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Sample records for host dh-ph domain

  1. The crystal structure of the RhoA-AKAP-Lbc DH-PH domain complex.

    PubMed

    Abdul Azeez, Kamal R; Knapp, Stefan; Fernandes, João M P; Klussmann, Enno; Elkins, Jonathan M

    2014-12-01

    The RhoGEF (Rho GTPase guanine-nucleotide-exchange factor) domain of AKAP-Lbc (A-kinase-anchoring protein-Lbc, also known as AKAP13) catalyses nucleotide exchange on RhoA and is involved in the development of cardiac hypertrophy. The RhoGEF activity of AKAP-Lbc has also been implicated in cancer. We have determined the X-ray crystal structure of the complex between RhoA-GDP and the AKAP-Lbc RhoGEF [DH (Dbl-homologous)-PH (pleckstrin homology)] domain to 2.1 Å (1 Å = 0.1 nm) resolution. The structure reveals important differences compared with related RhoGEF proteins such as leukaemia-associated RhoGEF. Nucleotide-exchange assays comparing the activity of the DH-PH domain to the DH domain alone showed no role for the PH domain in nucleotide exchange, which is explained by the RhoA-AKAP-Lbc structure. Comparison with a structure of the isolated AKAP-Lbc DH domain revealed a change in conformation of the N-terminal 'GEF switch' region upon binding to RhoA. Isothermal titration calorimetry showed that AKAP-Lbc has only micromolar affinity for RhoA, which combined with the presence of potential binding pockets for small molecules on AKAP-Lbc, raises the possibility of targeting AKAP-Lbc with GEF inhibitors.

  2. The N-Terminal DH-PH Domain of Trio Induces Cell Spreading and Migration by Regulating Lamellipodia Dynamics in a Rac1-Dependent Fashion

    PubMed Central

    van Rijssel, Jos; Hoogenboezem, Mark; Wester, Lynn; Hordijk, Peter L.; Van Buul, Jaap D.

    2012-01-01

    The guanine-nucleotide exchange factor Trio encodes two DH-PH domains that catalyze nucleotide exchange on Rac1, RhoG and RhoA. The N-terminal DH-PH domain is known to activate Rac1 and RhoG, whereas the C-terminal DH-PH domain can activate RhoA. The current study shows that the N-terminal DH-PH domain, upon expression in HeLa cells, activates Rac1 and RhoG independently from each other. In addition, we show that the flanking SH3 domain binds to the proline-rich region of the C-terminus of Rac1, but not of RhoG. However, this SH3 domain is not required for Rac1 or RhoG GDP-GTP exchange. Rescue experiments in Trio-shRNA-expressing cells showed that the N-terminal DH-PH domain of Trio, but not the C-terminal DH-PH domain, restored fibronectin-mediated cell spreading and migration defects that are observed in Trio-silenced cells. Kymograph analysis revealed that the N-terminal DH-PH domain, independent of its SH3 domain, controls the dynamics of lamellipodia. Using siRNA against Rac1 or RhoG, we found that Trio-D1-induced lamellipodia formation required Rac1 but not RhoG expression. Together, we conclude that the GEF Trio is responsible for lamellipodia formation through its N-terminal DH-PH domain in a Rac1-dependent manner during fibronectin-mediated spreading and migration. PMID:22238672

  3. The solution structure and dynamics of the DH-PH module of PDZRhoGEF in isolation and in complex with nucleotide-free RhoA

    PubMed Central

    Cierpicki, Tomasz; Bielnicki, Jakub; Zheng, Meiying; Gruszczyk, Jakub; Kasterka, Marta; Petoukhov, Maxim; Zhang, Aming; Fernandez, Erik J; Svergun, Dmitri I; Derewenda, Urszula; Bushweller, John H; Derewenda, Zygmunt S

    2009-01-01

    The DH-PH domain tandems of Dbl-homology guanine nucleotide exchange factors catalyze the exchange of GTP for GDP in Rho-family GTPases, and thus initiate a wide variety of cellular signaling cascades. Although several crystal structures of complexes of DH-PH tandems with cognate, nucleotide free Rho GTPases are known, they provide limited information about the dynamics of the complex and it is not clear how accurately they represent the structures in solution. We used a complementary combination of nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS), and hydrogen-deuterium exchange mass spectrometry (DXMS) to study the solution structure and dynamics of the DH-PH tandem of RhoA-specific exchange factor PDZRhoGEF, both in isolation and in complex with nucleotide free RhoA. We show that in solution the DH-PH tandem behaves as a rigid entity and that the mutual disposition of the DH and PH domains remains identical within experimental error to that seen in the crystal structure of the complex, thus validating the latter as an accurate model of the complex in vivo. We also show that the nucleotide-free RhoA exhibits elevated dynamics when in complex with DH-PH, a phenomenon not observed in the crystal structure, presumably due to the restraining effects of crystal contacts. The complex is readily and rapidly dissociated in the presence of both GDP and GTP nucleotides, with no evidence of intermediate ternary complexes. PMID:19670212

  4. Domain Name and Site Hosting Preferences: Empirical Evidence.

    ERIC Educational Resources Information Center

    O'Daniel, Thomas; Wai, Chew Kok

    2000-01-01

    Describes a study of commercial Web sites that analyzed the correlation between domain names and regional allocation of IP addresses. Explains Internet addresses and names, discusses results which showed that domain names don't always correspond to the location of the host, and offers suggestions for international sampling. (Contains 25…

  5. Domain Name and Site Hosting Preferences: Empirical Evidence.

    ERIC Educational Resources Information Center

    O'Daniel, Thomas; Wai, Chew Kok

    2000-01-01

    Describes a study of commercial Web sites that analyzed the correlation between domain names and regional allocation of IP addresses. Explains Internet addresses and names, discusses results which showed that domain names don't always correspond to the location of the host, and offers suggestions for international sampling. (Contains 25…

  6. Effectors of animal and plant pathogens use a common domain to bind host phosphoinositides.

    PubMed

    Salomon, Dor; Guo, Yirui; Kinch, Lisa N; Grishin, Nick V; Gardner, Kevin H; Orth, Kim

    2013-01-01

    Bacterial Type III Secretion Systems deliver effectors into host cells to manipulate cellular processes to the advantage of the pathogen. Many host targets of these effectors are found on membranes. Therefore, to identify their targets, effectors often use specialized membrane-localization domains to localize to appropriate host membranes. However, the molecular mechanisms used by many domains are unknown. Here we identify a conserved bacterial phosphoinositide-binding domain (BPD) that is found in functionally diverse Type III effectors of both plant and animal pathogens. We show that members of the BPD family functionally bind phosphoinositides and mediate localization to host membranes. Moreover, NMR studies reveal that the BPD of the newly identified Vibrio parahaemolyticus Type III effector VopR is unfolded in solution, but folds into a specific structure upon binding its ligand phosphatidylinositol-(4,5)-bisphosphate. Thus, our findings suggest a possible mechanism for promoting refolding of Type III effectors after delivery into host cells.

  7. Effectors of animal and plant pathogens use a common domain to bind host phosphoinositides

    PubMed Central

    Salomon, Dor; Guo, Yirui; Kinch, Lisa N.; Grishin, Nick V.; Gardner, Kevin H.; Orth, Kim

    2016-01-01

    Bacterial Type III Secretion Systems deliver effectors into host cells to manipulate cellular processes to the advantage of the pathogen. Many host targets of these effectors are found on membranes. Therefore, to identify their targets, effectors often use specialized membrane-localization domains to localize to appropriate host membranes. However, the molecular mechanisms used by many domains are unknown. Here we identify a conserved bacterial phosphoinositide-binding domain (BPD) that is found in functionally diverse Type III effectors of both plant and animal pathogens. We show that members of the BPD family functionally bind phosphoinositides and mediate localization to host membranes. Moreover, NMR studies reveal that the BPD of the newly identified Vibrio parahaemolyticus Type III effector VopR is unfolded in solution, but folds into a specific structure upon binding its ligand phosphatidylinositol-(4,5)-bisphosphate. Thus, our findings suggest a possible mechanism for promoting refolding of Type III effectors after delivery into host cells. PMID:24346350

  8. Viral Proteins Acquired from a Host Converge to Simplified Domain Architectures

    PubMed Central

    Rappoport, Nadav; Linial, Michal

    2012-01-01

    The infection cycle of viruses creates many opportunities for the exchange of genetic material with the host. Many viruses integrate their sequences into the genome of their host for replication. These processes may lead to the virus acquisition of host sequences. Such sequences are prone to accumulation of mutations and deletions. However, in rare instances, sequences acquired from a host become beneficial for the virus. We searched for unexpected sequence similarity among the 900,000 viral proteins and all proteins from cellular organisms. Here, we focus on viruses that infect metazoa. The high-conservation analysis yielded 187 instances of highly similar viral-host sequences. Only a small number of them represent viruses that hijacked host sequences. The low-conservation sequence analysis utilizes the Pfam family collection. About 5% of the 12,000 statistical models archived in Pfam are composed of viral-metazoan proteins. In about half of Pfam families, we provide indirect support for the directionality from the host to the virus. The other families are either wrongly annotated or reflect an extensive sequence exchange between the viruses and their hosts. In about 75% of cross-taxa Pfam families, the viral proteins are significantly shorter than their metazoan counterparts. The tendency for shorter viral proteins relative to their related host proteins accounts for the acquisition of only a fragment of the host gene, the elimination of an internal domain and shortening of the linkers between domains. We conclude that, along viral evolution, the host-originated sequences accommodate simplified domain compositions. We postulate that the trimmed proteins act by interfering with the fundamental function of the host including intracellular signaling, post-translational modification, protein-protein interaction networks and cellular trafficking. We compiled a collection of hijacked protein sequences. These sequences are attractive targets for manipulation of viral

  9. A Novel Extracellular Metallopeptidase Domain Shared by Animal Host-Associated Mutualistic and Pathogenic Microbes

    PubMed Central

    Nakjang, Sirintra; Ndeh, Didier A.; Wipat, Anil; Bolam, David N.; Hirt, Robert P.

    2012-01-01

    The mucosal microbiota is recognised as an important factor for our health, with many disease states linked to imbalances in the normal community structure. Hence, there is considerable interest in identifying the molecular basis of human-microbe interactions. In this work we investigated the capacity of microbes to thrive on mucosal surfaces, either as mutualists, commensals or pathogens, using comparative genomics to identify co-occurring molecular traits. We identified a novel domain we named M60-like/PF13402 (new Pfam entry PF13402), which was detected mainly among proteins from animal host mucosa-associated prokaryotic and eukaryotic microbes ranging from mutualists to pathogens. Lateral gene transfers between distantly related microbes explained their shared M60-like/PF13402 domain. The novel domain is characterised by a zinc-metallopeptidase-like motif and is distantly related to known viral enhancin zinc-metallopeptidases. Signal peptides and/or cell surface anchoring features were detected in most microbial M60-like/PF13402 domain-containing proteins, indicating that these proteins target an extracellular substrate. A significant subset of these putative peptidases was further characterised by the presence of associated domains belonging to carbohydrate-binding module family 5/12, 32 and 51 and other glycan-binding domains, suggesting that these novel proteases are targeted to complex glycoproteins such as mucins. An in vitro mucinase assay demonstrated degradation of mammalian mucins by a recombinant form of an M60-like/PF13402-containing protein from the gut mutualist Bacteroides thetaiotaomicron. This study reveals that M60-like domains are peptidases targeting host glycoproteins. These peptidases likely play an important role in successful colonisation of both vertebrate mucosal surfaces and the invertebrate digestive tract by both mutualistic and pathogenic microbes. Moreover, 141 entries across various peptidase families described in the MEROPS

  10. Analysis of functional domains of the host cell factor involved in VP16 complex formation.

    PubMed

    Hughes, T A; La Boissière, S; O'Hare, P

    1999-06-04

    We present biochemical analyses of the regions of the host cell factor (HCF) involved in VP16 complex formation and in the association between the N- and C-terminal domains of HCF itself. We show that the kelch repeat region of HCF (residues 1-380) is sufficient for VP16 complex formation, but that residues C-terminal to the repeats (positions 381-450) interfere with this activity. However, these latter residues are required for the interaction between the N- and C-terminal regions of HCF. The extreme C-terminal region of HCF, corresponding to an area of strong conservation with a Caenorhabditis elegans homologue, is sufficient for interaction with the N-terminal region. These results are discussed with respect to possible differences in the roles of HCF in VP16 activity versus its normal cellular function.

  11. Persistence of Functional Protein Domains in Mycoplasma Species and their Role in Host Specificity and Synthetic Minimal Life

    PubMed Central

    Kamminga, Tjerko; Koehorst, Jasper J.; Vermeij, Paul; Slagman, Simen-Jan; Martins dos Santos, Vitor A. P.; Bijlsma, Jetta J. E.; Schaap, Peter J.

    2017-01-01

    Mycoplasmas are the smallest self-replicating organisms and obligate parasites of a specific vertebrate host. An in-depth analysis of the functional capabilities of mycoplasma species is fundamental to understand how some of simplest forms of life on Earth succeeded in subverting complex hosts with highly sophisticated immune systems. In this study we present a genome-scale comparison, focused on identification of functional protein domains, of 80 publically available mycoplasma genomes which were consistently re-annotated using a standardized annotation pipeline embedded in a semantic framework to keep track of the data provenance. We examined the pan- and core-domainome and studied predicted functional capability in relation to host specificity and phylogenetic distance. We show that the pan- and core-domainome of mycoplasma species is closed. A comparison with the proteome of the “minimal” synthetic bacterium JCVI-Syn3.0 allowed us to classify domains and proteins essential for minimal life. Many of those essential protein domains, essential Domains of Unknown Function (DUFs) and essential hypothetical proteins are not persistent across mycoplasma genomes suggesting that mycoplasma species support alternative domain configurations that bypass their essentiality. Based on the protein domain composition, we could separate mycoplasma species infecting blood and tissue. For selected genomes of tissue infecting mycoplasmas, we could also predict whether the host is ruminant, pig or human. Functionally closely related mycoplasma species, which have a highly similar protein domain repertoire, but different hosts could not be separated. This study provides a concise overview of the functional capabilities of mycoplasma species, which can be used as a basis to further understand host-pathogen interaction or to design synthetic minimal life. PMID:28224116

  12. SET domain-mediated lysine methylation in lower organisms regulates growth and transcription in hosts.

    PubMed

    Nwasike, Chukwuazam; Ewert, Sinead; Jovanovic, Srdan; Haider, Shozeb; Mujtaba, Shiraz

    2016-07-01

    Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain-mediated lysine methylation, one of the major epigenetic marks, has been found to regulate chromatin-mediated gene transcription. Published studies have established further that methylation is not restricted to nuclear proteins but is involved in many cellular processes, including growth, differentiation, immune regulation, and cancer progression. The biological complexity of lysine methylation emerges from its capacity to cause gene activation or gene repression owing to the specific position of methylated-lysine moieties on the chromatin. Accumulating evidence suggests that despite the absence of chromatin, viruses and prokaryotes also express SET proteins, although their functional roles remain relatively less investigated. One possibility could be that SET proteins in lower organisms have more than one biological function, for example, in regulating growth or in manipulating host transcription machinery in order to establish infection. Thus, elucidating the role of an SET protein in host-pathogen interactions requires a thorough understanding of their functions. This review discusses the biological role of lysine methylation in prokaryotes and lower eukaryotes, as well as the underlying structural complexity and functional diversity of SET proteins. © 2016 New York Academy of Sciences.

  13. Characteristics of ferroelectric-ferroelastic domains in Néel-type skyrmion host GaV4S8

    NASA Astrophysics Data System (ADS)

    Butykai, Ádám; Bordács, Sándor; Kézsmárki, István; Tsurkan, Vladimir; Loidl, Alois; Döring, Jonathan; Neuber, Erik; Milde, Peter; Kehr, Susanne C.; Eng, Lukas M.

    2017-03-01

    GaV4S8 is a multiferroic semiconductor hosting Néel-type magnetic skyrmions dressed with electric polarization. At Ts = 42 K, the compound undergoes a structural phase transition of weakly first-order, from a non-centrosymmetric cubic phase at high temperatures to a polar rhombohedral structure at low temperatures. Below Ts, ferroelectric domains are formed with the electric polarization pointing along any of the four <111> axes. Although in this material the size and the shape of the ferroelectric-ferroelastic domains may act as important limiting factors in the formation of the Néel-type skyrmion lattice emerging below TC = 13 K, the characteristics of polar domains in GaV4S8 have not been studied yet. Here, we report on the inspection of the local-scale ferroelectric domain distribution in rhombohedral GaV4S8 using low-temperature piezoresponse force microscopy. We observed mechanically and electrically compatible lamellar domain patterns, where the lamellae are aligned parallel to the (100)-type planes with a typical spacing between 100 nm–1.2 μm. Since the magnetic pattern, imaged by atomic force microscopy using a magnetically coated tip, abruptly changes at the domain boundaries, we expect that the control of ferroelectric domain size in polar skyrmion hosts can be exploited for the spatial confinement and manipulation of Néel-type skyrmions.

  14. Characteristics of ferroelectric-ferroelastic domains in Néel-type skyrmion host GaV4S8

    PubMed Central

    Butykai, Ádám; Bordács, Sándor; Kézsmárki, István; Tsurkan, Vladimir; Loidl, Alois; Döring, Jonathan; Neuber, Erik; Milde, Peter; Kehr, Susanne C.; Eng, Lukas M.

    2017-01-01

    GaV4S8 is a multiferroic semiconductor hosting Néel-type magnetic skyrmions dressed with electric polarization. At Ts = 42 K, the compound undergoes a structural phase transition of weakly first-order, from a non-centrosymmetric cubic phase at high temperatures to a polar rhombohedral structure at low temperatures. Below Ts, ferroelectric domains are formed with the electric polarization pointing along any of the four 〈111〉 axes. Although in this material the size and the shape of the ferroelectric-ferroelastic domains may act as important limiting factors in the formation of the Néel-type skyrmion lattice emerging below TC = 13 K, the characteristics of polar domains in GaV4S8 have not been studied yet. Here, we report on the inspection of the local-scale ferroelectric domain distribution in rhombohedral GaV4S8 using low-temperature piezoresponse force microscopy. We observed mechanically and electrically compatible lamellar domain patterns, where the lamellae are aligned parallel to the (100)-type planes with a typical spacing between 100 nm–1.2 μm. Since the magnetic pattern, imaged by atomic force microscopy using a magnetically coated tip, abruptly changes at the domain boundaries, we expect that the control of ferroelectric domain size in polar skyrmion hosts can be exploited for the spatial confinement and manipulation of Néel-type skyrmions. PMID:28294193

  15. A host deficiency of discoidin domain receptor 2 (DDR2) inhibits both tumour angiogenesis and metastasis.

    PubMed

    Zhang, Shuya; Bu, Xin; Zhao, Hu; Yu, Jiangtian; Wang, Yingmei; Li, Di; Zhu, Chuchao; Zhu, Tong; Ren, Tingting; Liu, Xinping; Yao, Libo; Su, Jin

    2014-03-01

    Discoidin domain receptor 2 (DDR2) is a unique receptor tyrosine kinase (RTK) that signals in response to collagen binding and is implicated in tumour malignant phenotypes such as invasion and metastasis. Although it has been reported that DDR2 expression is up-regulated in activated endothelial cells (ECs), functional studies are lacking. Herein, we found that enforced expression of DDR2 promoted proliferation, migration and tube formation of primary human umbilical vein endothelial cells (HUVECs). The results of immunohistochemical analysis showed a strikingly high level of DDR2 in human tumour ECs. Most significantly, we discovered that a host deficiency of DDR2 inhibits subcutaneous angiogenesis induced by either VEGF or tumour cells. In addition, the remaining tumour vessels in DDR2-deficient mice exhibit some normalized properties. These vascular phenotypes are accompanied by the up-regulation of anti-angiogenic genes and down-regulation of pro-angiogenic genes, as well as by alleviated tumour hypoxia. By use of a tail vein metastasis model of melanoma, we uncovered that loss of stromal DDR2 also suppresses tumour metastasis to the lung. Hence, our current data disclose a new mechanism by which DDR2 affects tumour progression, and may strengthen the feasibility of targeting DDR2 as an anticancer strategy.

  16. LysM domains mediate lipochitin–oligosaccharide recognition and Nfr genes extend the symbiotic host range

    PubMed Central

    Radutoiu, Simona; Madsen, Lene H; Madsen, Esben B; Jurkiewicz, Anna; Fukai, Eigo; Quistgaard, Esben M H; Albrektsen, Anita S; James, Euan K; Thirup, Søren; Stougaard, Jens

    2007-01-01

    Legume–Rhizobium symbiosis is an example of selective cell recognition controlled by host/non-host determinants. Individual bacterial strains have a distinct host range enabling nodulation of a limited set of legume species and vice versa. We show here that expression of Lotus japonicus Nfr1 and Nfr5 Nod-factor receptor genes in Medicago truncatula and L. filicaulis, extends their host range to include bacterial strains, Mesorhizobium loti or DZL, normally infecting L. japonicus. As a result, the symbiotic program is induced, nodules develop and infection threads are formed. Using L. japonicus mutants and domain swaps between L. japonicus and L. filicaulis NFR1 and NFR5, we further demonstrate that LysM domains of the NFR1 and NFR5 receptors mediate perception of the bacterial Nod-factor signal and that recognition depends on the structure of the lipochitin–oligosaccharide Nod-factor. We show that a single amino-acid variation in the LysM2 domain of NFR5 changes recognition of the Nod-factor synthesized by the DZL strain and suggests a possible binding site for bacterial lipochitin–oligosaccharide signal molecules. PMID:17690687

  17. LysM domains mediate lipochitin-oligosaccharide recognition and Nfr genes extend the symbiotic host range.

    PubMed

    Radutoiu, Simona; Madsen, Lene H; Madsen, Esben B; Jurkiewicz, Anna; Fukai, Eigo; Quistgaard, Esben M H; Albrektsen, Anita S; James, Euan K; Thirup, Søren; Stougaard, Jens

    2007-09-05

    Legume-Rhizobium symbiosis is an example of selective cell recognition controlled by host/non-host determinants. Individual bacterial strains have a distinct host range enabling nodulation of a limited set of legume species and vice versa. We show here that expression of Lotus japonicus Nfr1 and Nfr5 Nod-factor receptor genes in Medicago truncatula and L. filicaulis, extends their host range to include bacterial strains, Mesorhizobium loti or DZL, normally infecting L. japonicus. As a result, the symbiotic program is induced, nodules develop and infection threads are formed. Using L. japonicus mutants and domain swaps between L. japonicus and L. filicaulis NFR1 and NFR5, we further demonstrate that LysM domains of the NFR1 and NFR5 receptors mediate perception of the bacterial Nod-factor signal and that recognition depends on the structure of the lipochitin-oligosaccharide Nod-factor. We show that a single amino-acid variation in the LysM2 domain of NFR5 changes recognition of the Nod-factor synthesized by the DZL strain and suggests a possible binding site for bacterial lipochitin-oligosaccharide signal molecules.

  18. Vaccinia Virus Immunomodulator A46: A Lipid and Protein-Binding Scaffold for Sequestering Host TIR-Domain Proteins

    PubMed Central

    Radakovics, Katharina; Smith, Terry K.; Bobik, Nina; Round, Adam; Djinović-Carugo, Kristina; Usón, Isabel

    2016-01-01

    Vaccinia virus interferes with early events of the activation pathway of the transcriptional factor NF-kB by binding to numerous host TIR-domain containing adaptor proteins. We have previously determined the X-ray structure of the A46 C-terminal domain; however, the structure and function of the A46 N-terminal domain and its relationship to the C-terminal domain have remained unclear. Here, we biophysically characterize residues 1–83 of the N-terminal domain of A46 and present the X-ray structure at 1.55 Å. Crystallographic phases were obtained by a recently developed ab initio method entitled ARCIMBOLDO_BORGES that employs tertiary structure libraries extracted from the Protein Data Bank; data analysis revealed an all β-sheet structure. This is the first such structure solved by this method which should be applicable to any protein composed entirely of β-sheets. The A46(1–83) structure itself is a β-sandwich containing a co-purified molecule of myristic acid inside a hydrophobic pocket and represents a previously unknown lipid-binding fold. Mass spectrometry analysis confirmed the presence of long-chain fatty acids in both N-terminal and full-length A46; mutation of the hydrophobic pocket reduced the lipid content. Using a combination of high resolution X-ray structures of the N- and C-terminal domains and SAXS analysis of full-length protein A46(1–240), we present here a structural model of A46 in a tetrameric assembly. Integrating affinity measurements and structural data, we propose how A46 simultaneously interferes with several TIR-domain containing proteins to inhibit NF-κB activation and postulate that A46 employs a bipartite binding arrangement to sequester the host immune adaptors TRAM and MyD88. PMID:27973613

  19. Magnetic Domain Walls as Hosts of Spin Superfluids and Generators of Skyrmions

    NASA Astrophysics Data System (ADS)

    Kim, Se Kwon; Tserkovnyak, Yaroslav

    2017-07-01

    A domain wall in a magnet with easy-axis anisotropy is shown to harbor spin superfluid associated with its spontaneous breaking of the U(1) spin-rotational symmetry. The spin superfluid is shown to have several topological properties, which are absent in conventional superfluids. First, the associated phase slips create and destroy Skyrmions to obey the conservation of the total Skyrmion charge, which allows us to use a domain wall as a generator and detector of Skyrmions. Second, the domain wall engenders the emergent magnetic flux for magnons along its length, which are proportional to the spin supercurrent flowing through it, and thereby provides a way to manipulate magnons. Third, the spin supercurrent can be driven by the magnon current traveling across it owing to the spin transfer between the domain wall and magnons, leading to the magnonic manipulation of the spin superfluid. The theory for superfluid spin transport within the domain wall is confirmed by numerical simulations.

  20. Domain analysis of symbionts and hosts (DASH) in a genome-wide survey of pathogenic human viruses

    PubMed Central

    2013-01-01

    Background In the coevolution of viruses and their hosts, viruses often capture host genes, gaining advantageous functions (e.g. immune system control). Identifying functional similarities shared by viruses and their hosts can help decipher mechanisms of pathogenesis and accelerate virus-targeted drug and vaccine development. Cellular homologs in viruses are usually documented using pairwise-sequence comparison methods. Yet, pairwise-sequence searches have limited sensitivity resulting in poor identification of divergent homologies. Results Methods based on profiles from multiple sequences provide a more sensitive alternative to identify similarities in host-pathogen systems. The present work describes a profile-based bioinformatics pipeline that we call the Domain Analysis of Symbionts and Hosts (DASH). DASH provides a web platform for the functional analysis of viral and host genomes. This study uses Human Herpesvirus 8 (HHV-8) as a model to validate the methodology. Our results indicate that HHV-8 shares at least 29% of its genes with humans (fourteen immunomodulatory and ten metabolic genes). DASH also suggests functions for fifty-one additional HHV-8 structural and metabolic proteins. We also perform two other comparative genomics studies of human viruses: (1) a broad survey of eleven viruses of disparate sizes and transcription strategies; and (2) a closer examination of forty-one viruses of the order Mononegavirales. In the survey, DASH detects human homologs in 4/5 DNA viruses. None of the non-retro-transcribing RNA viruses in the survey showed evidence of homology to humans. The order Mononegavirales are also non-retro-transcribing RNA viruses, however, and DASH found homology in 39/41 of them. Mononegaviruses display larger fractions of human similarities (up to 75%) than any of the other RNA or DNA viruses (up to 55% and 29% respectively). Conclusions We conclude that gene sharing probably occurs between humans and both DNA and RNA viruses, in viral

  1. N-Terminal Domain of Feline Calicivirus (FCV) Proteinase-Polymerase Contributes to the Inhibition of Host Cell Transcription

    PubMed Central

    Wu, Hongxia; Zu, Shaopo; Sun, Xue; Liu, Yongxiang; Tian, Jin; Qu, Liandong

    2016-01-01

    Feline Calicivirus (FCV) infection results in the inhibition of host protein synthesis, known as “shut-off”. However, the precise mechanism of shut-off remains unknown. Here, we found that the FCV strain 2280 proteinase-polymerase (PP) protein can suppress luciferase reporter gene expression driven by endogenous and exogenous promoters. Furthermore, we found that the N-terminal 263 aa of PP (PPN-263) determined its shut-off activity using the expression of truncated proteins. However, the same domain of the FCV strain F9 PP protein failed to inhibit gene expression. A comparison between strains 2280 and F9 indicated that Val27, Ala96 and Ala98 were key sites for the inhibition of host gene expression by strain 2280 PPN-263, and PPN-263 exhibited the ability to shut off host gene expression as long as it contained any two of the three amino acids. Because the N-terminus of the PP protein is required for its proteinase and shut-off activities, we investigated the ability of norovirus 3C-like proteins (3CLP) from the GII.4-1987 and -2012 isolates to interfere with host gene expression. The results showed that 3CLP from both isolates was able to shut off host gene expression, but 3CLP from GII.4-2012 had a stronger inhibitory activity than that from GII.4-1987. Finally, we found that 2280 PP and 3CLP significantly repressed reporter gene transcription but did not affect mRNA translation. Our results provide new insight into the mechanism of the FCV-mediated inhibition of host gene expression. PMID:27447663

  2. Envelope-binding domain in the cationic amino acid transporter determines the host range of ecotropic murine retroviruses.

    PubMed Central

    Albritton, L M; Kim, J W; Tseng, L; Cunningham, J M

    1993-01-01

    Infection of rodent cells by ecotropic type C retroviruses requires the expression of a cationic amino acid transporter composed of multiple membrane-spanning domains. By exchanging portions of cDNAs encoding the permissive mouse and nonpermissive human transporters and examining their abilities to specify virus infection upon expression in human 293 cells, we have identified the amino acid residues in the extracellular loop connecting the fifth and sixth membrane-spanning segments of the mouse transporter that are required for both envelope gp70 binding and infection. These findings strongly suggest that the role of the mouse transporter in determining infection is to provide an envelope-binding site. This role is analogous to those of host membrane proteins composed of a single membrane-spanning domain that serve as binding proteins or receptors for other enveloped viruses such as human immunodeficiency virus, Epstein-Barr virus, and murine and human coronaviruses. PMID:8445722

  3. Triatoma infestans Calreticulin: Gene Cloning and Expression of a Main Domain That Interacts with the Host Complement System.

    PubMed

    Weinberger, Katherine; Collazo, Norberto; Aguillón, Juan Carlos; Molina, María Carmen; Rosas, Carlos; Peña, Jaime; Pizarro, Javier; Maldonado, Ismael; Cattan, Pedro E; Apt, Werner; Ferreira, Arturo

    2017-02-08

    Triatoma infestans is an important hematophagous vector of Chagas disease, a neglected chronic illness affecting approximately 6 million people in Latin America. Hematophagous insects possess several molecules in their saliva that counteract host defensive responses. Calreticulin (CRT), a multifunctional protein secreted in saliva, contributes to the feeding process in some insects. Human CRT (HuCRT) and Trypanosoma cruzi CRT (TcCRT) inhibit the classical pathway of complement activation, mainly by interacting through their central S domain with complement component C1. In previous studies, we have detected CRT in salivary gland extracts from T. infestans We have called this molecule TiCRT. Given that the S domain is responsible for C1 binding, we have tested its role in the classical pathway of complement activation in vertebrate blood. We have cloned and characterized the complete nucleotide sequence of CRT from T. infestans, and expressed its S domain. As expected, this S domain binds to human C1 and, as a consequence, it inhibits the classical pathway of complement, at its earliest stage of activation, namely the generation of C4b. Possibly, the presence of TiCRT in the salivary gland represents an evolutionary adaptation in hematophagous insects to control a potential activation of complement proteins, present in the massive blood meal that they ingest, with deleterious consequences at least on the anterior digestive tract of these insects.

  4. The TIR Domain Containing Locus of Enterococcus faecalis Is Predominant among Urinary Tract Infection Isolates and Downregulates Host Inflammatory Response

    PubMed Central

    Kraemer, Thomas Daniel; Quintanar Haro, Orlando Daniel; Domann, Eugen; Chakraborty, Trinad; Tchatalbachev, Svetlin

    2014-01-01

    Based on Toll/interleukin-1 receptor (TIR) domain structure homology, we detected a previously uncharacterized gene encoding for a TIR domain containing protein (Tcp) in the genome of Enterococcus faecalis. We assigned this gene the name tcpF (as in Tcp of E. faecalis). Screening of E. faecalis samples revealed that tcpF is more common in isolates from urinary tract infections (UTIs) than in human faecal flora. tcpF alleles showed moderate single nucleotide polymorphism (SNP) among UTI isolates. Infection of mouse RAW264.7 macrophages with a tcpF knock-out mutant led to elevated cytokine response compared to the isogenic wild type E. faecalis strain. In silico analysis predicted significant tertiary structure homology to the TIR domain of human TLR1 (TLR1-TIR). When transiently expressed in cultured eukaryotic cells, TcpF caused suppression of TLR2-dependent NF-κB activation suggesting for TcpF a role as a factor in E. faecalis that benefits colonization by modulating the host's immune responses. PMID:25147569

  5. The TIR Domain Containing Locus of Enterococcus faecalis Is Predominant among Urinary Tract Infection Isolates and Downregulates Host Inflammatory Response.

