetic barrier for resistance than direct antiviral compounds. However the principle drawback of this strategy is the greater potential for cellular toxicity.

  4. Fecal metabolome of the Hadza hunter-gatherers: a host-microbiome integrative view

    Science.gov (United States)

    Turroni, Silvia; Fiori, Jessica; Rampelli, Simone; Schnorr, Stephanie L.; Consolandi, Clarissa; Barone, Monica; Biagi, Elena; Fanelli, Flaminia; Mezzullo, Marco; Crittenden, Alyssa N.; Henry, Amanda G.; Brigidi, Patrizia; Candela, Marco

    2016-01-01

    The recent characterization of the gut microbiome of traditional rural and foraging societies allowed us to appreciate the essential co-adaptive role of the microbiome in complementing our physiology, opening up significant questions on how the microbiota changes that have occurred in industrialized urban populations may have altered the microbiota-host co-metabolic network, contributing to the growing list of Western diseases. Here, we applied a targeted metabolomics approach to profile the fecal metabolome of the Hadza of Tanzania, one of the world’s few remaining foraging populations, and compared them to the profiles of urban living Italians, as representative of people in the post-industrialized West. Data analysis shows that during the rainy season, when the diet is primarily plant-based, Hadza are characterized by a distinctive enrichment in hexoses, glycerophospholipids, sphingolipids, and acylcarnitines, while deplete in the most common natural amino acids and derivatives. Complementary to the documented unique metagenomic features of their gut microbiome, our findings on the Hadza metabolome lend support to the notion of an alternate microbiome configuration befitting of a nomadic forager lifestyle, which helps maintain metabolic homeostasis through an overall scarcity of inflammatory factors, which are instead highly represented in the Italian metabolome. PMID:27624970

  5. Fecal metabolome of the Hadza hunter-gatherers: a host-microbiome integrative view.

    Science.gov (United States)

    Turroni, Silvia; Fiori, Jessica; Rampelli, Simone; Schnorr, Stephanie L; Consolandi, Clarissa; Barone, Monica; Biagi, Elena; Fanelli, Flaminia; Mezzullo, Marco; Crittenden, Alyssa N; Henry, Amanda G; Brigidi, Patrizia; Candela, Marco

    2016-09-14

    The recent characterization of the gut microbiome of traditional rural and foraging societies allowed us to appreciate the essential co-adaptive role of the microbiome in complementing our physiology, opening up significant questions on how the microbiota changes that have occurred in industrialized urban populations may have altered the microbiota-host co-metabolic network, contributing to the growing list of Western diseases. Here, we applied a targeted metabolomics approach to profile the fecal metabolome of the Hadza of Tanzania, one of the world's few remaining foraging populations, and compared them to the profiles of urban living Italians, as representative of people in the post-industrialized West. Data analysis shows that during the rainy season, when the diet is primarily plant-based, Hadza are characterized by a distinctive enrichment in hexoses, glycerophospholipids, sphingolipids, and acylcarnitines, while deplete in the most common natural amino acids and derivatives. Complementary to the documented unique metagenomic features of their gut microbiome, our findings on the Hadza metabolome lend support to the notion of an alternate microbiome configuration befitting of a nomadic forager lifestyle, which helps maintain metabolic homeostasis through an overall scarcity of inflammatory factors, which are instead highly represented in the Italian metabolome.

  6. Enhancing Integrated Pest Management in GM Cotton Systems Using Host Plant Resistance.

    Science.gov (United States)

    Trapero, Carlos; Wilson, Iain W; Stiller, Warwick N; Wilson, Lewis J

    2016-01-01

    Cotton has lost many ancestral defensive traits against key invertebrate pests. This is suggested by the levels of resistance to some pests found in wild cotton genotypes as well as in cultivated landraces and is a result of domestication and a long history of targeted breeding for yield and fiber quality, along with the capacity to control pests with pesticides. Genetic modification (GM) allowed integration of toxins from a bacteria into cotton to control key Lepidopteran pests. Since the mid-1990s, use of GM cotton cultivars has greatly reduced the amount of pesticides used in many cotton systems. However, pests not controlled by the GM traits have usually emerged as problems, especially the sucking bug complex. Control of this complex with pesticides often causes a reduction in beneficial invertebrate populations, allowing other secondary pests to increase rapidly and require control. Control of both sucking bug complex and secondary pests is problematic due to the cost of pesticides and/or high risk of selecting for pesticide resistance. Deployment of host plant resistance (HPR) provides an opportunity to manage these issues in GM cotton systems. Cotton cultivars resistant to the sucking bug complex and/or secondary pests would require fewer pesticide applications, reducing costs and risks to beneficial invertebrate populations and pesticide resistance. Incorporation of HPR traits into elite cotton cultivars with high yield and fiber quality offers the potential to further reduce pesticide use and increase the durability of pest management in GM cotton systems. We review the challenges that the identification and use of HPR against invertebrate pests brings to cotton breeding. We explore sources of resistance to the sucking bug complex and secondary pests, the mechanisms that control them and the approaches to incorporate these defense traits to commercial cultivars.

  7. Enhancing Integrated Pest Management in GM Cotton Systems Using Host Plant Resistance

    Science.gov (United States)

    Trapero, Carlos; Wilson, Iain W.; Stiller, Warwick N.; Wilson, Lewis J.

    2016-01-01

    Cotton has lost many ancestral defensive traits against key invertebrate pests. This is suggested by the levels of resistance to some pests found in wild cotton genotypes as well as in cultivated landraces and is a result of domestication and a long history of targeted breeding for yield and fiber quality, along with the capacity to control pests with pesticides. Genetic modification (GM) allowed integration of toxins from a bacteria into cotton to control key Lepidopteran pests. Since the mid-1990s, use of GM cotton cultivars has greatly reduced the amount of pesticides used in many cotton systems. However, pests not controlled by the GM traits have usually emerged as problems, especially the sucking bug complex. Control of this complex with pesticides often causes a reduction in beneficial invertebrate populations, allowing other secondary pests to increase rapidly and require control. Control of both sucking bug complex and secondary pests is problematic due to the cost of pesticides and/or high risk of selecting for pesticide resistance. Deployment of host plant resistance (HPR) provides an opportunity to manage these issues in GM cotton systems. Cotton cultivars resistant to the sucking bug complex and/or secondary pests would require fewer pesticide applications, reducing costs and risks to beneficial invertebrate populations and pesticide resistance. Incorporation of HPR traits into elite cotton cultivars with high yield and fiber quality offers the potential to further reduce pesticide use and increase the durability of pest management in GM cotton systems. We review the challenges that the identification and use of HPR against invertebrate pests brings to cotton breeding. We explore sources of resistance to the sucking bug complex and secondary pests, the mechanisms that control them and the approaches to incorporate these defense traits to commercial cultivars. PMID:27148323

  8. Yersinia virulence factors - a sophisticated arsenal for combating host defences [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Steve Atkinson

    2016-06-01

    Full Text Available The human pathogens Yersinia pseudotuberculosis and Yersinia enterocolitica cause enterocolitis, while Yersinia pestis is responsible for pneumonic, bubonic, and septicaemic plague. All three share an infection strategy that relies on a virulence factor arsenal to enable them to enter, adhere to, and colonise the host while evading host defences to avoid untimely clearance. Their arsenal includes a number of adhesins that allow the invading pathogens to establish a foothold in the host and to adhere to specific tissues later during infection. When the host innate immune system has been activated, all three pathogens produce a structure analogous to a hypodermic needle. In conjunction with the translocon, which forms a pore in the host membrane, the channel that is formed enables the transfer of six ‘effector’ proteins into the host cell cytoplasm. These proteins mimic host cell proteins but are more efficient than their native counterparts at modifying the host cell cytoskeleton, triggering the host cell suicide response. Such a sophisticated arsenal ensures that yersiniae maintain the upper hand despite the best efforts of the host to counteract the infecting pathogen.

  9. Functional variants of human papillomavirus type 16 demonstrate host genome integration and transcriptional alterations corresponding to their unique cancer epidemiology.

    Science.gov (United States)

    Jackson, Robert; Rosa, Bruce A; Lameiras, Sonia; Cuninghame, Sean; Bernard, Josee; Floriano, Wely B; Lambert, Paul F; Nicolas, Alain; Zehbe, Ingeborg

    2016-11-02

    Human papillomaviruses (HPVs) are a worldwide burden as they are a widespread group of tumour viruses in humans. Having a tropism for mucosal tissues, high-risk HPVs are detected in nearly all cervical cancers. HPV16 is the most common high-risk type but not all women infected with high-risk HPV develop a malignant tumour. Likely relevant, HPV genomes are polymorphic and some HPV16 single nucleotide polymorphisms (SNPs) are under evolutionary constraint instigating variable oncogenicity and immunogenicity in the infected host. To investigate the tumourigenicity of two common HPV16 variants, we used our recently developed, three-dimensional organotypic model reminiscent of the natural HPV infectious cycle and conducted various "omics" and bioinformatics approaches. Based on epidemiological studies we chose to examine the HPV16 Asian-American (AA) and HPV16 European Prototype (EP) variants. They differ by three non-synonymous SNPs in the transforming and virus-encoded E6 oncogene where AAE6 is classified as a high- and EPE6 as a low-risk variant. Remarkably, the high-risk AAE6 variant genome integrated into the host DNA, while the low-risk EPE6 variant genome remained episomal as evidenced by highly sensitive Capt-HPV sequencing. RNA-seq experiments showed that the truncated form of AAE6, integrated in chromosome 5q32, produced a local gene over-expression and a large variety of viral-human fusion transcripts, including long distance spliced transcripts. In addition, differential enrichment of host cell pathways was observed between both HPV16 E6 variant-containing epithelia. Finally, in the high-risk variant, we detected a molecular signature of host chromosomal instability, a common property of cancer cells. We show how naturally occurring SNPs in the HPV16 E6 oncogene cause significant changes in the outcome of HPV infections and subsequent viral and host transcriptome alterations prone to drive carcinogenesis. Host genome instability is closely linked to viral

  10. Lipoarabinomannan in urine during tuberculosis treatment: association with host and pathogen factors and mycobacteriuria

    Directory of Open Access Journals (Sweden)

    Wood Robin

    2012-02-01

    Full Text Available Abstract Background Detection of lipoarabinomannan (LAM, a Mycobacterium tuberculosis (Mtb cell wall antigen, is a potentially attractive diagnostic. However, the LAM-ELISA assay has demonstrated variable sensitivity in diagnosing TB in diverse clinical populations. We therefore explored pathogen and host factors potentially impacting LAM detection. Methods LAM-ELISA assay testing, sputum smear and culture status, HIV status, CD4 cell count, proteinuria and TB outcomes were prospectively determined in adults diagnosed with TB and commencing TB treatment at a South African township TB clinic. Sputum TB isolates were characterised by IS61110-based restriction fragment length polymorphism (RFLP and urines were tested for mycobacteriuria by Xpert® MTB/RIF assay. Results 32/199 (16.1% of patients tested LAM-ELISA positive. Median optical density and proportion testing LAM positive remained unchanged during 2 weeks of treatment and then declined over 24 weeks. LAM was associated with positive sputum smear and culture status, HIV infection and low CD4 cell counts but not proteinuria, RFLP strain or TB treatment outcome. The sensitivity of LAM for TB in HIV-infected patients with CD4 counts of ≥ 200, 100-199, 50-99, and Conclusions Urinary LAM was related to host immune factors, was unrelated to Mtb strain and declined steadily after an initial 2 weeks of TB treatment. The strong association of urine LAM with mycobacteriuria is a new finding, indicating frequent TB involvement of the renal tract in advanced HIV infection.

  11. Lipoarabinomannan in urine during tuberculosis treatment: association with host and pathogen factors and mycobacteriuria.

    Science.gov (United States)

    Wood, Robin; Racow, Kimberly; Bekker, Linda-Gail; Middelkoop, Keren; Vogt, Monica; Kreiswirth, Barry N; Lawn, Stephen D

    2012-02-27

    Detection of lipoarabinomannan (LAM), a Mycobacterium tuberculosis (Mtb) cell wall antigen, is a potentially attractive diagnostic. However, the LAM-ELISA assay has demonstrated variable sensitivity in diagnosing TB in diverse clinical populations. We therefore explored pathogen and host factors potentially impacting LAM detection. LAM-ELISA assay testing, sputum smear and culture status, HIV status, CD4 cell count, proteinuria and TB outcomes were prospectively determined in adults diagnosed with TB and commencing TB treatment at a South African township TB clinic. Sputum TB isolates were characterised by IS61110-based restriction fragment length polymorphism (RFLP) and urines were tested for mycobacteriuria by Xpert® MTB/RIF assay. 32/199 (16.1%) of patients tested LAM-ELISA positive. Median optical density and proportion testing LAM positive remained unchanged during 2 weeks of treatment and then declined over 24 weeks. LAM was associated with positive sputum smear and culture status, HIV infection and low CD4 cell counts but not proteinuria, RFLP strain or TB treatment outcome. The sensitivity of LAM for TB in HIV-infected patients with CD4 counts of ≥ 200, 100-199, 50-99, and Urinary LAM was related to host immune factors, was unrelated to Mtb strain and declined steadily after an initial 2 weeks of TB treatment. The strong association of urine LAM with mycobacteriuria is a new finding, indicating frequent TB involvement of the renal tract in advanced HIV infection.

  12. Host and viral factors contributing to CD8+ T cell failure in hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Christoph Neumann-Haefelin; Hans Christian Spangenberg; Hubert E Blum; Robert Thimme

    2007-01-01

    Virus-specific CD8+ T cells are thought to be the major anti-viral effector cells in hepatitis C virus (HCV)infection. Indeed, viral clearance is associated with vigorous CD8+ T cell responses targeting multiple epitopes. In the chronic phase of infection, HCV-specific CD8+ T cell responses are usually weak, narrowly focused and display often functional defects regarding cytotoxicity, cytokine production, and proliferative capacity. In the last few years, different mechanisms which might contribute to the failure of HCV-specific CD8+ T cells in chronic infection have been identified,including insufficient CD4+ help, deficient CD8+ T cell differentiation, viral escape mutations, suppression by viral factors, inhibitory cytokines, inhibitory ligands, and regulatory T cells. In addition, host genetic factors such as the host's human leukocyte antigen (HLA) background may play an important role in the efficiency of the HCVspecific CD8+ T cell response and thus outcome of infection. The growing understanding of the mechanisms contributing to T cell failure and persistence of HCV infection will contribute to the development of successful immunotherapeutical and -prophylactical strategies.

  13. Energy transfer between a nanosystem and its host fluid: A multiscale factorization approach

    Energy Technology Data Exchange (ETDEWEB)

    Sereda, Yuriy V.; Espinosa-Duran, John M.; Ortoleva, Peter J., E-mail: ortoleva@indiana.edu [Center for Cell and Virus Theory, Department of Chemistry, Indiana University, 800 E. Kirkwood Ave, Bloomington, Indiana 47405 (United States)

    2014-02-21

    Energy transfer between a macromolecule or supramolecular assembly and a host medium is considered from the perspective of Newton's equations and Lie-Trotter factorization. The development starts by demonstrating that the energy of the molecule evolves slowly relative to the time scale of atomic collisions-vibrations. The energy is envisioned to be a coarse-grained variable that coevolves with the rapidly fluctuating atomistic degrees of freedom. Lie-Trotter factorization is shown to be a natural framework for expressing this coevolution. A mathematical formalism and workflow for efficient multiscale simulation of energy transfer is presented. Lactoferrin and human papilloma virus capsid-like structure are used for validation.

  14. Host factors are dominant in the development of post-liver transplant non-alcoholic steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Salih; Boga; Armando; Salim; Munoz-Abraham; Manuel; I; Rodriguez-Davalos; Sukru; H; Emre; Dhanpat; Jain; Michael; L; Schilsky

    2016-01-01

    Non-alcoholic fatty liver disease(NAFLD) is a recognized problem in patients after orthotopic liver transplantation and may lead to recurrent graft injury. As the increased demand for liver allografts fail to match the available supply of donor organs, split liver transplantation(SLT) has emerged as an important technique to increase the supply of liver grafts. SLT allows two transplants to occur from one donor organ, and provides a unique model for observing the pathogenesis of NAFLD with respect to the role of recipient environmental and genetic factors. Here we report on two recipients of a SLT from the same deceased donor where only one developed non-alcoholic steatohepatitis(NASH), suggesting that host factors are critical for the development of NASH.

  15. Integrating Factors and Conservation Laws for Relativistic Mechanical System

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yi

    2005-01-01

    In this paper, we present a new method to construct the conservation laws for relativistic mechanical systems by finding corresponding integrating factors. First, the Lagrange equations of relativisticmechanical systems are established, and the definition of integrating factors of the systems is given; second, the necessary conditions for the existence of conserved quantities of the relativistic mechanical systems are studied in detail, and the relation between the conservation laws and the integrating factors of the systems is obtained and the generaized Killing equations for the determination of the integrating factors are given; finally, the conservation theorem and its inverse for the systems are established, and an example is given to illustrate the application of the results.

  16. Integrating factors and conservation theorems of constrained Birkhoffian systems

    Institute of Scientific and Technical Information of China (English)

    Qiao Yong-Fen; Zhao Shu-Hong; Li Ren-Jie

    2006-01-01

    In this paper the conservation theorems of the constrained Birkhoffian systems are studied by using the method of integrating factors. The differential equations of motion of the system are written. The definition of integrating factors is given for the system. The necessary conditions for the existence of the conserved quantity for the system are studied.The conservation theorem and its inverse for the system are established. Finally, an example is given to illustrate the application of the results.

  17. Graft-versus-host disease after orthotopic liver transplantation: multivariate analysis of risk factors.

    Science.gov (United States)

    Elfeki, Mohamed A; Pungpapong, Surakit; Genco, Petrina V; Nakhleh, Raouf E; Nguyen, Justin H; Harnois, Denise M

    2015-12-01

    Graft-versus-host disease (GVHD) is a rare, fatal complication following orthotopic liver transplantation (OLT). To date, several risk factors have been proposed, but reports on these factors have been inconclusive. This is a retrospective, case-control study of prospectively collected data from 2775 OLTs performed at our institution. Eight cases of GVHD after OLT were diagnosed on the basis of the patient's clinical characteristics, and the findings were confirmed with skin and colonic biopsies. Each case was matched to three controls based on the diagnosis of liver disease, recipient's age, and blood group. Univariate and multivariate analyses were performed to identify risk factors associated with the development of GVHD after OLT. The univariate and multivariate analyses identified two main risk factors associated with development of GVHD in OLT recipients, a difference between recipient and donor age of >20 yr, and any human leukocyte antigen class I matches. Taking these two risk factors into consideration while matching prospective donors and recipients may reduce further incidence of GVHD in OLT patients. However, further studies are recommended to validate these findings. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Factors affecting the integration of immigrant nurses into the nursing workforce: A double hermeneutic study.

    Science.gov (United States)

    Xiao, Lily Dongxia; Willis, Eileen; Jeffers, Lesley

    2014-04-01

    Variations in nursing practice and communication difficulties pose a challenge for the successful integration into the workforce of immigrant nurses. Evidence for this is found in cultural clashes, interpersonal conflicts, communication problems, prejudiced attitudes and discrimination towards immigrant nurses. While the evidence shows that integrating immigrant nurses into the nursing workforce is shaped by factors that are socially constructed, studies that examine social structures affecting workforce integration are sparse. The aim of this study was to examine interplaying relationships between social structures and nurses' actions that either enabled or inhibited workforce integration in hospital settings. Giddens' Structuration Theory with double hermeneutic methodology was used to interpret 24 immigrant and 20 senior nurses' perceptions of factors affecting workforce integration. Four themes were identified from the data. These were: (1) employer-sponsored visa as a constraint on adaptation, (2) two-way learning and adaptation in multicultural teams, (3) unacknowledged experiences and expertise as barriers to integration, and (4) unquestioned sub-group norms as barriers for group cohesion. The themes presented a critical perspective that unsuitable social structures (policies and resources) constrained nurses' performance in workforce integration in the context of nurse immigration. The direction of structural changes needed to improve workforce integration is illustrated throughout the discussions of policies and resources required for workforce integration at national and organisational levels, conditions for positive group interactions and group cohesion in organisations. Our study reveals inadequate rules and resources used to recruit, classify and utilise immigrant nurses at national and healthcare organisational levels can become structural constraints on their adaptation to professional nursing practice and integration into the workforce in a host

  19. Host factors and genetic susceptibility to infections due to intracellular bacteria and fastidious organisms.

    Science.gov (United States)

    Asner, S A; Morré, S A; Bochud, P-Y; Greub, G

    2014-12-01

    While genetic polymorphisms play a paramount role in tuberculosis (TB), less is known about their contribution to the severity of diseases caused by other intracellular bacteria and fastidious microorganisms. We searched electronic databases for observational studies reporting on host factors and genetic predisposition to infections caused by intracellular fastidious bacteria published up to 30 May 2014. The contribution of genetic polymorphisms was documented for TB. This includes genetic defects in the mononuclear phagocyte/T helper cell type 1 (Th1) pathway contributing to disseminated TB disease in children and genome-wide linkage analysis (GWAS) in reactivated pulmonary TB in adults. Similarly, experimental studies supported the role of host genetic factors in the clinical presentation of illnesses resulting from other fastidious intracellular bacteria. These include IL-6 -174G/C or low mannose-binding (MBL) polymorphisms, which are incriminated in chronic pulmonary conditions triggered by C. pneumoniae, type 2-like cytokine secretion polymorphisms, which are correlated with various clinical patterns of M. pneumoniae infections, and genetic variation in the NOD2 gene, which is an indicator of tubal pathology resulting from Chamydia trachomatis infections. Monocyte/macrophage migration and T lymphocyte recruitment defects are corroborated to ineffective granuloma formation observed among patients with chronic Q fever. Similar genetic polymorphisms have also been suggested for infections caused by T. whipplei although not confirmed yet. In conclusion, this review supports the paramount role of genetic factors in clinical presentations and severity of infections caused by intracellular fastidious bacteria. Genetic predisposition should be further explored through such as exome sequencing.

  20. Extrapulmonary tuberculosis: Mycobacterium tuberculosis strains and host risk factors in a large urban setting in Brazil.

    Directory of Open Access Journals (Sweden)

    Teresa Gomes

    Full Text Available BACKGROUND: Factors related to the development of extrapulmonary forms of tuberculosis (EPTB are still poorly understood, particularly in high-endemic countries like Brazil. The objective of the paper is to determine host and Mycobacterium tuberculosis (MTB strain-related factors associated with the development of EPTB in Espírito Santo state, Brazil. METHODS AND FINDINGS: We conducted a retrospective laboratory-based surveillance study of new tuberculosis (TB cases diagnosed in Espírito Santo state, Brazil between 1998 and 2007. We genotyped 612 isolates of MTB from 606 TB patients using spoligotyping and IS6110-restriction fragment length polymorphism (RFLP typing and compared sociodemographic and clinical characteristics of patients with pulmonary TB (PTB and EPTB. Among 606 patients, 464 (77% had PTB, 79 (13% had EPTB, 51 (8% had both, and 12 (2% had miliary TB. The IS6110 RFLP analysis demonstrated that 250 (41% isolates belonged to clustered RFLP patterns, 27 (11% of which were from EPTB. We identified 73 clusters including 35 (48% composed of 2 isolates each. By spoligotyping, 506 (83% MTB isolates fell into known patterns and 106 (17% fell into patterns with no family assignment; 297 (48% isolates belonged to the Latin-American Mediterranean family. Higher school level (4-7 years OR: 0.16 95% CI 0.34-0.73 and > 8 years of education, OR 0.06 95% CI 0.009-0.50 white ethnicity (OR: 2.54 95% CI 1.03-6.25 and HIV infection (OR: 16.83 95% CI 5.23-54.18 were associated with EPTB. No specific strain lineage or percentage of clustering was associated with EPTB. CONCLUSIONS: These results demonstrate that risk factors for EPTB are related more to host than to MTB strain lineage characteristics.

  1. Experimental infections with Mycoplasma agalactiae identify key factors involved in host-colonization.

    Directory of Open Access Journals (Sweden)

    Eric Baranowski

    Full Text Available Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i the development of a specific antibody response and (ii dynamic changes in expression of M. agalactiae surface variable proteins (Vpma, with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs.

  2. Influence of host factors and parasite biomass on the severity of imported Plasmodium falciparum malaria.

    Science.gov (United States)

    Argy, Nicolas; Kendjo, Eric; Augé-Courtoi, Claire; Cojean, Sandrine; Clain, Jérôme; Houzé, Pascal; Thellier, Marc; Hubert, Veronique; Deloron, Philippe; Houzé, Sandrine

    2017-01-01

    Imported malaria in France is characterized by various clinical manifestations observed in a heterogeneous population of patients such as travelers/expatriates and African migrants. In this population, host factors and parasite biomass associated with severe imported malaria are poorly known. From data collected by the Centre National de Référence du Paludisme, we identified epidemiological, demographic and biological features including parasite biomass and anti-plasmodial antibody levels (negative, positive and strongly positive serology) associated with different disease severity groups (very severe, moderately severe, and uncomplicated malaria) in 3 epidemiological groups (travelers/expatriates, first- and second-generation migrants). Age, ethnicity, absence of prior infection with P. falciparum, antibody levels, plasma PfHRP2 levels, total and circulating parasite biomass were related to severe malaria onset. Sequestered parasite biomass tended to be increased in very severe malaria, and was strongly correlated to the antibody level of the host. Prior exposure to P. falciparum is associated with high anti-plasmodial antibody levels which influence clinical presentation of imported malaria and its correlated circulating and sequestered parasite burden.

  3. The correlated factors of the uneven performances of the CDM host countries

    Science.gov (United States)

    Zhu, Jinshan

    2012-03-01

    The Kyoto Protocol’s Clean Development Mechanism (CDM) has experienced a rapid growth. Up to 2010, 2763 projects have been registered, standing for about 433 million ton CO2 equivalent (CO2-eq.) of annual carbon credits. However, the performances of CDM host countries are remarkably unbalanced. Previous literature suggested that economic and investment conditions, energy intensity, energy structure, the share of annual carbon credits from high global warming potential (GWP) green house gas (GHG), capacity and institutional buildings of domestic CDM governance can play important roles in promoting CDM. This quantitative analysis shows that domestic economic and investment conditions are the most decisive factors determining the performance of the CDM host countries. Additionally, the influence of carbon intensity of energy consumption is relatively modest, and energy intensity of GDP as well as the share of annual carbon credits from high GWP GHG is less significant. Moreover, several leading CDM countries are not as successful as they seem to be, when the influences of their vast territories, distinguished economic and investment conditions are excluded. Therefore, to simply transplant the CDM governances of these countries can hardly guarantee that other countries will boost their carbon credit outputs.

  4. Systems integration of biodefense omics data for analysis of pathogen-host interactions and identification of potential targets.

    Directory of Open Access Journals (Sweden)

    Peter B McGarvey

    Full Text Available The NIAID (National Institute for Allergy and Infectious Diseases Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents. The Biodefense Resource Center (www.proteomicsresource.org has developed a bioinformatics framework, employing a protein-centric approach to integrate and support mining and analysis of the large and heterogeneous data. Underlying this approach is a data warehouse with comprehensive protein + gene identifier and name mappings and annotations extracted from over 100 molecular databases. Value-added annotations are provided for key proteins from experimental findings using controlled vocabulary. The availability of pathogen and host omics data in an integrated framework allows global analysis of the data and comparisons across different experiments and organisms, as illustrated in several case studies presented here. (1 The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells infected by different bacterial (Bacillus anthracis and Salmonella typhimurium and viral (orthopox pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. (2 The analysis of a vaccinia-human protein interaction network supplemented with protein accumulation levels led to the identification of human Keratin, type II cytoskeletal 4 protein as a potential therapeutic target. (3 Comparison of complete genomes from pathogenic variants coupled with experimental information on complete proteomes allowed the identification and

  5. Identification and Structural Basis of Binding to Host Lung Glycogen by Streptococcal Virulence Factors

    Energy Technology Data Exchange (ETDEWEB)

    Lammerts van Bueren,A.; Higgins, M.; Wang, D.; Burke, R.; Boraston, A.

    2007-01-01

    The ability of pathogenic bacteria to recognize host glycans is often essential to their virulence. Here we report structure-function studies of previously uncharacterized glycogen-binding modules in the surface-anchored pullulanases from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA). Multivalent binding to glycogen leads to a strong interaction with alveolar type II cells in mouse lung tissue. X-ray crystal structures of the binding modules reveal a novel fusion of tandem modules into single, bivalent functional domains. In addition to indicating a structural basis for multivalent attachment, the structure of the SpuA modules in complex with carbohydrate provides insight into the molecular basis for glycogen specificity. This report provides the first evidence that intracellular lung glycogen may be a novel target of pathogenic streptococci and thus provides a rationale for the identification of the streptococcal {alpha}-glucan-metabolizing machinery as virulence factors.

  6. Time resolved bovine host reponse to virulence factors mapped in milk by selected reaction monitoring

    DEFF Research Database (Denmark)

    Bislev, Stine Lønnerup; Kusebauch, Ulrike; Codrea, Marius Cosmin

    TIME RESOLVED BOVINE HOST RESPONSE TO VIRULENCE FACTORS, MAPPED IN MILK BY SELECTED REACTION MONITORING S.L. Bislev1, U. Kusebauch2, M.C. Codrea1, R. Moritz2, C.M. Røntved1, E. Bendixen1 1 Department of Animal Science, Faculty of Science and Technology, Aarhus University, Tjele, Denmark; 2...... Institute for Systems Biology, Seattle, Washington, USA Mastitis is beyond doubt the largest health problem in modern milk production. Many different pathogens can cause infections in the mammary gland, and give rise to severe toll on animal welfare, economic gain as well as on excessive use of antibiotics...... in food production. Rapid diagnostic methods are still not available, and particularly pathogen-specific biomarkers would be highly valuable, as these may allow correct antibiotic treatment to be applied shortly after an udder infection has been observed. Moreover, with automatic milking systems and on...

  7. Time resolved bovine host reponse to virulence factors mapped in milk by selected reaction monitoring

    DEFF Research Database (Denmark)

    Bislev, Stine Lønnerup; Kusebauch, Ulrike; Codrea, Marius Cosmin

    in food production. Rapid diagnostic methods are still not available, and particularly pathogen-specific biomarkers would be highly valuable, as these may allow correct antibiotic treatment to be applied shortly after an udder infection has been observed. Moreover, with automatic milking systems and on-line....... Furthermore, this SRM approach provides a strong tool for investigating these proteins in very large scale experiments, particularly with the scope to investigate whether these candidate biomarkers are suited for monitoring animal health in milk production.......TIME RESOLVED BOVINE HOST RESPONSE TO VIRULENCE FACTORS, MAPPED IN MILK BY SELECTED REACTION MONITORING S.L. Bislev1, U. Kusebauch2, M.C. Codrea1, R. Moritz2, C.M. Røntved1, E. Bendixen1 1 Department of Animal Science, Faculty of Science and Technology, Aarhus University, Tjele, Denmark; 2...

  8. Host-related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans

    DEFF Research Database (Denmark)

    Bohn, Torsten; Desmarchelier, Charles; Dragsted, Lars Ove

    2017-01-01

    Carotenoid dietary intake and their endogenous levels have been associated with a decreased risk of several chronic diseases. There are indications that carotenoid bioavailability depends, in addition to the food matrix, on host factors. These include diseases (e.g. colitis), life-style habits (e.......g. smoking), gender and age, as well as genetic variations including single nucleotide polymorphisms that govern carotenoid metabolism. These are expected to explain interindividual differences that contribute to carotenoid uptake, distribution, metabolism and excretion, and therefore possibly also...... their association with disease risk. For instance, digestion enzymes fostering micellization (PNLIP, CES), expression of uptake/efflux transporters (SRARB1, CD36, NPC1L1), cleavage enzymes (BCO1/2), intracellular transporters (FABP2), secretion into chylomicrons (APOB, MTTP), carotenoid metabolism in the blood...

  9. Host-related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans

    DEFF Research Database (Denmark)

    Bohn, Torsten; Desmarchelier, Charles; Dragsted, Lars Ove

    2017-01-01

    Carotenoid dietary intake and their endogenous levels have been associated with a decreased risk of several chronic diseases. There are indications that carotenoid bioavailability depends, in addition to the food matrix, on host factors. These include diseases (e.g. colitis), life-style habits (e.......g. smoking), gender and age, as well as genetic variations including single nucleotide polymorphisms that govern carotenoid metabolism. These are expected to explain interindividual differences that contribute to carotenoid uptake, distribution, metabolism and excretion, and therefore possibly also...... their association with disease risk. For instance, digestion enzymes fostering micellization (PNLIP, CES), expression of uptake/efflux transporters (SRARB1, CD36, NPC1L1), cleavage enzymes (BCO1/2), intracellular transporters (FABP2), secretion into chylomicrons (APOB, MTTP), carotenoid metabolism in the blood...

  10. Highlights Regarding Host Predisposing Factors to Recurrent Vulvovaginal Candidiasis: Chronic Stress and Reduced Antioxidant Capacity.

    Directory of Open Access Journals (Sweden)

    Luciene Akimoto-Gunther

    Full Text Available We studied host factors that could predispose women to develop recurrent vulvovaginal candidiasis (RVVC, including glycemia, insulin resistance, chronic stress, antioxidant capacity, overall immune status, local inflammation and vaginal microbiota. The presence of yeasts in vaginal culture was screened in 277 women, with or without signs and symptoms of VVC and RVVC. The presence of an inflammatory process and microbiota were analyzed through vaginal bacterioscopy and cervical-vaginal cytology, respectively. Fasting-blood samples were collected by standard venipuncture for biochemical analyses. Flow cytometry was employed to obtain the T helper/T cytotoxic lymphocyte ratio, and insulin resistance was assessed by the HOMA index (HI. Yeasts were isolated from 71 (26% women: 23 (32.4% with a positive culture but without symptoms (COL, 22 (31% in an acute episode (VVC, and 26 (36.6% with RVVC. C. albicans was the main yeast isolated in all clinical profiles. The control group (negative culture comprised 206 women. Diabetes mellitus and insulin resistance were more associated with the positive-culture groups (COL, VVC and RVVC than with negative ones. The RVVC group showed lower mean levels of cortisol than the control group and lower antioxidant capacity than all other groups. The T Helper/T cytotoxic lymphocyte ratio was similar in all groups. The RVVC group showed a similar level of vaginal inflammation to the control group, and lower than in the COL and VVC groups. Only the CVV group showed a reduction in vaginal lactobacillus microbiota. Our data suggest that both chronic stress (decreased early-morning cortisol levels and reduced antioxidant capacity can be host predisposing factors to RVVC.

  11. Highlights Regarding Host Predisposing Factors to Recurrent Vulvovaginal Candidiasis: Chronic Stress and Reduced Antioxidant Capacity

    Science.gov (United States)

    Akimoto-Gunther, Luciene; Bonfim-Mendonça, Patrícia de Souza; Takahachi, Gisele; Irie, Mary Mayumi T.; Miyamoto, Sônia; Consolaro, Márcia Edilaine Lopes; Svidzinsk, Terezinha I. Estivalet

    2016-01-01

    We studied host factors that could predispose women to develop recurrent vulvovaginal candidiasis (RVVC), including glycemia, insulin resistance, chronic stress, antioxidant capacity, overall immune status, local inflammation and vaginal microbiota. The presence of yeasts in vaginal culture was screened in 277 women, with or without signs and symptoms of VVC and RVVC. The presence of an inflammatory process and microbiota were analyzed through vaginal bacterioscopy and cervical-vaginal cytology, respectively. Fasting-blood samples were collected by standard venipuncture for biochemical analyses. Flow cytometry was employed to obtain the T helper/T cytotoxic lymphocyte ratio, and insulin resistance was assessed by the HOMA index (HI). Yeasts were isolated from 71 (26%) women: 23 (32.4%) with a positive culture but without symptoms (COL), 22 (31%) in an acute episode (VVC), and 26 (36.6%) with RVVC. C. albicans was the main yeast isolated in all clinical profiles. The control group (negative culture) comprised 206 women. Diabetes mellitus and insulin resistance were more associated with the positive-culture groups (COL, VVC and RVVC) than with negative ones. The RVVC group showed lower mean levels of cortisol than the control group and lower antioxidant capacity than all other groups. The T Helper/T cytotoxic lymphocyte ratio was similar in all groups. The RVVC group showed a similar level of vaginal inflammation to the control group, and lower than in the COL and VVC groups. Only the CVV group showed a reduction in vaginal lactobacillus microbiota. Our data suggest that both chronic stress (decreased early-morning cortisol levels) and reduced antioxidant capacity can be host predisposing factors to RVVC. PMID:27415762

  12. Role of viral and host factors in interferon based therapy of hepatitis C virus infection

    Science.gov (United States)

    2013-01-01

    The current standard of care (SOC) for hepatitis C virus (HCV) infection is the combination of pegylated interferon (PEG-IFN), Ribavirin and protease inhibitor for HCV genotype 1. Nevertheless, this treatment is successful only in 70-80% of the patients. In addition, the treatment is not economical and is of immense physical burden for the subject. It has been established now, that virus-host interactions play a significant role in determining treatment outcomes. Therefore identifying biological markers that may predict the treatment response and hence treatment outcome would be useful. Both IFN and Ribavirin mainly act by modulating the immune system of the patient. Therefore, the treatment response is influenced by genetic variations of the human as well as the HCV genome. The goal of this review article is to summarize the impact of recent scientific advances in this area regarding the understanding of human and HCV genetic variations and their effect on treatment outcomes. Google scholar and PubMed have been used for literature research. Among the host factors, the most prominent associations are polymorphisms within the region of the interleukin 28B (IL28B) gene, but variations in other cytokine genes have also been linked with the treatment outcome. Among the viral factors, HCV genotypes are noteworthy. Moreover, for sustained virological responses (SVR), variations in core, p7, non-structural 2 (NS2), NS3 and NS5A genes are also important. However, all considered single nucleotide polymorphisms (SNPs) of IL28B and viral genotypes are the most important predictors for interferon based therapy of HCV infection. PMID:24079723

  13. Genome-Wide Search for Host Association Factors during Ovine Progressive Pneumonia Virus Infection.

    Directory of Open Access Journals (Sweden)

    Jesse Thompson

    Full Text Available Ovine progressive pneumonia virus (OPPV is an important virus that causes serious diseases in sheep and goats with a prevalence of 36% in the USA. Although OPPV was discovered more than half of a century ago, little is known about the infection and pathogenesis of this virus. In this report, we used RNA-seq technology to conduct a genome-wide probe for cellular factors that are associated with OPPV infection. A total of approximately 22,000 goat host genes were detected of which 657 were found to have been significantly up-regulated and 889 down-regulated at 12 hours post-infection. In addition to previously known restriction factors from other viral infections, a number of factors which may be specific for OPPV infection were uncovered. The data from this RNA-seq study will be helpful in our understanding of OPPV infection, and also for further study in the prevention and intervention of this viral disease.

  14. A novel role of the ferric reductase Cfl1 in cell wall integrity, mitochondrial function, and invasion to host cells in Candida albicans.

    Science.gov (United States)

    Yu, Qilin; Dong, Yijie; Xu, Ning; Qian, Kefan; Chen, Yulu; Zhang, Biao; Xing, Laijun; Li, Mingchun

    2014-11-01

    Candida albicans is an important opportunistic pathogen, causing both superficial mucosal infections and life-threatening systemic diseases. Iron acquisition is an important factor for pathogen-host interaction and also a significant element for the pathogenicity of this organism. Ferric reductases, which convert ferric iron into ferrous iron, are important components of the high-affinity iron uptake system. Sequence analyses have identified at least 17 putative ferric reductase genes in C. albicans genome. CFL1 was the first ferric reductase identified in C. albicans. However, little is known about its roles in C. albicans physiology and pathogenicity. In this study, we found that disruption of CFL1 led to hypersensitivity to chemical and physical cell wall stresses, activation of the cell wall integrity (CWI) pathway, abnormal cell wall composition, and enhanced secretion, indicating a defect in CWI in this mutant. Moreover, this mutant showed abnormal mitochondrial activity and morphology, suggesting a link between ferric reductases and mitochondrial function. In addition, this mutant displayed decreased ability of adhesion to both the polystyrene microplates and buccal epithelial cells and invasion of host epithelial cells. These findings revealed a novel role of C. albicans Cfl1 in maintenance of CWI, mitochondrial function, and interaction between this pathogen and the host.

  15. Leptospira seroprevalence and associations between seropositivity, clinical disease and host factors in horses

    Directory of Open Access Journals (Sweden)

    Engvall E Olsson

    2009-03-01

    Full Text Available Abstract Background A cross-sectional study was carried out to determine the seroprevalence of different serovars of Leptospira spp. and their association with clinical disease and host factors in Swedish horses. Methods Sera from 2017 horses brought to equine clinics during 1997–98 were investigated. The sera were examined by microscopic agglutination test for the presence of antibodies against the following L. interrogans serovars: Bratislava strain Jez, Icterohaemorrhagiae strain Kantorowicz and Pomona strain Pomona and also L. kirschneri sv Grippotyphosa strain Duyster and L. borgpetersenii sv Sejroe strain M 84. Host factors, disease factors, season, pasture access and outdoor confinement variables were analysed with respect to seropositivity to sv Bratislava and Icterohaemorrhagiae. Multivariable logistic regression was used to model seropositivity to sv Bratislava and Icterohaemorrhagiae (seroprevalence > 8%. Results The seroprevalence, at a cut-off 1:100, were for sv Bratislava (16.6%, Icterohaemorrhagiae (8.3%, Sejroe (1.2%, Pomona (0.5% and Grippotyphosa (0.4%. In the multivariable analysis, it was demonstrated that seroprevalence increased with age for sv Bratislava and Icterohaemorrhagiae. For sv Bratislava the seasons April – June and October – December and for sv Icterohaemorrhagiae October – December had higher seroprevalences than other seasons. Horses not used for racing had higher levels of seropositivity to sv Bratislava. Furthermore, horses with respiratory problems as well as horses with fatigue had higher levels of seropositivity to sv Bratislava. Ponies and coldbloods, and horses with access to pasture, had lower seroprevalence for sv Icterohaemorrhagiae. Healthy horses had lower seroprevalence for sv Icterohaemorrhagiae, than non-healthy horses. Conclusion There was no significant association between clinical signs and disease and positive titres to sv Bratislava (except for the association between respiratory

  16. Rare earth doped nanoparticles in organic and inorganic host materials for application in integrated optics

    NARCIS (Netherlands)

    Dekker, R.; Hilderink, L.T.H.; Diemeer, Mart; Stouwdam, J.W.; Sudarsan, V; van Veggel, F.C.J.M.; Driessen, A.; Worhoff, Kerstin; Misra, D; Masscher, P.; Sundaram, K.; Yen, W.M.; Capobianco, J.

    2006-01-01

    The preparation and the optical properties of lanthanum fluoride (LaF3) nanoparticles doped with erbium and neodymium will be discussed. Organic and inorganic materials in the form of polymers and sol-gels were used to serve as the hosts for the inorganic nanoparticles, respectively. The organic

  17. Integrating host gene expression and the microbiome to explore disease pathogenesis.

    Science.gov (United States)

    Byrd, Allyson L; Segre, Julia A

    2015-04-08

    In a recent study, rich clinical assessment and longitudinal study design are combined with host gene expression and microbial sequencing analyses to develop a framework for exploring disease etiology and outcomes in the context of human inflammatory disease.See related article: http://dx.doi.org/10.1186/s13059-015-0637-x.

  18. HIV Integration at Certain Sites in Host DNA Is Linked to the Expansion and Persistence of Infected Cells | Poster

    Science.gov (United States)

    Editor’s note: This article was originally published on the Center for Cancer Research website. When the Human Immunodeficiency Virus (HIV) infects a cell, the virus inserts a copy of its genetic material into the host cell’s DNA. The inserted genetic material, which is also called a provirus, is used to produce new viruses. Because the viral DNA can be inserted at many sites in the host cell DNA, the site of integration marks each infected cell. Patients infected with HIV are currently treated with combined antiretroviral therapy (cART), which prevents viral replication in the majority of treated patients. When cART is initiated, most HIV-infected cells die in one or two days, and more of the infected cells die over a period of weeks to months. However there are some long-lived infected cells that do not die, which prevents patients from being cured.

  19. Key factors of successful JIT integration with IBS - An overview

    Science.gov (United States)

    Asri, Mohammad Azwanie Naim Mohammad; Nawi, Mohd Nasrun Mohd; Nadarajan, Santhirasegaran

    2016-08-01

    The Just-In-Time (JIT) philosophy has been used for many decades to increase productivity through waste elimination process. The purpose of this paper is to contribute to the knowledge by addressing the transportation and material delivery activities in Industrialized Building System (IBS) and integrating JIT to improve the performance of those activities. The literature review has been conducted through relevant database. It was found that there is a need for more holistic approach to be adopted to integrate JIT in IBS project. This paper discusses the key success factors for effective integration between JIT and IBS in the context of transportation and material delivery activities.

  20. Analysis of the Pantoea ananatis pan-genome reveals factors underlying its ability to colonize and interact with plant, insect and vertebrate hosts.

    Science.gov (United States)

    De Maayer, Pieter; Chan, Wai Yin; Rubagotti, Enrico; Venter, Stephanus N; Toth, Ian K; Birch, Paul R J; Coutinho, Teresa A

    2014-05-27

    Pantoea ananatis is found in a wide range of natural environments, including water, soil, as part of the epi- and endophytic flora of various plant hosts, and in the insect gut. Some strains have proven effective as biological control agents and plant-growth promoters, while other strains have been implicated in diseases of a broad range of plant hosts and humans. By analysing the pan-genome of eight sequenced P. ananatis strains isolated from different sources we identified factors potentially underlying its ability to colonize and interact with hosts in both the plant and animal Kingdoms. The pan-genome of the eight compared P. ananatis strains consisted of a core genome comprised of 3,876 protein coding sequences (CDSs) and a sizeable accessory genome consisting of 1,690 CDSs. We estimate that ~106 unique CDSs would be added to the pan-genome with each additional P. ananatis genome sequenced in the future. The accessory fraction is derived mainly from integrated prophages and codes mostly for proteins of unknown function. Comparison of the translated CDSs on the P. ananatis pan-genome with the proteins encoded on all sequenced bacterial genomes currently available revealed that P. ananatis carries a number of CDSs with orthologs restricted to bacteria associated with distinct hosts, namely plant-, animal- and insect-associated bacteria. These CDSs encode proteins with putative roles in transport and metabolism of carbohydrate and amino acid substrates, adherence to host tissues, protection against plant and animal defense mechanisms and the biosynthesis of potential pathogenicity determinants including insecticidal peptides, phytotoxins and type VI secretion system effectors. P. ananatis has an 'open' pan-genome typical of bacterial species that colonize several different environments. The pan-genome incorporates a large number of genes encoding proteins that may enable P. ananatis to colonize, persist in and potentially cause disease symptoms in a wide range of

  1. Master integrals for the four-loop Sudakov form factor

    Directory of Open Access Journals (Sweden)

    Rutger H. Boels

    2016-01-01

    Full Text Available The light-like cusp anomalous dimension is a universal function in the analysis of infrared divergences. In maximally (N=4 supersymmetric Yang–Mills theory (SYM in the planar limit, it is known, in principle, to all loop orders. The non-planar corrections are not known in any theory, with the first appearing at the four-loop order. The simplest quantity which contains this correction is the four-loop two-point form factor of the stress tensor multiplet. This form factor was largely obtained in integrand form in a previous work for N=4 SYM, up to a free parameter. In this work, a reduction of the appearing integrals obtained by solving integration-by-parts (IBP identities using a modified version of Reduze is reported. The form factor is shown to be independent of the remaining parameter at integrand level due to an intricate pattern of cancellations after IBP reduction. Moreover, two of the integral topologies vanish after reduction. The appearing master integrals are cross-checked using independent algebraic-geometry techniques explored in the Mint package. The latter results provide the basis of master integrals applicable to generic form factors, including those in Quantum Chromodynamics. Discrepancies between explicitly solving the IBP relations and the MINT approach are highlighted. Remaining bottlenecks to completing the computation of the four-loop non-planar cusp anomalous dimension in N=4 SYM and beyond are identified.

  2. Sphingosine kinase 2 is a chikungunya virus host factor co-localized with the viral replication complex.

    Science.gov (United States)

    Reid, St Patrick; Tritsch, Sarah R; Kota, Krishna; Chiang, Chih-Yuan; Dong, Lian; Kenny, Tara; Brueggemann, Ernest E; Ward, Michael D; Cazares, Lisa H; Bavari, Sina

    2015-10-01

    Chikungunya virus (CHIKV) is a re-emerging alphavirus which causes severe and prolonged arthralgic febrile illness. The recent global spread of the virus and lack of approved therapeutic options makes it imperative to gain greater insight into the molecular mechanisms underlying CHIKV pathogenesis, in particular host factors recruited by the virus. In the current study, we identify sphingosine kinase 2 (SK2) as a CHIKV host factor co-localized with the viral replication complex (VRC) during infection. SK2 was demonstrated to co-localize with viral RNA and nonstructural proteins. Targeted impairment of SK2 expression or function significantly inhibited CHIKV infection. Furthermore, affinity purification-mass spectrometry studies revealed that SK2 associates with a number of proteins involved in cellular gene expression specifically during viral infection, suggesting a role in replication. Collectively these results identify SK2 as a novel CHIKV host factor.

  3. Caenorhabditis elegans-based screen identifies Salmonella virulence factors required for conserved host-pathogen interactions.

    Science.gov (United States)

    Tenor, Jennifer L; McCormick, Beth A; Ausubel, Frederick M; Aballay, Alejandro

    2004-06-01

    A Caenorhabditis elegans-Salmonella enterica host-pathogen model was used to identify both novel and previously known S. enterica virulence factors (HilA, HilD, InvH, SptP, RhuM, Spi4-F, PipA, VsdA, RepC, Sb25, RfaL, GmhA, LeuO, CstA, and RecC), including several related to the type III secretion system (TTSS) encoded in Salmonella pathogenicity island 1 (SPI-1). Mutants corresponding to presumptive novel virulence-related genes exhibited diminished ability to invade epithelial cells and/or to induce polymorphonuclear leukocyte migration in a tissue culture model of mammalian enteropathogenesis. When expressed in C. elegans intestinal cells, the S. enterica TTSS-exported effector protein SptP inhibited a conserved p38 MAPK signaling pathway and suppressed the diminished pathogenicity phenotype of an S. enterica sptP mutant. These results show that C. elegans is an attractive model to study the interaction between Salmonella effector proteins and components of the innate immune response, in part because there is a remarkable overlap between Salmonella virulence factors required for human and nematode pathogenesis.

  4. Host genetic risk factors for West Nile virus infection and disease progression.

    Directory of Open Access Journals (Sweden)

    Abigail W Bigham

    Full Text Available West Nile virus (WNV, a category B pathogen endemic in parts of Africa, Asia and Europe, emerged in North America in 1999, and spread rapidly across the continental U.S. Outcomes of infection with WNV range from asymptomatic to severe neuroinvasive disease manifested as encephalitis, paralysis, and/or death. Neuroinvasive WNV disease occurs in less than one percent of cases, and although host genetic factors are thought to influence risk for symptomatic disease, the identity of these factors remains largely unknown. We tested 360 common haplotype tagging and/or functional SNPs in 86 genes that encode key regulators of immune function in 753 individuals infected with WNV including: 422 symptomatic WNV cases and 331 cases with asymptomatic infections. After applying a Bonferroni correction for multiple tests and controlling for population stratification, SNPs in IRF3 (OR 0.54, p = 0.035 and MX1, (OR 0.19, p = 0.014 were associated with symptomatic WNV infection and a single SNP in OAS1 (OR 9.79, p = 0.003 was associated with increased risk for West Nile encephalitis and paralysis (WNE/P. Together, these results suggest that genetic variation in the interferon response pathway is associated with both risk for symptomatic WNV infection and WNV disease progression.

  5. Endogenous tissue factor pathway inhibitor has a limited effect on host defence in murine pneumococcal pneumonia.

    Science.gov (United States)

    van den Boogaard, Florry E; van 't Veer, Cornelis; Roelofs, Joris J T H; Meijers, Joost C M; Schultz, Marcus J; Broze, George J; van der Poll, Tom

    2015-07-01

    Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia. Coagulation and inflammation interact in the host response to infection. Tissue factor pathway inhibitor (TFPI) is a natural anticoagulant protein that inhibits tissue factor (TF), the main activator of inflammation-induced coagulation. It was the objective of this study to investigate the effect of endogenous TFPI levels on coagulation, inflammation and bacterial growth during S. pneumoniae pneumonia in mice. The effect of low endogenous TFPI levels was studied by administration of a neutralising anti-TFPI antibody to wild-type mice, and by using genetically modified mice expressing low levels of TFPI, due to a genetic deletion of the first Kunitz domain of TFPI (TFPIK1(-/-)) rescued with a human TFPI transgene. Pneumonia was induced by intranasal inoculation with S. pneumoniae and samples were obtained at 6, 24 and 48 hours after infection. Anti-TFPI reduced TFPI activity by ~50 %. Homozygous lowTFPI mice and heterozygous controls had ~10 % and ~50 % of normal TFPI activity, respectively. TFPI levels did not influence bacterial growth or dissemination. Whereas lung pathology was unaffected in all groups, mice with ~10 % (but not with ~50 %) of TFPI levels displayed elevated lung cytokine and chemokine concentrations 24 hours after infection. None of the groups with low TFPI levels showed an altered procoagulant response in lungs or plasma during pneumonia. These data argue against an important role for endogenous TFPI in the antibacterial, inflammatory and procoagulant response during pneumococcal pneumonia.