    PubMed

    Kraemer, Thomas Daniel; Quintanar Haro, Orlando Daniel; Domann, Eugen; Chakraborty, Trinad; Tchatalbachev, Svetlin

    2014-01-01

    Based on Toll/interleukin-1 receptor (TIR) domain structure homology, we detected a previously uncharacterized gene encoding for a TIR domain containing protein (Tcp) in the genome of Enterococcus faecalis. We assigned this gene the name tcpF (as in Tcp of E. faecalis). Screening of E. faecalis samples revealed that tcpF is more common in isolates from urinary tract infections (UTIs) than in human faecal flora. tcpF alleles showed moderate single nucleotide polymorphism (SNP) among UTI isolates. Infection of mouse RAW264.7 macrophages with a tcpF knock-out mutant led to elevated cytokine response compared to the isogenic wild type E. faecalis strain. In silico analysis predicted significant tertiary structure homology to the TIR domain of human TLR1 (TLR1-TIR). When transiently expressed in cultured eukaryotic cells, TcpF caused suppression of TLR2-dependent NF-κB activation suggesting for TcpF a role as a factor in E. faecalis that benefits colonization by modulating the host's immune responses.

  6. SH3 domain-mediated recruitment of host cell amphiphysins by alphavirus nsP3 promotes viral RNA replication.

    PubMed

    Neuvonen, Maarit; Kazlauskas, Arunas; Martikainen, Miika; Hinkkanen, Ari; Ahola, Tero; Saksela, Kalle

    2011-11-01

    Among the four non-structural proteins of alphaviruses the function of nsP3 is the least well understood. NsP3 is a component of the viral replication complex, and composed of a conserved aminoterminal macro domain implicated in viral RNA synthesis, and a poorly conserved carboxyterminal region. Despite the lack of overall homology we noted a carboxyterminal proline-rich sequence motif shared by many alphaviral nsP3 proteins, and found it to serve as a preferred target site for the Src-homology 3 (SH3) domains of amphiphysin-1 and -2. Nsp3 proteins of Semliki Forest (SFV), Sindbis (SINV), and Chikungunya viruses all showed avid and SH3-dependent binding to amphiphysins. Upon alphavirus infection the intracellular distribution of amphiphysin was dramatically altered and colocalized with nsP3. Mutations in nsP3 disrupting the amphiphysin SH3 binding motif as well as RNAi-mediated silencing of amphiphysin-2 expression resulted in impaired viral RNA replication in HeLa cells infected with SINV or SFV. Infection of Balb/c mice with SFV carrying an SH3 binding-defective nsP3 was associated with significantly decreased mortality. These data establish SH3 domain-mediated binding of nsP3 with amphiphysin as an important host cell interaction promoting alphavirus replication.

  7. An interaction domain in human SAMD9 is essential for myxoma virus host-range determinant M062 antagonism of host anti-viral function.

    PubMed

    Nounamo, Bernice; Li, Yibo; O'Byrne, Peter; Kearney, Aoife M; Khan, Amir; Liu, Jia

    2017-03-01

    In humans, deleterious mutations in the sterile α motif domain protein 9 (SAMD9) gene are associated with cancer, inflammation, weakening of the immune response, and developmental arrest. However, the biological function of SAMD9 and its sequence-structure relationships remain to be characterized. Previously, we found that an essential host range factor, M062 protein from myxoma virus (MYXV), antagonized the function of human SAMD9. In this study, we examine the interaction between M062 and human SAMD9 to identify regions that are critical to SAMD9 function. We also characterize the in vitro kinetics of the interaction. In an infection assay, exogenous expression of SAMD9 N-terminus leads to a potent inhibition of wild-type MYXV infection. We reason that this effect is due to the sequestration of viral M062 by the exogenously expressed N-terminal SAMD9 region. Our studies reveal the first molecular insight into viral M062-dependent mechanisms that suppress human SAMD9-associated antiviral function.

  8. Crystal structures of the Toll/Interleukin-1 receptor (TIR) domains from the Brucella protein TcpB and host adaptor TIRAP reveal mechanisms of molecular mimicry.

    PubMed

    Snyder, Greg A; Deredge, Daniel; Waldhuber, Anna; Fresquez, Theresa; Wilkins, David Z; Smith, Patrick T; Durr, Susi; Cirl, Christine; Jiang, Jiansheng; Jennings, William; Luchetti, Timothy; Snyder, Nathaniel; Sundberg, Eric J; Wintrode, Patrick; Miethke, Thomas; Xiao, T Sam

    2014-01-10

    The Toll/IL-1 receptor (TIR) domains are crucial innate immune signaling modules. Microbial TIR domain-containing proteins inhibit Toll-like receptor (TLR) signaling through molecular mimicry. The TIR domain-containing protein TcpB from Brucella inhibits TLR signaling through interaction with host adaptor proteins TIRAP/Mal and MyD88. To characterize the microbial mimicry of host proteins, we have determined the X-ray crystal structures of the TIR domains from the Brucella protein TcpB and the host adaptor protein TIRAP. We have further characterized homotypic interactions of TcpB using hydrogen/deuterium exchange mass spectrometry and heterotypic TcpB and TIRAP interaction by co-immunoprecipitation and NF-κB reporter assays. The crystal structure of the TcpB TIR domain reveals the microtubule-binding site encompassing the BB loop as well as a symmetrical dimer mediated by the DD and EE loops. This dimerization interface is validated by peptide mapping through hydrogen/deuterium exchange mass spectrometry. The human TIRAP TIR domain crystal structure reveals a unique N-terminal TIR domain fold containing a disulfide bond formed by Cys(89) and Cys(134). A comparison between the TcpB and TIRAP crystal structures reveals substantial conformational differences in the region that encompasses the BB loop. These findings underscore the similarities and differences in the molecular features found in the microbial and host TIR domains, which suggests mechanisms of bacterial mimicry of host signaling adaptor proteins, such as TIRAP.

  9. Crystal Structures of the Toll/Interleukin-1 Receptor (TIR) Domains from the Brucella Protein TcpB and Host Adaptor TIRAP Reveal Mechanisms of Molecular Mimicry*

    PubMed Central

    Snyder, Greg A.; Deredge, Daniel; Waldhuber, Anna; Fresquez, Theresa; Wilkins, David Z.; Smith, Patrick T.; Durr, Susi; Cirl, Christine; Jiang, Jiansheng; Jennings, William; Luchetti, Timothy; Snyder, Nathaniel; Sundberg, Eric J.; Wintrode, Patrick; Miethke, Thomas; Xiao, T. Sam

    2014-01-01

    The Toll/IL-1 receptor (TIR) domains are crucial innate immune signaling modules. Microbial TIR domain-containing proteins inhibit Toll-like receptor (TLR) signaling through molecular mimicry. The TIR domain-containing protein TcpB from Brucella inhibits TLR signaling through interaction with host adaptor proteins TIRAP/Mal and MyD88. To characterize the microbial mimicry of host proteins, we have determined the X-ray crystal structures of the TIR domains from the Brucella protein TcpB and the host adaptor protein TIRAP. We have further characterized homotypic interactions of TcpB using hydrogen/deuterium exchange mass spectrometry and heterotypic TcpB and TIRAP interaction by co-immunoprecipitation and NF-κB reporter assays. The crystal structure of the TcpB TIR domain reveals the microtubule-binding site encompassing the BB loop as well as a symmetrical dimer mediated by the DD and EE loops. This dimerization interface is validated by peptide mapping through hydrogen/deuterium exchange mass spectrometry. The human TIRAP TIR domain crystal structure reveals a unique N-terminal TIR domain fold containing a disulfide bond formed by Cys89 and Cys134. A comparison between the TcpB and TIRAP crystal structures reveals substantial conformational differences in the region that encompasses the BB loop. These findings underscore the similarities and differences in the molecular features found in the microbial and host TIR domains, which suggests mechanisms of bacterial mimicry of host signaling adaptor proteins, such as TIRAP. PMID:24275656

  10. Role of Nucleotide-Binding Oligomerization Domain-Containing (NOD) 2 in Host Defense during Pneumococcal Pneumonia.

    PubMed

    Hommes, Tijmen J; van Lieshout, Miriam H; van 't Veer, Cornelis; Florquin, Sandrine; Bootsma, Hester J; Hermans, Peter W; de Vos, Alex F; van der Poll, Tom

    2015-01-01

    Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD) 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2-/-) and wild-type (Wt) alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2-/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39), an isogenic capsule locus deletion mutant (D39Δcps) or serotype 3 S. pneumoniae (6303) via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2-/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2-/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2-/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2-/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δcps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2.

  11. Role of Nucleotide-Binding Oligomerization Domain-Containing (NOD) 2 in Host Defense during Pneumococcal Pneumonia

    PubMed Central

    Hommes, Tijmen J.; van Lieshout, Miriam H.; van ‘t Veer, Cornelis; Florquin, Sandrine; Bootsma, Hester J.; Hermans, Peter W.; de Vos, Alex F.; van der Poll, Tom

    2015-01-01

    Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD) 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2-/-) and wild-type (Wt) alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2-/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39), an isogenic capsule locus deletion mutant (D39Δcps) or serotype 3 S. pneumoniae (6303) via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2-/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2-/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2-/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2-/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δcps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2. PMID:26673231

  12. An antimicrobial protein of the gut symbiont Bacteroides fragilis with a MACPF domain of host immune proteins.

    PubMed

    Chatzidaki-Livanis, Maria; Coyne, Michael J; Comstock, Laurie E

    2014-12-01

    Bacteroidales are the most abundant Gram-negative bacteria of the human intestinal microbiota comprising more than half of the bacteria in many individuals. Some of the factors that these bacteria use to establish and maintain themselves in this ecosystem are beginning to be identified. However, ecological competition, especially interference competition where one organism directly harms another, is largely unexplored. To begin to understand the relevance of this ecological principle as it applies to these abundant gut bacteria and factors that may promote such competition, we screened Bacteroides fragilis for the production of antimicrobial molecules. We found that the production of extracellularly secreted antimicrobial molecules is widespread in this species. The first identified molecule, described in this manuscript, contains a membrane attack complex/perforin (MACPF) domain present in host immune molecules that kill bacteria and virally infected cells by pore formation, and mutations affecting key residues of this domain abrogated its activity. This antimicrobial molecule, termed BSAP-1, is secreted from the cell in outer membrane vesicles and no additional proteins are required for its secretion, processing or immunity of the producing cell. This study provides the first insight into secreted molecules that promote competitive interference among Bacteroidales strains of the human gut. © 2014 John Wiley & Sons Ltd.

  13. Jasmonate ZIM-domain (JAZ) protein regulates host and nonhost pathogen-induced cell death in tomato and Nicotiana benthamiana.

    PubMed

    Ishiga, Yasuhiro; Ishiga, Takako; Uppalapati, Srinivasa Rao; Mysore, Kirankumar S

    2013-01-01

    The nonhost-specific phytotoxin coronatine (COR) produced by several pathovars of Pseudomonas syringae functions as a jasmonic acid-isoleucine (JA-Ile) mimic and contributes to disease development by suppressing plant defense responses and inducing reactive oxygen species in chloroplast. It has been shown that the F-box protein CORONATINE INSENSITIVE 1 (COI1) is the receptor for COR and JA-Ile. JASMONATE ZIM DOMAIN (JAZ) proteins act as negative regulators for JA signaling in Arabidopsis. However, the physiological significance of JAZ proteins in P. syringae disease development and nonhost pathogen-induced hypersensitive response (HR) cell death is not completely understood. In this study, we identified JAZ genes from tomato, a host plant for P. syringae pv. tomato DC3000 (Pst DC3000), and examined their expression profiles in response to COR and pathogens. Most JAZ genes were induced by COR treatment or inoculation with COR-producing Pst DC3000, but not by the COR-defective mutant DB29. Tomato SlJAZ2, SlJAZ6 and SlJAZ7 interacted with SlCOI1 in a COR-dependent manner. Using virus-induced gene silencing (VIGS), we demonstrated that SlJAZ2, SlJAZ6 and SlJAZ7 have no effect on COR-induced chlorosis in tomato and Nicotiana benthamiana. However, SlJAZ2-, SlJAZ6- and SlJAZ7-silenced tomato plants showed enhanced disease-associated cell death to Pst DC3000. Furthermore, we found delayed HR cell death in response to the nonhost pathogen Pst T1 or a pathogen-associated molecular pattern (PAMP), INF1, in SlJAZ2- and SlJAZ6-silenced N. benthamiana. These results suggest that tomato JAZ proteins regulate the progression of cell death during host and nonhost interactions.

  14. In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains.

    PubMed

    Côté, Jean-François; Vuori, Kristiina

    2006-01-01

    Rho family GTPases regulate a large variety of biological processes, including the reorganization of the actin cytoskeleton. Like other members of the Ras superfamily of small GTP-binding proteins, Rho GTPases cycle between a GDP-bound (inactive) and a GTP-bound (active) state, and, when active, the GTPases relay extracellular signals to a large number of downstream effectors. Guanine nucleotide exchange factors (GEFs) promote the exchange of GDP for GTP on Rho GTPases, thereby activating them. Most Rho-GEFs mediate their effects through their signature domain known as the Dbl Homology-Pleckstrin Homology (DH-PH) module. Recently, we and others identified a family of evolutionarily conserved, DOCK180-related proteins that also display GEF activity toward Rho GTPases. The DOCK180-family of proteins lacks the canonical DH-PH module. Instead, they rely on a novel domain, termed DHR-2, DOCKER, or CZH2, to exchange GDP for GTP on Rho targets. In this chapter, the experimental approach that we used to uncover the exchange activity of the DHR-2 domain of DOCK180-related proteins will be described.

  15. Variants of biculturalism in migrant and host adolescents living in Italy and Spain: Testing the importance of life domains through the Relative Acculturation Extended Model.

    PubMed

    Mancini, Tiziana; Navas, Marisol; López-Rodríguez, Lucia; Bottura, Benedetta

    2017-05-09

    Several variants of biculturalism have recently been proposed (Schwartz, Birman, Benet-Martínez, & Unger, 2016). Nevertheless, few studies have identified different types of bicultural individuals, and no one has addressed the possibility that these types could depend on acculturation domains. By using the Relative Acculturation Extended Model (RAEM), this study aimed to explore if different variants of biculturalism could be individuated, and if some of these variants were sensitive to life domains. Four samples of migrant and host adolescents living in Italy (n = 173 and n = 186) and Spain (n = 139 and n = 156) answered a questionnaire about acculturation perceptions and preferences in central and peripheral life domains. Together with acculturation options consistent with Berry's (1997) model (full-assimilation, full-separation and full-marginalisation), some variants of biculturalism emerged from the latent class analysis: full-high and full-low integration, which were not sensitive to life domains; and "alternate" acculturation options that were sensitive to life domains, with participants switching from their original culture to the host culture according to the peripheral and central domains. Acculturation options varied across the four samples, with Italians switching more from one culture to another, and Spanish adolescents being more full-high or full-low integrated. © 2017 International Union of Psychological Science.

  16. Pseudomonas aeruginosa ExoT Induces Mitochondrial Apoptosis in Target Host Cells in a Manner That Depends on Its GTPase-activating Protein (GAP) Domain Activity.

    PubMed

    Wood, Stephen J; Goldufsky, Josef W; Bello, Daniella; Masood, Sara; Shafikhani, Sasha H

    2015-11-27

    Pseudomonas aeruginosa is the most common cause of hospital-acquired pneumonia and a killer of immunocompromised patients. We and others have demonstrated that the type III secretion system (T3SS) effector protein ExoT plays a pivotal role in facilitating P. aeruginosa pathogenesis. ExoT possesses an N-terminal GTPase-activating protein (GAP) domain and a C-terminal ADP-ribosyltransferase (ADPRT) domain. Because it targets multiple non-overlapping cellular targets, ExoT performs several distinct virulence functions for P. aeruginosa, including induction of apoptosis in a variety of target host cells. Both the ADPRT and the GAP domain activities contribute to ExoT-induced apoptosis. The ADPRT domain of ExoT induces atypical anoikis by transforming an innocuous cellular protein, Crk, into a cytotoxin, which interferes with integrin survival signaling. However, the mechanism underlying the GAP-induced apoptosis remains unknown. In this study, we demonstrate that the GAP domain activity is both necessary and sufficient to induce mitochondrial (intrinsic) apoptosis. We show that intoxication with GAP domain results in: (i) JNK1/2 activation; (ii) substantial increases in the mitochondrial levels of activated pro-apoptotic proteins Bax and Bid, and to a lesser extent Bim; (iii) loss of mitochondrial membrane potential and cytochrome c release; and (iv) activation of initiator caspase-9 and executioner caspase-3. Further, GAP-induced apoptosis is partially mediated by JNK1/2, but it is completely dependent on caspase-9 activity. Together, the ADPRT and the GAP domains make ExoT into a highly versatile and potent cytotoxin, capable of inducing multiple forms of apoptosis in target host cells. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. The TPR Domain in the Host Cyp40-like Cyclophilin Binds to the Viral Replication Protein and Inhibits the Assembly of the Tombusviral Replicase

    PubMed Central

    Lin, Jing-Yi; Qin, Jun; Nagy, Peter D.

    2012-01-01

    Replication of plus-stranded RNA viruses is greatly affected by numerous host-coded proteins acting either as susceptibility or resistance factors. Previous genome-wide screens and global proteomics approaches with Tomato bushy stunt tombusvirus (TBSV) in a yeast model host revealed the involvement of cyclophilins, which are a large family of host prolyl isomerases, in TBSV replication. In this paper, we identified those members of the large cyclophilin family that interacted with the viral replication proteins and inhibited TBSV replication. Further characterization of the most effective cyclophilin, the Cyp40-like Cpr7p, revealed that it strongly inhibits many steps during TBSV replication in a cell-free replication assay. These steps include viral RNA recruitment inhibited via binding of Cpr7p to the RNA-binding region of the viral replication protein; the assembly of the viral replicase complex and viral RNA synthesis. Since the TPR (tetratricopeptide repeats) domain, but not the catalytic domain of Cpr7p is needed for the inhibitory effect on TBSV replication, it seems that the chaperone activity of Cpr7p provides the negative regulatory function. We also show that three Cyp40-like proteins from plants can inhibit TBSV replication in vitro and Cpr7p is also effective against Nodamura virus, an insect pathogen. Overall, the current work revealed a role for Cyp40-like proteins and their TPR domains as regulators of RNA virus replication. PMID:22346747

  18. Biophysical studies on calcium and carbohydrate binding to carbohydrate recognition domain of Gal/GalNAc lectin from Entamoeba histolytica: insights into host cell adhesion.

    PubMed

    Yadav, Rupali; Verma, Kuldeep; Chandra, Mintu; Mukherjee, Madhumita; Datta, Sunando

    2016-09-01

    Entamoeba histolytica, an enteric parasite expresses a Gal/GalNAc-specific lectin that contributes to its virulence by establishing adhesion to host cell. In this study, carbohydrate recognition domain of Hgl (EhCRD) was purified and biophysical studies were conducted to understand the thermodynamic basis of its binding to carbohydrate and Ca(++) Here, we show that carbohydrate recognition domain (CRD) of the lectin binds to calcium through DPN motif. To decipher the role of calcium in carbohydrate binding and host cell adhesion, biophysical and cell-based studies were carried out. We demonstrated that the presence of the cation neither change the affinity of the lectin for carbohydrates nor alters its conformation. Mutation of the calcium-binding motif in EhCRD resulted in complete loss of ability to bind calcium but retained its affinity for carbohydrates. Purified EhCRD significantly diminished adhesion of the amebic trophozoites to Chinese Hamster Ovary (CHO) cells as well as triggered red blood cell agglutination. The calcium-binding defective mutant abrogated amebic adhesion to CHO cells similar to the wild-type protein, but it failed to agglutinate RBCs suggesting a differential role of the cation in these two processes. This study provides the first molecular description of the role of calcium in Gal/GalNAc mediated host cell adhesion.

  19. TIR domain-containing adaptor SARM is a late addition to the ongoing microbe–host dialog

    PubMed Central

    Zhang, Qing; Zmasek, Christian M.; Cai, Xiaohui; Godzik, Adam

    2011-01-01

    Toll/interleukin-1 receptor (TIR) domain-containing proteins play important roles in defense against pathogens in both animals and plants, connecting the immunity signaling pathways via a chain of specific protein–protein interactions. Among them is SARM, the only TIR domain-containing adaptor that can negatively regulate TLR signaling. By extensive phylogenetic analysis, we show here that SARM is closely related to bacterial proteins with TIR domains, suggesting that this family has a different evolutionary history from other animal TIR-containing adaptors, possibly emerging via a lateral gene transfer from bacteria to animals. We also show evidence of several similar, independent transfer events, none of which, however, survived in vertebrates. An evolutionary relationship between the animal SARM adaptor and bacterial proteins with TIR domains illustrates the possible role that bacterial TIR-containing proteins play in regulating eukaryotic immune responses and how this mechanism was possibly adapted by the eukaryotes themselves. PMID:21110998

  20. Phosphate transporters in marine phytoplankton and their viruses: cross-domain commonalities in viral-host gene exchanges.

    PubMed

    Monier, Adam; Welsh, Rory M; Gentemann, Chelle; Weinstock, George; Sodergren, Erica; Armbrust, E Virginia; Eisen, Jonathan A; Worden, Alexandra Z

    2012-01-01

    Phosphate (PO(4)) is an important limiting nutrient in marine environments. Marine cyanobacteria scavenge PO(4) using the high-affinity periplasmic phosphate binding protein PstS. The pstS gene has recently been identified in genomes of cyanobacterial viruses as well. Here, we analyse genes encoding transporters in genomes from viruses that infect eukaryotic phytoplankton. We identified inorganic PO(4) transporter-encoding genes from the PHO4 superfamily in several virus genomes, along with other transporter-encoding genes. Homologues of the viral pho4 genes were also identified in genome sequences from the genera that these viruses infect. Genome sequences were available from host genera of all the phytoplankton viruses analysed except the host genus Bathycoccus. Pho4 was recovered from Bathycoccus by sequencing a targeted metagenome from an uncultured Atlantic Ocean population. Phylogenetic reconstruction showed that pho4 genes from pelagophytes, haptophytes and infecting viruses were more closely related to homologues in prasinophytes than to those in what, at the species level, are considered to be closer relatives (e.g. diatoms). We also identified PHO4 superfamily members in ocean metagenomes, including new metagenomes from the Pacific Ocean. The environmental sequences grouped with pelagophytes, haptophytes, prasinophytes and viruses as well as bacteria. The analyses suggest that multiple independent pho4 gene transfer events have occurred between marine viruses and both eukaryotic and bacterial hosts. Additionally, pho4 genes were identified in available genomes from viruses that infect marine eukaryotes but not those that infect terrestrial hosts. Commonalities in marine host-virus gene exchanges indicate that manipulation of host-PO(4) uptake is an important adaptation for viral proliferation in marine systems. Our findings suggest that PO(4) -availability may not serve as a simple bottom-up control of marine phytoplankton.

  1. TIR domain-containing adaptor SARM is a late addition to the ongoing microbe-host dialog.

    PubMed

    Zhang, Qing; Zmasek, Christian M; Cai, Xiaohui; Godzik, Adam

    2011-04-01

    Toll/interleukin-1 receptor (TIR) domain-containing proteins play important roles in defense against pathogens in both animals and plants, connecting the immunity signaling pathways via a chain of specific protein-protein interactions. Among them is SARM, the only TIR domain-containing adaptor that can negatively regulate TLR signaling. By extensive phylogenetic analysis, we show here that SARM is closely related to bacterial proteins with TIR domains, suggesting that this family has a different evolutionary history from other animal TIR-containing adaptors, possibly emerging via a lateral gene transfer from bacteria to animals. We also show evidence of several similar, independent transfer events, none of which, however, survived in vertebrates. An evolutionary relationship between the animal SARM adaptor and bacterial proteins with TIR domains illustrates the possible role that bacterial TIR-containing proteins play in regulating eukaryotic immune responses and how this mechanism was possibly adapted by the eukaryotes themselves. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Members of a Novel Protein Family Containing Microneme Adhesive Repeat Domains Act as Sialic Acid-binding Lectins during Host Cell Invasion by Apicomplexan Parasites*

    PubMed Central

    Friedrich, Nikolas; Santos, Joana M.; Liu, Yan; Palma, Angelina S.; Leon, Ester; Saouros, Savvas; Kiso, Makoto; Blackman, Michael J.; Matthews, Stephen; Feizi, Ten; Soldati-Favre, Dominique

    2010-01-01

    Numerous intracellular pathogens exploit cell surface glycoconjugates for host cell recognition and entry. Unlike bacteria and viruses, Toxoplasma gondii and other parasites of the phylum Apicomplexa actively invade host cells, and this process critically depends on adhesins (microneme proteins) released onto the parasite surface from intracellular organelles called micronemes (MIC). The microneme adhesive repeat (MAR) domain of T. gondii MIC1 (TgMIC1) recognizes sialic acid (Sia), a key determinant on the host cell surface for invasion by this pathogen. By complementation and invasion assays, we demonstrate that TgMIC1 is one important player in Sia-dependent invasion and that another novel Sia-binding lectin, designated TgMIC13, is also involved. Using BLAST searches, we identify a family of MAR-containing proteins in enteroparasitic coccidians, a subclass of apicomplexans, including T. gondii, suggesting that all these parasites exploit sialylated glycoconjugates on host cells as determinants for enteric invasion. Furthermore, this protein family might provide a basis for the broad host cell range observed for coccidians that form tissue cysts during chronic infection. Carbohydrate microarray analyses, corroborated by structural considerations, show that TgMIC13, TgMIC1, and its homologue Neospora caninum MIC1 (NcMIC1) share a preference for α2–3- over α2–6-linked sialyl-N-acetyllactosamine sequences. However, the three lectins also display differences in binding preferences. Intense binding of TgMIC13 to α2–9-linked disialyl sequence reported on embryonal cells and relatively strong binding to 4-O-acetylated-Sia found on gut epithelium and binding of NcMIC1 to 6′sulfo-sialyl Lewisx might have implications for tissue tropism. PMID:19901027

  3. The leucine-rich repeat domain can determine effective interaction between RPS2 and other host factors in arabidopsis RPS2-mediated disease resistance.

    PubMed Central

    Banerjee, D; Zhang, X; Bent, A F

    2001-01-01

    Like many other plant disease resistance genes, Arabidopsis thaliana RPS2 encodes a product with nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domains. This study explored the hypothesized interaction of RPS2 with other host factors that may be required for perception of Pseudomonas syringae pathogens that express avrRpt2 and/or for the subsequent induction of plant defense responses. Crosses between Arabidopsis ecotypes Col-0 (resistant) and Po-1 (susceptible) revealed segregation of more than one gene that controls resistance to P. syringae that express avrRpt2. Many F(2) and F(3) progeny exhibited intermediate resistance phenotypes. In addition to RPS2, at least one additional genetic interval associated with this defense response was identified and mapped using quantitative genetic methods. Further genetic and molecular genetic complementation experiments with cloned RPS2 alleles revealed that the Po-1 allele of RPS2 can function in a Col-0 genetic background, but not in a Po-1 background. The other resistance-determining genes of Po-1 can function, however, as they successfully conferred resistance in combination with the Col-0 allele of RPS2. Domain-swap experiments revealed that in RPS2, a polymorphism at six amino acids in the LRR region is responsible for this allele-specific ability to function with other host factors. PMID:11333251

  4. Overlapping Motifs (PTAP and PPEY) within the Ebola Virus VP40 Protein Function Independently as Late Budding Domains: Involvement of Host Proteins TSG101 and VPS-4

    PubMed Central

    Licata, Jillian M.; Simpson-Holley, Martha; Wright, Nathan T.; Han, Ziying; Paragas, Jason; Harty, Ronald N.

    2003-01-01

    The VP40 protein of Ebola virus can bud from mammalian cells in the form of lipid-bound, virus-like particles (VLPs), and late budding domains (L-domains) are conserved motifs (PTAP, PPxY, or YxxL; where “x” is any amino acid) that facilitate the budding of VP40-containing VLPs. VP40 is unique in that potential overlapping L-domains with the sequences PTAP and PPEY are present at amino acids 7 to 13 of VP40 (PTAPPEY). L-domains are thought to function by interacting with specific cellular proteins, such as the ubiquitin ligase Nedd4, and a component of the vacuolar protein sorting (vps) pathway, tsg101. Mutational analysis of the PTAPPEY sequence of VP40 was performed to understand further the contribution of each individual motif in promoting VP40 budding. In addition, the contribution of tsg101 and a second member of the vps pathway, vps4, in facilitating budding was addressed. Our results indicate that (i) both the PTAP and PPEY motifs contribute to efficient budding of VP40-containing VLPs; (ii) PTAP and PPEY can function as L-domains when separated and moved from the N terminus (amino acid position 7) to the C terminus (amino acid position 316) of full-length VP40; (iii) A VP40-PTAP/tsg101 interaction recruits tsg101 into budding VLPs; (iv) a VP40-PTAP/tsg101 interaction recruits VP40 into lipid raft microdomains; and (v) a dominant-negative mutant of vps4 (E228Q), but not wild-type vps4, significantly inhibited the budding of Ebola virus (Zaire). These results provide important insights into the complex interplay between viral and host proteins during the late stages of Ebola virus budding. PMID:12525615

  5. Overlapping motifs (PTAP and PPEY) within the Ebola virus VP40 protein function independently as late budding domains: involvement of host proteins TSG101 and VPS-4.

    PubMed

    Licata, Jillian M; Simpson-Holley, Martha; Wright, Nathan T; Han, Ziying; Paragas, Jason; Harty, Ronald N

    2003-02-01

    The VP40 protein of Ebola virus can bud from mammalian cells in the form of lipid-bound, virus-like particles (VLPs), and late budding domains (L-domains) are conserved motifs (PTAP, PPxY, or YxxL; where "x" is any amino acid) that facilitate the budding of VP40-containing VLPs. VP40 is unique in that potential overlapping L-domains with the sequences PTAP and PPEY are present at amino acids 7 to 13 of VP40 (PTAPPEY). L-domains are thought to function by interacting with specific cellular proteins, such as the ubiquitin ligase Nedd4, and a component of the vacuolar protein sorting (vps) pathway, tsg101. Mutational analysis of the PTAPPEY sequence of VP40 was performed to understand further the contribution of each individual motif in promoting VP40 budding. In addition, the contribution of tsg101 and a second member of the vps pathway, vps4, in facilitating budding was addressed. Our results indicate that (i) both the PTAP and PPEY motifs contribute to efficient budding of VP40-containing VLPs; (ii) PTAP and PPEY can function as L-domains when separated and moved from the N terminus (amino acid position 7) to the C terminus (amino acid position 316) of full-length VP40; (iii) A VP40-PTAP/tsg101 interaction recruits tsg101 into budding VLPs; (iv) a VP40-PTAP/tsg101 interaction recruits VP40 into lipid raft microdomains; and (v) a dominant-negative mutant of vps4 (E228Q), but not wild-type vps4, significantly inhibited the budding of Ebola virus (Zaire). These results provide important insights into the complex interplay between viral and host proteins during the late stages of Ebola virus budding.

  6. A LysM and SH3-domain containing region of the Listeria monocytogenes p60 protein stimulates accessory cells to promote activation of host NK cells.

    PubMed

    Schmidt, Rebecca L; Filak, Holly C; Lemon, Jack D; Potter, Terry A; Lenz, Laurel L

    2011-11-01

    Listeria monocytogenes (Lm) infection induces rapid and robust activation of host natural killer (NK) cells. Here we define a region of the abundantly secreted Lm endopeptidase, p60, that potently but indirectly stimulates NK cell activation in vitro and in vivo. Lm expression of p60 resulted in increased IFNγ production by naïve NK cells co-cultured with treated dendritic cells (DCs). Moreover, recombinant p60 protein stimulated activation of naive NK cells when co-cultured with TLR or cytokine primed DCs in the absence of Lm. Intact p60 protein weakly digested bacterial peptidoglycan (PGN), but neither muropeptide recognition by RIP2 nor the catalytic activity of p60 was required for NK cell activation. Rather, the immune stimulating activity mapped to an N-terminal region of p60, termed L1S. Treatment of DCs with a recombinant L1S polypeptide stimulated them to activate naïve NK cells in a cell culture model. Further, L1S treatment activated NK cells in vivo and increased host resistance to infection with Francisella tularensis live vaccine strain (LVS). These studies demonstrate an immune stimulating function for a bacterial LysM domain-containing polypeptide and suggest that recombinant versions of L1S or other p60 derivatives can be used to promote NK cell activation in therapeutic contexts.

  7. Probe-hosted silicon photomultipliers for time-domain functional near-infrared spectroscopy: phantom and in vivo tests.

    PubMed

    Re, Rebecca; Martinenghi, Edoardo; Mora, Alberto Dalla; Contini, Davide; Pifferi, Antonio; Torricelli, Alessandro

    2016-10-01

    We report the development of a compact probe for time-domain (TD) functional near-infrared spectroscopy (fNIRS) based on a fast silicon photomultiplier (SiPM) that can be put directly in contact with the sample without the need of optical fibers for light collection. We directly integrated an avalanche signal amplification stage close to the SiPM, thus reducing the size of the detection channel and optimizing the signal immunity to electromagnetic interferences. The whole detection electronics was placed in a plastic screw holder compatible with the electroencephalography standard cap for measurement on brain or with custom probe holders. The SiPM is inserted into a transparent and insulating resin to avoid the direct contact of the scalp with the 100-V bias voltage. The probe was integrated in an instrument for TD fNIRS spectroscopy. The system was characterized on tissue phantoms in terms of temporal resolution, responsivity, linearity, and capability to detect deep absorption changes. Preliminary in vivo tests on adult volunteers were performed to monitor hemodynamic changes in the arm during a cuff occlusion and in the brain cortex during a motor task.

  8. Avian and 1918 Spanish influenza a virus NS1 proteins bind to Crk/CrkL Src homology 3 domains to activate host cell signaling.

    PubMed

    Heikkinen, Leena S; Kazlauskas, Arunas; Melén, Krister; Wagner, Ralf; Ziegler, Thedi; Julkunen, Ilkka; Saksela, Kalle

    2008-02-29

    NS1 (nonstructural protein 1) is an important virulence factor of the influenza A virus. We observed that NS1 proteins of the 1918 pandemic virus (A/Brevig Mission/1/18) and many avian influenza A viruses contain a consensus Src homology 3 (SH3) domain-binding motif. Screening of a comprehensive human SH3 phage library revealed the N-terminal SH3 of Crk and CrkL as the preferred binding partners. Studies with recombinant proteins confirmed avid binding of NS1 proteins of the 1918 virus and a representative avian H7N3 strain to Crk/CrkL SH3 but not to other SH3 domains tested, including p85alpha and p85beta. Endogenous CrkL readily co-precipitated NS1 from cells infected with the H7N3 virus. In transfected cells association with CrkL was observed for NS1 of the 1918 and H7N3 viruses but not A/Udorn/72 or A/WSN/33 NS1 lacking this sequence motif. SH3 binding was dispensable for suppression of interferon-induced gene expression by NS1 but was associated with enhanced phosphatidylinositol 3-kinase signaling, as evidenced by increased Akt phosphorylation. Thus, the Spanish Flu virus resembles avian influenza A viruses in its ability to recruit Crk/CrkL to modulate host cell signaling.

  9. The Host-Pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains

    PubMed Central

    2011-01-01

    Background Cyclophilin A (CypA) represents a potential key molecule in future antiretroviral therapy since inhibition of CypA suppresses human immunodeficiency virus type 1 (HIV-1) replication. CypA interacts with the virus proteins Capsid (CA) and Vpr, however, the mechanism through which CypA influences HIV-1 infectivity still remains unclear. Results Here the interaction of full-length HIV-1 Vpr with the host cellular factor CypA has been characterized and quantified by surface plasmon resonance spectroscopy. A C-terminal region of Vpr, comprising the 16 residues 75GCRHSRIGVTRQRRAR90, with high binding affinity for CypA has been identified. This region of Vpr does not contain any proline residues but binds much more strongly to CypA than the previously characterized N-terminal binding domain of Vpr, and is thus the first protein binding domain to CypA described involving no proline residues. The fact that the mutant peptide Vpr75-90 R80A binds more weakly to CypA than the wild-type peptide confirms that Arg-80 is a key residue in the C-terminal binding domain. The N- and C-terminal binding regions of full-length Vpr bind cooperatively to CypA and have allowed a model of the complex to be created. The dissociation constant of full-length Vpr to CypA was determined to be approximately 320 nM, indicating that the binding may be stronger than that of the well characterized interaction of HIV-1 CA with CypA. Conclusions For the first time the interaction of full-length Vpr and CypA has been characterized and quantified. A non-proline-containing 16-residue region of C-terminal Vpr which binds specifically to CypA with similar high affinity as full-length Vpr has been identified. The fact that this is the first non-proline containing binding motif of any protein found to bind to CypA, changes the view on how CypA is able to interact with other proteins. It is interesting to note that several previously reported key functions of HIV-1 Vpr are associated with the

  10. Bacterial Genome Partitioning: N-Terminal Domain of IncC Protein Encoded by Broad-Host-Range Plasmid RK2 Modulates Oligomerisation and DNA Binding

    PubMed Central

    Batt, Sarah M.; Bingle, Lewis E.H.; Dafforn, Tim R.; Thomas, Christopher M.

    2009-01-01

    ParA Walker ATPases form part of the machinery that promotes better-than-random segregation of bacterial genomes. ParA proteins normally occur in one of two forms, differing by their N-terminal domain (NTD) of approximately 100 aa, which is generally associated with site-specific DNA binding. Unusually, and for as yet unknown reasons, parA (incC) of IncP-1 plasmids is translated from alternative start codons producing two forms, IncC1 (364 aa) and IncC2 (259 aa), whose ratio varies between hosts. IncC2 could be detected as an oligomeric form containing dimers, tetramers and octamers, but the N-terminal extension present in IncC1 favours nucleotide-stimulated dimerisation as well as high-affinity and ATP-dependent non-specific DNA binding. The IncC1 NTD does not dimerise or bind DNA alone, but it does bind IncC2 in the presence of nucleotides. Mixing IncC1 and IncC2 improved polymerisation and DNA binding. Thus, the NTD may modulate the polymerisation interface, facilitating polymerisation/depolymerisation and DNA binding, to promote the cycle that drives partitioning. PMID:19109978

  11. Functional interaction of nuclear domain 10 and its components with cytomegalovirus after infections: cross-species host cells versus native cells.

    PubMed

    Cosme, Ruth Cruz; Martínez, Francisco Puerta; Tang, Qiyi

    2011-04-28

    Species-specificity is one of the major characteristics of cytomegaloviruses (CMVs) and is the primary reason for the lack of a mouse model for the direct infection of human CMV (HCMV). It has been determined that CMV cross-species infections are blocked at the post-entry level by intrinsic cellular defense mechanisms, but few details are known. It is important to explore how CMVs interact with the subnuclear structure of the cross-species host cell. In our present study, we discovered that nuclear domain 10 (ND10) of human cells was not disrupted by murine CMV (MCMV) and that the ND10 of mouse cells was not disrupted by HCMV, although the ND10-disrupting protein, immediate-early protein 1 (IE1), also colocalized with ND10 in cross-species infections. In addition, we found that the UL131-repaired HCMV strain AD169 (vDW215-BADrUL131) can infect mouse cells to produce immediate-early (IE) and early (E) proteins but that neither DNA replication nor viral particles were detectable in mouse cells. Unrepaired AD169 can express IE1 only in mouse cells. In both HCMV-infected mouse cells and MCMV-infected human cells, the knocking-down of ND10 components (PML, Daxx, and SP100) resulted in significantly increased viral-protein production. Our observations provide evidence to support our hypothesis that ND10 and ND10 components might be important defensive factors against the CMV cross-species infection.

  12. NMR Solution Structure of the Terminal Immunoglobulin-like Domain from the Leptospira Host-Interacting Outer Membrane Protein, LigB

    PubMed Central

    2015-01-01

    A number of surface proteins specific to pathogenic strains of Leptospira have been identified. The Lig protein family has shown promise as a marker in typing leptospiral isolates for pathogenesis and as an antigen in vaccines. We used NMR spectroscopy to solve the solution structure of the twelfth immunoglobulin-like (Ig-like) repeat domain from LigB (LigB-12). The fold is similar to that of other bacterial Ig-like domains and comprised mainly of β-strands that form a β-sandwich based on a Greek-key folding arrangement. Based on sequence analysis and conservation of structurally important residues, homology models for the other LigB Ig-like domains were generated. The set of LigB models illustrates the electrostatic differences between the domains as well as the possible interactions between neighboring domains. Understanding the structure of the extracellular portion of LigB and related proteins is important for developing diagnostic methods and new therapeutics directed toward leptospirosis. PMID:25068811

  13. Establishing the Yeast Kluyveromyces lactis as an Expression Host for Production of the Saposin-Like Domain of the Aspartic Protease Cirsin

    PubMed Central

    Curto, Pedro; Lufrano, Daniela; Pinto, Cátia; Custódio, Valéria; Gomes, Ana Catarina; Trejo, Sebastián A.; Bakás, Laura; Vairo-Cavalli, Sandra; Faro, Carlos

    2014-01-01

    Typical plant aspartic protease zymogens comprise a characteristic and plant-specific insert (PSI). PSI domains can interact with membranes, and a role as a defensive weapon against pathogens has been proposed. However, the potential of PSIs as antimicrobial agents has not been fully investigated and explored yet due to problems in producing sufficient amounts of these domains in bacteria. Here, we report the development of an expression platform for the production of the PSI domain of cirsin in the generally regarded as safe (GRAS) yeast Kluyveromyces lactis. We successfully generated K. lactis transformants expressing and secreting significant amounts of correctly processed and glycosylated PSI, as well as its nonglycosylated mutant. A purification protocol with protein yields of ∼4.0 mg/liter was established for both wild-type and nonglycosylated PSIs, which represents the highest reported yield for a nontagged PSI domain. Subsequent bioactivity assays targeting phytopathogenic fungi indicated that the PSI of cirsin is produced in a biologically active form in K. lactis and provided clear evidence for its antifungal activity. This yeast expression system thereby emerges as a promising production platform for further exploring the biotechnological potential of these plant saposin-like proteins. PMID:24123748

  14. Construction of high level prokaryotic expression and purification system of PD-L1 extracellular domain by using Escherichia coli host cell machinery.

    PubMed

    Kalim, Muhammad; Chen, Jie; Wang, Shenghao; Lin, Caiyao; Ullah, Saif; Liang, Keying; Ding, Qian; Chen, Shuqing; Zhan, Jinbiao

    2017-10-01

    Programmed cell death 1 ligand 1 (PD-L1) is a trans-membrane protein highly expressed on the membrane of cancer cell, which binds inhibitory receptor of PD-1 on the T cells and attenuates anti-tumor immune response.The strategy of blocking PD1 and PD-L1 interaction has been widely used for anti-cancer drug development. The DNA encoding extracellular domain of PD-L1 was cloned and expressed with the pET30(+) and Escherichia coli BL21(DE3) system. Cloning of PD-L1 extracellular domain was confirmed by PCR and enzymatic digestion. Sequence analysis of cloned targeted genes showed 100% homology of original sequence. The recombinant protein was expressed using 1mM/mL IPTG and purified by affinity chromatography on a column of Ni-NTA and confirmed by SDS-PAGE and western blot analysis. Results showed that our constructed pET30(+)/PDL1-ECD system efficiently produces desired recombinant protein with molecular weight of 38.1kDa. The prokaryotic expression system provides an easy method to express PD-L1 extracellular domain that further facilitate the role of PD-1/PD-L1 binding inhibition and helps in valuable drug and antibodies production. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  15. Two TIR-like domain containing proteins in a newly emerging zoonotic Staphylococcus aureus strain sequence type 398 are potential virulence factors by impacting on the host innate immune response

    PubMed Central

    Patterson, Nicholas J.; Günther, Juliane; Gibson, Amanda J.; Offord, Victoria; Coffey, Tracey J.; Splitter, Gary; Monk, Ian; Seyfert, Hans-Martin; Werling, Dirk

    2014-01-01

    Staphylococcus aureus, sequence type (ST) 398, is an emerging pathogen and the leading cause of livestock-associated methicillin-resistant S. aureus infections in Europe and North America. This strain is characterized by high promiscuity in terms of host-species and also lacks several traditional S. aureus virulence factors. This does not, however, explain the apparent ease with which it crosses species-barriers. Recently, TIR-domain containing proteins (Tcps) which inhibit the innate immune response were identified in some Gram-negative bacteria. Here we report the presence of two proteins, S. aureus TIR-like Protein 1 (SaTlp1) and S. aureus TIR-like Protein 2 (SaTlp2), expressed by ST398 which contain domain of unknown function 1863 (DUF1863), similar to the Toll/IL-1 receptor (TIR) domain. In contrast to the Tcps in Gram-negative bacteria, our data suggest that SaTlp1 and SaTlp2 increase activation of the transcription factor NF-κB as well as downstream pro-inflammatory cytokines and immune effectors. To assess the role of both proteins as potential virulence factors knock-out mutants were created. These showed a slightly enhanced survival rate in a murine infectious model compared to the wild-type strain at one dose. Our data suggest that both proteins may act as factors contributing to the enhanced ability of ST398 to cross species-barriers. PMID:25538689

  16. Two TIR-like domain containing proteins in a newly emerging zoonotic Staphylococcus aureus strain sequence type 398 are potential virulence factors by impacting on the host innate immune response.

    PubMed

    Patterson, Nicholas J; Günther, Juliane; Gibson, Amanda J; Offord, Victoria; Coffey, Tracey J; Splitter, Gary; Monk, Ian; Seyfert, Hans-Martin; Werling, Dirk

    2014-01-01

    Staphylococcus aureus, sequence type (ST) 398, is an emerging pathogen and the leading cause of livestock-associated methicillin-resistant S. aureus infections in Europe and North America. This strain is characterized by high promiscuity in terms of host-species and also lacks several traditional S. aureus virulence factors. This does not, however, explain the apparent ease with which it crosses species-barriers. Recently, TIR-domain containing proteins (Tcps) which inhibit the innate immune response were identified in some Gram-negative bacteria. Here we report the presence of two proteins, S. aureus TIR-like Protein 1 (SaTlp1) and S. aureus TIR-like Protein 2 (SaTlp2), expressed by ST398 which contain domain of unknown function 1863 (DUF1863), similar to the Toll/IL-1 receptor (TIR) domain. In contrast to the Tcps in Gram-negative bacteria, our data suggest that SaTlp1 and SaTlp2 increase activation of the transcription factor NF-κB as well as downstream pro-inflammatory cytokines and immune effectors. To assess the role of both proteins as potential virulence factors knock-out mutants were created. These showed a slightly enhanced survival rate in a murine infectious model compared to the wild-type strain at one dose. Our data suggest that both proteins may act as factors contributing to the enhanced ability of ST398 to cross species-barriers.

  17. Orientia tsutsugamushi Ank9 is a multifunctional effector that utilizes a novel GRIP-like Golgi localization domain for Golgi-to-endoplasmic reticulum trafficking and interacts with host COPB2.

    PubMed

    Beyer, Andrea R; Rodino, Kyle G; VieBrock, Lauren; Green, Ryan S; Tegels, Brittney K; Oliver, Lee D; Marconi, Richard T; Carlyon, Jason A

    2017-01-19

    Orientia tsutsugamushi causes scrub typhus, a potentially fatal infection that afflicts 1 million people annually. This obligate intracellular bacterium boasts one of the largest microbial arsenals of ankyrin repeat-containing protein (Ank) effectors, most of which target the endoplasmic reticulum (ER) by undefined mechanisms. Ank9 is the only one proven to function during infection. Here, we demonstrate that Ank9 bears a motif that mimics the GRIP domain of eukaryotic golgins and is necessary and sufficient for its Golgi localization. Ank9 reaches the ER exclusively by retrograde trafficking from the Golgi. Consistent with this observation, it binds COPB2, a host protein that mediates Golgi-to-ER transport. Ank9 destabilizes the Golgi and ER in a Golgi localization domain-dependent manner and induces the activating transcription factor 4-dependent unfolded protein response. The Golgi is also destabilized in cells infected with O. tsutsugamushi or treated with COPB2 small interfering RNA. COPB2 reduction and/or the cellular events that it invokes, such as Golgi destabilization, benefit Orientia replication. Thus, Ank9 or bacterial negative modulation of COPB2 might contribute to the bacterium's intracellular replication. This report identifies a novel microbial Golgi localization domain, links Ank9 to the ability of O. tsutsugamushi to perturb Golgi structure, and describes the first mechanism by which any Orientia effector targets the secretory pathway.

  18. A hexapeptide of the receptor-binding domain of SARS corona virus spike protein blocks viral entry into host cells via the human receptor ACE2.

    PubMed

    Struck, Anna-Winona; Axmann, Marco; Pfefferle, Susanne; Drosten, Christian; Meyer, Bernd

    2012-06-01

    In vitro infection of Vero E6 cells by SARS coronavirus (SARS-CoV) is blocked by hexapeptide Tyr-Lys-Tyr-Arg-Tyr-Leu. The peptide also inhibits proliferation of coronavirus NL63. On human cells both viruses utilize angiotensin-converting enzyme 2 (ACE2) as entry receptor. Blocking the viral entry is specific as alpha virus Sindbis shows no reduction in infectivity. Peptide (438)YKYRYL(443) is part of the receptor-binding domain (RBD) of the spike protein of SARS-CoV. Peptide libraries were screened by surface plasmon resonance (SPR) to identify RBD binding epitopes. (438)YKYRYL(443) carries the dominant binding epitope and binds to ACE2 with K(D)=46 μM. The binding mode was further characterized by saturation transfer difference (STD) NMR spectroscopy and molecular dynamic simulations. Based on this information the peptide can be used as lead structure to design potential entry inhibitors against SARS-CoV and related viruses. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Functional properties of the carboxy-terminal host cell-binding domains of the two toxins, TcdA and TcdB, expressed by Clostridium difficile.

    PubMed

    Dingle, Tanis; Wee, Stefanie; Mulvey, George L; Greco, Antonio; Kitova, Elena N; Sun, Jiangxiao; Lin, Shuangjun; Klassen, John S; Palcic, Monica M; Ng, Kenneth K S; Armstrong, Glen D

    2008-09-01

    The biological and ligand-binding properties of recombinant C-terminal cell-binding domains (CBDs) and subdomains of the two large exotoxins, Toxin A (TcdA) and Toxin B (TcdB) expressed by Clostridium difficile were examined in the hemagglutination and Verocytotoxicity neutralization assays and by qualitative affinity chromatography using Sepharose-linked alpha Gal(1,3)betaGal(1,4)beta Glc as well as the direct electrospray ionization mass spectrometry (ES-MS) assay. These studies revealed that, whereas the full-length TcdA CBD agglutinated rabbit erythrocytes, neutralized TcdA-mediated Vero cell death and bound to alpha Gal(1,3)betaGal(1,4)beta Glc-derivatized Sepharose, the TcdB CBD was inactive in these functional assays. Moreover, retention by alpha Gal(1,3)betaGal(1,4)beta Glc-derivatized Sepharose corresponded to the number of available TcdA subdomain ligand-binding sites. By contrast, the ES-MS assays revealed that both the TcdA and TcdB CBD bind to 8-methoxycarbonyloctyl-alpha Gal(1,3)betaGal(1,4)beta Glc sequences with similar avidities. Additional ES-MS experiments using chemically altered alpha Gal(1,3)betaGal(1,4)beta Glc sequences also revealed that the TcdA and TcdB CBD will tolerate a fair amount of structural variation in their complementary glycan ligands. Although the studies are consistent with the known ligand-binding properties of the TcdA and TcdB holotoxins, they also revealed subtle heretofore unrecognized functional differences in their receptor recognition properties.

  20. A cupin domain-containing protein with a quercetinase activity (VdQase) regulates Verticillium dahliae's pathogenicity and contributes to counteracting host defenses

    PubMed Central

    El Hadrami, Abdelbasset; Islam, Md. Rashidul; Adam, Lorne R.; Daayf, Fouad

    2015-01-01

    We previously identified rutin as part of potato root responses to its pathogen Verticillium dahliae. Rutin was directly toxic to the pathogen at doses greater than 160 μM, a threshold below which many V. dahliae pathogenicity-related genes were up-regulated. We identified and characterized a cupin domain-containing protein (VdQase) with a dioxygenase activity and a potential role in V. dahliae-potato interactions. The pathogenicity of VdQase knock-out mutants generated through Agrobacterium tumefasciens-mediated transformation was significantly reduced on susceptible potato cultivar Kennebec compared to wild type isolates. Fluorescence microscopy revealed a higher accumulation of flavonols in the stems of infected potatoes and a higher concentration of rutin in the leaves in response to the VdQase mutants as compared to wild type isolates. This, along with the HPLC characterization of high residual and non-utilized quercetin in presence of the knockout mutants, indicates the involvement of VdQase in the catabolism of quercetin and possibly other flavonols in planta. Quantification of Salicylic and Jasmonic Acids (SA, JA) in response to the mutants vs. wild type isolates revealed involvement of VdQase in the interference with signaling, suggesting a role in pathogenicity. It is hypothesized that the by-product of dioxygenation 2-protocatechuoylphloroglucinolcarboxylic acid, after dissociating into phloroglucinol and protocatechuoyl moieties, becomes a starting point for benzoic acid and SA, thereby interfering with the JA pathway and affecting the interaction outcome. These events may be key factors for V. dahliae in countering potato defenses and becoming notorious in the rhizosphere. PMID:26113857

  1. Host Cell Factor and an Uncharacterized SANT Domain Protein Are Stable Components of ATAC, a Novel dAda2A/dGcn5-Containing Histone Acetyltransferase Complex in Drosophila

    PubMed Central

    Guelman, Sebastián; Suganuma, Tamaki; Florens, Laurence; Swanson, Selene K.; Kiesecker, Cheri L.; Kusch, Thomas; Anderson, Scott; Yates, John R.; Washburn, Michael P.; Abmayr, Susan M.; Workman, Jerry L.

    2006-01-01

    Gcn5 is a conserved histone acetyltransferase (HAT) found in a number of multisubunit complexes from Saccharomyces cerevisiae, mammals, and flies. We previously identified Drosophila melanogaster homologues of the yeast proteins Ada2, Ada3, Spt3, and Tra1 and showed that they associate with dGcn5 to form at least two distinct HAT complexes. There are two different Ada2 homologues in Drosophila named dAda2A and dAda2B. dAda2B functions within the Drosophila version of the SAGA complex (dSAGA). To gain insight into dAda2A function, we sought to identify novel components of the complex containing this protein, ATAC (Ada two A containing) complex. Affinity purification and mass spectrometry revealed that, in addition to dAda3 and dGcn5, host cell factor (dHCF) and a novel SANT domain protein, named Atac1 (ATAC component 1), copurify with this complex. Coimmunoprecipitation experiments confirmed that these proteins associate with dGcn5 and dAda2A, but not with dSAGA-specific components such as dAda2B and dSpt3. Biochemical fractionation revealed that ATAC has an apparent molecular mass of 700 kDa and contains dAda2A, dGcn5, dAda3, dHCF, and Atac1 as stable subunits. Thus, ATAC represents a novel histone acetyltransferase complex that is distinct from previously purified Gcn5/Pcaf-containing complexes from yeast and mammalian cells. PMID:16428443

  2. Methods for production of proteins in host cells

    DOEpatents

    Donnelly, Mark; Joachimiak, Andrzej

    2004-01-13

    The present invention provides methods for the production of proteins, particularly toxic proteins, in host cells. The invention provides methods which use a fusion protein comprising a chaperonin binding domain in host cells induced or regulated to have increased levels of chaperonin which binds the chaperonin binding domain.

  3. A Unified Approach to Intra-Domain Security

    SciTech Connect

    Shue, Craig A; Kalafut, Andrew J.; Gupta, Prof. Minaxi

    2009-01-01

    While a variety of mechanisms have been developed for securing individual intra-domain protocols, none address the issue in a holistic manner. We develop a unified framework to secure prominent networking protocols within a single domain. We begin with a secure version of the DHCP protocol, which has the additional feature of providing each host with a certificate. We then leverage these certificates to secure ARP, prevent spoofing within the domain, and secure SSH and VPN connections between the domain and hosts which have previously interacted with it locally. In doing so, we also develop an incrementally deployable public key infrastructure which can later be leveraged to support inter-domain authentication.

  4. Host defenses against cryptococcosis.

    PubMed

    Price, Michael S; Perfect, John R

    2011-01-01

    The interaction of pathogenic Cryptococcus species with their various hosts is somewhat unique compared to other fungal pathogens such as Aspergillus fumigatus and Candida albicans. Cryptococcus shares an intimate association with host immune cells, leading to enhanced intracellular growth. Furthermore, unlike most other fungal pathogens, the signs and symptoms of cryptococcal disease are typically self-inflicted by the host during the host's attempt to clear this invader from sensitive organ systems such as the central nervous system. In this review, we will summarize the story of host-Cryptococcus interactions to date and explore strategies to exploit the current knowledge for treatment of cryptococcal infections.

  5. Estimating parasite host range.

    PubMed

    Dallas, Tad; Huang, Shan; Nunn, Charles; Park, Andrew W; Drake, John M

    2017-08-30

    Estimating the number of host species that a parasite can infect (i.e. host range) provides key insights into the evolution of host specialism and is a central concept in disease ecology. Host range is rarely estimated in real systems, however, because variation in species relative abundance and the detection of rare species makes it challenging to confidently estimate host range. We applied a non-parametric richness indicator to estimate host range in simulated and empirical data, allowing us to assess the influence of sampling heterogeneity and data completeness. After validating our method on simulated data, we estimated parasite host range for a sparsely sampled global parasite occurrence database (Global Mammal Parasite Database) and a repeatedly sampled set of parasites of small mammals from New Mexico (Sevilleta Long Term Ecological Research Program). Estimation accuracy varied strongly with parasite taxonomy, number of parasite occurrence records, and the shape of host species-abundance distribution (i.e. the dominance and rareness of species in the host community). Our findings suggest that between 20% and 40% of parasite host ranges are currently unknown, highlighting a major gap in our understanding of parasite specificity, host-parasite network structure, and parasite burdens. © 2017 The Author(s).

  6. Glob-Hosts

    SciTech Connect

    Behlendorf, B.; Garlick, J.

    2007-08-31

    The glob-hosts utility manipulates hostlist strings in UNIX shell scripts. Hostlists are a parseable string representatin of list of hosts, which compress nicely when a group of hosts are named with contiguous numeric suffixes. For example, the hosts blue1, blue2, and blue3 can be represented by the hostlist string "blue1, blue2, blue3" or equivalently "blue[1-3]". The globhost utility cn peform the following operations on a hostlist string: count, size, expand, nth, union, minus, intersection, and exclude.

  7. Extending Black Domain Name List by Using Co-occurrence Relation between DNS Queries

    NASA Astrophysics Data System (ADS)

    Sato, Kazumichi; Ishibashi, Keisuke; Toyono, Tsuyoshi; Hasegawa, Haruhisa; Yoshino, Hideaki

    Botnet threats, such as server attacks or sending of spam e-mail, have been increasing. Therefore, infected hosts must be found and their malicious activities mitigated. An effective method for finding infected hosts is to use a blacklist of domain names. When a bot receives attack commands from a Command and Control (C&C) server, it attempts to resolve domain names of C&C servers. We can thus detect infected hosts by finding these that send queries on black domain names. However, we cannot find all infected hosts because of the inaccuracy of blacklists. There are many black domain names, and the lifetimes of these domain names are short; therefore a blacklist cannot cover all black domain names. We thus present a method for finding unknown black domain names by using DNS query data and an existing blacklist of known black domain names. To achieve this, we focus on DNS queries sent by infected hosts. One bot sends several queries on black domain names due to C&C server redundancy. We use the co-occurrence relation of two different domain names to find unknown black domain names and extend the blacklist. If a domain name frequently co-occurs with a known black name, we assume that the domain name is also black. A cross-validation evaluation of the proposed method showed that 91.2% of domain names that are on the validation list scored in the top 1%.

  8. Data hosting infrastructure for primary biodiversity data

    PubMed Central

    2011-01-01

    Background Today, an unprecedented volume of primary biodiversity data are being generated worldwide, yet significant amounts of these data have been and will continue to be lost after the conclusion of the projects tasked with collecting them. To get the most value out of these data it is imperative to seek a solution whereby these data are rescued, archived and made available to the biodiversity community. To this end, the biodiversity informatics community requires investment in processes and infrastructure to mitigate data loss and provide solutions for long-term hosting and sharing of biodiversity data. Discussion We review the current state of biodiversity data hosting and investigate the technological and sociological barriers to proper data management. We further explore the rescuing and re-hosting of legacy data, the state of existing toolsets and propose a future direction for the development of new discovery tools. We also explore the role of data standards and licensing in the context of data hosting and preservation. We provide five recommendations for the biodiversity community that will foster better data preservation and access: (1) encourage the community's use of data standards, (2) promote the public domain licensing of data, (3) establish a community of those involved in data hosting and archival, (4) establish hosting centers for biodiversity data, and (5) develop tools for data discovery. Conclusion The community's adoption of standards and development of tools to enable data discovery is essential to sustainable data preservation. Furthermore, the increased adoption of open content licensing, the establishment of data hosting infrastructure and the creation of a data hosting and archiving community are all necessary steps towards the community ensuring that data archival policies become standardized. PMID:22373257

  9. Broad host range plasmids.

    PubMed

    Jain, Aayushi; Srivastava, Preeti

    2013-11-01

    Plasmids are and will remain important cloning vehicles for biotechnology. They have also been associated with the spread of a number of diseases and therefore are a subject of environmental concern. With the advent of sequencing technologies, the database of plasmids is increasing. It will be of immense importance to identify the various bacterial hosts in which the plasmid can replicate. The present review article describes the features that confer broad host range to the plasmids, the molecular basis of plasmid host range evolution, and applications in recombinant DNA technology and environment.

  10. Uropathogens and Host Characteristics▿

    PubMed Central

    Tabibian, James H.; Gornbein, Jeffrey; Heidari, Arash; Dien, Sarah L.; Lau, Valerie H.; Chahal, Puneet; Churchill, Bernard M.; Haake, David A.

    2008-01-01

    Uropathogens other than Escherichia coli occur with greater frequency in patients with risk factors for urinary tract infection (UTI). However, little is known about associations between uropathogen species and host characteristics. Three hundred nineteen urine specimens containing a balanced distribution of uropathogen species were selected from inpatients and outpatients at a university hospital clinical microbiology laboratory. Information on host characteristics was retrospectively collected by chart review. Differences in the frequencies of host characteristics in UTI groups, as defined by the causative uropathogen, were compared by chi-square/Fisher analysis. Multivariate classification and regression tree analysis were used to identify host characteristic subsets that distinguish among uropathogen groups. In this exploratory study, several uropathogen species were found to be strongly linked to host characteristics relevant to UTI. Patients with Pseudomonas aeruginosa UTIs were more likely to have undergone urinary tract procedures (43% versus 15% overall), to have a neurogenic bladder (29% versus 12% overall), to have received recent antibiotic therapy (52% versus 24% overall), and to be male (76% versus 28% overall). Patients with Proteus mirabilis UTIs were more likely to have a foreign body in the lower urinary tract (48% versus 30% overall). The classification tree identified males over the age of 27 years who had undergone a prior urinary tract procedure as belonging to a host characteristic profile associated with P. aeruginosa UTI: 38% of patients with P. aeruginosa UTIs fit this profile. These data may be useful for planning future targeted prophylaxis studies. PMID:18842936

  11. A Cloud-Oriented Cross-Domain Security Architecture

    DTIC Science & Technology

    2010-11-01

    A Cloud-Oriented Cross -Domain Security Architecture Thuy D. Nguyen, Mark A. Gondree, David J. Shifflett, Jean Khosalim, Timothy E. Levin, Cynthia...to support a cloud of cross -domain services, hosted within a federation of multilevel secure (MLS) MYSEA servers. The MYSEA cloud supports single...sign on, service replication, and network-layer quality of security service. This new cross - domain, distributed architecture follows the consumption

  12. Understanding the Public Domain.

    ERIC Educational Resources Information Center

    Russell, Carrie

    2003-01-01

    This overview of the public domain covers: defining the public domain; figuring out if a work is protected by copyright; being sure a work is in the public domain; asserting the copyright protection and term; the Creative Commons initiative; building the Information Commons; when permission is needed for using a public domain work; and special…

  13. A survey of host range genes in poxvirus genomes

    PubMed Central

    Bratke, Kirsten A.; McLysaght, Aoife; Rothenburg, Stefan

    2014-01-01

    Poxviruses are widespread pathogens, which display extremely different host ranges. Whereas some poxviruses, including variola virus, display narrow host ranges, others such as cowpox viruses naturally infect a wide range of mammals. The molecular basis for differences in host range are poorly understood but apparently depend on the successful manipulation of the host antiviral response. Some poxvirus genes have been shown to confer host tropism in experimental settings and are thus called host range factors. Identified host range genes include vaccinia virus K1L, K3L, E3L, B5R, C7L and SPI-1, cowpox virus CP77/CHOhr, ectromelia virus p28 and 022, and myxoma virus T2, T4, T5, 11L, 13L, 062R and 063R. These genes encode for ankyrin repeat-containing proteins, tumor necrosis factor receptor II homologs, apoptosis inhibitor T4-related proteins, Bcl-2-related proteins, pyrin domain-containing proteins, cellular serine protease inhibitors (serpins), short complement-like repeats containing proteins, KilA-N/RING domain-containing proteins, as well as inhibitors of the double-stranded RNA-activated protein kinase PKR. We conducted a systematic survey for the presence of known host range genes and closely related family members in poxvirus genomes, classified them into subgroups based on their phylogenetic relationship and correlated their presence with the poxvirus phylogeny. Common themes in the evolution of poxvirus host range genes are lineage-specific duplications and multiple independent inactivation events. Our analyses yield new insights into the evolution of poxvirus host range genes. Implications of our findings for poxvirus host range and virulence are discussed. PMID:23268114

  14. NASA HOST project overview

    NASA Technical Reports Server (NTRS)

    Sokolowski, Daniel E.