  6. Modern Integration Units: Comparative Analysis Of The Growth Factors

    Directory of Open Access Journals (Sweden)

    Bulat Doskalievich Khusainov

    2015-03-01

    Full Text Available In the article, the results of the research, which purpose is to ground and assess the factors of economic growth of regional integration communities and national economies of member countries that develop them, are presented. The foreign trade, mutual trade turnover, and domestic demand are allocated as such factors. The authors has applied the novelty in their methodology which in contrast to the traditional assessment method of growth factors of integration communities and their participants, is based on comparison of two components — external and domestic demand, based on dividing the external demand on two components: the first one is pure export (the difference between export and import is a component of cumulative demand of goods in integration community, i.e. the pure export of mutual trade; the second one is a pure export of foreign trade of goods outside of the integration association. Scope of the research is seven most known regional integrated units arose at different times and being at different stages of development — the European Union, North American Free Trade Area, Association of Southeast Asian Nations, Southern American Common Market, Asia-Pacific Economic Cooperation, and also member countries of the Eurasian integration — the Customs Union and Common Free Market Zone developed into the Eurasian Economic Union in January 1, 2015. In conclusion, it is noted that the integration develops successfully only in the conditions of the rise in national economies of the participating countries. Crisis economies have to deal more with internal problems than to resolve integration issues.

  7. Propionibacterium acnes CAMP factor and host acid sphingomyelinase contribute to bacterial virulence: potential targets for inflammatory acne treatment.

    Directory of Open Access Journals (Sweden)

    Teruaki Nakatsuji

    Full Text Available BACKGROUND: In the progression of acne vulgaris, the disruption of follicular epithelia by an over-growth of Propionibacterium acnes (P. acnes permits the bacteria to spread and become in contact with various skin and immune cells. METHODOLOGY/PRINCIPAL FINDINGS: We have demonstrated in the present study that the Christie, Atkins, Munch-Peterson (CAMP factor of P. acnes is a secretory protein with co-hemolytic activity with sphingomyelinase that can confer cytotoxicity to HaCaT keratinocytes and RAW264.7 macrophages. The CAMP factor from bacteria and acid sphingomyelinase (ASMase from the host cells were simultaneously present in the culture supernatant only when the cells were co-cultured with P. acnes. Either anti-CAMP factor serum or desipramine, a selective ASMase inhibitor, significantly abrogated the P. acnes-induced cell death of HaCaT and RAW264.7 cells. Intradermal injection of ICR mouse ears with live P. acnes induced considerable ear inflammation, macrophage infiltration, and an increase in cellular soluble ASMase. Suppression of ASMase by systemic treatment with desipramine significantly reduced inflammatory reaction induced by intradermal injection with P. acnes, suggesting the contribution of host ASMase in P. acnes-induced inflammatory reaction in vivo. Vaccination of mice with CAMP factor elicited a protective immunity against P. acnes-induced ear inflammation, indicating the involvement of CAMP factor in P. acnes-induced inflammation. Most notably, suppression of both bacterial CAMP factor and host ASMase using vaccination and specific antibody injection, respectively, cooperatively alleviated P. acnes-induced inflammation. CONCLUSIONS/SIGNIFICANCE: These findings envision a novel infectious mechanism by which P. acnes CAMP factor may hijack host ASMase to amplify bacterial virulence to degrade and invade host cells. This work has identified both CAMP factor and ASMase as potential molecular targets for the development of drugs

  8. Natural and human induced factors influencing the abundance of Schistosoma host snails in Zambia.

    Science.gov (United States)

    Monde, Concillia; Syampungani, Stephen; van den Brink, Paul J

    2016-06-01

    Schistosomiasis remains a global public health problem affecting about 240 million people. In Zambia, 2 million are infected while 3 million live with the risk of getting infected. Research and interventions relating to schistosomiasis are mainly linked to disease epidemiology. Malacological and ecological aspects of the disease are superficially understood. Developing effective control measures requires an understanding of interacting environmental and socioeconomic factors of host snails vis-a-vis schistosomiasis. Therefore, the present work involved collecting social and environmental data in a large field study in two zones in Zambia that are different in terms of temperature and rainfall amounts. Social data collected through questionnaires included demographic, educational and knowledge of schistosomiasis disease dynamics. Environmental data included physicochemical factors, aquatic plants and snails. Gender (P < 0.001) significantly influences livelihood strategies, while age (P = 0.069) and level of education (P = 0.086) have a moderate influence in zone I. In zone III, none of these factors (age, P = 0.378; gender, P = 0.311; education, P = 0.553) play a significant role. Environmental parameters explained 43 and 41 % variation in species composition for zones I and III, respectively. Most respondents' (52 %, 87 %) perception is that there are more cases of bilharzia in hot season than in other seasons (rainy season 23 %, 7 %; cold season 8 %, 0 % and year round 17 %, 6 %) for zone I and zone III, respectively.

  9. The Effect of Rural Factors on Migrant Integration in China /

    OpenAIRE

    Tyner, Adam

    2014-01-01

    This dissertation examines the integration of rural-to- urban migrant workers in the People's Republic of China through the lens of rural factors. Although there is a commonly held belief that migrants' marginalization in the cities is a result of urban policies which exclude them from urban society in general and urban public services specifically, the dissertation argues that rural factors such as land rights play a role in migrants' marginalization by perpetuating incentives for migrants t...

  10. The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3' ends.

    Science.gov (United States)

    Xie, Mingyi; Zhang, Wei; Shu, Mei-Di; Xu, Acer; Lenis, Diana A; DiMaio, Daniel; Steitz, Joan A

    2015-07-15

    Herpesvirus saimiri (HVS) is an oncogenic γ-herpesvirus that produces microRNAs (miRNAs) by cotranscription of precursor miRNA (pre-miRNA) hairpins immediately downstream from viral small nuclear RNAs (snRNA). The host cell Integrator complex, which recognizes the snRNA 3' end processing signal (3' box), generates the 5' ends of HVS pre-miRNA hairpins. Here, we identify a novel 3' box-like sequence (miRNA 3' box) downstream from HVS pre-miRNAs that is essential for miRNA biogenesis. In vivo knockdown and rescue experiments confirmed that the 3' end processing of HVS pre-miRNAs also depends on Integrator activity. Interaction between Integrator and HVS primary miRNA (pri-miRNA) substrates that contain only the miRNA 3' box was confirmed by coimmunoprecipitation and an in situ proximity ligation assay (PLA) that we developed to localize specific transient RNA-protein interactions inside cells. Surprisingly, in contrast to snRNA 3' end processing, HVS pre-miRNA 3' end processing by Integrator can be uncoupled from transcription, enabling new approaches to study Integrator enzymology.

  11. Ecological factors driving the long-term evolution of influenza's host range

    Science.gov (United States)

    Cobey, Sarah; Pascual, Mercedes; Dieckmann, Ulf

    2010-01-01

    The evolution of a pathogen's host range is shaped by the ecology of its hosts and by the physiological traits that determine host specificity. For many pathogen traits, there is a trade-off: a phenotype suitable for infecting one set of hosts poorly infects another. Introducing and analysing a simple evo-epidemiological model, here we study how such a trade-off is expected to affect evolution of the host ranges of influenza viruses. We examine a quantitative trait underlying host specificity, given by an influenza virus's degree of adaptation to certain conformations of sialic acid receptors, and investigate how this receptor preference evolves in a minimal network of host species, including humans, that differ in life history and receptor physiology. Using adaptive dynamics theory, we establish thresholds in interspecific transmission rates and host population sizes that govern the emergence and persistence of human-adapted viruses. These ecological thresholds turn out to be largely independent of the strength of the evolutionary trade-off, underscoring the importance of ecological conditions in determining a disease's host range. PMID:20444714

  12. KAP1 Is a Host Restriction Factor That Promotes Human Adenovirus E1B-55K SUMO Modification

    DEFF Research Database (Denmark)

    Bürck, Carolin; Mund, Andreas; Berscheminski, Julia

    2016-01-01

    characterized, but represent a decisive moment in establishing a productive infection. Here, we identify a novel host viral restriction factor, KAP1. This heterochromatin associated transcription factor regulates the dynamic organization of host chromatin structure via its ability to influence epigenetic marks...... epigenetic gene silencing and to promote SUMO modification of E1B-55K by a so far unknown mechanism. IMPORTANCE: Here we describe a novel cellular restriction factor for Human Adenovirus (HAdV) that sheds light on very early modulation processes in viral infection. We reported that chromatin formation...... and cellular SWI/SNF chromatin remodeling play a key role in HAdV transcriptional regulation (1-4). We observed that the cellular chromatin-associated factor, and epigenetic reader SPOC1 represses HAdV infection and gene expression. Here, we illustrate the role of the SPOC1 interacting factor KAP1 during...

  13. M062 is a host range factor essential for myxoma virus pathogenesis and functions as an antagonist of host SAMD9 in human cells.

    Science.gov (United States)

    Liu, Jia; Wennier, Sonia; Zhang, Leiliang; McFadden, Grant

    2011-04-01

    Myxoma virus (MYXV) M062R is a functional homolog of the C7L family of host range genes from orthopoxviruses. We constructed a targeted M062R-knockout-MYXV (vMyxM062-KO) and characterized its properties in vitro and in vivo. In European rabbits, infection by vMyxM062-KO was completely asymptomatic. The surviving rabbits did not gain full protection against the subsequent lethal-dose challenge with wild-type MYXV. We also looked for cellular tropism defects in a variety of cultured cells. In all of the rabbit cells tested, vMyxM062-KO conducts an abortive infection, although it initiates viral DNA replication. In many, but not all, human cancer cells that are permissive for wild-type MYXV, vMyxM062-KO exhibited a profound replication defect. We categorized human cells tested into two groups: (i) type A, which support productive replication for wild-type MYXV but are unable to produce significant levels of progeny virus by vMyxM062-KO, and (ii) type B, which are permissive to infections by both wild-type MYXV and vMyxM062-KO. Furthermore, using proteomic strategies, we identified sterile α motif domain containing 9 (SAMD9), an interferon-regulated cellular protein implicated in human inflammatory disorders, as a unique host binding partner of M062 in human cells. Significantly, knocking down SAMD9 in type A human cancer cells led to a substantial rescue of vMyxM062-KO infection. In summary, M062 is a novel host range factor that controls productive MYXV replication in rabbit cells and in a wide variety of human cells. M062 also binds and antagonizes cellular SAMD9 in human cells, suggesting that SAMD9 is a novel innate antiviral factor against poxviruses.

  14. Modes of Minorities’ Integration: Explaining Historical, Economic and Political Factors

    Directory of Open Access Journals (Sweden)

    Andrada COSTOIU

    2008-11-01

    Full Text Available There are a great number of states in which different ethnic minorities coexist, each of them having their own culture, language and history. In some of these states, the ethnic minorities have been subjected to marginalization and acculturation, in other states the minority groups were recognized as being distinct parts of the nation and were granted equal rights of participation in the public arena. This paper attempts to explain why states opt for such different ways of integrating their minorities. It first develops a typology of minorities’ integration and than, by using the example of two nation-states that fit into each type of integration model it discusses the historical, political and economical factors that could explain each pattern of minorities’ integration.

  15. Conformal anomaly of generalized form factors and finite loop integrals

    CERN Document Server

    Chicherin, Dmitry

    2017-01-01

    We reveal a new mechanism of conformal symmetry breaking at Born level. It occurs in generalized form factors with several local operators and an on-shell state of massless particles. The effect is due to hidden singularities on collinear configurations of the momenta. This conformal anomaly is different from the holomorphic anomaly of amplitudes. We present a number of examples in four and six dimensions. We find an application of the new conformal anomaly to finite loop momentum integrals with one or more massless legs. The collinear region around a massless leg creates a contact anomaly, made visible by the loop integration. The anomalous conformal Ward identity for an $\\ell-$loop integral is a 2nd-order differential equation whose right-hand side is an $(\\ell-1)-$loop integral. We show several examples, in particular the four-dimensional scalar double box.

  16. Temporal SILAC-based quantitative proteomics identifies host factors involved in chikungunya virus replication.

    Science.gov (United States)

    Treffers, Emmely E; Tas, Ali; Scholte, Florine E M; Van, Myrthe N; Heemskerk, Matthias T; de Ru, Arnoud H; Snijder, Eric J; van Hemert, Martijn J; van Veelen, Peter A

    2015-07-01

    Chikungunya virus (CHIKV) is an arthropod-borne reemerging human pathogen that generally causes a severe persisting arthritis. Since 2005, the virus has infected millions of people during outbreaks in Africa, Indian Ocean Islands, Asia, and South/Central America. Many steps of the replication and expression of CHIKV's 12-kb RNA genome are highly dependent on cellular factors, which thus constitute potential therapeutic targets. SILAC and LC-MS/MS were used to define the temporal dynamics of the cellular response to infection. Using samples harvested at 8, 10, and 12 h postinfection, over 4700 proteins were identified and per time point 2800-3500 proteins could be quantified in both biological replicates. At 8, 10, and 12 h postinfection, 13, 38, and 106 proteins, respectively, were differentially expressed. The majority of these proteins showed decreased abundance. Most subunits of the RNA polymerase II complex were progressively degraded, which likely contributes to the transcriptional host shut-off observed during CHIKV infection. Overexpression of four proteins that were significantly downregulated (Rho family GTPase 3 (Rnd3), DEAD box helicase 56 (DDX56), polo-like kinase 1 (Plk1), and ubiquitin-conjugating enzyme E2C (UbcH10) reduced susceptibility of cells to CHIKV infection, suggesting that infection-induced downregulation of these proteins is beneficial for CHIKV replication. All MS data have been deposited in the ProteomeXchange with identifier PXD001330 (http://proteomecentral.proteomexchange.org/dataset/PXD001330).

  17. The contribution of tumor and host tissue factor expression to oncogene-driven gliomagenesis.

    Science.gov (United States)

    Magnus, Nathalie; Meehan, Brian; Garnier, Delphine; Hashemi, Maryam; Montermini, Laura; Lee, Tae Hoon; Milsom, Chloe; Pawlinski, Rafal; Ohlfest, John; Anderson, Mark; Mackman, Nigel; Rak, Janusz

    2014-11-14

    Glioblastoma multiforme (GBM) is an aggressive form of glial brain tumors, associated with angiogenesis, thrombosis, and upregulation of tissue factor (TF), the key cellular trigger of coagulation and signaling. Since TF is upregulated by oncogenic mutations occurring in different subsets of human brain tumors we investigated whether TF contributes to tumourigenesis driven by oncogenic activation of EGFR (EGFRvIII) and RAS pathways in the brain. Here we show that TF expression correlates with poor prognosis in glioma, but not in GBM. In situ, the TF protein expression is heterogeneously expressed in adult and pediatric gliomas. GBM cells harboring EGFRvIII (U373vIII) grow aggressively as xenografts in SCID mice and their progression is delayed by administration of monoclonal antibodies blocking coagulant (CNTO 859) and signaling (10H10) effects of TF in vivo. Mice in which TF gene is disrupted in the neuroectodermal lineage exhibit delayed progression of spontaneous brain tumors driven by oncogenic N-ras and SV40 large T antigen (SV40LT) expressed under the control of sleeping beauty transposase. Reduced host TF levels in low-TF/SCID hypomorphic mice mitigated growth of glioma subcutaneously but not in the brain. Thus, we suggest that tumor-associated TF may serve as therapeutic target in the context of oncogene-driven disease progression in a subset of glioma.

  18. A chromosomally encoded virulence factor protects the Lyme disease pathogen against host-adaptive immunity.

    Directory of Open Access Journals (Sweden)

    Xiuli Yang

    2009-03-01

    Full Text Available Borrelia burgdorferi, the bacterial pathogen of Lyme borreliosis, differentially expresses select genes in vivo, likely contributing to microbial persistence and disease. Expression analysis of spirochete genes encoding potential membrane proteins showed that surface-located membrane protein 1 (lmp1 transcripts were expressed at high levels in the infected murine heart, especially during early stages of infection. Mice and humans with diagnosed Lyme borreliosis also developed antibodies against Lmp1. Deletion of lmp1 severely impaired the pathogen's ability to persist in diverse murine tissues including the heart, and to induce disease, which was restored upon chromosomal complementation of the mutant with the lmp1 gene. Lmp1 performs an immune-related rather than a metabolic function, as its deletion did not affect microbial persistence in immunodeficient mice, but significantly decreased spirochete resistance to the borreliacidal effects of anti-B. burgdorferi sera in a complement-independent manner. These data demonstrate the existence of a virulence factor that helps the pathogen evade host-acquired immune defense and establish persistent infection in mammals.

  19. Host Factors Invovled in the Entry of Coronaviruses into Mammalian Cells

    NARCIS (Netherlands)

    Burkard, C.

    2015-01-01

    Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell. While some viruses fuse with the plasma membrane, many viruses are endocytosed prior to fusion. Specific cues in the endosomal microenvironment induce conformational changes in the viral fus

  20. Identical accumulation and immobilization of sulfated and nonsulfated Nod factors in host and nonhost root hair cell walls

    NARCIS (Netherlands)

    Goedhart, J.; Bono, J.J.; Bisseling, T.; Gadella, T.W.J.

    2003-01-01

    Nod factors are signaling molecules secreted by Rhizobium bacteria. These lipo-chitooligosaccharides (LCOs) are required for symbiosis with legumes and can elicit specific responses at subnanomolar concentrations on a compatible host. How plants perceive LCOs is unclear. In this study, using fluores

  1. Analyses of risk factors for intestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    燕法红

    2014-01-01

    Objective To investigate the risk factors of intestinal acute graft-versus-host disease(aGVHD)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods The clinical data of 534 cases of 533 patients undergoing allo-HSCT during Jan 2004 and Sep 2012were retrospectively analyzed.The effects of donor-recipient HLA

  2. EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy

    Science.gov (United States)

    Lupberger, Joachim; Zeisel, Mirjam B.; Xiao, Fei; Thumann, Christine; Fofana, Isabel; Zona, Laetitia; Davis, Christopher; Mee, Christopher J.; Turek, Marine; Gorke, Sebastian; Royer, Cathy; Fischer, Benoit; Zahid, Muhammad N.; Lavillette, Dimitri; Fresquet, Judith; Cosset, François-Loïc; Rothenberg, S Michael; Pietschmann, Thomas; Patel, Arvind H.; Pessaux, Patrick; Doffoël, Michel; Raffelsberger, Wolfgang; Poch, Olivier; Mckeating, Jane A.; Brino, Laurent; Baumert, Thomas F.

    2011-01-01

    Hepatitis C virus (HCV) is a major cause of liver disease. Therapeutic options are limited and preventive strategies are absent. Entry is the first step of infection and requires the cooperative interaction of several host cell factors. Using a functional RNAi kinase screen we identified epidermal growth factor receptor and ephrin receptor A2 as host co-factors for HCV entry. Blocking of kinase function by approved inhibitors broadly inhibited HCV infection of all major HCV genotypes and viral escape variants in cell culture and an animal model in vivo. Receptor tyrosine kinases (RTKs) mediate HCV entry by regulating CD81-claudin-1 co-receptor associations and membrane fusion. These results identify RTKs as novel HCV entry co-factors and uncover that kinase inhibitors have significant antiviral activity. Inhibition of RTK function may constitute a novel approach for prevention and treatment of HCV infection. PMID:21516087

  3. Biotic mortality factors affecting emerald ash borer (Agrilus planipennis) are highly dependent on life stage and host tree crown condition.

    Science.gov (United States)

    Jennings, D E; Duan, J J; Shrewsbury, P M

    2015-10-01

    Emerald ash borer (EAB), Agrilus planipennis, is a serious invasive forest pest in North America responsible for killing tens to hundreds of millions of ash trees since it was accidentally introduced in the 1990 s. Although host-plant resistance and natural enemies are known to be important sources of mortality for EAB in Asia, less is known about the importance of different sources of mortality at recently colonized sites in the invaded range of EAB, and how these relate to host tree crown condition. To further our understanding of EAB population dynamics, we used a large-scale field experiment and life-table analyses to quantify the fates of EAB larvae and the relative importance of different biotic mortality factors at 12 recently colonized sites in Maryland. We found that the fates of larvae were highly dependent on EAB life stage and host tree crown condition. In relatively healthy trees (i.e., with a low EAB infestation) and for early instars, host tree resistance was the most important mortality factor. Conversely, in more unhealthy trees (i.e., with a moderate to high EAB infestation) and for later instars, parasitism and predation were the major sources of mortality. Life-table analyses also indicated how the lack of sufficient levels of host tree resistance and natural enemies contribute to rapid population growth of EAB at recently colonized sites. Our findings provide further evidence of the mechanisms by which EAB has been able to successfully establish and spread in North America.

  4. Lewis Structures Technology, 1988. Volume 3: Structural Integrity Fatigue and Fracture Wind Turbines HOST

    Science.gov (United States)

    1988-01-01

    The charter of the Structures Division is to perform and disseminate results of research conducted in support of aerospace engine structures. These results have a wide range of applicability to practioners of structural engineering mechanics beyond the aerospace arena. The specific purpose of the symposium was to familiarize the engineering structures community with the depth and range of research performed by the division and its academic and industrial partners. Sessions covered vibration control, fracture mechanics, ceramic component reliability, parallel computing, nondestructive evaluation, constitutive models and experimental capabilities, dynamic systems, fatigue and damage, wind turbines, hot section technology (HOST), aeroelasticity, structural mechanics codes, computational methods for dynamics, structural optimization, and applications of structural dynamics, and structural mechanics computer codes.

  5. Integrated Impacts of environmental factors on the degradation of fumigants

    Science.gov (United States)

    Lee, J.; Yates, S. R.

    2007-12-01

    Volatilization of fumigants has been concerned as one of air pollution sources. Fumigants are used to control nematodes and soil-born pathogens for a pre-plant treatment to increase the production of high-cash crops. One of technologies to reduce the volatilization of fumigants to atmosphere is to enhance the degradation of fumigants in soil. Fumigant degradation is affected by environmental factors such as moisture content, temperature, initial concentration of injected fumigants, and soil properties. However, effects of each factor on the degradation were limitedly characterized and integrated Impacts from environmental factors has not been described yet. Degradation of 1,3- dichloropropene (1,3-D) was investigated in various condition of temperatures (20-60 °C), moisture contents (0 ¡V 30 %) and initial concentrations (0.6 ¡V 60 mg/kg) with Arlington sandy loam soil. Abiotic and biotic degradation processes were distinguished using two sterilization methods with HgCl2 and autoclave and impacts of environmental factors were separately assessed for abiotic and biotic degradations. Initially, degradation rates (k) of cis and trans 1,3-D isomers were estimated by first-order kinetics and modified depending on impacts from environmental factors. Arrhenius equation and Walker¡¦s equation which were conventionally used to describe temperature and moisture effects on degradation were assessed for integrated impacts from environmental factors and logarithmical correlation was observed between initial concentrations of applied fumigants and degradation rates. Understanding integrated impacts of environmental factors on degradation will help to design more effective emission reduction schemes in various conditions and provide more practical parameters for modeling simulations.

  6. Alternative sigma factor sigmaH modulates prophage integration and excision in Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Liang Tao

    2010-05-01

    Full Text Available The prophage is one of the most important components of variable regions in bacterial genomes. Some prophages carry additional genes that may enhance the toxicity and survival ability of their host bacteria. This phenomenon is predominant in Staphylococcus aureus, a very common human pathogen. Bioinformatics analysis of several staphylococcal prophages revealed a highly conserved 40-bp untranslated region upstream of the int gene. A small transcript encoding phage integrase was identified to be initiated from the region, demonstrating that the untranslated region contained a promoter for int. No typical recognition sequence for either sigma(A or sigma(B was identified in the 40-bp region. Experiments both in vitro and in vivo demonstrated that sigma(H recognized the promoter and directed transcription. Genetic deletion of sigH altered the int expression, and subsequently, the excision proportion of prophage DNAs. Phage assays further showed that sigH affected the ability of spontaneous lysis and lysogenization in S. aureus, suggesting that sigH plays a role in stabilizing the lysogenic state. These findings revealed a novel mechanism of prophage integration specifically regulated by a host-source alternative sigma factor. This mechanism suggests a co-evolution strategy of staphylococcal prophages and their host bacteria.

  7. Drosophila host model reveals new enterococcus faecalis quorum-sensing associated virulence factors.

    Science.gov (United States)

    Teixeira, Neuza; Varahan, Sriram; Gorman, Matthew J; Palmer, Kelli L; Zaidman-Remy, Anna; Yokohata, Ryoji; Nakayama, Jiro; Hancock, Lynn E; Jacinto, António; Gilmore, Michael S; de Fátima Silva Lopes, Maria

    2013-01-01

    Enterococcus faecalis V583 is a vancomycin-resistant clinical isolate which belongs to the hospital-adapted clade, CC2. This strain harbours several factors that have been associated with virulence, including the fsr quorum-sensing regulatory system that is known to control the expression of GelE and SprE proteases. To discriminate between genes directly regulated by Fsr, and those indirectly regulated as the result of protease expression or activity, we compared gene expression in isogenic mutants of V583 variously defective in either Fsr quorum sensing or protease expression. Quorum sensing was artificially induced by addition of the quorum signal, GBAP, exogenously in a controlled manner. The Fsr regulon was found to be restricted to five genes, gelE, sprE, ef1097, ef1351 and ef1352. Twelve additional genes were found to be dependent on the presence of GBAP-induced proteases. Induction of GelE and SprE by GBAP via Fsr resulted in accumulation of mRNA encoding lrgAB, and this induction was found to be lytRS dependent. Drosophila infection was used to discern varying levels of toxicity stemming from mutations in the fsr quorum regulatory system and the genes that it regulates, highlighting the contribution of LrgAB and bacteriocin EF1097 to infection toxicity. A contribution of SprE to infection toxicity was also detected. This work brought to light new players in E. faecalis success as a pathogen and paves the way for future studies on host tolerance mechanisms to infections caused by this important nosocomial pathogen.

  8. Ecological and genetic factors influencing the transition between host-use strategies in sympatric Heliconius butterflies.

    Science.gov (United States)

    Merrill, R M; Naisbit, R E; Mallet, J; Jiggins, C D

    2013-09-01

    Shifts in host-plant use by phytophagous insects have played a central role in their diversification. Evolving host-use strategies will reflect a trade-off between selection pressures. The ecological niche of herbivorous insects is partitioned along several dimensions, and if populations remain in contact, recombination will break down associations between relevant loci. As such, genetic architecture can profoundly affect the coordinated divergence of traits and subsequently the ability to exploit novel habitats. The closely related species Heliconius cydno and H. melpomene differ in mimetic colour pattern, habitat and host-plant use. We investigate the selection pressures and genetic basis underlying host-use differences in these two species. Host-plant surveys reveal that H. melpomene specializes on a single species of Passiflora. This is also true for the majority of other Heliconius species in secondary growth forest at our study site, as expected under a model of interspecific competition. In contrast, H. cydno, which uses closed-forest habitats where both Heliconius and Passiflora are less common, appears not to be restricted by competition and uses a broad selection of the available Passiflora. However, other selection pressures are likely involved, and field experiments reveal that early larval survival of both butterfly species is highest on Passiflora menispermifolia, but most markedly so for H. melpomene, the specialist on that host. Finally, we demonstrate an association between host-plant acceptance and colour pattern amongst interspecific hybrids, suggesting that major loci underlying these important ecological traits are physically linked in the genome. Together, our results reveal ecological and genetic associations between shifts in habitat, host use and mimetic colour pattern that have likely facilitated both speciation and coexistence.

  9. A paradigm for endosymbiotic life: cell differentiation of Rhizobium bacteria provoked by host plant factors.

    Science.gov (United States)

    Kondorosi, Eva; Mergaert, Peter; Kereszt, Attila

    2013-01-01

    Symbiosis between Rhizobium bacteria and legumes leads to the formation of the root nodule. The endosymbiotic bacteria reside in polyploid host cells as membrane-surrounded vesicles where they reduce atmospheric nitrogen to support plant growth by supplying ammonia in exchange for carbon sources and energy. The morphology and physiology of endosymbionts, despite their common function, are highly divergent in different hosts. In galegoid plants, the endosymbionts are terminally differentiated, uncultivable polyploid cells, with remarkably elongated and even branched Y-shaped cells. Bacteroid differentiation is controlled by host peptides, many of which have antibacterial activity and require the bacterial function of BacA. Although the precise and combined action of several hundred host peptides and BacA has yet to be discovered, similarities, especially to certain insect-bacterium symbioses involving likewise host peptides for manipulation of endosymbionts, suggest convergent evolution. Rhizobium-legume symbiosis provides a rich source of information for understanding host-controlled endosymbiotic life in eukaryotic cells.

  10. Genetic Factors and Host Traits Predict Spore Morphology for a Butterfly Pathogen

    Directory of Open Access Journals (Sweden)

    Jacobus C. de Roode

    2013-08-01

    Full Text Available Monarch butterflies (Danaus plexippus throughout the world are commonly infected by the specialist pathogen Ophryocystis elektroscirrha (OE. This protozoan is transmitted when larvae ingest infectious stages (spores scattered onto host plant leaves by infected adults. Parasites replicate internally during larval and pupal stages, and adult monarchs emerge covered with millions of dormant spores on the outsides of their bodies. Across multiple monarch populations, OE varies in prevalence and virulence. Here, we examined geographic and genetic variation in OE spore morphology using clonal parasite lineages derived from each of four host populations (eastern and western North America, South Florida and Hawaii. Spores were harvested from experimentally inoculated, captive-reared adult monarchs. Using light microscopy and digital image analysis, we measured the size, shape and color of 30 replicate spores per host. Analyses examined predictors of spore morphology, including parasite source population and clone, parasite load, and the following host traits: family line, sex, wing area, and wing color (orange and black pigmentation. Results showed significant differences in spore size and shape among parasite clones, suggesting genetic determinants of morphological variation. Spore size also increased with monarch wing size, and monarchs with larger and darker orange wings tended to have darker colored spores, consistent with the idea that parasite development depends on variation in host quality and resources. We found no evidence for effects of source population on variation in spore morphology. Collectively, these results provide support for heritable variation in spore morphology and a role for host traits in affecting parasite development.

  11. Transcription factor binding sites are genetic determinants of retroviral integration in the human genome.

    Directory of Open Access Journals (Sweden)

    Barbara Felice

    Full Text Available Gamma-retroviruses and lentiviruses integrate non-randomly in mammalian genomes, with specific preferences for active chromatin, promoters and regulatory regions. Gene transfer vectors derived from gamma-retroviruses target at high frequency genes involved in the control of growth, development and differentiation of the target cell, and may induce insertional tumors or pre-neoplastic clonal expansions in patients treated by gene therapy. The gene expression program of the target cell is apparently instrumental in directing gamma-retroviral integration, although the molecular basis of this phenomenon is poorly understood. We report a bioinformatic analysis of the distribution of transcription factor binding sites (TFBSs flanking >4,000 integrated proviruses in human hematopoietic and non-hematopoietic cells. We show that gamma-retroviral, but not lentiviral vectors, integrate in genomic regions enriched in cell-type specific subsets of TFBSs, independently from their relative position with respect to genes and transcription start sites. Analysis of sequences flanking the integration sites of Moloney leukemia virus (MLV- and human immunodeficiency virus (HIV-derived vectors carrying mutations in their long terminal repeats (LTRs, and of HIV vectors packaged with an MLV integrase, indicates that the MLV integrase and LTR enhancer are the viral determinants of the selection of TFBS-rich regions in the genome. This study identifies TFBSs as differential genomic determinants of retroviral target site selection in the human genome, and suggests that transcription factors binding the LTR enhancer may synergize with the integrase in tethering retroviral pre-integration complexes to transcriptionally active regulatory regions. Our data indicate that gamma-retroviruses and lentiviruses have evolved dramatically different strategies to interact with the host cell chromatin, and predict a higher risk in using gamma-retroviral vs. lentiviral vectors for human

  12. Effect of stiffness and thickness ratio of host plate and piezoelectric patches on reduction of the stress concentration factor

    Science.gov (United States)

    Fesharaki, Javad Jafari; Madani, Seyed Ghasem; Golabi, Sa'id

    2016-09-01

    This paper focuses on the effects of stiffness ratio and thickness ratio on reducing stress concentration factor using piezoelectric patches in a rectangular plate with a hole, as a classical shape. Various locations of actuators and induction of positive/negative strains into the host plate are investigated and the best location of patches is presented. The study investigated the ratio effects and piezoelectric patches bounded on a rectangular host plate having various thicknesses and materials. Results show that the best position of actuators varies based on values of thickness and stiffness ratios of the host plate and piezoelectric patches. Also, the location of maximum stress concentration is transmitted from top and bottom of the hole to another point around the edge by changing the location of the piezoelectric actuators. To verify the results, some experimental tests are applied. The results show good agreement between the finite element analysis and experimental tests.

  13. Host evolution in Mastomys natalensis (Rodentia: Muridae): An integrative approach using geometric morphometrics and genetics.

    Science.gov (United States)

    Lalis, Aude; Evin, Allowen; Janier, Marc; Koivogui, Lamine; Denys, Christiane

    2015-11-01

    The commensal rodent Mastomys natalensis is the natural reservoir of Lassa arenavirus (LASV), which causes hemorrhagic fever in West Africa. To study a possible effect of the virus on phenotypic and genotypic variation of its persistently infected host, we compared LASV-positive and non-infected wild-caught M. natalensis. The LASV effects on the phenotypic variation were explored using standard external morphometric measurements, geometric morphometric analyses of the cranial size and shape, and brain case volume. The genetic variability of M. natalensis specimens was assessed using 9 polymorphic microsatellite markers. Independent of sex and age, LASV-infected animals had smaller external body measurements, reproductive organs, skull size and brain case volume. Cranial shape differences between the 2 groups are represented by a lateral constriction of the entire skull. The genetic variability revealed consanguinity only among the LASV-positive rodents. We hypothesize that growth impairment may result in a selective disadvantage for LASV-infected M. natalensis, leading to a preferably commensal lifestyle in areas where the LAVS is endemic and, thereby, increasing the risk of LASV transmission to humans. © 2015 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and Wiley Publishing Asia Pty Ltd.

  14. Complementary methodologies to investigate human gut microbiota in host health, working towards integrative systems biology.

    Science.gov (United States)

    Méndez-García, Celia; Barbas, Coral; Ferrer, Manuel; Rojo, David

    2017-09-05

    In 1680, Antonie van Leewenhoek noted compositional differences in his oral and fecal microbiota, pioneering the study of the diversity of the human microbiome. From Leewenhoek to modern successful attempts of changing the gut microbiota landscape to cure disease, there has been an exponential increase in the recognition of our resident microbes as part of ourselves. Thus, the human host and microbiome have evolved in parallel to configure a balanced system in which microbes survive in homeostasis with our innate and acquired immune system, unless disease occurs. A growing number of studies have demonstrated a correlation between the presence/absence of microbial taxa, and some of their functional molecules (i.e. genes, proteins, and metabolites), with health and disease states. Nevertheless, misleading experimental design on human subjects, and the cost and lack of standardized animal models pose challenges to answering the question of whether changes in the microbiome composition are cause or consequence of a certain biological state. In this review, we evaluate the state of the art of methodologies that enable the study of the gut microbiome, encouraging a change in broadly used analytic strategies by choosing effector molecules (proteins, metabolites) in combination with coding nucleic acids. We further explore microbial and effector microbial products imbalances that relate to disease and health. Copyright © 2017 American Society for Microbiology.

  15. Microscopy-based Assays for High-throughput Screening of Host Factors Involved in Brucella Infection of Hela Cells.

    Science.gov (United States)

    Casanova, Alain; Low, Shyan H; Emmenlauer, Mario; Conde-Alvarez, Raquel; Salcedo, Suzana P; Gorvel, Jean-Pierre; Dehio, Christoph

    2016-08-05

    Brucella species are facultative intracellular pathogens that infect animals as their natural hosts. Transmission to humans is most commonly caused by direct contact with infected animals or by ingestion of contaminated food and can lead to severe chronic infections. Brucella can invade professional and non-professional phagocytic cells and replicates within endoplasmic reticulum (ER)-derived vacuoles. The host factors required for Brucella entry into host cells, avoidance of lysosomal degradation, and replication in the ER-like compartment remain largely unknown. Here we describe two assays to identify host factors involved in Brucella entry and replication in HeLa cells. The protocols describe the use of RNA interference, while alternative screening methods could be applied. The assays are based on the detection of fluorescently labeled bacteria in fluorescently labeled host cells using automated wide-field microscopy. The fluorescent images are analyzed using a standardized image analysis pipeline in CellProfiler which allows single cell-based infection scoring. In the endpoint assay, intracellular replication is measured two days after infection. This allows bacteria to traffic to their replicative niche where proliferation is initiated around 12 hr after bacterial entry. Brucella which have successfully established an intracellular niche will thus have strongly proliferated inside host cells. Since intracellular bacteria will greatly outnumber individual extracellular or intracellular non-replicative bacteria, a strain constitutively expressing GFP can be used. The strong GFP signal is then used to identify infected cells. In contrast, for the entry assay it is essential to differentiate between intracellular and extracellular bacteria. Here, a strain encoding for a tetracycline-inducible GFP is used. Induction of GFP with simultaneous inactivation of extracellular bacteria by gentamicin enables the differentiation between intracellular and extracellular

  16. Master integrals for the four-loop Sudakov form factor

    CERN Document Server

    Boels, Rutger; Yang, Gang

    2016-01-01

    The light-like cusp anomalous dimension is a universal function in the analysis of infrared divergences. In maximally ($\\mathcal{N}=4$) supersymmetric Yang-Mills theory (SYM) in the planar limit, it is known, in principle, to all loop orders. The non-planar corrections are not known in any theory, with the first appearing at the four-loop order. Probably the simplest quantity which contains this correction is the four-loop two-point form factor of the stress tensor multiplet. This form factor was obtained in integrand form in a previous work for $\\mathcal{N}=4$ SYM, up to a single parameter. In this work, a reduction of the appearing integrals obtained by solving integration-by-parts (IBP) identities using (a tweaked version of) Reduze is reported. The form factor is shown to be independent of the remaining parameter at integrand level due to an intricate pattern of cancellations after IBP reduction. The appearing master integrals are cross-checked using algebraic techniques explored in the Mint package. The ...

  17. Eop1 from a Rubus strain of Erwinia amylovora functions as a host-range limiting factor.

    Science.gov (United States)

    Asselin, J E; Bonasera, J M; Kim, J F; Oh, C-S; Beer, S V

    2011-08-01

    Strains of Erwinia amylovora, the bacterium causing the disease fire blight of rosaceous plants, are separated into two groups based on host range: Spiraeoideae and Rubus strains. Spiraeoideae strains have wide host ranges, infecting plants in many rosaceous genera, including apple and pear. In the field, Rubus strains infect the genus Rubus exclusively, which includes raspberry and blackberry. Based on comparisons of limited sequence data from a Rubus and a Spiraeoideae strain, the gene eop1 was identified as unusually divergent, and it was selected as a possible host specificity factor. To test this, eop1 genes from a Rubus strain and a Spiraeoideae strain were cloned and mutated. Expression of the Rubus-strain eop1 reduced the virulence of E. amylovora in immature pear fruit and in apple shoots. Sequencing the orfA-eop1 regions of several strains of E. amylovora confirmed that forms of eop1 are conserved among strains with similar host ranges. This work provides evidence that eop1 from a Rubus-specific strain can function as a determinant of host specificity in E. amylovora.

  18. SymbioGenomesDB: a database for the integration and access to knowledge on host-symbiont relationships.

    Science.gov (United States)

    Reyes-Prieto, Mariana; Vargas-Chávez, Carlos; Latorre, Amparo; Moya, Andrés

    2015-01-01

    Symbiotic relationships occur naturally throughout the tree of life, either in a commensal, mutualistic or pathogenic manner. The genomes of multiple organisms involved in symbiosis are rapidly being sequenced and becoming available, especially those from the microbial world. Currently, there are numerous databases that offer information on specific organisms or models, but none offer a global understanding on relationships between organisms, their interactions and capabilities within their niche, as well as their role as part of a system, in this case, their role in symbiosis. We have developed the SymbioGenomesDB as a community database resource for laboratories which intend to investigate and use information on the genetics and the genomics of organisms involved in these relationships. The ultimate goal of SymbioGenomesDB is to host and support the growing and vast symbiotic-host relationship information, to uncover the genetic basis of such associations. SymbioGenomesDB maintains a comprehensive organization of information on genomes of symbionts from diverse hosts throughout the Tree of Life, including their sequences, their metadata and their genomic features. This catalog of relationships was generated using computational tools, custom R scripts and manual integration of data available in public literature. As a highly curated and comprehensive systems database, SymbioGenomesDB provides web access to all the information of symbiotic organisms, their features and links to the central database NCBI. Three different tools can be found within the database to explore symbiosis-related organisms, their genes and their genomes. Also, we offer an orthology search for one or multiple genes in one or multiple organisms within symbiotic relationships, and every table, graph and output file is downloadable and easy to parse for further analysis. The robust SymbioGenomesDB will be constantly updated to cope with all the data being generated and included in major

  19. To be or not to be: The host genetic factor and beyond in Helicobacter pylori mediated gastro-duodenal diseases.

    Science.gov (United States)

    Datta De, Dipanjana; Roychoudhury, Susanta

    2015-03-14

    Helicobacter pylori (H. pylori) have long been associated with a spectrum of disease outcomes in the gastro-duodenal system. Heterogeneity in bacterial virulence factors or strains is not enough to explain the divergent disease phenotypes manifested by the infection. This review focuses on host genetic factors that are involved during infection and eventually are thought to influence the disease phenotype. We have summarized the different host genes that have been investigated for association studies in H. pylori mediated duodenal ulcer or gastric cancer. We discuss that as the bacteria co-evolved with the host; these host gene also show much variation across different ethnic population. We illustrate the allelic distribution of interleukin-1B, across different population which is one of the most popular candidate gene studied with respect to H. pylori infections. Further, we highlight that several polymorphisms in the pathway gene can by itself or collectively affect the acid secretion pathway axis (gastrin: somatostatin) thereby resulting in a spectrum of disease phenotype.

  20. Identification of host cytosolic sensors and bacterial factors regulating the type I interferon response to Legionella pneumophila.

    Directory of Open Access Journals (Sweden)

    Kathryn M Monroe

    2009-11-01

    Full Text Available Legionella pneumophila is a gram-negative bacterial pathogen that replicates in host macrophages and causes a severe pneumonia called Legionnaires' Disease. The innate immune response to L. pneumophila remains poorly understood. Here we focused on identifying host and bacterial factors involved in the production of type I interferons (IFN in response to L. pneumophila. It was previously suggested that the delivery of L. pneumophila DNA to the host cell cytosol is the primary signal that induces the type I IFN response. However, our data are not easily reconciled with this model. We provide genetic evidence that two RNA-sensing proteins, RIG-I and MDA5, participate in the IFN response to L. pneumophila. Importantly, these sensors do not seem to be required for the IFN response to L. pneumophila DNA, whereas we found that RIG-I was required for the response to L. pneumophila RNA. Thus, we hypothesize that bacterial RNA, or perhaps an induced host RNA, is the primary stimulus inducing the IFN response to L. pneumophila. Our study also identified a secreted effector protein, SdhA, as a key suppressor of the IFN response to L. pneumophila. Although viral suppressors of cytosolic RNA-sensing pathways have been previously identified, analogous bacterial factors have not been described. Thus, our results provide new insights into the molecular mechanisms by which an intracellular bacterial pathogen activates and also represses innate immune responses.

  1. Adaptation to toxic hosts as a factor in the evolution of insecticide resistance.

    Science.gov (United States)

    Alyokhin, Andrei; Chen, Yolanda H

    2017-06-01

    Insecticide resistance is a serious economic problem that jeopardizes sustainability of chemical control of herbivorous insects and related arthropods. It can be viewed as a specific case of adaptation to toxic chemicals, which has been driven in large part, but not exclusively, by the necessity for insect pests to tolerate defensive compounds produced by their host plants. Synthetic insecticides may simply change expression of specific sets of detoxification genes that have evolved due to ancestral associations with host plants. Feeding on host plants with more abundant or novel secondary metabolites has even been shown to prime insect herbivores to tolerate pesticides. Clear understanding of basic evolutionary processes is important for achieving lasting success in managing herbivorous arthropods. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Influence of temperature on symptom expression, detection of host factors in virus infected Piper nigrum L.

    Science.gov (United States)

    Umadevi, P; Bhat, A I; Krishnamurthy, K S; Anandaraj, M

    2016-05-01

    Expression of symptoms in black pepper plants (Piper nigrum) infected with Piper yellow mottle virus (PYMoV) vary depending on the season, being high during summer months. Here, we explored the influence of temperature on symptom expression in PYMoV infected P. nigrum. Our controlled environment study revealed increase in virus titer, total proteins, IAA and reducing sugars when exposed to temperature stress. There was change in the 2-D separated protein before and after exposure. The 2-D proteomics LC-MS identified host and viral proteins suggesting virus-host interaction during symptom expression. The analysis as well as detection of host biochemical compounds may help in understanding the detailed mechanisms underlying the viral replication and damage to the crop, and thereby plan management strategies.

  3. Zero modes method and form factors in quantum integrable models

    Directory of Open Access Journals (Sweden)

    S. Pakuliak

    2015-04-01

    Full Text Available We study integrable models solvable by the nested algebraic Bethe ansatz and possessing GL(3-invariant R-matrix. Assuming that the monodromy matrix of the model can be expanded into series with respect to the inverse spectral parameter, we define zero modes of the monodromy matrix entries as the first nontrivial coefficients of this series. Using these zero modes we establish new relations between form factors of the elements of the monodromy matrix. We prove that all of them can be obtained from the form factor of a diagonal matrix element in special limits of Bethe parameters. As a result we obtain determinant representations for form factors of all the entries of the monodromy matrix.

  4. Virulence factors of Actinobacillus pleuropneumoniae involved in colonization, persistence and induction of lesions in its porcine host

    Science.gov (United States)

    Chiers, Koen; De Waele, Tine; Pasmans, Frank; Ducatelle, Richard; Haesebrouck, Freddy

    2010-01-01

    Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia. The virulence factors of this microorganism involved in colonization and the induction of lung lesions have been thoroughly studied and some have been well characterized. A. pleuropneumoniae binds preferentially to cells of the lower respiratory tract in a process involving different adhesins and probably biofilm formation. Apx toxins and lipopolysaccharides exert pathogenic effects on several host cells, resulting in typical lung lesions. Lysis of host cells is essential for the bacterium to obtain nutrients from the environment and A. pleuropneumoniae has developed several uptake mechanisms for these nutrients. In addition to persistence in lung lesions, colonization of the upper respiratory tract – and of the tonsils in particular – may also be important for long-term persistent asymptomatic infection. Information on virulence factors involved in tonsillar and nasal cavity colonization and persistence is scarce, but it can be speculated that similar features as demonstrated for the lung may play a role. PMID:20546697

  5. EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy.

    Science.gov (United States)

    Lupberger, Joachim; Zeisel, Mirjam B; Xiao, Fei; Thumann, Christine; Fofana, Isabel; Zona, Laetitia; Davis, Christopher; Mee, Christopher J; Turek, Marine; Gorke, Sebastian; Royer, Cathy; Fischer, Benoit; Zahid, Muhammad N; Lavillette, Dimitri; Fresquet, Judith; Cosset, François-Loïc; Rothenberg, S Michael; Pietschmann, Thomas; Patel, Arvind H; Pessaux, Patrick; Doffoël, Michel; Raffelsberger, Wolfgang; Poch, Olivier; McKeating, Jane A; Brino, Laurent; Baumert, Thomas F

    2011-05-01

    Hepatitis C virus (HCV) is a major cause of liver disease, but therapeutic options are limited and there are no prevention strategies. Viral entry is the first step of infection and requires the cooperative interaction of several host cell factors. Using a functional RNAi kinase screen, we identified epidermal growth factor receptor and ephrin receptor A2 as host cofactors for HCV entry. Blocking receptor kinase activity by approved inhibitors broadly impaired infection by all major HCV genotypes and viral escape variants in cell culture and in a human liver chimeric mouse model in vivo. The identified receptor tyrosine kinases (RTKs) mediate HCV entry by regulating CD81-claudin-1 co-receptor associations and viral glycoprotein-dependent membrane fusion. These results identify RTKs as previously unknown HCV entry cofactors and show that tyrosine kinase inhibitors have substantial antiviral activity. Inhibition of RTK function may constitute a new approach for prevention and treatment of HCV infection.

  6. Host and Environmental Factors Modulate the Exposure of Free-Ranging and Farmed Red Deer (Cervus elaphus) to Coxiella burnetii

    OpenAIRE

    González-Barrio, David; Velasco Ávila , Ana Luisa; Boadella, Mariana; Beltrán-Beck, Beatriz; Barasona, José Ángel; Santos, João P. V.; Queirós, João; García-Pérez, Ana L; Barral, Marta; Ruiz-Fons, Francisco

    2015-01-01

    The control of multihost pathogens, such as Coxiella burnetii, should rely on accurate information about the roles played by the main hosts. We aimed to determine the involvement of the red deer (Cervus elaphus) in the ecology of C. burnetii. We predicted that red deer populations from broad geographic areas within a European context would be exposed to C. burnetii, and therefore, we hypothesized that a series of factors would modulate the exposure of red deer to C. burnetii. To test this hyp...

  7. Behavioural risk factors in two generations of non-Western migrants: do trends converge towards the host population?

    OpenAIRE

    Hosper, K.; Nierkens, V.; Nicolaou, M; Stronks, K

    2007-01-01

    Migrant mortality does not conform to a single pattern of convergence towards prevalence rates in the host population. To understand better how migrant mortality develops, it is necessary to further investigate how the underlying behavioural determinants change following migration. We studied whether the prevalence of behavioural risk factors over two generations of Turkish and Moroccan migrants converge towards the prevalence rates in the Dutch population. From a random sample from the popul...

  8. First Integrals, Integrating Factors, and Invariant Solutions of the Path Equation Based on Noether and -Symmetries

    Directory of Open Access Journals (Sweden)

    Gülden Gün

    2013-01-01

    Full Text Available We analyze Noether and -symmetries of the path equation describing the minimum drag work. First, the partial Lagrangian for the governing equation is constructed, and then the determining equations are obtained based on the partial Lagrangian approach. For specific altitude functions, Noether symmetry classification is carried out and the first integrals, conservation laws and group invariant solutions are obtained and classified. Then, secondly, by using the mathematical relationship with Lie point symmetries we investigate -symmetry properties and the corresponding reduction forms, integrating factors, and first integrals for specific altitude functions of the governing equation. Furthermore, we apply the Jacobi last multiplier method as a different approach to determine the new forms of -symmetries. Finally, we compare the results obtained from different classifications.

  9. European Monetary Integration as a Development Factor of Eurocurrency Market

    Directory of Open Access Journals (Sweden)

    Ćurić Predrag

    2016-12-01

    Full Text Available Economic interconnection among the European countries influenced the birth of a single economic space with a common monetary policy. In addition, the abolition of the gold standard represented an important external factor that followed the same path. In parallel with these processes, the conditions were created for developing a Eurocurrency market which favoured financial integration of Europe, as well as the creation of a single European currency. In accordance with such economic flows, Eurocurrency market emerged as a distinguished international financial market, crucial for the development of international banking. Thus, business entities were allowed to access the capital which represents the transfer of the international accumulation of the exporting country onto the European capital market, thereby resulting in more efficient financing of the member states. Thanks to similar economic effects, these processes of European monetary integrations have become imperative to other countries in the region.

  10. Factors affecting virus dynamics and microbial host-virus interactions in marine environments

    NARCIS (Netherlands)

    Mojica, K.D.A.; Brussaard, C.P.D.

    2015-01-01

    Marine microorganisms constitute the largest percentage of living biomass and serve as the major driving force behind nutrient and energy cycles. While viruses only comprise a small percentage of this biomass (i.e., 5%), they dominate in numerical abundance and genetic diversity. Through host infect

  11. Factors affecting virus dynamics and microbial host-virus interactions in marine environments

    NARCIS (Netherlands)

    Mojica, K.D.A.; Brussaard, C.P.D.