    1989-01-01

    NASA's Hot Section Technology (HOST) program has developed improved analytical models for the aerothermal environment, thermomechanical loading, material behavior, structural response, and service life of aircraft gas turbine engines' hot section components. These models, in conjunction with sophisticated computer codes, can be used in design analyses of critical combustor and turbine elements. Toward these ends, efforts were undertaken in instrumentation, combustion, turbine heat transfer, structural analysis, fatigue-fracture, and surface protection. Attention is presently given to the organization of HOST activities and their specific subject matter.

  15. Host age modulates within-host parasite competition

    PubMed Central

    Izhar, Rony; Routtu, Jarkko; Ben-Ami, Frida

    2015-01-01

    In many host populations, one of the most striking differences among hosts is their age. While parasite prevalence differences in relation to host age are well known, little is known on how host age impacts ecological and evolutionary dynamics of diseases. Using two clones of the water flea Daphnia magna and two clones of its bacterial parasite Pasteuria ramosa, we examined how host age at exposure influences within-host parasite competition and virulence. We found that multiply-exposed hosts were more susceptible to infection and suffered higher mortality than singly-exposed hosts. Hosts oldest at exposure were least often infected and vice versa. Furthermore, we found that in young multiply-exposed hosts competition was weak, allowing coexistence and transmission of both parasite clones, whereas in older multiply-exposed hosts competitive exclusion was observed. Thus, age-dependent parasite exposure and host demography (age structure) could together play an important role in mediating parasite evolution. At the individual level, our results demonstrate a previously unnoticed interaction of the host's immune system with host age, suggesting that the specificity of immune function changes as hosts mature. Therefore, evolutionary models of parasite virulence might benefit from incorporating age-dependent epidemiological parameters. PMID:25994010

  16. Domains in multiband superconductors

    NASA Astrophysics Data System (ADS)

    Tanaka, Y.; Yanagisawa, T.; Crisan, A.; Shirage, P. M.; Iyo, A.; Tokiwa, K.; Nishio, T.; Sundaresan, A.; Terada, N.

    2011-11-01

    Multiband superconductors can have several types of domains that are inhibited in conventional single-band superconductors. These domains are phase domains and chiral domains and their domain wall are an interband phase difference soliton. In a superconductor with an odd number of electronic bands (five or more) and with positive interband Josephson interactions, we find other types of domains with different interband phase differences. We call these domains configuration domains because pseudo-order parameters for each band are dispersed in the complex plain and several configurations, which have several local minima. Fractional vortices serve as hubs for phase difference solitons (configuration domain walls). The divergence of the number of configurations with local minima would pose a serious problem for the stability of superconductivity.

  17. Host Phylogeny Determines Viral Persistence and Replication in Novel Hosts

    PubMed Central

    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

  18. An endoparasitoid wasp influences host DNA methylation

    PubMed Central

    Kumar, Sunil; Kim, Yonggyun

    2017-01-01

    Parasitism by endoparasitoid wasps changes the expression of various host genes, and alters host immune and developmental processes. However, it is not clearly understood how parasitism changes host gene expression in a whole genome scale. This study focused on an epigenetic control of Cotesia plutellae, an endoparasitoid wasp, against its host, Plutella xylostella. Two DNA methyltransferases (DNMT-1 and DNMT-2) are encoded in the genome of P. xylostella. In addition, methyl-binding domain proteins (MBDs) and DNA demethylation factor, ten-eleven translation protein (TET) are encoded. DNA methylation of P. xylostella genomic DNA was confirmed by restriction digestion with Gla I specific to 5-methylcytosine. DNA methylation intensity in parasitized (P) larvae was decreased compared to that in nonparasitized (NP) larvae, especially at late parasitic stage, at which expression levels of both DNMT-1 and DNMT-2 were also decreased. DNA demethylation of P. xylostella was confirmed in both NP and P larvae by restriction digestion with PvuRts1I recognizing 5-hydroxymethyl cytosine. Parasitism also suppressed expression levels of TET and MBDs. Treatment of 5-aza-2′-deoxycytidine (AZA) reduced DNA methylation intensity of NP larvae, causing suppression of hemocyte-spreading behavior and delay of immature development. RNA interference of DNMT-1 or DNMT-2 mimicked the adverse effects of AZA. PMID:28230192

  19. Solution structure of leptospiral LigA4 Big domain

    SciTech Connect

    Mei, Song; Zhang, Jiahai; Zhang, Xuecheng; Tu, Xiaoming

    2015-11-13

    Pathogenic Leptospiraspecies express immunoglobulin-like proteins which serve as adhesins to bind to the extracellular matrices of host cells. Leptospiral immunoglobulin-like protein A (LigA), a surface exposed protein containing tandem repeats of bacterial immunoglobulin-like (Big) domains, has been proved to be involved in the interaction of pathogenic Leptospira with mammalian host. In this study, the solution structure of the fourth Big domain of LigA (LigA4 Big domain) from Leptospira interrogans was solved by nuclear magnetic resonance (NMR). The structure of LigA4 Big domain displays a similar bacterial immunoglobulin-like fold compared with other Big domains, implying some common structural aspects of Big domain family. On the other hand, it displays some structural characteristics significantly different from classic Ig-like domain. Furthermore, Stains-all assay and NMR chemical shift perturbation revealed the Ca{sup 2+} binding property of LigA4 Big domain. - Highlights: • Determining the solution structure of a bacterial immunoglobulin-like domain from a surface protein of Leptospira. • The solution structure shows some structural characteristics significantly different from the classic Ig-like domains. • A potential Ca{sup 2+}-binding site was identified by strains-all and NMR chemical shift perturbation.

  20. Development of the Digital Engineering Laboratory Computer Network: Host-to-Node/Host-to-Host Protocols.

    DTIC Science & Technology

    1981-12-01

    HOST-TO-HOST PROTOCOLS THESIS AFIT,’GCS/EE/8lD-8 John W. Geist Capt USAF Approved for public release; distribution unlimited. AFIT/GCS/EE/81D-8...DEVELOPMENT OF THE DIGITAL ENGINEERING LABORATORY COMPUTER NETWORK: HOST-TO-NODE/HOST-TO-HOST PROTOCOLS THESIS Presented to the Faculty of the School of...development and operational implementation. I wish to express my appreciation to Dr. Gary B. Lamont, my thesis advisor, for his valued support and

  1. Internationalized Domain Names.

    ERIC Educational Resources Information Center

    Wielansky, Marc D.

    2002-01-01

    Reports on an investigation of what may appear at first to be an arcane topic--the internationalization of domain names on the Internet. Concludes that expanding domain names internationally poses challenges to the inherent open structure of the Internet; to its ease of use for those accustomed to Latin-alphabet-only domain names; and to corporate…

  2. Natural host defense mechanisms.

    PubMed

    Heggers, J P

    1979-10-01

    Severe injury, whether the result of a major accident, a large burn, or a complicated surgical operation, often results in sepsis. Under such conditions both specific and nonspecific host defense systems are affected. The individual facets of major concern are chemotaxis, phagocytosis, intracellular killing, complement depletion, and depression of humoral and cellular mediated immunity. The most profound changes occur in cell-mediated immunity. Within a few hours o injury, the number of circulating T cells becomes depleted, concomitantly thoracic duct lymphocytes are markedly reduced. This change is not only quantitative but functional. The clinical impact of these deficient host defense mechanisms lies in the fact that low virulent organisms may become a lethal threat to the injured patient. Currently, investigators are attempting to reverse thse deficiencies through the use of immunotherapy.

  3. Hosting a Katrina Evacuee.

    NASA Astrophysics Data System (ADS)

    Hoagland, David

    2008-03-01

    No individual or institution anticipated the impact on the academic research community of hurricane Katrina. When Tulane physicist Wayne Reed asked me to host his research group just a day or two after the disaster, with no authorization or understanding of the commitment, I agreed immediately and then pondered implications. Fortunately, colleagues helped in making the commitment real, only the bureaucracy of my public university posing small hindrances. Industry was remarkably generous in providing Reed with significant ``loaner'' equipment, and amazingly, a suite of custom Reed experiments was running within weeks. At the end, the most productive collaborations for Reed seemed not to have been with my group, with its similar research, but to other groups at my institution, particularly the synthetic chemists, who gained access to methods previously unique to Tulane while offering samples previously unique to UMass. Quickly designed projects exploiting this match turned out remarkably productive. Although begun with trepidation, hosting of Reed had huge positive benefits to me and UMass, and I believe, also to Reed and Tulane. Some key lessons for the future: (i) industry has capacity and willingness to help academic research during disruption (ii) commitment of a host institution must be immediate, without a wait for formal approvals or arrangement of special funding -- delay leads only to discouragement, (iii) continuing academic progress of displaced students must come first, and (iv) intellectual synergy rather than overlap should be the basis for seeking a host. Lastly, NSF or other funding agency should consider a program directly addressing the research needs of unexpectedly disrupted academic scientists, and most particularly, graduate students who face greatly extended studies.

  4. Fatty acid-producing hosts

    DOEpatents

    Pfleger, Brian F; Lennen, Rebecca M

    2013-12-31

    Described are hosts for overproducing a fatty acid product such as a fatty acid. The hosts include an exogenous nucleic acid encoding a thioesterase and, optionally, an exogenous nucleic acid encoding an acetyl-CoA carboxylase, wherein an acyl-CoA synthetase in the hosts are functionally delected. The hosts prefereably include the nucleic acid encoding the thioesterase at an intermediate copy number. The hosts are preferably recominantly stable and growth-competent at 37.degree. C. Methods of producing a fatty acid product comprising culturing such hosts at 37.degree. C. are also described.

  5. Protein-Protein Interactions in Virus-Host Systems.

    PubMed

    Brito, Anderson F; Pinney, John W

    2017-01-01

    To study virus-host protein interactions, knowledge about viral and host protein architectures and repertoires, their particular evolutionary mechanisms, and information on relevant sources of biological data is essential. The purpose of this review article is to provide a thorough overview about these aspects. Protein domains are basic units defining protein interactions, and the uniqueness of viral domain repertoires, their mode of evolution, and their roles during viral infection make viruses interesting models of study. Mutations at protein interfaces can reduce or increase their binding affinities by changing protein electrostatics and structural properties. During the course of a viral infection, both pathogen and cellular proteins are constantly competing for binding partners. Endogenous interfaces mediating intraspecific interactions-viral-viral or host-host interactions-are constantly targeted and inhibited by exogenous interfaces mediating viral-host interactions. From a biomedical perspective, blocking such interactions is the main mechanism underlying antiviral therapies. Some proteins are able to bind multiple partners, and their modes of interaction define how fast these "hub proteins" evolve. "Party hubs" have multiple interfaces; they establish simultaneous/stable (domain-domain) interactions, and tend to evolve slowly. On the other hand, "date hubs" have few interfaces; they establish transient/weak (domain-motif) interactions by means of short linear peptides (15 or fewer residues), and can evolve faster. Viral infections are mediated by several protein-protein interactions (PPIs), which can be represented as networks (protein interaction networks, PINs), with proteins being depicted as nodes, and their interactions as edges. It has been suggested that viral proteins tend to establish interactions with more central and highly connected host proteins. In an evolutionary arms race, viral and host proteins are constantly changing their interface

  6. Graft-versus-host disease

    MedlinePlus

    GVHD; Bone marrow transplant - graft-versus-host disease; Stem cell transplant - graft-versus-host disease; Allogeneic transplant - ... GVHD may occur after a bone marrow, or stem cell, transplant in which someone receives bone marrow ...

  7. Conducting Ferroelectric Walls, Domain Topology, and Domain Switching Kinetics in a Hybrid Improper Ferroelectric

    NASA Astrophysics Data System (ADS)

    Cheong, Sang-Wook; Rutgers CenterEmergent Materials Team

    Charged polar interfaces such as charged ferroelectric domain walls or heterostructured interfaces of ZnO/(Zn,Mg)O and LaAlO 3 /SrTiO 3 , across which the normal component of electric polarization changes suddenly, can host large two-dimensional conduction. Charged ferroelectric domain walls can be highly conducting but energetically unfavored; however, they were found to be mysteriously abundant in hybrid improper ferroelectric (Ca,Sr) 3 Ti 2 O 7 single crystals. From the exploration of antiphase domain boundaries, which are hidden in piezoresponse force microscopy, using dark-field electron microscopy, we have explored the macroscopic topology of polarization domains and antiphase domains. We found that the macroscopic domain topology is directly responsible for the presence of charged domain walls, and is closely related with the polarization domain switching mechanism in (Ca,Sr) 3 Ti 2 O 7 . Rutgers Center for Emergent Materials and Department of Physics and Astronomy, Rutgers University, Piscataway, New Jersey 08854, USA.

  8. Comparing mechanisms of host manipulation across host and parasite taxa

    USGS Publications Warehouse

    Lafferty, Kevin D.; Shaw, Jenny C.

    2013-01-01

    Parasites affect host behavior in several ways. They can alter activity, microhabitats or both. For trophically transmitted parasites (the focus of our study), decreased activity might impair the ability of hosts to respond to final-host predators, and increased activity and altered microhabitat choice might increase contact rates between hosts and final-host predators. In an analysis of trophically transmitted parasites, more parasite groups altered activity than altered microhabitat choice. Parasites that infected vertebrates were more likely to impair the host’s reaction to predators, whereas parasites that infected invertebrates were more likely to increase the host’s contact with predators. The site of infection might affect how parasites manipulate their hosts. For instance, parasites in the central nervous system seem particularly suited to manipulating host behavior. Manipulative parasites commonly occupy the body cavity, muscles and central nervous systems of their hosts. Acanthocephalans in the data set differed from other taxa in that they occurred exclusively in the body cavity of invertebrates. In addition, they were more likely to alter microhabitat choice than activity. Parasites in the body cavity (across parasite types) were more likely to be associated with increased host contact with predators. Parasites can manipulate the host through energetic drain, but most parasites use more sophisticated means. For instance, parasites target four physiological systems that shape behavior in both invertebrates and vertebrates: neural, endocrine, neuromodulatory and immunomodulatory. The interconnections between these systems make it difficult to isolate specific mechanisms of host behavioral manipulation.

  9. Stable charged antiparallel domain walls in hyperferroelectrics

    NASA Astrophysics Data System (ADS)

    Liu, S.; Cohen, R. E.

    2017-06-01

    Charge-neutral 180° domain walls that separate domains of antiparallel polarization directions are common structural topological defects in ferroelectrics. In normal ferroelectrics, charged 180° domain walls running perpendicular to the polarization directions are highly energetically unfavorable because of the depolarization field and are difficult to stabilize. We explore both neutral and charged 180° domain walls in hyperferroelectrics, a class of proper ferroelectrics with persistent polarization in the presence of a depolarization field, using density functional theory. We obtain zero temperature equilibrium structures of head-to-head and tail-to-tail walls in recently discovered ABC-type hexagonal hyperferroelectrics. Charged domain walls can also be stabilized in canonical ferroelectrics represented by LiNbO3 without any dopants, defects or mechanical clamping. First-principles electronic structure calculations show that charged domain walls can reduce and even close the band gap of host materials and support quasi-two-dimensional electron(hole) gas with enhanced electrical conductivity.

  10. Allergic Host Defenses

    PubMed Central

    Palm, Noah W.; Rosenstein, Rachel K.

    2012-01-01

    Allergies are generally thought to be a detrimental outcome of a mistargeted immune response that evolved to provide immunity to macro-parasites. Here we present arguments to suggest that allergic immunity plays an important role in host defense against noxious environmental substances, including venoms, hematophagous fluids, environmental xenobiotics and irritants. We argue that appropriately targeted allergic reactions are beneficial, although they can become detrimental when excessive. Furthermore, we suggest that allergic hypersensitivity evolved to elicit anticipatory responses and to promote avoidance of suboptimal environments. PMID:22538607

  11. Host Specificity of Bacterial Pathogens

    PubMed Central

    Bäumler, Andreas; Fang, Ferric C.

    2013-01-01

    Most pathogens are able to infect multiple hosts but some are highly adapted to a single-host species. A detailed understanding of the basis of host specificity can provide important insights into molecular pathogenesis, the evolution of pathogenic microbes, and the potential for pathogens to cross the species barrier to infect new hosts. Comparative genomics and the development of humanized mouse models have provided important new tools with which to explore the basis of generalism and specialism. This review will examine host specificity of bacterial pathogens with a focus on generalist and specialist serovars of Salmonella enterica. PMID:24296346

  12. Domains and Naive Theories.

    PubMed

    Gelman, Susan A; Noles, Nicholaus S

    2011-09-01

    Human cognition entails domain-specific cognitive processes that influence memory, attention, categorization, problem-solving, reasoning, and knowledge organization. This review examines domain-specific causal theories, which are of particular interest for permitting an examination of how knowledge structures change over time. We first describe the properties of commonsense theories, and how commonsense theories differ from scientific theories, illustrating with children's classification of biological and non-biological kinds. We next consider the implications of domain-specificity for broader issues regarding cognitive development and conceptual change. We then examine the extent to which domain-specific theories interact, and how people reconcile competing causal frameworks. Future directions for research include examining how different content domains interact, the nature of theory change, the role of context (including culture, language, and social interaction) in inducing different frameworks, and the neural bases for domain-specific reasoning.

  13. Domains and Naive Theories

    PubMed Central

    Gelman, Susan A.; Noles, Nicholaus S.

    2013-01-01

    Human cognition entails domain-specific cognitive processes that influence memory, attention, categorization, problem-solving, reasoning, and knowledge organization. This review examines domain-specific causal theories, which are of particular interest for permitting an examination of how knowledge structures change over time. We first describe the properties of commonsense theories, and how commonsense theories differ from scientific theories, illustrating with children’s classification of biological and non-biological kinds. We next consider the implications of domain-specificity for broader issues regarding cognitive development and conceptual change. We then examine the extent to which domain-specific theories interact, and how people reconcile competing causal frameworks. Future directions for research include examining how different content domains interact, the nature of theory change, the role of context (including culture, language, and social interaction) in inducing different frameworks, and the neural bases for domain-specific reasoning. PMID:24187603

  14. The Drosophila melanogaster host model

    PubMed Central

    Igboin, Christina O.; Griffen, Ann L.; Leys, Eugene J.

    2012-01-01

    The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen–host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial–host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis–host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed. PMID:22368770

  15. Host genetics affect microbial ecosystems via host immunity.

    PubMed

    El Kafsi, Hela; Gorochov, Guy; Larsen, Martin

    2016-10-01

    Genetic evolution of multicellular organisms has occurred in response to environmental challenges, including competition for nutrients, climate change, physical and chemical stressors, and pathogens. However, fitness of an organism is dependent not only on defense efficacy, but also on the ability to take advantage of symbiotic organisms. Indeed, microbes not only encompass pathogenicity, but also enable efficient nutrient uptake from diets nondegradable by the host itself. Moreover, microbes play important roles in the development of host immunity. Here we review associations between specific host genes and variance in microbiota composition and compare with interactions between microbes and host immunity. Recent genome-wide association studies reveal that symbiosis between host and microbiota is the exquisite result of genetic coevolution. Moreover, a subset of microbes from human and mouse microbiota have been identified to interact with humoral and cellular immunity. Interestingly, microbes associated with both host genetics and host immunity are taxonomically related. Most involved are Bifidobacterium, Lactobacillus, and Akkermansia, which are dually associated with both host immunity and host genetics. We conclude that future therapeutics targeting microbiota in the context of chronic inflammatory diseases need to consider both immune and genetic host features associated with microbiota homeostasis.

  16. Phantom domain walls

    NASA Astrophysics Data System (ADS)

    Avelino, P. P.; Ferreira, V. M. C.; Menezes, J.; Sousa, L.

    2017-08-01

    We consider a model with two real scalar fields which admits phantom domain wall solutions. We investigate the structure and evolution of these phantom domain walls in an expanding homogeneous and isotropic universe. In particular, we show that the increase of the tension of the domain walls with cosmic time, associated to the evolution of the phantom scalar field, is responsible for an additional damping term in their equations of motion. We describe the macroscopic dynamics of phantom domain walls, showing that extended phantom defects whose tension varies on a cosmological time scale cannot be the dark energy.

  17. Visualizing domain wall and reverse domain superconductivity.

    PubMed

    Iavarone, M; Moore, S A; Fedor, J; Ciocys, S T; Karapetrov, G; Pearson, J; Novosad, V; Bader, S D

    2014-08-28

    In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application.

  18. Visualizing domain wall and reverse domain superconductivity

    PubMed Central

    Iavarone, M.; Moore, S. A.; Fedor, J.; Ciocys, S. T.; Karapetrov, G.; Pearson, J.; Novosad, V.; Bader, S. D.

    2014-01-01

    In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application. PMID:25164004

  19. Host range, host specificity and hypothesized host shift events among viruses of lower vertebrates.

    PubMed

    Bandín, Isabel; Dopazo, Carlos P

    2011-05-18

    The successful replication of a viral agent in a host is a complex process that often leads to a species specificity of the virus and can make interspecies transmission difficult. Despite this difficulty, natural host switch seems to have been frequent among viruses of lower vertebrates, especially fish viruses, since there are several viruses known to be able to infect a wide range of species. In the present review we will focus on well documented reports of broad host range, variations in host specificity, and host shift events hypothesized for viruses within the genera Ranavirus, Novirhabdovirus, Betanodavirus, Isavirus, and some herpesvirus.

  20. Host range, host specificity and hypothesized host shift events among viruses of lower vertebrates

    PubMed Central

    2011-01-01

    The successful replication of a viral agent in a host is a complex process that often leads to a species specificity of the virus and can make interspecies transmission difficult. Despite this difficulty, natural host switch seems to have been frequent among viruses of lower vertebrates, especially fish viruses, since there are several viruses known to be able to infect a wide range of species. In the present review we will focus on well documented reports of broad host range, variations in host specificity, and host shift events hypothesized for viruses within the genera Ranavirus, Novirhabdovirus, Betanodavirus, Isavirus, and some herpesvirus. PMID:21592358

  1. Solution structure of leptospiral LigA4 Big domain.

    PubMed

    Mei, Song; Zhang, Jiahai; Zhang, Xuecheng; Tu, Xiaoming

    2015-11-13

    Pathogenic Leptospiraspecies express immunoglobulin-like proteins which serve as adhesins to bind to the extracellular matrices of host cells. Leptospiral immunoglobulin-like protein A (LigA), a surface exposed protein containing tandem repeats of bacterial immunoglobulin-like (Big) domains, has been proved to be involved in the interaction of pathogenic Leptospira with mammalian host. In this study, the solution structure of the fourth Big domain of LigA (LigA4 Big domain) from Leptospira interrogans was solved by nuclear magnetic resonance (NMR). The structure of LigA4 Big domain displays a similar bacterial immunoglobulin-like fold compared with other Big domains, implying some common structural aspects of Big domain family. On the other hand, it displays some structural characteristics significantly different from classic Ig-like domain. Furthermore, Stains-all assay and NMR chemical shift perturbation revealed the Ca(2+) binding property of LigA4 Big domain. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Avian host defense peptides.

    PubMed

    Cuperus, Tryntsje; Coorens, Maarten; van Dijk, Albert; Haagsman, Henk P

    2013-11-01

    Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense of many organisms. It is becoming increasingly clear that in the animal kingdom the functions of HDPs are not confined to direct antimicrobial actions. Research in mammals has indicated that HDPs have many immunomodulatory functions and are also involved in other physiological processes ranging from development to wound healing. During the past five years our knowledge about avian HDPs has increased considerably. This review addresses our current knowledge on the evolution, regulation and biological functions of HDPs of birds.

  3. Environment or Host?

    PubMed Central

    Dirac, M. Ashworth; Horan, Kathleen L.; Doody, David R.; Meschke, J. Scott; Park, David R.; Jackson, Lisa A.; Weiss, Noel S.; Winthrop, Kevin L.

    2012-01-01

    Rationale: Mycobacterium avium complex lung disease is an increasingly common and chronically debilitating problem. Several host traits have been suggested or confirmed as risk factors. Potential environmental and behavioral risk factors have also been proposed. Few have been evaluated in comparative studies. Objectives: To determine if aerosol-generating activities in the home and garden, features of the home water supply, or several pulmonary and immune-compromising conditions are associated with Mycobacterium avium complex lung disease. Methods: Cases were recruited from academic medical centers and by informal referrals from nonuniversity practices in Washington and Oregon. Control subjects were recruited by random-digit dialing and matched to cases by age, sex, and partial telephone number. Associations were measured as odds ratios (OR) estimated using conditional logistic regression. Measurements and Main Results: Known and potential risk factors were measured by in-home interview. Fifty-two matched pairs were studied. Six of 12 examined host traits were associated with disease, including history of chronic obstructive pulmonary disease (OR, 10; 95% confidence interval [CI], 1.2–80), pneumonia hospitalization (OR, 3.4; 95% CI, 1.1–11), and steroid use (OR, 8; 95% CI, 1.6–41). In contrast, 11 of the 14 aerosol-generating activities and all five features of home water supply studied bore little or no association with disease. Conclusions: Aerosol-generating activities seem not to be risk factors for Mycobacterium avium complex lung disease in HIV-negative adults, but prior lung disease and immune-suppressing drugs seem to be associated with susceptibility. PMID:22859521

  4. Causal Learning Across Domains

    ERIC Educational Resources Information Center

    Schulz, Laura E.; Gopnik, Alison

    2004-01-01

    Five studies investigated (a) children's ability to use the dependent and independent probabilities of events to make causal inferences and (b) the interaction between such inferences and domain-specific knowledge. In Experiment 1, preschoolers used patterns of dependence and independence to make accurate causal inferences in the domains of…

  5. A Domain Analysis Bibliography

    DTIC Science & Technology

    1990-06-01

    Bauhaus , a prototype CASE workstation for D-SAPS development. [ARAN88A] Guillermo F. Arango. Domain Engineering for Software Reuse. PhD thesis...34 VITA90B: Domain Analysis within the ISEC Rapid Center 48 CMU/SEI-90-SR-3 Appendix III Alphabetical by Organization/Project BAUHAUS * ALLE87A

  6. Modeling Protein Domain Function

    ERIC Educational Resources Information Center

    Baker, William P.; Jones, Carleton "Buck"; Hull, Elizabeth

    2007-01-01

    This simple but effective laboratory exercise helps students understand the concept of protein domain function. They use foam beads, Styrofoam craft balls, and pipe cleaners to explore how domains within protein active sites interact to form a functional protein. The activity allows students to gain content mastery and an understanding of the…

  7. Domains of Learning.

    ERIC Educational Resources Information Center

    Gagne, Robert M.

    In planning educational research, recognition needs to be made of five domains of learning: (1) motor skills, (2) verbal information, (3) intellectual skills, (4) cognitive strategies, and (5) attitudes. In being cognizant of these domains, the researcher is able to distinguish the parts of a content area which are subject to different…

  8. Modeling Protein Domain Function

    ERIC Educational Resources Information Center

    Baker, William P.; Jones, Carleton "Buck"; Hull, Elizabeth

    2007-01-01

    This simple but effective laboratory exercise helps students understand the concept of protein domain function. They use foam beads, Styrofoam craft balls, and pipe cleaners to explore how domains within protein active sites interact to form a functional protein. The activity allows students to gain content mastery and an understanding of the…

  9. Domain wall filters

    SciTech Connect

    Baer, Oliver; Narayanan, Rajamani; Neuberger, Herbert; Witzel, Oliver

    2007-03-15

    We propose using the extra dimension separating the domain walls carrying lattice quarks of opposite handedness to gradually filter out the ultraviolet fluctuations of the gauge fields that are felt by the fermionic excitations living in the bulk. This generalization of the homogeneous domain wall construction has some theoretical features that seem nontrivial.

  10. Sac phosphatase domain proteins.

    PubMed Central

    Hughes, W E; Cooke, F T; Parker, P J

    2000-01-01

    Advances in our understanding of the roles of phosphatidylinositol phosphates in controlling cellular functions such as endocytosis, exocytosis and the actin cytoskeleton have included new insights into the phosphatases that are responsible for the interconversion of these lipids. One of these is an entirely novel class of phosphatase domain found in a number of well characterized proteins. Proteins containing this Sac phosphatase domain include the yeast Saccharomyces cerevisiae proteins Sac1p and Fig4p. The Sac phosphatase domain is also found within the mammalian phosphoinositide 5-phosphatase synaptojanin and the yeast synaptojanin homologues Inp51p, Inp52p and Inp53p. These proteins therefore contain both Sac phosphatase and 5-phosphatase domains. This review describes the Sac phosphatase domain-containing proteins and their actions, with particular reference to the genetic and biochemical insights provided by study of the yeast Saccharomyces cerevisiae. PMID:10947947

  11. Host Stress Drives Salmonella Recrudescence

    PubMed Central

    Verbrugghe, Elin; Dhaenens, Maarten; Leyman, Bregje; Boyen, Filip; Shearer, Neil; Van Parys, Alexander; Haesendonck, Roel; Bert, Wim; Favoreel, Herman; Deforce, Dieter; Thompson, Arthur; Haesebrouck, Freddy; Pasmans, Frank

    2016-01-01

    Host stress is well known to result in flare-ups of many bacterial, viral and parasitic infections. The mechanism by which host stress is exploited to increase pathogen loads, is poorly understood. Here we show that Salmonella enterica subspecies enterica serovar Typhimurium employs a dedicated mechanism, driven by the scsA gene, to respond to the host stress hormone cortisol. Through this mechanism, cortisol increases Salmonella proliferation inside macrophages, resulting in increased intestinal infection loads in DBA/2J mice. ScsA directs overall Salmonella virulence gene expression under conditions that mimic the intramacrophagic environment of Salmonella, and stimulates the host cytoskeletal alterations that are required for increased Salmonella proliferation inside cortisol exposed macrophages. We thus provide evidence that in a stressed host, the complex interplay between a pathogen and its host endocrine and innate immune system increases intestinal pathogen loads to facilitate pathogen dispersal. PMID:26857846

  12. Cross Domain Analogies for Learning Domain Theories

    DTIC Science & Technology

    2007-01-01

    Example Problem and Worked Solution All problems and worked solutions used in this work were taken from the same physics textbook ( Giancoli 1991...domain theory. We close with a discussion of related work and our plans for the future. Representations and Problem Solving Representing physics ...small compared to the 30,000+ concepts and 8,000+ predicates already defined in the KB. Thus, objects, relations, and events that appear in physics

  13. Functional Interchangeability of Late Domains, Late Domain Cofactors and Ubiquitin in Viral Budding

    PubMed Central

    Zhadina, Maria; Bieniasz, Paul D.

    2010-01-01

    The membrane scission event that separates nascent enveloped virions from host cell membranes often requires the ESCRT pathway, which can be engaged through the action of peptide motifs, termed late (L-) domains, in viral proteins. Viral PTAP and YPDL-like L-domains bind directly to the ESCRT-I and ALIX components of the ESCRT pathway, while PPxY motifs bind Nedd4-like, HECT-domain containing, ubiquitin ligases (e.g. WWP1). It has been unclear precisely how ubiquitin ligase recruitment ultimately leads to particle release. Here, using a lysine-free viral Gag protein derived from the prototypic foamy virus (PFV), where attachment of ubiquitin to Gag can be controlled, we show that several different HECT domains can replace the WWP1 HECT domain in chimeric ubiquitin ligases and drive budding. Moreover, artificial recruitment of isolated HECT domains to Gag is sufficient to stimulate budding. Conversely, the HECT domain becomes dispensable if the other domains of WWP1 are directly fused to an ESCRT-1 protein. In each case where budding is driven by a HECT domain, its catalytic activity is essential, but Gag ubiquitination is dispensable, suggesting that ubiquitin ligation to trans-acting proteins drives budding. Paradoxically, however, we also demonstrate that direct fusion of a ubiquitin moiety to the C-terminus of PFV Gag can also promote budding, suggesting that ubiquitination of Gag can substitute for ubiquitination of trans-acting proteins. Depletion of Tsg101 and ALIX inhibits budding that is dependent on ubiquitin that is fused to Gag, or ligated to trans-acting proteins through the action of a PPxY motif. These studies underscore the flexibility in the ways that the ESCRT pathway can be engaged, and suggest a model in which the identity of the protein to which ubiquitin is attached is not critical for subsequent recruitment of ubiquitin-binding components of the ESCRT pathway and viral budding to proceed. PMID:20975941

  14. Functional interchangeability of late domains, late domain cofactors and ubiquitin in viral budding.

    PubMed

    Zhadina, Maria; Bieniasz, Paul D

    2010-10-21

    The membrane scission event that separates nascent enveloped virions from host cell membranes often requires the ESCRT pathway, which can be engaged through the action of peptide motifs, termed late (L-) domains, in viral proteins. Viral PTAP and YPDL-like L-domains bind directly to the ESCRT-I and ALIX components of the ESCRT pathway, while PPxY motifs bind Nedd4-like, HECT-domain containing, ubiquitin ligases (e.g. WWP1). It has been unclear precisely how ubiquitin ligase recruitment ultimately leads to particle release. Here, using a lysine-free viral Gag protein derived from the prototypic foamy virus (PFV), where attachment of ubiquitin to Gag can be controlled, we show that several different HECT domains can replace the WWP1 HECT domain in chimeric ubiquitin ligases and drive budding. Moreover, artificial recruitment of isolated HECT domains to Gag is sufficient to stimulate budding. Conversely, the HECT domain becomes dispensable if the other domains of WWP1 are directly fused to an ESCRT-1 protein. In each case where budding is driven by a HECT domain, its catalytic activity is essential, but Gag ubiquitination is dispensable, suggesting that ubiquitin ligation to trans-acting proteins drives budding. Paradoxically, however, we also demonstrate that direct fusion of a ubiquitin moiety to the C-terminus of PFV Gag can also promote budding, suggesting that ubiquitination of Gag can substitute for ubiquitination of trans-acting proteins. Depletion of Tsg101 and ALIX inhibits budding that is dependent on ubiquitin that is fused to Gag, or ligated to trans-acting proteins through the action of a PPxY motif. These studies underscore the flexibility in the ways that the ESCRT pathway can be engaged, and suggest a model in which the identity of the protein to which ubiquitin is attached is not critical for subsequent recruitment of ubiquitin-binding components of the ESCRT pathway and viral budding to proceed.