    2014-01-01

    Marine microorganisms constitute the largest percentage of living biomass and serve as the major driving force behind nutrient and energy cycles. While viruses only comprise a small percentage of this biomass (i.e., 5%), they dominate in numerical abundance and genetic diversity. Through host infect

  12. Factors affecting virus dynamics and microbial host-virus interactions in marine environments

    NARCIS (Netherlands)

    Mojica, K.D.A.; Brussaard, C.P.D.

    2014-01-01

    Marine microorganisms constitute the largest percentage of living biomass and serve as the major driving force behind nutrient and energy cycles. While viruses only comprise a small percentage of this biomass (i.e., 5%), they dominate in numerical abundance and genetic diversity. Through host infect

  13. Factors affecting virus dynamics and microbial host-virus interactions in marine environments

    NARCIS (Netherlands)

    Mojica, K.D.A.; Brussaard, C.P.D.

    2015-01-01

    Marine microorganisms constitute the largest percentage of living biomass and serve as the major driving force behind nutrient and energy cycles. While viruses only comprise a small percentage of this biomass (i.e., 5%), they dominate in numerical abundance and genetic diversity. Through host infect

  14. Genetic structure in the seabuckthorn carpenter moth (Holcocerus hippophaecolus in China: the role of outbreak events, geographical and host factors.

    Directory of Open Access Journals (Sweden)

    Jing Tao

    Full Text Available Understanding factors responsible for structuring genetic diversity is of fundamental importance in evolutionary biology. The seabuckthorn carpenter moth (Holcocerus hippophaecolus Hua is a native species throughout the north of China and is considered the main threat to seabuckthorn, Hippophae rhamnoides L. We assessed the influence of outbreaks, environmental factors and host species in shaping the genetic variation and structure of H. hippophaecolus by using Amplified Fragment Length Polymorphism (AFLP markers. We rejected the hypothesis that outbreak-associated genetic divergence exist, as evidenced by genetic clusters containing a combination of populations from historical outbreak areas, as well as non-outbreak areas. Although a small number of markers (4 of 933 loci were identified as candidates under selection in response to population densities. H. hippophaecolus also did not follow an isolation-by-distance pattern. We rejected the hypothesis that outbreak and drought events were driving the genetic structure of H. hippophaecolus. Rather, the genetic structure appears to be influenced by various confounding bio-geographical factors. There were detectable genetic differences between H. hippophaecolus occupying different host trees from within the same geographic location. Host-associated genetic divergence should be confirmed by further investigation.

  15. Investigating the host galaxies of luminous AGN in the local universe with integral field spectroscopy

    Science.gov (United States)

    McElroy, Rebecca; Croom, Scott; Husemann, Bernd; Close AGN Reference Survey; SAMI Galaxy Survey

    2017-01-01

    This thesis investigates how galaxies and their super massive black holes coevolve. We use integral field spectroscopy to search for evidence of AGN feedback and triggering. We demonstrate that outflows are ubiquitous among luminous local type 2 AGN using observations from the AAT's SPIRAL instrument. Using multiple component Gaussian emission line decomposition we are able to disentangle the kinematic and ionisation properties of these winds. This allows us to argue that the outflows from these AGN are directly impacting the surrounding ISM within the galaxies. We search for evidence of AGN triggering using data from The Close AGN Reference Survey (CARS). CARS aims to provide a detailed multi-wavelength view of 40 nearby (0.01 type not once, but twice. So called ‘changing look’ AGN are an uncommon phenomenon, but twice changed AGN are much rarer. This AGN first transitioned from a narrow line AGN (type 2) to a broad line AGN (type 1) in the 1980s. It was recently observed as part of CARS. Examination of the MUSE data for this particular source showed that it no longer had the spectral features typical of a type 1 AGN. The continuum emission from the accretion disk was no longer visible and the broad lines were dramatically diminished. In this talk we describe the possible reasons for this change, supported by analysis of multi-epoch optical photometry and spectroscopy, alongside data obtained through director’s discretionary time from Chandra, HST, and the VLA. We then conclude by discussing the implications of this discovery on our understanding of AGN timescales and the physics behind AGN spectral types.

  16. Factors Influencing Learning Environments in an Integrated Experiential Program

    Science.gov (United States)

    Koci, Peter

    The research conducted for this dissertation examined the learning environment of a specific high school program that delivered the explicit curriculum through an integrated experiential manner, which utilized field and outdoor experiences. The program ran over one semester (five months) and it integrated the grade 10 British Columbian curriculum in five subjects. A mixed methods approach was employed to identify the students' perceptions and provide richer descriptions of their experiences related to their unique learning environment. Quantitative instruments were used to assess changes in students' perspectives of their learning environment, as well as other supporting factors including students' mindfulness, and behaviours towards the environment. Qualitative data collection included observations, open-ended questions, and impromptu interviews with the teacher. The qualitative data describe the factors and processes that influenced the learning environment and give a richer, deeper interpretation which complements the quantitative findings. The research results showed positive scores on all the quantitative measures conducted, and the qualitative data provided further insight into descriptions of learning environment constructs that the students perceived as most important. A major finding was that the group cohesion measure was perceived by students as the most important attribute of their preferred learning environment. A flow chart was developed to help the researcher conceptualize how the learning environment, learning process, and outcomes relate to one another in the studied program. This research attempts to explain through the consideration of this case study: how learning environments can influence behavioural change and how an interconnectedness among several factors in the learning process is influenced by the type of learning environment facilitated. Considerably more research is needed in this area to understand fully the complexity learning

  17. A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria.

    Science.gov (United States)

    Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2016-07-29

    Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens.

  18. An Integrated Simulation System for Human Factors Study

    CERN Document Server

    Wang, Ying; Bennis, Fouad; Chablat, Damien

    2007-01-01

    It has been reported that virtual reality can be a useful tool for ergonomics study. The proposed integrated simulation system aims at measuring operator's performance in an interactive way for 2D control panel design. By incorporating some sophisticated virtual reality hardware/software, the system allows natural human-system and/or human-human interaction in a simulated virtual environment; enables dynamic objective measurement of human performance; and evaluates the quality of the system design in human factors perspective based on the measurement. It can also be for operation training for some 2D control panels.

  19. Heat shock factors: integrators of cell stress, development and lifespan.

    Science.gov (United States)

    Akerfelt, Malin; Morimoto, Richard I; Sistonen, Lea

    2010-08-01

    Heat shock factors (HSFs) are essential for all organisms to survive exposures to acute stress. They are best known as inducible transcriptional regulators of genes encoding molecular chaperones and other stress proteins. Four members of the HSF family are also important for normal development and lifespan-enhancing pathways, and the repertoire of HSF targets has thus expanded well beyond the heat shock genes. These unexpected observations have uncovered complex layers of post-translational regulation of HSFs that integrate the metabolic state of the cell with stress biology, and in doing so control fundamental aspects of the health of the proteome and ageing.

  20. Behavioural risk factors in two generations of non-Western migrants: do trends converge towards the host population?

    Science.gov (United States)

    Hosper, Karen; Nierkens, Vera; Nicolaou, Mary; Stronks, Karien

    2007-01-01

    Migrant mortality does not conform to a single pattern of convergence towards prevalence rates in the host population. To understand better how migrant mortality develops, it is necessary to further investigate how the underlying behavioural determinants change following migration. We studied whether the prevalence of behavioural risk factors over two generations of Turkish and Moroccan migrants converge towards the prevalence rates in the Dutch population. From a random sample from the population register of Amsterdam, 291 Moroccan and 505 Turkish migrants, aged 15-30, participated in a structured interview that included questions on smoking, alcohol consumption, physical inactivity and weight/height. Data from the Dutch population were available from Statistics Netherlands. By calculating age-adjusted Odds Ratio's, prevalence rates among both generations were compared with prevalence rates in the host population for men and women separately. We found indications of convergence across generations towards the prevalence rates in the host population for smoking in Turkish men, for overweight in Turkish and Moroccan women and for physical inactivity in Turkish women. Alcohol consumption, however, remained low in all subgroups and did not converge towards the higher rates in the host population. In addition, we found a reversed trend among Turkish women regarding smoking: the second generation smoked significantly more, while the first generation did not differ from ethnic Dutch. In general, behavioural risk factors in two generations of non-Western migrants in the Netherlands seem to converge towards the prevalence rates in the Dutch population. However, some subgroups and risk factors showed a different pattern.

  1. PlnTFDB: an integrative plant transcription factor database

    Directory of Open Access Journals (Sweden)

    Ruzicic Slobodan

    2007-02-01

    Full Text Available Abstract Background Transcription factors (TFs are key regulatory proteins that enhance or repress the transcriptional rate of their target genes by binding to specific promoter regions (i.e. cis-acting elements upon activation or de-activation of upstream signaling cascades. TFs thus constitute master control elements of dynamic transcriptional networks. TFs have fundamental roles in almost all biological processes (development, growth and response to environmental factors and it is assumed that they play immensely important functions in the evolution of species. In plants, TFs have been employed to manipulate various types of metabolic, developmental and stress response pathways. Cross-species comparison and identification of regulatory modules and hence TFs is thought to become increasingly important for the rational design of new plant biomass. Up to now, however, no computational repository is available that provides access to the largely complete sets of transcription factors of sequenced plant genomes. Description PlnTFDB is an integrative plant transcription factor database that provides a web interface to access large (close to complete sets of transcription factors of several plant species, currently encompassing Arabidopsis thaliana (thale cress, Populus trichocarpa (poplar, Oryza sativa (rice, Chlamydomonas reinhardtii and Ostreococcus tauri. It also provides an access point to its daughter databases of a species-centered representation of transcription factors (OstreoTFDB, ChlamyTFDB, ArabTFDB, PoplarTFDB and RiceTFDB. Information including protein sequences, coding regions, genomic sequences, expressed sequence tags (ESTs, domain architecture and scientific literature is provided for each family. Conclusion We have created lists of putatively complete sets of transcription factors and other transcriptional regulators for five plant genomes. They are publicly available through http://plntfdb.bio.uni-potsdam.de. Further data will be

  2. Factors associated with clinical inertia: an integrative review

    Science.gov (United States)

    Aujoulat, Isabelle; Jacquemin, Patricia; Rietzschel, Ernst; Scheen, André; Tréfois, Patrick; Wens, Johan; Darras, Elisabeth; Hermans, Michel P

    2014-01-01

    Failure to initiate or intensify therapy according to evidence-based guidelines is increasingly being acknowledged as a phenomenon that contributes to inadequate management of chronic conditions, and is referred to as clinical inertia. However, the number and complexity of factors associated with the clinical reasoning that underlies the decision-making processes in medicine calls for a critical examination of the consistency of the concept. Indeed, in the absence of information on and justification of treatment decisions that were made, clinical inertia may be only apparent, and actually reflect good clinical practice. This integrative review seeks to address the factors generally associated with clinical inaction, in order to better delineate the concept of true clinical inertia. PMID:24868181

  3. The late endosomal adaptor p14 is a macrophage host-defense factor against Salmonella infection.

    Science.gov (United States)

    Taub, Nicole; Nairz, Manfred; Hilber, Diana; Hess, Michael W; Weiss, Günter; Huber, Lukas A

    2012-06-01

    The outcome of an infection depends on the balance between host resistance and bacterial virulence. Here, we show that the late endosomal adaptor p14 (also known as LAMTOR2) is one of the components for cellular host defense against the intracellular pathogen Salmonella enterica serovar Typhimurium. During Salmonella infection, the complex of p14 and MP1 is required for the accurately timed transport of Salmonella through the endolysosomal system. Loss of p14 opens a time window that allows Salmonella to populate a replication niche, in which early and late antimicrobial effector systems, comprising NADPH phagocytic oxidase and inducible nitric oxide synthase, respectively, are inappropriately activated. Thus, p14 supports the accurate transport of Salmonella through the endolysosomal system, thereby limiting bacterial replication in both, professional phagocytes and in non-phagocytic cells in vitro, and helps mice to successfully battle Salmonella infection in vivo.

  4. Novel Burkholderia mallei Virulence Factors Linked to Specific Host-Pathogen Protein Interactions

    Science.gov (United States)

    2013-06-23

    fundamental molecular host-pathogen interac- tions that mediate these activities have gathered less atten- tion. Although the transcriptional immune response...Hines, H. B., and Jeddeloh, J. A. (2004) Quorum sensing: A transcriptional regulatory system involved in the pathogenicity of Burkholderia mallei...orthology database for prokaryotes and eukaryotes inferred by evolutionary evidence. BMC Bioinformatics 13, 143 25. Yu, C., Zavaljevski, N., Desai, V

  5. Potential host-related risk factors for recurrent urinary tract infection in Saudi women of childbearing age.

    Science.gov (United States)

    Ahmed, Abul-Fotouh Abdel-Maguid; Solyman, Awatif Abdel-Karim; Kamal, Sanaa Moharram

    2016-08-01

    Risk factors for recurrent urinary tract infection (rUTI) in women may differ between individuals, age, and the community. This study aimed to evaluate host related risk factors for rUTI in sexually active Saudi women during the childbearing period. A case-control study was conducted in five healthcare centers and included married, nonpregnant women aged 18-40 years. A total of 217 women had rUTI (cases) and 252 did not (controls). A validated questionnaire, with a face-to-face interview, was applied to assess various demographic, behavioral, medical, and sexual data. Additionally, a thorough physical examination, saliva and blood analyses, uroflowmetry, and genitourinary ultrasonography were performed. Multivariate logistic regression analysis was used to identify the significant host related risk factors associated with rUTI. In multivariate analysis, attributable risks for rUTI were a history of childhood UTI [odds ratio (OR) = 6.8)] back-to-front douching/wiping after bowel movement (OR = 2.6), younger age at first intercourse (OR = 6.3), increased frequency of sexual intercourse (OR = 4.8), obstructed urinary flow (OR = 1.9), and genital prolapse (OR = 3.4). A total of 9.68 % of cases and none of the controls had high postvoid residual urine (positive predictive value for rUTI = 100 %). This is the first reported study to evaluate host related risk factors for rUTI in childbearing-age women in Saudi Arabia. Study findings indicate the association between rUTI and various factors that have been already established, with addition of improper rectal hygiene as a potential risk for recurrence.

  6. Coordinated destruction of cellular messages in translation complexes by the gammaherpesvirus host shutoff factor and the mammalian exonuclease Xrn1.

    Science.gov (United States)

    Covarrubias, Sergio; Gaglia, Marta M; Kumar, G Renuka; Wong, Wesley; Jackson, Andrew O; Glaunsinger, Britt A

    2011-10-01

    Several viruses encode factors that promote host mRNA degradation to silence gene expression. It is unclear, however, whether cellular mRNA turnover pathways are engaged to assist in this process. In Kaposi's sarcoma-associated herpesvirus this phenotype is enacted by the host shutoff factor SOX. Here we show that SOX-induced mRNA turnover is a two-step process, in which mRNAs are first cleaved internally by SOX itself then degraded by the cellular exonuclease Xrn1. SOX therefore bypasses the regulatory steps of deadenylation and decapping normally required for Xrn1 activation. SOX is likely recruited to translating mRNAs, as it cosediments with translation initiation complexes and depletes polysomes. Cleaved mRNA intermediates accumulate in the 40S fraction, indicating that recognition occurs at an early stage of translation. This is the first example of a viral protein commandeering cellular mRNA turnover pathways to destroy host mRNAs, and suggests that Xrn1 is poised to deplete messages undergoing translation in mammalian cells.

  7. Coordinated destruction of cellular messages in translation complexes by the gammaherpesvirus host shutoff factor and the mammalian exonuclease Xrn1.

    Directory of Open Access Journals (Sweden)

    Sergio Covarrubias

    2011-10-01

    Full Text Available Several viruses encode factors that promote host mRNA degradation to silence gene expression. It is unclear, however, whether cellular mRNA turnover pathways are engaged to assist in this process. In Kaposi's sarcoma-associated herpesvirus this phenotype is enacted by the host shutoff factor SOX. Here we show that SOX-induced mRNA turnover is a two-step process, in which mRNAs are first cleaved internally by SOX itself then degraded by the cellular exonuclease Xrn1. SOX therefore bypasses the regulatory steps of deadenylation and decapping normally required for Xrn1 activation. SOX is likely recruited to translating mRNAs, as it cosediments with translation initiation complexes and depletes polysomes. Cleaved mRNA intermediates accumulate in the 40S fraction, indicating that recognition occurs at an early stage of translation. This is the first example of a viral protein commandeering cellular mRNA turnover pathways to destroy host mRNAs, and suggests that Xrn1 is poised to deplete messages undergoing translation in mammalian cells.

  8. Herpes simplex virus virion host shutoff protein requires a mammalian factor for efficient in vitro endoribonuclease activity.

    Science.gov (United States)

    Lu, P; Jones, F E; Saffran, H A; Smiley, J R

    2001-02-01

    The virion host shutoff protein (vhs) of herpes simplex virus (HSV) triggers global shutoff of host protein synthesis and accelerated mRNA turnover during virus infection and induces endoribonucleolytic cleavage of exogenous RNA substrates when it is produced in a rabbit reticulocyte (RRL) in vitro translation system. Although vhs induces RNA turnover in the absence of other HSV gene products, it is not yet known whether cellular factors are required for its activity. As one approach to addressing this question, we expressed vhs in the budding yeast Saccharomyces cerevisiae. Expression of vhs inhibited colony formation, and the severity of this effect varied with the carbon source. The biological relevance of this effect was assessed by examining the activity of five mutant forms of vhs bearing previously characterized in-frame linker insertions. The results indicated a complete concordance between the growth inhibition phenotype in yeast and mammalian host cell shutoff. Despite these results, expression of vhs did not trigger global mRNA turnover in vivo, and cell extracts of yeast expressing vhs displayed little if any vhs-dependent endoribonuclease activity. However, activity was readily detected when such extracts were mixed with RRL. These data suggest that the vhs-dependent endoribonuclease requires one or more mammalian macromolecular factors for efficient activity.

  9. Genetic Factors in Rhizobium Affecting the Symbiotic Carbon Costs of N2 Fixation and Host Plant Biomass Production

    DEFF Research Database (Denmark)

    Skøt, L.; Hirsch, P. R.; Witty, J. F.

    1986-01-01

    The effect of genetic factors in Rhizobium on host plant biomass production and on the carbon costs of N2 fixation in pea root nodules was studied. Nine strains of Rhizobium leguminosarum were constructed, each containing one of three symbiotic plasmids in combination with one of three different...... with the background of B151. The relationship between nitrogenase activity, carbon costs of N2 fixation and host plant biomass production is discussed....... the lowest carbon costs of N2 fixation (7.10–8.10 μmol C/μmol N2), but shoot dry weight of those plants was also smaller than that of plants nodulated by strains with the background of B151 or JI8400. Nodules formed by these two strain types had carbon costs of N2 fixation varying between 11.26 and 13...

  10. Individual host factors associated with Onchocerca volvulus microfilarial densities 15, 80 and 180 days after a first dose of ivermectin.

    Science.gov (United States)

    Pion, Sébastien D S; Grout, Lise; Kamgno, Joseph; Nana-Djeunga, Hugues; Boussinesq, Michel

    2011-09-01

    Reduction in Onchocerca volvulus skin microfilarial densities after treatment with ivermectin shows wide between-host variation. Data from two separate studies conducted in Cameroon on onchocerciasis patients treated for the first time with ivermectin were analyzed to identify host factors associated with microfilarial density at different time-points after treatment. In one site (Nkam valley), the dataset included 103 adult males for whom age, number of palpable onchocercal nodules and microfilarial densities on D0 (pre-treatment), D15, D80 and D180 were available. In the other site (Vina valley), analyses were conducted on 965 individuals of both sexes aged 5 years and over; in this dataset, available information included age, gender, exact dose of ivermectin received, onchocerciasis endemicity level in the village of residence and microfilarial densities on D0 and D180. Negative binomial regression models of microfilarial density at the different intervals post-treatment were fitted, using maximum likelihood, with the available independent variables. Gender and age were found to be associated with microfilarial density on D180. The initial microfilarial density influenced post-treatment densities at all the time-points. All other things being equal, microfilarial densities on D180 were higher in individuals harbouring a higher number of nodules or living in communities with high endemicity levels. This study demonstrates that O. volvulus microfilarial density measured after a first treatment with ivermectin, and thus probably the rate of skin repopulation by microfilariae (mf) varies according to several host factors. Should such factors also influence ivermectin efficacy after repeated treatment, then they should be taken into account to determine whether sub-optimal responses to treatment reported from various areas in Africa are actually due to parasite-related factors, particularly to the emergence of resistant populations.

  11. Critical factors in the implementation process of integrated management systems

    Directory of Open Access Journals (Sweden)

    Ademir Antonio Ferreira

    2015-09-01

    Full Text Available This study is the result of research whose purpose was to study the implementation process of integrated management systems, called ERP Enterprise Resource Planning in the business environment. This study, more specifically, tried to identify the variables in this process and that, somehow, made it easy or caused some type of difficulty implementing the system. Based on the mixed method approach (Creswell, 2003, the study was performed by means of the content analysis of technical and scientific publications about this theme and by means of a field research for data collection from primary sources. The content analysis was based on the per mile procedure by Bardin (1977, making it possible to identify critical factors that may be found in the implementation of ERP system projects. Primary data was collected from structured interviews with the managers in charge of the implementation of the system, in each of the 12 companies in different sectors of the economy and based in Brazil. Based on this information, it was possible to test the factors extracted from the content analysis and then develop a list of factors that may effectively influence the implementation process of the system. In order to recognize the possible relations between the selected factors, the Spearman (rsp correlation coefficient was applied and the multiple regression analysis was performed by means of the stepwise procedure. The purpose of the regression analysis was to determine the relation of the “Assessment of the Implementation” dependent variable with other dependent variables in the selected categories. The results of these analyses showed that the support of the top management, the communication process for the clear evidence of this support, the technical support of the ERP program provider together with the project team expertise, training and qualification processes of the team in the system operation are significantly correlated and relevant factors for a

  12. Citrobacter rodentium NleB Protein Inhibits Tumor Necrosis Factor (TNF) Receptor-associated Factor 3 (TRAF3) Ubiquitination to Reduce Host Type I Interferon Production.

    Science.gov (United States)

    Gao, Xiaofei; Pham, Thanh H; Feuerbacher, Leigh Ann; Chen, Kangming; Hays, Michael P; Singh, Gyanendra; Rueter, Christian; Hurtado-Guerrero, Ramon; Hardwidge, Philip R

    2016-08-26

    Interferon signaling plays important roles in both intestinal homeostasis and in the host response to pathogen infection. The extent to which bacterial pathogens inhibit this host pathway is an understudied area of investigation. We characterized Citrobacter rodentium strains bearing deletions in individual type III secretion system effector genes to determine whether this pathogen inhibits the host type I IFN response and which effector is responsible. The NleB effector limited host IFN-β production by inhibiting Lys(63)-linked ubiquitination of TNF receptor-associated factor 3 (TRAF3). Inhibition was dependent on the glycosyltransferase activity of NleB. GAPDH, a target of NleB during infection, bound to TRAF3 and was required for maximal TRAF3 ubiquitination. NleB glycosyltransferase activity inhibited GAPDH-TRAF3 binding, resulting in reduced TRAF3 ubiquitination. Collectively, our data reveal important interplay between GAPDH and TRAF3 and suggest a mechanism by which the NleB effector inhibits type I IFN signaling.

  13. Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

    Directory of Open Access Journals (Sweden)

    Gisela Canedo-Marroquín

    2017-08-01

    Full Text Available The Human Respiratory Syncytial Virus (hRSV is a major cause of acute lower respiratory tract infections (ARTIs and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F, the Glycoprotein (G, and the Small Hydrophobic (SH protein, which are located on the virus surface. In addition, the Nucleoprotein (N, Phosphoprotein (P large polymerase protein (L part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2. HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.

  14. Factors Controlling Nanoparticle Pharmacokinetics: An Integrated Analysis and Perspective

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moien; Hunter, A.C.; Andresen, T.L.

    2012-01-01

    of interrelated core and interfacial physicochemical and biological factors. Pertinent to realizing therapeutic goals, definitive maps that establish the interdependency of nanoparticle size, shape, and surface characteristics in relation to interfacial forces, biodistribution, controlled drug release, excretion......, and adverse effects must be outlined. These concepts are critically evaluated and an integrated perspective is provided on the basis of the recent application of nanoscience approaches to nanocarrier design and engineering. The future of this exciting field is bright; some regulatory-approved products...... are already on the market and many are in late-phase clinical trials. With concomitant advances in extensive computational knowledge of the genomics and epigenomics of interindividual variations in drug responses, the boundaries toward development of personalized nanomedicines can be pushed further....

  15. Geometrical form factor calculation using Monte Carlo integration for lidar

    Science.gov (United States)

    Mao, Feiyue; Gong, Wei; Li, Jun

    2012-06-01

    We proposed a geometrical form factor (GFF) calculation using Monte Carlo integration (GFF-MC) for lidar that is practical and can be applied to any laser intensity distribution. Theoretical results have been calculated with our method based on the functions of measured, uniform and Gaussian laser intensity distribution. Two experimental GFF traces on clear days are obtained to verify the validity of the theoretical results. The results indicated that the measured distribution function outperformed the Gaussian and uniform functions. That means that the deviation of the measured laser intensity distribution from an ideal one can be too large to neglect. In addition, the theoretical GFF of the uniform distribution had a larger error than that of the Gaussian distribution. Furthermore, the effects of the inclination angle of the laser beam and the central obstruction of the support structure of the second mirror of the telescope are discussed in this study.

  16. Integrated Human Factors Design Guidelines for Sound Interface

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Lee, Yong Hee; Oh, In Seok; Lee, Hyun Chul [KAERI, Daejeon (Korea, Republic of); Cha, Woo Chang [Kumoh National Univ. of Technology, Gumi (Korea, Republic of)

    2004-05-15

    Digital MMI, such as CRT, LCD etc., has been used increasingly in the design of main control room of the Korean standard nuclear power plants following the YGN units 3 and 4. The utilization of digital MMI may introduce various kind of sound interface into the control room design. In this project, for five top-level guideline items, including Sound Formats, Alarms, Sound Controls, Communications, and Environments, a total of 147 detail guidelines were developed and a database system for these guidelines was developed. The integrated human factors design guidelines for sound interface and the database system developed in this project will be useful for the design of sound interface of digital MMI in Korean NPPs.

  17. Factors affecting rural volunteering in palliative care - an integrated review.

    Science.gov (United States)

    Whittall, Dawn; Lee, Susan; O'Connor, Margaret

    2016-12-01

    To review factors shaping volunteering in palliative care in Australian rural communities using Australian and International literature. Identify gaps in the palliative care literature and make recommendations for future research. A comprehensive literature search was conducted using Proquest, Scopus, Sage Premier, Wiley online, Ovid, Cochran, Google Scholar, CINAHL and Informit Health Collection. The literature was synthesised and presented in an integrated thematic narrative. Australian Rural communities. While Australia, Canada, the United States (US) and the United Kingdom (UK) are leaders in palliative care volunteer research, limited research specifically focuses on volunteers in rural communities with the least occurring in Australia. Several interrelated factors influence rural palliative care provision, in particular an increasingly ageing population which includes an ageing volunteer and health professional workforce. Also current and models of palliative care practice fail to recognise the innumerable variables between and within rural communities such as distance, isolation, lack of privacy, limited health care services and infrastructure, and workforce shortages. These issues impact palliative care provision and are significant for health professionals, volunteers, patients and caregivers. The three key themes of this integrated review include: (i) Geography, ageing rural populations in palliative care practice, (ii) Psychosocial impact of end-end-of life care in rural communities and (iii) Palliative care models of practice and volunteering in rural communities. The invisibility of volunteers in rural palliative care research is a concern in understanding the issues affecting the sustainability of quality palliative care provision in rural communities. Recommendations for future Australian research includes examination of the suitability of current models of palliative care practice in addressing the needs of rural communities; the recruitment

  18. Factors associated with clinical inertia: an integrative review

    Directory of Open Access Journals (Sweden)

    Aujoulat I

    2014-05-01

    Full Text Available Isabelle Aujoulat,1 Patricia Jacquemin,1 Ernst Rietzschel,2 André Scheen,3 Patrick Tréfois,4 Johan Wens,5 Elisabeth Darras,1 Michel P Hermans6 1Université Catholique de Louvain, Institute of Health and Society, Brussels, 2Ghent University, Department of Cardiovascular Diseases and Department of Public Health, Faculty of Medicine and Health Sciences, Ghent, 3University of Liège, Division of Diabetes, Nutrition and Metabolic Disorders and Clinical Pharmacology Unit, CHU Liège, Liège, 4Société Scientifique de Médecine Générale, Brussels, 5University of Antwerp, Faculty of Medicine and Health Sciences, Primary and Interdisciplinary Care Antwerp, 6Université Catholique de Louvain, Institute of Experimental and Clinical Research and Cliniques Universitaires Saint-Luc, Department of Endocrinology and Nutrition, Brussels, Belgium Abstract: Failure to initiate or intensify therapy according to evidence-based guidelines is increasingly being acknowledged as a phenomenon that contributes to inadequate management of chronic conditions, and is referred to as clinical inertia. However, the number and complexity of factors associated with the clinical reasoning that underlies the decision-making processes in medicine calls for a critical examination of the consistency of the concept. Indeed, in the absence of information on and justification of treatment decisions that were made, clinical inertia may be only apparent, and actually reflect good clinical practice. This integrative review seeks to address the factors generally associated with clinical inaction, in order to better delineate the concept of true clinical inertia. Keywords: clinical inertia, evidence-based medicine, clinical decision, integrative review, concept clarification, physician adherence to guidelines

  19. Dual RNA-sequencing of Eucalyptus nitens during Phytophthora cinnamomi challenge reveals pathogen and host factors influencing compatibility

    Directory of Open Access Journals (Sweden)

    Febe Elizabeth Meyer

    2016-03-01

    Full Text Available Damage caused by Phytophthora cinnamomi Rands remains an important concern on forest tree species. The pathogen causes root and collar rot, stem cankers and dieback of various economically important Eucalyptus spp. In South Africa, susceptible cold tolerant Eucalyptus plantations have been affected by various Phytophthora spp. with P. cinnamomi considered one of the most virulent. The molecular basis of this compatible interaction is poorly understood. In this study, susceptible Eucalyptus nitens plants were stem inoculated with P. cinnamomi and tissue was harvested five days post inoculation. Dual RNA-sequencing, a technique which allows the concurrent detection of both pathogen and host transcripts during infection, was performed. Approximately 1% of the reads mapped to the draft genome of P. cinnamomi while 78% of the reads mapped to the Eucalyptus grandis genome. The highest expressed P. cinnamomi gene in planta was a putative crinkler effector (CRN1. Phylogenetic analysis indicated the high similarity of this P. cinnamomi CRN1 to that of Phytophthora infestans. Some CRN effectors are known to target host nuclei to suppress defense. In the host, over 1400 genes were significantly differentially expressed in comparison to mock inoculated trees, including suites of pathogenesis related (PR genes. In particular, a PR-9 peroxidase gene with a high similarity to a Carica papaya PR-9 ortholog previously shown to be suppressed upon infection by Phytophthora palmivora was down-regulated two-fold. This PR-9 gene may represent a cross-species effector target during P. cinnamomi infection. This study identified pathogenicity factors, potential manipulation targets and attempted host defense mechanisms activated by E. nitens that contributed to the susceptible outcome of the interaction.

  20. Interleukin-16 Gene Polymorphisms Are Considerable Host Genetic Factors for Patients’ Susceptibility to Chronic Hepatitis B Infection

    Directory of Open Access Journals (Sweden)

    Sara Romani

    2014-01-01

    Full Text Available Host genetic background is known as an important factor in patients’ susceptibility to infectious diseases such as viral hepatitis. The aim of this study was to determine the effect of genetic polymorphisms of interleukin-16 (IL-16 cytokine on susceptibility of hepatitis B virus (HBV infected patients to develop chronic HBV infection. Genotyping was conducted using PCR followed by enzymatic digestion and RFLP (restriction fragment length polymorphism analysis. We genotyped three single nucleotide polymorphisms (SNPs in the Il-16 gene (rs11556218 T>G, rs4778889 T>C, and rs4072111 C>T to test for relationship between variation at these loci and patients’ susceptibility to chronic HBV infection. Allele frequency of Il-16 gene rs4072111 and rs11556218 was significantly different between chronic HBV patients and healthy blood donors. Genotype frequency of rs4778889 polymorphism of Il-16 gene was significantly different when chronic HBV patients and HBV clearance subjects were compared. Our results showed that Il-16 gene polymorphisms are considerable host genetic factors when we chase biomarkers for prognosis of HBV infected patients.

  1. Serratia marcescens suppresses host cellular immunity via the production of an adhesion-inhibitory factor against immunosurveillance cells.

    Science.gov (United States)

    Ishii, Kenichi; Adachi, Tatsuo; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

    2014-02-28

    Injection of a culture supernatant of Serratia marcescens into the bloodstream of the silkworm Bombyx mori increased the number of freely circulating immunosurveillance cells (hemocytes). Using a bioassay with live silkworms, serralysin metalloprotease was purified from the culture supernatant and identified as the factor responsible for this activity. Serralysin inhibited the in vitro attachment of both silkworm hemocytes and murine peritoneal macrophages. Incubation of silkworm hemocytes or murine macrophages with serralysin resulted in degradation of the cellular immune factor BmSPH-1 or calreticulin, respectively. Furthermore, serralysin suppressed in vitro phagocytosis of bacteria by hemocytes and in vivo bacterial clearance in silkworms. Disruption of the ser gene in S. marcescens attenuated its host killing ability in silkworms and mice. These findings suggest that serralysin metalloprotease secreted by S. marcescens suppresses cellular immunity by decreasing the adhesive properties of immunosurveillance cells, thereby contributing to bacterial pathogenesis.

  2. Integrated traffic conflict model for estimating crash modification factors.

    Science.gov (United States)

    Shahdah, Usama; Saccomanno, Frank; Persaud, Bhagwant

    2014-10-01

    Crash modification factors (CMFs) for road safety treatments are usually obtained through observational models based on reported crashes. Observational Bayesian before-and-after methods have been applied to obtain more precise estimates of CMFs by accounting for the regression-to-the-mean bias inherent in naive methods. However, sufficient crash data reported over an extended period of time are needed to provide reliable estimates of treatment effects, a requirement that can be a challenge for certain types of treatment. In addition, these studies require that sites analyzed actually receive the treatment to which the CMF pertains. Another key issue with observational approaches is that they are not causal in nature, and as such, cannot provide a sound "behavioral" rationale for the treatment effect. Surrogate safety measures based on high risk vehicle interactions and traffic conflicts have been proposed to address this issue by providing a more "causal perspective" on lack of safety for different road and traffic conditions. The traffic conflict approach has been criticized, however, for lacking a formal link to observed and verified crashes, a difficulty that this paper attempts to resolve by presenting and investigating an alternative approach for estimating CMFs using simulated conflicts that are linked formally to observed crashes. The integrated CMF estimates are compared to estimates from an empirical Bayes (EB) crash-based before-and-after analysis for the same sample of treatment sites. The treatment considered involves changing left turn signal priority at Toronto signalized intersections from permissive to protected-permissive. The results are promising in that the proposed integrated method yields CMFs that closely match those obtained from the crash-based EB before-and-after analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Return Wishes of Refugees in the Netherlands : The Role of Integration, Host National Identification and Perceived Discrimination

    NARCIS (Netherlands)

    Di Saint Pierre, Francesca; Martinovic, Borja; De Vroome, Thomas

    2015-01-01

    This study examined refugees' wishes to return to their home country. Previous research on return intentions among economic migrants has pointed at the relevance of three aspects of integration: employment and education (structural integration), language proficiency (cultural integration) and contac

  4. Improving Aspergillus niger as a production host through manipulation of pH responding transcription factors

    DEFF Research Database (Denmark)

    Poulsen, Lars; Bruno, K.S.; Thykær, Jette

    ). In the present study the effect of modulation of transcription factors in Aspergillus niger, which is an industrially important micro-organism used in various processes including organic acid and enzyme production, was investigated. The strategy described in this work focuses on regulation connected to p...

  5. Pediatric acute respiratory distress syndrome: Host factors in Down syndrome and the general population

    NARCIS (Netherlands)

    M. Bruijn

    2013-01-01

    We find that Down syndrome is an important risk factor for developing acute respiratory distress syndrome (ARDS) in children, but the reason why remains to be elucidated. In addition, we find several differences between adult and pediatric ARDS. The association between C-reactive protein (CRP) level

  6. Genomic analysis of host - Peste des petits ruminants vaccine viral transcriptome uncovers transcription factors modulating immune regulatory pathways.

    Science.gov (United States)

    Manjunath, Siddappa; Kumar, Gandham Ravi; Mishra, Bishnu Prasad; Mishra, Bina; Sahoo, Aditya Prasad; Joshi, Chaitanya G; Tiwari, Ashok K; Rajak, Kaushal Kishore; Janga, Sarath Chandra

    2015-02-24

    Peste des petits ruminants (PPR), is an acute transboundary viral disease of economic importance, affecting goats and sheep. Mass vaccination programs around the world resulted in the decline of PPR outbreaks. Sungri 96 is a live attenuated vaccine, widely used in Northern India against PPR. This vaccine virus, isolated from goat works efficiently both in sheep and goat. Global gene expression changes under PPR vaccine virus infection are not yet well defined. Therefore, in this study we investigated the host-vaccine virus interactions by infecting the peripheral blood mononuclear cells isolated from goat with PPRV (Sungri 96 vaccine virus), to quantify the global changes in the transcriptomic signature by RNA-sequencing. Viral genome of Sungri 96 vaccine virus was assembled from the PPRV infected transcriptome confirming the infection and demonstrating the feasibility of building a complete non-host genome from the blood transcriptome. Comparison of infected transcriptome with control transcriptome revealed 985 differentially expressed genes. Functional analysis showed enrichment of immune regulatory pathways under PPRV infection. Key genes involved in immune system regulation, spliceosomal and apoptotic pathways were identified to be dysregulated. Network analysis revealed that the protein - protein interaction network among differentially expressed genes is significantly disrupted in infected state. Several genes encoding TFs that govern immune regulatory pathways were identified to co-regulate the differentially expressed genes. These data provide insights into the host - PPRV vaccine virus interactome for the first time. Our findings suggested dysregulation of immune regulatory pathways and genes encoding Transcription Factors (TFs) that govern these pathways in response to viral infection.

  7. Tumor and Host Factors Controlling Antitumor Immunity and Efficacy of Cancer Immunotherapy.

    Science.gov (United States)

    Spranger, Stefani; Sivan, Ayelet; Corrales, Leticia; Gajewski, Thomas F

    2016-01-01

    Despite recent clinical advances in immunotherapy, a fraction of cancer patients fails to respond to these interventions. Evidence from preclinical mouse models as well as clinical samples has provided evidence that the extent of activated T cell infiltration within the tumor microenvironment is associated with clinical response to immunotherapies including checkpoint blockade. Therefore, understanding the molecular mechanisms mediating the lack of T cell infiltration into the tumor microenvironment will be instrumental for the development of new therapeutic strategies to render those patients immunotherapy responsive. Recent data have suggested that major sources of intersubject heterogeneity include differences in somatic mutations in specific oncogene pathways between cancers of individual subjects and also environmental factors including commensal microbial composition. Successful identification of such causal factors should lead to new therapeutic approaches that may facilitate T cell entry into noninflamed tumors and expand the fraction of patients capable of responding to novel immunotherapies.

  8. No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity

    Science.gov (United States)

    Garcia-Etxebarria, Koldo; Bracho, María Alma; Galán, Juan Carlos; Pumarola, Tomàs; Castilla, Jesús; Ortiz de Lejarazu, Raúl; Rodríguez-Dominguez, Mario; Quintela, Inés; Bonet, Núria; Garcia-Garcerà, Marc; Domínguez, Angela; González-Candelas, Fernando; Calafell, Francesc

    2015-01-01

    While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10−8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course. PMID:26379185

  9. Effect of host-related factors on the intensity of liver fibrosis in patients with chronic hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Costa Luciano Bello

    2002-01-01

    Full Text Available There is increasing interest in the identification of factors associated with liver disease progression in patients infected with hepatitis C virus (HCV. We assessed host-related factors associated with a histologically advanced stage of this disease and determined the rate of liver fibrosis progression in HCV-infected patients. We included patients submitted to liver biopsy, who were anti-HCV and HCV RNA positive, who showed a parenteral risk factor (blood transfusion or intravenous drug use, and who gave information about alcohol consumption.Patients were divided into two groups for analysis: group 1 - grades 0 to 2; group 2 - grades 3 to 4. The groups were compared in terms of sex, age at the time of infection, estimated duration of infection and alcoholism. The rate of fibrosis progression (index of fibrosis was determined based on the relationship between disease stage and duration of infection (years. Logistic regression analysis revealed that age at the time of infection (P or = 40 years (median = 0.47. The main factors associated with a more rapid fibrosis progression were age at the time of infection and the estimated duration of infection. Patients who acquired HCV after 40 years of age showed a higher rate of fibrosis progression.

  10. Comprehensive assessment of host responses to ionizing radiation by nuclear factor-κB bioluminescence imaging-guided transcriptomic analysis.

    Directory of Open Access Journals (Sweden)

    Chung-Ta Chang

    Full Text Available The aim of this study was to analyze the host responses to ionizing radiation by nuclear factor-κB (NF-κB bioluminescence imaging-guided transcriptomic tool. Transgenic mice carrying the NF-κB-driven luciferase gene were exposed to a single dose of 8.5 Gy total-body irradiation. In vivo imaging showed that a maximal NF-κB-dependent bioluminescent intensity was observed at 3 h after irradiation and ex vivo imaging showed that liver, intestine, and brain displayed strong NF-κB activations. Microarray analysis of these organs showed that irradiation altered gene expression signatures in an organ-specific manner and several pathways associated with metabolism and immune system were significantly altered. Additionally, the upregulation of fatty acid binding protein 4, serum amyloid A2, and serum amyloid A3 genes, which participate in both inflammation and lipid metabolism, suggested that irradiation might affect the cross pathways of metabolism and inflammation. Moreover, the alteration of chemokine (CC-motif ligand 5, chemokine (CC-motif ligand 20, and Jagged 1 genes, which are involved in the inflammation and enterocyte proliferation, suggested that these genes might be involved in the radiation enteropathy. In conclusion, this report describes the comprehensive evaluation of host responses to ionizing radiation. Our findings provide the fundamental information about the in vivo NF-κB activity and transcriptomic pattern after irradiation. Moreover, novel targets involved in radiation injury are also suggested.

  11. Characterization of a protein tyrosine phosphatase as a host factor promoting baculovirus replication in silkworm, Bombyx mori.

    Science.gov (United States)

    Wang, Fei; Xue, Renju; Li, Xianyang; Hu, Cuimei; Xia, Qingyou

    2016-04-01

    The relevance of protein tyrosine phosphatase (PTP) to host-pathogen interaction is highlighted in mammalian studies, whereas less is known in insects. Here we presented the categorization of the PTP complement of silkworm and characterized their homologous relationship with human and fruit fly PTPs. Among the 36 PTP genes, ptp-h, which was proposed to be the origin of baculovirus ptp belongs to atypical VH1-like dual-specific PTP subset and encodes a catalytic active protein. The maximum expression level of Bmptp-h was at 5th instar and in fat body. Bombyx mori nucleopolyhedrovirus (BmNPV) infection potently induced its expression in silkworm larvae and in BmE cells. Knock-down of Bmptp-h by RNA interference significantly inhibited viral replication, and over-expression enhanced viral replication as determined by viral DNA abundance and BmNPV-GFP positive cells. These results suggest that BmPTP-h might be one of the host factors that is beneficial to baculovirus infection by promoting viral replication.

  12. The role of host and microbial factors in the pathogenesis of pneumococcal bacteraemia arising from a single bacterial cell bottleneck.

    Directory of Open Access Journals (Sweden)

    Alice Gerlini

    2014-03-01

    Full Text Available The pathogenesis of bacteraemia after challenge with one million pneumococci of three isogenic variants was investigated. Sequential analyses of blood samples indicated that most episodes of bacteraemia were monoclonal events providing compelling evidence for a single bacterial cell bottleneck at the origin of invasive disease. With respect to host determinants, results identified novel properties of splenic macrophages and a role for neutrophils in early clearance of pneumococci. Concerning microbial factors, whole genome sequencing provided genetic evidence for the clonal origin of the bacteraemia and identified SNPs in distinct sub-units of F0/F1 ATPase in the majority of the ex vivo isolates. When compared to parental organisms of the inoculum, ex-vivo pneumococci with mutant alleles of the F0/F1 ATPase had acquired the capacity to grow at low pH at the cost of the capacity to grow at high pH. Although founded by a single cell, the genotypes of pneumococci in septicaemic mice indicate strong selective pressure for fitness, emphasising the within-host complexity of the pathogenesis of invasive disease.

  13. Screening and identification of host factors interacting with UL14 of herpes simplex virus 1.

    Science.gov (United States)

    Wu, Fuqing; Xing, Junji; Wang, Shuai; Li, Meili; Zheng, Chunfu

    2011-08-01

    The UL14 protein of herpes simplex virus type 1 (HSV-1) is highly conserved in herpesvirus family. However, its exact function during the HSV-1 replication cycle is little known. In the present study, a high throughput yeast two-hybrid system was employed to screen the cellular factors interacting with UL14, and five target candidates were yielded: (1) TSC22 domain family protein 3 (TSC22D3); (2) Mediator of RNA polymerase II transcription subunit 8 isoform 1(MED8); (3) Runt-related transcription factor 3 (RUNX3); (4) Arrestin beta-2 (ARRB2); (5) Cereblon (CRBN). Indirect immunofluorescent assay showed that both TSC22D3 and MED8 co-localized with UL14. Co-immunoprecipitation assay demonstrated that UL14 could be immunoprecipitated by TSC22D3, suggesting that UL14 interacted with TSC22D3 under physiological condition. In summary, this study opened up new avenues toward delineating the function and physiological significance of UL14 during the HSV-1 replication cycle.

  14. Identification of Burkholderia cenocepacia strain H111 virulence factors using nonmammalian infection hosts

    DEFF Research Database (Denmark)

    Schwager, Stephan; Agnoli, Kirsty; Köthe, Manuela;

    2013-01-01

    Burkholderia cenocepacia H111, a strain isolated from a cystic fibrosis patient, has been shown to effectively kill the nematode Caenorhabditis elegans. We used the C. elegans model of infection to screen a mini-Tn5 mutant library of B. cenocepacia H111 for attenuated virulence....... Of the approximately 5,500 B. cenocepacia H111 random mini-Tn5 insertion mutants that were screened, 22 showed attenuated virulence in C. elegans. Except for the quorum-sensing regulator cepR, none of the mutated genes coded for the biosynthesis of classical virulence factors such as extracellular proteases...... or siderophores. Instead, the mutants contained insertions in metabolic and regulatory genes. Mutants attenuated in virulence in the C. elegans infection model were also tested in the Drosophila melanogaster pricking model, and those also attenuated in this model were further tested in Galleria mellonella. Six...

  15. Multi-faceted proteomic characterization of host protein complement of Rift Valley fever virus virions and identification of specific heat shock proteins, including HSP90, as important viral host factors.

    Science.gov (United States)

    Nuss, Jonathan E; Kehn-Hall, Kylene; Benedict, Ashwini; Costantino, Julie; Ward, Michael; Peyser, Brian D; Retterer, Cary J; Tressler, Lyal E; Wanner, Laura M; McGovern, Hugh F; Zaidi, Anum; Anthony, Scott M; Kota, Krishna P; Bavari, Sina; Hakami, Ramin M

    2014-01-01

    Rift Valley fever is a potentially fatal disease of humans and domestic animals caused by Rift Valley fever virus (RVFV). Infection with RVFV in ruminants can cause near 100% abortion rates and recent outbreaks in naïve human populations have suggested case fatality rates of greater than thirty percent. To elucidate the roles that host proteins play during RVFV infection, proteomic analysis of RVFV virions was conducted using complementary analytical approaches, followed by functional validation studies of select identified host factors. Coupling the more traditional Gel LC/MS/MS approach (SDS PAGE followed by liquid chromatography tandem mass spectrometry) with an alternative technique that preserves protein complexes allowed the protein complement of these viral particles to be thoroughly examined. In addition to viral proteins present within the virions and virion-associated host proteins, multiple macromolecular complexes were identified. Bioinformatic analysis showed that host chaperones were among over-represented protein families associated with virions, and functional experiments using siRNA gene silencing and small molecule inhibitors identified several of these heat shock proteins, including heat shock protein 90 (HSP90), as important viral host factors. Further analysis indicated that HSP inhibition effects occur during the replication/transcription phase of the virus life cycle, leading to significant lowering of viral titers without compromising the functional capacity of released virions. Overall, these studies provide much needed further insight into interactions between RVFV and host cells, increasing our understanding of the infection process and suggesting novel strategies for anti-viral development. In particular, considering that several HSP90 inhibitors have been advancing through clinical trials for cancer treatment, these results also highlight the exciting potential of repurposing HSP90 inhibitors to treat RVF.

  16. Multi-faceted proteomic characterization of host protein complement of Rift Valley fever virus virions and identification of specific heat shock proteins, including HSP90, as important viral host factors.

    Directory of Open Access Journals (Sweden)

    Jonathan E Nuss

    Full Text Available Rift Valley fever is a potentially fatal disease of humans and domestic animals caused by Rift Valley fever virus (RVFV. Infection with RVFV in ruminants can cause near 100% abortion rates and recent outbreaks in naïve human populations have suggested case fatality rates of greater than thirty percent. To elucidate the roles that host proteins play during RVFV infection, proteomic analysis of RVFV virions was conducted using complementary analytical approaches, followed by functional validation studies of select identified host factors. Coupling the more traditional Gel LC/MS/MS approach (SDS PAGE followed by liquid chromatography tandem mass spectrometry with an alternative technique that preserves protein complexes allowed the protein complement of these viral particles to be thoroughly examined. In addition to viral proteins present within the virions and virion-associated host proteins, multiple macromolecular complexes were identified. Bioinformatic analysis showed that host chaperones were among over-represented protein families associated with virions, and functional experiments using siRNA gene silencing and small molecule inhibitors identified several of these heat shock proteins, including heat shock protein 90 (HSP90, as important viral host factors. Further analysis indicated that HSP inhibition effects occur during the replication/transcription phase of the virus life cycle, leading to significant lowering of viral titers without compromising the functional capacity of released virions. Overall, these studies provide much needed further insight into interactions between RVFV and host cells, increasing our understanding of the infection process and suggesting novel strategies for anti-viral development. In particular, considering that several HSP90 inhibitors have been advancing through clinical trials for cancer treatment, these results also highlight the exciting potential of repurposing HSP90 inhibitors to treat RVF.

  17. Host-viral effects of chromatin assembly factor 1 interaction with HCMV IE2

    Institute of Scientific and Technical Information of China (English)

    Sung-Bau Lee; Li-Jung Juan; Chung-Fan Lee; Derick S-C Ou; Kalpana Dulal; Liang-Hao Chang; Chen-Han Ma; Chien-Fu Huang; Hua Zhu; Young-Sun Lin

    2011-01-01

    Chromatin assembly factor 1 (CAF1) consisting of p150, p60 and p48 is known to assemble histones onto newly synthesized DNA and thus maintain the chromatin structure. Here, we show that CAF1 expression was induced in human cytomegalovirus (HCMV)-infected cells, concomitantly with global chromatin decondensation. This apparent conflict was thought to result, in part, from CAF1 mislocalization to compartments of HCMV DNA synthesis through binding of its largest subunit p150 to viral immediate-early protein 2 (IE2). p150 interaction with p60 and IE2 facilitated HCMV DNA synthesis. The IE2Q548R mutation, previously reported to result in impaired HCMV growth with unknown mechanism, disrupted IE2/p150 and IE2/histones association in our study. Moreover, IE2 interaction with histones partly depends on p150, and the HCMV-induced chromatin decondensation was reduced in cells ectopically expressing the p150 mutant defective in IE2 binding. These results not only indicate that CAF1 was hijacked by IE2 to facilitate the replication of the HCMV genome, suggesting chromatin assembly plays an important role in herpesviral DNA synthesis, but also provide a model of the virus-induced chromatin instability through CAF1.

  18. Allele frequency of antiretroviral host factor TRIMCyp in wild-caught cynomolgus macaques (Macaca fascicularis)

    Science.gov (United States)

    Saito, Akatsuki; Kawamoto, Yoshi; Higashino, Atsunori; Yoshida, Tomoyuki; Ikoma, Tomoko; Suzaki, Yuriko; Ami, Yasushi; Shioda, Tatsuo; Nakayama, Emi E.; Akari, Hirofumi

    2012-01-01

    A recent study showed that the frequency of an antiretroviral factor TRIM5 gene-derived isoform, TRIMCyp, in cynomolgus macaques (Macaca fascicularis) varies widely according to the particular habitat examined. However, whether the findings actually reflect the prevalence of TRIMCyp in wild cynomolgus macaques is still uncertain because the previous data were obtained with captive monkeys in breeding and rearing facilities. Here, we characterized the TRIM5 gene in cynomolgus macaques captured in the wild, and found that the frequency of the TRIMCyp allele was comparable to those in captive monkeys. This suggests that the previous results with captive monkeys do indeed reflect the natural allele frequency and that breeding and rearing facilities may not affect the frequency of TRIM5 alleles. Interestingly, the prevalence of a minor haplotype of TRIMCyp in wild macaques from the Philippines was significantly lower than in captive ones, suggesting that it is advantageous for wild monkeys to possess the major haplotype of TRIMCyp. Overall, our results add to our understanding of the geographic and genetic prevalence of cynomolgus macaque TRIMCyp. PMID:22969754

  19. siRNA Screen Identifies Trafficking Host Factors that Modulate Alphavirus Infection.