  15. 2015 Cross-Domain Deterrence Seminar Summary Report

    SciTech Connect

    Juarez, A.

    2016-01-11

    Lawrence Livermore National Laboratory (LLNL) hosted the 2nd Annual Cross-Domain Deterrence Seminar on November 17th, 2015 in Livermore, CA. The seminar was sponsored by LLNL’s Center for Global Security Research (CGSR), National Security Office (NSO), and Global Security program. This summary covers the seminar’s panels and subsequent discussions.

  16. Visualizing Knowledge Domains.

    ERIC Educational Resources Information Center

    Borner, Katy; Chen, Chaomei; Boyack, Kevin W.

    2003-01-01

    Reviews visualization techniques for scientific disciplines and information retrieval and classification. Highlights include historical background of scientometrics, bibliometrics, and citation analysis; map generation; process flow of visualizing knowledge domains; measures and similarity calculations; vector space model; factor analysis;…

  17. Stability of domain structures in multi-domain proteins

    PubMed Central

    Bhaskara, Ramachandra M.; Srinivasan, Narayanaswamy

    2011-01-01

    Multi-domain proteins have many advantages with respect to stability and folding inside cells. Here we attempt to understand the intricate relationship between the domain-domain interactions and the stability of domains in isolation. We provide quantitative treatment and proof for prevailing intuitive ideas on the strategies employed by nature to stabilize otherwise unstable domains. We find that domains incapable of independent stability are stabilized by favourable interactions with tethered domains in the multi-domain context. Stability of such folds to exist independently is optimized by evolution. Specific residue mutations in the sites equivalent to inter-domain interface enhance the overall solvation, thereby stabilizing these domain folds independently. A few naturally occurring variants at these sites alter communication between domains and affect stability leading to disease manifestation. Our analysis provides safe guidelines for mutagenesis which have attractive applications in obtaining stable fragments and domain constructs essential for structural studies by crystallography and NMR. PMID:22355559

  18. Determination of host RNA helicases activity in viral replication

    PubMed Central

    Sharma, Amit; Boris-Lawrie, Kathleen

    2016-01-01

    RNA helicases are encoded by all eukaryotic and prokaryotic cells and a minority of viruses. Activity of RNA helicases is necessary for all steps in the expression of cells and viruses and the host innate response to virus infection. Their vast functional repertoire is attributable to the core ATPase-dependent helicase domain in conjunction with flanking domains that are interchangeable and engage viral and cellular cofactors. Here, we address the important issue of host RNA helicases that are necessary for replication of a virus. The chapter covers approaches to identification and characterization of candidate helicases and methods to define the biochemical and biophysical parameters of specificity and functional activity of the enzymes. We discuss the context of cellular RNA helicase activity and virion-associated RNA helicases. The methodology and choice of controls fosters the assessment of the virologic scope of RNA helicases across divergent cell lineages and viral replication cycles. PMID:22713331

  19. Stennis hosts 2010 Special Olympics

    NASA Technical Reports Server (NTRS)

    2010-01-01

    Sarah Johnson, 28, of Gulfport, carries in the Olympic torch to signal the start of the 2010 Area III Special Olympic games at NASA's John C. Stennis Space Center on March 27. Stennis volunteers hosted special needs athletes from across the area for the event. Stennis is an annual host of the games.

  20. Ethanol production by recombinant hosts

    DOEpatents

    Ingram, Lonnie O.; Beall, David S.; Burchhardt, Gerhard F. H.; Guimaraes, Walter V.; Ohta, Kazuyoshi; Wood, Brent E.; Shanmugam, Keelnatham T.

    1995-01-01

    Novel plasmids comprising genes which code for the alcohol dehydrogenase and pyruvate decarboxylase are described. Also described are recombinant hosts which have been transformed with genes coding for alcohol dehydrogenase and pyruvate. By virtue of their transformation with these genes, the recombinant hosts are capable of producing significant amounts of ethanol as a fermentation product. Also disclosed are methods for increasing the growth of recombinant hosts and methods for reducing the accumulation of undesirable metabolic products in the growth medium of these hosts. Also disclosed are recombinant host capable of producing significant amounts of ethanol as a fermentation product of oligosaccharides and plasmids comprising genes encoding polysaccharases, in addition to the genes described above which code for the alcohol dehydrogenase and pyruvate decarboxylase. Further, methods are described for producing ethanol from oligomeric feedstock using the recombinant hosts described above. Also provided is a method for enhancing the production of functional proteins in a recombinant host comprising overexpressing an adhB gene in the host. Further provided are process designs for fermenting oligosaccharide-containing biomass to ethanol.

  1. Ethanol production by recombinant hosts

    DOEpatents

    Fowler, David E.; Horton, Philip G.; Ben-Bassat, Arie

    1996-01-01

    Novel plasmids comprising genes which code for the alcohol dehydrogenase and pyruvate decarboxylase are described. Also described are recombinant hosts which have been transformed with genes coding for alcohol dehydrogenase and pyruvate. By virtue of their transformation with these genes, the recombinant hosts are capable of producing significant amounts of ethanol as a fermentation product. Also disclosed are methods for increasing the growth of recombinant hosts and methods for reducing the accumulation of undesirable metabolic products in the growth medium of these hosts. Also disclosed are recombinant host capable of producing significant amounts of ethanol as a fermentation product of oligosaccharides and plasmids comprising genes encoding polysaccharases, in addition to the genes described above which code for the alcohol dehydrogenase and pyruvate decarboxylase. Further, methods are described for producing ethanol from oligomeric feedstock using the recombinant hosts described above. Also provided is a method for enhancing the production of functional proteins in a recombinant host comprising overexpressing an adhB gene in the host. Further provided are process designs for fermenting oligosaccharide-containing biomass to ethanol.

  2. Stennis hosts 2010 Special Olympics

    NASA Image and Video Library

    2010-03-27

    Sarah Johnson, 28, of Gulfport, carries in the Olympic torch to signal the start of the 2010 Area III Special Olympic games at NASA's John C. Stennis Space Center on March 27. Stennis volunteers hosted special needs athletes from across the area for the event. Stennis is an annual host of the games.

  3. Software architecture design domain

    SciTech Connect

    White, S.A.

    1996-12-31

    Software architectures can provide a basis for the capture and subsequent reuse of design knowledge. The goal of software architecture is to allow the design of a system to take place at a higher level of abstraction; a level concerned with components, connections, constraints, rationale. This architectural view of software adds a new layer of abstraction to the traditional design phase of software development. It has resulted in a flurry of activity towards techniques, tools, and architectural design languages developed specifically to assist with this activity. An analysis of architectural descriptions, even though they differ in notation, shows a common set of key constructs that are present across widely varying domains. These common aspects form a core set of constructs that should belong to any ADL in order to for the language to offer the ability to specify software systems at the architectural level. This analysis also revealed a second set of constructs which served to expand the first set thereby improving the syntax and semantics. These constructs are classified according to whether they provide representation and analysis support for architectures belonging to many varying application domains (domain-independent construct class) or to a particular application domain (domain-dependent constructs). This paper presents the constructs of these two classes, their placement in the architecture design domain and shows how they may be used to classify, select, and analyze proclaimed architectural design languages (ADLs).

  4. Salmonellae interactions with host processes.

    PubMed

    LaRock, Doris L; Chaudhary, Anu; Miller, Samuel I

    2015-04-01

    Salmonellae invasion and intracellular replication within host cells result in a range of diseases, including gastroenteritis, bacteraemia, enteric fever and focal infections. In recent years, considerable progress has been made in our understanding of the molecular mechanisms that salmonellae use to alter host cell physiology; through the delivery of effector proteins with specific activities and through the modulation of defence and stress response pathways. In this Review, we summarize our current knowledge of the complex interplay between bacterial and host factors that leads to inflammation, disease and, in most cases, control of the infection by its animal hosts, with a particular focus on Salmonella enterica subsp. enterica serovar Typhimurium. We also highlight gaps in our knowledge of the contributions of salmonellae and the host to disease pathogenesis, and we suggest future avenues for further study.

  5. Increased magnetic damping of a single domain wall and adjacent magnetic domains detected by spin torque diode in a nanostripe

    NASA Astrophysics Data System (ADS)

    Lequeux, Steven; Sampaio, Joao; Bortolotti, Paolo; Devolder, Thibaut; Matsumoto, Rie; Yakushiji, Kay; Kubota, Hitoshi; Fukushima, Akio; Yuasa, Shinji; Nishimura, Kazumasa; Nagamine, Yoshinori; Tsunekawa, Koji; Cros, Vincent; Grollier, Julie

    2015-11-01

    Spin torque resonance has been used to simultaneously probe the dynamics of a magnetic domain wall and of magnetic domains in a nanostripe magnetic tunnel junction. Due to the large associated resistance variations, we are able to analyze quantitatively the resonant properties of these single nanoscale magnetic objects. In particular, we find that the magnetic damping of both the domains and the domain wall is doubled compared to the damping value of the host magnetic layer. We estimate the contributions to the damping arising from the dipolar couplings between the different layers in the junction and from the intralayer spin pumping effect, and find that they cannot explain the large damping enhancement that we observe. We conclude that the measured increased damping is intrinsic to large amplitudes excitations of spatially localized modes or solitons such as vibrating or propagating domain walls.

  6. Domain engineering of the metastable domains in the 4f-uniaxial-ferromagnet CeRu2Ga2B

    PubMed Central

    Wulferding, D.; Kim, H.; Yang, I.; Jeong, J.; Barros, K.; Kato, Y.; Martin, I.; Ayala-Valenzuela, O. E.; Lee, M.; Choi, H. C.; Ronning, F.; Civale, L.; Baumbach, R. E.; Bauer, E. D.; Thompson, J. D.; Movshovich, R.; Kim, Jeehoon

    2017-01-01

    In search of novel, improved materials for magnetic data storage and spintronic devices, compounds that allow a tailoring of magnetic domain shapes and sizes are essential. Good candidates are materials with intrinsic anisotropies or competing interactions, as they are prone to host various domain phases that can be easily and precisely selected by external tuning parameters such as temperature and magnetic field. Here, we utilize vector magnetic fields to visualize directly the magnetic anisotropy in the uniaxial ferromagnet CeRu2Ga2B. We demonstrate a feasible control both globally and locally of domain shapes and sizes by the external field as well as a smooth transition from single stripe to bubble domains, which opens the door to future applications based on magnetic domain tailoring. PMID:28393931

  7. Domain engineering of the metastable domains in the 4f-uniaxial-ferromagnet CeRu2Ga2B

    DOE PAGES

    Wulferding, Dirk; Kim, Hoon; Yang, Ilkyu; ...

    2017-04-10

    In search of novel, improved materials for magnetic data storage and spintronic devices, compounds that allow a tailoring of magnetic domain shapes and sizes are essential. Good candidates are materials with intrinsic anisotropies or competing interactions, as they are prone to host various domain phases that can be easily and precisely selected by external tuning parameters such as temperature and magnetic field. Here, we utilize vector magnetic fields to visualize directly the magnetic anisotropy in the uniaxial ferromagnet CeRu2Ga2B. We demonstrate a feasible control both globally and locally of domain shapes and sizes by the external field as well asmore » a smooth transition from single stripe to bubble domains, which opens the door to future applications based on magnetic domain tailoring.« less

  8. Increased magnetic damping of a single domain wall and adjacent magnetic domains detected by spin torque diode in a nanostripe

    SciTech Connect

    Lequeux, Steven; Sampaio, Joao; Bortolotti, Paolo; Cros, Vincent; Grollier, Julie; Matsumoto, Rie; Yakushiji, Kay; Kubota, Hitoshi; Fukushima, Akio; Yuasa, Shinji; Nishimura, Kazumasa; Nagamine, Yoshinori; Tsunekawa, Koji

    2015-11-02

    Spin torque resonance has been used to simultaneously probe the dynamics of a magnetic domain wall and of magnetic domains in a nanostripe magnetic tunnel junction. Due to the large associated resistance variations, we are able to analyze quantitatively the resonant properties of these single nanoscale magnetic objects. In particular, we find that the magnetic damping of both the domains and the domain wall is doubled compared to the damping value of the host magnetic layer. We estimate the contributions to the damping arising from the dipolar couplings between the different layers in the junction and from the intralayer spin pumping effect, and find that they cannot explain the large damping enhancement that we observe. We conclude that the measured increased damping is intrinsic to large amplitudes excitations of spatially localized modes or solitons such as vibrating or propagating domain walls.

  9. Domain engineering of the metastable domains in the 4f-uniaxial-ferromagnet CeRu2Ga2B

    NASA Astrophysics Data System (ADS)

    Wulferding, D.; Kim, H.; Yang, I.; Jeong, J.; Barros, K.; Kato, Y.; Martin, I.; Ayala-Valenzuela, O. E.; Lee, M.; Choi, H. C.; Ronning, F.; Civale, L.; Baumbach, R. E.; Bauer, E. D.; Thompson, J. D.; Movshovich, R.; Kim, Jeehoon

    2017-04-01

    In search of novel, improved materials for magnetic data storage and spintronic devices, compounds that allow a tailoring of magnetic domain shapes and sizes are essential. Good candidates are materials with intrinsic anisotropies or competing interactions, as they are prone to host various domain phases that can be easily and precisely selected by external tuning parameters such as temperature and magnetic field. Here, we utilize vector magnetic fields to visualize directly the magnetic anisotropy in the uniaxial ferromagnet CeRu2Ga2B. We demonstrate a feasible control both globally and locally of domain shapes and sizes by the external field as well as a smooth transition from single stripe to bubble domains, which opens the door to future applications based on magnetic domain tailoring.

  10. Protein–Protein Interactions in Virus–Host Systems

    PubMed Central

    Brito, Anderson F.; Pinney, John W.

    2017-01-01

    To study virus–host protein interactions, knowledge about viral and host protein architectures and repertoires, their particular evolutionary mechanisms, and information on relevant sources of biological data is essential. The purpose of this review article is to provide a thorough overview about these aspects. Protein domains are basic units defining protein interactions, and the uniqueness of viral domain repertoires, their mode of evolution, and their roles during viral infection make viruses interesting models of study. Mutations at protein interfaces can reduce or increase their binding affinities by changing protein electrostatics and structural properties. During the course of a viral infection, both pathogen and cellular proteins are constantly competing for binding partners. Endogenous interfaces mediating intraspecific interactions—viral–viral or host–host interactions—are constantly targeted and inhibited by exogenous interfaces mediating viral–host interactions. From a biomedical perspective, blocking such interactions is the main mechanism underlying antiviral therapies. Some proteins are able to bind multiple partners, and their modes of interaction define how fast these “hub proteins” evolve. “Party hubs” have multiple interfaces; they establish simultaneous/stable (domain–domain) interactions, and tend to evolve slowly. On the other hand, “date hubs” have few interfaces; they establish transient/weak (domain–motif) interactions by means of short linear peptides (15 or fewer residues), and can evolve faster. Viral infections are mediated by several protein–protein interactions (PPIs), which can be represented as networks (protein interaction networks, PINs), with proteins being depicted as nodes, and their interactions as edges. It has been suggested that viral proteins tend to establish interactions with more central and highly connected host proteins. In an evolutionary arms race, viral and host proteins are constantly

  11. Non-immune immunoglobulins shield Schistosoma japonicum from host immunorecognition.

    PubMed

    Wu, Chuang; Hou, Nan; Piao, Xianyu; Liu, Shuai; Cai, Pengfei; Xiao, Yan; Chen, Qijun

    2015-08-24

    Schistosomiasis is a major human parasitic disease with a global impact. Schistosoma japonicum, the most difficult to control, can survive within host veins for decades. Mechanisms of immune evasion by the parasite, including antigenic variation and surface masking, have been implicated but not well defined. In this study, we defined the immunoglobulin-binding proteomes of S. japonicum using human IgG, IgM, and IgE as the molecular bait for affinity purification, followed by protein identification by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Several proteins situated at the tegument of S. japonicum were able to nonselectively bind to the Fc domain of host immunoglobulins, indicating a mechanism for the avoidance of host immune attachment and recognition. The profile of the immunoglobulin-binding proteomes provides further clues for immune evasion mechanisms adopted by S. japonicum.

  12. Non-immune immunoglobulins shield Schistosoma japonicum from host immunorecognition

    PubMed Central

    Wu, Chuang; Hou, Nan; Piao, Xianyu; Liu, Shuai; Cai, Pengfei; Xiao, Yan; Chen, Qijun

    2015-01-01

    Schistosomiasis is a major human parasitic disease with a global impact. Schistosoma japonicum, the most difficult to control, can survive within host veins for decades. Mechanisms of immune evasion by the parasite, including antigenic variation and surface masking, have been implicated but not well defined. In this study, we defined the immunoglobulin-binding proteomes of S. japonicum using human IgG, IgM, and IgE as the molecular bait for affinity purification, followed by protein identification by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Several proteins situated at the tegument of S. japonicum were able to nonselectively bind to the Fc domain of host immunoglobulins, indicating a mechanism for the avoidance of host immune attachment and recognition. The profile of the immunoglobulin-binding proteomes provides further clues for immune evasion mechanisms adopted by S. japonicum. PMID:26299686

  13. Structure-based prediction of host-pathogen protein interactions.

    PubMed

    Mariano, Rachelle; Wuchty, Stefan

    2017-03-16

    The discovery, validation, and characterization of protein-based interactions from different species are crucial for translational research regarding a variety of pathogens, ranging from the malaria parasite Plasmodium falciparum to HIV-1. Here, we review recent advances in the prediction of host-pathogen protein interfaces using structural information. In particular, we observe that current methods chiefly perform machine learning on sequence and domain information to produce large sets of candidate interactions that are further assessed and pruned to generate final, highly probable sets. Structure-based studies have also emphasized the electrostatic properties and evolutionary transformations of pathogenic interfaces, supplying crucial insight into antigenic determinants and the ways pathogens compete for host protein binding. Advancements in spectroscopic and crystallographic methods complement the aforementioned techniques, permitting the rigorous study of true positives at a molecular level. Together, these approaches illustrate how protein structure on a variety of levels functions coordinately and dynamically to achieve host takeover.

  14. Emerging Supramolecular Therapeutic Carriers Based on Host-Guest Interactions.

    PubMed

    Karim, Anis Abdul; Dou, Qingqing; Li, Zibiao; Loh, Xian Jun

    2016-05-06

    Recent advances in host-guest chemistry have significantly influenced the construction of supramolecular soft biomaterials. The highly selective and non-covalent interactions provide vast possibilities of manipulating supramolecular self-assemblies at the molecular level, allowing a rational design to control the sizes and morphologies of the resultant objects as carrier vehicles in a delivery system. In this Focus Review, the most recent developments of supramolecular self-assemblies through host-guest inclusion, including nanoparticles, micelles, vesicles, hydrogels, and various stimuli-responsive morphology transition materials are presented. These sophisticated materials with diverse functions, oriented towards therapeutic agent delivery, are further summarized into several active domains in the areas of drug delivery, gene delivery, co-delivery and site-specific targeting deliveries. Finally, the possible strategies for future design of multifunctional delivery carriers by combining host-guest chemistry with biological interface science are proposed.

  15. Domains in Ferroelectric Nanostructures

    NASA Astrophysics Data System (ADS)

    Gregg, Marty

    2010-03-01

    Ferroelectric materials have great potential in influencing the future of small scale electronics. At a basic level, this is because ferroelectric surfaces are charged, and so interact strongly with charge-carrying metals and semiconductors - the building blocks for all electronic systems. Since the electrical polarity of the ferroelectric can be reversed, surfaces can both attract and repel charges in nearby materials, and can thereby exert complete control over both charge distribution and movement. It should be no surprise, therefore, that microelectronics industries have already looked very seriously at harnessing ferroelectric materials in a variety of applications, from solid state memory chips (FeRAMs) to field effect transistors (FeFETs). In all such applications, switching the direction of the polarity of the ferroelectric is a key aspect of functional behavior. The mechanism for switching involves the field-induced nucleation and growth of domains. Domain coarsening, through domain wall propagation, eventually causes the entire ferroelectric to switch its polar direction. It is thus the existence and behavior of domains that determine the switching response, and ultimately the performance of the ferroelectric device. A major issue, associated with the integration of ferroelectrics into microelectronic devices, has been that the fundamental properties associated with ferroelectrics, when in bulk form, appear to change quite dramatically and unpredictably when at the nanoscale: new modes of behaviour, and different functional characteristics from those seen in bulk appear. For domains, in particular, the proximity of surfaces and boundaries have a dramatic effect: surface tension and depolarizing fields both serve to increase the equilibrium density of domains, such that minor changes in scale or morphology can have major ramifications for domain redistribution. Given the importance of domains in dictating the overall switching characteristics of a device

  16. Extending Protein Domain Boundary Predictors to Detect Discontinuous Domains

    PubMed Central

    Xue, Zhidong; Jang, Richard; Govindarajoo, Brandon; Huang, Yichu; Wang, Yan

    2015-01-01

    A variety of protein domain predictors were developed to predict protein domain boundaries in recent years, but most of them cannot predict discontinuous domains. Considering nearly 40% of multidomain proteins contain one or more discontinuous domains, we have developed DomEx to enable domain boundary predictors to detect discontinuous domains by assembling the continuous domain segments. Discontinuous domains are predicted by matching the sequence profile of concatenated continuous domain segments with the profiles from a single-domain library derived from SCOP and CATH, and Pfam. Then the matches are filtered by similarity to library templates, a symmetric index score and a profile-profile alignment score. DomEx recalled 32.3% discontinuous domains with 86.5% precision when tested on 97 non-homologous protein chains containing 58 continuous and 99 discontinuous domains, in which the predicted domain segments are within ±20 residues of the boundary definitions in CATH 3.5. Compared with our recently developed predictor, ThreaDom, which is the state-of-the-art tool to detect discontinuous-domains, DomEx recalled 26.7% discontinuous domains with 72.7% precision in a benchmark with 29 discontinuous-domain chains, where ThreaDom failed to predict any discontinuous domains. Furthermore, combined with ThreaDom, the method ranked number one among 10 predictors. The source code and datasets are available at https://github.com/xuezhidong/DomEx. PMID:26502173

  17. Cucumis melo endornavirus: Genome organization, host range and co-divergence with the host.

    PubMed

    Sabanadzovic, Sead; Wintermantel, William M; Valverde, Rodrigo A; McCreight, James D; Aboughanem-Sabanadzovic, Nina

    2016-03-02

    A high molecular weight dsRNA was isolated from a Cucumis melo L. plant (referred to as 'CL01') of an unknown cultivar and completely sequenced. Sequence analyses showed that dsRNA is associated with an endornavirus for which a name Cucumis melo endornavirus (CmEV) is proposed. The genome of CmEV-CL01 consists of 15,078 nt, contains a single, 4939 codons-long ORF and terminates with a stretch of 10 cytosine residues. Comparisons of the putative CmEV-encoded polyprotein with available references in protein databases revealed a unique genome organization characterized by the presence of the following domains: viral helicase Superfamily 1 (Hel-1), three glucosyltransferases (doublet of putative capsular polysaccharide synthesis proteins and a putative C_28_Glycosyltransferase), and an RNA-dependent RNA polymerase (RdRp). The presence of three glycome-related domains of different origin makes the genome organization of CmEV unique among endornaviruses. Phylogenetic analyses of viral RdRp domains showed that CmEV belongs to a specific lineage within the family Endornaviridae made exclusively of plant-infecting endornaviruses. An RT-PCR based survey demonstrated high incidence of CmEV among melon germplasm accession (>87% of tested samples). Analyses of partial genome sequences of CmEV isolates from 26 different melon genotypes suggest fine-tuned virus adaptation and co-divergence with the host. Finally, results of the present study revealed that CmEV is present in plants belonging to three different genera in the family Cucurbitaceae. Such diverse host range is unreported for known endornaviruses and suggests a long history of CmEV association with cucurbits predating their speciation.

  18. Hosts and parasites as aliens.

    PubMed

    Taraschewski, H

    2006-06-01

    Over the past decades, various free-living animals (hosts) and their parasites have invaded recipient areas in which they had not previously occurred, thus gaining the status of aliens or exotics. In general this happened to a low extent for hundreds of years. With variable frequency, invasions have been followed by the dispersal and establishment of non-indigenous species, whether host or parasite. In the literature thus far, colonizations by both hosts and parasites have not been treated and reviewed together, although both are usually interwoven in various ways. As to those factors permitting invasive success and colonization strength, various hypotheses have been put forward depending on the scientific background of respective authors and on the conspicuousness of certain invasions. Researchers who have tried to analyse characteristic developmental patterns, the speed of dispersal or the degree of genetic divergence in populations of alien species have come to different conclusions. Among parasitologists, the applied aspects of parasite invasions, such as the negative effects on economically important hosts, have long been at the centre of interest. In this contribution, invasions by hosts as well as parasites are considered comparatively, revealing many similarities and a few differences. Two helminths, the liver fluke, Fasciola hepatica, of cattle and sheep and the swimbladder nematode, Anguillicola crassus, of eels are shown to be useful as model parasites for the study of animal invasions and environmental global change. Introductions of F. hepatica have been associated with imports of cattle or other grazing animals. In various target areas, susceptible lymnaeid snails serving as intermediate hosts were either naturally present and/or were introduced from the donor continent of the parasite (Europe) and/or from other regions which were not within the original range of the parasite, partly reflecting progressive stages of a global biota change. In several

  19. Axion domain wall baryogenesis

    SciTech Connect

    Daido, Ryuji; Kitajima, Naoya; Takahashi, Fuminobu

    2015-07-28

    We propose a new scenario of baryogenesis, in which annihilation of axion domain walls generates a sizable baryon asymmetry. Successful baryogenesis is possible for a wide range of the axion mass and decay constant, m≃10{sup 8}–10{sup 13} GeV and f≃10{sup 13}–10{sup 16} GeV. Baryonic isocurvature perturbations are significantly suppressed in our model, in contrast to various spontaneous baryogenesis scenarios in the slow-roll regime. In particular, the axion domain wall baryogenesis is consistent with high-scale inflation which generates a large tensor-to-scalar ratio within the reach of future CMB B-mode experiments. We also discuss the gravitational waves produced by the domain wall annihilation and its implications for the future gravitational wave experiments.

  20. Axion domain wall baryogenesis

    SciTech Connect

    Daido, Ryuji; Kitajima, Naoya; Takahashi, Fuminobu E-mail: kitajima@tuhep.phys.tohoku.ac.jp

    2015-07-01

    We propose a new scenario of baryogenesis, in which annihilation of axion domain walls generates a sizable baryon asymmetry. Successful baryogenesis is possible for a wide range of the axion mass and decay constant, m ≅ 10{sup 8}–10{sup 13} GeV and f ≅ 10{sup 13}–10{sup 16} GeV . Baryonic isocurvature perturbations are significantly suppressed in our model, in contrast to various spontaneous baryogenesis scenarios in the slow-roll regime. In particular, the axion domain wall baryogenesis is consistent with high-scale inflation which generates a large tensor-to-scalar ratio within the reach of future CMB B-mode experiments. We also discuss the gravitational waves produced by the domain wall annihilation and its implications for the future gravitational wave experiments.

  1. Function and evolution of ubiquitous bacterial signaling adapter phosphopeptide recognition domain FHA.

    PubMed

    Weiling, Hong; Xiaowen, Yu; Chunmei, Li; Jianping, Xie

    2013-03-01

    Forkhead-associated domain (FHA) is a phosphopeptide recognition domain embedded in some regulatory proteins. With similar fold type to important eukaryotic signaling molecules such as Smad2 and IRF3, the role of bacterial FHA domain is intensively pursued. Reported bacterial FHA domain roles include: regulation of glutamate and lipids production, regulation of cell shape, type III secretion, ethambutol resistance, sporulation, signal transduction, carbohydrate storage and transport, and pathogenic and symbiotic host-bacterium interactions. To provide basis for the studies of other bacterial FHA domain containing proteins, the status of bacterial FHA functionality and evolution were summarized. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  2. Mistletoe ecophysiology: Host-parasite interactions

    Treesearch

    G. Glatzel; B. W. Geils

    2009-01-01

    Mistletoes are highly specialized perennial flowering plants adapted to parasitic life on aerial parts of their hosts. In our discussion on the physiological interactions between parasite and host, we focus on water relations, mineral nutrition, and the effect of host vigour. When host photosynthesis is greatest, the xylem water potential of the host is most negative....

  3. Optimal domain decomposition strategies

    NASA Technical Reports Server (NTRS)

    Yoon, Yonghyun; Soni, Bharat K.

    1995-01-01

    The primary interest of the authors is in the area of grid generation, in particular, optimal domain decomposition about realistic configurations. A grid generation procedure with optimal blocking strategies has been developed to generate multi-block grids for a circular-to-rectangular transition duct. The focus of this study is the domain decomposition which optimizes solution algorithm/block compatibility based on geometrical complexities as well as the physical characteristics of flow field. The progress realized in this study is summarized in this paper.

  4. Meningococcal interactions with the host.

    PubMed

    Carbonnelle, Etienne; Hill, Darryl J; Morand, Philippe; Griffiths, Natalie J; Bourdoulous, Sandrine; Murillo, Isabel; Nassif, Xavier; Virji, Mumtaz

    2009-06-24

    Neisseria meningitidis interacts with host tissues through hierarchical, concerted and co-ordinated actions of a number of adhesins; many of which undergo antigenic and phase variation, a strategy that helps immune evasion. Three major structures, pili, Opa and Opc predominantly influence bacterial adhesion to host cells. Pili and Opa proteins also determine host and tissue specificity while Opa and Opc facilitate efficient cellular invasion. Recent studies have also implied a role of certain adhesin-receptor pairs in determining increased host susceptibility to infection. This chapter examines our current knowledge of meningococcal adhesion and invasion mechanisms particularly related to human epithelial and endothelial cells which are of primary importance in the disease process.

  5. Stennis hosts 2010 Special Olympics

    NASA Technical Reports Server (NTRS)

    2010-01-01

    B.J. Matherne, 27, of Gulfport, scores a soccer goal during one of the 2010 Special Olympic games at NASA's John C. Stennis Space Center on March 27. Stennis serves as an annual host for the special needs event. Each year, local, regional and national Special Olympics events are hosted in more than 150 countries for persons with special needs. An international Special Olympics competition is held every two years.

  6. Host factors in childhood diarrhoea.

    PubMed

    Khan, M A; Yunus, M

    1990-06-01

    Host factors play a significant role in children under five who are the worst sufferers of this widespread and global scourge, both in regard to mortality and morbidity. This study deals with some of the host factors in relation to diarrhoea in a rural population. Age was found to have a definite and direct relationship to diarrhoea. Male children were effected more. Poor hygiene, malnutrition and the receipt of supplementary feeds, were found to have a significant association with childhood diarrhoeas.

  7. Hypothesis: Bacteria Control Host Appetites

    PubMed Central

    Molina, Franck; Gewirtz, Andrew T.

    2013-01-01

    To help investigate the relationship between inflammatory and other diseases and the composition of the gut microbiota, we propose that a positive-feedback loop exists between the preferences of the host for a particular dietary regimen, the composition of the gut microbiota that depends on this regimen, and the preferences of the host as influenced by the gut microbiota. We cite evidence in support of this hypothesis and make testable predictions. PMID:23144247

  8. Domain Validity and Generalizability

    ERIC Educational Resources Information Center

    Kaiser, Henry F.; Michael, William B.

    1975-01-01

    An alternative derivation of Tryon's basic formula for the coefficient of domain validity or the coefficient of generalizability developed by Cronbach, Rajaratnam, and Glaser is provided. This derivation, which is also the generalized Kuder-Richardson coefficient, requires a relatively minimal number of assumptions compared with that in previously…

  9. Cellulose binding domain proteins

    DOEpatents

    Shoseyov, O.; Shpiegl, I.; Goldstein, M.; Doi, R.

    1998-11-17

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  10. Cellulose binding domain proteins

    SciTech Connect

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc; Doi, Roy

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  11. The Domains of TESOL.