    Science.gov (United States)

    Radoshitzky, Sheli R; Pegoraro, Gianluca; Chī, Xi Olì; D Ng, Lián; Chiang, Chih-Yuan; Jozwick, Lucas; Clester, Jeremiah C; Cooper, Christopher L; Courier, Duane; Langan, David P; Underwood, Knashka; Kuehl, Kathleen A; Sun, Mei G; Caì, Yíngyún; Yú, Shu Qìng; Burk, Robin; Zamani, Rouzbeh; Kota, Krishna; Kuhn, Jens H; Bavari, Sina

    2016-03-01

    Little is known about the repertoire of cellular factors involved in the replication of pathogenic alphaviruses. To uncover molecular regulators of alphavirus infection, and to identify candidate drug targets, we performed a high-content imaging-based siRNA screen. We revealed an actin-remodeling pathway involving Rac1, PIP5K1- α, and Arp3, as essential for infection by pathogenic alphaviruses. Infection causes cellular actin rearrangements into large bundles of actin filaments termed actin foci. Actin foci are generated late in infection concomitantly with alphavirus envelope (E2) expression and are dependent on the activities of Rac1 and Arp3. E2 associates with actin in alphavirus-infected cells and co-localizes with Rac1-PIP5K1-α along actin filaments in the context of actin foci. Finally, Rac1, Arp3, and actin polymerization inhibitors interfere with E2 trafficking from the trans-Golgi network to the cell surface, suggesting a plausible model in which transport of E2 to the cell surface is mediated via Rac1- and Arp3-dependent actin remodeling.

  20. siRNA Screen Identifies Trafficking Host Factors that Modulate Alphavirus Infection.

    Directory of Open Access Journals (Sweden)

    Sheli R Radoshitzky

    2016-03-01

    Full Text Available Little is known about the repertoire of cellular factors involved in the replication of pathogenic alphaviruses. To uncover molecular regulators of alphavirus infection, and to identify candidate drug targets, we performed a high-content imaging-based siRNA screen. We revealed an actin-remodeling pathway involving Rac1, PIP5K1- α, and Arp3, as essential for infection by pathogenic alphaviruses. Infection causes cellular actin rearrangements into large bundles of actin filaments termed actin foci. Actin foci are generated late in infection concomitantly with alphavirus envelope (E2 expression and are dependent on the activities of Rac1 and Arp3. E2 associates with actin in alphavirus-infected cells and co-localizes with Rac1-PIP5K1-α along actin filaments in the context of actin foci. Finally, Rac1, Arp3, and actin polymerization inhibitors interfere with E2 trafficking from the trans-Golgi network to the cell surface, suggesting a plausible model in which transport of E2 to the cell surface is mediated via Rac1- and Arp3-dependent actin remodeling.

  1. Butterfly Larval Host Plant use in a Tropical Urban Context: Life History Associations, Herbivory, and Landscape Factors

    Science.gov (United States)

    Tiple, Ashish D.; Khurad, Arun M.; Dennis, Roger L. H.

    2011-01-01

    This study examines butterfly larval host plants, herbivory and related life history attributes within Nagpur City, India. The larval host plants of 120 butterfly species are identified and their host specificity, life form, biotope, abundance and perennation recorded; of the 126 larval host plants, most are trees (49), with fewer herbs (43), shrubs (22), climbers (7) and stem parasites (2). They include 89 wild, 23 cultivated, 11 wild/cultivated and 3 exotic plant species; 78 are perennials, 43 annuals and 5 biannuals. Plants belonging to Poaceae and Fabaceae are most widely used by butterfly larvae. In addition to distinctions in host plant family affiliation, a number of significant differences between butterfly families have been identified in host use patterns: for life forms, biotopes, landforms, perennation, host specificity, egg batch size and ant associations. These differences arising from the development of a butterfly resource database have important implications for conserving butterfly species within the city area. Differences in overall butterfly population sizes within the city relate mainly to the number of host plants used, but other influences, including egg batch size and host specificity are identified. Much of the variation in population size is unaccounted for and points to the need to investigate larval host plant life history and strategies as population size is not simply dependent on host plant abundance. PMID:21864159

  2. Recurrent invasive pneumococcal disease in children--host factors and vaccination response.

    Science.gov (United States)

    Ingels, Helene Andrea Sinclair

    2015-07-01

    Streptococcus pneumoniae is still a leading cause of septicaemia, pneumonia and meningitis in young children world-wide with over half a million children dying annually from pneumococcal disease.  Some children are prone to repeated episodes of invasive pneumococcal disease (IPD) because of an underlying predisposing disease. Recurrent IPD (rIPD) is a rarity and published reports on rIPD are limited by having few children included, selected groups of patients or short follow-up periods. Deficiencies in the innate or adaptive immune system have been described in children with rIPD, but the frequency of immunodeficiency among such patients is unknown. The aim of this PhD thesis was to examine paediatric cases of laboratory-confirmed rIPD, over a 33-year period in Denmark, to determine risk factors and study aspects of the immunological background for this problem in children. In October 2007, a seven-valent pneumococcal conjugate vaccine (PCV7) was implemented in the Danish infant immunization programme. An additional aim of the thesis was to examine the impact of vaccination on a population level, following the first three years of general PCV7 vaccination in Denmark. The thesis consists of three papers, which are all directly or indirectly based on data retrieved from the National Streptococcus Pneumoniae Registry. This registry is nationwide and dates back to 1938. The registry contains data from all laboratory-confirmed cases of IPD in Denmark and is continually updated for national surveillance. In Paper 1, we conducted a 33-year retrospective nationwide study of paediatric rIPD. By using data from the National Streptococcus Pneumoniae Registry combined with clinical data from hospital records, we could describe one of the largest known cohorts of children (n:59) with rIPD . We covered epidemiological, microbiological, and clinical features of this clinical entity. Of all children experiencing rIPD, 47% had a known predisposing underlying disease at the time of

  3. Factors affecting social integration of noninstitutionalized mentally retarded adults.

    Science.gov (United States)

    Reiter, S; Levi, A M

    1980-07-01

    The social integration of noninstitutionalized moderately and mildly mentally retarded young adults was investigated. A group of moderately and mildly retarded adults (study group) was compared with a group of borderline retarded (control group) adults on employability, behavior at work, social integration and social skills, personality, and self-concept. Findings indicated that the study group was less well integrated at work and in society than was the control group and showed lack of social skills. The retarded adults who had nonretarded friends showed better social-educational skills than did the other subjects. Findings suggest that even retarded individuals who grow up in the community need help in order to become socially independent. The existence of a special social club for retarded adults was found to fulfill the functions of a sheltered framework. Participants in the club showed more positive self-concepts; however, the club did not seem to prepare them for social integration in the general community.

  4. Coupling, Q-Factor, and Integration Aspects of Microsphere Applications

    Science.gov (United States)

    Ilchenko, V. S.; Yao, X. S.; Maleki, L.

    2000-01-01

    With suggested applications varying from microlaser and cavity QED through optical locking of diode lasers to modulators and sensors, high-Q silica microspheres with whispering-gallery (WG) modes so far remain the subject of tabletop feasibility demonstrations. Despite the uniquely high quality-factor and submillimeter dimensions suitable for tight packaging, this novel type of high-finesse cavity still has to be adapted to fiber- and integrated-optic hardware. In the visible and near infrared-band experiments (633-850nm) measuring the ringdown time tau of free oscillations, Q = (0.6 to 0.8 ) x 10(exp 10) has been obtained in silica spheres of diameter -800 microns (corresponding tau = 3 to 4 microseconds). It was proved that under normal laboratory conditions, quality-factor is subject to deterioration within several-minute scale down to (2 ... 3 ) x 10(exp 9). The responsible mechanism was identified as adsorption of a monolayer of atmospheric water, so that preservation of the ultimate Q requires manipulation in dry environment, or fast packaging into sealed devices. Larger Q can be expected closer to minimum of attenuation in fused silica alpha = 0.2 dB/km; Q greater than or equal to 1 x 10(exp 11) at lambda=1.55 microns, with corresponding energy storage time tau approx. 0.1ms. Experiments are currently underway to determine whether this high Q can be realized experimentally. The evident difficulty is that OH-related optical absorption has its peaks located near the reported minimum of attenuation in silica. We can also mention here that some of proposed fiber materials, yet not ready for fiber drawing, have been predicted to have smaller attenuation than fused silica and may be suitable for microsphere fabrication (sodium-magnesium silicate glass, alpha = 0.06dB/km). WG modes possess very small radiative loss (it does not prevent Q-10(exp 20) and more) and therefore are electromagnetically isolated and cannot be excited by free-space beams. If no modification

  5. Salmonella typhimurium's transthyretin-like protein is a host-specific factor important in fecal survival in chickens.

    Directory of Open Access Journals (Sweden)

    Sarah C Hennebry

    Full Text Available The transthyretin-like protein (TLP from Salmonella enterica subspecies I is a periplasmic protein with high level structural similarity to a protein found in mammals and fish. In humans, the protein homologue, transthyretin, binds and carries retinol and thyroxine, and a series of other, unrelated aromatic compounds. Here we show that the amino acid sequence of the TLP from different species, subspecies and serovars of the Salmonella genus is highly conserved and demonstrate that the TLP gene is constitutively expressed in S. Typhimurium and that copper and other divalent metal ions severely inhibit enzyme activity of the TLP, a cyclic amidohydrolase that hydrolyses 5-hydroxyisourate (5-HIU. In order to determine the in vivo role of the S. Typhimurium TLP, we constructed a strain of mouse-virulent S. Typhimurium SL1344 bearing a mutation in the TLP gene (SL1344 ΔyedX. We assessed the virulence of this strain via oral inoculation of mice and chickens. Whilst SL1344 ΔyedX induced a systemic infection in both organisms, the bacterial load detected in the faeces of infected chickens was significantly reduced when compared to the load of S. Typhimurium SL1344. These data demonstrate that the TLP gene is required for survival of S. Typhimurium in a high uric acid environment such as chicken faeces, and that metabolic traits of Salmonellae in natural and contrived hosts may be fundamentally different. Our data also highlight the importance of using appropriate animal models for the study of bacterial pathogenesis especially where host-specific virulence factors or traits are the subject of the study.

  6. Role of Intrinsic (Graft) Versus Extrinsic (Host) Factors in the Growth of Transplanted Organs Following Allogeneic and Xenogeneic Transplantation.

    Science.gov (United States)

    Tanabe, T; Watanabe, H; Shah, J A; Sahara, H; Shimizu, A; Nomura, S; Asfour, A; Danton, M; Boyd, L; Dardenne Meyers, A; Ekanayake-Alper, D K; Sachs, D H; Yamada, K

    2017-01-24

    In our studies of life-supporting α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidneys, we found that some recipients developed increased serum creatinine with growth of the grafts, without histological or immunological evidence of rejection. We hypothesized that the rapid growth of orthotopic pig grafts in smaller baboon recipients may have led to deterioration of organ function. To test this hypothesis for both kidneys and lungs, we assessed whether the growth of outbred (Yorkshire) organ transplants in miniature swine was regulated by intrinsic (graft) or extrinsic (host environment) factors. Yorkshire kidneys exhibited persistent growth in miniature swine, reaching 3.7 times their initial volume over 3 mo versus 1.2 times for miniature swine kidneys over the same time period. Similar rapid early growth of lung allografts was observed and, in this case, led to organ dysfunction. For xenograft kidneys, a review of our results suggests that there is a threshold for kidney graft volume of 25 cm(3) /kg of recipient body weight at which cortical ischemia is induced in transplanted GalT-KO kidneys in baboons. These results suggest that intrinsic factors are responsible, at least in part, for growth of donor organs and that this property should be taken into consideration for growth-curve-mismatched transplants, especially for life-supporting organs transplanted into a limited recipient space.

  7. The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection

    Science.gov (United States)

    Sun, Xingmin; Hirota, Simon A.

    2014-01-01

    Clostridium difficile (C. difficile) is the most common cause of nosocomial antibiotic-associated diarrhea and the etiologic agent of pseudomembranous colitis. The clinical manifestation of Clostridium difficile infection (CDI) is highly variable, from asymptomatic carriage, to mild self-limiting diarrhea, to the more severe pseudomembranous colitis. Furthermore, in extreme cases, colonic inflammation and tissue damage can lead to toxic megacolon, a condition requiring surgical intervention. C. difficile expresses two key virulence factors; the exotoxins, toxin A (TcdA) and toxin B (TcdB), which are glucosyltransferases that target host-cell monomeric GTPases. In addition, some hypervirulent strains produce a third toxin, binary toxin or C. difficile transferase (CDT), which may contribute to the pathogenesis of CDI. More recently, other factors such as surface layer proteins (SLPs) and flagellin have also been linked to the inflammatory responses observed in CDI. Although the adaptive immune response can influence the severity of CDI, the innate immune responses to C. difficile and its toxins play crucial roles in CDI onset, progression, and overall prognosis. Despite this, the innate immune responses in CDI have drawn relatively little attention from clinical researchers. Targeting these responses may prove useful clinically as adjuvant therapies, especially in refractory and/or recurrent CDI. This review will focus on recent advances in our understanding of how C. difficile and its toxins modulate innate immune responses that contribute to CDI pathogenesis. PMID:25242213

  8. Computation of form factors in massless QCD with finite master integrals

    Science.gov (United States)

    von Manteuffel, Andreas; Panzer, Erik; Schabinger, Robert M.

    2016-06-01

    We present the bare one-, two-, and three-loop form factors in massless quantum chromodynamics as linear combinations of finite master integrals. Using symbolic integration, we compute their ɛ expansions and thereby reproduce all known results with an independent method. Remarkably, in our finite basis, only integrals with a less-than-maximal number of propagators contribute to the cusp anomalous dimensions. We report on indications of this phenomenon at four loops, including the result for a finite, irreducible, twelve-propagator form factor integral. Together with this article, we provide our automated software setup for the computation of finite master integrals.

  9. On the Computation of Form Factors in Massless QCD with Finite Master Integrals

    CERN Document Server

    von Manteuffel, Andreas; Schabinger, Robert M

    2015-01-01

    We present the bare one-, two-, and three-loop form factors in massless Quantum Chromodynamics as linear combinations of finite master integrals. Using symbolic integration, we compute their $\\epsilon$ expansions and thereby reproduce all known results with an independent method. Remarkably, in our finite basis, only integrals with a less-than-maximal number of propagators contribute to the cusp anomalous dimensions. We report on indications of this phenomenon at four loops, including the result for a finite, irreducible, twelve-propagator form factor integral. Together with this article, we provide our automated software setup for the computation of finite master integrals.

  10. Integrating Factors and Conservation Laws of Generalized Birkhoff System Dynamics in Event Space

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yi

    2009-01-01

    In this paper, the conservation laws or generalized Birkhoff system in event space are studied by using the method of integrating factors. Firstly, the generalized Pfaff-Birkhoff principle and the generalized Birkhoff equations are established, and the definition of the integrating factors for the system is given. Secondly, based on the concept of integrating factors, the conservation theorems and their inverse for the generalized Birkhoff system in the event space are presented in detail, and the relation between the conservation laws and the integrating factors of the system is obtained and the generalized Killing equations for the determination of the integrating factors are given. Finally, an example is given to illustrate the application of the results.

  11. Evaluating the Biological and Ecological Factors Influencing Transmission of Larval Digenetic Trematodes: A Test of Second Intermediate Host Specificity of Two North American Halipegus Species.

    Science.gov (United States)

    Stigge, Heather A; Bolek, Matthew G

    2016-12-01

    approximate 2-fold difference in the average percentage of worms that established in odonates from the ostracod, Cypridopsis sp., than from the harpacticoid copepod, Phyllognathopus sp., and the difference was nearly 3-fold between Cypridopsis sp. and the cyclopoid copepod, Thermocyclops sp. Therefore, despite all 3 microcrustacean species becoming infected, not all species were equally suited for transmission and completion of the life cycle. Differences among the 3 microcrustacean species in cercaria ingestion, metacercarial growth and development, and odonate predation rates on infected microcrustacean species were important factors in determining transmission of the 2 Halipegus species to odonate hosts.

  12. A granulin-like growth factor secreted by the carcinogenic liver fluke, Opisthorchis viverrini, promotes proliferation of host cells.

    Directory of Open Access Journals (Sweden)

    Michael J Smout

    2009-10-01

    Full Text Available The human liver fluke, Opisthorchis viverrini, infects millions of people throughout south-east Asia and is a major cause of cholangiocarcinoma, or cancer of the bile ducts. The mechanisms by which chronic infection with O. viverrini results in cholangiocarcinogenesis are multi-factorial, but one such mechanism is the secretion of parasite proteins with mitogenic properties into the bile ducts, driving cell proliferation and creating a tumorigenic environment. Using a proteomic approach, we identified a homologue of human granulin, a potent growth factor involved in cell proliferation and wound healing, in the excretory/secretory (ES products of the parasite. O. viverrini granulin, termed Ov-GRN-1, was expressed in most parasite tissues, particularly the gut and tegument. Furthermore, Ov-GRN-1 was detected in situ on the surface of biliary epithelial cells of hamsters experimentally infected with O. viverrini. Recombinant Ov-GRN-1 was expressed in E. coli and refolded from inclusion bodies. Refolded protein stimulated proliferation of murine fibroblasts at nanomolar concentrations, and proliferation was inhibited by the MAPK kinase inhibitor, U0126. Antibodies raised to recombinant Ov-GRN-1 inhibited the ability of O. viverrini ES products to induce proliferation of murine fibroblasts and a human cholangiocarcinoma cell line in vitro, indicating that Ov-GRN-1 is the major growth factor present in O. viverrini ES products. This is the first report of a secreted growth factor from a parasitic worm that induces proliferation of host cells, and supports a role for this fluke protein in establishment of a tumorigenic environment that may ultimately manifest as cholangiocarcinoma.

  13. A granulin-like growth factor secreted by the carcinogenic liver fluke, Opisthorchis viverrini, promotes proliferation of host cells.

    Directory of Open Access Journals (Sweden)

    Michael J Smout

    2009-10-01

    Full Text Available The human liver fluke, Opisthorchis viverrini, infects millions of people throughout south-east Asia and is a major cause of cholangiocarcinoma, or cancer of the bile ducts. The mechanisms by which chronic infection with O. viverrini results in cholangiocarcinogenesis are multi-factorial, but one such mechanism is the secretion of parasite proteins with mitogenic properties into the bile ducts, driving cell proliferation and creating a tumorigenic environment. Using a proteomic approach, we identified a homologue of human granulin, a potent growth factor involved in cell proliferation and wound healing, in the excretory/secretory (ES products of the parasite. O. viverrini granulin, termed Ov-GRN-1, was expressed in most parasite tissues, particularly the gut and tegument. Furthermore, Ov-GRN-1 was detected in situ on the surface of biliary epithelial cells of hamsters experimentally infected with O. viverrini. Recombinant Ov-GRN-1 was expressed in E. coli and refolded from inclusion bodies. Refolded protein stimulated proliferation of murine fibroblasts at nanomolar concentrations, and proliferation was inhibited by the MAPK kinase inhibitor, U0126. Antibodies raised to recombinant Ov-GRN-1 inhibited the ability of O. viverrini ES products to induce proliferation of murine fibroblasts and a human cholangiocarcinoma cell line in vitro, indicating that Ov-GRN-1 is the major growth factor present in O. viverrini ES products. This is the first report of a secreted growth factor from a parasitic worm that induces proliferation of host cells, and supports a role for this fluke protein in establishment of a tumorigenic environment that may ultimately manifest as cholangiocarcinoma.

  14. Identification of the key weather factors affecting overwintering success of Apolygus lucorum eggs in dead host tree branches.

    Science.gov (United States)

    Pan, Hongsheng; Liu, Bing; Lu, Yanhui; Desneux, Nicolas

    2014-01-01

    Understanding the effects of weather on insect population dynamics is crucial to simulate and forecast pest outbreaks, which is becoming increasingly important with the effects of climate change. The mirid bug Apolygus lucorum is an important pest on cotton, fruit trees and other crops in China, and primarily lays its eggs on dead parts of tree branches in the fall for subsequent overwintering. As such, the eggs that hatch the following spring are most strongly affected by ambient weather factors, rather than by host plant biology. In this study, we investigated the effects of three major weather factors: temperature, relative humidity and rainfall, on the hatching rate of A. lucorum eggs overwintering on dead branches of Chinese date tree (Ziziphus jujuba). Under laboratory conditions, rainfall (simulated via soaking) was necessary for the hatching of overwintering A. lucorum eggs. In the absence of rainfall (unsoaked branches), very few nymphs successfully emerged under any of the tested combinations of temperature and relative humidity. In contrast, following simulated rainfall, the hatching rate of the overwintering eggs increased dramatically. Hatching rate and developmental rate were positively correlated with relative humidity and temperature, respectively. Under field conditions, the abundance of nymphs derived from overwintering eggs was positively correlated with rainfall amount during the spring seasons of 2009-2013, while the same was not true for temperature and relative humidity. Overall, our findings indicate that rainfall is the most important factor affecting the hatching rate of overwintering A. lucorum eggs on dead plant parts and nymph population levels during the spring season. It provides the basic information for precisely forecasting the emergence of A. lucorum and subsequently timely managing its population in spring, which will make it possible to regional control of this insect pest widely occurring in multiple crops in summer.

  15. Holliday junction affinity of the base excision repair factor Endo III contributes to cholera toxin phage integration.

    Science.gov (United States)

    Bischerour, Julien; Spangenberg, Claudia; Barre, François-Xavier

    2012-09-12

    Toxigenic conversion of Vibrio cholerae bacteria results from the integration of a filamentous phage, CTX phage. Integration is driven by the bacterial Xer recombinases, which catalyse the exchange of a single pair of strands between the phage single-stranded DNA and the host double-stranded DNA genomes; replication is thought to convert the resulting pseudo-Holliday junction (HJ) intermediate into the final recombination product. The natural tendency of the Xer recombinases to recycle HJ intermediates back into substrate should thwart this integration strategy, which prompted a search for additional co-factors aiding directionality of the process. Here, we show that Endo III, a ubiquitous base excision repair enzyme, facilitates CTX phage-integration in vivo. In vitro, we show that it prevents futile Xer recombination cycles by impeding new rounds of strand exchanges once the pseudo-HJ is formed. We further demonstrate that this activity relies on the unexpected ability of Endo III to bind to HJs even in the absence of the recombinases. These results explain how tandem copies of the phage genome can be created, which is crucial for subsequent virion production.

  16. Integrating high-content imaging and chemical genetics to probe host cellular pathways critical for Yersinia pestis infection.

    Directory of Open Access Journals (Sweden)

    Krishna P Kota

    Full Text Available The molecular machinery that regulates the entry and survival of Yersinia pestis in host macrophages is poorly understood. Here, we report the development of automated high-content imaging assays to quantitate the internalization of virulent Y. pestis CO92 by macrophages and the subsequent activation of host NF-κB. Implementation of these assays in a focused chemical screen identified kinase inhibitors that inhibited both of these processes. Rac-2-ethoxy-3 octadecanamido-1-propylphosphocholine (a protein Kinase C inhibitor, wortmannin (a PI3K inhibitor, and parthenolide (an IκB kinase inhibitor, inhibited pathogen-induced NF-κB activation and reduced bacterial entry and survival within macrophages. Parthenolide inhibited NF-κB activation in response to stimulation with Pam3CSK4 (a TLR2 agonist, E. coli LPS (a TLR4 agonist or Y. pestis infection, while the PI3K and PKC inhibitors were selective only for Y. pestis infection. Together, our results suggest that phagocytosis is the major stimulus for NF-κB activation in response to Y. pestis infection, and that Y. pestis entry into macrophages may involve the participation of protein kinases such as PI3K and PKC. More importantly, the automated image-based screening platform described here can be applied to the study of other bacteria in general and, in combination with chemical genetic screening, can be used to identify host cell functions facilitating the identification of novel antibacterial therapeutics.

  17. The Factors Influencing Young Children's Social Interaction in Technology Integration

    Science.gov (United States)

    Lim, Eun Mee

    2015-01-01

    When technology integration is accomplished successfully in early childhood education settings, children tend to interact more with one another and exchange information related to computer tasks as well as the overall classroom on-going curriculum themes. Therefore, to explore how young children are interacting in computer areas when using…

  18. Host and environmental risk factors associated with Cryptosporidium scophthalmi (Apicomplexa) infection in cultured turbot, Psetta maxima (L.) (Pisces, Teleostei).

    Science.gov (United States)

    Alvarez-Pellitero, Pilar; Perez, Andrés; Quiroga, M Isabel; Redondo, M José; Vázquez, Sonia; Riaza, Ana; Palenzuela, Oswaldo; Sitjà-Bobadilla, Ariadna; Nieto, José M

    2009-11-12

    An epidemiological cohort study of Cryptosporidium scophthalmi in cultured turbot Psetta maxima L. of Northwestern Spain was conducted along a four-year period. Four different ongrowing cohorts were monitored monthly from introduction into the ongrowing tanks (10-50 g) until reaching market size (400-1400 g). The association of host and environmental factors with five categories of parasite abundance was assessed using a multivariable regression framework. Epidemiological factors assessed here were water temperature, weight, length, month of collection, season, age, origin, condition factor, water filtration, and status to the myxozoan Enteromyxum scophthalmi infection. E. scophthalmi was included into the analysis because it targets the same organ than C. scophthalmi and it was prevalent in the studied population. The multivariable analysis demonstrated the statistically significant association between several factors and parasite abundance. C. scophthalmi abundance was associated (P<0.05) with age, condition factor, season, and status to E. scophthalmi infection. Young animals, with poor condition factor, during spring or summer, and not infected with the myxozoan were most likely to be highly infected by C. scophthalmi. Inclusion of these four variables significantly (P<0.05) improved the model, compared to the model that did not include any of these epidemiological factors. Increasing levels of C. scophthalmi abundance were associated (P<0.01) with higher severity of C. scophthalmi-compatible lesions. The frequency of distribution of C. scophthalmi abundance was clearly right-skewed and fitted a negative binomial distribution, whereas the intensity of infection fitted a Poisson distribution. The quantification of the variance-to-mean ratio stratified by age demonstrated overdispersion for 8-16 months old fish, although this bivariate association is likely affected by several other factors, as suggested by the results of the multivariable analysis. The negative

  19. Host genetic factors in American cutaneous leishmaniasis: a critical appraisal of studies conducted in an endemic area of Brazil

    Directory of Open Access Journals (Sweden)

    Léa Cristina Castellucci

    2014-06-01

    Full Text Available American cutaneous leishmaniasis (ACL is a vector-transmitted infectious disease with an estimated 1.5 million new cases per year. In Brazil, ACL represents a significant public health problem, with approximately 30,000 new reported cases annually, representing an incidence of 18.5 cases per 100,000 inhabitants. Corte de Pedra is in a region endemic for ACL in the state of Bahia (BA, northeastern Brazil, with 500-1,300 patients treated annually. Over the last decade, population and family-based candidate gene studies were conducted in Corte de Pedra, founded on previous knowledge from studies on mice and humans. Notwithstanding limitations related to sample size and power, these studies contribute important genetic biomarkers that identify novel pathways of disease pathogenesis and possible new therapeutic targets. The present paper is a narrative review about ACL immunogenetics in BA, highlighting in particular the interacting roles of the wound healing gene FLI1 with interleukin-6 and genes SMAD2 and SMAD3 of the transforming growth factor beta signalling pathway. This research highlights the need for well-powered genetic and functional studies on Leishmania braziliensis infection as essential to define and validate the role of host genes in determining resistance/susceptibility regarding this disease.

  20. Population dynamics of intermediate snail hosts of Fasciola hepatica and some environmental factors in San Juan y Martinez municipality, Cuba

    Directory of Open Access Journals (Sweden)

    Roberto Cañete

    2004-05-01

    Full Text Available The variation of abundances of intermediate snail hosts of Fasciola hepatica in Cuba (Fossaria cubensis and Pseudosuccinea columella was studied during one year under natural conditions at five sampling sites in San Juan y Martinez municipality, Pinar del Rio province, Cuba. The effect of some environmental variables on the lymnaeid abundances was also studied. A canonical correspondence analysis showed that both species do not generally occur together in the same habitat and that most factors affect them in an opposite fashion, although both of them correlate positively through time to the diversity of the habitats. F. cubensis prefers the sites that are in or closer to the city whereas P. columella is more abundant in rural sites. Lymnaeid abundances are mainly affected by nitrite and nitrate concentrations as well as by the abundance of the thiarid Tarebia granifera. F. cubensis is more abundant in polluted habitats with low densities (or absence of T. granifera whereas P. columella prefers cleaner habitats and can coexist with the thiarid, even at its higher densities. The implications of divergent preferences of the two lymnaeids for the control of fasciolosis are discussed.

  1. Secreted effectors of the tomato leaf mould fungus Cladosporium fulvum are virulence factors that target host defense

    Science.gov (United States)

    Cladosporium fulvum is a biotrophic fungal pathogen that causes leaf mould of tomato. Inside the leaf, C. fulvum does not penetrate host cells or develop haustoria but remains confined to the intercellular space between mesophyll cells. Ten effector proteins that are secreted during host colonizatio...

  2. Effect Of Selected Factors On The Safety Integrity Level (SIL

    Directory of Open Access Journals (Sweden)

    Stanisław Młynarski

    2015-11-01

    Full Text Available The presented paper concerns the functional safety problems of technical systems. The characteristics of safety assessment, described in IEC 61508 standard are an introduction to the problems associated with the methodology of the calculation of Safety Integrity Levels (SIL. The parameters obtained from reliability indicators, were calculated for the purpose of assessing the impact of repair time for the elements of a given system on the SIL. The calculated values of failure rate and the probability of dangerous failure show the sensitivity of the system at different time to repair values for various reliability-wise configurations. The indicators characterizing the safety level, calculated of the system with no repair time are the basis for demonstrating the influence of repair on the safety integrity level.

  3. The interplay of host genetic factors and Epstein-Barr virus in the development of nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Maria Li Lung; Arthur Kwok Leung Cheung; Josephine Mun Yee Ko; Hong Lok Lung; Yue Cheng; Wei Dai

    2014-01-01

    The interplay between host cell genetics and Epstein-Barr virus (EBV) infection contributes to the development of nasopharyngeal carcinoma (NPC). Understanding the host genetic and epigenetic alterations and the influence of EBV on cell signaling and host gene regulation will aid in understanding the molecular pathogenesis of NPC and provide useful biomarkers and targets for diagnosis and therapy. In this review, we provide an update of the oncogenes and tumor suppressor genes associated with NPC, as wel as genes associated with NPC risk including those involved in carcinogen detoxification and DNA repair. We also describe the importance of host genetics that govern the human leukocyte antigen (HLA) complex and immune responses, and we describe the impact of EBV infection on host cell signaling changes and epigenetic regulation of gene expression. High-power genomic sequencing approaches are needed to elucidate the genetic basis for inherited susceptibility to NPC and to identify the genes and pathways driving its molecular pathogenesis.

  4. Matrix factorization method for the Hamiltonian structure of integrable systems

    Indian Academy of Sciences (India)

    S Ghosh; B Talukdar; S Chakraborti

    2003-07-01

    We demonstrate that the process of matrix factorization provides a systematic mathematical method to investigate the Hamiltonian structure of non-linear evolution equations characterized by hereditary operators with Nijenhuis property.

  5. Coxsackievirus mutants that can bypass host factor PI4KIIIbeta and the need for high levels of PI4P lipids for replication

    NARCIS (Netherlands)

    Schaar, H.M. van der; Linden, L. van der; Lanke, K.H.W.; Strating, J.R.P.M.; Purstinger, G.; Vries, E. de; Haan, C.A. de; Neyts, J.; Kuppeveld, F.J.M. van

    2012-01-01

    RNA viruses can rapidly mutate and acquire resistance to drugs that directly target viral enzymes, which poses serious problems in a clinical context. Therefore, there is a growing interest in the development of antiviral drugs that target host factors critical for viral replication, since they are

  6. Risk factors for unstable blood glucose level: integrative review of the risk factors related to the nursing diagnosis

    OpenAIRE

    Teixeira,Andressa Magalhães; Tsukamoto, Rosangela; Lopes,Camila Takáo; Silva, Rita de Cassia Gengo e

    2017-01-01

    ABSTRACT Objective: to identify evidence in the literature on the possible risk factors for the risk of unstable blood glucose diagnosis in individuals with type 2 diabetes mellitus, and to compare them with the risk factors described by NANDA International. Method: an integrative literature review guided by the question: what are the risk factors for unstable blood glucose level in people with type 2 diabetes mellitus? Primary studies were included whose outcomes were variations in glycemi...

  7. Interactions Between Symbiotic Microbiome and Mammalian Host Metabolism

    Institute of Scientific and Technical Information of China (English)

    TANG HuiHu; XIAO ChaoNi; WANG YuLan

    2009-01-01

    @@ Interactions between the symbiotic microbiota (microbiome) and host metabolism are of significant importance for host physiology and pathophysiology,drug efficacy and nutritional functions.As a systems approach,metabonomie analyses have a major role to play in understanding such interactions since metabonomics is the branch of science concern with the quantitative understandings of the metabolite complement of integrated living systems and its dynamic responses to the changes of both endogenous factors and exogenous factors.

  8. On-shell Diagrams, Gra{\\ss}mannians and Integrability for Form Factors

    CERN Document Server

    Frassek, Rouven; Nandan, Dhritiman; Wilhelm, Matthias

    2015-01-01

    We apply on-shell and integrability methods that have been developed in the context of scattering amplitudes in N=4 SYM theory to tree-level form factors of this theory. Focussing on the colour-ordered super form factors of the chiral part of the stress-energy multiplet as an example, we show how to systematically construct on-shell diagrams for these form factors with the minimal form factor as an additional building block. Moreover, we obtain analytic representations in terms of Gra{\\ss}mannian integrals in spinor helicity, twistor and momentum twistor variables. While Yangian invariance is broken by the operator insertion, we find that form factors are eigenstates of the integrable transfer matrix. As a consequence, we can construct them via the method of R operators, which also allows to introduce deformations that preserve the integrable structure.

  9. Endoplasmic Reticulum α-Glycosidases of Candida albicans Are Required for N Glycosylation, Cell Wall Integrity, and Normal Host-Fungus Interaction▿

    Science.gov (United States)

    Mora-Montes, Héctor M.; Bates, Steven; Netea, Mihai G.; Díaz-Jiménez, Diana F.; López-Romero, Everardo; Zinker, Samuel; Ponce-Noyola, Patricia; Kullberg, Bart Jan; Brown, Alistair J. P.; Odds, Frank C.; Flores-Carreón, Arturo; Gow, Neil A. R.

    2007-01-01

    The cell surface of Candida albicans is enriched in highly glycosylated mannoproteins that are involved in the interaction with the host tissues. N glycosylation is a posttranslational modification that is initiated in the endoplasmic reticulum (ER), where the Glc3Man9GlcNAc2 N-glycan is processed by α-glucosidases I and II and α1,2-mannosidase to generate Man8GlcNAc2. This N-oligosaccharide is then elaborated in the Golgi to form N-glycans with highly branched outer chains rich in mannose. In Saccharomyces cerevisiae, CWH41, ROT2, and MNS1 encode for α-glucosidase I, α-glucosidase II catalytic subunit, and α1,2-mannosidase, respectively. We disrupted the C. albicans CWH41, ROT2, and MNS1 homologs to determine the importance of N-oligosaccharide processing on the N-glycan outer-chain elongation and the host-fungus interaction. Yeast cells of Cacwh41Δ, Carot2Δ, and Camns1Δ null mutants tended to aggregate, displayed reduced growth rates, had a lower content of cell wall phosphomannan and other changes in cell wall composition, underglycosylated β-N-acetylhexosaminidase, and had a constitutively activated PKC-Mkc1 cell wall integrity pathway. They were also attenuated in virulence in a murine model of systemic infection and stimulated an altered pro- and anti-inflammatory cytokine profile from human monocytes. Therefore, N-oligosaccharide processing by ER glycosidases is required for cell wall integrity and for host-fungus interactions. PMID:17933909

  10. Factors that influence the acceptance of integrated community energy systems

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, A. S.; Tschanz, J. F.; Mosena, D.; Erley, D.; Gil, E.; Slovak, P.; Lenth, C. S.

    1977-01-01

    This report is part of a series of studies designed to analyze the commercialization potential of various concepts of community-scale energy systems that have been termed Integrated Community Energy Systems (ICES). The study reported here concerns ways that affected individuals and organizations will respond to proposed ICES development projects. The intent is an initial examination of several institutional sectors that will: (1) anticipate responses that could impede ICES proposals and (2) provide an information base from which strategies to address adverse responses can be formulated.

  11. Risk factors associated with mental health issues in adolescents: a integrative review

    Directory of Open Access Journals (Sweden)

    Agnes Caroline Souza Pinto

    2014-06-01

    Full Text Available Objective: To identify the risk factors associated with mental health issues in adolescents. Method: An integrative review was conducted in four databases with publications from 2007 to 2013. The terms Adolescent and Mental Health were used to search adequate articles as DeCs/MeSH bases. Results: Publications were found in different journals in different fields of knowledge and the quantitative research was the most frequent. The mental health issues were categorized as individual factors; drug related factors, school factors, family factors, social factors and STDs/Aids related factors. The most addressed category was individual factors, with 23 publications. Conclusion: The integrative review allowed to point important questions to be addressed in preventive actions by the health professional, including the nurse, to create a space that works with risk conditioning factors in adolescents for mental health aggravation.

  12. Integrating human factors research and surgery: a review.

    Science.gov (United States)

    Shouhed, Daniel; Gewertz, Bruce; Wiegmann, Doug; Catchpole, Ken

    2012-12-01

    To provide a review of human factors research within the context of surgery. We searched PubMed for relevant studies published from the earliest available date through February 29, 2012. The search was performed using the following keywords: human factors, surgery, errors, teamwork, communication, stress, disruptions, interventions, checklists, briefings, and training. Additional articles were identified by a manual search of the references from the key articles. As 2 human factors specialists, a senior clinician, and a junior clinician, we carefully selected the most appropriate exemplars of research findings with specific relevance to surgical error and safety. Seventy-seven articles of relevance were selected and reviewed in detail. Opinion pieces and editorials were disregarded; the focus was solely on articles based on empirical evidence, with a particular emphasis on prospectively designed studies. The themes that emerged related to the development of human factors theories, the application of those theories within surgery, a specific interest in the concept of flow, and the theoretical basis and value of human-related interventions for improving safety and flow in surgery. Despite increased awareness of safety, errors routinely continue to occur in surgical care. Disruptions in the flow of an operation, such as teamwork and communication failures, contribute significantly to such adverse events. While it is apparent that some incidence of human error is unavoidable, there is much evidence in medicine and other fields that systems can be better designed to prevent or detect errors before a patient is harmed. The complexity of factors leading to surgical errors requires collaborations between surgeons and human factors experts to carry out the proper prospective and observational studies. Only when we are guided by this valid and real-world data can useful interventions be identified and implemented.

  13. Parasite host range and the evolution of host resistance

    NARCIS (Netherlands)

    Gorter, F.A.; Hall, A.R.; A., Buckling; P.D., Scanlan

    2015-01-01

    Parasite host range plays a pivotal role in the evolution and ecology of hosts
    and the emergence of infectious disease. Although the factors that promote
    host range and the epidemiological consequences of variation in host range
    are relatively well characterized, the effect of parasite

  14. Myxoma virus M064 is a novel member of the poxvirus C7L superfamily of host range factors that controls the kinetics of myxomatosis in European rabbits.

    Science.gov (United States)

    Liu, Jia; Wennier, Sonia; Moussatche, Nissin; Reinhard, Mary; Condit, Richard; McFadden, Grant

    2012-05-01

    The myxoma virus (MYXV) carries three tandem C7L-like host range genes (M062R, M063R, and M064R). However, despite the fact that the sequences of these three genes are similar, they possess very distinctive functions in vivo. The role of M064 in MYXV pathogenesis was investigated and compared to the roles of M062 and M063. We report that M064 is a virulence factor that contributes to MYXV pathogenesis but lacks the host range properties associated with M062 and M063.

  15. Poxvirus host range protein CP77 contains an F-box-like domain that is necessary to suppress NF-kappaB activation by tumor necrosis factor alpha but is independent of its host range function.

    Science.gov (United States)

    Chang, Shu-Jung; Hsiao, Jye-Chian; Sonnberg, Stephanie; Chiang, Cheng-Ting; Yang, Min-Hsiang; Tzou, Der-Lii; Mercer, Andrew A; Chang, Wen

    2009-05-01

    Tumor necrosis factor alpha (TNF-alpha) activates the nuclear factor kappaB (NF-kappaB) signaling pathway that regulates expression of many cellular factors playing important roles in innate immune responses and inflammation in infected hosts. Poxviruses employ many strategies to inhibit NF-kappaB activation in cells. In this report, we describe a poxvirus host range protein, CP77, which blocked NF-kappaB activation by TNF-alpha. Immunofluorescence analyses revealed that nuclear translocation of NF-kappaB subunit p65 protein in TNF-alpha-treated HeLa cells was blocked by CP77. CP77 did so without blocking IkappaBalpha phosphorylation, suggesting that upstream kinase activation was not affected by CP77. Using GST pull-down, we showed that CP77 bound to the NF-kappaB subunit p65 through the N-terminal six-ankyrin-repeat region in vitro. CP77 also bound to Cullin-1 and Skp1 of the SCF complex through a C-terminal 13-amino-acid F-box-like sequence. Both regions of CP77 are required to block NF-kappaB activation. We thus propose a model in which poxvirus CP77 suppresses NF-kappaB activation by two interactions: the C-terminal F-box of CP77 binding to the SCF complex and the N-terminal six ankyrins binding to the NF-kappaB subunit p65. In this way, CP77 attenuates innate immune response signaling in cells. Finally, we expressed CP77 or a CP77 F-box deletion protein from a vaccinia virus host range mutant (VV-hr-GFP) and showed that either protein was able to rescue the host range defect, illustrating that the F-box region, which is important for NF-kappaB modulation and binding to SCF complex, is not required for CP77's host range function. Consistently, knocking down the protein level of NF-kappaB did not relieve the growth restriction of VV-hr-GFP in HeLa cells.

  16. The ubiquitin ligase TRIM27 functions as a host restriction factor antagonized by Mycobacterium tuberculosis PtpA during mycobacterial infection

    Science.gov (United States)

    Wang, Jing; Teng, Jade L. L.; Zhao, Dongdong; Ge, Pupu; Li, Bingxi; Woo, Patrick C. Y.; Liu, Cui Hua

    2016-01-01

    Macrophage-mediated innate immune responses play crucial roles in host defense against pathogens. Recent years have seen an explosion of host proteins that act as restriction factors blocking viral replication in infected cells. However, the essential factors restricting Mycobacterium tuberculosis (Mtb) and their regulatory roles during mycobacterial infection remain largely unknown. We previously reported that Mtb tyrosine phosphatase PtpA, a secreted effector protein required for intracellular survival of Mtb, inhibits innate immunity by co-opting the host ubiquitin system. Here, we identified a new PtpA-interacting host protein TRIM27, which is reported to possess a conserved RING domain and usually acts as an E3 ubiquitin ligase that interferes with various cellular processes. We further demonstrated that TRIM27 restricts survival of mycobacteria in macrophages by promoting innate immune responses and cell apoptosis. Interestingly, Mtb PtpA could antagonize TRIM27-promoted JNK/p38 MAPK pathway activation and cell apoptosis through competitively binding to the RING domain of TRIM27. TRIM27 probably works as a potential restriction factor for Mtb and its function is counteracted by Mtb effector proteins such as PtpA. Our study suggests a potential tuberculosis treatment via targeting of the TRIM27-PtpA interfaces. PMID:27698396

  17. Enterovirus-induced miR-141 contributes to shutoff of host protein translation by targeting the translation initiation factor eIF4E.

    Science.gov (United States)

    Ho, Bing-Ching; Yu, Sung-Liang; Chen, Jeremy J W; Chang, Sui-Yuan; Yan, Bo-Shiun; Hong, Qi-Sheng; Singh, Sher; Kao, Chuan-Liang; Chen, Hsuan-Yu; Su, Kang-Yi; Li, Ker-Chau; Cheng, Chiou-Ling; Cheng, Hao-Wei; Lee, Jen-Yi; Lee, Chun-Nan; Yang, Pan-Chyr

    2011-01-20

    Viruses rely on the host translation machinery to complete their life cycles. Picornaviruses use an internal ribosome entry site to initiate cap-independent protein translation and in parallel host cap-dependent translation is shut off. This process is thought to occur primarily via cleavage of host translation initiation factors eIF4GI and eIF4GII by viral proteases. Here we describe another mechanism whereby miR-141 induced upon enterovirus infection targets the cap-dependent translation initiation factor, eIF4E, for shutoff of host protein synthesis. Knockdown of miR-141 reduces viral propagation, and silencing of eIF4E can completely reverse the inhibitory effect of the miR-141 antagomiR on viral propagation. Ectopic expression of miR-141 promotes the switch from cap-dependent to cap-independent translation. Moreover, we identified a transcription factor, EGR1, which is partly responsible for miR-141 induction in response to enterovirus infection. Our results suggest that upregulation of miR-141 upon enterovirus infection can facilitate viral propagation by expediting the translational switch.

  18. Staphylococcal Ecb protein and host complement regulator factor H enhance functions of each other in bacterial immune evasion.

    Science.gov (United States)

    Amdahl, Hanne; Jongerius, Ilse; Meri, Taru; Pasanen, Tanja; Hyvärinen, Satu; Haapasalo, Karita; van Strijp, Jos A; Rooijakkers, Suzan H; Jokiranta, T Sakari

    2013-08-15

    Staphylococcus aureus is a major human pathogen causing more than a tenth of all septicemia cases and often superficial and deep infections in various tissues. One of the immune evasion strategies of S. aureus is to secrete proteins that bind to the central complement opsonin C3b. One of these, extracellular complement binding protein (Ecb), is known to interfere directly with functions of C3b. Because C3b is also the target of the physiological plasma complement regulator, factor H (FH), we studied the effect of Ecb on the complement regulatory functions of FH. We show that Ecb enhances acquisition of FH from serum onto staphylococcal surfaces. Ecb and FH enhance mutual binding to C3b and also the function of each other in downregulating complement activation. Both Ecb and the C-terminal domains 19-20 of FH bind to the C3d part of C3b. We show that the mutual enhancing effect of Ecb and FH on binding to C3b depends on binding of the FH domain 19 to the C3d part of C3b next to the binding site of Ecb on C3d. Our results show that Ecb, FH, and C3b form a tripartite complex. Upon exposure of serum-sensitive Haemophilus influenzae to human serum, Ecb protected the bacteria, and this effect was enhanced by the addition of the C-terminal domains 19-20 of FH. This finding indicates that the tripartite complex formation could give additional protection to bacteria and that S. aureus is thereby able to use host FH and bacterial Ecb in a concerted action to eliminate C3b at the site of infection.

  19. A conserved helicase processivity factor is needed for conjugation and replication of an integrative and conjugative element.

    Directory of Open Access Journals (Sweden)

    Jacob Thomas

    Full Text Available Integrative and conjugative elements (ICEs are agents of horizontal gene transfer and have major roles in evolution and acquisition of new traits, including antibiotic resistances. ICEs are found integrated in a host chromosome and can excise and transfer to recipient bacteria via conjugation. Conjugation involves nicking of the ICE origin of transfer (oriT by the ICE-encoded relaxase and transfer of the nicked single strand of ICE DNA. For ICEBs1 of Bacillus subtilis, nicking of oriT by the ICEBs1 relaxase NicK also initiates rolling circle replication. This autonomous replication of ICEBs1 is critical for stability of the excised element in growing cells. We found a conserved and previously uncharacterized ICE gene that is required for conjugation and replication of ICEBs1. Our results indicate that this gene, helP (formerly ydcP, encodes a helicase processivity factor that enables the host-encoded helicase PcrA to unwind the double-stranded ICEBs1 DNA. HelP was required for both conjugation and replication of ICEBs1, and HelP and NicK were the only ICEBs1 proteins needed for replication from ICEBs1 oriT. Using chromatin immunoprecipitation, we measured association of HelP, NicK, PcrA, and the host-encoded single-strand DNA binding protein Ssb with ICEBs1. We found that NicK was required for association of HelP and PcrA with ICEBs1 DNA. HelP was required for association of PcrA and Ssb with ICEBs1 regions distal, but not proximal, to oriT, indicating that PcrA needs HelP to progress beyond nicked oriT and unwind ICEBs1. In vitro, HelP directly stimulated the helicase activity of the PcrA homologue UvrD. Our findings demonstrate that HelP is a helicase processivity factor needed for efficient unwinding of ICEBs1 for conjugation and replication. Homologues of HelP and PcrA-type helicases are encoded on many known and putative ICEs. We propose that these factors are essential for ICE conjugation, replication, and genetic stability.

  20. Analytic results for planar three-loop integrals for massive form factors

    Science.gov (United States)

    Henn, Johannes M.; Smirnov, Alexander V.; Smirnov, Vladimir A.

    2016-12-01

    We use the method of differential equations to analytically evaluate all planar three-loop Feynman integrals relevant for form factor calculations involving massive particles. Our results for ninety master integrals at general q 2 are expressed in terms of multiple polylogarithms, and results for fiftyone master integrals at the threshold q 2 = 4 m 2 are expressed in terms of multiple polylogarithms of argument one, with indices equal to zero or to a sixth root of unity.

  1. Analytic results for planar three-loop integrals for massive form factors

    CERN Document Server

    Henn, Johannes M; Smirnov, Vladimir A

    2016-01-01

    We use the method of differential equations to analytically evaluate all planar three-loop Feynman integrals relevant for form factor calculations involving massive particles. Our results for ninety master integrals at general $q^2$ are expressed in terms of multiple polylogarithms, and results for fiftyone master integrals at the threshold $q^2=4m^2$ are expressed in terms of multiple polylogarithms of argument one, with indices equal to zero or to a sixth root of unity.

  2. Abiotic and biotic factors associated with tick population dynamics on a mammalian host: Ixodes hexagonus infesting otters, Lutra lutra.

    Directory of Open Access Journals (Sweden)

    Ellie Sherrard-Smith

    Full Text Available The Eurasian otter, Lutra lutra, hosts several parasites with zoonotic potential. As this semiaquatic mammal has large ranges across terrestrial, freshwater and marine habitats, it has the capacity for wide dispersion of pathogens. Despite this, parasites of otters have received relatively little attention. Here, we examine their ectoparasite load and assess whether this is influenced by abiotic or biotic variables. Climatic phenomena such as the North Atlantic Oscillation (NAO affect weather conditions in northern Europe. Consequently parasite distributions, particularly species with life stages exposed to the external environment, can be affected. We assessed the extent to which inter-annual variations in large-scale weather patterns (specifically the NAO and Central England (CE temperatures and host characteristics influenced tick prevalence and intensity. Ectoparasites consisted of a single species, the nidiculous tick Ixodes hexagonus (prevalence = 24.3%; mean intensity = 7.2; range = 1-122; on n = 820 otter hosts. The prevalence, but not intensity of infestation, was associated with high CE temperatures, while both prevalence and intensity were associated with positive phases of the NAO. Such associations indicate that I. hexagonus are most abundant when weather conditions are warmer and wetter. Ticks were more prevalent on juvenile than sub-adult or adult otters, which probably reflects the length of time the hosts spend in the holt where these ticks quest. High tick number was associated with poor host condition, so either poor condition hosts are more susceptible to ticks, or tick infestations negatively impact on host condition. Otters are clearly an important and common host for I. hexagonus, which has implications for vector-borne diseases. This work is the first to consider the impacts of long-term weather patterns on I. hexagonus and uses wild-animal cadavers to illustrate the importance of abiotic and biotic pressures impacting

  3. Integrated high quality factor lithium niobate microdisk resonators

    CERN Document Server

    Wang, Cheng; Lin, Zin; Atikian, Haig A; Venkataraman, Vivek; Huang, I-Chun; Stark, Peter; Lončar, Marko

    2014-01-01

    Lithium Niobate (LN) is an important nonlinear optical material. Here we demonstrate LN microdisk resonators that feature optical quality factor ~ 100,000, realized using robust and scalable fabrication techniques, that operate over a wide wavelength range spanning visible and near infrared. Using our resonators, and leveraging LN's large second order optical nonlinearity, we demonstrate on-chip second harmonic generation with a conversion efficiency of 0.109 W-1.

  4. Infection by Toxoplasma gondii Specifically Induces Host c-Myc and the Genes This Pivotal Transcription Factor Regulates

    Science.gov (United States)

    Franco, Magdalena; Shastri, Anjali J.

    2014-01-01

    Toxoplasma gondii infection has previously been described to cause dramatic changes in the host transcriptome by manipulating key regulators, including STATs, NF-κB, and microRNAs. Here, we report that Toxoplasma tachyzoites also mediate rapid and sustained induction of another pivotal regulator of host cell transcription, c-Myc. This induction is seen in cells infected with all three canonical types of Toxoplasma but not the closely related apicomplexan parasite Neospora caninum. Coinfection of cells with both Toxoplasma and Neospora still results in an increase in the level of host c-Myc, showing that c-Myc is actively upregulated by Toxoplasma infection (rather than repressed by Neospora). We further demonstrate that this upregulation may be mediated through c-Jun N-terminal protein kinase (JNK) and is unlikely to be a nonspecific host response, as heat-killed Toxoplasma parasites do not induce this increase and neither do nonviable parasites inside the host cell. Finally, we show that the induced c-Myc is active and that transcripts dependent on its function are upregulated, as predicted. Hence, c-Myc represents an additional way in which Toxoplasma tachyzoites have evolved to specifically alter host cell functions during intracellular growth. PMID:24532536

  5. An siRNA Screen Identifies the U2 snRNP Spliceosome as a Host Restriction Factor for Recombinant Adeno-associated Viruses.

    Science.gov (United States)

    Schreiber, Claire A; Sakuma, Toshie; Izumiya, Yoshihiro; Holditch, Sara J; Hickey, Raymond D; Bressin, Robert K; Basu, Upamanyu; Koide, Kazunori; Asokan, Aravind; Ikeda, Yasuhiro

    2015-08-01

    Adeno-associated viruses (AAV) have evolved to exploit the dynamic reorganization of host cell machinery during co-infection by adenoviruses and other helper viruses. In the absence of helper viruses, host factors such as the proteasome and DNA damage response machinery have been shown to effectively inhibit AAV transduction by restricting processes ranging from nuclear entry to second-strand DNA synthesis. To identify host factors that might affect other key steps in AAV infection, we screened an siRNA library that revealed several candidate genes including the PHD finger-like domain protein 5A (PHF5A), a U2 snRNP-associated protein. Disruption of PHF5A expression selectively enhanced transgene expression from AAV by increasing transcript levels and appears to influence a step after second-strand synthesis in a serotype and cell type-independent manner. Genetic disruption of U2 snRNP and associated proteins, such as SF3B1 and U2AF1, also increased expression from AAV vector, suggesting the critical role of U2 snRNP spliceosome complex in this host-mediated restriction. Notably, adenoviral co-infection and U2 snRNP inhibition appeared to target a common pathway in increasing expression from AAV vectors. Moreover, pharmacological inhibition of U2 snRNP by meayamycin B, a potent SF3B1 inhibitor, substantially enhanced AAV vector transduction of clinically relevant cell types. Further analysis suggested that U2 snRNP proteins suppress AAV vector transgene expression through direct recognition of intact AAV capsids. In summary, we identify U2 snRNP and associated splicing factors, which are known to be affected during adenoviral infection, as novel host restriction factors that effectively limit AAV transgene expression. Concurrently, we postulate that pharmacological/genetic manipulation of components of the spliceosomal machinery might enable more effective gene transfer modalities with recombinant AAV vectors.

  6. An siRNA Screen Identifies the U2 snRNP Spliceosome as a Host Restriction Factor for Recombinant Adeno-associated Viruses.

    Directory of Open Access Journals (Sweden)

    Claire A Schreiber

    2015-08-01

    Full Text Available Adeno-associated viruses (AAV have evolved to exploit the dynamic reorganization of host cell machinery during co-infection by adenoviruses and other helper viruses. In the absence of helper viruses, host factors such as the proteasome and DNA damage response machinery have been shown to effectively inhibit AAV transduction by restricting processes ranging from nuclear entry to second-strand DNA synthesis. To identify host factors that might affect other key steps in AAV infection, we screened an siRNA library that revealed several candidate genes including the PHD finger-like domain protein 5A (PHF5A, a U2 snRNP-associated protein. Disruption of PHF5A expression selectively enhanced transgene expression from AAV by increasing transcript levels and appears to influence a step after second-strand synthesis in a serotype and cell type-independent manner. Genetic disruption of U2 snRNP and associated proteins, such as SF3B1 and U2AF1, also increased expression from AAV vector, suggesting the critical role of U2 snRNP spliceosome complex in this host-mediated restriction. Notably, adenoviral co-infection and U2 snRNP inhibition appeared to target a common pathway in increasing expression from AAV vectors. Moreover, pharmacological inhibition of U2 snRNP by meayamycin B, a potent SF3B1 inhibitor, substantially enhanced AAV vector transduction of clinically relevant cell types. Further analysis suggested that U2 snRNP proteins suppress AAV vector transgene expression through direct recognition of intact AAV capsids. In summary, we identify U2 snRNP and associated splicing factors, which are known to be affected during adenoviral infection, as novel host restriction factors that effectively limit AAV transgene expression. Concurrently, we postulate that pharmacological/genetic manipulation of components of the spliceosomal machinery might enable more effective gene transfer modalities with recombinant AAV vectors.

  7. Design and management of production systems: Integration of human factors and ergonomics

    DEFF Research Database (Denmark)

    Jensen, Per Langå; Broberg, Ole; Hasle, Peter

    2006-01-01

    Integration of ergonomics, human factors and occupational health and safety into design and management of pro-duction systems has for years been the major strategy for professional within the field. The traditional approach based on establishing ergonomic criteria’s to be integrated into other...

  8. Factors Influencing the Integration of Technology by Community College Adjunct Faculty

    Science.gov (United States)

    Paver, Jonathan David

    2012-01-01

    This research examined the factors that predict intention to integrate technology into instruction by community college adjunct faculty. For this study the integration of technology was defined as beyond simple occasional use, within the next academic year. The decomposed theory of planned behavior was tested for its predictive ability with this…

  9. Factors Influencing the Integration of Technology by Community College Adjunct Faculty

    Science.gov (United States)

    Paver, Jonathan David

    2012-01-01

    This research examined the factors that predict intention to integrate technology into instruction by community college adjunct faculty. For this study the integration of technology was defined as beyond simple occasional use, within the next academic year. The decomposed theory of planned behavior was tested for its predictive ability with this…

  10. Exploring the Relationship between Factors of Implementation, Treatment Integrity and Reading Fluency

    Science.gov (United States)

    Henninger, Kira Liese

    2010-01-01

    Treatment integrity has always had a presence in research, but now more than ever must become a priority owing to the changes in Special Education Law. The present study intends to explore the relationship between factors of implementation, treatment integrity of intervention implementation, and reading fluency. Participants included students in…

  11. Extending "the Rubber Rope": Convergent Series, Divergent Series and the Integrating Factor

    Science.gov (United States)

    McCartney, Mark

    2013-01-01

    A well-known mathematical puzzle regarding a worm crawling along an elastic rope is considered. The resulting generalizations provide examples for use in a teaching context including applications of series summation, the use of the integrating factor for the solution of differential equations, and the evaluation of definite integrals. A number of…

  12. Understanding the Contextual Factors that Influence School Counselors' Multicultural Diversity Integration Practices

    Science.gov (United States)

    Packer-Williams, Catherine L.; Jay, Michelle L.; Evans, Kathy M.

    2010-01-01

    This study explores the contextual factors that influence a school counselor's decision to actively integrate multicultural diversity in his/her work. Through using the Integrating Multicultural Diversity Questionnaire (IMDQ) the effectiveness of multicultural diversity training, the types of multicultural diversity practices that are used with…

  13. A novel approach - the propensity to propagate (PTP method for controlling for host factors in studying the transmission of Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Hanna Nebenzahl-Guimaraes

    Full Text Available RATIONALE: Understanding the genetic variations among Mycobacterium tuberculosis (MTB strains with differential ability to transmit would be a major step forward in preventing transmission. OBJECTIVES: To describe a method to extend conventional proxy measures of transmissibility by adjusting for patient-related factors, thus strengthening the causal association found with bacterial factors. METHODS: Clinical, demographic and molecular fingerprinting data were obtained during routine surveillance of verified MTB cases reported in the Netherlands between 1993 and 2011, and the phylogenetic lineages of the isolates were inferred. Odds ratios for host risk factors for clustering were used to obtain a measure of each patient's and cluster's propensity to propagate (CPP. Mean and median cluster sizes across different categories of CPP were compared amongst four different phylogenetic lineages. RESULTS: Both mean and median cluster size grew with increasing CPP category. On average, CPP values from Euro-American lineage strains were higher than Beijing and EAI strains. There were no significant differences between the mean and median cluster sizes among the four phylogenetic lineages within each CPP category. CONCLUSIONS: Our finding that the distribution of CPP scores was unequal across four different phylogenetic lineages supports the notion that host-related factors should be controlled for to attain comparability in measuring the different phylogenetic lineages' ability to propagate. Although Euro-American strains were more likely to be in clusters in an unadjusted analysis, no significant differences among the four lineages persisted after we controlled for host factors.

  14. Integrating Factors and Conservation Theorems of Lagrangian Equations for Nonconservative Mechanical System in Generalized Classical Mechanics

    Institute of Scientific and Technical Information of China (English)

    QIAO Yong-Fen; ZHAO Shu-Hong

    2006-01-01

    The conservation theorems of the generalized Lagrangian equations for nonconservative mechanical system are studied by using method of integrating factors. Firstly, the differential equations of motion of system are given, and the definition of integrating factors is given. Next, the necessary conditions for the existence of the conserved quantity are studied in detail. Finally, the conservation theorem and its inverse for the system are established, and an example is given to illustrate the application of the result.

  15. Nuclear factor erythroid 2-related factor 2 (Nrf2 regulates airway epithelial barrier integrity

    Directory of Open Access Journals (Sweden)

    Yoshitaka Shintani

    2015-09-01

    Conclusions: Our results indicated that the Nrf2/AOX1 pathway was important for enhancing airway epithelial barrier integrity. Because the airway epithelium of asthmatics is susceptible to reduced barrier integrity, this pathway might be a new therapeutic target for asthma.

  16. Positive semidefinite integrated covariance estimation, factorizations and asynchronicity

    DEFF Research Database (Denmark)

    Sauri, Orimar; Lunde, Asger; Laurent, Sébastien;

    2017-01-01

    An estimator of the ex-post covariation of log-prices under asynchronicity and microstructure noise is proposed. It uses the Cholesky factorization of the covariance matrix in order to exploit the heterogeneity in trading intensities to estimate the different parameters sequentially with as many...... observations as possible. The estimator is positive semidefinite by construction. We derive asymptotic results and confirm their good finite sample properties by means of a Monte Carlo simulation. In the application we forecast portfolio Value-at-Risk and sector risk exposures for a portfolio of 52 stocks. We...

  17. An improved Tn7-lux reporter for broad host range, chromosomally-integrated promoter fusions in Gram-negative bacteria.

    Science.gov (United States)

    Glassing, Angela; Lewis, Thomas A

    2015-11-01

    An improved vector for chromosomally-integrated promoter-lux fusions is described. The modified vector was tested in parallel with the unmodified vector using the well-characterized Escherichia coli araBAD promoter in the Pseudomonas aeruginosa attTn7 site. The modified mini-Tn7 showed reduced background luminescence, and increased luminescence upon induction, giving >16-fold higher induction ratio.

  18. An improved Tn7-lux reporter for broad host range, chromosomally-integrated promoter fusions in Gram-negative bacteria

    Science.gov (United States)

    Glassing, Angela; Lewis, Thomas A.

    2015-01-01

    An improved vector for chromosomally-integrated promoter-lux fusions is described. The modified vector was tested in parallel with the unmodified vector using the well-characterized E. coli araBAD promoter in the Pseudomonas aeruginosa attTn7 site. The modified mini-Tn7 showed reduced background luminescence, and increased luminescence upon induction, giving >16-fold higher induction ratio. PMID:26341612

  19. On-shell diagrams, Graßmannians and integrability for form factors

    Energy Technology Data Exchange (ETDEWEB)

    Frassek, Rouven [Department of Mathematical Sciences, Durham University,South Road, Durham DH1 3LE (United Kingdom); Meidinger, David; Nandan, Dhritiman; Wilhelm, Matthias [Institut für Mathematik und Institut für Physik, Humboldt-Universität zu Berlin,IRIS Gebäude, Zum Großen Windkanal 6, 12489 Berlin (Germany)

    2016-01-29

    We apply on-shell and integrability methods that have been developed in the context of scattering amplitudes in N=4 SYM theory to tree-level form factors of this theory. Focussing on the colour-ordered super form factors of the chiral part of the stress-tensor multiplet as an example, we show how to systematically construct on-shell diagrams for these form factors with the minimal form factor as further building block in addition to the three-point amplitudes. Moreover, we obtain analytic representations in terms of Graßmannian integrals in spinor helicity, twistor and momentum twistor variables. While Yangian invariance is broken by the operator insertion, we find that the form factors are eigenstates of the integrable spin-chain transfer matrix built from the monodromy matrix that yields the Yangian generators. Constructing them via the method of R operators allows to introduce deformations that preserve the integrable structure. We finally show that the integrable properties extend to minimal tree-level form factors of generic composite operators as well as certain leading singularities of their n-point loop-level form factors.

  20. Angiogenic Type I Collagen Extracellular Matrix Integrated with Recombinant Bacteriophages Displaying Vascular Endothelial Growth Factors.

    Science.gov (United States)

    Yoon, Junghyo; Korkmaz Zirpel, Nuriye; Park, Hyun-Ji; Han, Sewoon; Hwang, Kyung Hoon; Shin, Jisoo; Cho, Seung-Woo; Nam, Chang-Hoon; Chung, Seok

    2016-01-21

    Here, a growth-factor-integrated natural extracellular matrix of type I collagen is presented that induces angiogenesis. The developed matrix adapts type I collagen nanofibers integrated with synthetic colloidal particles of recombinant bacteriophages that display vascular endothelial growth factor (VEGF). The integration is achieved during or after gelation of the type I collagen and the matrix enables spatial delivery of VEGF into a desired region. Endothelial cells that contact the VEGF are found to invade into the matrix to form tube-like structures both in vitro and in vivo, proving the angiogenic potential of the matrix.

  1. Factors influencing groundwater quality: towards an integrated management approach.

    Science.gov (United States)

    De Giglio, O; Quaranta, A; Barbuti, G; Napoli, C; Caggiano, G; Montagna, M T

    2015-01-01

    The safety of groundwater resources is a serious issue, particularly when these resources are the main source of water for drinking, irrigation and industrial use in coastal areas. In Italy, 85% of the water used by the public is of underground origin. The aim of this report is to analyze the main factors that make groundwater vulnerable. Soil characteristics and filtration capacity can promote or hinder the diffusion of environmental contaminants. Global climate change influences the prevalence and degree of groundwater contamination. Anthropic pressure causes considerable exploitation of water resources, leading to reduced water availability and the progressive deterioration of water quality. Management of water quality will require a multidisciplinary, dynamic and practical approach focused on identifying the measures necessary to reduce contamination and mitigate the risks associated with the use of contaminated water resources.

  2. Time to accelerate integration of human factors and ergonomics in patient safety.

    Science.gov (United States)

    Gurses, Ayse P; Ozok, A Ant; Pronovost, Peter J

    2012-04-01

    Progress toward improving patient safety has been slow despite engagement of the health care community in improvement efforts. A potential reason for this sluggish pace is the inadequate integration of human factors and ergonomics principles and methods in these efforts. Patient safety problems are complex and rarely caused by one factor or component of a work system. Thus, health care would benefit from human factors and ergonomics evaluations to systematically identify the problems, prioritize the right ones, and develop effective and practical solutions. This paper gives an overview of the discipline of human factors and ergonomics and describes its role in improving patient safety. We provide examples of how human factors and ergonomics principles and methods have improved both care processes and patient outcomes. We provide five major recommendations to better integrate human factors and ergonomics in patient safety improvement efforts: build capacity among health care workers to understand human factors and ergonomics, create market forces that demand the integration of human factors and ergonomics design principles into medical technologies, increase the number of human factors and ergonomic practitioners in health care organizations, expand investments in improvement efforts informed by human factors and ergonomics, and support interdisciplinary research to improve patient safety. In conclusion, human factors and ergonomics must play a more prominent role in health care if we want to increase the pace in improving patient safety.

  3. Relevant Factors in The Post-Merger Systems Integration and Information Technology in Brazilian Banks

    Directory of Open Access Journals (Sweden)

    Marcel Ginotti Pires

    2017-01-01

    Full Text Available This article discusses the factors present in post-merger integration of Systems and Information Technology (SIT that lead to positive and negative results in mergers and acquisitions (M & A. The research comprised three of the largest acquiring banks in Brazil. We adopted two methods of research, qualitative, to operationalize the theoretical concepts and quantitative, to test the hypotheses. We interviewed six executives of banks that held relevant experience in M & A processes. Subsequently, we applied questionnaires to IT professionals who were involved in the SIT integration processes. The results showed that the quality and expertise of the integration teams and managing the integration were the most relevant factors in the processes, with positive results for increased efficiency and the increased capacity of SIT. Negative results were due to failures in exploiting learning opportunities, the loss of employees and the inexpressive record of integration procedures.

  4. Model correction factor method for reliability problems involving integrals of non-Gaussian random fields

    DEFF Research Database (Denmark)

    Franchin, P.; Ditlevsen, Ove Dalager; Kiureghian, Armen Der

    2002-01-01

    The model correction factor method (MCFM) is used in conjunction with the first-order reliability method (FORM) to solve structural reliability problems involving integrals of non-Gaussian random fields. The approach replaces the limit-state function with an idealized one, in which the integrals...... are considered to be Gaussian. Conventional FORM analysis yields the linearization point of the idealized limit-state surface. A model correction factor is then introduced to push the idealized limit-state surface onto the actual limit-state surface. A few iterations yield a good approximation of the reliability...... reliability method; Model correction factor method; Nataf field integration; Non-Gaussion random field; Random field integration; Structural reliability; Pile foundation reliability...

  5. Incidence, risk factors, and outcome of cytomegalovirus viremia and gastroenteritis in patients with gastrointestinal graft-versus-host disease.

    Science.gov (United States)

    Bhutani, Divaya; Dyson, Gregory; Manasa, Richard; Deol, Abhinav; Ratanatharathorn, Voravit; Ayash, Lois; Abidi, Muneer; Lum, Lawrence G; Al-Kadhimi, Zaid; Uberti, Joseph P

    2015-01-01

    Gastrointestinal (GI) graft-versus-host disease (GVHD) is one of the most common causes of morbidity and mortality after allogeneic stem cell transplantation. In addition, cytomegalovirus (CMV) infection of the gastrointestinal tract can complicate the post-transplantation course of these patients and it can be difficult to differentiate the 2 diagnoses given that they can present with similar symptoms. We retrospectively analyzed 252 patients who were diagnosed with GI GVHD to evaluate the incidence, risk factors, and outcomes of CMV viremia and CMV gastroenteritis in these patients. The median age at the time of transplantation was 51 years, 35% were related donor transplantations, and 65% were unrelated donor transplantations. A total of 114 (45%) patients developed CMV viremia at a median of 34 days (range, 14 to 236 days) after transplantation. Only recipient CMV IgG serostatus was significantly associated with development of CMV viremia (P gastroenteritis; 2 patients had evidence of CMV gastroenteritis and GVHD on the first biopsy and 29 on the second biopsy. Median time to development of CMV gastroenteritis was 52 days (range, 19 to 236 days) after transplantation. Using death as a competing risk, the cumulative incidence of CMV gastroenteritis at 1 year was 16.4%. The incidence of CMV gastroenteritis in relation to the donor/recipient serostatus was as follows: D+/R+, 22%; D-/R+, 31%; D+/R-, 12%; and D-/R-, 0. Median follow-up time for the 252 patients was 35.4 (95% CI 23.8 to 44.8) months. The estimated overall survival rate at 1 and 2 years was .45 (95% confidence interval [CI], .39 to .52) and .39 (95% CI, .33 to .46), respectively. Of the examined variables, those related to the overall survival were maximal clinical GVHD grade (P gastroenteritis (P = .008). Development of CMV viremia was not associated with increased mortality. In conclusion, CMV gastroenteritis is common complication in patients with GI GVHD and can adversely affect the prognosis.

  6. Host-pathogen systems biology: logical modelling of hepatocyte growth factor and Helicobacter pylori induced c-Met signal transduction

    Directory of Open Access Journals (Sweden)

    Kähne Thilo

    2008-01-01

    Full Text Available Abstract Background The hepatocyte growth factor (HGF stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of tissues, including epithelial cells, on binding to the receptor tyrosine kinase c-Met. Abnormal c-Met signalling contributes to tumour genesis, in particular to the development of invasive and metastatic phenotypes. The human microbial pathogen Helicobacter pylori can induce chronic gastritis, peptic ulceration and more rarely, gastric adenocarcinoma. The H. pylori effector protein cytotoxin associated gene A (CagA, which is translocated via a type IV secretion system (T4SS into epithelial cells, intracellularly modulates the c-Met receptor and promotes cellular processes leading to cell scattering, which could contribute to the invasiveness of tumour cells. Using a logical modelling framework, the presented work aims at analysing the c-Met signal transduction network and how it is interfered by H. pylori infection, which might be of importance for tumour development. Results A logical model of HGF and H. pylori induced c-Met signal transduction is presented in this work. The formalism of logical interaction hypergraphs (LIH was used to construct the network model. The molecular interactions included in the model were all assembled manually based on a careful meta-analysis of published experimental results. Our model reveals the differences and commonalities of the response of the network upon HGF and H. pylori induced c-Met signalling. As another important result, using the formalism of minimal intervention sets, phospholipase Cγ1 (PLCγ1 was identified as knockout target for repressing the activation of the extracellular signal regulated kinase 1/2 (ERK1/2, a signalling molecule directly linked to cell scattering in H. pylori infected cells. The model predicted only an effect on ERK1/2 for the H. pylori stimulus, but not for HGF treatment. This result could be confirmed experimentally in MDCK cells using a specific

  7. Ranking of integration factors within supply chains of forward and backward types - recommendations from researches

    Directory of Open Access Journals (Sweden)

    Bernd Hentschel

    2015-06-01

    Full Text Available Background: Integration trends are one of main determinants of the development of modern logistics. After the period of interest focused mainly on supply chains realizing one-way flows only, at present there is a time for supply chains characterized by two-way flows, realizing at the same time both forward and backward flows. The possibility of various configurations of such chains requires identification of integration factors and determination of their influence on the results of the whole supply chain. Experiences of the science as well as the practice of supply chains show the urgent need of learning of reasons of the integration within supply chains of the two-way type.  Material and methods: The researches on modeling and simulation of integration processes within supply chains of forward and backward type were carried out in the environment of iGrafx Process 2013 for Six Sigma. The empirical material obtained in these researches was put to the statistical analysis by the used of Minitab 17. The identification of the significance of differences was made with the help of analysis of variance ANOVA. Additionally the analysis of differences in form of absolute averages was made.  The following measures are main ones for the evaluation of the integration of a supply chain of forward and backward types: cashflow, profitability, service level.  Results: 8 192 simulation experiments were made for 6 integration factors: accessibility of recycled materials, production planning, stock management, integration of transport, unification of packing materials and optimization of the material flow. Based on the analysis of the significance and values of differences, the results of the influence of each integration factor on global results of supply chains of forward and backward type were obtained. They were used to prepare the ranking of integration factors. The main factors, forming the integration shape of two-way supply chains were: stock

  8. Global genetic differentiation in a cosmopolitan pest of stored beans: effects of geography, host-plant usage and anthropogenic factors.

    Directory of Open Access Journals (Sweden)

    Midori Tuda

    Full Text Available Genetic differentiation can be promoted allopatrically by geographic isolation of populations due to limited dispersal ability and diversification over time or sympatrically through, for example, host-race formation. In crop pests, the trading of crops across the world can lead to intermixing of genetically distinct pest populations. However, our understanding of the importance of allopatric and sympatric genetic differentiation in the face of anthropogenic genetic intermixing is limited. Here, we examined global sequence variation in two mitochondrial and one nuclear genes in the seed beetle Callosobruchus maculatus that uses different legumes as hosts. We analyzed 180 samples from 42 populations of this stored bean pest from tropical and subtropical continents and archipelagos: Africa, the Middle East, South and Southeast Asia, Oceania and South America. For the mitochondrial genes, there was weak but significant genetic differentiation across continents/archipelagos. Further, we found pronounced differentiation among subregions within continents/archipelagos both globally and within Africa but not within Asia. We suggest that multiple introductions into Asia and subsequent intermixing within Asia have generated this pattern. The isolation by distance hypothesis was supported globally (with or without continents controlled but not when host species was restricted to cowpeas Vigna unguiculata, the ancestral host of C. maculatus. We also document significant among-host differentiation both globally and within Asia, but not within Africa. We failed to reject a scenario of a constant population size in the recent past combined with selective neutrality for the mitochondrial genes. We conclude that mitochondrial DNA differentiation is primarily due to geographic isolation within Africa and to multiple invasions by different alleles, followed by host shifts, within Asia. The weak inter-continental differentiation is most likely due to frequent inter

  9. Global genetic differentiation in a cosmopolitan pest of stored beans: effects of geography, host-plant usage and anthropogenic factors.

    Science.gov (United States)

    Tuda, Midori; Kagoshima, Kumiko; Toquenaga, Yukihiko; Arnqvist, Göran

    2014-01-01

    Genetic differentiation can be promoted allopatrically by geographic isolation of populations due to limited dispersal ability and diversification over time or sympatrically through, for example, host-race formation. In crop pests, the trading of crops across the world can lead to intermixing of genetically distinct pest populations. However, our understanding of the importance of allopatric and sympatric genetic differentiation in the face of anthropogenic genetic intermixing is limited. Here, we examined global sequence variation in two mitochondrial and one nuclear genes in the seed beetle Callosobruchus maculatus that uses different legumes as hosts. We analyzed 180 samples from 42 populations of this stored bean pest from tropical and subtropical continents and archipelagos: Africa, the Middle East, South and Southeast Asia, Oceania and South America. For the mitochondrial genes, there was weak but significant genetic differentiation across continents/archipelagos. Further, we found pronounced differentiation among subregions within continents/archipelagos both globally and within Africa but not within Asia. We suggest that multiple introductions into Asia and subsequent intermixing within Asia have generated this pattern. The isolation by distance hypothesis was supported globally (with or without continents controlled) but not when host species was restricted to cowpeas Vigna unguiculata, the ancestral host of C. maculatus. We also document significant among-host differentiation both globally and within Asia, but not within Africa. We failed to reject a scenario of a constant population size in the recent past combined with selective neutrality for the mitochondrial genes. We conclude that mitochondrial DNA differentiation is primarily due to geographic isolation within Africa and to multiple invasions by different alleles, followed by host shifts, within Asia. The weak inter-continental differentiation is most likely due to frequent inter-continental gene

  10. An integrated approach to rotorcraft human factors research

    Science.gov (United States)

    Hart, Sandra G.; Hartzell, E. James; Voorhees, James W.; Bucher, Nancy M.; Shively, R. Jay

    1988-01-01

    As the potential of civil and military helicopters has increased, more complex and demanding missions in increasingly hostile environments have been required. Users, designers, and manufacturers have an urgent need for information about human behavior and function to create systems that take advantage of human capabilities, without overloading them. Because there is a large gap between what is known about human behavior and the information needed to predict pilot workload and performance in the complex missions projected for pilots of advanced helicopters, Army and NASA scientists are actively engaged in Human Factors Research at Ames. The research ranges from laboratory experiments to computational modeling, simulation evaluation, and inflight testing. Information obtained in highly controlled but simpler environments generates predictions which can be tested in more realistic situations. These results are used, in turn, to refine theoretical models, provide the focus for subsequent research, and ensure operational relevance, while maintaining predictive advantages. The advantages and disadvantages of each type of research are described along with examples of experimental results.

  11. An Investigation of Relationships between Internal and External Factors Affecting Technology Integration in Classrooms

    Science.gov (United States)

    Hur, Jung Won; Shannon, David; Wolf, Sara

    2016-01-01

    Various factors affecting technology integration have been identified, but little research has examined the relationships between factors, especially internal and external ones, and whether they directly or indirectly influenced each other. To fill this research gap, this study examined the significance and relationships of five factors…

  12. An Investigation of Relationships between Internal and External Factors Affecting Technology Integration in Classrooms

    Science.gov (United States)

    Hur, Jung Won; Shannon, David; Wolf, Sara

    2016-01-01

    Various factors affecting technology integration have been identified, but little research has examined the relationships between factors, especially internal and external ones, and whether they directly or indirectly influenced each other. To fill this research gap, this study examined the significance and relationships of five factors…

  13. Factors Affecting Technology Integration in K-12 Classrooms: A Path Model

    Science.gov (United States)

    Inan, Fethi A.; Lowther, Deborah L.

    2010-01-01

    The purpose of this study was to examine the direct and indirect effects of teachers' individual characteristics and perceptions of environmental factors that influence their technology integration in the classroom. A research-based path model was developed to explain causal relationships between these factors and was tested based on data gathered…

  14. The prediction of bereavement outcome : development of an integrative risk factor framework

    NARCIS (Netherlands)

    Stroebe, Margaret Susan; Folkman, Susan; Hansson, Robert O; Schut, Henk

    2006-01-01

    We propose an integrative risk factor framework to enhance understanding of individual differences in adjustment to bereavement and to encourage more systematic analysis of factors contributing to bereavement outcome (e.g., examination of interactions between variables and establishing pathways in t

  15. Host factor I, Hfq, binds to Escherichia coli ompA mRNA in a growth rate-dependent fashion and regulates its stability

    DEFF Research Database (Denmark)

    Vytvytska, O; Jakobsen, J S; Balcunaite, G

    1998-01-01

    ompA was purified and identified as Hfq, a host factor initially recognized for its function in phage Qbeta replication. The ompA RNA-binding activity parallels the amount of Hfq, which is elevated in bacteria cultured at slow growth rate, a condition leading to facilitated degradation of the ompA m...... suggest a regulatory role for Hfq that specifically facilitates the ompA mRNA degradation in a growth rate-dependent manner....

  16. On the importance of macroeconomic factors for the foreign student’s decision to stay in the host country

    DEFF Research Database (Denmark)

    Vasiljeva, Kristine

    The paper tests empirically whether the macroeconomic variables suggested by migration theories have a significant impact on the foreign student’s decision to stay in their host country. The analysis is based on the combination of country level variables and individual register data. The mean...

  17. Interaction of CSFV E2 protein with swine host factors as detected by yeast two-hybrid system.

    Directory of Open Access Journals (Sweden)

    Douglas P Gladue

    Full Text Available E2 is one of the envelope glycoproteins of pestiviruses, including classical swine fever virus (CSFV and bovine viral diarrhea virus (BVDV. E2 is involved in several critical functions, including virus entry into target cells, induction of a protective immune response and virulence in swine. However, there is no information regarding any host binding partners for the E2 proteins. Here, we utilized the yeast two-hybrid system and identified fifty-seven host proteins as positive binding partners which bound E2 from both CSFV and BVDV with the exception of two proteins that were found to be positive for binding only to CSFV E2. Alanine scanning of CSFV E2 demonstrated that the binding sites for these cellular proteins on E2 are likely non-linear binding sites. The possible roles of the identified host proteins are discussed as the results presented here will be important for future studies to elucidate mechanisms of host protein-virus interactions during pestivirus infection. However, due to the limitations of the yeast two hybrid system, the proteins identified is not exhaustive and each interaction identified needs to be confirmed by independent experimental approaches in the context of virus-infected cells before any definitive conclusion can be drawn on relevance for the virus life cycle.

  18. Cell-mediated immunity to histocompatibility antigens : controlling factors, with emphasis on Graft-versus-host reactions in mice

    NARCIS (Netherlands)

    H. Bril (Herman)

    1984-01-01

    textabstractGraft-versus-Host (GvH) disease is characterized by weight loss, diarrhea, skin lesions, hypofunction of the immune system with concomitant infections, etc. This syndrome is potentially lethal. GvH reactions, which underly this disease, may occur when immunocompetent T lymphocytes are tr

  19. Form factors of the monodromy matrix entries in gl(2|1)-invariant integrable models

    CERN Document Server

    Hutsalyuk, A; Pakuliak, S Z; Ragoucy, E; Slavnov, N A

    2016-01-01

    We study integrable models solvable by the nested algebraic Bethe ansatz and described by $\\mathfrak{gl}(2|1)$ or $\\mathfrak{gl}(1|2)$ superalgebras. We obtain explicit determinant representations for form factors of the monodromy matrix entries. We show that all form factors are related to each other at special limits of the Bethe parameters. Our results allow one to obtain determinant formulas for form factors of local operators in the supersymmetric t-J model.

  20. Form factors of the monodromy matrix entries in gl (2 | 1)-invariant integrable models

    Science.gov (United States)

    Hutsalyuk, A.; Liashyk, A.; Pakuliak, S. Z.; Ragoucy, E.; Slavnov, N. A.

    2016-10-01

    We study integrable models solvable by the nested algebraic Bethe ansatz and described by gl (2 | 1) or gl (1 | 2) superalgebras. We obtain explicit determinant representations for form factors of the monodromy matrix entries. We show that all form factors are related to each other at special limits of the Bethe parameters. Our results allow one to obtain determinant formulas for form factors of local operators in the supersymmetric t- J model.

  1. Constraints on host choice: why do parasitic birds rarely exploit some common potential hosts?

    Science.gov (United States)

    Grim, Tomáš; Samaš, Peter; Moskát, Csaba; Kleven, Oddmund; Honza, Marcel; Moksnes, Arne; Røskaft, Eivin; Stokke, Bård G

    2011-05-01

    1. Why are some common and apparently suitable resources avoided by potential users? This interesting ecological and evolutionary conundrum is vividly illustrated by obligate brood parasites. Parasitic birds lay their eggs into nests of a wide range of host species, including many rare ones, but do not parasitize some commonly co-occurring potential hosts. 2. Attempts to explain the absence of parasitism in common potential hosts are limited and typically focused on single-factor explanations while ignoring other potential factors. We tested why thrushes Turdus spp. are extremely rarely parasitized by common cuckoos Cuculus canorus despite breeding commonly in sympatry and building the most conspicuous nests among forest-breeding passerines. 3. No single examined factor explained cuckoo avoidance of thrushes. Life-history traits of all six European thrush species and the 10 most frequently used cuckoo hosts in Europe were similar except body/egg size, nest design and nestling diet. 4. Experiments (n = 1211) in several populations across Europe showed that host defences at egg-laying and incubation stages did not account for the lack of cuckoo parasitism in thrushes. However, cross-fostering experiments disclosed that various factors during the nestling period prevent cuckoos from successfully parasitizing thrushes. Specifically, in some thrush species, the nest cup design forced cuckoo chicks to compete with host chicks with fatal consequences for the parasite. Other species were reluctant to care even for lone cuckoo chicks. 5. Importantly, in an apparently phylogenetically homogenous group of hosts, there were interspecific differences in factors responsible for the absence of cuckoo parasitism. 6. This study highlights the importance of considering multiple potential factors and their interactions for understanding absence of parasitism in potential hosts of parasitic birds. In the present study, comparative and experimental procedures are integrated, which

  2. The Yersinia Virulence Factor YopM Hijacks Host Kinases to Inhibit Type III Effector-Triggered Activation of the Pyrin Inflammasome.

    Science.gov (United States)

    Chung, Lawton K; Park, Yong Hwan; Zheng, Yueting; Brodsky, Igor E; Hearing, Patrick; Kastner, Daniel L; Chae, Jae Jin; Bliska, James B

    2016-09-14

    Pathogenic Yersinia, including Y. pestis, the agent of plague in humans, and Y. pseudotuberculosis, the related enteric pathogen, deliver virulence effectors into host cells via a prototypical type III secretion system to promote pathogenesis. These effectors, termed Yersinia outer proteins (Yops), modulate multiple host signaling responses. Studies in Y. pestis and Y. pseudotuberculosis have shown that YopM suppresses infection-induced inflammasome activation; however, the underlying molecular mechanism is largely unknown. Here we show that YopM specifically restricts the pyrin inflammasome, which is triggered by the RhoA-inactivating enzymatic activities of YopE and YopT, in Y. pseudotuberculosis-infected macrophages. The attenuation of a yopM mutant is fully reversed in pyrin knockout mice, demonstrating that YopM inhibits pyrin to promote virulence. Mechanistically, YopM recruits and activates the host kinases PRK1 and PRK2 to negatively regulate pyrin by phosphorylation. These results show how a virulence factor can hijack host kinases to inhibit effector-triggered pyrin inflammasome activation. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. An Integrated View of the Effects of Wine Polyphenols and Their Relevant Metabolites on Gut and Host Health

    Directory of Open Access Journals (Sweden)

    Carolina Cueva

    2017-01-01

    Full Text Available Over the last few decades, polyphenols, and flavonoids in particular, have attracted the interest of researchers, as they have been associated with the health-promoting effects derived from diets rich in vegetables and fruits, including moderate wine consumption. Recent scientific evidence suggests that wine polyphenols exert their effects through interactions with the gut microbiota, as they seem to modulate microbiota and, at the same time, are metabolized by intestinal bacteria into specific bioavailable metabolites. Microbial metabolites are better absorbed than their precursors and may be responsible for positive health activities in the digestive system (local effects and, after being absorbed, in tissues and organs (systemic effects. Differences in gut microbiota composition and functionality among individuals can affect polyphenol activity and, therefore, their health effects. The aim of this review is to integrate the understanding of the metabolism and mechanisms of action of wine polyphenols at both local and systemic levels, underlining their impact on the gut microbiome and the inter-individual variability associated with polyphenols’ metabolism and further physiological effects. The advent of promising dietary approaches linked to wine polyphenols beyond the gut microbiota community and metabolism are also discussed.

  4. Spatial and temporal factors affecting parasite genotypes encountered by hosts: empirical data from American dog ticks (Dermacentor variabilis) parasitising raccoons (Procyon lotor).

    Science.gov (United States)

    Dharmarajan, G; Beasley, J C; Rhodes, O E

    2010-06-01

    The American dog tick (Dermacentor variabilis) is an important vector of numerous pathogens of humans and animals. In this study, we analysed population genetic patterns in D. variabilis at scales of the host individual (infrapopulation) and population (component population) to elucidate fine-scale spatial and temporal factors influencing transmission dynamics. We genotyped D. variabilis collected from raccoons (Procyon lotor) trapped in two habitat patches (located in Indiana, USA) which were spatially proximate (5.9 km) and limited in size (10.48 Ha and 25.47 Ha, respectively). Despite the fine spatial sampling scale, our analyses revealed significant genetic differentiation amongst component populations and infrapopulations (within each component population), indicating a non-random pattern of encountering tick genotypes by raccoons at both scales evaluated. We found evidence for male-biased dispersal in the ticks themselves (in one component population) and an age-bias in spatial scales at which raccoons encountered ticks in the environment. At the scale of the component population, our analyses revealed that raccoons encountered ticks from a limited number of D. variabilis family groups, likely due to high reproductive variance amongst individual ticks. Finally, we found evidence for a temporal effect with raccoons encountering ticks in the environment as "clumps" of related individuals. While the genetic structure of parasite populations are increasingly being investigated at small spatial scales (e.g. the infrapopulation), our data reveal that genetic structuring can originate at scales below that of the infrapopulation, due to the interaction between temporal and biological factors affecting the encounter of parasites by individual hosts. Ultimately, our data indicate that genetic structure in parasites must be viewed as a consequence of both spatial and temporal variance in host-parasite interactions, which in turn are driven by demographic factors related

  5. Nonnegative Matrix Factorization Numerical Method for Integrated Photonic Cavity Based Spectroscopy

    Directory of Open Access Journals (Sweden)

    Zhengyu Huang

    2014-01-01

    Full Text Available Nonnegative matrix factorization numerical method has been used to improve the spectral resolution of integrated photonic cavity based spectroscopy. Based on the experimental results for integrated photonic cavity device on Optics Letters 32, 632 (2007, the theoretical results show that the spectral resolution can be improved more than 3 times from 5.5 nm to 1.8 nm. It is a promising way to release the difficulty of fabricating high-resolution devices.

  6. Soluble tumour necrosis factor (TNF)-receptor levels in serum as markers of anti-viral host reactivity

    DEFF Research Database (Denmark)

    Bartholdy, C; Nansen, A; Marker, O

    1999-01-01

    The role of soluble receptors for TNF-alpha (sTNF-Rs) as markers of virus-induced host responses was studied by the use of murine model infections. A marked elevation in serum levels of sTNF-R75, but not sTNF-R55, was found 1 day after infection with vesicular stomatitis virus (VSV). In mice......-gamma. A simple correlation between release of sTNF-Rs in vivo and macrophage activation in vitro was not present. These findings indicate that sTNF-R75 is indeed a sensitive marker of both innate and specific cell-mediated host reactivity during viral infection, but it is not correlated to a single immunological...

  7. Calculation of the molecular integrals with the range-separated correlation factor

    Energy Technology Data Exchange (ETDEWEB)

    Silkowski, Michał; Lesiuk, Michał, E-mail: lesiuk@tiger.chem.uw.edu.pl; Moszynski, Robert [Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw (Poland)

    2015-03-28

    Explicitly correlated quantum chemical calculations require calculations of five types of two-electron integrals beyond the standard electron repulsion integrals. We present a novel scheme, which utilises general ideas of the McMurchie-Davidson technique, to compute these integrals when the so-called “range-separated” correlation factor is used. This correlation factor combines the well-known short range behaviour resulting from the electronic cusp condition, with the exact long-range asymptotics derived for the helium atom [Lesiuk, Jeziorski, and Moszynski, J. Chem. Phys. 139, 134102 (2013)]. Almost all steps of the presented procedure are formulated recursively, so that an efficient implementation and control of the precision are possible. Additionally, the present formulation is very flexible and general, and it allows for use of an arbitrary correlation factor in the electronic structure calculations with minor or no changes.

  8. Calculation of the molecular integrals with the range-separated correlation factor

    CERN Document Server

    Silkowski, Michał; Moszynski, Robert

    2014-01-01

    Explicitly correlated quantum chemical calculations require calculations of five types of molecular integrals beyond the standard electron repulsion integrals. We present a novel scheme, which utilises general ideas of the McMurchie-Davidson technique, to compute these integrals when the so-called \\range-separated" correlation factor is used. This correlation factor combines the well-known short range behaviour, resulting from the electronic cusp condition, with the exact long-range asymptotics found for the helium atom [M. Lesiuk, B. Jeziorski, and R. Moszynski, J. Chem. Phys. $\\textbf{139}$, 134102 (2013)]. Almost all steps of the presented procedure are formulated recursively, so that an efficient implementation and control of the precision are possible. Additionally, the present formulation is very flexible and general, and it allows for use of an arbitrary correlation factor in the electronic structure calculations with minor or no changes.

  9. Invasion biology in non-free-living species: interactions between abiotic (climatic) and biotic (host availability) factors in geographical space in crayfish commensals (Ostracoda, Entocytheridae).

    Science.gov (United States)

    Mestre, Alexandre; Aguilar-Alberola, Josep A; Baldry, David; Balkis, Husamettin; Ellis, Adam; Gil-Delgado, Jose A; Grabow, Karsten; Klobučar, Göran; Kouba, Antonín; Maguire, Ivana; Martens, Andreas; Mülayim, Ayşegül; Rueda, Juan; Scharf, Burkhard; Soes, Menno; S Monrós, Juan; Mesquita-Joanes, Francesc

    2013-12-01

    In invasion processes, both abiotic and biotic factors are considered essential, but the latter are usually disregarded when modeling the potential spread of exotic species. In the framework of set theory, interactions between biotic (B), abiotic (A), and movement-related (M) factors in the geographical space can be hypothesized with BAM diagrams and tested using ecological niche models (ENMs) to estimate A and B areas. The main aim of our survey was to evaluate the interactions between abiotic (climatic) and biotic (host availability) factors in geographical space for exotic symbionts (i.e., non-free-living species), using ENM techniques combined with a BAM framework and using exotic Entocytheridae (Ostracoda) found in Europe as model organisms. We carried out an extensive survey to evaluate the distribution of entocytherids hosted by crayfish in Europe by checking 94 European localities and 12 crayfish species. Both exotic entocytherid species found, Ankylocythere sinuosa and Uncinocythere occidentalis, were widely distributed in W Europe living on the exotic crayfish species Procambarus clarkii and Pacifastacus leniusculus, respectively. No entocytherids were observed in the remaining crayfish species. The suitable area for A. sinuosa was mainly restricted by its own limitations to minimum temperatures in W and N Europe and precipitation seasonality in circum-Mediterranean areas. Uncinocythere occidentalis was mostly restricted by host availability in circum-Mediterranean regions due to limitations of P. leniusculus to higher precipitation seasonality and maximum temperatures. The combination of ENMs with set theory allows studying the invasive biology of symbionts and provides clues about biogeographic barriers due to abiotic or biotic factors limiting the expansion of the symbiont in different regions of the invasive range. The relative importance of abiotic and biotic factors on geographical space can then be assessed and applied in conservation plans. This

  10. Use of in vivo Expression Technology for the Identification of Putative Host Adaptation Factors of the Lyme Disease Spirochete.

    Science.gov (United States)

    Casselli, Timothy; Bankhead, Troy

    2015-01-01

    The causative agent of Lyme disease, Borrelia burgdorferi, is an obligate parasite that requires either a tick vector or a mammalian host for survival. Identification of the bacterial genes that are specifically expressed during infection of the mammalian host could provide targets for novel therapeutics and vaccines. In vivo expression technology (IVET) is a reporter-based promoter trap system that utilizes selectable markers to identify promoters of bacterial host-specific genes. Using previously characterized genes for in vivo and in vitro selection, this study utilized an IVET system that allows for selection of B. burgdorferi sequences that act as active promoters only during murine infection. This promoter trap system was able to successfully distinguish active promoter sequences both in vivo and in vitro from control sequences and a library of cloned B. burgdorferi genomic fragments. However, a bottleneck effect during the experimental mouse infection limited the utility for genome-wide promoter screening. Overall, IVET was demonstrated as a tool for the identification of in vivo-induced promoter elements of B. burgdorferi, and the observed infection bottleneck apparent using a polyclonal infection pool provides insight into the dynamics of experimental infection with B. burgdorferi.

  11. Integrable dissipative nonlinear second order differential equations via factorizations and Abel equations

    Energy Technology Data Exchange (ETDEWEB)

    Mancas, Stefan C. [Department of Mathematics, Embry–Riddle Aeronautical University, Daytona Beach, FL 32114-3900 (United States); Rosu, Haret C., E-mail: hcr@ipicyt.edu.mx [IPICYT, Instituto Potosino de Investigacion Cientifica y Tecnologica, Apdo Postal 3-74 Tangamanga, 78231 San Luis Potosí, SLP (Mexico)

    2013-09-02

    We emphasize two connections, one well known and another less known, between the dissipative nonlinear second order differential equations and the Abel equations which in their first-kind form have only cubic and quadratic terms. Then, employing an old integrability criterion due to Chiellini, we introduce the corresponding integrable dissipative equations. For illustration, we present the cases of some integrable dissipative Fisher, nonlinear pendulum, and Burgers–Huxley type equations which are obtained in this way and can be of interest in applications. We also show how to obtain Abel solutions directly from the factorization of second order nonlinear equations.

  12. On adjoint symmetry equations, integrating factors and solutions of nonlinear ODEs

    Energy Technology Data Exchange (ETDEWEB)

    Guha, Partha [Max Planck Institute for Mathematics in the Sciences, Inselstrasse 22, D-04103 Leipzig (Germany); Choudhury, A Ghose [Department of Physics, Surendranath College, 24/2 Mahatma Gandhi Road, Calcutta-700 009 (India); Khanra, Barun [Sailendra Sircar Vidyalaya, 62A Shyampukur Street, Calcutta-700 004 (India)], E-mail: partha.guha@mis.mpg.de, E-mail: a_ghosechoudhury@rediffmail.com, E-mail: barunkhanra@rediffmail.com

    2009-03-20

    We consider the role of the adjoint equation in determining explicit integrating factors and first integrals of nonlinear ODEs. In Chandrasekar et al (2006 J. Math. Phys. 47 023508), the authors have used an extended version of the Prelle-Singer method for a class of nonlinear ODEs of the oscillator type. In particular, we show that their method actually involves finding a solution of the adjoint symmetry equation. Next, we consider a coupled second-order nonlinear ODE system and derive the corresponding coupled adjoint equations. We illustrate how the coupled adjoint equations can be solved to arrive at a first integral.

  13. Design for human factors (DfHF): a grounded theory for integrating human factors into production design processes.

    Science.gov (United States)

    Village, Judy; Searcy, Cory; Salustri, Filipo; Patrick Neumann, W

    2015-01-01

    The 'design for human factors' grounded theory explains 'how' human factors (HF) went from a reactive, after-injury programme in safety, to being proactively integrated into each step of the production design process. In this longitudinal case study collaboration with engineers and HF Specialists in a large electronics manufacturer, qualitative data (e.g. meetings, interviews, observations and reflections) were analysed using a grounded theory methodology. The central tenet in the theory is that when HF Specialists acclimated to the engineering process, language and tools, and strategically aligned HF to the design and business goals of the organisation, HF became a means to improve business performance. This led to engineers 'pulling' HF Specialists onto their team. HF targets were adopted into engineering tools to communicate HF concerns quantitatively, drive continuous improvement, visibly demonstrate change and lead to benchmarking. Senior management held engineers accountable for HF as a key performance indicator, thus integrating HF into the production design process. Practitioner Summary: Research and practice lack explanations about how HF can be integrated early in design of production systems. This three-year case study and the theory derived demonstrate how ergonomists changed their focus to align with design and business goals to integrate HF into the design process.

  14. Integrals of random fields treated by the model correction factor method

    DEFF Research Database (Denmark)

    Franchin, P.; Ditlevsen, Ove Dalager; Kiureghian, Armen Der

    2002-01-01

    The model correction factor method (MCFM) is used in conjunction with the first-order reliability method (FORM) to solve structural reliability problems involving integrals of non-Gaussian random fields. The approach replaces the limit-state function with an idealized one, in which the integrals...... are considered to be Gaussian. Conventional FORM analysis yields the linearization point of the idealized limit-state surface. A model correction factor is then introduced to push the idealized limit-state surface onto the actual limit-state surface. A few iterations yield a good approximation of the reliability...

  15. The in vivo role of stem cell factor (c-kit ligand) on mastocytosis and host protective immunity to the intestinal nematode Trichinella spiralis in mice.

    Science.gov (United States)

    Grencis, R K; Else, K J; Huntley, J F; Nishikawa, S I

    1993-01-01

    The role of stem cell factor (SCF) in the generation of intestinal mast cell hyperplasia and host protective immunity following helminth infection was investigated using the Trichinella spiralis/mouse model. In vivo administration of a monoclonal antibody specific for the receptor for SCF (c-kit) was found to completely prevent the generation of intestinal mastocytosis normally observed following T. spiralis infection. This was reflected by markedly reduced intestinal mast cell protease (IMCP) levels in both tissue and serum. Moreover, animals treated with anti-c-kit antibody failed to show any evidence of worm expulsion from the gut. The data demonstrate for the first time, a critical role for the SCF in the generation of mucosal mastocytosis and host protective immunity following an intestinal helminth infection.

  16. An integrated graphic–taxonomic–associative approach to analyze human factors in aviation accidents

    Directory of Open Access Journals (Sweden)

    Gong Lei

    2014-04-01

    Full Text Available Human factors are critical causes of modern aviation accidents. However, existing accident analysis methods encounter limitations in addressing aviation human factors, especially in complex accident scenarios. The existing graphic approaches are effective for describing accident mechanisms within various categories of human factors, but cannot simultaneously describe inadequate human–aircraft–environment interactions and organizational deficiencies effectively, and highly depend on analysts’ skills and experiences. Moreover, the existing methods do not emphasize latent unsafe factors outside accidents. This paper focuses on the above three limitations and proposes an integrated graphic–taxonomic–associative approach. A new graphic model named accident tree (AcciTree, with a two-mode structure and a reaction-based concept, is developed for accident modeling and safety defense identification. The AcciTree model is then integrated with the well-established human factors analysis and classification system (HFACS to enhance both reliability of the graphic part and logicality of the taxonomic part for improving completeness of analysis. An associative hazard analysis technique is further put forward to extend analysis to factors outside accidents, to form extended safety requirements for proactive accident prevention. Two crash examples, a research flight demonstrator by our team and an industrial unmanned aircraft, illustrate that the integrated approach is effective for identifying more unsafe factors and safety requirements.