    ERIC Educational Resources Information Center

    Robinett, Betty Wallace

    The domains of Teachers of English to Speakers of Other Languages (TESOL) are those spheres of concern involving persons who speak languages other than English or dialects of English other than the standard. This clientele has been classified traditionally in terms of programs in English as a foreign language, English as a second language, English…

  12. Clusters, factories and domains

    PubMed Central

    Gillespie, Peter J

    2010-01-01

    During S-phase of the cell cycle, chromosomal DNA is replicated according to a complex replication timing program, with megabase-sized domains replicating at different times. DNA fiber analysis reveals that clusters of adjacent replication origins fire near-synchronously. Analysis of replicating cells by light microscopy shows that DNA synthesis occurs in discrete foci or factories. The relationship between timing domains, origin clusters and replication foci is currently unclear. Recent work, using a hybrid Xenopus/hamster replication system, has shown that when CDK levels are manipulated during S-phase the activation of replication factories can be uncoupled from progression through the replication timing program. Here, we use data from this hybrid system to investigate potential relationships between timing domains, origin clusters and replication foci. We suggest that each timing domain typically comprises several replicon clusters, which are usually processed sequentially by replication factories. We discuss how replication might be regulated at different levels to create this complex organization and the potential involvement of CDKs in this process. PMID:20724827

  13. Functional expression of Phanerochaete chrysosporium cellobiose dehydrogenase flavin domain in Escherichia coli.

    PubMed

    Desriani; Ferri, Stefano; Sode, Koji

    2010-06-01

    Cellobiose dehydrogenase (CDH; EC 1.1.99.18) is an extracellular glycosylated protein composed of two distinct domains, a C-terminal catalytic flavin domain and an N-terminal cytochrome-b-type heme domain, which transfers electrons from the flavin domain to external electron acceptors. The soluble flavin domain of the Phanerochaete chrysosporium CDH was successfully expressed in Escherichia coli. The enzyme showed dye-mediated CDH activity higher than that of the complete CDH, composed of flavin domain and heme domain, prepared using Pichia pastoris as the host microorganism. The ability to conveniently express the recombinant CDH flavin domain in E. coli provides great opportunities for the molecular engineering of the catalytic properties of CDH.

  14. Host defence to pulmonary mycosis

    PubMed Central

    Mody, Christopher H; Warren, Peter W

    1999-01-01

    OBJECTIVE: To provide a basic understanding of the mechanisms of host defense to pathogenic fungi. This will help physicians understand why some patients are predisposed to fungal infections and update basic scientists on how microbial immunology applies to fungal disease. DATA SOURCES: English articles from 1966 to present were identified from a MEDLINE search. STUDY SELECTION: Articles were identified by a MEDLINE search of ‘exp lung/’ or ‘exp lung diseases/’ and ‘exp fungi/’. The titles and abstracts were screened to identify articles that contained salient information pertaining to host defense of respiratory mycoses. DATA EXTRACTION: Information was summarized from the articles pertaining to host defense of pulmonary mycosis that had been identified by the MEDLINE search. DATA SYNTHESIS: Fungi represent a unique and highly diverse group of pathogenic organisms that have become an increasingly prevalent cause of life-threatening illness. A worldwide increase in persons with immunodeficiency has been a major contributing factor to the increase in fungal disease. As a result, clinicians are faced with an expanding array of fungal infections that pose diagnostic and therapeutic challenges. The respiratory tract is the route of acquisition for many important fungal infections; thus, understanding the host defense in the lung is an essential component of understanding host defense to fungal disease. With this understanding, fungi may be divided on the basis of the predilection of certain mycosis for specific immune defects. CONCLUSIONS: By separating fungi based on the host immune defects that predispose to disease, in conjunction with traditional divisions based on the geographic distribution of fungi, clinicians are able to focus their diagnostic efforts and to identify fungal pathogens better. In addition, an understanding of the normal host defense mechanisms that serve to control fungal infections is essential to the development of novel antifungal

  15. Magnetic domain and domain wall in Co/Pt multilayer

    NASA Astrophysics Data System (ADS)

    Talapatra, A.; Mohanty, J.

    2016-05-01

    We report systematic micromagnetic investigation of formation of magnetic domains in perpendicularly magnetized Co/Pt multilayer with the variation in magnetic anisotropy and stack thickness. The lowering of anisotropy makes the domain wall broader and domain formation less efficient. Domain sizeincreases with increasing thickness of the stack to minimize the stray field energy.The minimization of energy of the system due to domain formation makes the M-H loop narrower whereas, lower stack thickness results in a wider loop. The magnetization reversalin this system occurs due tothe nucleation and growth of reverse domains.

  16. Crystal Structures of the Outer Membrane Domain of Intimin and Invasin from Enterohemorrhagic E. coli and Enteropathogenic Y. pseudotuberculosis

    SciTech Connect

    Fairman, James W.; Dautin, Nathalie; Wojtowicz, Damian; Liu, Wei; Noinaj, Nicholas; Barnard, Travis J.; Udho, Eshwar; Przytycka, Teresa M.; Cherezov, Vadim; Buchanan, Susan K.

    2012-12-10

    Intimins and invasins are virulence factors produced by pathogenic Gram-negative bacteria. They contain C-terminal extracellular passenger domains that are involved in adhesion to host cells and N-terminal {beta} domains that are embedded in the outer membrane. Here, we identify the domain boundaries of an E. coli intimin {beta} domain and use this information to solve its structure and the {beta} domain structure of a Y. pseudotuberculosis invasin. Both {beta} domain structures crystallized as monomers and reveal that the previous range of residues assigned to the {beta} domain also includes a protease-resistant domain that is part of the passenger. Additionally, we identify 146 nonredundant representative members of the intimin/invasin family based on the boundaries of the highly conserved intimin and invasin {beta} domains. We then use this set of sequences along with our structural data to find and map the evolutionarily constrained residues within the {beta} domain.

  17. Identification of FAM111A as an SV40 Host Range Restriction and Adenovirus Helper Factor

    PubMed Central

    Padi, Megha; Korkhin, Anna; James, Robert L.; Adelmant, Guillaume; Yoon, Rosa; Guo, Luxuan; Berrios, Christian; Zhang, Ying; Calderwood, Michael A.; Velmurgan, Soundarapandian; Cheng, Jingwei; Marto, Jarrod A.; Hill, David E.; Cusick, Michael E.; Vidal, Marc; Florens, Laurence; Washburn, Michael P.; Litovchick, Larisa; DeCaprio, James A.

    2012-01-01

    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. PMID:23093934

  18. Frequency domain measurement systems

    NASA Technical Reports Server (NTRS)

    Eischer, M. C.

    1978-01-01

    Stable frequency sources and signal processing blocks were characterized by their noise spectra, both discrete and random, in the frequency domain. Conventional measures are outlined, and systems for performing the measurements are described. Broad coverage of system configurations which were found useful is given. Their functioning and areas of application are discussed briefly. Particular attention is given to some of the potential error sources in the measurement procedures, system configurations, double-balanced-mixer-phase-detectors, and application of measuring instruments.

  19. Magnetic bubble domain memories

    NASA Technical Reports Server (NTRS)

    Ypma, J. E.

    1974-01-01

    Some attractive features of Bubble Domain Memory and its relation to existing technologies are discussed. Two promising applications are block access mass memory and tape recorder replacement. The required chip capabilities for these uses are listed, and the specifications for a block access mass memory designed to fit between core and HPT disk are presented. A feasibility model for a tape recorder replacement is introduced.

  20. Public domain optical character recognition

    NASA Astrophysics Data System (ADS)

    Garris, Michael D.; Blue, James L.; Candela, Gerald T.; Dimmick, Darrin L.; Geist, Jon C.; Grother, Patrick J.; Janet, Stanley A.; Wilson, Charles L.

    1995-03-01

    A public domain document processing system has been developed by the National Institute of Standards and Technology (NIST). The system is a standard reference form-based handprint recognition system for evaluating optical character recognition (OCR), and it is intended to provide a baseline of performance on an open application. The system's source code, training data, performance assessment tools, and type of forms processed are all publicly available. The system recognizes the handprint entered on handwriting sample forms like the ones distributed with NIST Special Database 1. From these forms, the system reads hand-printed numeric fields, upper and lowercase alphabetic fields, and unconstrained text paragraphs comprised of words from a limited-size dictionary. The modular design of the system makes it useful for component evaluation and comparison, training and testing set validation, and multiple system voting schemes. The system contains a number of significant contributions to OCR technology, including an optimized probabilistic neural network (PNN) classifier that operates a factor of 20 times faster than traditional software implementations of the algorithm. The source code for the recognition system is written in C and is organized into 11 libraries. In all, there are approximately 19,000 lines of code supporting more than 550 subroutines. Source code is provided for form registration, form removal, field isolation, field segmentation, character normalization, feature extraction, character classification, and dictionary-based postprocessing. The recognition system has been successfully compiled and tested on a host of UNIX workstations. This paper gives an overview of the recognition system's software architecture, including descriptions of the various system components along with timing and accuracy statistics.

  1. Effects of basic human values on host community acculturation orientations.

    PubMed

    Sapienza, Irene; Hichy, Zira; Guarnera, Maria; Nuovo, Santo Di

    2010-08-01

    Although literature provides evidence for the relationship between values and acculturation, the relationship between host community acculturation orientations has not yet been investigated. In this study we tested the effects of four high-order values (openness to change, self-transcendence, conservation, and self-enhancement, devised according to Schwartz's model) on host community acculturation orientations towards immigrants (devised according the interactive acculturation model) in the public domain of employment and the private domain of endogamy/exogamy. Participants were 264 Italian University students, who completed a questionnaire containing the Portrait Values Questionnaire, a measure of personal values, and the Host Community Acculturation Scale, aimed at measuring Italian acculturation strategies towards three groups of immigrants: Immigrants (the general category), Chinese (the valued immigrant group), and Albanians (the devalued immigrant group). Results showed that personal values are related to the adoption of acculturation orientations: In particular, the values that mostly impacted on acculturation orientations were self-transcendence and conservation. Values concerning self-transcendence encourage the adoption of integrationism, integrationism-transformation, and individualism and reduce the adoption of assimilationism, segregationism, and exclusionism. Values concerning conservation encourage the adoption of assimilation, segregation and exclusion orientations and reduce the adoption of both types of integrationism and individualism. Minor effects were found regarding self-enhancement and openness to change.

  2. The inflammasome in host defense.

    PubMed

    Chen, Gang; Pedra, Joao H F

    2010-01-01

    Nod-like receptors have emerged as an important family of sensors in host defense. These receptors are expressed in macrophages, dendritic cells and monocytes and play an important role in microbial immunity. Some Nod-like receptors form the inflammasome, a protein complex that activates caspase-1 in response to several stimuli. Caspase-1 activation leads to processing and secretion of pro-inflammatory cytokines such as interleukin (IL)-1β and IL-18. Here, we discuss recent advances in the inflammasome field with an emphasis on host defense. We also compare differential requirements for inflammasome activation in dendritic cells, macrophages and monocytes.

  3. Host diversity begets parasite diversity: Bird final hosts and trematodes in snail intermediate hosts

    USGS Publications Warehouse

    Hechinger, R.F.; Lafferty, K.D.

    2005-01-01

    An unappreciated facet of biodiversity is that rich communities and high abundance may foster parasitism. For parasites that sequentially use different host species throughout complex life cycles, parasite diversity and abundance in 'downstream' hosts should logically increase with the diversity and abundance of 'upstream' hosts (which carry the preceding stages of parasites). Surprisingly, this logical assumption has little empirical support, especially regarding metazoan parasites. Few studies have attempted direct tests of this idea and most have lacked the appropriate scale of investigation. In two different studies, we used time-lapse videography to quantify birds at fine spatial scales, and then related bird communities to larval trematode communities in snail populations sampled at the same small spatial scales. Species richness, species heterogeneity and abundance of final host birds were positively correlated with species richness, species heterogeneity and abundance of trematodes in host snails. Such community-level interactions have rarely been demonstrated and have implications for community theory, epidemiological theory and ecosystem management. ?? 2005 The Royal Society.

  4. Host diversity begets parasite diversity: bird final hosts and trematodes in snail intermediate hosts

    PubMed Central

    Hechinger, Ryan F; Lafferty, Kevin D

    2005-01-01

    An unappreciated facet of biodiversity is that rich communities and high abundance may foster parasitism. For parasites that sequentially use different host species throughout complex life cycles, parasite diversity and abundance in ‘downstream’ hosts should logically increase with the diversity and abundance of ‘upstream’ hosts (which carry the preceding stages of parasites). Surprisingly, this logical assumption has little empirical support, especially regarding metazoan parasites. Few studies have attempted direct tests of this idea and most have lacked the appropriate scale of investigation. In two different studies, we used time-lapse videography to quantify birds at fine spatial scales, and then related bird communities to larval trematode communities in snail populations sampled at the same small spatial scales. Species richness, species heterogeneity and abundance of final host birds were positively correlated with species richness, species heterogeneity and abundance of trematodes in host snails. Such community-level interactions have rarely been demonstrated and have implications for community theory, epidemiological theory and ecosystem management. PMID:16024365

  5. Context-Dependent Effects of L Domains and Ubiquitination on Viral Budding

    PubMed Central

    Martin-Serrano, Juan; Perez-Caballero, David; Bieniasz, Paul D.

    2004-01-01

    Many enveloped viruses encode late assembly domains, or L domains, that facilitate virion egress. PTAP-type L domains act by recruiting the ESCRT-I (endosomal sorting complex required for transport I) component Tsg101, and YPXL/LXXLF-type L domains recruit AIP-1/ALIX, both of which are class E vacuolar protein sorting (VPS) factors, normally required for the generation of vesicles within endosomes. The binding cofactors for PPXY-type L domains have not been unambiguously resolved but may include Nedd4-like ubiquitin ligases. Largely because they act as autonomous binding sites for host factors, L domains are generally transferable and active in a context-independent manner. Ebola virus matrix protein (EbVP40) contains two overlapping L-domain motifs within the sequence ILPTAPPEYMEA. Here, we show that both motifs are required for efficient EbVP40 budding. However, upon transplantation into two different retroviral contexts, the relative contributions of the PTAP and PPEY motifs differ markedly. In a murine leukemia virus carrying the EbVP40 sequence, both motifs contributed to overall L domain activity, and budding proceeded in a partly Tsg101-independent manner. Conversely, when transplanted into the context of human immunodeficiency virus type 1 (HIV-1), EbVP40 L-domain activity was entirely due to a PTAP-Tsg101 interaction. In fact, a number of PPXY-type L domains were inactive in the context of HIV-1. Surprisingly, PTAP and YPXL-type L domains that simulated HIV-1 budding reduced the amount of ubiquitin conjugated to Gag, while inactive PPXY-type L domains increased Gag ubiquitination. These observations suggest that active L domains recruit deubiquitinating enzymes as a consequence of class E VPS factor recruitment. Moreover, context-dependent L-domain function may reflect distinct requirements for host functions during the morphogenesis of different viral particles or the underlying presence of additional, as yet undiscovered L domains. PMID:15140952

  6. Context-dependent effects of L domains and ubiquitination on viral budding.

    PubMed

    Martin-Serrano, Juan; Perez-Caballero, David; Bieniasz, Paul D

    2004-06-01

    Many enveloped viruses encode late assembly domains, or L domains, that facilitate virion egress. PTAP-type L domains act by recruiting the ESCRT-I (endosomal sorting complex required for transport I) component Tsg101, and YPXL/LXXLF-type L domains recruit AIP-1/ALIX, both of which are class E vacuolar protein sorting (VPS) factors, normally required for the generation of vesicles within endosomes. The binding cofactors for PPXY-type L domains have not been unambiguously resolved but may include Nedd4-like ubiquitin ligases. Largely because they act as autonomous binding sites for host factors, L domains are generally transferable and active in a context-independent manner. Ebola virus matrix protein (EbVP40) contains two overlapping L-domain motifs within the sequence ILPTAPPEYMEA. Here, we show that both motifs are required for efficient EbVP40 budding. However, upon transplantation into two different retroviral contexts, the relative contributions of the PTAP and PPEY motifs differ markedly. In a murine leukemia virus carrying the EbVP40 sequence, both motifs contributed to overall L domain activity, and budding proceeded in a partly Tsg101-independent manner. Conversely, when transplanted into the context of human immunodeficiency virus type 1 (HIV-1), EbVP40 L-domain activity was entirely due to a PTAP-Tsg101 interaction. In fact, a number of PPXY-type L domains were inactive in the context of HIV-1. Surprisingly, PTAP and YPXL-type L domains that simulated HIV-1 budding reduced the amount of ubiquitin conjugated to Gag, while inactive PPXY-type L domains increased Gag ubiquitination. These observations suggest that active L domains recruit deubiquitinating enzymes as a consequence of class E VPS factor recruitment. Moreover, context-dependent L-domain function may reflect distinct requirements for host functions during the morphogenesis of different viral particles or the underlying presence of additional, as yet undiscovered L domains.

  7. Cooperative folding of intrinsically disordered domains drives assembly of a strong elongated protein

    NASA Astrophysics Data System (ADS)

    Gruszka, Dominika T.; Whelan, Fiona; Farrance, Oliver E.; Fung, Herman K. H.; Paci, Emanuele; Jeffries, Cy M.; Svergun, Dmitri I.; Baldock, Clair; Baumann, Christoph G.; Brockwell, David J.; Potts, Jennifer R.; Clarke, Jane

    2015-06-01

    Bacteria exploit surface proteins to adhere to other bacteria, surfaces and host cells. Such proteins need to project away from the bacterial surface and resist significant mechanical forces. SasG is a protein that forms extended fibrils on the surface of Staphylococcus aureus and promotes host adherence and biofilm formation. Here we show that although monomeric and lacking covalent cross-links, SasG maintains a highly extended conformation in solution. This extension is mediated through obligate folding cooperativity of the intrinsically disordered E domains that couple non-adjacent G5 domains thermodynamically, forming interfaces that are more stable than the domains themselves. Thus, counterintuitively, the elongation of the protein appears to be dependent on the inherent instability of its domains. The remarkable mechanical strength of SasG arises from tandemly arrayed `clamp' motifs within the folded domains. Our findings reveal an elegant minimal solution for the assembly of monomeric mechano-resistant tethers of variable length.

  8. An internal thioester in a pathogen surface protein mediates covalent host binding.

    PubMed

    Walden, Miriam; Edwards, John M; Dziewulska, Aleksandra M; Bergmann, Rene; Saalbach, Gerhard; Kan, Su-Yin; Miller, Ona K; Weckener, Miriam; Jackson, Rosemary J; Shirran, Sally L; Botting, Catherine H; Florence, Gordon J; Rohde, Manfred; Banfield, Mark J; Schwarz-Linek, Ulrich

    2015-06-02

    To cause disease and persist in a host, pathogenic and commensal microbes must adhere to tissues. Colonization and infection depend on specific molecular interactions at the host-microbe interface that involve microbial surface proteins, or adhesins. To date, adhesins are only known to bind to host receptors non-covalently. Here we show that the streptococcal surface protein SfbI mediates covalent interaction with the host protein fibrinogen using an unusual internal thioester bond as a 'chemical harpoon'. This cross-linking reaction allows bacterial attachment to fibrin and SfbI binding to human cells in a model of inflammation. Thioester-containing domains are unexpectedly prevalent in Gram-positive bacteria, including many clinically relevant pathogens. Our findings support bacterial-encoded covalent binding as a new molecular principle in host-microbe interactions. This represents an as yet unexploited target to treat bacterial infection and may also offer novel opportunities for engineering beneficial interactions.

  9. A domain-centric analysis of oomycete plant pathogen genomes reveals unique protein organization.

    PubMed

    Seidl, Michael F; Van den Ackerveken, Guido; Govers, Francine; Snel, Berend

    2011-02-01

    Oomycetes comprise a diverse group of organisms that morphologically resemble fungi but belong to the stramenopile lineage within the supergroup of chromalveolates. Recent studies have shown that plant pathogenic oomycetes have expanded gene families that are possibly linked to their pathogenic lifestyle. We analyzed the protein domain organization of 67 eukaryotic species including four oomycete and five fungal plant pathogens. We detected 246 expanded domains in fungal and oomycete plant pathogens. The analysis of genes differentially expressed during infection revealed a significant enrichment of genes encoding expanded domains as well as signal peptides linking a substantial part of these genes to pathogenicity. Overrepresentation and clustering of domain abundance profiles revealed domains that might have important roles in host-pathogen interactions but, as yet, have not been linked to pathogenicity. The number of distinct domain combinations (bigrams) in oomycetes was significantly higher than in fungi. We identified 773 oomycete-specific bigrams, with the majority composed of domains common to eukaryotes. The analyses enabled us to link domain content to biological processes such as host-pathogen interaction, nutrient uptake, or suppression and elicitation of plant immune responses. Taken together, this study represents a comprehensive overview of the domain repertoire of fungal and oomycete plant pathogens and points to novel features like domain expansion and species-specific bigram types that could, at least partially, explain why oomycetes are such remarkable plant pathogens.

  10. Visual mimicry of host nestlings by cuckoos

    PubMed Central

    Langmore, Naomi E.; Stevens, Martin; Maurer, Golo; Heinsohn, Robert; Hall, Michelle L.; Peters, Anne; Kilner, Rebecca M.

    2011-01-01

    Coevolution between antagonistic species has produced instances of exquisite mimicry. Among brood-parasitic cuckoos, host defences have driven the evolution of mimetic eggs, but the evolutionary arms race was believed to be constrained from progressing to the chick stage, with cuckoo nestlings generally looking unlike host young. However, recent studies on bronze-cuckoos have confounded theoretical expectations by demonstrating cuckoo nestling rejection by hosts. Coevolutionary theory predicts reciprocal selection for visual mimicry of host young by cuckoos, although this has not been demonstrated previously. Here we show that, in the eyes of hosts, nestlings of three bronze-cuckoo species are striking visual mimics of the young of their morphologically diverse hosts, providing the first evidence that coevolution can select for visual mimicry of hosts in cuckoo chicks. Bronze-cuckoos resemble their own hosts more closely than other host species, but the accuracy of mimicry varies according to the diversity of hosts they exploit. PMID:21227972

  11. Infected cell protein 0 functional domains and their coordination in herpes simplex virus replication

    PubMed Central

    Gu, Haidong

    2016-01-01

    Herpes simplex virus 1 (HSV-1) is a ubiquitous human pathogen that establishes latent infection in ganglia neurons. Its unique life cycle requires a balanced “conquer and compromise” strategy to deal with the host anti-viral defenses. One of HSV-1 α (immediate early) gene products, infected cell protein 0 (ICP0), is a multifunctional protein that interacts with and modulates a wide range of cellular defensive pathways. These pathways may locate in different cell compartments, which then migrate or exchange factors upon stimulation, for the purpose of a concerted and effective defense. ICP0 is able to simultaneously attack multiple host pathways by either degrading key restrictive factors or modifying repressive complexes. This is a viral protein that contains an E3 ubiquitin ligase, translocates among different cell compartments and interacts with major defensive complexes. The multiple functional domains of ICP0 can work independently and at the same time coordinate with each other. Dissecting the functional domains of ICP0 and delineating the coordination of these domains will help us understand HSV-1 pathogenicity as well as host defense mechanisms. This article focuses on describing individual ICP0 domains, their biochemical properties and their implication in HSV-1 infection. By putting individual domain functions back into the picture of host anti-viral defense network, this review seeks to elaborate the complex interactions between HSV-1 and its host. PMID:26870669

  12. Infected cell protein 0 functional domains and their coordination in herpes simplex virus replication.

    PubMed

    Gu, Haidong

    2016-02-12

    Herpes simplex virus 1 (HSV-1) is a ubiquitous human pathogen that establishes latent infection in ganglia neurons. Its unique life cycle requires a balanced "conquer and compromise" strategy to deal with the host anti-viral defenses. One of HSV-1 α (immediate early) gene products, infected cell protein 0 (ICP0), is a multifunctional protein that interacts with and modulates a wide range of cellular defensive pathways. These pathways may locate in different cell compartments, which then migrate or exchange factors upon stimulation, for the purpose of a concerted and effective defense. ICP0 is able to simultaneously attack multiple host pathways by either degrading key restrictive factors or modifying repressive complexes. This is a viral protein that contains an E3 ubiquitin ligase, translocates among different cell compartments and interacts with major defensive complexes. The multiple functional domains of ICP0 can work independently and at the same time coordinate with each other. Dissecting the functional domains of ICP0 and delineating the coordination of these domains will help us understand HSV-1 pathogenicity as well as host defense mechanisms. This article focuses on describing individual ICP0 domains, their biochemical properties and their implication in HSV-1 infection. By putting individual domain functions back into the picture of host anti-viral defense network, this review seeks to elaborate the complex interactions between HSV-1 and its host.

  13. Undiscovered Bat Hosts of Filoviruses

    PubMed Central

    Schmidt, John Paul; Alexander, Laura W.; Bowden, Sarah E.; Hayman, David T. S.; Drake, John M.

    2016-01-01

    Ebola and other filoviruses pose significant public health and conservation threats by causing high mortality in primates, including humans. Preventing future outbreaks of ebolavirus depends on identifying wildlife reservoirs, but extraordinarily high biodiversity of potential hosts in temporally dynamic environments of equatorial Africa contributes to sporadic, unpredictable outbreaks that have hampered efforts to identify wild reservoirs for nearly 40 years. Using a machine learning algorithm, generalized boosted regression, we characterize potential filovirus-positive bat species with estimated 87% accuracy. Our model produces two specific outputs with immediate utility for guiding filovirus surveillance in the wild. First, we report a profile of intrinsic traits that discriminates hosts from non-hosts, providing a biological caricature of a filovirus-positive bat species. This profile emphasizes traits describing adult and neonate body sizes and rates of reproductive fitness, as well as species’ geographic range overlap with regions of high mammalian diversity. Second, we identify several bat species ranked most likely to be filovirus-positive on the basis of intrinsic trait similarity with known filovirus-positive bats. New bat species predicted to be positive for filoviruses are widely distributed outside of equatorial Africa, with a majority of species overlapping in Southeast Asia. Taken together, these results spotlight several potential host species and geographical regions as high-probability targets for future filovirus surveillance. PMID:27414412

  14. Host Event Based Network Monitoring

    SciTech Connect

    Jonathan Chugg

    2013-01-01

    The purpose of INL’s research on this project is to demonstrate the feasibility of a host event based network monitoring tool and the effects on host performance. Current host based network monitoring tools work on polling which can miss activity if it occurs between polls. Instead of polling, a tool could be developed that makes use of event APIs in the operating system to receive asynchronous notifications of network activity. Analysis and logging of these events will allow the tool to construct the complete real-time and historical network configuration of the host while the tool is running. This research focused on three major operating systems commonly used by SCADA systems: Linux, WindowsXP, and Windows7. Windows 7 offers two paths that have minimal impact on the system and should be seriously considered. First is the new Windows Event Logging API, and, second, Windows 7 offers the ALE API within WFP. Any future work should focus on these methods.

  15. AVTC Hosts TechnoCamp

    ERIC Educational Resources Information Center

    Miner, Brenda

    2006-01-01

    The Area Vo-Tech Center (AVTC) in Russellville, Arkansas, recently hosted its first TechnoCamp to encourage enrollment based on the aptitude and interest level of the students enrolling in the various programs. The center currently offers student enrollment in auto technology, computer engineering, cosmetology, construction technology, drafting…

  16. Biosignatures of Pathogen and Host

    SciTech Connect

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

    2002-08-27

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

  17. Gastrointestinal mucormycosis in immunocompromised hosts.

    PubMed

    Dioverti, M Veronica; Cawcutt, Kelly A; Abidi, Maheen; Sohail, M Rizwan; Walker, Randall C; Osmon, Douglas R

    2015-12-01

    Invasive mucormycosis is a rare fungal infection in immunocompromised hosts, but it carries a high mortality rate. Primary gastrointestinal disease is the least frequent form of presentation. Early diagnosis and treatment are critical in the management; however, symptoms are typically non-specific in gastrointestinal disease, leading to delayed therapy. To describe the clinical presentation, diagnosis, treatment and outcomes of gastrointestinal mucormycosis in immunocompromised hosts, we reviewed all cases of primary gastrointestinal mucormycosis in immunocompromised hosts reported in English literature as well as in our Institution from January 1st 1991 to December 31st 2013 for a total of 31 patients. About 52% of patients underwent solid organ transplant (SOT), while the rest had an underlying haematologic malignancy. Abdominal pain was the most common presenting symptom, followed by gastrointestinal bleeding and fever. Gastric disease was more common in SOT, whereas those with haematologic malignancy presented with intestinal disease (P = 0.002). Although gastrointestinal mucormycosis remains an uncommon condition in immunocompromised hosts, it carries significant morbidity and mortality, particularly in cases with intestinal involvement. A high index of suspicion is of utmost importance to institute early and appropriate therapy and improve outcomes.

  18. AVTC Hosts TechnoCamp

    ERIC Educational Resources Information Center

    Miner, Brenda

    2006-01-01

    The Area Vo-Tech Center (AVTC) in Russellville, Arkansas, recently hosted its first TechnoCamp to encourage enrollment based on the aptitude and interest level of the students enrolling in the various programs. The center currently offers student enrollment in auto technology, computer engineering, cosmetology, construction technology, drafting…

  19. Molecular Dynamics Studies on the HIV-1 Integrase Catalytic Domain

    SciTech Connect

    Lins, Roberto D.; Briggs, J. M.; Straatsma, TP; Carlson, Heather A.; Greenwald, Jason; Choe, Senyon; Mccammon, Andy

    1999-06-30

    The HIV-1 integrase, which is essential for viral replication, catalyzes the insertion of viral DNA into the host chromosome, thereby recruiting host cell machinery into making viral proteins. It represents the third main HIV enzyme target for inhibitor design, the first two being the reverse transcriptase and the protease. Two 1-ns molecular dynamics simulations have been carried out on completely hydrated models of the HIV-1 integrase catalytic domain, one with no metal ions and another with one magnesium ion in the catalytic site. The simulations predict that the region of the active site that is missing in the published crystal structures has (at the time of this work) more secondary structure than previously thought. The flexibility of this region has been discussed with respect to the mechanistic function of the enzyme. The results of these simulations will be used as part of inhibitor design projects directed against the catalytic domain of the enzyme.

  20. Genome cartography through domain annotation

    PubMed Central

    Ponting, Chris P; Dickens, Nicholas J

    2001-01-01

    The evolutionary history of eukaryotic proteins involves rapid sequence divergence, addition and deletion of domains, and fusion and fission of genes. Although the protein repertoires of distantly related species differ greatly, their domain repertoires do not. To account for the great diversity of domain contexts and an unexpected paucity of ortholog conservation, we must categorize the coding regions of completely sequenced genomes into domain families, as well as protein families.

  1. WW or WoW: the WW domains in a union of bliss.

    PubMed

    Sudol, Marius; Recinos, Claudia C; Abraczinskas, Jennifer; Humbert, Jasper; Farooq, Amjad

    2005-12-01

    WW domains are small protein modules that recognize proline-rich peptide motifs or phosphorylated-serine/threonine proline sites in cognate proteins. Within host proteins these modules are joined to other protein domains or to a variety of catalytic domains acting together as adaptors or targeting anchors of enzymes. An important aspect of signaling by WW domains is their ability to recognize their cognate ligands in tandem. Tandem WW domains not only act in a synergistic manner but also appear to chaperone the function of each other. In this review, we focus on structure, function, and mechanism of the tandem WW domains co-operativity as well as independent actions. We emphasize here the implications of tandem arrangement and cooperative function of the domains for signaling pathways.

  2. Structure of NS1A effector domain from the influenza A/Udorn/72 virus

    SciTech Connect

    Xia, Shuangluo; Monzingo, Arthur F.; Robertus, Jon D.

    2009-01-01

    The structure of the effector domain of the influenza protein NS1, a validated antiviral drug target, has been solved in two space groups. The nonstructural protein NS1A from influenza virus is a multifunctional virulence factor and a potent inhibitor of host immunity. It has two functional domains: an N-terminal 73-amino-acid RNA-binding domain and a C-terminal effector domain. Here, the crystallographic structure of the NS1A effector domain of influenza A/Udorn/72 virus is presented. Structure comparison with the NS1 effector domain from mouse-adapted influenza A/Puerto Rico/8/34 (PR8) virus strain reveals a similar monomer conformation but a different dimer interface. Further analysis and evaluation shows that the dimer interface observed in the structure of the PR8 NS1 effector domain is likely to be a crystallographic packing effect. A hypothetical model of the intact NS1 dimer is presented.

  3. Runaway dilatonic domain walls

    SciTech Connect

    Aguirre, Anthony; Johnson, Matthew C.; Larfors, Magdalena

    2010-02-15

    We explore the stability of domain wall and bubble solutions in theories with compact extra dimensions. The energy density stored inside of the wall can destabilize the volume modulus of a compactification, leading to solutions containing either a timelike singularity or a region where space decompactifies, depending on the metric ansatz. We determine the structure of such solutions both analytically and using numerical simulations, and analyze how they arise in compactifications of Einstein-Maxwell theory and type IIB string theory. The existence of instabilities has important implications for the formation of networks of topological defects and the population of vacua during eternal inflation.

  4. Host defense reinforces host–parasite cospeciation

    PubMed Central

    Clayton, Dale H.; Bush, Sarah E.; Goates, Brad M.; Johnson, Kevin P.