  17. Hα Intensity Map of the Repeating Fast Radio Burst FRB 121102 Host Galaxy from Subaru/Kyoto 3DII AO-assisted Optical Integral-field Spectroscopy

    Science.gov (United States)

    Kokubo, Mitsuru; Mitsuda, Kazuma; Sugai, Hajime; Ozaki, Shinobu; Minowa, Yosuke; Hattori, Takashi; Hayano, Yutaka; Matsubayashi, Kazuya; Shimono, Atsushi; Sako, Shigeyuki; Doi, Mamoru

    2017-08-01

    We present the Hα intensity map of the host galaxy of the repeating fast radio burst FRB 121102 at a redshift of z = 0.193 obtained with the AO-assisted Kyoto 3DII optical integral-field unit mounted on the 8.2 m Subaru Telescope. We detected a compact Hα-emitting (i.e., star-forming) region in the galaxy, which has a much smaller angular size (GMOS z\\prime -band image (≃ 1\\buildrel{\\prime\\prime}\\over{.} 4 (4.6 kpc) at FWHM with ellipticity b/a=0.45). The spatial offset between the centroid of the Hα emission region and the position of the radio bursts is 0\\buildrel{\\prime\\prime}\\over{.} 08+/- 0\\buildrel{\\prime\\prime}\\over{.} 02 (0.26 ± 0.07 kpc), indicating that FRB 121102 is located within the star-forming region. This close spatial association of FRB 121102 with the star-forming region is consistent with expectations from young pulsar/magnetar models for FRB 121102, and it also suggests that the observed Hα emission region can make a major dispersion measure (DM) contribution to the host galaxy DM component of FRB 121102. Nevertheless, the largest possible value of the DM contribution from the Hα emission region inferred from our observations still requires a significant amount of ionized baryons in intergalactic medium (IGM; the so-called “missing” baryons) as the DM source of FRB 121102, and we obtain a 90% confidence level lower limit on the cosmic baryon density in the IGM in the low-redshift universe as {{{Ω }}}{IGM}> 0.012. Based on data collected at Subaru Telescope, which is operated by the National Astronomical Observatory of Japan.

  18. Structure factors for tunneling ionization rates of molecules: General Hartree-Fock-based integral representation

    Science.gov (United States)

    Madsen, Lars Bojer; Jensen, Frank; Dnestryan, Andrey I.; Tolstikhin, Oleg I.

    2017-07-01

    In the leading-order approximation of the weak-field asymptotic theory (WFAT), the dependence of the tunneling ionization rate of a molecule in an electric field on its orientation with respect to the field is determined by the structure factor of the ionizing molecular orbital. The WFAT yields an expression for the structure factor in terms of a local property of the orbital in the asymptotic region. However, in general quantum chemistry approaches molecular orbitals are expanded in a Gaussian basis which does not reproduce their asymptotic behavior correctly. This hinders the application of the WFAT to polyatomic molecules, which are attracting increasing interest in strong-field physics. Recently, an integral-equation approach to the WFAT for tunneling ionization of one electron from an arbitrary potential has been developed. The structure factor is expressed in an integral form as a matrix element involving the ionizing orbital. The integral is not sensitive to the asymptotic behavior of the orbital, which resolves the difficulty mentioned above. Here, we extend the integral representation for the structure factor to many-electron systems treated within the Hartree-Fock method and show how it can be implemented on the basis of standard quantum chemistry software packages. We validate the methodology by considering noble-gas atoms and the CO molecule, for which accurate structure factors exist in the literature. We also present benchmark results for CO2 and for NH3 in the pyramidal and planar geometries.

  19. Factors Affecting the Formation of 2:1 Host:Guest Inclusion Complexes of 2-[(R-Phenylamine]-1,4-naphthalenediones (PAN in β- and γ-Cyclodextrins

    Directory of Open Access Journals (Sweden)

    Christopher K. Jankowski

    2016-11-01

    Full Text Available The molecular hosts cyclodextrins form inclusion complexes with a wide variety of guests, resulting in complexes with various host:guest stoichiometries. In the case of a series of 19 1,4-naphthoquinolines as guests with either β- or γ-cyclodextrin studied using electrospray mass spectroscopy, in most cases only 1:1 complexes were observed, with 2:1 host:guest complexes observed in just 6 out of 38 host:guest combinations. It is shown that these higher-order complexes were observed only in the case of small (or no electronically withdrawing substituents, and were much less likely in the case of the larger γ-cyclodextrin host. The size and electronic properties of the substituents involved shows that both steric and electronic factors must be taken into account in predicting which cyclodextrin host:guest stoichiometries will be stable enough to form (or once formed, be robust enough to be observed in the ESI-MS experiments. It is clear that the prediction of host-guest stoichiometry for a specific host-guest pair is complicated, and involves a subtle interplay of both electronic and steric factors. However, there are definite trends, which can be used to help predict host:guest stoichiometry for a given host-guest pair.

  20. Polyakov's spin factor for a classical spinning particle via BRST invariant path integral

    CERN Document Server

    Cho, J; Lee, H; Jin-Ho Cho; Seungjoon Hyun; Hyuk-Jae Lee

    1994-01-01

    For the "classical" formulation of a massive spinning particle, the propagator is obtained along with the spin factor. We treat the system with two kinds of constraints that were recently shown to be concerned with the reparametrization invariance and "quasi-supersymmetry". In the path integral, the BRST invariant Lagrangian is used and the same spin factor is obtained as in the pseudo-classical formulation.

  1. Which psychological factors influence Internet addiction? Evidence through an integrative model

    OpenAIRE

    Burnay, Jonathan; Billieux, Joël; Blairy, Sylvie; Laroi, Frank

    2015-01-01

    Since the appearance of Internet, several preoccupations have appeared as a result, with Internet addiction being one of the most common. The goals of the present study were two-fold. First, to examine which psychological factors are relevant to explain Internet addiction, including impulsivity, passion and social provision. Second, to incorporate all these factors into an integrative model. Based on multiple regressions and path analysis, results revealed a positive relation between Internet...

  2. The Staphylococcus aureus protein Sbi acts as a complement inhibitor and forms a tripartite complex with host complement Factor H and C3b.

    Directory of Open Access Journals (Sweden)

    Katrin Haupt

    2008-12-01

    Full Text Available The Gram-positive bacterium Staphylococcus aureus, similar to other pathogens, binds human complement regulators Factor H and Factor H related protein 1 (FHR-1 from human serum. Here we identify the secreted protein Sbi (Staphylococcus aureus binder of IgG as a ligand that interacts with Factor H by a-to our knowledge-new type of interaction. Factor H binds to Sbi in combination with C3b or C3d, and forms tripartite SbiratioC3ratioFactor H complexes. Apparently, the type of C3 influences the stability of the complex; surface plasmon resonance studies revealed a higher stability of C3d complexed to Sbi, as compared to C3b or C3. As part of this tripartite complex, Factor H is functionally active and displays complement regulatory activity. Sbi, by recruiting Factor H and C3b, acts as a potent complement inhibitor, and inhibits alternative pathway-mediated lyses of rabbit erythrocytes by human serum and sera of other species. Thus, Sbi is a multifunctional bacterial protein, which binds host complement components Factor H and C3 as well as IgG and beta(2-glycoprotein I and interferes with innate immune recognition.

  3. Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Emily F A van 't Wout

    2015-06-01

    Full Text Available Pseudomonas aeruginosa infection can be disastrous in chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Its toxic effects are largely mediated by secreted virulence factors including pyocyanin, elastase and alkaline protease (AprA. Efficient functioning of the endoplasmic reticulum (ER is crucial for cell survival and appropriate immune responses, while an excess of unfolded proteins within the ER leads to "ER stress" and activation of the "unfolded protein response" (UPR. Bacterial infection and Toll-like receptor activation trigger the UPR most likely due to the increased demand for protein folding of inflammatory mediators. In this study, we show that cell-free conditioned medium of the PAO1 strain of P. aeruginosa, containing secreted virulence factors, induces ER stress in primary bronchial epithelial cells as evidenced by splicing of XBP1 mRNA and induction of CHOP, GRP78 and GADD34 expression. Most aspects of the ER stress response were dependent on TAK1 and p38 MAPK, except for the induction of GADD34 mRNA. Using various mutant strains and purified virulence factors, we identified pyocyanin and AprA as inducers of ER stress. However, the induction of GADD34 was mediated by an ER stress-independent integrated stress response (ISR which was at least partly dependent on the iron-sensing eIF2α kinase HRI. Our data strongly suggest that this increased GADD34 expression served to protect against Pseudomonas-induced, iron-sensitive cell cytotoxicity. In summary, virulence factors from P. aeruginosa induce ER stress in airway epithelial cells and also trigger the ISR to improve cell survival of the host.

  4. CRISPR Outsourcing: Commissioning IHF for Site-Specific Integration of Foreign DNA at the CRISPR Array.

    Science.gov (United States)

    Wei, Yunzhou; Terns, Michael P

    2016-06-16

    In this issue of Molecular Cell, Nuñez et al. (2016) report that site-specific integration of foreign DNA into CRISPR loci by the Cas1-Cas2 integrase complex is promoted by a host factor, IHF (integration host factor), that binds and bends CRISPR leader DNA.

  5. Digitally Controlled Integrated Electronic Ballast with Dimming and Power Factor Correction Features

    Directory of Open Access Journals (Sweden)

    C. Aguilar-Castillo

    2010-12-01

    Full Text Available This paper presents a digitally controlled integrated electronic ballast with dimming and power factor correctionfeatures. The control circuit is based on a low-cost PIC16C71 microcontroller where the different strategies for energysaving have been implemented. The ballast is operating in closed loop achieving tight lamp current regulation througha digital Proportional-Integral algorithm. The integrated power stage is based on a frequency-controlled single-switchboost rectifier plus a half-bridge series resonant parallel loaded inverter sharing one power switch. The single-switchboost rectifier works in discontinuous inductor current mode with automatic power factor correction. Detailed analysisof the power stages and experimental results using 42-watt electronic ballast are presented.

  6. Integrating human factors and artificial intelligence in the development of human-machine cooperation

    NARCIS (Netherlands)

    Maanen, P.P. van; Lindenberg, J.; Neericx, M.A.

    2005-01-01

    Increasing machine intelligence leads to a shift from a mere interactive to a much more complex cooperative human-machine relation requiring a multidisciplinary development approach. This paper presents a generic multidisciplinary cognitive engineering method CE+ for the integration of human factors

  7. Pedagogical Factors Affecting Integration of Computers in Mathematics Instruction in Secondary Schools in Kenya

    Science.gov (United States)

    Wanjala, Martin M. S.; Aurah, Catherine M.; Symon, Koros C.

    2015-01-01

    The paper reports findings of a study which sought to examine the pedagogical factors that affect the integration of computers in mathematics instruction as perceived by teachers in secondary schools in Kenya. This study was based on the Technology Acceptance Model (TAM). A descriptive survey design was used for this study. Stratified and simple…

  8. Teachers' Perspectives: Factors That Impact Implementation of Integrated Curriculum in K-3 Classrooms

    Science.gov (United States)

    Fu, Yao; Sibert, Susan

    2017-01-01

    The purpose of this study was to uncover the factors that may influence K-3 in-service teachers' implementation of integrated curriculum (IC). To provide a consistent research base, the broad definition of IC and Jacob's model were adopted to clarify the controversial concept of IC. Survey data were collected from forty-two teachers from ten…

  9. Strategic Planning with Critical Success Factors and Future Scenarios: An Integrated Strategic Planning Framework

    Science.gov (United States)

    2010-11-01

    This report explores the value of enhancing typical strategic planning techniques with the critical success factor (CSF) method and scenario planning...It synthesizes documented theory and research in strategic planning , CSFs, and future scenarios. It proposes an enhanced, integrated information...framework for strategic planning that can help organizations understand the broad range of interrelated elements that influence strategy development

  10. Homeschooled Students in College: Background Influences, College Integration, and Environmental Pull Factors

    Science.gov (United States)

    Bolle-Brummond, Mary Beth; Wessel, Roger D.

    2012-01-01

    How do pre-entry attributes of homeschooled students influence their college experience? What are their academic and social integration patterns? What role did outside factors play in their college experience? Using Tinto's research as a foundation, this study examined the influence of pre-entry attributes on the college experience, academic and…

  11. Coxsackievirus mutants that can bypass host factor PI4KⅢβ and the need for high levels of PI4P lipids for replication

    Institute of Scientific and Technical Information of China (English)

    Hilde M van der Schaar; Lonneke van der Linden; Kjerstin H W Lanke; Jeroen R P M Strating; Gerhard Pürstinger; Erik de Vries; Cornelis A M de Haan; Johan Neyts; Frank J M van Kuppeveld

    2012-01-01

    RNA viruses can rapidly mutate and acquire resistance to drugs that directly target viral enzymes,which poses serious problems in a clinical context.Therefore,there is a growing interest in the development of antiviral drugs that target host factors critical for viral replication,since they are unlikely to mutate in response to therapy.We recently demonstrated that phosphatidylinositol-4-kinase Ⅲβ (PI4KⅢβ) and its product phosphatidylinositol-4-phosphate (PI4P) are essential for replication of enteroviruses,a group of medically important RNA viruses including poliovirus (PV),coxsackievirus,rhinovirus,and enterovirus 71.Here,we show that enviroxime and GW5074 decreased PI4P levels at the Golgi complex by directly inhibiting PI4KⅢβ.Coxsackievirus mutants resistant to these inhibitors harbor single point mutations in the non-structural protein 3A.These 3A mutations did not confer compound-resistance by restoring the activity of PI4KⅢβ in the presence of the compounds.Instead,replication of the mutant viruses no longer depended on PI4KⅢβ,since their replication was insensitive to siRNA-mediated depletion of PI4KⅢβ.The mutant viruses also did not rely on other isoforms of PI4K.Consistently,no high level of PI4P could be detected at the replication sites induced by the mutant viruses in the presence of the compounds.Collectively,these findings indicate that through specific single point mutations in 3A,CVB3 can bypass an essential host factor and lipid for its propagation,which is a new example of RNA viruses acquiring resistance against antiviral compounds,even when they directly target host factors.

  12. The Glycoproteins of All Filovirus Species Use the Same Host Factors for Entry into Bat and Human Cells but Entry Efficiency Is Species Dependent.

    Directory of Open Access Journals (Sweden)

    Markus Hoffmann

    Full Text Available Ebola and marburgviruses, members of the family Filoviridae, can cause severe hemorrhagic fever in humans. The ongoing Ebola virus (EBOV disease epidemic in Western Africa claimed more than 11,300 lives and was associated with secondary cases outside Africa, demonstrating that filoviruses pose a global health threat. Bats constitute an important natural reservoir of filoviruses, including viruses of the recently identified Cuevavirus genus within the Filoviridae family. However, the interactions of filoviruses with bat cells are incompletely understood. Here, we investigated whether filoviruses employ different strategies to enter human and bat cells. For this, we examined host cell entry driven by glycoproteins (GP from all filovirus species into cell lines of human and fruit bat origin. We show that all GPs were able to mediate entry into human and most fruit bat cell lines with roughly comparable efficiency. In contrast, the efficiency of entry into the cell line EidNi/41 derived from a straw-colored fruit bat varied markedly between the GPs of different filovirus species. Furthermore, inhibition studies demonstrated that filoviruses employ the same host cell factors for entry into human, non-human primate and fruit bat cell lines, including cysteine proteases, two pore channels and NPC1 (Niemann-Pick C1 molecule. Finally, processing of GP by furin and the presence of the mucin-like domain in GP were dispensable for entry into both human and bat cell lines. Collectively, these results show that filoviruses rely on the same host cell factors for entry into human and fruit bat cells, although the efficiency of the usage of these factors might differ between filovirus species.

  13. Effect of sex-hormone levels, sex, body mass index and other host factors on human craniofacial bone regeneration with bioactive tricalcium phosphate grafts.

    Science.gov (United States)

    Knabe, Christine; Mele, Aynur; Kann, Peter Herbert; Peleska, Barbara; Adel-Khattab, Doaa; Renz, Harald; Reuss, Alexander; Bohner, Marc; Stiller, Michael

    2017-04-01

    Little is known regarding the associations between sex-hormone levels, sex, body mass index (BMI), age, other host factors and biomaterial stimulated bone regeneration in the human craniofacial skeleton. The aim of this study was to elucidate the associations between these factors and bone formation after sinus floor augmentation procedures (SFA) utilizing a bioactive tricalcium phosphate (TCP) bone grafting material. We conducted a prospective study in a human population in which 60 male and 60 female participants underwent SFA and dental implant placement using a staged approach. BMI as well as levels of serum estradiol (E2), total testosterone (TT), and the free androgen index (FAI) were measured by radioimmunoassay and electrochemoluminescent-immunoassay. At implant placement, 6 months after SFA, bone biopsy specimens were harvested for hard tissue histology, the amount of bone formation was evaluated by histomorphometry and immunohistochemical analysis of osteogenic marker expression. The Wilcoxon rank-sum U test, Spearman correlations and linear regression analysis were used to explore the association between bone formation and BMI, hormonal and other host factors. BMI and log E2 were significantly positively associated with bone formation in male individuals (p BMI enhanced TCP stimulated craniofacial i.e. intramembranous bone repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Risk factors for unstable blood glucose level: integrative review of the risk factors related to the nursing diagnosis

    Directory of Open Access Journals (Sweden)

    Andressa Magalhães Teixeira

    Full Text Available ABSTRACT Objective: to identify evidence in the literature on the possible risk factors for the risk of unstable blood glucose diagnosis in individuals with type 2 diabetes mellitus, and to compare them with the risk factors described by NANDA International. Method: an integrative literature review guided by the question: what are the risk factors for unstable blood glucose level in people with type 2 diabetes mellitus? Primary studies were included whose outcomes were variations in glycemic levels, published in English, Portuguese or Spanish, in PubMed or CINAHL between 2010 and 2015. Results: altered levels of glycated hemoglobin, body mass index>31 kg/m2, previous history of hypoglycemia, cognitive deficit/dementia, autonomic cardiovascular neuropathy, comorbidities and weight loss corresponded to risk factors described in NANDA International. Other risk factors identified were: advanced age, black skin color, longer length of diabetes diagnosis, daytime sleepiness, macroalbuminuria, genetic polymorphisms, insulin therapy, use of oral antidiabetics, and use of metoclopramide, inadequate physical activity and low fasting glycemia. Conclusions: risk factors for the diagnosis, risk for unstable blood glucose level, for persons with type 2 diabetes mellitus were identified, and 42% of them corresponded to those of NANDA International. These findings may contribute to the practice of clinical nurses in preventing the deleterious effects of glycemic variation.

  15. A Systems Biology Approach to Reveal Putative Host-Derived Biomarkers of Periodontitis by Network Topology Characterization of MMP-REDOX/NO and Apoptosis Integrated Pathways.

    Science.gov (United States)

    Zeidán-Chuliá, Fares; Gürsoy, Mervi; Neves de Oliveira, Ben-Hur; Özdemir, Vural; Könönen, Eija; Gürsoy, Ulvi K

    2015-01-01

    Periodontitis, a formidable global health burden, is a common chronic disease that destroys tooth-supporting tissues. Biomarkers of the early phase of this progressive disease are of utmost importance for global health. In this context, saliva represents a non-invasive biosample. By using systems biology tools, we aimed to (1) identify an integrated interactome between matrix metalloproteinase (MMP)-REDOX/nitric oxide (NO) and apoptosis upstream pathways of periodontal inflammation, and (2) characterize the attendant topological network properties to uncover putative biomarkers to be tested in saliva from patients with periodontitis. Hence, we first generated a protein-protein network model of interactions ("BIOMARK" interactome) by using the STRING 10 database, a search tool for the retrieval of interacting genes/proteins, with "Experiments" and "Databases" as input options and a confidence score of 0.400. Second, we determined the centrality values (closeness, stress, degree or connectivity, and betweenness) for the "BIOMARK" members by using the Cytoscape software. We found Ubiquitin C (UBC), Jun proto-oncogene (JUN), and matrix metalloproteinase-14 (MMP14) as the most central hub- and non-hub-bottlenecks among the 211 genes/proteins of the whole interactome. We conclude that UBC, JUN, and MMP14 are likely an optimal candidate group of host-derived biomarkers, in combination with oral pathogenic bacteria-derived proteins, for detecting periodontitis at its early phase by using salivary samples from patients. These findings therefore have broader relevance for systems medicine in global health as well.

  16. Understanding Transcription Factor Regulation by Integrating Gene Expression and DNase I Hypersensitive Sites

    Directory of Open Access Journals (Sweden)

    Guohua Wang

    2015-01-01

    Full Text Available Transcription factors are proteins that bind to DNA sequences to regulate gene transcription. The transcription factor binding sites are short DNA sequences (5–20 bp long specifically bound by one or more transcription factors. The identification of transcription factor binding sites and prediction of their function continue to be challenging problems in computational biology. In this study, by integrating the DNase I hypersensitive sites with known position weight matrices in the TRANSFAC database, the transcription factor binding sites in gene regulatory region are identified. Based on the global gene expression patterns in cervical cancer HeLaS3 cell and HelaS3-ifnα4h cell (interferon treatment on HeLaS3 cell for 4 hours, we present a model-based computational approach to predict a set of transcription factors that potentially cause such differential gene expression. Significantly, 6 out 10 predicted functional factors, including IRF, IRF-2, IRF-9, IRF-1 and IRF-3, ICSBP, belong to interferon regulatory factor family and upregulate the gene expression levels responding to the interferon treatment. Another factor, ISGF-3, is also a transcriptional activator induced by interferon alpha. Using the different transcription factor binding sites selected criteria, the prediction result of our model is consistent. Our model demonstrated the potential to computationally identify the functional transcription factors in gene regulation.

  17. Integrated Framework based on Critical Success Factors for E-Commerce

    Directory of Open Access Journals (Sweden)

    M. L. R. Varela

    2017-01-01

    Full Text Available E-commerce has been increasingly applied as it promotes economic growth by enabling online shops to compete within a global market scenario. There are critical success factors that permit to distinguish a good business on the Internet and this knowledge may allow reaching an important competitive advantage for business sustainability. As many disciplines are involved, when determining critical success factors, e-commerce requires an effective coordination and integration in a collaborative way. In e-commerce, as well as in any other ecosystem, the breaking down of some integrating elements may provoke a collapse on the whole system. The various stakeholders involved in a given business should, therefore, be involved and work together to achieve a high-quality product that fully satisfies the end customer's needs and wishes. To meet the above requirement, this paper proposes a multi-perspective critical success factors (MPCSF model for online shopping.

  18. Micro-ring resonator quality factor enhancement via an integrated Fabry-Perot cavity

    Directory of Open Access Journals (Sweden)

    Jiayang Wu

    2017-05-01

    Full Text Available We propose and experimentally demonstrate the enhancement in the filtering quality (Q factor of an integrated micro-ring resonator (MRR by embedding it in an integrated Fabry-Perot (FP cavity formed by cascaded Sagnac loop reflectors. By utilizing coherent interference within the FP cavity to reshape the transmission spectrum of the MRR, both the Q factor and the extinction ratio (ER can be significantly improved. The device is theoretically analyzed and practically fabricated on a silicon-on-insulator wafer. Experimental results show that up to 11-times improvement in the Q factor, together with an 8-dB increase in the ER, can be achieved via our proposed method. The impact of varying structural parameters on the device performance is also investigated and verified by the measured spectra of the fabricated devices with different structural parameters.

  19. Clustering and Integrating of Heterogeneous Microbiome Data by Joint Symmetric Nonnegative Matrix Factorization with Laplacian Regularization.

    Science.gov (United States)

    Ma, Yuanyuan; Hu, Xiaohua; He, Tingting; Jiang, Xingpeng

    2017-09-26

    Many datasets existed in the real world are often comprised of different representations or views which provide complementary information to each other. To integrate information from multiple views, data integration approaches such as nonnegative matrix factorization (NMF) have been developed to combine multiple heterogeneous data simultaneously to obtain a comprehensive representation. In this paper, we proposed a novel variant of symmetric nonnegative matrix factorization (SNMF), called Laplacian regularization based joint symmetric nonnegative matrix factorization (LJ-SNMF) for clustering multi-view data. We conduct extensive experiments on several realistic datasets including Human Microbiome Project data. The experimental results show that the proposed method outperforms other variants of NMF, which suggests the potential application of LJ-SNMF in clustering multi-view datasets. Additionally, we also demonstrate the capability of LJ-SNMF in community finding.

  20. Genome sequencing reveals diversification of virulence factor content and possible host adaptation in distinct subpopulations of Salmonella enterica

    Directory of Open Access Journals (Sweden)

    Rodriguez-Rivera Lorraine D

    2011-08-01

    Full Text Available Abstract Background Divergence of bacterial populations into distinct subpopulations is often the result of ecological isolation. While some studies have suggested the existence of Salmonella enterica subsp. enterica subclades, evidence for these subdivisions has been ambiguous. Here we used a comparative genomics approach to define the population structure of Salmonella enterica subsp. enterica, and identify clade-specific genes that may be the result of ecological specialization. Results Multi-locus sequence analysis (MLSA and single nucleotide polymorphisms (SNPs data for 16 newly sequenced and 30 publicly available genomes showed an unambiguous subdivision of S. enterica subsp. enterica into at least two subpopulations, which we refer to as clade A and clade B. Clade B strains contain several clade-specific genes or operons, including a β-glucuronidase operon, a S-fimbrial operon, and cell surface related genes, which strongly suggests niche specialization of this subpopulation. An additional set of 123 isolates was assigned to clades A and B by using qPCR assays targeting subpopulation-specific SNPs and genes of interest. Among 98 serovars examined, approximately 20% belonged to clade B. All clade B isolates contained two pathogenicity related genomic islands, SPI-18 and a cytolethal distending toxin islet; a combination of these two islands was previously thought to be exclusive to serovars Typhi and Paratyphi A. Presence of β-glucuronidase in clade B isolates specifically suggests an adaptation of this clade to the vertebrate gastrointestinal environment. Conclusions S. enterica subsp. enterica consists of at least two subpopulations that differ specifically in genes involved in host and tissue tropism, utilization of host specific carbon and nitrogen sources and are therefore likely to differ in ecology and transmission characteristics.

  1. Pediatric spinal epidural abscess in an immunocompetent host without risk factors: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Alessandra Vergori

    2015-01-01

    The rarity and the possible differential diagnosis can lead to underestimate SEA occurrence in children without risk factors. It seems therefore essential to maintain a high attention to pediatric SEAs. A prompt diagnosis and adequate therapy are essential prognostic factors for remission.

  2. The Potential Role of Recombinant Hematopoietic Colony-Stimulating Factors in Preventing Infections in the Immunocompromised Host

    Directory of Open Access Journals (Sweden)

    James Rusthoven

    1991-01-01

    Full Text Available Hematopoietic colony-stimulating factors coordinate the proliferation and maturation of bone marrow and peripheral blood cells during normal hematopoiesis. Most of these factors are now available as recombinant human colony-stimulating factors, and preclinical and clinical testing is proceeding rapidly. Granulocyte and granulocyte/macrophage colony-stimulating factors have been the most extensively studied to date. In human clinical trials, granulocyte colony-stimulating factor improves neutrophil counts and function, reduces episodes of febrile neutropenia, improves neutrophil recovery after disease- or treatment-induced myelosuppression, and reduces the number of serious infections in several neutropenic disease states. Granulocyte/macrophage colony-stimulating factor has similar biological properties but may also improve eosinophil proliferation and function, and platelet cell recovery after myelotoxic bone marrow injury, Interleukin-1 boosts the effects of granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor, but also may promote the resolution of established infections in conjunction with antibiotics. The therapeutic realities and future therapeutic implications of these agents for the therapy of infections, cancer and hemopoietic disorders are discussed.

  3. Guidelines for Hosted Payload Integration

    Science.gov (United States)

    2014-06-06

    D’Angelo Lockheed Martin Jeff Mendenhall MIT/Lincoln Labs Brent Armand Orbital Sciences Angela Phillips Raytheon Space and Airborne Systems Jonathan...ian.a.mcdonald@baesystems. com Kurt Meister Honeywell kurt.meister@honeywell.com Jeff Mendenhall MIT mendenhall @ll.mit.edu Jo Merritt AVTEC jmerritt

  4. Host Phylogeny Determines Viral Persistence and Replication in Novel Hosts

    Science.gov (United States)

    Longdon, Ben; Hadfield, Jarrod D.; Webster, Claire L.

    2011-01-01

    Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts. PMID:21966271

  5. Design stars: how small DNA viruses remodel the host nucleus.

    Science.gov (United States)

    Jiang, Mengxi; Imperiale, Michael J

    2012-05-01

    Numerous host components are encountered by viruses during the infection process. While some of these host structures are left unchanged, others may go through dramatic remodeling processes. In this review, we summarize these host changes that occur during small DNA virus infections, with a focus on host nuclear components and pathways. Although these viruses differ significantly in their genome structures and infectious pathways, there are common nuclear targets that are altered by various viral factors. Accumulating evidence suggests that these nuclear remodeling processes are often essential for productive viral infections and/or viral-induced transformation. Understanding the complex interactions between viruses and these host structures and pathways will help to build a more integrated network of how the virus completes its life cycle and point toward the design of novel therapeutic regimens that either prevent harmful viral infections or employ viruses as nontraditional treatment options or molecular tools.

  6. Risk Factors for Steroid-Refractory Acute Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation from Matched Related or Unrelated Donors.

    Science.gov (United States)

    Calmettes, Claire; Vigouroux, Stéphane; Labopin, Myriam; Tabrizi, Reza; Turlure, Pascal; Lafarge, Xavier; Marit, Gérald; Pigneux, Arnaud; Leguay, Thibaut; Bouabdallah, Krimo; Dilhuydy, Marie-Sarah; Duclos, Cédric; Mohr, Catherine; Lascaux, Axelle; Dumas, Pierre-Yves; Dimicoli-Salazar, Sophie; Saint-Lézer, Arnaud; Milpied, Noël

    2015-05-01

    We performed a retrospective study to identify pretransplantation risk factors for steroid-refractory (SR) acute graft-versus host disease (aGVHD) after allogeneic stem cell transplantation from matched donors in 630 adult patients who underwent transplantation at our center between 2000 and 2012. The cumulative incidence (CI) of SR aGVHD was 11.3% ± 2.3%. The identified independent risk factors were matched unrelated donor (hazard ratio [HR], 2.52; P = .001), female donor for male recipient (HR, 1.84; P = .023) and absence of antithymocyte globulin (HR, 2.02; P = .005). Three risk groups were defined according to the presence of these risk factors. In the whole cohort, the CI of SR aGVHD was 3.5% ± 1.7% in the low-risk group (0 risk factor, n = 115), 9.3% ± 1.6% in the intermediate-risk group (1 risk factor, n = 323), and 19.3% ± 2.9% in the high-risk group (2 or 3 risk factors, n = 192). Our study suggests that pretransplantation characteristics might help identify patients at high risk for SR aGVHD. A risk adapted first-line treatment of aGVHD could be evaluated in those patients.

  7. [Integrated Management Area of Vascular Risk: A new organisational model for global control of risk factors].

    Science.gov (United States)

    Armario, P; Jericó, C; Vila, L; Freixa, R; Martin-Castillejos, C; Rotllan, M

    2016-11-17

    Cardiovascular disease (CVD), is a major cause of morbidity and mortality that increases the cost of care. Currently there is a low degree of control of the main cardiovascular risk factors, although we have a good therapeutic arsenal. To achieve the improvement of this reality, a good coordination and multidisciplinary participation are essential. The development of new organizational models such as the Integrated Management Area of Vascular Risk can facilitate the therapeutic harmonization and unification of the health messages offered by different levels of care, based on clinical practice guidelines, in order to provide patient-centred integrated care.

  8. Application of the Jacobi method and integrating factors to a class of Painleve-Gambier equations

    Energy Technology Data Exchange (ETDEWEB)

    Yasar, Emrullah [Department of Mathematics, Faculty of Arts and Sciences, Uludag University, 16059 Bursa (Turkey); Reis, Murat, E-mail: eyasar@uludag.edu.t, E-mail: reis@uludag.edu.t [Department of Mechanical Engineering, Faculty of Engineering and Architecture, Uludag University, 16059 Bursa (Turkey)

    2010-07-23

    In this work, we consider the motion of chain ball drawing with constant force in the frictionless surface which is a class of the Painleve-Gambier equations. We apply Jacobi's method which enables us to obtain Lagrangians of any second-order differential equation. It is comprised that the Lagrangian obtained by Musielak's method is the particular case of the many Lagrangians that can be obtained by Jacobi's method. In addition, we obtain integrating factors and first integrals for the equation in question by Ibragimov's variational derivative approach.

  9. Downregulation of transcription factor aflR in Aspergillus flavus confers reduction to aflatoxin accumulation in transgenic maize with alteration of host plant architecture.

    Science.gov (United States)

    Masanga, Joel Okoyo; Matheka, Jonathan Mutie; Omer, Rasha Adam; Ommeh, Sheila Cecily; Monda, Ethel Oranga; Alakonya, Amos Emitati

    2015-08-01

    We report success of host-induced gene silencing in downregulation of aflatoxin biosynthesis in Aspergillus flavus infecting maize transformed with a hairpin construct targeting transcription factor aflR. Infestation of crops by aflatoxin-producing fungi results in economic losses as well as negative human and animal health effects. Currently, the control strategies against aflatoxin accumulation are not effective to the small holder farming systems in Africa and this has led to widespread aflatoxin exposure especially in rural populations of sub-Saharan Africa that rely on maize as a staple food crop. A recent strategy called host-induced gene silencing holds great potential for developing aflatoxin-resistant plant germplasm for the African context where farmers are unable to make further investments other than access to the germplasm. We transformed maize with a hairpin construct targeting the aflatoxin biosynthesis transcription factor aflR. The developed transgenic maize were challenged with an aflatoxigenic Aspergillus flavus strain from Eastern Kenya, a region endemic to aflatoxin outbreaks. Our results indicated that aflR was downregulated in A. flavus colonizing transgenic maize. Further, maize kernels from transgenic plants accumulated significantly lower levels of aflatoxins (14-fold) than those from wild type plants. Interestingly, we observed that our silencing cassette caused stunting and reduced kernel placement in the transgenic maize. This could have been due to "off-target" silencing of unintended genes in transformed plants by aflR siRNAs. Overall, this work indicates that host-induced gene silencing has potential in developing aflatoxin-resistant germplasm.

  10. C7L family of poxvirus host range genes inhibits antiviral activities induced by type I interferons and interferon regulatory factor 1.

    Science.gov (United States)

    Meng, Xiangzhi; Schoggins, John; Rose, Lloyd; Cao, Jingxin; Ploss, Alexander; Rice, Charles M; Xiang, Yan

    2012-04-01

    Vaccinia virus (VACV) K1L and C7L function equivalently in many mammalian cells to support VACV replication and antagonize antiviral activities induced by type I interferons (IFNs). While K1L is limited to orthopoxviruses, genes that are homologous to C7L are found in diverse mammalian poxviruses. In this study, we showed that the C7L homologues from sheeppox virus and swinepox virus could rescue the replication defect of a VACV mutant deleted of both K1L and C7L (vK1L(-)C7L(-)). Interestingly, the sheeppox virus C7L homologue could rescue the replication of vK1L(-)C7L(-) in human HeLa cells but not in murine 3T3 and LA-4 cells, in contrast to all other C7L homologues. Replacing amino acids 134 and 135 of the sheeppox virus C7L homologue, however, made it functional in the two murine cell lines, suggesting that these two residues are critical for antagonizing a putative host restriction factor which has some subtle sequence variation in human and murine cells. Furthermore, the C7L family of host range genes from diverse mammalian poxviruses were all capable of antagonizing type I IFN-induced antiviral activities against VACV. Screening of a library of more than 350 IFN-stimulated genes (ISGs) identified interferon-regulated factor 1 (IRF1) as an inhibitor of vK1L(-)C7L(-) but not wild-type VACV. Expression of either K1L or C7L, however, rendered vK1L(-)C7L(-) resistant to IRF1-induced antiviral activities. Altogether, our data show that K1L and C7L antagonize IRF1-induced antiviral activities and that the host modulation function of C7L is evolutionally conserved in all poxviruses that can readily replicate in tissue-cultured mammalian cells.

  11. Persistence of uropathogenic Escherichia coli strains in the host for long periods of time: relationship between phylogenetic groups and virulence factors.

    Science.gov (United States)

    Narciso, A; Nunes, F; Amores, T; Lito, L; Melo-Cristino, J; Duarte, A

    2012-06-01

    Escherichia coli cause the majority of urinary tract infections (UTIs). Virulence plays an important role in the initial stages of interaction with the host, facilitating colonization of the urinary tract tissue. The purpose of this study was to assess whether there is a relationship between virulence and antibiotic resistance in the persistence of uropathogenic E. coli strains. This study included five patients with UTI between 2001 and 2009. The antibiotic resistance phenotype of 29 E. coli isolates was determined by the disk diffusion method. Clonal relationship was determined through M13 polymerase chain reaction (PCR) fingerprinting. Phylogeny, virulence factors, β-lactamases, and replicon typing were studied through PCR. Antibiogram profiles were found from different patients and corresponded to CTX-M-2, CTX-M-15, CTX-M-32, and TEM-52 enzymes. Plasmids belonged essentially to incompatibility group IncF. No clonal relationship was observed among isolates from different patients, except for patients 4 and 5. Phylogenetic group A was predominant. Our work showed that commensal group A possesses the same virulence factors as the pathogenic groups B1 and D. E. coli common pilus and type 1 fimbriae could play an important role in the persistence in the host and in symptomatic UTI, respectively, which, combined with extended-spectrum β-lactamases (ESBLs), are a cause of the dissemination of microorganisms in the hospital and the community.

  12. The alternative sigma factor B modulates virulence gene expression in a murine Staphylococcus aureus infection model but does not influence kidney gene expression pattern of the host.

    Science.gov (United States)

    Depke, Maren; Burian, Marc; Schäfer, Tina; Bröker, Barbara M; Ohlsen, Knut; Völker, Uwe

    2012-01-01

    Infections caused by Staphylococcus aureus are associated with significant morbidity and mortality and are an increasing threat not only in hospital settings. The expression of the staphylococcal virulence factor repertoire is known to be affected by the alternative sigma factor B (SigB). However, its impact during infection still is a matter of debate. Kidney tissues of controls or mice infected with S. aureus HG001 or its isogenic sigB mutant were analyzed by transcriptome profiling to monitor the host response, and additionally expression of selected S. aureus genes was monitored by RT-qPCR. Direct transcript analysis by RT-qPCR revealed significant SigB activity in all mice infected with the wild-type strain, but not in its isogenic sigB mutant (p<0.0001). Despite a clear-cut difference in the SigB-dependent transcription pattern of virulence genes (clfA, aur, and hla), the host reaction to infection (either wild type or sigB mutant) was almost identical. Despite its significant activity in vivo, loss of SigB did neither have an effect on the outcome of infection nor on murine kidney gene expression pattern. Thus, these data support the role of SigB as virulence modulator rather than being a virulence determinant by itself.

  13. Host factors analysis in early failure of dental implant%影响种植体早期失败的宿主因素分析

    Institute of Scientific and Technical Information of China (English)

    申会

    2011-01-01

    种植修复已成为牙缺失常用的修复方法,10年成功率约达到90%,但是种植体失败的情况仍有发生。现有的研究表明:种植体失败多发生在植入后早期,而且发生早期失败的患者其晚期失败的风险也增加;但是,人们并不明确种植体早期失败的影响因素,早期失败的发生可能与宿主、种植体、术者和外科技术等多种因素有关。选择合适的患者是制定治疗计划的关键,对宿主影响因素的分析可用以指导临床,进一步提高种植的成功率。故本文就影响种植体早期失败的宿主因素作一综述。%Nowadays, the replacement of missing teeth with endosseous implants for the rehabilitation of edentulous or partially edentulous patients has become a standard of care, and the ten-year success rate is up to 90%. However, dental implants fail occasionally. Available studies indicate that dental implants failure usually occurs in the early stage, and the risk of late failure increases for the patients with early failure. However, the impact factors on the incidence of implant early failure are not definite. A variety of factors may have a potential influence on the incidence of dental implant early failure, such as host factors, character of implants, clinicians, surgical technique and soon. Proper patient selection is a key issue in treatment planning, and analysis of host factors will guide clinical practice. This review focused on the effect of host factors on implant early failure.

  14. A population-based study to investigate host genetic factors associated with hepatitis B infection and pathogenesis in the Chinese population

    Directory of Open Access Journals (Sweden)

    O'Brien Stephen J

    2008-01-01

    Full Text Available Abstract Background Hepatitis B virus (HBV infection is a significant public health problem that may lead to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC. Approximately 30% of the world's population has been infected with HBV and approximately 350 million (5–6% are persistent carriers. More than 120 million Chinese are infected with HBV. The role of host genetic factors and their interactions with environmental factors leading to chronic HBV infection and its complications are not well understood. We believe that a better understanding of these factors and interactions will lead to more effective diagnostic and therapeutic options. Methods/Design This is a population-based, case-control study protocol to enroll 2200 Han Chinese from medical centers in northern and western China. Adult subjects in the following groups are being enrolled: healthy donors (n = 200, HBV infected persons achieving virus clearance (n = 400, asymptomatic HBV persistent carriers (n = 400, chronic hepatitis B cases (n = 400, decompensated liver cirrhosis with HBV infection cases (n = 400, and hepatocellular carcinoma with HBV infection cases (n = 400. In addition, for haplotype inference and quality control of sample handling and genotyping results, children of 1000 cases will be asked to provide a buccal sample for DNA extraction. With the exception of adult patients presenting with liver cirrhosis or HCC, all other cases and controls will be 40 years or older at enrollment. A questionnaire is being administered to capture dietary and environmental risk factors. Both candidate-gene and genome-wide association approaches will be used to assess the role of single genetic factors and higher order interactions with other genetic or environmental factors in HBV diseases. Conclusion This study is designed and powered to detect single gene effects as well as gene-gene and environmental-gene interactions. The identification of allelic polymorphisms in

  15. Low rank factorization of the Coulomb integrals for periodic coupled cluster theory

    CERN Document Server

    Hummel, Felix; Grüneis, Andreas

    2016-01-01

    We study the decomposition of the Coulomb integrals of periodic systems into a tensor contraction of six matrices of which only two are distinct. We find that the Coulomb integrals can be well approximated in this form already with small matrices compared to the number of real space grid points. The cost of computing the matrices scales as O(N^4) using a regularized form of the alternating least squares algorithm. The studied factorization of the Coulomb integrals can be exploited to reduce the scaling of the computational cost of expensive tensor contractions appearing in the amplitude equations of coupled cluster methods with respect to system size. We apply the developed methodologies to calculate the adsorption energy of a single water molecule on a hexagonal boron nitride monolayer in a plane wave basis set and periodic boundary conditions.

  16. Integrative Review of Admission Factors Related to Associate Degree Nursing Program Success.

    Science.gov (United States)

    Olsen, Jeanette M

    2017-02-01

    High attrition in associate degree nursing (ADN) programs contributes to the nursing shortage and causes hardship for students, families, faculty, colleges, and taxpayers. The purpose of this integrative literature review is to identify admission criteria related to ADN program success to inform evidence-based admission policies and reduce attrition. Integrative review methodology, suggested by Whittemore and Knafl, was used. A systematic search of existing professional literature was conducted using five databases and key word searches. The final sample included 26 documents that were analyzed and synthesized with the matrix method. Five categories of admission criteria and factors related to success in ADN programs were revealed from the analysis of findings: academic aptitude, demographic factors, psychological hardiness, specialty skills and experience, and socioeconomic support. ADN programs with a goal of decreasing attrition may want to implement admission selection guidelines that consider applicant criteria and attributes across all five dimensions. [J Nurs Educ. 2017;56(2):85-93.]. Copyright 2017, SLACK Incorporated.

  17. HTLV-1 Tax mediated downregulation of miRNAs associated with chromatin remodeling factors in T cells with stably integrated viral promoter.

    Directory of Open Access Journals (Sweden)

    Saifur Rahman

    Full Text Available RNA interference (RNAi is a natural cellular mechanism to silence gene expression and is predominantly mediated by microRNAs (miRNAs that target messenger RNA. Viruses can manipulate the cellular processes necessary for their replication by targeting the host RNAi machinery. This study explores the effect of human T-cell leukemia virus type 1 (HTLV-1 transactivating protein Tax on the RNAi pathway in the context of a chromosomally integrated viral long terminal repeat (LTR using a CD4(+ T-cell line, Jurkat. Transcription factor profiling of the HTLV-1 LTR stably integrated T-cell clone transfected with Tax demonstrates increased activation of substrates and factors associated with chromatin remodeling complexes. Using a miRNA microarray and bioinformatics experimental approach, Tax was also shown to downregulate the expression of miRNAs associated with the translational regulation of factors required for chromatin remodeling. These observations were validated with selected miRNAs and an HTLV-1 infected T cells line, MT-2. miR-149 and miR-873 were found to be capable of directly targeting p300 and p/CAF, chromatin remodeling factors known to play critical role in HTLV-1 pathogenesis. Overall, these results are first in line establishing HTLV-1/Tax-miRNA-chromatin concept and open new avenues toward understanding retroviral latency and/or replication in a given cell type.

  18. Assessing social capacity and vulnerability of private households to natural hazards - integrating psychological and governance factors

    Science.gov (United States)

    Werg, J.; Grothmann, T.; Schmidt, P.

    2013-06-01

    People are unequally affected by extreme weather events in terms of mortality, morbidity and financial losses; this is the case not only for developing, but also for industrialized countries. Previous research has established indicators for identifying who is particularly vulnerable and why, focusing on socio-demographic factors such as income, age, gender, health and minority status. However, these factors can only partly explain the large disparities in the extent to which people are affected by natural hazards. Moreover, these factors are usually not alterable in the short to medium term, which limits their usefulness for strategies of reducing social vulnerability and building social capacity. Based on a literature review and an expert survey, we propose an approach for refining assessments of social vulnerability and building social capacity by integrating psychological and governance factors.

  19. ANALYSIS OF INFLUENCE FACTORS OF ECONOMIC EFFICIENCY ON THE ECONOMY OF THE INTEGRATED STRUCTURES

    Directory of Open Access Journals (Sweden)

    I. P. Bogomolova

    2014-01-01

    Full Text Available Currently in Russia, special attention is paid to the food industry, providing a key influence on the state's economy and food security of the country. The food industry not only creates substantial part of the gross domestic product, which is one of the main sources of fillings budgets of all levels, and contributes to the strengthening of the state in world markets. These circum-stances make it necessary to increase the efficiency of industrial structures by mobilizing factors affecting the economy of enterprises, including by shifting emphasis on the integration of food industry enterprises in General competitiveness of the goods produced, the stability of the entire industry, its leading industries and organizations. The article substantiates the expediency of application of integrated structures, discusses the methods and tools of analysis of influence factors of economic efficiency on the economy of inte-grated structures. Evaluation is recommended in two key areas: assessment of the financial condition and evaluation of training and development of staff, taking into account the strategic objectives of integrated structures. The analysis makes it possible to correctly allocate financial resources and to achieve balanced economic performance management through more effective use of credit re-sources, the rational management of economic parameters optimization of the number of employees and production capacity.

  20. Integration of human factors principles in LARG organizations--a conceptual model.

    Science.gov (United States)

    Figueira, Sara; Machado, V Cruz; Nunes, Isabel L

    2012-01-01

    Nowadays many companies are undergoing organizational transformations in order to meet the changing market demands. Thus, in order to become more competitive, supply chains (SC) are adopting new management paradigms to improve SC performance: lean, agile, resilient and green (LARG paradigms). The implementation of new production paradigms demands particular care with the issues related with Human Factors to avoid health and safety problems to workers and losses to companies. Thus, the successful introduction of these new production paradigms depends among others on a Human Factors oriented approach. This work presents a conceptual framework that allows integrating ergonomic and safety design principles during the different implementation phases of lean, agile, resilient and green practices.

  1. Integrating factors and conservation theorem for holonomic nonconservative dynamical systems in generalized classical mechanics

    Institute of Scientific and Technical Information of China (English)

    乔永芬; 张耀良; 韩广才

    2002-01-01

    In this paper, we present a general approach to the construction of conservation laws for generalized classical dynamical systems. Firstly, we give the definition of integrating factors and, secondly, we study in detail the necessary conditions for the existence of conserved quantities. Then we establish the conservation theorem and its inverse for the Hamilton's canonical equations of motion of holonomic nonconservative dynamical systems in generalized classical mechanics. Finally, we give an example to illustrate the application of the results.

  2. Actuality and Influencing Factors of Integrated Production Capacity of Foodstuff in Heilongjiang Province

    Institute of Scientific and Technical Information of China (English)

    Zhou Hui-qiu; Zhang De-hua

    2012-01-01

    Heilongjiang Province is an important marketable grain depot in China. Since the reform and opening up, Heilongjiang Province production capacity of foodstuff is increasingly growing into a new level. This paper started with the actuality of Heilongjiang Province integrated production capacity of foodstuff, and analyzed its major factors empirically through the mathematical model, then proposed some measures to enhance Heilongjiang Province production capacity of foodstuff which ensured China foodstuff security

  3. Anti-tumor necrosis factor-a for the treatment of steroid-refractory acute graft-versus-host disease

    Directory of Open Access Journals (Sweden)

    M.C. Nogueira

    2007-12-01

    Full Text Available Allogeneic stem cell transplantation has been increasingly performed for a variety of hematologic diseases. Clinically significant acute graft-versus-host disease (GVHD occurs in 9 to 50% of patients who receive allogeneic grafts, resulting in high morbidity and mortality. There is no standard therapy for patients with acute GVHD who do not respond to steroids. Studies have shown a possible benefit of anti-TNF-a (infliximabfor the treatment of acute GVHD. We report here on the outcomes of 10 recipients of related or unrelated stem cell transplants who received 10 mg/kg infliximab, iv, once weekly for a median of 3.5 doses (range: 1-6 for the treatment of severe acute GVHD and who were not responsive to standard therapy. All patients had acute GVHD grades II to IV (II = 2, III = 3, IV = 5. Overall, 9 patients responded and 1 patient had progressive disease. Among the responders, 3 had complete responses and 6 partial responses. All patients with cutaneous or gastrointestinal involvement responded, while only 2 of 6 patients with liver disease showed any response. None of the 10 patients had any kind of immediate toxicity. Four patients died, all of them with sepsis. Six patients are still alive after a median follow-up time of 544 days (92-600 after transplantation. Considering the severity of the cases and the bad prognosis associated with advanced acute GVHD, we find our results encouraging. Anti-TNF-a seems to be a useful agent for the treatment of acute GVHD.

  4. An ergonomics action research demonstration: integrating human factors into assembly design processes.

    Science.gov (United States)

    Village, J; Greig, M; Salustri, F; Zolfaghari, S; Neumann, W P

    2014-01-01

    In action research (AR), the researcher participates 'in' the actions in an organisation, while simultaneously reflecting 'on' the actions to promote learning for both the organisation and the researchers. This paper demonstrates a longitudinal AR collaboration with an electronics manufacturing firm where the goal was to improve the organisation's ability to integrate human factors (HF) proactively into their design processes. During the three-year collaboration, all meetings, workshops, interviews and reflections were digitally recorded and qualitatively analysed to inform new 'actions'. By the end of the collaboration, HF tools with targets and sign-off by the HF specialist were integrated into several stages of the design process, and engineers were held accountable for meeting the HF targets. We conclude that the AR approach combined with targeting multiple initiatives at different stages of the design process helped the organisation find ways to integrate HF into their processes in a sustainable way. Researchers acted as a catalyst to help integrate HF into the engineering design process in a sustainable way. This paper demonstrates how an AR approach can help achieve HF integration, the benefits of using a reflective stance and one method for reporting an AR study.

  5. An efficient viral vector for functional genomic studies of Prunus fruit trees and its induced resistance to Plum pox virus via silencing of a host factor gene.

    Science.gov (United States)

    Cui, Hongguang; Wang, Aiming

    2017-03-01

    RNA silencing is a powerful technology for molecular characterization of gene functions in plants. A commonly used approach to the induction of RNA silencing is through genetic transformation. A potent alternative is to use a modified viral vector for virus-induced gene silencing (VIGS) to degrade RNA molecules sharing similar nucleotide sequence. Unfortunately, genomic studies in many allogamous woody perennials such as peach are severely hindered because they have a long juvenile period and are recalcitrant to genetic transformation. Here, we report the development of a viral vector derived from Prunus necrotic ringspot virus (PNRSV), a widespread fruit tree virus that is endemic in all Prunus fruit production countries and regions in the world. We show that the modified PNRSV vector, harbouring the sense-orientated target gene sequence of 100-200 bp in length in genomic RNA3, could efficiently trigger the silencing of a transgene or an endogenous gene in the model plant Nicotiana benthamiana. We further demonstrate that the PNRSV-based vector could be manipulated to silence endogenous genes in peach such as eukaryotic translation initiation factor 4E isoform (eIF(iso)4E), a host factor of many potyviruses including Plum pox virus (PPV). Moreover, the eIF(iso)4E-knocked down peach plants were resistant to PPV. This work opens a potential avenue for the control of virus diseases in perennial trees via viral vector-mediated silencing of host factors, and the PNRSV vector may serve as a powerful molecular tool for functional genomic studies of Prunus fruit trees.

  6. Integrating products of Bessel functions with an additional exponential or rational factor

    Science.gov (United States)

    Van Deun, Joris; Cools, Ronald

    2008-04-01

    We provide two MATLAB programs to compute integrals of the form ex∏i=1kJν_i(ax)dxand 0∞xr+x∏i=1kJν_i(ax)dx with Jν_i(x) the Bessel function of the first kind and (real) order ν. The parameter m is a real number such that ∑ν+m>-1 (to assure integrability near zero), r is real and the numbers c and a are all strictly positive. The program can deliver accurate error estimates. Program summaryProgram title: BESSELINTR, BESSELINTC Catalogue identifier: AEAH_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEAH_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 1601 No. of bytes in distributed program, including test data, etc.: 13 161 Distribution format: tar.gz Programming language: Matlab (version ⩾6.5), Octave (version ⩾2.1.69) Computer: All supporting Matlab or Octave Operating system: All supporting Matlab or Octave RAM: For k Bessel functions our program needs approximately ( 500+140k) double precision variables Classification: 4.11 Nature of problem: The problem consists in integrating an arbitrary product of Bessel functions with an additional rational or exponential factor over a semi-infinite interval. Difficulties arise from the irregular oscillatory behaviour and the possible slow decay of the integrand, which prevents truncation at a finite point. Solution method: The interval of integration is split into a finite and infinite part. The integral over the finite part is computed using Gauss-Legendre quadrature. The integrand on the infinite part is approximated using asymptotic expansions and this approximation is integrated exactly with the aid of the upper incomplete gamma function. In the case where a rational factor is present, this factor is first expanded in a Taylor series around infinity. Restrictions: Some (and eventually all

  7. Integration

    DEFF Research Database (Denmark)

    Emerek, Ruth

    2004-01-01

    Bidraget diskuterer de forskellige intergrationsopfattelse i Danmark - og hvad der kan forstås ved vellykket integration......Bidraget diskuterer de forskellige intergrationsopfattelse i Danmark - og hvad der kan forstås ved vellykket integration...

  8. Construction and analysis of regulatory genetic networks in cervical cancer based on involved microRNAs, target genes, transcription factors and host genes.

    Science.gov (United States)

    Wang, Ning; Xu, Zhiwen; Wang, Kunhao; Zhu, Minghui; Li, Yang

    2014-04-01

    Over recent years, genes and microRNA (miRNA/miR) have been considered as key biological factors in human carcinogenesis. During cancer development, genes may act as multiple identities, including target genes of miRNA, transcription factors and host genes. The present study concentrated on the regulatory networks consisting of the biological factors involved in cervical cancer in order to investigate their features and affect on this specific pathology. Numerous raw data was collected and organized into purposeful structures, and adaptive procedures were defined for application to the prepared data. The networks were therefore built with the factors as basic components according to their interacting associations. The networks were constructed at three levels of interdependency, including a differentially-expressed network, a related network and a global network. Comparisons and analyses were made at a systematic level rather than from an isolated gene or miRNA. Critical hubs were extracted in the core networks and notable features were discussed, including self-adaption feedback regulation. The present study expounds the pathogenesis from a novel point of view and is proposed to provide inspiration for further investigation and therapy.

  9. Effects of host restriction factors and the HTLV-1 subtype on susceptibility to HTLV-1-associated myelopathy/tropical spastic paraparesis.

    Science.gov (United States)

    Nozuma, Satoshi; Matsuura, Eiji; Kodama, Daisuke; Tashiro, Yuichi; Matsuzaki, Toshio; Kubota, Ryuji; Izumo, Shuji; Takashima, Hiroshi

    2017-04-19

    Although human T-lymphotropic virus type 1 (HTLV-1) infection is a prerequisite for the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), specific provirus mutations in HAM/TSP have not yet been reported. In this study, we examined whether HAM/TSP patients had the disease-specific genomic variants of HTLV-1 by analyzing entire sequences of HTLV-1 proviruses in these patients, including familial cases. In addition, we investigated the genetic variants of host restriction factors conferring antiretroviral activity to determine which mutations may be related to resistance or susceptibility to HAM/TSP. The subjects included 30 patients with familial HAM/TSP (f-HAM/TSP), 92 patients with sporadic HAM/TSP (s-HAM/TSP), and 89 asymptomatic HTLV-1 carriers (ACs). In all 211 samples, 37 samples (18%) were classified into transcontinental subtype and 174 samples (82%) were classified as Japanese subtype. Among three groups, the percentage of transcontinental subtype in f-HAM/TSP, s-HAM/TSP and ACs was 33, 23 and 7%, respectively. The frequency of transcontinental subtype was significantly higher in both f-HAM/TSP (p < 0.001) and s-HAM/TSP (p < 0.001) than in ACs. Fifty mutations in HTLV-1 sequences were significantly more frequent in HAM/TSP patients than in ACs, however, they were common only in transcontinental subtype. Among these mutations, ten common mutations causing amino acid changes in the HTLV-1 sequences were specific to the transcontinental subtype. We examined host restriction factors, and detected a rare variant in TRIM5α in HAM/TSP patients. The patients with TRIM5α 136Q showed lower proviral loads (PVLs) than those with 136R (354 vs. 654 copies/10(4) PBMC, p = 0.003). The patients with the 304L variant of TRIM5α had significantly higher PVLs than those with 304H (1669 vs. 595 copies/10(4) PBMC, p = 0.025). We could not find any HAM/TSP-specific mutations of host restriction factors. Transcontinental subtype is

  10. An integrative literature review of contextual factors in perioperative information management systems.

    Science.gov (United States)

    Wilbanks, Bryan A

    2013-12-01

    Perioperative information management systems are used to generate the official documentation of patient care throughout the surgical experience. Successful implementation of perioperative information management systems requires a careful assessment of the contextual factors (ie, the social, cultural, and physical environment) that are present at the site. Failure to sufficiently assess these contextual factors is one of the leading causes of unsuccessful system implementation and can result in decreased patient safety, poor documentation quality, inefficient work processes, and wasted financial resources. Clearly defining and identifying the contextual factors are necessary to improve the performance and utilization of information management systems. The purpose of this article was to provide an integrative review of the empirical and theoretical literature on the contextual factors present in the perioperative environment to help guide future research and clinical practice. Specifically, this review addresses a gap in the literature regarding the descriptions of the contextual factors and how these factors affect implementation practices and system use. By clearly identifying these contextual factors and determining their relationship to successful system implementations, informatics specialists can tailor implementation and assessment tools to both patients and perioperative settings.

  11. The streptomycin mouse model for Salmonella diarrhea: functional analysis of the microbiota, the pathogen's virulence factors, and the host's mucosal immune response.

    Science.gov (United States)

    Kaiser, Patrick; Diard, Médéric; Stecher, Bärbel; Hardt, Wolf-Dietrich

    2012-01-01

    The mammalian intestine is colonized by a dense microbial community, the microbiota. Homeostatic and symbiotic interactions facilitate the peaceful co-existence between the microbiota and the host, and inhibit colonization by most incoming pathogens ('colonization resistance'). However, if pathogenic intruders overcome colonization resistance, a fierce, innate inflammatory defense can be mounted within hours, the adaptive arm of the immune system is initiated, and the pathogen is fought back. The molecular nature of the homeostatic interactions, the pathogen's ability to overcome colonization resistance, and the triggering of native and adaptive mucosal immune responses are still poorly understood. To study these mechanisms, the streptomycin mouse model for Salmonella diarrhea is of great value. Here, we review how S. Typhimurium triggers mucosal immune responses by active (virulence factor elicited) and passive (MyD88-dependent) mechanisms and introduce the S. Typhimurium mutants available for focusing on either response. Interestingly, mucosal defense turns out to be a double-edged sword, limiting pathogen burdens in the gut tissue but enhancing pathogen growth in the gut lumen. This model allows not only studying the molecular pathogenesis of Salmonella diarrhea but also is ideally suited for analyzing innate defenses, microbe handling by mucosal phagocytes, adaptive secretory immunoglobulin A responses, probing microbiota function, and homeostatic microbiota-host interactions. Finally, we discuss the general need for defined assay conditions when using animal models for enteric infections and the central importance of littermate controls.

  12. MIGRATION INTEGRATION AS A FACTOR OF ECONOMIC AND REGIONAL DEVELOPMENT IN THE EUROPEAN UNION

    Directory of Open Access Journals (Sweden)

    Petronela Daniela FERARU

    2015-10-01

    Full Text Available International migration, together with economic and financial crisis or the different socio-economic development of Member States, is a serious threat to security in Europe. Population migration as a threatening factor, places the European Union in the face of a decision to establish clear policies for the establishment of a climate of external security, both for the migrant population and for the rest of the population. All in all, this study will centre on the following hypothesis: the better we know the challenges of international migration in the European Union and its Member States the more the European policies to mitigate negative effects of the world will be diminished. The aim is to highlight aspects pertaining to migration integration as a factor of economic, social and regional development in the European Union, and less as a factor of destabilization and insecurity. In other words, a good knowledge of the phenomenon leads to drawing up effective policies to reduce hazards, risks, threats and negative effects that happen today due to the increasing number of immigrants. Finally, the study will present a series of conclusions, including on the work hypothesis verification and some proposals related to migration integration efficiency as a factor of regional and economic development in the European Union.

  13. Technical factors that affect anastomotic integrity following esophagectomy: systematic review and meta-analysis.

    Science.gov (United States)

    Markar, Sheraz R; Arya, Shobhit; Karthikesalingam, Alan; Hanna, George B

    2013-12-01

    Due to the significant contribution of anastomotic leak, with its disastrous consequences to patient morbidity and mortality, multiple parameters have been proposed and individually meta-analyzed for the formation of the ideal esophagogastric anastomosis following cancer resection. The purpose of this pooled analysis was to examine the main technical parameters that impact on anastomotic integrity. Medline, Embase, trial registries, and conference proceedings were searched. Technical factors evaluated included hand-sewn versus stapled esophagogastric anastomosis (EGA), cervical versus thoracic EGA, minimally invasive versus open esophagectomy, anterior versus posterior route of reconstruction and ischemic conditioning of the gastric conduit. The outcome of interest was the incidence of anastomotic leak, for which pooled odds ratios were calculated for each technical factor. No significant difference in the incidence of anastomotic leak was demonstrated for the following technical factors: hand-sewn versus stapled EGA, minimally invasive versus open esophagectomy, anterior versus posterior route of reconstruction and ischemic conditioning of the gastric conduit. Four randomized, controlled trials comprising 298 patients were included that compared cervical and thoracic EGA. Anastomotic leak was seen more commonly in the cervical group (13.64 %) than in the thoracic group (2.96 %). Pooled analysis demonstrated a significantly increased incidence of anastomotic leak in the cervical group (pooled odds ratio = 4.73; 95 % CI 1.61-13.9; P = 0.005). A tailored surgical approach to the patient's physiology and esophageal cancer stage is the most important factor that influences anastomotic integrity after esophagectomy.

  14. Pediatric spinal epidural abscess in an immunocompetent host without risk factors: Case report and review of the literature.

    Science.gov (United States)

    Vergori, Alessandra; Cerase, Alfonso; Migliorini, Lucia; Pluchino, Maria Grazia; Oliveri, Giuseppe; Arrigucci, Umberto; De Luca, Andrea; Montagnani, Francesca

    2015-01-01

    Spinal epidural abscesses (SEAs) are unusual bacterial infections, with possible devastating neurologic sequelae. Despite abundance of case series in adults, reports in children are scanty. We describe a spontaneous SEA due to methicillin susceptible Staphylococcus aureus (MSSA) in a previously healthy 15-year old male, and we perform a literature review regarding management of pediatric SEAs without risk factors, from 2001 to 2014. We found a total of 12 cases (8 males, average age 9.6 years). Clinical presentation was mainly fever, back pain and elevation of inflammation markers. All cases were initially misdiagnosed. Lumbar puncture was performed in 36% of patients. Etiological diagnosis was obtained in 8 cases. MSSA was isolated in 4 patients, methicillin-resistant S. aureus in 1 patient, and S. aureus with unknown susceptibility patterns in 2 cases. The average of therapy duration was 6 weeks. Patients' spine was always evaluated by gadolinium-enhanced magnetic resonance imaging; most abscesses were localized at thoracic and lumbar area, without osteomyelitis. In 8 cases, laminectomy and/or abscess drainage were performed in association with medical therapy; 3 cases were successfully treated with antimicrobial therapy only; no data were available in one case. A good outcome was obtained in all patients, except a reported residual headache and paraspinal pain lasting for 3 years. The rarity and the possible differential diagnosis can lead to underestimate SEA occurrence in children without risk factors. It seems therefore essential to maintain a high attention to pediatric SEAs. A prompt diagnosis and adequate therapy are essential prognostic factors for remission.

  15. Age as a factor in sensory integration function in Taiwanese children

    Directory of Open Access Journals (Sweden)

    Lin CK

    2013-07-01

    Full Text Available Chin-Kai Lin,1 Huey-Min Wu,2 Hsin-Yi Wang,3 Mei-Hui Tseng,4,5 Chung-Hui Lin61Department of Early Childhood Education, National Taichung University of Education, Taichung, Taiwan; 2Research Center for Testing and Assessment, National Academy for Educational Research, New Taipei, Taiwan; 3Department of Special Education, National Taichung University of Education, Taichung, Taiwan; 4School of Occupational Therapy, College of Medicine, National Taiwan University, Taipei, Taiwan; 5Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan; 6School of Occupational Therapy, College of Medical Science and Technology, Chung Shan Medical University, Taichung, TaiwanObjective: Sensory integration progresses along a normal developmental sequence. However, few studies have explored how age difference affects the way sensory integration functions in Taiwanese children as they develop. Therefore, this study aims to pinpoint the role of age in sensory integration.Method: A purposive sampling plan was employed. The study population comprised 1,000 Chinese children aged 36 to 131 months (mean = 74.48 months, standard deviation = 25.69 months. Subjects were scored on seven subsets of the Test of Sensory Integration Function (TSIF. An analysis of variance (ANOVA was used to identify differences between four age groups (ages 3−4, 5−6, 7−8, and 9−10 years, in the categories of the TSIF.Results: ANOVA revealed that age is a significant factor in each of the seven tasks of sensory integration associated with various stages of development. The effect of age was significant in all four groups for the subscale of Bilateral Integration Sequences. The function of sensory integration for the children aged 5−8 years did not produce statistically significant results for the subscale of Postural Movement, Sensory Discrimination, Sensory Seeking, or Attention and Activity. For the subscale of Sensory Modulation and Emotional

  16. Improving the convergence of closed and open path integral molecular dynamics via higher order Trotter factorization schemes

    Science.gov (United States)

    Pérez, Alejandro; Tuckerman, Mark E.

    2011-08-01

    Higher order factorization schemes are developed for path integral molecular dynamics in order to improve the convergence of estimators for physical observables as a function of the Trotter number. The methods are based on the Takahashi-Imada and Susuki decompositions of the Boltzmann operator. The methods introduced improve the averages of the estimators by using the classical forces needed to carry out the dynamics to construct a posteriori weighting factors for standard path integral molecular dynamics. The new approaches are straightforward to implement in existing path integral codes and carry no significant overhead. The Suzuki higher order factorization was also used to improve the end-to-end distance estimator in open path integral molecular dynamics. The new schemes are tested in various model systems, including an ab initio path integral molecular dynamics calculation on the hydrogen molecule and a quantum water model. The proposed algorithms have potential utility for reducing the cost of path integral molecular dynamics calculations of bulk systems.

  17. Integrative review of factors related to the nursing diagnosis nausea during antineoplastic chemotherapy 1

    Science.gov (United States)

    Moysés, Aline Maria Bonini; Durant, Lais Corsino; de Almeida, Ana Maria; Gozzo, Thais de Oliveira

    2016-01-01

    ABSTRACT Objective: to identify factors related to the nursing diagnosis nausea among cancer patients undergoing chemotherapy. Method: integrative review conducted in four electronic databases (PUBMED, EMBASE, CINAHL and LILACS) using the key words: neoplasia, antineoplastic agents and nausea. Results: only 30 out of 1,258 papers identified met the inclusion criteria. The most frequent related factors were: being younger than 50 years old, motion sickness, being a woman, emetogenic potential of the chemotherapy, anxiety, conditioned stimulus, and expecting nausea after treatment. Conclusion: this review's findings, coupled with the incidence of nausea among cancer patients undergoing chemotherapy, reveal an important difference between evidence found and that used by NANDA International, Inc. Even though it provides an appropriate definition of related factors, it does not mention chemotherapy, despite the various studies addressing the topic using different designs and presenting various objectives and outcomes. PMID:27737380

  18. A Tri-Factor Model for Integrating Ratings Across Multiple Informants

    Science.gov (United States)

    Bauer, Daniel J.; Howard, Andrea L.; Baldasaro, Ruth E.; Curran, Patrick J.; Hussong, Andrea M.; Chassin, Laurie; Zucker, Robert A.

    2014-01-01

    Psychologists often obtain ratings for target individuals from multiple informants such as parents or peers. In this paper we propose a tri-factor model for multiple informant data that separates target-level variability from informant-level variability and item-level variability. By leveraging item-level data, the tri-factor model allows for examination of a single trait rated on a single target. In contrast to many psychometric models developed for multitrait-multimethod data, the tri-factor model is predominantly a measurement model. It is used to evaluate item quality in scale development, test hypotheses about sources of target variability (e.g., sources of trait differences) versus informant variability (e.g., sources of rater bias), and generate integrative scores that are purged of the subjective biases of single informants. PMID:24079932

  19. Host factor I, Hfq, binds to Escherichia coli ompA mRNA in a growth rate-dependent fashion and regulates its stability

    DEFF Research Database (Denmark)

    Vytvytska, O; Jakobsen, J S; Balcunaite, G

    1998-01-01

    The stability of the ompA mRNA depends on the bacterial growth rate. The 5' untranslated region is the stability determinant of this transcript and the target of the endoribonuclease, RNase E, the key player of mRNA degradation. An RNA-binding protein with affinity for the 5' untranslated region...... ompA was purified and identified as Hfq, a host factor initially recognized for its function in phage Qbeta replication. The ompA RNA-binding activity parallels the amount of Hfq, which is elevated in bacteria cultured at slow growth rate, a condition leading to facilitated degradation of the ompA m...... no affinity for the lpp transcript whose degradation, like that of bulk mRNA, is not affected by bacterial growth rate. Compatible with our results, we found that the intracellular concentration of RNase E and its associated degradosome components is independent of bacterial growth rate. Thus our results...

  20. Identification of an HIV-1 replication inhibitor which rescues host restriction factor APOBEC3G in Vif-APOBEC3G complex.

    Science.gov (United States)

    Zhang, Shaoyang; Zhong, Limei; Chen, Bing; Pan, Ting; Zhang, Xue; Liang, Liting; Li, Qianwen; Zhang, Ziying; Chen, Hui; Zhou, Jie; Luo, Haihua; Zhang, Hui; Bai, Chuan

    2015-10-01

    HIV-1 Vif protein is one of the most crucial accessory proteins for viral replication. It efficiently counteracts the important host restriction factor APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G, A3G) which is lethal to HIV-1 by causing G to A mutation of viral genome. Vif protein mediates degradation of APOBEC3G via the complicated protein-protein interactions of Vif, APOBEC3G, Elongin C/B and Cullin 5. The importance of Vif-APOBEC3G complex makes it a good potential target to develop new therapeutics of HIV-1. We identified a potent HIV-1 replication inhibitor (ZBMA-1, IC50 = 1.01 μM) that efficiently protected APOBEC3G protein by targeting Vif-APOBEC3G complex. The co-immunoprecipitation and docking studies indicated that compound ZBMA-1 affected the binding of Elongin C with Vif protein.

  1. Human factors analysis and design methods for nuclear waste retrieval systems: Human factors design methodology and integration plan

    Science.gov (United States)

    Casey, S. M.

    1980-06-01

    The nuclear waste retrieval system intended to be used for the removal of storage canisters (each canister containing a spent fuel rod assembly) located in an underground salt bed depository is discussed. The implementation of human factors engineering principles during the design and construction of the retrieval system facilities and equipment is reported. The methodology is structured around a basic system development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Examples of application of the techniques in the analysis of human tasks, and equipment required in the removal of spent fuel canisters is provided. The framework for integrating human engineering with the rest of the system development effort is documented.

  2. Influencing factors of distribution of Trichinella larvae in host muscles%旋毛虫幼虫在宿主肌组织中分布的影响因素

    Institute of Scientific and Technical Information of China (English)

    李立宏; 姜文静

    2012-01-01

    The distribution states of Trichinella spimlis larvae in host muscles are very complicated, and they are possibly in-fluenced by many factors, such as host species, the physiological condition of host muscles, Trichinella species, the encapsulat-ing condition of Trichinella spiralis encapsulated larvae, the level of infection and others. This paper summarizes the advance in the study of the influencing factors of distribution of Trichinella spiralis encapsulated larvae in host muscles.%旋毛虫幼虫在宿主肌组织中的分布受多种因素的影响,如宿主种类、肌肉生理状况、旋毛虫种别、旋毛虫幼虫能否成囊、感染量等.本文对旋毛虫幼虫在宿主肌组织分布的影响因素作一综述.

  3. Both mosquito-derived xanthurenic acid and a host blood-derived factor regulate gametogenesis of Plasmodium in the midgut of the mosquito.

    Science.gov (United States)

    Arai, M; Billker, O; Morris, H R; Panico, M; Delcroix, M; Dixon, D; Ley, S V; Sinden, R E

    2001-08-01

    Gametogenesis of Plasmodium in vitro can be induced by the combined stimulus of a 5 degrees C fall in temperature and the presence of xanthurenic acid (XA). In-vitro experiments showed that P. gallinaceum (EC(50)=80 nM) is much more sensitive to XA than P. berghei (9 microM), P. yoelii (8 microM), and P. falciparum (2 microM). However, in the mosquito vector, we do not know whether the temperature shift and XA are the only gametocyte-activating factors (GAF), nor do we know with certainty the true source(s) of XA in the mosquito blood meal. Previous studies indicate that XA is the only source of GAF in the mosquito. By defining, and then contrasting, the ability of an XA-deficient mutant of Aedes aegypti, with the wild-type mosquito to support exflagellation and ookinete formation in vivo, we determined the roles of parasite-, mosquito- and host blood-derived GAF in the regulation of gametogenesis of P. gallinaceum. Removal of both host and vector sources of GAF totally inhibited both exflagellation and ookinete production, whilst the lack of either single source resulted in only a partial reduction of exflagellation and ookinete formation in the mosquito gut. Both sources can be effectively replaced/substituted by synthetic XA. This suggests (1) both mosquito- and vertebrate-derived factors act as GAF in the mosquito gut in vivo; (2) the parasite itself is unable to produce any significant GAF activity. Studies are underway to determine whether vertebrate-derived GAF is XA. These data may form the basis of further studies of the development of new methods of interrupting malarial transmission.

  4. Detecting transforming growth factor-β release from liver cells using an aptasensor integrated with microfluidics.

    Science.gov (United States)

    Matharu, Zimple; Patel, Dipali; Gao, Yandong; Haque, Amranul; Zhou, Qing; Revzin, Alexander

    2014-09-02

    We developed a cell-culture/biosensor platform consisting of aptamer-modified Au electrodes integrated with reconfigurable microfluidics for monitoring of transforming growth factor-beta 1 (TGF-β1), an important inflammatory and pro-fibrotic cytokine. Aptamers were thiolated, labeled with redox reporters, and self-assembled on gold surfaces. The biosensor was determined to be specific for TGF-β1 with an experimental detection limit of 1 ng/mL and linear range extending to 250 ng/mL. Upon determining figures of merit, aptasensor was miniaturized and integrated with human hepatic stellate cells inside microfluidic devices. Reconfigurable microfluidics were developed to ensure that seeding of "sticky" stromal cells did not foul the electrode and compromise sensor performance. This microsystem with integrated aptasensors was used to monitor TGF-β1 release from activated stellate cells over the course of 20 h. The electrochemical response went down upon infusing anti-TGF-β1 antibodies into the microfluidic devices containing activated stellate cells. To further validate aptasensor responses, stellate cells were stained for markers of activation (e.g., alpha smooth muscle actin) and were also tested for presence of TGF-β1 using enzyme linked immunosorbent assay (ELISA). Given the importance of TGF-β1 as a fibrogenic signal, a microsystem with integrated biosensors for local and continuous detection of TGF-β1 may prove to be an important tool to study fibrosis of the liver and other organs.

  5. [Integrity].

    Science.gov (United States)

    Gómez Rodríguez, Rafael Ángel

    2014-01-01

    To say that someone possesses integrity is to claim that that person is almost predictable about responses to specific situations, that he or she can prudentially judge and to act correctly. There is a closed interrelationship between integrity and autonomy, and the autonomy rests on the deeper moral claim of all humans to integrity of the person. Integrity has two senses of significance for medical ethic: one sense refers to the integrity of the person in the bodily, psychosocial and intellectual elements; and in the second sense, the integrity is the virtue. Another facet of integrity of the person is la integrity of values we cherish and espouse. The physician must be a person of integrity if the integrity of the patient is to be safeguarded. The autonomy has reduced the violations in the past, but the character and virtues of the physician are the ultimate safeguard of autonomy of patient. A field very important in medicine is the scientific research. It is the character of the investigator that determines the moral quality of research. The problem arises when legitimate self-interests are replaced by selfish, particularly when human subjects are involved. The final safeguard of moral quality of research is the character and conscience of the investigator. Teaching must be relevant in the scientific field, but the most effective way to teach virtue ethics is through the example of the a respected scientist.

  6. The B-domain of factor VIII reduces cell membrane attachement to host cells in serum free conditions

    DEFF Research Database (Denmark)

    Kolind, Mille Petersen; Nørby, Peder Lisby; Flintegaard, Thomas Veje

    2010-01-01

    engineered extensively throughout the years to increase the low production yields that initially were obtained from mammalian cell cultures. The scope of this work was to investigate the interaction of rFVIII with the cell membrane surface of the producing cells in serum free medium. We wondered whether...... binding of rFVIII to the cell membrane could be a factor diminishing the production yield. We studied the contribution of the rFVIII B-domain to membrane attachment by transfecting several constructs containing increasing lengths of the B-domain into cells under serum free conditions. We found that 90......% of rFVIII is attached to the cell membrane of the producing cell when the rFVIII variant contains a short B-domain (21 aa). By increasing the length of the B-domain the membrane attached fraction can be reduced to 50% of the total expressed rFVIII. Further, our studies show that the N...

  7. Population differences in host immune factors may influence survival of Gunnison's prairie dogs (Cynomys Gunnisoni) during plague outbreaks

    Science.gov (United States)

    Busch, Joseph D.; Van Andel, Roger; Cordova, Jennifer; Colman, Rebecca E.; Keim, Paul; Rocke, Tonie E.; Leid, Jeff G.; Van Pelt, William E.; Wagner, David M.

    2011-01-01

    Over the past 40 yr, epizootics of plague (Yersinia pestis) in northern Arizona have reduced populations of the Gunnison’s prairie dog (Cynomys gunnisoni), with the exception of a large population found in the Aubrey Valley (AV). To examine potential mechanisms accounting for their survival, we collected prairie dog serum samples in 2005–2006 from AV and a neighboring population near Seligman (SE), Arizona. We quantified gene expression at 58 diverse immune proteins using a multiplexed enzyme-linked immunosorbent assay panel. We found a subset of proteins important in coagulation and inflammation (tissue factor [TF], calbindin [Cal], and thrombopoietin [TPO]) and T-cell responses (CD40L and CD40) that were present in AV at levels two to eight times greater than SE. These results suggest that AV and SE animals might differ in their ability to mount an immune response.

  8. Recipient CTLA-4*CT60-AA genotype is a prognostic factor for acute graft-versus-host disease in hematopoietic stem cell transplantation for thalassemia

    Science.gov (United States)

    Orrù, Sandro; Orrù, Nicola; Manolakos, Emmanouil; Littera, Roberto; Caocci, Giovanni; Giorgiani, Giovanna; Bertaina, Alice; Pagliara, Daria; Giardini, Claudio; Nesci, Sonia; Locatelli, Franco; Carcassi, Carlo; La Nasa, Giorgio

    2012-01-01

    Polymorphisms of the cytotoxic T-lymphocyte antigen-4 gene (CTLA-4) have been associated with autoimmune diseases and it has recently been reported that donor genotypes correlate with the outcome of allogeneic hematopoietic stem cell transplantation in leukemia patients. With the aim of confirming this finding in thalassemia patients, we investigated the influence of genotype distribution of 3 CTLA-4 gene polymorphisms in 72 thalassemia patients and their unrelated donors. A significant association was observed for recipient CT60-AA genotype and onset of grade II–IV (63.2% vs 24.5%; p = 0.001) and grade III–IV (36.4% vs 7.6%; p = 0.005) acute graft-versus-host disease (aGVHD). The same association was observed for the 88-base-pair allele of the CTLA-4 (AT)n polymorphism, which was determined to be in complete linkage disequilibrium with the CT60 A allele. Multinomial Cox regression demonstrated that this association was independent of CT60 donor genotypes or other risk factors (p = 0.016; hazard ratio = 2.8). Our data confirm that the genetic variability in CTLA-4 is an important prognostic factor for aGVHD and suggest that some of the risk factors for this complication are generated by recipient cells that persist after the myeloablative conditioning regimen. PMID:22245568

  9. Lensed Quasar Hosts

    CERN Document Server

    Peng, C Y; Rix, H W; Keeton, C R; Falco, E E; Kochanek, C S; Lehár, J; McLeod, B A; Peng, Chien Y.; Impey, Chris D.; Rix, Hans-Walter; Keeton, Charles R.; Falco, Emilio E.; Kochanek, Chris S.; Lehar, Joseph; Leod, Brian A. Mc

    2006-01-01

    Gravitational lensing assists in the detection of quasar hosts by amplifying and distorting the host light away from the unresolved quasar core images. We present the results of HST observations of 30 quasar hosts at redshifts 1 1.7 is a factor of 3--6 higher than the local value. But, depending on the stellar content the ratio may decline at z>4 (if E/S0-like), flatten off to 6--10 times the local value (if Sbc-like), or continue to rise (if Im-like). We infer that galaxy bulge masses must have grown by a factor of 3--6 over the redshift range 3>z>1, and then changed little since z~1. This suggests that the peak epoch of galaxy formation for massive galaxies is above z~1. We also estimate the duty cycle of luminous AGNs at z>1 to be ~1%, or 10^7 yrs, with sizable scatter.

  10. Selective factors associated with the evolution of codon usage in natural populations of arboviruses and their practical application to infer possible hosts for emerging viruses

    Science.gov (United States)

    Arboviruses (arthropod borne viruses) have life cycles that include both vertebrate and invertebrate hosts with substantial differences in vector and host specificity between different viruses. Most arboviruses utilize RNA for their genetic material and are completely dependent on host tRNAs for the...

  11. Integrating cognitive and motivational factors in depression: initial tests of a goal-orientation approach.

    Science.gov (United States)

    Dykman, B M

    1998-01-01

    Attempts to predict depression from a strictly cognitive perspective have met with limited success. A goal-orientation model is proposed that integrates motivational and cognitive factors in attempting to explain and predict depression. The model proposes that people differ in their goal orientation, with some people being more validation seeking (VS) and others being more growth seeking (GS). The model predicts that compared with GS persons, VS persons will show greater anxiety in anticipation of a stressful event and greater self-esteem loss, task disengagement, and depression after a negative event. A goal-orientation measure was developed (Study 1), and the predictive validity of the model was tested (Studies 2-5). Findings suggest that the explanatory and predictive power of the cognitive theories can be enhanced, and the arsenal of the cognitive therapist enlarged, by integrating motivational and cognitive approaches to depression.

  12. The Cleavage and Polyadenylation Specificity Factor 6 (CPSF6) Subunit of the Capsid-recruited Pre-messenger RNA Cleavage Factor I (CFIm) Complex Mediates HIV-1 Integration into Genes.

    Science.gov (United States)

    Rasheedi, Sheeba; Shun, Ming-Chieh; Serrao, Erik; Sowd, Gregory A; Qian, Juan; Hao, Caili; Dasgupta, Twishasri; Engelman, Alan N; Skowronski, Jacek

    2016-05-27

    HIV-1 favors integration into active genes and gene-enriched regions of host cell chromosomes, thus maximizing the probability of provirus expression immediately after integration. This requires cleavage and polyadenylation specificity factor 6 (CPSF6), a cellular protein involved in pre-mRNA 3' end processing that binds HIV-1 capsid and connects HIV-1 preintegration complexes to intranuclear trafficking pathways that link integration to transcriptionally active chromatin. CPSF6 together with CPSF5 and CPSF7 are known subunits of the cleavage factor I (CFIm) 3' end processing complex; however, CPSF6 could participate in additional protein complexes. The molecular mechanisms underpinning the role of CPSF6 in HIV-1 infection remain to be defined. Here, we show that a majority of cellular CPSF6 is incorporated into the CFIm complex. HIV-1 capsid recruits CFIm in a CPSF6-dependent manner, which suggests that the CFIm complex mediates the known effects of CPSF6 in HIV-1 infection. To dissect the roles of CPSF6 and other CFIm complex subunits in HIV-1 infection, we analyzed virologic and integration site targeting properties of a CPSF6 variant with mutations that prevent its incorporation into CFIm We show, somewhat surprisingly, that CPSF6 incorporation into CFIm is not required for its ability to direct preferential HIV-1 integration into genes. The CPSF5 and CPSF7 subunits appear to have only a minor, if any, role in this process even though they appear to facilitate CPSF6 binding to capsid. Thus, CPSF6 alone controls the key molecular interactions that specify HIV-1 preintegration complex trafficking to active chromatin.

  13. The Impact of Multilevel Factors on Technology Integration: The Case of Taiwanese Grade 1-9 Teachers and Schools

    Science.gov (United States)

    Hsu, Shihkuan; Kuan, Ping-Yin

    2013-01-01

    Technology integration is influenced by many factors related to the teacher and the school environment. While many studies have examined factors that influence teachers' use of Information and Communication Technology (ICT) at the teacher level, a growing number of studies have suggested that it is beneficial to examine those factors using…

  14. Integration of developmental and environmental signals via a polyadenylation factor in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Man Liu

    Full Text Available The ability to integrate environmental and developmental signals with physiological responses is critical for plant survival. How this integration is done, particularly through posttranscriptional control of gene expression, is poorly understood. Previously, it was found that the 30 kD subunit of Arabidopsis cleavage and polyadenylation specificity factor (AtCPSF30 is a calmodulin-regulated RNA-binding protein. Here we demonstrated that mutant plants (oxt6 deficient in AtCPSF30 possess a novel range of phenotypes--reduced fertility, reduced lateral root formation, and altered sensitivities to oxidative stress and a number of plant hormones (auxin, cytokinin, gibberellic acid, and ACC. While the wild-type AtCPSF30 (C30G was able to restore normal growth and responses, a mutant AtCPSF30 protein incapable of interacting with calmodulin (C30GM could only restore wild-type fertility and responses to oxidative stress and ACC. Thus, the interaction with calmodulin is important for part of AtCPSF30 functions in the plant. Global poly(A site analysis showed that the C30G and C30GM proteins can restore wild-type poly(A site choice to the oxt6 mutant. Genes associated with hormone metabolism and auxin responses are also affected by the oxt6 mutation. Moreover, 19 genes that are linked with calmodulin-dependent CPSF30 functions, were identified through genome-wide expression analysis. These data, in conjunction with previous results from the analysis of the oxt6 mutant, indicate that the polyadenylation factor AtCPSF30 is a regulatory hub where different signaling cues are transduced, presumably via differential mRNA 3' end formation or alternative polyadenylation, into specified phenotypic outcomes. Our results suggest a novel function of a polyadenylation factor in environmental and developmental signal integration.

  15. Effects of a novel entomopathogenic nematode-infected host formulation on cadaver integrity, nematode yield, and suppression of Diaprepes abbreviatus and Aethina tumida.

    Science.gov (United States)

    Shapiro-Ilan, David I; Morales-Ramos, Juan A; Rojas, Maria G; Tedders, Walker L

    2010-02-01

    An alternative approach to applying entomopathogenic nematodes entails the distribution of nematodes in their infected insect hosts. Protection of the infected host from rupturing, and improving ease of handling, may be necessary to facilitate application. In this study our objective was to test the potential of a new method of formulating the infected hosts, i.e., enclosing the infected host in masking tape. Tenebrio molitor L. cadavers infected with Heterorhabditis indica Poinar, Karunakar and David or Steinernema carpocapsae (Weiser) were wrapped in tape using an automatic packaging machine; the machine was developed to reduce labor and to standardize the final product. The effects of the tape formulation on the ability to protect the cadavers from mechanical damage, nematode yield, and pest control efficacy were tested. After exposure to mechanical agitation at 7-d-post-infection, S. carpocapsae cadavers in tape were more resistant to rupture than cadavers without tape, yet H. indica cadavers 7-d-post-infection were not affected by mechanical agitation (with or without tape), nor was either nematode affected when 4-d-old cadavers were tested. Experiments indicated that infective juvenile yield was not affected by the tape formulation. Laboratory experiments were conducted measuring survival of the root weevil, Diaprepes abbreviatus (L.), or the small hive beetle, Aethina tumida Murray, after the application of two H. indica-infected hosts with or without tape per 15 cm pot (filled with soil). A greenhouse experiment was also conducted in a similar manner measuring survival of D. abbreviatus. In all experiments, both the tape and no-tape treatments caused significant reductions in insect survival relative to the control, and no differences were detected between the nematode treatments. Fifteen days post-application, the infected host treatments caused up to 78% control in A. tumida, 91% control in D. abbreviatus in the lab, and 75% in the greenhouse. These

  16. Human factors analysis and design methods for nuclear waste retrieval systems. Human factors design methodology and integration plan

    Energy Technology Data Exchange (ETDEWEB)

    Casey, S.M.

    1980-06-01

    The purpose of this document is to provide an overview of the recommended activities and methods to be employed by a team of human factors engineers during the development of a nuclear waste retrieval system. This system, as it is presently conceptualized, is intended to be used for the removal of storage canisters (each canister containing a spent fuel rod assembly) located in an underground salt bed depository. This document, and the others in this series, have been developed for the purpose of implementing human factors engineering principles during the design and construction of the retrieval system facilities and equipment. The methodology presented has been structured around a basic systems development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Within each of these phases, the recommended activities of the human engineering team have been stated, along with descriptions of the human factors engineering design techniques applicable to the specific design issues. Explicit examples of how the techniques might be used in the analysis of human tasks and equipment required in the removal of spent fuel canisters have been provided. Only those techniques having possible relevance to the design of the waste retrieval system have been reviewed. This document is intended to provide the framework for integrating human engineering with the rest of the system development effort. The activities and methodologies reviewed in this document have been discussed in the general order in which they will occur, although the time frame (the total duration of the development program in years and months) in which they should be performed has not been discussed.

  17. Silencing of the host factor eIF(iso)4E gene confers plum pox virus resistance in plum.

    Science.gov (United States)

    Wang, Xinhua; Kohalmi, Susanne E; Svircev, Antonet; Wang, Aiming; Sanfaçon, Hélène; Tian, Lining

    2013-01-01

    Plum pox virus (PPV) causes the most economically-devastating viral disease in Prunus species. Unfortunately, few natural resistance genes are available for the control of PPV. Recessive resistance to some potyviruses is associated with mutations of eukaryotic translation initiation factor 4E (eIF4E) or its isoform eIF(iso)4E. In this study, we used an RNA silencing approach to manipulate the expression of eIF4E and eIF(iso)4E towards the development of PPV resistance in Prunus species. The eIF4E and eIF(iso)4E genes were cloned from plum (Prunus domestica L.). The sequence identity between plum eIF4E and eIF(iso)4E coding sequences is 60.4% at the nucleotide level and 52.1% at the amino acid level. Quantitative real-time RT-PCR analysis showed that these two genes have a similar expression pattern in different tissues. Transgenes allowing the production of hairpin RNAs of plum eIF4E or eIF(iso)4E were introduced into plum via Agrobacterium-mediated transformation. Gene expression analysis confirmed specific reduced expression of eIF4E or eIF(iso)4E in the transgenic lines and this was associated with the accumulation of siRNAs. Transgenic plants were challenged with PPV-D strain and resistance was evaluated by measuring the concentration of viral RNA. Eighty-two percent of the eIF(iso)4E silenced transgenic plants were resistant to PPV, while eIF4E silenced transgenic plants did not show PPV resistance. Physical interaction between PPV-VPg and plum eIF(iso)4E was confirmed. In contrast, no PPV-VPg/eIF4E interaction was observed. These results indicate that eIF(iso)4E is involved in PPV infection in plum, and that silencing of eIF(iso)4E expression can lead to PPV resistance in Prunus species.

  18. Silencing of the host factor eIF(iso4E gene confers plum pox virus resistance in plum.

    Directory of Open Access Journals (Sweden)

    Xinhua Wang

    Full Text Available Plum pox virus (PPV causes the most economically-devastating viral disease in Prunus species. Unfortunately, few natural resistance genes are available for the control of PPV. Recessive resistance to some potyviruses is associated with mutations of eukaryotic translation initiation factor 4E (eIF4E or its isoform eIF(iso4E. In this study, we used an RNA silencing approach to manipulate the expression of eIF4E and eIF(iso4E towards the development of PPV resistance in Prunus species. The eIF4E and eIF(iso4E genes were cloned from plum (Prunus domestica L.. The sequence identity between plum eIF4E and eIF(iso4E coding sequences is 60.4% at the nucleotide level and 52.1% at the amino acid level. Quantitative real-time RT-PCR analysis showed that these two genes have a similar expression pattern in different tissues. Transgenes allowing the production of hairpin RNAs of plum eIF4E or eIF(iso4E were introduced into plum via Agrobacterium-mediated transformation. Gene expression analysis confirmed specific reduced expression of eIF4E or eIF(iso4E in the transgenic lines and this was associated with the accumulation of siRNAs. Transgenic plants were challenged with PPV-D strain and resistance was evaluated by measuring the concentration of viral RNA. Eighty-two percent of the eIF(iso4E silenced transgenic plants were resistant to PPV, while eIF4E silenced transgenic plants did not show PPV resistance. Physical interaction between PPV-VPg and plum eIF(iso4E was confirmed. In contrast, no PPV-VPg/eIF4E interaction was observed. These results indicate that eIF(iso4E is involved in PPV infection in plum, and that silencing of eIF(iso4E expression can lead to PPV resistance in Prunus species.

  19. Sami in the History of the Norwegian-Russian Borderland: Factor of Tension or Regional Integration?

    Directory of Open Access Journals (Sweden)

    Vladislav I. Goldin

    2015-09-01

    Full Text Available This article is based of an extensive array of documents and cartographic materials of the leading archives of the Russian Federation and Norway. The authors focus their attention on the history of Russian-Norwegian border and the Sami aspect of its development. On the Scandinavian continent, the population of frontier areas was often a factor of political tension, but the ethnic picture of the Russian-Norwegian borderland distinguished by the fact that the frontier status of the Skolt was the integration factor for the formation of economic cooperation between the border provinces of Russia and Norway. This thesis the authors explain by the peculiarities of the States policy regarding the border territories, ethnic groups, economic activities and economic interaction of Skolt with other communities, as well as their perception of own inhabited space.

  20. A ToxA-like protein from Cochliobolus heterostrophus induces light-dependent leaf necrosis and acts as a virulence factor with host selectivity on maize.

    Science.gov (United States)

    Lu, Shunwen; Gillian Turgeon, B; Edwards, Michael C

    2015-08-01

    ToxA, the first discovered fungal proteinaceous host-selective toxin (HST), was originally identified in 1989 from the tan spot fungus Pyrenophora tritici-repentis (Ptr). About 25years later, a homolog was identified in the leaf/glume blotch fungus Stagonospora nodorum (Parastagonospora nodorum), also a pathogen of wheat. Here we report the identification and function of a ToxA-like protein from the maize pathogen Cochliobolus heterostrophus (Ch) that possesses necrosis-inducing activity specifically against maize. ChToxA is encoded by a 535-bp open reading frame featuring a ToxA-specific intron with unusual splicing sites (5'-ATAAGT…TAC-3') at conserved positions relative to PtrToxA. The protein shows 64% similarity to PtrToxA and is predicted to adopt a similar three-dimensional structure, although lacking the arginyl-glycyl-aspartic acid (RGD) motif reported to be required for internalization into sensitive wheat mesophyll cells. Reverse-transcriptase PCR revealed that the ChTOXA gene expression is up-regulated in planta, relative to axenic culture. Plant assays indicated that the recombinant ChToxA protein induces light-dependent leaf necrosis in a host-selective manner on maize inbred lines. Gene deletion experiments confirmed that ChtoxA mutants are reduced in virulence on specific ChToxA-sensitive maize lines, relative to virulence caused by wild-type strains. Database searches identified potential ChToxA homologues in other plant-pathogenic ascomycetes. Sequence and phylogenetic analyses revealed that the corresponding ToxA-like proteins include one member recently shown to be associated with formation of penetration hypha. These results provide the first evidence that C. heterostrophus is capable of producing proteinaceous HSTs as virulence factors in addition to well-known secondary metabolite-type toxins produced biosynthetically by polyketide synthase megaenzymes. Further studies on ChToxA may provide new insights into effector evolution in host

  1. Temporal activation of anti- and pro-apoptotic factors in human gingival fibroblasts infected with the periodontal pathogen, Porphyromonas gingivalis: potential role of bacterial proteases in host signalling

    Directory of Open Access Journals (Sweden)

    Takehara Tadamichi

    2006-03-01

    Full Text Available Abstract Background Porphyromonas gingivalis is the foremost oral pathogen of adult periodontitis in humans. However, the mechanisms of bacterial invasion and the resultant destruction of the gingival tissue remain largely undefined. Results We report host-P. gingivalis interactions in primary human gingival fibroblast (HGF cells. Quantitative immunostaining revealed the need for a high multiplicity of infection for optimal infection. Early in infection (2–12 h, P. gingivalis activated the proinflammatory transcription factor NF-kappa B, partly via the PI3 kinase/AKT pathway. This was accompanied by the induction of cellular anti-apoptotic genes, including Bfl-1, Boo, Bcl-XL, Bcl2, Mcl-1, Bcl-w and Survivin. Late in infection (24–36 h the anti-apoptotic genes largely shut down and the pro-apoptotic genes, including Nip3, Hrk, Bak, Bik, Bok, Bax, Bad, Bim and Moap-1, were activated. Apoptosis was characterized by nuclear DNA degradation and activation of caspases-3, -6, -7 and -9 via the intrinsic mitochondrial pathway. Use of inhibitors revealed an anti-apoptotic function of NF-kappa B and PI3 kinase in P. gingivalis-infected HGF cells. Use of a triple protease mutant P. gingivalis lacking three major gingipains (rgpA rgpB kgp suggested a role of some or all these proteases in myriad aspects of bacteria-gingival interaction. Conclusion The pathology of the gingival fibroblast in P. gingivalis infection is affected by a temporal shift from cellular survival response to apoptosis, regulated by a number of anti- and pro-apoptotic molecules. The gingipain group of proteases affects bacteria-host interactions and may directly promote apoptosis by intracellular proteolytic activation of caspase-3.

  2. Host Cell Factor-1 Recruitment to E2F-Bound and Cell-Cycle-Control Genes Is Mediated by THAP11 and ZNF143

    Directory of Open Access Journals (Sweden)

    J. Brandon Parker

    2014-11-01

    Full Text Available Host cell factor-1 (HCF-1 is a metazoan transcriptional coregulator essential for cell-cycle progression and cell proliferation. Current models suggest a mechanism whereby HCF-1 functions as a direct coregulator of E2F proteins, facilitating the expression of genes necessary for cell proliferation. In this report, we show that HCF-1 recruitment to numerous E2F-bound promoters is mediated by the concerted action of zinc finger transcription factors THAP11 and ZNF143, rather than E2F proteins directly. THAP11, ZNF143, and HCF-1 form a mutually dependent complex on chromatin, which is independent of E2F occupancy. Disruption of the THAP11/ZNF143/HCF-1 complex results in altered expression of cell-cycle control genes and leads to reduced cell proliferation, cell-cycle progression, and cell viability. These data establish a model in which a THAP11/ZNF143/HCF-1 complex is a critical component of the transcriptional regulatory network governing cell proliferation.

  3. Expression of a viral polymerase-bound host factor turns human cell lines permissive to a plant- and insect-infecting virus

    Science.gov (United States)

    de Medeiros, Ricardo B.; Figueiredo, Juliana; Resende, Renato de O.; De Avila, Antonio C.

    2005-01-01

    Tospoviruses are the only plant-infecting members of the Bunyaviridae family of ambisense ssRNA viruses. Tomato spotted wilt tospovirus (TSWV), the type-member, also causes mild infection on its main insect vector, Frankliniella occidentalis. Herein, we identified an F. occidentalis putative transcription factor (FoTF) that binds to the TSWV RNA-dependent RNA polymerase and to viral RNA. Using in vitro RNA synthesis assays, we show that addition of purified FoTF improves viral replication, but not transcription. Expression of FoTF deletion mutants, unable to bind the RNA-dependent RNA polymerase or viral RNA, blocks TSWV replication in F. occidentalis cells. Finally, expression of FoTF wild-type turns human cell lines permissive to TSWV replication. These data indicate that FoTF is a host factor required for TSWV replication in vitro and in vivo, provide an experimental system that could be used to compare molecular defense mechanisms in plant, insect, and human cells against the same pathogen (TSWV), and could lead to a better understanding of evolutionary processes of ambisense RNA viruses. PMID:15657123

  4. Validation of the Intrapersonal Technology Integration Scale: Assessing the Influence of Intrapersonal Factors that Influence Technology Integration

    Science.gov (United States)

    Niederhauser, Dale S.; Perkmen, Serkan

    2008-01-01

    Teachers' beliefs about their self-efficacy for integrating technology, their outcome expectations for integrating technology, and their interest in using technology to support student learning influence their intentions for incorporating technology into their instructional practices. To date, instruments developed to examine the relationships…

  5. Adaptive Estimation of Multiple Fading Factors for GPS/INS Integrated Navigation Systems

    Directory of Open Access Journals (Sweden)

    Chen Jiang

    2017-06-01

    Full Text Available The Kalman filter has been widely applied in the field of dynamic navigation and positioning. However, its performance will be degraded in the presence of significant model errors and uncertain interferences. In the literature, the fading filter was proposed to control the influences of the model errors, and the H-infinity filter can be adopted to address the uncertainties by minimizing the estimation error in the worst case. In this paper, a new multiple fading factor, suitable for the Global Positioning System (GPS and the Inertial Navigation System (INS integrated navigation system, is proposed based on the optimization of the filter, and a comprehensive filtering algorithm is constructed by integrating the advantages of the H-infinity filter and the proposed multiple fading filter. Measurement data of the GPS/INS integrated navigation system are collected under actual conditions. Stability and robustness of the proposed filtering algorithm are tested with various experiments and contrastive analysis are performed with the measurement data. Results demonstrate that both the filter divergence and the influences of outliers are restrained effectively with the proposed filtering algorithm, and precision of the filtering results are improved simultaneously.

  6. Integrated estimation of the effect of physical factors on human functional state during mental work.

    Science.gov (United States)

    Suvorov, G A; Afanasieva, R F; Mikhailova, N S; Babayan, M A; Bobrov, A F; Sokolov, S N

    2001-01-01

    The purpose of this study was to develop a model for an integrated estimation of the functional state of the human organism (FSHO) and an integral estimation of physical factors (PF) for hygienic rating. Tests were performed twice with 3 men in 0.7-clo clothing during 4-hr mental work with 9 combinations of 4 PF: wideband noise (55- 83 dB(A)), whole-body vibration (6 Hz, a(z) = 0.2-1.8 ms(-2)), air temperature (18-30 degrees C), and illumination (1, 3, 5 lx). Thermoregulatory, cardiovascular, and psychophysiological reactions and temporary threshold of hearing (TTS2) shifts were studied. For the integral estimation of PF influence on FSHO the model F(y1,y2..........ym) = f(x1,x2,.......xn) was used, relating both FSHO and PF sets. The most important physiological parameters in creating FSHO are defined and the contribution of individual parameters of FSHO and PF is found.

  7. Effect of organizational and environmental factors on service differentiation strategy of integrated healthcare networks.