    2003-01-01

    Cospeciation occurs when interacting groups, such as hosts and parasites, speciate in tandem, generating congruent phylogenies. Cospeciation can be a neutral process in which parasites speciate merely because they are isolated on diverging host islands. Adaptive evolution may also play a role, but this has seldom been tested. We explored the adaptive basis of cospeciation by using a model system consisting of feather lice (Columbicola) and their pigeon and dove hosts (Columbiformes). We reconstructed phylogenies for both groups by using nuclear and mitochondrial DNA sequences. Both phylogenies were well resolved and well supported. Comparing these phylogenies revealed significant cospeciation and correlated evolution of host and parasite body size. The match in body size suggested that adaptive constraints limit the range of hosts lice can use. We tested this hypothesis by transferring lice among hosts of different sizes to simulate host switches. The results of these experiments showed that lice cannot establish viable populations on novel hosts that differ in size from the native host. To determine why size matters, we measured three components of louse fitness: attachment, feeding, and escape from host defense (preening). Lice could remain attached to, and feed on, hosts varying in size by an order of magnitude. However, they could not escape from preening on novel hosts that differed in size from the native host. Overall, our results suggest that host defense reinforces cospeciation in birds and feather lice by preventing lice from switching between hosts of different sizes. PMID:14673114

  5. Field Evolution of Antiferromagnetic Domains and Domain Walls

    NASA Astrophysics Data System (ADS)

    Fullerton, Eric E.; Hellwig, Olav; Berger, Andreas K.

    2003-03-01

    We have used magnetron sputtered [Co(4Å)Pt(7Å)]X Co(4Å)Ru(9Å)N multiplayer films to create artificially layered antiferromagnets. In contrast to atomic antiferromagnets our model system has an antiferromagnetic (AF) exchange energy comparable to the Zeemann energy in moderate fields and allows to fine tune the relative magnitude of the different magnetic energy terms by varying the parameters X and N. With increasing X and N we observe a transition from traditionally observed sharp AF domain walls towards AF domain walls with a finite width which consist of ferromagnetic stripes, i.e. the AF domains have zero net moment whereas the domain walls carry a finite magnetic moment. Such AF domain walls have not been observed before and are a direct consequence of balancing out exchange and Zeeman energy. We also show that such domain walls are expected from theoretical energy calculations. In this contribution we study the nature and field evolution of the AF stripe domain walls by Magnetic Force Microscopy (MFM). The surface sensitivity of MFM and the finite moment of the AF domain walls allow us to image AF domains as well as domain walls. We are showing first experiments to study the AF domain wall evolution in real space while applying an external field. O.H. was supported by the Deutsche Forschungsgemeinschaft via a Forschungsstipendium under the contract number HE 3286/1-1.

  6. The YTH Domain Is a Novel RNA Binding Domain*

    PubMed Central

    Zhang, Zhaiyi; Theler, Dominik; Kaminska, Katarzyna H.; Hiller, Michael; de la Grange, Pierre; Pudimat, Rainer; Rafalska, Ilona; Heinrich, Bettina; Bujnicki, Janusz M.; Allain, Frédéric H.-T.; Stamm, Stefan

    2010-01-01

    The YTH (YT521-B homology) domain was identified by sequence comparison and is found in 174 different proteins expressed in eukaryotes. It is characterized by 14 invariant residues within an α-helix/β-sheet structure. Here we show that the YTH domain is a novel RNA binding domain that binds to a short, degenerated, single-stranded RNA sequence motif. The presence of the binding motif in alternative exons is necessary for YT521-B to directly influence splice site selection in vivo. Array analyses demonstrate that YT521-B predominantly regulates vertebrate-specific exons. An NMR titration experiment identified the binding surface for single-stranded RNA on the YTH domain. Structural analyses indicate that the YTH domain is related to the pseudouridine synthase and archaeosine transglycosylase (PUA) domain. Our data show that the YTH domain conveys RNA binding ability to a new class of proteins that are found in all eukaryotic organisms. PMID:20167602

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

    PubMed Central

    Hofmann-Winkler, Heike; Kaup, Franziska; Pöhlmann, Stefan

    2012-01-01

    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. PMID:23342362

  8. Determinants of Host Society Acculturation and Its Relationship with Health Behaviors and Outcomes: A New Research and Intervention Framework.

    PubMed

    Andreeva, Valentina A; Unger, Jennifer B

    2015-10-01

    Host society acculturation (or reverse acculturation) is a complex, multifactorial process reflecting the attitude- and behavior-level impact of immigrants on the host society. However, this phenomenon has rarely been the subject of systematic research in the area of public health. Using qualitative and quantitative findings from different health behavior domains, we strove to identify potential individual- and environment-level determinants of host society acculturation. Next, we developed a context-driven multilevel public health research and intervention framework for the study of the relationship between host society acculturation and health practices and outcomes. The framework posits a number of associations to be evaluated by future multidisciplinary research nationally and internationally.

  9. Pathogens and host immunity in the ancient human oral cavity

    PubMed Central

    Warinner, Christina; Matias Rodrigues, João F.; Vyas, Rounak; Trachsel, Christian; Shved, Natallia; Grossmann, Jonas; Radini, Anita; Hancock, Y.; Tito, Raul Y.; Fiddyment, Sarah; Speller, Camilla; Hendy, Jessica; Charlton, Sophy; Luder, Hans Ulrich; Salazar-García, Domingo C.; Eppler, Elisabeth; Seiler, Roger; Hansen, Lars; Samaniego Castruita, José Alfredo; Barkow-Oesterreicher, Simon; Teoh, Kai Yik; Kelstrup, Christian; Olsen, Jesper V.; Nanni, Paolo; Kawai, Toshihisa; Willerslev, Eske; von Mering, Christian; Lewis, Cecil M.; Collins, Matthew J.; Gilbert, M. Thomas P.; Rühli, Frank; Cappellini, Enrico

    2014-01-01

    Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize: (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) the first evidence of ancient human-associated putative antibiotic resistance genes, (iv) a genome reconstruction of the periodontal pathogen Tannerella forsythia, (v) 239 bacterial and 43 human proteins, allowing confirmation of a long-term association between host immune factors, “red-complex” pathogens, and periodontal disease, and (vi) DNA sequences matching dietary sources. Directly datable and nearly ubiquitous, dental calculus permits the simultaneous investigation of pathogen activity, host immunity, and diet, thereby extending the direct investigation of common diseases into the human evolutionary past. PMID:24562188

  10. Pathogens and host immunity in the ancient human oral cavity.

    PubMed

    Warinner, Christina; Rodrigues, João F Matias; Vyas, Rounak; Trachsel, Christian; Shved, Natallia; Grossmann, Jonas; Radini, Anita; Hancock, Y; Tito, Raul Y; Fiddyment, Sarah; Speller, Camilla; Hendy, Jessica; Charlton, Sophy; Luder, Hans Ulrich; Salazar-García, Domingo C; Eppler, Elisabeth; Seiler, Roger; Hansen, Lars H; Castruita, José Alfredo Samaniego; Barkow-Oesterreicher, Simon; Teoh, Kai Yik; Kelstrup, Christian D; Olsen, Jesper V; Nanni, Paolo; Kawai, Toshihisa; Willerslev, Eske; von Mering, Christian; Lewis, Cecil M; Collins, Matthew J; Gilbert, M Thomas P; Rühli, Frank; Cappellini, Enrico

    2014-04-01

    Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first, to our knowledge, high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) ancient human-associated putative antibiotic resistance genes, (iv) a genome reconstruction of the periodontal pathogen Tannerella forsythia, (v) 239 bacterial and 43 human proteins, allowing confirmation of a long-term association between host immune factors, 'red complex' pathogens and periodontal disease, and (vi) DNA sequences matching dietary sources. Directly datable and nearly ubiquitous, dental calculus permits the simultaneous investigation of pathogen activity, host immunity and diet, thereby extending direct investigation of common diseases into the human evolutionary past.

  11. Twin domains in epitaxial thin MnSi layers on Si(111)

    NASA Astrophysics Data System (ADS)

    Trabel, M.; Tarakina, N. V.; Pohl, C.; Constantino, J. A.; Gould, C.; Brunner, K.; Molenkamp, L. W.

    2017-06-01

    Thin layers of MnSi, the first discovered host material of a skyrmion lattice, are epitaxially grown on Si(111) and their crystal properties are investigated by X-ray diffraction and transmission electron microscopy (TEM) measurements. Azimuthal ϕ -scans of asymmetric X-ray reflections reveal the formation of twinned domains with their unit cell rotated ±30 ° in plane with respect to the Si unit cell. The intensities of corresponding reflections indicate the same volume fractions for both domain types. Cross-sectional TEM confirms the presence of these domains and reveals a typical domain size of about 200 nm.

  12. MPEG-4 AVC domain watermarking transparency

    NASA Astrophysics Data System (ADS)

    Duta, S.; Mitrea, M.; Prêteux, F.; Belhaj, M.

    2008-04-01

    The ever-increasing Internet distribution of video content is echoed in ever-increasing efforts to devise systems balancing copyright protection and user rights. Watermarking is such an example: by persistently and imperceptibly associating some data with the host video, it offers at the same time a reliable and user-friendly solution for copyright infringement tracking. This paper takes a closer look at the apparent contradiction between watermarking (using the visual redundancy of the video to embed the data) and compression (eliminating the visual redundancy in order to speed up distribution and to alleviate storage requirements). In this respect, the viability of compressed domain watermarking is evaluated by analysing the visual effects of the MPEG-4 AVC stream alteration. The corpus consists of 10 video sequences of about 25 minutes each, coded at 256kbps and 64 kbps.

  13. Identification of sequence motifs involved in Dengue virus-host interactions.

    PubMed

    Asnet Mary, J; Paramasivan, R; Shenbagarathai, R

    2016-01-01

    Dengue fever is a rapidly spreading mosquito-borne virus infection, which remains a serious global public health problem. As there is no specific treatment or commercial vaccine available for effective control of the disease, the attempts on developing novel control strategies are underway. Viruses utilize the surface receptor proteins of host to enter into the cells. Though various proteins were said to be receptors of Dengue virus (DENV) using Virus Overlay Protein Binding Assay, the precise interaction between DENV and host is not explored. Understanding the structural features of domain III envelope glycoprotein would help in developing efficient antiviral inhibitors. Therefore, an attempt was made to identify the sequence motifs present in domain III envelope glycoprotein of Dengue virus. Computational analysis revealed that the NGR motif is present in the domain III envelope glycoprotein of DENV-1 and DENV-3. Similarly, DENV-1, DENV-2 and DENV-4 were found to contain Yxxphi motif which is a tyrosine-based sorting signal responsible for the interaction with a mu subunit of adaptor protein complex. High-throughput virtual screening resulted in five compounds as lead molecules based on glide score, which ranges from -4.664 to -6.52 kcal/Mol. This computational prediction provides an additional tool for understanding the virus-host interactions and helps to identify potential targets in the host. Further, experimental evidence is warranted to confirm the virus-host interactions and also inhibitory activity of reported lead compounds.

  14. Host modulation by therapeutic agents

    PubMed Central

    Elavarasu, Sugumari; Sekar, Santhosh; Murugan, Thamaraiselvan

    2012-01-01

    Periodontal disease susceptible group present advanced periodontal breakdown even though they achieve a high standard of oral hygiene. Various destructive enzymes and inflammatory mediators are involved in destruction. These are elevated in case of periodontal destruction. Host modulation aims at bringing these enzymes and mediators to normal level. Doxycycline, nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, nitrous oxide (NO) synthase inhibitors, recombinant human interleukin-11 (rhIL-11), omega-3 fatty acid, mouse anti-human interleukin-6 receptor antibody (MRA), mitogen-activated protein kinase (MAPK) inhibitors, nuclear factor-kappa B (NF-kb) inhibitors, osteoprotegerin, and tumor necrosis factor antagonist (TNF-α) are some of the therapeutic agents that have host modulation properties. PMID:23066265

  15. Graft-versus-host disease.

    PubMed

    Vogelsang, G B; Wagner, J E

    1990-06-01

    Graft-versus-host disease (GVHD) is caused by immunologic recognition of the patient by the donor marrow graft after allogeneic bone marrow transplantation. Despite advances in understanding and new agents and methods to treat GVHD, the disease and complications related to it and its treatment are the principal causes of death after transplantation. This article reviews the pathogenesis, prediction, prophylaxis, and treatment of both acute and chronic GVHD.

  16. Guidelines for Hosted Payload Integration

    DTIC Science & Technology

    2014-06-06

    different applications and from lack of communication, even in co-developed projects. Timely sharing of key design information is mandatory, since design...same causes, can also result in unanticipated incompatibilities. 3 1.3 Preventing Harm Harm that a Payload can create at the system level can...should be available for integration with the Host prior to all relevant system level testing. To further mitigate interface risks, flight-like or high

  17. Host thin films incorporating nanoparticles

    NASA Astrophysics Data System (ADS)

    Qureshi, Uzma

    The focus of this research project was the investigation of the functional properties of thin films that incorporate a secondary nanoparticulate phase. In particular to assess if the secondary nanoparticulate material enhanced a functional property of the coating on glass. In order to achieve this, new thin film deposition methods were developed, namely use of nanopowder precursors, an aerosol assisted transport technique and an aerosol into atmospheric pressure chemical vapour deposition system. Aerosol assisted chemical vapour deposition (AACVD) was used to deposit 8 series of thin films on glass. Five different nanoparticles silver, gold, ceria, tungsten oxide and zinc oxide were tested and shown to successfully deposit thin films incorporating nanoparticles within a host matrix. Silver nanoparticles were synthesised and doped within a titania film by AACVD. This improved solar control properties. A unique aerosol assisted chemical vapour deposition (AACVD) into atmospheric pressure chemical vapour deposition (APCVD) system was used to deposit films of Au nanoparticles and thin films of gold nanoparticles incorporated within a host titania matrix. Incorporation of high refractive index contrast metal oxide particles within a host film altered the film colour. The key goal was to test the potential of nanopowder forms and transfer the suspended nanopowder via an aerosol to a substrate in order to deposit a thin film. Discrete tungsten oxide nanoparticles or ceria nanoparticles within a titanium dioxide thin film enhanced the self-cleaning and photo-induced super-hydrophilicity. The nanopowder precursor study was extended by deposition of zinc oxide thin films incorporating Au nanoparticles and also ZnO films deposited from a ZnO nanopowder precursor. Incorporation of Au nanoparticles within a VO: host matrix improved the thermochromic response, optical and colour properties. Composite VC/TiC and Au nanoparticle/V02/Ti02 thin films displayed three useful

  18. Palmitoylation, pathogens and their host.

    PubMed

    Blanc, Mathieu; Blaskovic, Sanja; van der Goot, F Gisou

    2013-02-01

    S-Palmitoylation, the only reversible post-translational lipid modification, confers unique biochemical and functional properties to proteins. Although it has long been known that viral proteins are palmitoylated, recent studies reveal that this modification plays a critical role for pathogens of all kinds and at multiple steps of their life cycle. The present review examines the involvement of S-palmitoylation in infection by viruses, bacteria and parasites and illustrates how pathogens have evolved to manipulate the host palmitoylation machinery.

  19. Biology of Cryptosporidium from marsupial hosts.

    PubMed

    Power, Michelle L

    2010-01-01

    The majority of biological data on Cryptosporidium has been collected from humans and domestic animal hosts which creates a bias in knowledge on the biodiversity and evolution of this parasite genus. Further to understanding Cryptosporidium biology are studies encompassing broad hosts that represent diverse taxa sampled across wide geographic ranges. Marsupials represent a group of wildlife hosts from which limited information on Cryptosporidium is available. As marsupial hosts are an ancient mammalian lineage they represent an important group for studying parasite evolution. This review summarises information of the biology, epidemiology and evolution of Cryptosporidium in marsupial hosts, and discusses the importance of further understanding interactions in this parasite-host system.

  20. Do symbiotic bacteria subvert host immunity?

    PubMed

    Hooper, Lora V

    2009-05-01

    The mammalian intestine is home to dense and complex indigenous bacterial communities. Most of these bacteria establish beneficial symbiotic relationships with their hosts, making important contributions to host metabolism and digestive efficiency. The vast numbers of intestinal bacteria and their proximity to host tissues raise the question of how symbiotic host-bacterial relationships are established without eliciting potentially harmful immune responses. In light of the varied ways in which pathogenic bacteria manipulate host immunity, this Opinion article explores the role of immune suppression, subversion and evasion in the establishment of symbiotic host-bacterial associations.

  1. Ascariasis: host-pathogen biology.

    PubMed

    Pawlowski, Z S

    1982-01-01

    Ascaris lumbricoides is one of the most common intestinal parasites in humans. Daily global contamination of the soil by A. lumbricoides eggs is enormous (approximately 9 x 10(14) eggs/day). Physical factors, particularly temperature and moisture, are critical in determining the maturation of eggs to the infective stage and their survival. Transmission of the infection to humans, on the other hand, depends more on various socioeconomic factors. In theory, ascariasis is preventable; it is indeed on the way to disappearing completely in developed societies where there is a high standard of sanitation. Ascariasis remains a problem in developing countries, however, where methods of disposal of human excreta are inadequate. The intensity of invasion is regulated by specific and nonspecific responses of the host to migrating A. lumbricoides larvae. Whether or not ascariasis becomes symptomatic depends on the intensity of the infection, the nutritional and immunologic status of the host, and the possible complications that may arise. Host responses to A. lumbricoides are brisk during the larval migratory stage in which hypersensitivity reactions may become clinically manifest, whereas people are rather tolerant of intestinal infections with adult worms. The role of ascariasis in the prevalence of allergic asthma still remains unclear. Complications due to migration of adult worms into the biliary duct system and to intestinal obstructions are the major causes of acute morbidity and mortality in ascariasis.

  2. The Microbiome and Host Behavior.

    PubMed

    Vuong, Helen E; Yano, Jessica M; Fung, Thomas C; Hsiao, Elaine Y

    2017-03-08

    The microbiota is increasingly recognized for its ability to influence the development and function of the nervous system and several complex host behaviors. In this review, we discuss emerging roles for the gut microbiota in modulating host social and communicative behavior, stressor-induced behavior, and performance in learning and memory tasks. We summarize effects of the microbiota on host neurophysiology, including brain microstructure, gene expression, and neurochemical metabolism across regions of the amygdala, hippocampus, frontal cortex, and hypothalamus. We further assess evidence linking dysbiosis of the gut microbiota to neurobehavioral diseases, such as autism spectrum disorder and major depression, drawing upon findings from animal models and human trials. Finally, based on increasing associations between the microbiota, neurophysiology, and behavior, we consider whether investigating mechanisms underlying the microbiota-gut-brain axis could lead to novel approaches for treating particular neurological conditions. Expected final online publication date for the Annual Review of Neuroscience Volume 40 is July 8, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  3. Hosting anions. The energetic perspective.

    PubMed

    Schmidtchen, Franz P

    2010-10-01

    Hosting anions addresses the widely spread molecular recognition event of negatively charged species by dedicated organic compounds in condensed phases at equilibrium. The experimentally accessible energetic features comprise the entire system including the solvent, any buffers, background electrolytes or other components introduced for e.g. analysis. The deconvolution of all these interaction types and their dependence on subtle structural variation is required to arrive at a structure-energy correlation that may serve as a guide in receptor construction. The focus on direct host-guest interactions (lock-and-key complementarity) that have dominated the binding concepts of artificial receptors in the past must be widened in order to account for entropic contributions which constitute very significant fractions of the total free energy of interaction. Including entropy necessarily addresses the ambiguity and fuzziness of the host-guest structural ensemble and requires the appreciation of the fact that most liquid phases possess distinct structures of their own. Apparently, it is the perturbation of the intrinsic solvent structure occurring upon association that rules ion binding in polar media where ions are soluble and abundant. Rather than specifying peculiar structural elements useful in anion binding this critical review attempts an illumination of the concepts and individual energetic contributions resulting in the final observation of specific anion recognition (95 references).

  4. Bats host major mammalian paramyxoviruses

    PubMed Central

    Drexler, Jan Felix; Corman, Victor Max; Müller, Marcel Alexander; Maganga, Gael Darren; Vallo, Peter; Binger, Tabea; Gloza-Rausch, Florian; Rasche, Andrea; Yordanov, Stoian; Seebens, Antje; Oppong, Samuel; Sarkodie, Yaw Adu; Pongombo, Célestin; Lukashev, Alexander N.; Schmidt-Chanasit, Jonas; Stöcker, Andreas; Carneiro, Aroldo José Borges; Erbar, Stephanie; Maisner, Andrea; Fronhoffs, Florian; Buettner, Reinhard; Kalko, Elisabeth K.V.; Kruppa, Thomas; Franke, Carlos Roberto; Kallies, René; Yandoko, Emmanuel R.N.; Herrler, Georg; Reusken, Chantal; Hassanin, Alexandre; Krüger, Detlev H.; Matthee, Sonja; Ulrich, Rainer G.; Leroy, Eric M.; Drosten, Christian

    2012-01-01

    The large virus family Paramyxoviridae includes some of the most significant human and livestock viruses, such as measles-, distemper-, mumps-, parainfluenza-, Newcastle disease-, respiratory syncytial virus and metapneumoviruses. Here we identify an estimated 66 new paramyxoviruses in a worldwide sample of 119 bat and rodent species (9,278 individuals). Major discoveries include evidence of an origin of Hendra- and Nipah virus in Africa, identification of a bat virus conspecific with the human mumps virus, detection of close relatives of respiratory syncytial virus, mouse pneumonia- and canine distemper virus in bats, as well as direct evidence of Sendai virus in rodents. Phylogenetic reconstruction of host associations suggests a predominance of host switches from bats to other mammals and birds. Hypothesis tests in a maximum likelihood framework permit the phylogenetic placement of bats as tentative hosts at ancestral nodes to both the major Paramyxoviridae subfamilies (Paramyxovirinae and Pneumovirinae). Future attempts to predict the emergence of novel paramyxoviruses in humans and livestock will have to rely fundamentally on these data. PMID:22531181

  5. Bats host major mammalian paramyxoviruses.

    PubMed

    Drexler, Jan Felix; Corman, Victor Max; Müller, Marcel Alexander; Maganga, Gael Darren; Vallo, Peter; Binger, Tabea; Gloza-Rausch, Florian; Cottontail, Veronika M; Rasche, Andrea; Yordanov, Stoian; Seebens, Antje; Knörnschild, Mirjam; Oppong, Samuel; Adu Sarkodie, Yaw; Pongombo, Célestin; Lukashev, Alexander N; Schmidt-Chanasit, Jonas; Stöcker, Andreas; Carneiro, Aroldo José Borges; Erbar, Stephanie; Maisner, Andrea; Fronhoffs, Florian; Buettner, Reinhard; Kalko, Elisabeth K V; Kruppa, Thomas; Franke, Carlos Roberto; Kallies, René; Yandoko, Emmanuel R N; Herrler, Georg; Reusken, Chantal; Hassanin, Alexandre; Krüger, Detlev H; Matthee, Sonja; Ulrich, Rainer G; Leroy, Eric M; Drosten, Christian

    2012-04-24

    The large virus family Paramyxoviridae includes some of the most significant human and livestock viruses, such as measles-, distemper-, mumps-, parainfluenza-, Newcastle disease-, respiratory syncytial virus and metapneumoviruses. Here we identify an estimated 66 new paramyxoviruses in a worldwide sample of 119 bat and rodent species (9,278 individuals). Major discoveries include evidence of an origin of Hendra- and Nipah virus in Africa, identification of a bat virus conspecific with the human mumps virus, detection of close relatives of respiratory syncytial virus, mouse pneumonia- and canine distemper virus in bats, as well as direct evidence of Sendai virus in rodents. Phylogenetic reconstruction of host associations suggests a predominance of host switches from bats to other mammals and birds. Hypothesis tests in a maximum likelihood framework permit the phylogenetic placement of bats as tentative hosts at ancestral nodes to both the major Paramyxoviridae subfamilies (Paramyxovirinae and Pneumovirinae). Future attempts to predict the emergence of novel paramyxoviruses in humans and livestock will have to rely fundamentally on these data.

  6. Swarming in bounded domains

    NASA Astrophysics Data System (ADS)

    Armbruster, Dieter; Motsch, Sébastien; Thatcher, Andrea

    2017-04-01

    The Vicsek model is a prototype for the emergence of collective motion. In free space, it is characterized by a swarm of particles all moving in the same direction. Since this dynamic does not include attraction among particles, the swarm, while aligning in velocity space, has no spatial coherence. Adding specular reflection at the boundaries generates global spatial coherence of the swarms while maintaining its velocity alignment. We investigate numerically how the geometry of the domain influences the Vicsek model using three type of geometry: a channel, a disk and a rectangle. Varying the parameters of the Vicsek model (e.g. noise levels and influence horizons), we discuss the mechanisms that generate spatial coherence and show how they create new dynamical solutions of the swarming motions in these geometries. Several observables are introduced to characterize the simulated patterns (e.g. mass profile, center of mass, connectivity of the swarm).

  7. Beyond the Number Domain

    PubMed Central

    Cantlon, Jessica F.; Platt, Michael L.; Brannon, Elizabeth M.

    2009-01-01

    In a world without numbers, we would be unable to build a skyscraper, hold a national election, plan a wedding, or pay for a chicken at the market. The numerical symbols used in all these behaviors build on the approximate number system (ANS) which represents the number of discrete objects or events as a continuous mental magnitude. In this review, we first discuss evidence that the ANS bears a set of behavioral and brain signatures that are universally displayed across animal species, human cultures, and development. We then turn to the question of whether the ANS constitutes a specialized cognitive and neural domain--a question central to understanding how this system works, the nature of its evolutionary and developmental trajectory, and its physical instantiation in the brain. PMID:19131268

  8. Twinning, Epitaxy and Domain Switching in Ferroelastic Inclusion Compounds

    NASA Technical Reports Server (NTRS)

    Hollingsworth, Mark D.; Peterson, Matthew L.

    2003-01-01

    Our research is in the area of solid-state organic chemistry, which lies at the interface between physical organic chemistry and materials science. We use crystalline solids as models to probe fundamental issues about physical processes, molecular interactions and chemical reactions that are important for fabrication, stabilization and application of technological materials. Much of our most recent work has focused on the phenomena of ferroelastic and ferroelectric domain switching, in which application of an external force or electric field to a crystal causes the molecules inside the crystal to reorient, in tandem, to a new orientational state. To better understand and control the domain switching process, we have designed and synthesized over twenty closely related, ferroelastic organic crystals. Our approach has been to use crystalline inclusion compounds, in which one molecule (the guest) is trapped within the crystalline framework of a second molecule (the host). By keeping the host constant and varying the proportions and kinds of guests, it has been possible to tailor these materials so that domain switching is rapid and reversible (which is desirable for high technology applications). Inclusion compounds therefore serve as powerful systems for understanding the specific molecular mechanisms that control domain switching.

  9. Ectoparasite fitness in auxiliary hosts: phylogenetic distance from a principal host matters.

    PubMed

    Khokhlova, I S; Fielden, L J; Degen, A A; Krasnov, B R

    2012-10-01

    We studied reproductive performance in two flea species (Parapulex chephrenis and Xenopsylla ramesis) exploiting either a principal or one of eight auxiliary host species. We predicted that fleas would produce more eggs and adult offspring when exploiting (i) a principal host than an auxiliary host and (ii) an auxiliary host phylogenetically close to a principal host than an auxiliary host phylogenetically distant from a principal host. In both flea species, egg production per female after one feeding and production of new imago after a timed period of an uninterrupted stay on a host differed significantly between host species. In general, egg and/or new imago production in fleas feeding on an auxiliary host was lower than in fleas feeding on the principal host, except for the auxiliary host that was the closest relative of the principal host. When all auxiliary host species were considered, we did not find any significant relationship between either egg or new imago production in fleas exploiting an auxiliary host and phylogenetic distance between this host and the principal host. However, when the analyses were restricted to auxiliary hosts belonging to the same family as the principal host (Muridae), new imago production (for P. chephrenis) or both egg and new imago production (for X. ramesis) in an auxiliary host decreased significantly with an increase in phylogenetic distance between the auxiliary and principal host. Our results demonstrated that a parasite achieves higher fitness in auxiliary hosts that are either the most closely related to or the most distant from its principal host. This may affect host associations of a parasite invading new areas. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

  10. Conserved domains and SINE diversity during animal evolution.

    PubMed

    Luchetti, Andrea; Mantovani, Barbara

    2013-10-01

    Eukaryotic genomes harbour a number of mobile genetic elements (MGEs); moving from one genomic location to another, they are known to impact on the host genome. Short interspersed elements (SINEs) are well-represented, non-autonomous retroelements and they are likely the most diversified MGEs. In some instances, sequence domains conserved across unrelated SINEs have been identified; remarkably, one of these, called Nin, has been conserved since the Radiata-Bilateria splitting. Here we report on two new domains: Inv, derived from Nin, identified in insects and in deuterostomes, and Pln, restricted to polyneopteran insects. The identification of Inv and Pln sequences allowed us to retrieve new SINEs, two in insects and one in a hemichordate. The diverse structural combination of the different domains in different SINE families, during metazoan evolution, offers a clearer view of SINE diversity and their frequent de novo emergence through module exchange, possibly underlying the high evolutionary success of SINEs. © 2013 Elsevier Inc. All rights reserved.

  11. Dissociation of GDP dissociation inhibitor and membrane translocation are required for efficient activation of Rac by the Dbl homology-pleckstrin homology region of Tiam.

    PubMed

    Robbe, Karine; Otto-Bruc, Annie; Chardin, Pierre; Antonny, Bruno

    2003-02-14

    Small G proteins of the Rho/Rac/Cdc42 family are associated with lipid membranes through their prenylated C termini. Alternatively, these proteins form soluble complexes with GDI proteins. To assess how this membrane partitioning influences the activation of Rac by guanine nucleotide exchange factors, GDP-to-GTP exchange reactions were performed in the presence of liposomes using different forms of Rac-GDP. We show that both non-prenylated Rac-GDP and the soluble complex between prenylated Rac-GDP and GDI are poorly activated by the Dbl homology-pleckstrin homology (DH-PH) domain of the exchange factor Tiam1, whereas prenylated Rac-GDP bound to liposomes is activated about 10 times more rapidly. Sedimentation experiments with liposomes reveal that the DH-PH region of Tiam1 forms, with nucleotide-free prenylated Rac, a membrane-bound complex from which GDI is excluded. Taken together, these experiments demonstrate that the dissociation of Rac-GDP from GDI and its translocation to membrane lipids favor DH-PH-catalyzed nucleotide exchange because the steric hindrance caused by GDI is relieved and because the membrane environment favors functional interaction between the DH-PH domain and the small G protein.

  12. Host compatibility rather than vector-host-encounter rate determines the host range of avian Plasmodium parasites.

    PubMed

    Medeiros, Matthew C I; Hamer, Gabriel L; Ricklefs, Robert E

    2013-06-07

    Blood-feeding arthropod vectors are responsible for transmitting many parasites between vertebrate hosts. While arthropod vectors often feed on limited subsets of potential host species, little is known about the extent to which this influences the distribution of vector-borne parasites in some systems. Here, we test the hypothesis that different vector species structure parasite-host relationships by restricting access of certain parasites to a subset of available hosts. Specifically, we investigate how the feeding patterns of Culex mosquito vectors relate to distributions of avian malaria parasites among hosts in suburban Chicago, IL, USA. We show that Plasmodium lineages, defined by cytochrome b haplotypes, are heterogeneously distributed across avian hosts. However, the feeding patterns of the dominant vectors (Culex restuans and Culex pipiens) are similar across these hosts, and do not explain the distributions of Plasmodium parasites. Phylogenetic similarity of avian hosts predicts similarity in their Plasmodium parasites. This effect was driven primarily by the general association of Plasmodium parasites with particular host superfamilies. Our results suggest that a mosquito-imposed encounter rate does not limit the distribution of avian Plasmodium parasites across hosts. This implies that compatibility between parasites and their avian hosts structure Plasmodium host range.

  13. Coevolution between pathogen-derived proteinases and proteinase inhibitors of host insects.

    PubMed

    Vilcinskas, Andreas

    2010-01-01

    Virulence is thought to coevolve as a result of reciprocal selection between pathogens and their hosts. This paper focuses on coevolution between microbial proteinases operating as virulence factors and host defense molecules of insects. Owing to shorter generation times and smaller genomes, microbes exhibit a high evolutionary adaptability in comparison with their hosts. Indeed, the latter can only compete with pathogens if they evolve mechanisms providing a comparable genetic plasticity. Gene or domain duplication and shuffling by recombination is the driving force behind the countermeasures in host defense effectors. Recent literature provides evidence for both diversifications of fungal proteinases involved in pathogenesis and expansion host proteinase inhibitors subsets contributing to insect innate immunity. For example, the pathogen-associated spectrum of proteolytic enzymes encompasses thermolysin-like metalloproteinases that putatively promoted the evolution of corresponding host inhibitors of these virulence factors which complement the insect repertoire of antimicrobial defense molecules. Beyond mutual diversification of effector molecules coevolution resulted also in sophisticated molecular adaptations of host insects such as sensing and feedback-loop regulation of microbial metalloproteinases and corresponding countermeasures of pathogens providing evasion of host immunity induced by these virulence factors.