    Science.gov (United States)

    Lin, Y J; Wan, T T

    2001-02-01

    During the past decade, the missions/goals of medical providers of healthcare services in the United States have shifted--from emphasizing individual, independent illness treatments to focusing on the continuum of care, population-based wellness, and providing the appropriate care in the most efficient way. Integrated healthcare networks (IHNs)--or integrated healthcare delivery systems--have been focusing heavily on their level of various partnership integration (i.e. service differentiation strategy) in order to offer a full continuum of care. The aim of this study, using the individual IHN as the unit of analysis, was to identify organizational and environmental factors that influence IHN administrators to focus on their service differentiation of market lines, including the establishment of third-party payers' contracts, the affiliation of managed-care organizations, and the alliances of various nonhospital medical providers, to provide a continuum of care. The study findings show that tax status of an IHN, its age, and market competition affect its service differentiation strategy in the provision of a full continuum of care.

  8. ARE METHODS USED TO INTEGRATE STANDARDIZED MANAGEMENT SYSTEMS A CONDITIONING FACTOR OF THE LEVEL OF INTEGRATION? AN EMPIRICAL STUDY

    Directory of Open Access Journals (Sweden)

    Merce Bernardo

    2011-09-01

    Full Text Available Organizations are increasingly implementing multiple Management System Standards (M SSs and considering managing the related Management Systems (MSs as a single system.The aim of this paper is to analyze if methods us ed to integrate standardized MSs condition the level of integration of those MSs. A descriptive methodology has been applied to 343 Spanish organizations registered to, at least, ISO 9001 and ISO 14001. Seven groups of these organizations using different combinations of methods have been analyzed Results show that these organizations have a high level of integration of their MSs. The most common method used, was the process map. Organizations using a combination of different methods achieve higher levels of integration than those using a single method. However, no evidence has been found to confirm the relationship between the method used and the integration level achieved.

  9. Measuring Integrated Socioemotional Guidance at School: Factor Structure and Reliability of the Socioemotional Guidance Questionnaire (SEG-Q)

    Science.gov (United States)

    Jacobs, Karen; Struyf, Elke

    2013-01-01

    Socioemotional guidance of students has recently become an integral part of education, however no instrument exists to measure integrated socioemotional guidance. This study therefore examines the factor structure and reliability of the Socioemotional Guidance Questionnaire. Psychometric properties of the Socioemotional Guidance Questionnaire and…

  10. Critical Success Factors for Integrated Library System Implementation in Academic Libraries: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Shea-Tinn Yeh

    2016-09-01

    Full Text Available Integrated library system (ILS supports the entire business operations of an academic library from acquiring and processing library resources to making them available to user communities and preserving them for future use. As libraries’ needs evolve, there is a pressing demand for libraries to migrate from one generation of ILS to the next. This complex migration process is often the single largest investment in both budget and personnel involvement, but its success is by no means guaranteed. We draw upon enterprise resource planning (ERP and critical success factors (CSFs literature to identify the most salient CSFs for ILS migration success through a qualitative study with four cases. We identified that top management involvement, vendor support, user involvement, selection process, project team competence, project management and tracking, interdepartmental communication, data analysis and conversion, user education and training, and user emotion management are the CSFs that determine a migration project success.  Keywords: Integrated library systems, information systems, library automation, critical success factors, and academic libraries.

  11. Semi-implicit integration factor methods on sparse grids for high-dimensional systems

    Science.gov (United States)

    Wang, Dongyong; Chen, Weitao; Nie, Qing

    2015-07-01

    Numerical methods for partial differential equations in high-dimensional spaces are often limited by the curse of dimensionality. Though the sparse grid technique, based on a one-dimensional hierarchical basis through tensor products, is popular for handling challenges such as those associated with spatial discretization, the stability conditions on time step size due to temporal discretization, such as those associated with high-order derivatives in space and stiff reactions, remain. Here, we incorporate the sparse grids with the implicit integration factor method (IIF) that is advantageous in terms of stability conditions for systems containing stiff reactions and diffusions. We combine IIF, in which the reaction is treated implicitly and the diffusion is treated explicitly and exactly, with various sparse grid techniques based on the finite element and finite difference methods and a multi-level combination approach. The overall method is found to be efficient in terms of both storage and computational time for solving a wide range of PDEs in high dimensions. In particular, the IIF with the sparse grid combination technique is flexible and effective in solving systems that may include cross-derivatives and non-constant diffusion coefficients. Extensive numerical simulations in both linear and nonlinear systems in high dimensions, along with applications of diffusive logistic equations and Fokker-Planck equations, demonstrate the accuracy, efficiency, and robustness of the new methods, indicating potential broad applications of the sparse grid-based integration factor method.

  12. The telerobot workstation testbed for the shuttle aft flight deck: A project plan for integrating human factors into system design

    Science.gov (United States)

    Sauerwein, Timothy

    1989-01-01

    The human factors design process in developing a shuttle orbiter aft flight deck workstation testbed is described. In developing an operator workstation to control various laboratory telerobots, strong elements of human factors engineering and ergonomics are integrated into the design process. The integration of human factors is performed by incorporating user feedback at key stages in the project life-cycle. An operator centered design approach helps insure the system users are working with the system designer in the design and operation of the system. The design methodology is presented along with the results of the design and the solutions regarding human factors design principles.

  13. Factors influencing nursing students' academic and clinical performance and attrition: an integrative literature review.

    Science.gov (United States)

    Pitt, Victoria; Powis, David; Levett-Jones, Tracy; Hunter, Sharyn

    2012-11-01

    Predicted workforce shortages have resulted in government initiatives to increase student numbers in preregistration nursing education. In tandem schools of nursing need to ensure students' progress and complete. The aim of this review was to identify factors that influence preregistration nursing students' academic performance, clinical performance and attrition. An integrative review of both quantitative and qualitative literature was conducted using validated appraisal checklists. The review included studies published from 1999 to 2011 in the databases: MEDLINE, CINAHL, Proquest nursing, Proquest Education (via Proquest 5000), ERIC, Journals@Ovid, PsychINFO and ScienceDirect. Studies were categorised according to their impact on academic progression, clinical progression and attrition. Forty four studies were found; most used quantitative methodologies. The review identified that few studies explored factors that impact on students' clinical performance. The four categories that potentially impact on nursing students' academic performance and attrition were: demographic, academic, cognitive and personality/behavioural factors. The challenge for universities committed to students' success is to develop strategies aimed at addressing these factors that are appropriate to specific contexts and student cohorts.

  14. An Integrative Literature Review of Organisational Factors Associated with Admission and Discharge Delays in Critical Care

    Directory of Open Access Journals (Sweden)

    Laura-Maria Peltonen

    2015-01-01

    Full Text Available The literature shows that delayed admission to the intensive care unit (ICU and discharge delays from the ICU are associated with increased adverse events and higher costs. Identifying factors related to delays will provide information to practice improvements, which contribute to better patient outcomes. The aim of this integrative review was to explore the incidence of patients’ admission and discharge delays in critical care and to identify organisational factors associated with these delays. Seven studies were included. The major findings are as follows: (1 explanatory research about discharge delays is scarce and one study on admission delays was found, (2 delays are a common problem mostly due to organisational factors, occurring in 38% of admissions and 22–67% of discharges, and (3 redesigning care processes by improving information management and coordination between units and interdisciplinary teams could reduce discharge delays. In conclusion, patient outcomes can be improved through efficient and safe care processes. More exploratory research is needed to identify factors that contribute to admission and discharge delays to provide evidence for clinical practice improvements. Shortening delays requires an interdisciplinary and multifaceted approach to the whole patient flow process. Conclusions should be made with caution due to the limited number of articles included in this review.

  15. Data integration for identification of important transcription factors of STAT6-mediated cell fate decisions.

    Science.gov (United States)

    Jargosch, M; Kröger, S; Gralinska, E; Klotz, U; Fang, Z; Chen, W; Leser, U; Selbig, J; Groth, D; Baumgrass, R

    2016-06-24

    Data integration has become a useful strategy for uncovering new insights into complex biological networks. We studied whether this approach can help to delineate the signal transducer and activator of transcription 6 (STAT6)-mediated transcriptional network driving T helper (Th) 2 cell fate decisions. To this end, we performed an integrative analysis of publicly available RNA-seq data of Stat6-knockout mouse studies together with STAT6 ChIP-seq data and our own gene expression time series data during Th2 cell differentiation. We focused on transcription factors (TFs), cytokines, and cytokine receptors and delineated 59 positively and 41 negatively STAT6-regulated genes, which were used to construct a transcriptional network around STAT6. The network illustrates that important and well-known TFs for Th2 cell differentiation are positively regulated by STAT6 and act either as activators for Th2 cells (e.g., Gata3, Atf3, Satb1, Nfil3, Maf, and Pparg) or as suppressors for other Th cell subpopulations such as Th1 (e.g., Ar), Th17 (e.g., Etv6), or iTreg (e.g., Stat3 and Hif1a) cells. Moreover, our approach reveals 11 TFs (e.g., Atf5, Creb3l2, and Asb2) with unknown functions in Th cell differentiation. This fact together with the observed enrichment of asthma risk genes among those regulated by STAT6 underlines the potential value of the data integration strategy used here. Thus, our results clearly support the opinion that data integration is a useful tool to delineate complex physiological processes.

  16. Delineating the effect of host environmental signals on a fully virulent strain of Bacillus anthracis using an integrated transcriptomics and proteomics approach

    NARCIS (Netherlands)

    Panda, G.; Basak, T.; Tanwer, P.; Sengupta, S.; Martins dos Santos, V.A.P.; Bhatnagar, R.

    2014-01-01

    Pathogenic bacteria sense the host environment and regulate expression of virulence-related genes. Environmental signals like temperature, bicarbonate/CO2 and glucose induce toxin production in Bacillus anthracis, but the mechanisms by which these signals contribute to virulence and overall physiolo

  17. Interactions between the spatial and temporal stimulus factors that influence multisensory integration in human performance

    Science.gov (United States)

    Stevenson, Ryan A.; Fister, Juliane Krueger; Barnett, Zachary P.; Nidiffer, Aaron R.; Wallace, Mark T.

    2012-01-01

    In natural environments, human sensory systems work in a coordinated and integrated manner to perceive and respond to external events. Previous research has shown that the spatial and temporal relationships of sensory signals are paramount in determining how information is integrated across sensory modalities, but in ecologically plausible settings, these factors are not independent. In the current study we provide a novel exploration of the impact on behavioral performance for systematic manipulations of the spatial location and temporal synchrony of a visual-auditory stimulus pair. Simple auditory and visual stimuli were presented across a range of spatial locations and stimulus onset asynchronies (SOAs), and participants performed both a spatial localization and simultaneity judgment task. Response times in localizing paired visual-auditory stimuli were slower in the periphery and at larger SOAs, but most importantly, an interaction was found between the two factors, in which the effect of SOA was greater in peripheral as opposed to central locations. Simultaneity judgments also revealed a novel interaction between space and time: individuals were more likely to judge stimuli as synchronous occurring in the periphery at large SOAs. The results of this study provide novel insights into (a) how the speed of spatial localization of an audiovisual stimulus is affected by location and temporal coincidence and the interaction between these two factors, and (b) how the location of a multisensory stimulus impacts judgments concerning the temporal relationship of the paired stimuli. These findings provide strong evidence for a complex interdependency between spatial location and temporal structure in determining the ultimate behavioral and perceptual outcome associated with a paired multisensory (i.e., visual-auditory) stimulus. PMID:22447249

  18. Application of variational principles and adjoint integrating factors for constructing numerical GFD models

    Science.gov (United States)

    Penenko, Vladimir; Tsvetova, Elena; Penenko, Alexey

    2015-04-01

    The proposed method is considered on an example of hydrothermodynamics and atmospheric chemistry models [1,2]. In the development of the existing methods for constructing numerical schemes possessing the properties of total approximation for operators of multiscale process models, we have developed a new variational technique, which uses the concept of adjoint integrating factors. The technique is as follows. First, a basic functional of the variational principle (the integral identity that unites the model equations, initial and boundary conditions) is transformed using Lagrange's identity and the second Green's formula. As a result, the action of the operators of main problem in the space of state functions is transferred to the adjoint operators defined in the space of sufficiently smooth adjoint functions. By the choice of adjoint functions the order of the derivatives becomes lower by one than those in the original equations. We obtain a set of new balance relationships that take into account the sources and boundary conditions. Next, we introduce the decomposition of the model domain into a set of finite volumes. For multi-dimensional non-stationary problems, this technique is applied in the framework of the variational principle and schemes of decomposition and splitting on the set of physical processes for each coordinate directions successively at each time step. For each direction within the finite volume, the analytical solutions of one-dimensional homogeneous adjoint equations are constructed. In this case, the solutions of adjoint equations serve as integrating factors. The results are the hybrid discrete-analytical schemes. They have the properties of stability, approximation and unconditional monotony for convection-diffusion operators. These schemes are discrete in time and analytic in the spatial variables. They are exact in case of piecewise-constant coefficients within the finite volume and along the coordinate lines of the grid area in each

  19. Risk factors for unstable blood glucose level: integrative review of the risk factors related to the nursing diagnosis.

    Science.gov (United States)

    Teixeira, Andressa Magalhães; Tsukamoto, Rosangela; Lopes, Camila Takáo; Silva, Rita de Cassia Gengo E

    2017-06-05

    to identify evidence in the literature on the possible risk factors for the risk of unstable blood glucose diagnosis in individuals with type 2 diabetes mellitus, and to compare them with the risk factors described by NANDA International. an integrative literature review guided by the question: what are the risk factors for unstable blood glucose level in people with type 2 diabetes mellitus? Primary studies were included whose outcomes were variations in glycemic levels, published in English, Portuguese or Spanish, in PubMed or CINAHL between 2010 and 2015. altered levels of glycated hemoglobin, body mass index>31 kg/m2, previous history of hypoglycemia, cognitive deficit/dementia, autonomic cardiovascular neuropathy, comorbidities and weight loss corresponded to risk factors described in NANDA International. Other risk factors identified were: advanced age, black skin color, longer length of diabetes diagnosis, daytime sleepiness, macroalbuminuria, genetic polymorphisms, insulin therapy, use of oral antidiabetics, and use of metoclopramide, inadequate physical activity and low fasting glycemia. risk factors for the diagnosis, risk for unstable blood glucose level, for persons with type 2 diabetes mellitus were identified, and 42% of them corresponded to those of NANDA International. These findings may contribute to the practice of clinical nurses in preventing the deleterious effects of glycemic variation. identificar evidências na literatura acerca de possíveis fatores de risco do diagnóstico risco de glicemia instável para pessoas com diabetes mellitus tipo 2 e compará-los com os fatores de risco descritos pela NANDA International . revisão integrativa norteada pela pergunta: quais são os fatores de risco de glicemia instável em pessoas com diabetes mellitus tipo 2? Incluíram-se estudos primários cujos desfechos eram variações nos níveis glicêmicos, publicados em inglês, português ou espanhol no PubMed ou CINAHL entre 2010 e 2015. observou

  20. In-vehicle human factors for integrated multi-function systems: Making ITS user-friendly

    Energy Technology Data Exchange (ETDEWEB)

    Spelt, P.F.; Scott, S.

    1998-04-01

    As more and more Intelligent Transportation System in-vehicle equipment enters the general consumer market, the authors are about to find out how different design engineers are from ordinary drivers. Driver information systems are being developed and installed in vehicles at an ever-increasing rate. These systems provide information on diverse topics of concern and convenience to the driver, such as routing and navigation, emergency and collision warnings, and a variety of motorists services, or yellow pages functions. Most of these systems are being developed and installed in isolation from each other, with separate means of gathering the information and of displaying it to the driver. The current lack of coordination among on-board systems threatens to create a situation in which different messages on separate displays will be competing with each other for the drivers attention. Urgent messages may go unnoticed, and the number of messages may distract the driver from the most critical task of controlling the vehicle. Thus, without good human factors design and engineering for integrating multiple systems in the vehicle, consumers may find ITS systems confusing and frustrating to use. The current state of the art in human factors research and design for in-vehicle systems has a number of fundamental gaps. Some of these gaps were identified during the Intelligent Vehicle Initiative Human Factors Technology Workshop, sponsored by the US Department of Transportation, in Troy, Michigan, December 10--11, 1997. One task for workshop participants was to identify needed research areas or topics relating to in-vehicle human factors. The top ten unmet research needs from this workshop are presented. Many of these gaps in human factors research knowledge indicate the need for standardization in the functioning of interfaces for safety-related devices such as collision avoidance systems (CAS) and adaptive cruise controls (ACC). Such standards and guidelines will serve to make

  1. The prediction of bereavement outcome: development of an integrative risk factor framework.

    Science.gov (United States)

    Stroebe, Margaret Susan; Folkman, Susan; Hansson, Robert O; Schut, Henk

    2006-11-01

    We propose an integrative risk factor framework to enhance understanding of individual differences in adjustment to bereavement and to encourage more systematic analysis of factors contributing to bereavement outcome (e.g., examination of interactions between variables and establishing pathways in the adaptation process). The examination of individual differences in adaptation to bereavement is essential for practical (e.g. targeting high risk individuals for intervention) and theoretical (e.g. testing the validity of theoretical claims about sources of differences) purposes. And yet, existing theoretical approaches have not led to systematic empirical examination and empirical studies in the current literature are fraught with shortcomings. Derived from Cognitive Stress Theory [Lazarus, R. S. & Folkman, S. (1984). Stress, appraisal, and coping. New York: Springer] and the stressor-specific Dual Process Model of Coping with Bereavement [Stroebe, M. S., & Schut, H. A. W. (1999). The dual process model of coping with bereavement: Rationale and description. Death Studies, 23, 197-224], the framework incorporates an analysis of stressors, intra/interpersonal risk/protective factors, and appraisal and coping processes that are postulated to impact on outcome. Advantages of using the approach are outlined. Challenges in undertaking such research are addressed.

  2. Transcription factor RFX1 is crucial for maintenance of genome integrity in Fusarium graminearum.

    Science.gov (United States)

    Min, Kyunghun; Son, Hokyoung; Lim, Jae Yun; Choi, Gyung Ja; Kim, Jin-Cheol; Harris, Steven D; Lee, Yin-Won

    2014-03-01

    The survival of cellular organisms depends on the faithful replication and transmission of DNA. Regulatory factor X (RFX) transcription factors are well conserved in animals and fungi, but their functions are diverse, ranging from the DNA damage response to ciliary gene regulation. We investigated the role of the sole RFX transcription factor, RFX1, in the plant-pathogenic fungus Fusarium graminearum. Deletion of rfx1 resulted in multiple defects in hyphal growth, conidiation, virulence, and sexual development. Deletion mutants of rfx1 were more sensitive to various types of DNA damage than the wild-type strain. Septum formation was inhibited and micronuclei were produced in the rfx1 deletion mutants. The results of the neutral comet assay demonstrated that disruption of rfx1 function caused spontaneous DNA double-strand breaks (DSBs). The transcript levels of genes involved in DNA DSB repair were upregulated in the rfx1 deletion mutants. DNA DSBs produced micronuclei and delayed septum formation in F. graminearum. Green fluorescent protein (GFP)-tagged RFX1 localized in nuclei and exhibited high expression levels in growing hyphae and conidiophores, where nuclear division was actively occurring. RNA-sequencing-based transcriptomic analysis revealed that RFX1 suppressed the expression of many genes, including those required for the repair of DNA damage. Taken together, these findings indicate that the transcriptional repressor rfx1 performs crucial roles during normal cell growth by maintaining genome integrity.

  3. A plastic stress intensity factor approach to turbine disk structural integrity assessment

    Directory of Open Access Journals (Sweden)

    V. Shlyannikov

    2016-07-01

    Full Text Available This study based on a new fracture mechanics parameter is concerned with assessing the integrity of cracked steam turbine disk which operate under startup-shutdown cyclic loading conditions. Damage accumulation and growth in service have occurred on the inner surface of slot fillet of key. In order to determine elastic-plastic fracture mechanics parameters full-size stress-strain state analysis of turbine disk was performed for a quote-elliptical part-through cracks under considering loading conditions. As a result distributions of elastic and plastic stress intensity factors along crack front in slot fillet of key of turbine disk depending on surface crack form are defined. An engineering approach to the prediction of carrying capacity of cracked turbine disk which is sensitive to the loading history at maintenance is proposed. The predictions of the rate of crack growth and residual lifetime of steam turbine disk are compared for elastic and elastic-plastic solutions. It is shown that the previously proposed elastic crack growth models provide overestimate the lifetime with respect to the present one. An advantage to use the plastic stress intensity factor to characterize the fracture resistance as the self-dependent unified parameter for a variety of turbine disk configurations rather than the magnitude of the elastic stress intensity factors alone is discussed.

  4. Accessible protocol for practice classroom about physical and chemical factors that affect the biomembranes integrity

    Directory of Open Access Journals (Sweden)

    Thiago Barros Galvão

    2012-12-01

    Full Text Available The aim of the current work is to review a protocol used in practical classes to demonstrate some factors that affect biomembrane integrity. Sugar-beet fragments were utilized as the experimental model as membrane damage could be visualized by leakage of betacyanins, hydrophilic pigments accumulated in the cell vacuoles. The tests were carried out as discrete experiments utilizing physical agents and chemical products present in the student daily routine. To test the effect of temperature, sugar-beet fragments were submitted to heat, cold or both at different times of exposition. When chemical products were tested, sugar-beet fragments were exposed to organic solvents (common alcohol and acetone or polar and amphipathic substances (disinfectant, detergent, hydrogen peroxide, and sodium hypochlorite. The obtained results were discussed in terms of the capacity of the physical and chemical factors to cause membrane damage. The review of this protocol using reagents that are present in the student daily routine were able to demonstrate clearly the effect of the different tested factors, allowing the utilization of this practical class under limited conditions.

  5. A membrane-bound NAC transcription factor as an integrator of biotic and abiotic stress signals.

    Science.gov (United States)

    Seo, Pil Joon; Park, Chung-Mo

    2010-05-01

    Transcription factors are central components of gene regulatory networks that mediate virtually all aspects of growth and developmental processes in biological systems. The activity of transcription factors is regulated at multiple steps, such as gene transcription, posttranscriptional RNA processing, posttranslational modification, protein-protein interactions, and controlled protein turnover. Controlled activation of dormant, membrane-bound transcription factor (MTF) is an intriguing regulatory mechanism that ensures quick transcriptional responses to environmental fluctuations in plants, in which various stress hormones serve as signaling mediators. NTL6 is proteolytically activated upon exposure to cold and induces expression of the Pathogenesis-Related (PR) genes. The membrane-mediated cold signaling in inducing pathogen resistance is considered to be an adaptive strategy that protects plants against infection by hydrophilic pathogens frequently occurring during cold season. We found that NTL6 also mediates abscisic acid (ABA) regulation of abiotic stress responses in Arabidopsis. NTL6 is proteolytically activated by ABA. Transgenic plants overexpressing a nuclear NTL6 form (35S:6ΔC) exhibited a hypersensitive response to ABA and high salinity in seed germination. Taken together, these observations indicate that NTL6 plays an integrative role in plant responses to both biotic and abiotic stress conditions.

  6. Greybody factors for Schwarzschild black holes: Path-ordered exponentials and product integrals

    CERN Document Server

    Gray, Finnian

    2015-01-01

    In recent work concerning the sparsity of the Hawking flux [arXiv:1506.03975v2], we found it necessary to re-examine what is known regarding the greybody factors of black holes, with a view to extending and expanding on some old results from the 1970s. Focussing specifically on Schwarzschild black holes, we re-calculated and re-assessed the greybody factors using a path-ordered-exponential approach, a technique which has the virtue of providing a semi-explicit formula for the relevant Bogoliubov coefficients. These path-ordered-exponentials, (being based on a "transfer matrix" formalism), are closely related to so-called "product integrals", leading to quite straightforward and direct numerical evaluation, while avoiding any need for numerically solving differential equations. Furthermore, while considerable analytic information is already available regarding both the high-frequency and low-frequency asymptotics of these greybody factors, numerical approaches seem better adapted to finding suitable "global mo...

  7. [Factors associated with the danger of accidental falls among institutionalized elderly individuals: an integrative review].

    Science.gov (United States)

    Gomes, Erika Carla Cavalcanti; Marques, Ana Paula de Oliveira; Leal, Márcia Carréra Campos; Barros, Benvinda Pereira de

    2014-08-01

    The scope of this research is to identify the major risk factors associated with accidental falls among the elderly. It involves an integrative review of the literature between 2002 and 2012 in English and Portuguese. The selection of articles was based on the following key words in the Lilacs, Medline and BDENF databases: accidental falls, homes for the elderly and health services. In the final sample 19 articles were selected, of which 11 were national and 8 were international. They indicate that the major factors related to the risk of accidental falls in Homes for the Elderly are: being female, being diagnosed with chronic disease, treatment with benzodiazepine, earlier cases of accident falls, and mobility restriction. The research reveals that architectonic and furniture inadequacies in Homes for the Elderly may be predisposing factors for accidental falls. Analysis of the articles reveals the need for further longitudinal studies and, consequently, enhanced monitoring of the conditions of the functional capacity of the elderly, especially the risks related to falls, considered one of the leading causes of death among institutionalized elderly individuals.

  8. Host translation shutoff mediated by non-structural protein 2 is a critical factor in the antiviral state resistance of Venezuelan equine encephalitis virus.

    Science.gov (United States)

    Bhalla, Nishank; Sun, Chengqun; Metthew Lam, L K; Gardner, Christina L; Ryman, Kate D; Klimstra, William B

    2016-09-01

    Most previous studies of interferon-alpha/beta (IFN-α/β) response antagonism by alphaviruses have focused upon interruption of IFN-α/β induction and/or receptor signaling cascades. Infection of mice with Venezuelan equine encephalitis alphavirus (VEEV) or Sindbis virus (SINV) induces serum IFN-α/β, that elicits a systemic antiviral state in uninfected cells successfully controlling SINV but not VEEV replication. Furthermore, VEEV replication is more resistant than that of SINV to a pre-existing antiviral state in vitro. While host macromolecular shutoff is proposed as a major antagonist of IFN-α/β induction, the underlying mechanisms of alphavirus resistance to a pre-existing antiviral state are not fully defined, nor is the mechanism for the greater resistance of VEEV. Here, we have separated viral transcription and translation shutoff with multiple alphaviruses, identified the viral proteins that induce each activity, and demonstrated that VEEV nonstructural protein 2-induced translation shutoff is likely a critical factor in enhanced antiviral state resistance of this alphavirus.

  9. Optimization of five environmental factors to increase beta-propeller phytase production in Pichia pastoris and impact on the physiological response of the host.

    Science.gov (United States)

    Viader-Salvadó, José M; Castillo-Galván, Miguel; Fuentes-Garibay, José A; Iracheta-Cárdenas, María M; Guerrero-Olazarán, Martha

    2013-01-01

    Recently, we engineered Pichia pastoris Mut(s) strains to produce several beta-propeller phytases, one from Bacillus subtilis and the others designed by a structure-guided consensus approach. Furthermore, we demonstrated the ability of P. pastoris to produce and secrete these phytases in an active form in shake-flask cultures. In the present work, we used a design of experiments strategy (Simplex optimization method) to optimize five environmental factors that define the culture conditions in the induction step to increase beta-propeller phytase production in P. pastoris bioreactor cultures. With the optimization process, up to 347,682 U (82,814 U/L or 6.4 g/L culture medium) of phytase at 68 h of induction was achieved. In addition, the impact of the optimization process on the physiological response of the host was evaluated. The results indicate that the increase in extracellular phytase production through the optimization process was correlated with an increase in metabolic activity of P. pastoris, shown by an increase in oxygen demand and methanol consumption, that increase the specific growth rate. The increase in extracellular phytase production also occurred with a decrease in extracellular protease activity. Moreover, the optimized culture conditions increased the recombinant protein secretion by up to 88%, along with the extracellular phytase production efficiency per cell.

  10. Host factors determine anti-GM1 response following oral challenge of chickens with Guillain-Barre syndrome derived Campylobacter jejuni strain GB11.

    Directory of Open Access Journals (Sweden)

    C Wim Ang

    Full Text Available BACKGROUND: Anti-ganglioside antibodies with a pathogenic potential are present in C. jejuni-associated Guillain-Barré syndrome (GBS patients and are probably induced by molecular mimicry. Immunization studies in rabbits and mice have demonstrated that these anti-ganglioside antibodies can be induced using purified lipo-oligosaccharides (LOS from C. jejuni in a strong adjuvant. METHODOLOGY/PRINCIPAL FINDINGS: To investigate whether natural colonization of chickens with a ganglioside-mimicking C. jejuni strain induces an anti-ganglioside response, and to investigate the diversity in anti-ganglioside response between and within genetically different chicken lines, we orally challenged chickens with different C. jejuni strains. Oral challenge of chickens with a C. jejuni strain from a GBS patient, containing a LOS that mimics ganglioside GM1, induced specific IgM and IgG anti-LOS and anti-GM1 antibodies. Inoculation of chickens with the Penner HS:3 serostrain, without a GM1-like structure, induced anti-LOS but no anti-ganglioside antibodies. We observed different patterns of anti-LOS/ganglioside response between and within the five strains of chickens. CONCLUSIONS: Natural infection of chickens with C. jejuni induces anti-ganglioside antibodies. The production of antibodies is governed by both microbial and host factors.

  11. Effects of plant tissue factors of the acceptance of four greenhouse vegetable host plants by the greenhouse whitefly: an electrical penetration graph (EPG) study

    NARCIS (Netherlands)

    Lei, H.; Lenteren, van J.C.; Xu, R.M.

    2001-01-01

    A combination of biological control and host-plant resistance is needed to control greenhouse whitefly, Trialeurodes vaporariorum (Westwood). The high level of susceptibility of several host plants to whitefly, based on their performance on these plants, is well documented. These studies only

  12. Seasonal variation in abiotic factors and ferulic acid toxicity in snail-attractant pellets against the intermediate host snail Lymnaea acuminata.

    Science.gov (United States)

    Agrahari, P; Singh, D K

    2013-11-01

    Laboratory evaluation was made to access the seasonal variations in abiotic environmental factors temperature, pH, dissolved oxygen, carbon dioxide, electrical conductivity and ferulic acid toxicity in snail-attractant pellets (SAP) against the intermediate host snail Lymnaea acuminata in each month of the years 2010 and 2011. On the basis of a 24-h toxicity assay, it was noted that lethal concentration values of 4.03, 3.73% and 4.45% in SAP containing starch and 4.16, 4.23% and 4.29% in SAP containing proline during the months of May, June and September, respectively, were most effective in killing the snails, while SAP containing starch/proline + ferulic acid was least effective in the month of January/February (24-h lethal concentration value was 7.67%/7.63% in SAP). There was a significant positive correlation between lethal concentration value of ferulic acid containing SAP and levels of dissolved O2 /pH of water in corresponding months. On the contrary, a negative correlation was observed between lethal concentration value and dissolved CO2 /temperature of test water in the same months. To ascertain that such a relationship between toxicity and abiotic factors is not co-incidental, the nervous tissue of treated (40% and 80% of 24-h lethal concentration value) and control group of snails was assayed for the activity of acetylcholinesterase (AChE) in each of the 12 months of the same year. There was a maximum inhibition of 58.43% of AChE, in snails exposed to 80% of the 24-h lethal concentration value of ferulic acid + starch in the month of May. This work shows conclusively that the best time to control snail population with SAP containing ferulic acid is during the months of May, June and September.

  13. KSHV miRNAs Decrease Expression of Lytic Genes in Latently Infected PEL and Endothelial Cells by Targeting Host Transcription Factors

    Directory of Open Access Journals (Sweden)

    Karlie Plaisance-Bonstaff

    2014-10-01

    Full Text Available Kaposi’s sarcoma-associated herpesvirus (KSHV microRNAs are encoded in the latency-associated region. Knockdown of KSHV miR-K12-3 and miR-K12-11 increased expression of lytic genes in BC-3 cells, and increased virus production from latently infected BCBL-1 cells. Furthermore, iSLK cells infected with miR-K12-3 and miR-K12-11 deletion mutant viruses displayed increased spontaneous reactivation and were more sensitive to inducers of reactivation than cells infected with wild type KSHV. Predicted binding sites for miR-K12-3 and miR-K12-11 were found in the 3’UTRs of the cellular transcription factors MYB, Ets-1, and C/EBPα, which activate RTA, the KSHV replication and transcription activator. Targeting of MYB by miR-K12-11 was confirmed by cloning the MYB 3’UTR downstream from the luciferase reporter. Knockdown of miR‑K12-11 resulted in increased levels of MYB transcript, and knockdown of miR-K12-3 increased both C/EBPα and Ets-1 transcripts. Thus, miR-K12-11 and miR-K12-3 contribute to maintenance of latency by decreasing RTA expression indirectly, presumably via down‑regulation of MYB, C/EBPα and Ets-1, and possibly other host transcription factors.

  14. Integrating the environmental factor into the strategy updating rule to promote cooperation in evolutionary games

    Institute of Scientific and Technical Information of China (English)

    Zhao Lin; Zhou Xin; Liang Zhi; Wu Jia-Rui

    2012-01-01

    Many previous studies have shown that the environment plays an important role for social individuals.In this paper,we integrate the environmental factor,which is defined as the average payoff of all a player's neighbours,with the standard Fermi updating rule by introducing a tunable parameter,ω.It is found that the level of cooperation increases remarkably,and that the cooperators can better resist the invasion of defection with an increase in ω.This interesting phenomenon is then explained from a microscopic view.In addition,the universality of this mechanism is also proved with the help of the small-world network and the random regular graph.This work may be helpful in understanding cooperation behaviour in species from unicellular organisms up to human beings.

  15. An integration factor method for stochastic and stiff reaction–diffusion systems

    Energy Technology Data Exchange (ETDEWEB)

    Ta, Catherine; Wang, Dongyong; Nie, Qing, E-mail: qnie@uci.edu

    2015-08-15

    Stochastic effects are often present in the biochemical systems involving reactions and diffusions. When the reactions are stiff, existing numerical methods for stochastic reaction diffusion equations require either very small time steps for any explicit schemes or solving large nonlinear systems at each time step for the implicit schemes. Here we present a class of semi-implicit integration factor methods that treat the diffusion term exactly and reaction implicitly for a system of stochastic reaction–diffusion equations. Our linear stability analysis shows the advantage of such methods for both small and large amplitudes of noise. Direct use of the method to solving several linear and nonlinear stochastic reaction–diffusion equations demonstrates good accuracy, efficiency, and stability properties. This new class of methods, which are easy to implement, will have broader applications in solving stochastic reaction–diffusion equations arising from models in biology and physical sciences.

  16. Monetary IntegrationFactor of Economic Cohesion and Solidarity among EU Member States

    Directory of Open Access Journals (Sweden)

    Tatiana Adina Coman

    2007-10-01

    Full Text Available The success of the EU is based on the convergence of the monetary policies of the Member States, and a genuine Single Market includesthe monetary union. The monetary integration represents a factor of the economic cohesion and of the solidarity among the Member States. In orderto have a united Europe, this is an advantage in the relationships with other states of the world. The major objectives of the monetary union are: aThe finalization of the Single Market through the elimination of uncertainty and of the inherent costs of the exchange system, but also of the costs forthe protection against the risks of the currency fluctuations, and through the insurance of the total comparability of costs and prices inside the EU.The Single Market will stimulate the intra-communitarian trade by helping the citizens and by supporting the business environment; b Economicgrowth; c Europe’s monetary stability and the increase of its financial power.

  17. Integration of human factors and ergonomics during medical device design and development: it's all about communication.

    Science.gov (United States)

    Vincent, Christopher James; Li, Yunqiu; Blandford, Ann

    2014-05-01

    Manufacturers of interactive medical devices, such as infusion pumps, need to ensure that devices minimise the risk of unintended harm during use. However, development teams face challenges in incorporating Human Factors. The aim of the research reported here was to better understand the constraints under which medical device design and development take place. We report the results of a qualitative study based on 19 semi-structured interviews with professionals involved in the design, development and deployment of interactive medical devices. A thematic analysis was conducted. Multiple barriers to designing for safety and usability were identified. In particular, we identified barriers to communication both between the development organisation and the intended users and between different teams within the development organisation. We propose the use of mediating representations. Artefacts such as personas and scenarios, known to provide integration across multiple perspectives, are an essential component of designing for safety and usability.

  18. Suppression of initiation-negative strains of Escherichia coli by integration of the sex factor F.

    Science.gov (United States)

    Tresguerres, E F; Nandadasa, H G; Pritchard, R H

    1975-01-01

    Data are presented suggesting that the most critical factor determining whether an Hfr dnaAts strain can synthesize deoxyribonucleic acid and form colonies at temperatures that are nonpermissive for corresponding F- strains is neither the site of insertion of F nor the presence of additional mutations in the F particle or the chromosome; it is whether the particle is capable of autonomous replication at the temperature used. Consequently, suppression of the DnaA phenotype in Hfr strains occurs at 40 C but not, in most of them, at 42 C without the occurrence of additional mutations. The site of insertion of F may also be important since it is shown that in one Hfr dnaA strain partial suppression does occur at 42 C. In addition, it is shown that strains exhibiting suppression by integration of F at 40 C on minimal agar plates do not do so at this temperature on nutrient agar plates. PMID:1089635

  19. Membrane and integrative nuclear fibroblastic growth factor receptor (FGFR) regulation of FGF-23.

    Science.gov (United States)

    Han, Xiaobin; Xiao, Zhousheng; Quarles, L Darryl

    2015-04-17

    Fibroblastic growth factor receptor 1 (FGFR1) signaling pathways are implicated in the regulation of FGF-23 gene transcription, but the molecular pathways remain poorly defined. We used low molecular weight (LMW, 18 kDa) FGF-2 and high molecular weight (HMW) FGF-2 isoforms, which, respectively, activate cell surface FGF receptors and intranuclear FGFR1, to determine the roles of membrane FGFRs and integrative nuclear FGFR1 signaling (INFS) in the regulation of FGF-23 gene transcription in osteoblasts. We found that LMW-FGF-2 induced NFAT and Ets1 binding to conserved cis-elements in the proximal FGF-23 promoter and stimulated FGF-23 promoter activity through PLCγ/calcineurin/NFAT and MAPK pathways in SaOS-2 and MC3T3-E1 osteoblasts. In contrast, HMW-FGF-2 stimulated FGF-23 promoter activity in osteoblasts through a cAMP-dependent binding of FGFR1 and cAMP-response element-binding protein (CREB) to a conserved cAMP response element (CRE) contiguous with the NFAT binding site in the FGF-23 promoter. Mutagenesis of the NFAT and CRE binding sites, respectively, inhibited the effects of LMW-FGF-2 and HMW-FGF-23 to stimulate FGF-23 promoter activity. FGF-2 activation of both membrane FGFRs and INFS-dependent FGFR1 pathways may provide a means to integrate systemic and local regulation of FGF-23 transcription under diverse physiological and pathological conditions.

  20. Success Factors in Integrated Natural Resource Management R&D: Lessons from Practice

    Directory of Open Access Journals (Sweden)

    Jürgen Hagmann

    2002-01-01

    Full Text Available This paper analyzes integrated natural resource management (INRM lessons and success factors based on a practical case study over more than 10 years in Zimbabwe. The work was geared toward enhancing the adaptive management capacity of the stakeholders in their resource-use systems. One main result was the development and institutionalization of an approach for participatory and integrated NRM research and extension. The INRM approach described is grounded in a learning paradigm and a combination of theories: the constructivist perspective to development, systemic intervention, and learning process approaches. Participatory action research and experiential learning, in which researchers engage themselves as actors rather than neutral analysts in an R&D process to explore the livelihood system and develop appropriate solutions together with the resource users, has shown high potential. However, this should be guided by a clear strategy, impact orientation, and high-quality process facilitation at different levels. The case study revealed the importance of a "reflective practitioner" approach by all actors. More effective response to the challenges of increasing complexity in NRM requires a shift in thinking from the linearity of research-extension-farmer to alternative, multiple-actor institutional arrangements and innovation systems. To overcome the weak attribution of research outcomes to actual impact, it also suggests an alternative to conventional impact assessment in INRM R&D interventions.

  1. Transcriptional and Bioinformatic Analysis Provide a Relationship between Host Response Changes to Marek’s Disease Viruses Infection and an Integrated Long Terminal Repeat

    Directory of Open Access Journals (Sweden)

    Ning eCui

    2016-04-01

    Full Text Available GX0101, Marek’s disease virus (MDV strain with a long terminal repeat (LTR insert of reticuloendotheliosis virus (REV, was isolated from CVI988/Rispens vaccinated birds showing tumors. We have constructed a LTR deleted strain GX0101∆LTR in our previous study. To compare the host responses to GX0101 and GX0101∆LTR, chicken embryo fibroblasts (CEF cells were infected with two MDV strains and a gene-chip containing chicken genome was employed to examine gene transcription changes in host cells in the present study. Of the 42 368 chicken transcripts on the chip, there were 2199 genes that differentially expressed in CEF infected with GX0101 compared to GX0101∆LTR significantly. Differentially expressed genes were distributed to 25 possible gene networks according to their intermolecular connections and were annotated to 56 pathways. The insertion of REV LTR showed the greatest influence on cancer formation and metastasis, followed with immune changes, atherosclerosis and nervous system disorders in MDV-infected CEF cells. Based on these bio functions, GX0101 infection was predicated with a greater growth and survival inhibition but lower oncogenicity in chickens than GX0101∆LTR, at least in the acute phase of infection. In summary, the insertion of REV LTR altered the expression of host genes in response to MDV infection, possibly resulting in novel phenotypic properties in chickens. Our study has provided the evidence of retroviral insertional changes of host responses to herpesvirus infection for the first time, which will promote to elucidation of the possible relationship between the LTR insertion and the observed phenotypes.

  2. Human factors considerations of IR sensors for the Canadian Integrated Soldier System Project (ISSP)

    Science.gov (United States)

    Frim, John; Bossi, Linda; Tack, Dave

    2009-05-01

    The Integrated Soldier System Project (ISSP) is the cornerstone of Canada's future soldier modernization effort, which seeks to "significantly enhance tactical level individual and team Lethality, Mobility and C4I performance in the complex, network-enabled, command-centric, effects-based digitized battlespace." This capital acquisition project is supported by a number of R&D Technology Demonstration Projects within Defence R&D Canada. Several of these projects focus on the human factors aspects of future technologies, such as IR sensors. The Soldier Information Requirements Technology Demonstration (SIREQ TD) project examined the performance impact of NVGs, LWIR imaging systems, and fused systems (both optical and digital fusion) on target detection, recognition and identification. NVGs were shown to provide good identification performance while LWIR systems excelled in detection tasks. Fused systems show promise of augmenting the respective stand alone capabilities of each sensor type, but more work is required to optimize fusion algorithms. The Soldier Integrated Headwear Technology Demonstration (SIHS TD) project is looking at the human factors aspects of mounting a range of vision enhancement sensors on a helmet, including optimal placement of both sensors and displays with respect to center of mass, total head borne weight, and visual offset and parallax issues. Overall headwear system weight should be less than 2.5 kg, and if an offset from the eye is required then a horizontal offset (vice vertical or oblique) of the sensor appears most acceptable. These findings have implications on the design of future IR and fused sensor systems for dismounted soldiers.

  3. Human Factors, Habitability and Environmental Health and the Human Integration Design Handbook. Volume 2

    Science.gov (United States)

    Houbec, Keith; Tillman, Barry; Connolly, Janis

    2010-01-01

    For decades, Space Life Sciences and NASA as an Agency have considered NASA-STD-3000, Man-Systems Integration Standards, a significant contribution to human spaceflight programs and to human-systems integration in general. The document has been referenced in numerous design standards both within NASA and by organizations throughout the world. With research program and project results being realized, advances in technology and new information in a variety of topic areas now available, the time arrived to update this extensive suite of requirements and design information. During the past several years, a multi-NASA center effort has been underway to write the update to NASA-STD-3000 with standards and design guidance that would be applicable to all future human spaceflight programs. NASA-STD-3001 - Volumes 1 and 2 - and the Human Integration Design Handbook (HIDH) were created. Volume 1, Crew Health, establishes NASA s spaceflight crew health standards for the pre-flight, in-flight, and post-flight phases of human spaceflight. Volume 2, Human Factors, Habitability and Environmental Health, focuses on the requirements of human-system integration and how the human crew interacts with other systems, and how the human and the system function together to accomplish the tasks for mission success. The HIDH is a compendium of human spaceflight history and knowledge, and provides useful background information and research findings. And as the HIDH is a stand-alone companion to the Standards, the maintenance of the document has been streamlined. This unique and flexible approach ensures that the content is current and addresses the fundamental advances of human performance and human capabilities and constraints research. Current work focuses on the development of new sections of Volume 2 and collecting updates to the HIDH. The new sections in development expand the scope of the standard and address mission operations and support operations. This effort is again collaboration

  4. Integral emission factors for methane determined using urban flux measurements and local-scale inverse models

    Science.gov (United States)

    Christen, Andreas; Johnson, Mark; Molodovskaya, Marina; Ketler, Rick; Nesic, Zoran; Crawford, Ben; Giometto, Marco; van der Laan, Mike

    2013-04-01

    The most important long-lived greenhouse gas (LLGHG) emitted during combustion of fuels is carbon dioxide (CO2), however also traces of the LLGHGs methane (CH4) and nitrous oxide (N2O) are released, the quantities of which depend largely on the conditions of the combustion process. Emission factors determine the mass of LLGHGs emitted per energy used (or kilometre driven for cars) and are key inputs for bottom-up emission modelling. Emission factors for CH4 are typically determined in the laboratory or on a test stand for a given combustion system using a small number of samples (vehicles, furnaces), yet associated with larger uncertainties when scaled to entire fleets. We propose an alternative, different approach - Can integrated emission factors be independently determined using direct micrometeorological flux measurements over an urban surface? If so, do emission factors determined from flux measurements (top-down) agree with up-scaled emission factors of relevant combustion systems (heating, vehicles) in the source area of the flux measurement? Direct flux measurements of CH4 were carried out between February and May, 2012 over a relatively densely populated, urban surface in Vancouver, Canada by means of eddy covariance (EC). The EC-system consisted of an ultrasonic anemometer (CSAT-3, Campbell Scientific Inc.) and two open-path infrared gas analyzers (Li7500 and Li7700, Licor Inc.) on a tower at 30m above the surface. The source area of the EC system is characterised by a relative homogeneous morphometry (5.3m average building height), but spatially and temporally varying emission sources, including two major intersecting arterial roads (70.000 cars drive through the 50% source area per day) and seasonal heating in predominantly single-family houses (natural gas). An inverse dispersion model (turbulent source area model), validated against large eddy simulations (LES) of the urban roughness sublayer, allows the determination of the spatial area that

  5. Host genetic and environmental effects on mouse intestinal microbiota.

    Science.gov (United States)

    Campbell, James H; Foster, Carmen M; Vishnivetskaya, Tatiana; Campbell, Alisha G; Yang, Zamin K; Wymore, Ann; Palumbo, Anthony V; Chesler, Elissa J; Podar, Mircea

    2012-11-01

    The mammalian gut harbors complex and variable microbial communities, across both host phylogenetic space and conspecific individuals. A synergy of host genetic and environmental factors shape these communities and account for their variability, but their individual contributions and the selective pressures involved are still not well understood. We employed barcoded pyrosequencing of V1-2 and V4 regions of bacterial small subunit ribosomal RNA genes to characterize the effects of host genetics and environment on cecum assemblages in 10 genetically distinct, inbred mouse strains. Eight of these strains are the foundation of the Collaborative Cross (CC), a panel of mice derived from a genetically diverse set of inbred founder strains, designed specifically for complex trait analysis. Diversity of gut microbiota was characterized by complementing phylogenetic and distance-based, sequence-clustering approaches. Significant correlations were found between the mouse strains and their gut microbiota, reflected by distinct bacterial communities. Cohabitation and litter had a reduced, although detectable effect, and the microbiota response to these factors varied by strain. We identified bacterial phylotypes that appear to be discriminative and strain-specific to each mouse line used. Cohabitation of different strains of mice revealed an interaction of host genetic and environmental factors in shaping gut bacterial consortia, in which bacterial communities became more similar but retained strain specificity. This study provides a baseline analysis of intestinal bacterial communities in the eight CC progenitor strains and will be linked to integrated host genotype, phenotype and microbiota research on the resulting CC panel.

  6. Host Genetic and Environmental Effects on Mouse Cecum Microbiota

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, James H [ORNL; Foster, Carmen M [ORNL; Vishnivetskaya, Tatiana A [ORNL; Campbell, Alisha G [ORNL; Yang, Zamin Koo [ORNL; Wymore, Ann [ORNL; Palumbo, Anthony Vito [ORNL; Podar, Mircea [ORNL

    2012-01-01

    The mammalian gut harbors complex and variable microbial communities, across both host phylogenetic space and conspecific individuals. A synergy of host genetic and environmental factors shape these communities and account for their variability, but their individual contributions and the selective pressures involved are still not well understood. We employed barcoded pyrosequencing of V1-2 and V4 regions of bacterial small subunit ribosomal RNA genes to characterize the effects of host genetics and environment on cecum assemblages in 10 genetically distinct, inbred mouse strains. Eight of these strains are the foundation of the Collaborative Cross (CC), a panel of mice derived from a genetically diverse set of inbred founder strains, designed specifically for complex trait analysis. Diversity of gut microbiota was characterized by complementing phylogenetic and distance-based, sequence-clustering approaches. Significant correlations were found between the mouse strains and their gut microbiota, reflected by distinct bacterial communities. Cohabitation and litter had a reduced, although detectable effect, and the microbiota response to these factors varied by strain. We identified bacterial phylotypes that appear to be discriminative and strain-specific to each mouse line used. Cohabitation of different strains of mice revealed an interaction of host genetic and environmental factors in shaping gut bacterial consortia, in which bacterial communities became more similar but retained strain specificity. This study provides a baseline analysis of intestinal bacterial communities in the eight CC progenitor strains and will be linked to integrated host genotype, phenotype and microbiota research on the resulting CC panel.

  7. Identification of the minimal connected network of transcription factors by transcriptomic and genomic data integration.

    Science.gov (United States)

    Essaghir, Ahmed

    2014-01-01

    Thanks to high-throughput experiments, biological conditions can be investigated at both the entire genomic and transcriptomic levels. In addition, protein-protein interaction (PPI) data are widely available for well-studied organisms, such as human. In this chapter, we will present an integrative approach that makes use of these data to find the PPI module involving the key regulated transcription factors shared by a number of given conditions. These conditions could be for instance different cancer types. Briefly, for the studied conditions, we need to identify commonly affected chromosomal regions subjected to copy number alterations together with the identification of differentially expressed list of genes in each condition. Transcription factor activity will be inferred from these regulated gene lists. Then, we will define TFs, for which the activity could be explained by an associative effect of both loci copy number alteration and gene expression levels of their coding genes. PPI networks could be mined, afterwards, using appropriate algorithms to find the significant module that connect those TFs together. This module could be viewed as the minimal connected network of TFs, the regulation of which is shared between the investigated conditions.

  8. Psychosocial biomarker research: integrating social, emotional and economic factors into population studies of aging and health.

    Science.gov (United States)

    Steptoe, Andrew

    2011-04-01

    There are complex reciprocal relationships between health and social, emotional and economic factors in aging populations. Social and affective neurosciences are rapidly developing an understanding of the mechanisms underlying these phenomena using sophisticated behavioural, neuroimaging and psychophysiological methods. These techniques are often complex and expensive, so are generally used in relatively small selected samples rather than in large-scale cohort studies. However, an understanding of the significance of these processes in health and well-being depends on integrating findings from social and affective neuroscience into population-level studies. The aim of this article is to describe how a population perspective on the determinants of health and well-being in old age articulates with the agenda of social, affective and economic neuroscience, particularly through the application of psychosocial biomarker research. Social and affective neuroscience and epidemiological approaches provide complementary research strategies for understanding the mechanisms linking social, emotional and economic factors with health risk. This will be illustrated primarily from findings from two studies conducted at University College London, the Whitehall II Study and the English Longitudinal Study of Ageing.

  9. An integrative review of social and occupational factors influencing health and wellbeing.

    Science.gov (United States)

    Gallagher, MaryBeth; Muldoon, Orla T; Pettigrew, Judith

    2015-01-01

    Therapeutic approaches to health and wellbeing have traditionally assumed that meaningful activity or occupation contributes to health and quality of life. Within social psychology, everyday activities and practices that fill our lives are believed to be shaped by structural and systemic factors and in turn these practices can form the basis of social identities. In occupational therapy these everyday activities are called occupations. Occupations can be understood as a contextually bound synthesis of meaningful doing, being, belonging and becoming that influence health and wellbeing. We contend that an integrative review of occupational therapy and social psychology literature will enhance our ability to understand the relationship between social structures, identity and dimensions of occupation by elucidating how they inform one another, and how taken together they augment our understanding of health and wellbeing This review incorporates theoretical and empirical works purposively sampled from databases within EBSCO including CINAHL, psychINFO, psychArticles, and Web of Science. Search terms included: occupation, therapy, social psychology, occupational science, health, wellbeing, identity, structures and combinations of these terms. In presenting this review, we argue that doing, being and belonging may act as an important link to widely acknowledged relationships between social factors and health and wellbeing, and that interventions targeting individual change may be problematic.