  14. Hosts and geographic distribution of Arceuthobium oxycedri

    Treesearch

    W. M. Ciesla; B. W. Geils; R. P. Adams

    2002-01-01

    Data on hosts and geographic distribution of the juniper dwarf mistletoe, Arceuthobium oxycedri, are updated in light of changes in host nomenclature, political geography, and interpretation of reports and labels. Seventeen species of Juniperus, 3 Chamaecyparis, 5 Cupressus, and 1

  15. Multifunctionalities driven by ferroic domains

    SciTech Connect

    Yang, J. C.; Huang, Y. L.; Chu, Y. H.; He, Q.

    2014-08-14

    Considerable attention has been paid to ferroic systems in pursuit of advanced applications in past decades. Most recently, the emergence and development of multiferroics, which exhibit the coexistence of different ferroic natures, has offered a new route to create functionalities in the system. In this manuscript, we step from domain engineering to explore a roadmap for discovering intriguing phenomena and multifunctionalities driven by periodic domain patters. As-grown periodic domains, offering exotic order parameters, periodic local perturbations and the capability of tailoring local spin, charge, orbital and lattice degrees of freedom, are introduced as modeling templates for fundamental studies and novel applications. We discuss related significant findings on ferroic domain, nanoscopic domain walls, and conjunct heterostructures based on the well-organized domain patterns, and end with future prospects and challenges in the field.

  16. Ligand binding by PDZ domains.

    PubMed

    Chi, Celestine N; Bach, Anders; Strømgaard, Kristian; Gianni, Stefano; Jemth, Per

    2012-01-01

    The postsynaptic density protein-95/disks large/zonula occludens-1 (PDZ) protein domain family is one of the most common protein-protein interaction modules in mammalian cells, with paralogs present in several hundred human proteins. PDZ domains are found in most cell types, but neuronal proteins, for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context.

  17. Nucleation of holin domains and holes optimizes lysis timing of E. coli by phage λ

    NASA Astrophysics Data System (ADS)

    Ryan, Gillian; Rutenberg, Andrew

    2007-03-01

    Holin proteins regulate the precise scheduling of Escherichia coli lysis during infection by bacteriophage λ. Inserted into the host bacterium's inner membrane during infection, holins aggregate to form rafts and then holes within those rafts. We present a two-stage nucleation model of holin action, with the nucleation of condensed holin domains followed by the nucleation of holes within these domains. Late nucleation of holin rafts leads to a weak dependence of lysis timing on host cell size, though both nucleation events contribute equally to timing errors. Our simulations recover the accurate scheduling observed experimentally, and also suggest that phage-λ lysis of E.coli is optimized.

  18. Domain topology and domain switching kinetics in a hybrid improper ferroelectric

    PubMed Central

    Huang, F. -T.; Xue, F.; Gao, B.; Wang, L. H.; Luo, X.; Cai, W.; Lu, X. -Z.; Rondinelli, J. M.; Chen, L. Q.; Cheong, S. -W.

    2016-01-01

    Charged polar interfaces such as charged ferroelectric walls or heterostructured interfaces of ZnO/(Zn,Mg)O and LaAlO3/SrTiO3, across which the normal component of electric polarization changes suddenly, can host large two-dimensional conduction. Charged ferroelectric walls, which are energetically unfavourable in general, were found to be mysteriously abundant in hybrid improper ferroelectric (Ca,Sr)3Ti2O7 crystals. From the exploration of antiphase boundaries in bilayer-perovskites, here we discover that each of four polarization-direction states is degenerate with two antiphase domains, and these eight structural variants form a Z4 × Z2 domain structure with Z3 vortices and five distinct types of domain walls, whose topology is directly relevant to the presence of abundant charged walls. We also discover a zipper-like nature of antiphase boundaries, which are the reversible creation/annihilation centres of pairs of two types of ferroelectric walls (and also Z3-vortex pairs) in 90° and 180° polarization switching. Our results demonstrate the unexpectedly rich nature of hybrid improper ferroelectricity. PMID:27215944

  19. Domain topology and domain switching kinetics in a hybrid improper ferroelectric.

    PubMed

    Huang, F-T; Xue, F; Gao, B; Wang, L H; Luo, X; Cai, W; Lu, X-Z; Rondinelli, J M; Chen, L Q; Cheong, S-W

    2016-05-24

    Charged polar interfaces such as charged ferroelectric walls or heterostructured interfaces of ZnO/(Zn,Mg)O and LaAlO3/SrTiO3, across which the normal component of electric polarization changes suddenly, can host large two-dimensional conduction. Charged ferroelectric walls, which are energetically unfavourable in general, were found to be mysteriously abundant in hybrid improper ferroelectric (Ca,Sr)3Ti2O7 crystals. From the exploration of antiphase boundaries in bilayer-perovskites, here we discover that each of four polarization-direction states is degenerate with two antiphase domains, and these eight structural variants form a Z4 × Z2 domain structure with Z3 vortices and five distinct types of domain walls, whose topology is directly relevant to the presence of abundant charged walls. We also discover a zipper-like nature of antiphase boundaries, which are the reversible creation/annihilation centres of pairs of two types of ferroelectric walls (and also Z3-vortex pairs) in 90° and 180° polarization switching. Our results demonstrate the unexpectedly rich nature of hybrid improper ferroelectricity.

  20. Modified host cells with efflux pumps

    DOEpatents

    Dunlop, Mary J.; Keasling, Jay D.; Mukhopadhyay, Aindrila

    2016-08-30

    The present invention provides for a modified host cell comprising a heterologous expression of an efflux pump capable of transporting an organic molecule out of the host cell wherein the organic molecule at a sufficiently high concentration reduces the growth rate of or is lethal to the host cell.

  1. Understanding host switching through ecological fitting

    USDA-ARS?s Scientific Manuscript database

    Despite the fact that parasites are highly specialized to their hosts, extensive empirical evidence demonstrates that host switching rather than co-speciation is the most important factor influencing the origin of host-parasite associations. Ecological fitting in sloppy fitness space has been propos...

  2. Comparative structural and functional analysis of orthomyxovirus polymerase cap-snatching domains.

    PubMed

    Guilligay, Delphine; Kadlec, Jan; Crépin, Thibaut; Lunardi, Thomas; Bouvier, Denis; Kochs, Georg; Ruigrok, Rob W H; Cusack, Stephen

    2014-01-01

    Orthomyxovirus Influenza A virus (IAV) heterotrimeric polymerase performs transcription of viral mRNAs by cap-snatching, which involves generation of capped primers by host pre-mRNA binding via the PB2 subunit cap-binding site and cleavage 10-13 nucleotides from the 5' cap by the PA subunit endonuclease. Thogotoviruses, tick-borne orthomyxoviruses that includes Thogoto (THOV), Dhori (DHOV) and Jos (JOSV) viruses, are thought to perform cap-snatching by cleaving directly after the cap and thus have no heterogeneous, host-derived sequences at the 5' extremity of their mRNAs. Based on recent work identifying the cap-binding and endonuclease domains in IAV polymerase, we determined the crystal structures of two THOV PB2 domains, the putative cap-binding and the so-called '627-domain', and the structures of the putative endonuclease domains (PA-Nter) of THOV and DHOV. Despite low sequence similarity, corresponding domains have the same fold confirming the overall architectural similarity of orthomyxovirus polymerases. However the putative Thogotovirus cap-snatching domains in PA and PB2 have non-conservative substitutions of key active site residues. Biochemical analysis confirms that, unlike the IAV domains, the THOV and DHOV PA-Nter domains do not bind divalent cations and have no endonuclease activity and the THOV central PB2 domain does not bind cap analogues. On the other hand, sequence analysis suggests that other, non-influenza, orthomyxoviruses, such as salmon anemia virus (isavirus) and Quaranfil virus likely conserve active cap-snatching domains correlating with the reported occurrence of heterogeneous, host-derived sequences at the 5' end of the mRNAs of these viruses. These results highlight the unusual nature of transcription initiation by Thogotoviruses.

  3. Digesting blood of an auxiliary host in fleas: effect of phylogenetic distance from a principal host.

    PubMed

    Khokhlova, Irina S; Fielden, Laura J; Degen, A Allan; Krasnov, Boris R

    2012-04-15

    Fleas are haematophagous ectoparasites that exhibit varying degrees of host specificity. Flea abundance is highest on principal hosts and lower on auxiliary hosts but may vary greatly among auxiliary hosts. We investigated the feeding and energy expenditure for digestion in two flea species Parapulex chephrenis and Xenopsylla ramesis on a principal host (Acomys cahirinus and Meriones crassus, respectively) and eight auxiliary host species. We predicted that fleas would perform better - that is (i) a higher proportion of fleas would take a blood meal, (ii) fleas would take larger blood meals and (iii) fleas would spend less energy on digestion - if they fed on (i) a principal host compared with an auxiliary host and (ii) an auxiliary host phylogenetically close to a principal host compared with an auxiliary host phylogenetically distant from a principal host. Energy costs of digestion were estimated using CO(2) emission and represented energy cost during the first stage of blood digestion. Contrary to our predictions, fleas did not always perform better on a principal than on an auxiliary host or on auxiliary hosts phylogenetically closer to the principal host than on auxiliary hosts phylogenetically distant from a principal host. Variation in flea feeding performance may result from the interplay of several factors including co-occurrence between hosts and susceptibility of a host to flea attacks, the species-specific level of immunocompetence of a host and the level of host specificity of a flea. This study describes the first investigation into the metabolic expenditure of parasitism and its relationship to phylogenetic relationships amongst hosts.

  4. Ontology-based representation and analysis of host-Brucella interactions.

    PubMed

    Lin, Yu; Xiang, Zuoshuang; He, Yongqun

    2015-01-01

    Biomedical ontologies are representations of classes of entities in the biomedical domain and how these classes are related in computer- and human-interpretable formats. Ontologies support data standardization and exchange and provide a basis for computer-assisted automated reasoning. IDOBRU is an ontology in the domain of Brucella and brucellosis. Brucella is a Gram-negative intracellular bacterium that causes brucellosis, the most common zoonotic disease in the world. In this study, IDOBRU is used as a platform to model and analyze how the hosts, especially host macrophages, interact with virulent Brucella strains or live attenuated Brucella vaccine strains. Such a study allows us to better integrate and understand intricate Brucella pathogenesis and host immunity mechanisms. Different levels of host-Brucella interactions based on different host cell types and Brucella strains were first defined ontologically. Three important processes of virulent Brucella interacting with host macrophages were represented: Brucella entry into macrophage, intracellular trafficking, and intracellular replication. Two Brucella pathogenesis mechanisms were ontologically represented: Brucella Type IV secretion system that supports intracellular trafficking and replication, and Brucella erythritol metabolism that participates in Brucella intracellular survival and pathogenesis. The host cell death pathway is critical to the outcome of host-Brucella interactions. For better survival and replication, virulent Brucella prevents macrophage cell death. However, live attenuated B. abortus vaccine strain RB51 induces caspase-2-mediated proinflammatory cell death. Brucella-associated cell death processes are represented in IDOBRU. The gene and protein information of 432 manually annotated Brucella virulence factors were represented using the Ontology of Genes and Genomes (OGG) and Protein Ontology (PRO), respectively. Seven inference rules were defined to capture the knowledge of host

  5. Generic Model Host System Design

    SciTech Connect

    Chu, Chungming; Wu, Juhao; Qiang, Ji; Shen, Guobao; /Brookhaven

    2012-06-22

    There are many simulation codes for accelerator modelling; each one has some strength but not all. A platform which can host multiple modelling tools would be ideal for various purposes. The model platform along with infrastructure support can be used not only for online applications but also for offline purposes. Collaboration is formed for the effort of providing such a platform. In order to achieve such a platform, a set of common physics data structure has to be set. Application Programming Interface (API) for physics applications should also be defined within a model data provider. A preliminary platform design and prototype is discussed.

  6. HostDesigner, Version 3

    SciTech Connect

    Hay, Benjamin; McCann, Billy Wayne

    2015-09-18

    HostDesigner is a computer-aided molecular design code that enables the general application of de novo structure-based methods to problems in chemistry and material science. Its purpose is to identify organic molecules with 3D structures that match user-input specifications. To accomplish this, the code connects chemical fragments to build millions of potential molecules, evaluates the resulting structures based on geometric constraints, and outputs a rank-ordered list of candidates. Example applications include the design of metal ion sequestering agents for use in separations processes, molecules that form self-assembled nanoscale containers, and molecular building blocks for metal-organic frameworks.

  7. Mapping the Moral Domain

    PubMed Central

    Graham, Jesse; Nosek, Brian A.; Haidt, Jonathan; Iyer, Ravi; Koleva, Spassena; Ditto, Peter H.

    2010-01-01

    The moral domain is broader than the empathy and justice concerns assessed by existing measures of moral competence, and it is not just a subset of the values assessed by value inventories. To fill the need for reliable and theoretically-grounded measurement of the full range of moral concerns, we developed the Moral Foundations Questionnaire (MFQ) based on a theoretical model of five universally available (but variably developed) sets of moral intuitions: Harm/care, Fairness/reciprocity, Ingroup/loyalty, Authority/respect, and Purity/sanctity. We present evidence for the internal and external validity of the scale and the model, and in doing so present new findings about morality: 1. Comparative model fitting of confirmatory factor analyses provides empirical justification for a five-factor structure of moral concerns. 2. Convergent/discriminant validity evidence suggests that moral concerns predict personality features and social group attitudes not previously considered morally relevant. 3. We establish pragmatic validity of the measure in providing new knowledge and research opportunities concerning demographic and cultural differences in moral intuitions. These analyses provide evidence for the usefulness of Moral Foundations Theory in simultaneously increasing the scope and sharpening the resolution of psychological views of morality. PMID:21244182

  8. Mapping the moral domain.

    PubMed

    Graham, Jesse; Nosek, Brian A; Haidt, Jonathan; Iyer, Ravi; Koleva, Spassena; Ditto, Peter H

    2011-08-01

    The moral domain is broader than the empathy and justice concerns assessed by existing measures of moral competence, and it is not just a subset of the values assessed by value inventories. To fill the need for reliable and theoretically grounded measurement of the full range of moral concerns, we developed the Moral Foundations Questionnaire on the basis of a theoretical model of 5 universally available (but variably developed) sets of moral intuitions: Harm/Care, Fairness/Reciprocity, Ingroup/Loyalty, Authority/Respect, and Purity/Sanctity. We present evidence for the internal and external validity of the scale and the model, and in doing so we present new findings about morality: (a) Comparative model fitting of confirmatory factor analyses provides empirical justification for a 5-factor structure of moral concerns; (b) convergent/discriminant validity evidence suggests that moral concerns predict personality features and social group attitudes not previously considered morally relevant; and (c) we establish pragmatic validity of the measure in providing new knowledge and research opportunities concerning demographic and cultural differences in moral intuitions. These analyses provide evidence for the usefulness of Moral Foundations Theory in simultaneously increasing the scope and sharpening the resolution of psychological views of morality.

  9. Discoidin Domain Receptor 1

    PubMed Central

    Song, Sunmi; Shackel, Nicholas A.; Wang, Xin M.; Ajami, Katerina; McCaughan, Geoffrey W.; Gorrell, Mark D.

    2011-01-01

    Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and is activated by collagens. Transcriptional profiling of cirrhosis in human liver using a DNA array and quantitative PCR detected elevated mRNA expression of DDR1 compared with that in nondiseased liver. The present study characterized DDR1 expression in cirrhotic and nondiseased human liver and examined the cellular effects of DDR1 expression. mRNA expression of all five isoforms of DDR1 was detected in human liver, whereas DDR1a demonstrated differential expression in liver with hepatitis C virus and primary biliary cirrhosis compared with nondiseased liver. In addition, immunoblot analysis detected shed fragments of DDR1 more readily in cirrhotic liver than in nondiseased liver. Inasmuch as DDR1 is subject to protease-mediated cleavage after prolonged interaction with collagen, this differential expression may indicate more intense activation of DDR1 protein in cirrhotic compared with nondiseased liver. In situ hybridization and immunofluorescence localized intense DDR1 mRNA and protein expression to epithelial cells including hepatocytes at the portal-parenchymal interface and the luminal aspect of the biliary epithelium. Overexpression of DDR1a altered hepatocyte behavior including increased adhesion and less migration on extracelular matrix substrates. DDR1a regulated extracellular expression of matrix metalloproteinases 1 and 2. These data elucidate DDR1 function pertinent to cirrhosis and indicate the importance of epithelial cell–collagen interactions in chronic liver injury. PMID:21356365

  10. CDD: a conserved domain database for interactive domain family analysis.

    PubMed

    Marchler-Bauer, Aron; Anderson, John B; Derbyshire, Myra K; DeWeese-Scott, Carol; Gonzales, Noreen R; Gwadz, Marc; Hao, Luning; He, Siqian; Hurwitz, David I; Jackson, John D; Ke, Zhaoxi; Krylov, Dmitri; Lanczycki, Christopher J; Liebert, Cynthia A; Liu, Chunlei; Lu, Fu; Lu, Shennan; Marchler, Gabriele H; Mullokandov, Mikhail; Song, James S; Thanki, Narmada; Yamashita, Roxanne A; Yin, Jodie J; Zhang, Dachuan; Bryant, Stephen H

    2007-01-01

    The conserved domain database (CDD) is part of NCBI's Entrez database system and serves as a primary resource for the annotation of conserved domain footprints on protein sequences in Entrez. Entrez's global query interface can be accessed at http://www.ncbi.nlm.nih.gov/Entrez and will search CDD and many other databases. Domain annotation for proteins in Entrez has been pre-computed and is readily available in the form of 'Conserved Domain' links. Novel protein sequences can be scanned against CDD using the CD-Search service; this service searches databases of CDD-derived profile models with protein sequence queries using BLAST heuristics, at http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi. Protein query sequences submitted to NCBI's protein BLAST search service are scanned for conserved domain signatures by default. The CDD collection contains models imported from Pfam, SMART and COG, as well as domain models curated at NCBI. NCBI curated models are organized into hierarchies of domains related by common descent. Here we report on the status of the curation effort and present a novel helper application, CDTree, which enables users of the CDD resource to examine curated hierarchies. More importantly, CDD and CDTree used in concert, serve as a powerful tool in protein classification, as they allow users to analyze protein sequences in the context of domain family hierarchies.

  11. Varied interactions between proviruses and adjacent host chromatin.

    PubMed Central

    Conklin, K F; Groudine, M

    1986-01-01

    Retroviruses integrated at unique locations in the host genome can be expressed at different levels. We have analyzed the preintegration sites of three transcriptionally competent avian endogenous proviruses (evs) to determine whether the various levels of provirus expression correlate with their location in active or inactive regions of chromatin. Our results show that in three of four cell types, the chromatin conformation (as defined by relative nuclease sensitivity) of virus preintegration sites correlates with the level of expression of the resident provirus in ev+ cells: two inactive proviruses (ev-1 and ev-2) reside in nuclease-resistant chromatin domains and one active provirus (ev-3) resides in a nuclease-sensitive domain. Nuclear runoff transcription assays reveal that the preintegration sites of the active and inactive viruses are not transcribed. However, in erythrocytes of 15-day-old chicken embryos (15d RBCs), the structure and activity of the ev-3 provirus is independent of the conformation of its preintegration site. In this cell type, the ev-3 preintegration site is organized in a nuclease-resistant conformation, while the ev-3 provirus is in a nuclease-sensitive conformation and is transcribed. In addition, the nuclease sensitivity of host sequences adjacent to ev-3 is altered in ev-3+ 15d RBCs relative to that found in 15d RBCs that lack ev-3. These data suggest that the relationship between preintegration site structure and retrovirus expression is more complex than previously described. Images PMID:3025623

  12. Fido, a Novel AMPylation Domain Common to Fic, Doc, and AvrB

    PubMed Central

    Kinch, Lisa N.; Yarbrough, Melanie L.; Orth, Kim; Grishin, Nick V.

    2009-01-01

    Background The Vibrio parahaemolyticus type III secreted effector VopS contains a fic domain that covalently modifies Rho GTPase threonine with AMP to inhibit downstream signaling events in host cells. The VopS fic domain includes a conserved sequence motif (HPFx[D/E]GN[G/K]R) that contributes to AMPylation. Fic domains are found in a variety of species, including bacteria, a few archaea, and metazoan eukaryotes. Methodology/Principal Findings We show that the AMPylation activity extends to a eukaryotic fic domain in Drosophila melanogaster CG9523, and use sequence and structure based computational methods to identify related domains in doc toxins and the type III effector AvrB. The conserved sequence motif that contributes to AMPylation unites fic with doc. Although AvrB lacks this motif, its structure reveals a similar topology to the fic and doc folds. AvrB binds to a peptide fragment of its host virulence target in a similar manner as fic binds peptide substrate. AvrB also orients a phosphate group from a bound ADP ligand near the peptide-binding site and in a similar position as a bound fic phosphate. Conclusions/Significance The demonstrated eukaryotic fic domain AMPylation activity suggests that the VopS effector has exploited a novel host posttranslational modification. Fic domain-related structures give insight to the AMPylation active site and to the VopS fic domain interaction with its host GTPase target. These results suggest that fic, doc, and AvrB stem from a common ancestor that has evolved to AMPylate protein substrates. PMID:19503829

  13. Hydrophobic Compounds Reshape Membrane Domains

    PubMed Central

    Barnoud, Jonathan; Rossi, Giulia; Marrink, Siewert J.; Monticelli, Luca

    2014-01-01

    Cell membranes have a complex lateral organization featuring domains with distinct composition, also known as rafts, which play an essential role in cellular processes such as signal transduction and protein trafficking. In vivo, perturbations of membrane domains (e.g., by drugs or lipophilic compounds) have major effects on the activity of raft-associated proteins and on signaling pathways, but they are difficult to characterize because of the small size of the domains, typically below optical resolution. Model membranes, instead, can show macroscopic phase separation between liquid-ordered and liquid-disordered domains, and they are often used to investigate the driving forces of membrane lateral organization. Studies in model membranes have shown that some lipophilic compounds perturb membrane domains, but it is not clear which chemical and physical properties determine domain perturbation. The mechanisms of domain stabilization and destabilization are also unknown. Here we describe the effect of six simple hydrophobic compounds on the lateral organization of phase-separated model membranes consisting of saturated and unsaturated phospholipids and cholesterol. Using molecular simulations, we identify two groups of molecules with distinct behavior: aliphatic compounds promote lipid mixing by distributing at the interface between liquid-ordered and liquid-disordered domains; aromatic compounds, instead, stabilize phase separation by partitioning into liquid-disordered domains and excluding cholesterol from the disordered domains. We predict that relatively small concentrations of hydrophobic species can have a broad impact on domain stability in model systems, which suggests possible mechanisms of action for hydrophobic compounds in vivo. PMID:25299598

  14. Ontology development for Sufism domain

    NASA Astrophysics Data System (ADS)

    Iqbal, Rizwan

    2012-01-01

    Domain ontology is a descriptive representation of any particular domain which in detail describes the concepts in a domain, the relationships among those concepts and organizes them in a hierarchal manner. It is also defined as a structure of knowledge, used as a means of knowledge sharing to the community. An Important aspect of using ontologies is to make information retrieval more accurate and efficient. Thousands of domain ontologies from all around the world are available online on ontology repositories. Ontology repositories like SWOOGLE currently have over 1000 ontologies covering a wide range of domains. It was found that up to date there was no ontology available covering the domain of "Sufism". This unavailability of "Sufism" domain ontology became a motivation factor for this research. This research came up with a working "Sufism" domain ontology as well a framework, design of the proposed framework focuses on the resolution to problems which were experienced while creating the "Sufism" ontology. The development and working of the "Sufism" domain ontology are covered in detail in this research. The word "Sufism" is a term which refers to Islamic mysticism. One of the reasons to choose "Sufism" for ontology creation is its global curiosity. This research has also managed to create some individuals which inherit the concepts from the "Sufism" ontology. The creation of individuals helps to demonstrate the efficient and precise retrieval of data from the "Sufism" domain ontology. The experiment of creating the "Sufism" domain ontology was carried out on a tool called Protégé. Protégé is a tool which is used for ontology creation, editing and it is open source.

  15. Ontology development for Sufism domain

    NASA Astrophysics Data System (ADS)

    Iqbal, Rizwan

    2011-12-01

    Domain ontology is a descriptive representation of any particular domain which in detail describes the concepts in a domain, the relationships among those concepts and organizes them in a hierarchal manner. It is also defined as a structure of knowledge, used as a means of knowledge sharing to the community. An Important aspect of using ontologies is to make information retrieval more accurate and efficient. Thousands of domain ontologies from all around the world are available online on ontology repositories. Ontology repositories like SWOOGLE currently have over 1000 ontologies covering a wide range of domains. It was found that up to date there was no ontology available covering the domain of "Sufism". This unavailability of "Sufism" domain ontology became a motivation factor for this research. This research came up with a working "Sufism" domain ontology as well a framework, design of the proposed framework focuses on the resolution to problems which were experienced while creating the "Sufism" ontology. The development and working of the "Sufism" domain ontology are covered in detail in this research. The word "Sufism" is a term which refers to Islamic mysticism. One of the reasons to choose "Sufism" for ontology creation is its global curiosity. This research has also managed to create some individuals which inherit the concepts from the "Sufism" ontology. The creation of individuals helps to demonstrate the efficient and precise retrieval of data from the "Sufism" domain ontology. The experiment of creating the "Sufism" domain ontology was carried out on a tool called Protégé. Protégé is a tool which is used for ontology creation, editing and it is open source.

  16. Structure-Function Relationships Underlying the Capacity of Bordetella Adenylate Cyclase Toxin to Disarm Host Phagocytes.

    PubMed

    Novak, Jakub; Cerny, Ondrej; Osickova, Adriana; Linhartova, Irena; Masin, Jiri; Bumba, Ladislav; Sebo, Peter; Osicka, Radim

    2017-09-24

    Bordetellae, pathogenic to mammals, produce an immunomodulatory adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) that enables them to overcome the innate immune defense of the host. CyaA subverts host phagocytic cells by an orchestrated action of its functional domains, where an extremely catalytically active adenylyl cyclase enzyme is delivered into phagocyte cytosol by a pore-forming repeat-in-toxin (RTX) cytolysin moiety. By targeting sentinel cells expressing the complement receptor 3, known as the CD11b/CD18 (αMβ₂) integrin, CyaA compromises the bactericidal functions of host phagocytes and supports infection of host airways by Bordetellae. Here, we review the state of knowledge on structural and functional aspects of CyaA toxin action, placing particular emphasis on signaling mechanisms by which the toxin-produced 3',5'-cyclic adenosine monophosphate (cAMP) subverts the physiology of phagocytic cells.

  17. Structure and function of Toll/interleukin-1 receptor/resistance protein (TIR) domains.

    PubMed

    Ve, Thomas; Williams, Simon J; Kobe, Bostjan

    2015-02-01

    The Toll/interleukin-1 receptor/resistance protein (TIR) domain is a protein-protein interaction domain consisting of 125-200 residues, widely distributed in animals, plants and bacteria but absent from fungi, archea and viruses. In plants and animals, these domains are found in proteins with functions in innate immune pathways, while in bacteria, some TIR domain-containing proteins interfere with the innate immune pathways in the host. TIR domains function as protein scaffolds, mostly involving self-association and homotypic interactions with other TIR domains. In the last 15 years, the three-dimensional structures of TIR domains from several mammalian, plant and bacterial proteins have been reported. These structures, jointly with functional data including the identification of interacting proteins, have started to provide insight into the molecular basis of the assembly of animal and plant immune signaling complexes, and for host immunosuppression by bacterial pathogens. This review focuses on the current knowledge of the structures of the TIR domains and how the structure relates to function.

  18. Approaches to assessing host resistance.

    PubMed Central

    Bradley, S G; Morahan, P S

    1982-01-01

    There is increasing evidence that chronic, subclinical exposure to certain environmental pollutants may upset immune responsiveness and alter susceptibility of animals to infectious agents. Environmental chemicals or drugs may affect diverse aspects of the immune system, leading to immunosuppression, immunopotentiation, hypersensitivity or perturbed innate host resistance. A variety of infectious models is available that involves relatively well defined target organs and host defense mechanisms; for example, infections with encephalomyocarditis virus, Herpesvirus simplex, Listeria monocytogenes, Streptococcus pneumoniae, Escherichia coli or Plasmodium berghei. Important variables in infectious models used to assess immunotoxicity include species and strain of animal used, their age and sex, the route of exposure, and dose of the chemical. No one infectious model has yet emerged as a routine screening tool to detect and assess the subtle effects that may occur in immune responses when animals are exposed to doses of environmental pollutants that cause no adverse effect at a gross level. The selection of useful test systems is complicated because it is difficult to measure the effects of chronic, subclinical exposure to chemicals and sublethal challenges of microorganisms. PMID:6277617

  19. Host defences against Giardia lamblia.

    PubMed

    Lopez-Romero, G; Quintero, J; Astiazarán-García, H; Velazquez, C

    2015-08-01

    Giardia spp. is a protozoan parasite that inhabits the upper small intestine of mammals and other species and is the aetiological agent of giardiasis. It has been demonstrated that nitric oxide, mast cells and dendritic cells are the first line of defence against Giardia. IL-6 and IL-17 play an important role during infection. Several cytokines possess overlapping functions in regulating innate and adaptive immune responses. IgA and CD4(+) T cells are fundamental to the process of Giardia clearance. It has been suggested that CD4(+) T cells play a double role during the anti-Giardia immune response. First, they activate and stimulate the differentiation of B cells to generate Giardia-specific antibodies. Second, they act through a B-cell-independent mechanism that is probably mediated by Th17 cells. Several Giardia proteins that stimulate humoral and cellular immune responses have been described. Variant surface proteins, α-1 giardin, and cyst wall protein 2 can induce host protective responses to future Giardia challenges. The characterization and evaluation of the protective potential of the immunogenic proteins that are associated with Giardia will offer new insights into host-parasite interactions and may aid in the development of an effective vaccine against the parasite. © 2015 John Wiley & Sons Ltd.

  20. Host Evasion by Burkholderia cenocepacia

    PubMed Central

    Ganesan, Shyamala; Sajjan, Umadevi S.

    2012-01-01

    Burkholderia cenocepacia is an opportunistic respiratory pathogen of individuals with cystic fibrosis (CF). Some strains of B. cenocepacia are highly transmissible and resistant to almost all antibiotics. Approximately one-third of B. cenocepacia infected CF patients go on to develop fatal “cepacia syndrome.” During the last two decades, substantial progress has been made with regards to evasion of host innate defense mechanisms by B. cenocepacia. Almost all strains of B. cenocepacia have the capacity to survive and replicate intracellularly in both airway epithelial cells and macrophages, which are primary sentinels of the lung and play a pivotal role in clearance of infecting bacteria. Those strains of B. cenocepacia, which express both cable pili and the associated 22 kDa adhesin are also capable of transmigrating across airway epithelium and persist in mouse models of infection. In this review, we will discuss how this type of interaction between B. cenocepacia and host may lead to persistence of bacteria as well as lung inflammation in CF patients. PMID:22919590

  1. How Biofilms Evade Host Defenses.

    PubMed

    Roilides, Emmanuel; Simitsopoulou, Maria; Katragkou, Aspasia; Walsh, Thomas J

    2015-06-01

    The steps involved during the biofilm growth cycle include attachment to a substrate followed by more permanent adherence of the microorganisms, microcolony arrangement, and cell detachment required for the dissemination of single or clustered cells to other organ systems. Various methods have been developed for biofilm detection and quantitation. Biofilm-producing microorganisms can be detected in tissue culture plates, using silicone tubes and staining methods, and by visual assessment using scanning electron microscopy or confocal scanning laser microscopy. Quantitative measurement of biofilm growth is determined by using methods that include dry cell weight assays, colony-forming-unit counting, DNA quantification, or XTT 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide reduction assay. Upon infection, innate immune defense strategies are able to establish an immediate response through effector mechanisms mediated by immune cells, receptors, and several humoral factors. We present an overview of the life cycle of biofilms and their diversity, detection methods for biofilm development, and host immune responses to pathogens. We then focus on current concepts in bacterial and fungal biofilm immune evasion mechanisms. This appears to be of particular importance because the use of host immune responses may represent a novel therapeutic approach against biofilms.

  2. Bacterial TIR-containing proteins and host innate immune system evasion.

    PubMed

    Rana, Rohini R; Zhang, Minghao; Spear, Abigail M; Atkins, Helen S; Byrne, Bernadette

    2013-02-01

    The innate immune system provides the first line of host defence against invading pathogens. Key to upregulation of the innate immune response are Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns (PAMPs) and trigger a signaling pathway culminating in the production of inflammatory mediators. Central to this TLR signaling pathway are heterotypic protein-protein interactions mediated through Toll/interleukin-1 receptor (TIR) domains found in both the cytoplasmic regions of TLRs and adaptor proteins. Pathogenic bacteria have developed a range of ingenuous strategies to evade the host immune mechanisms. Recent work has identified a potentially novel evasion mechanism involving bacterial TIR domain proteins. Such domains have been identified in a wide range of pathogenic bacteria, and there is evidence to suggest that they interfere directly with the TLR signaling pathway and thus inhibit the activation of NF-κB. The individual TIR domains from the pathogenic bacteria Salmonella enterica serovar Enteritidis, Brucella sp, uropathogenic E. coli and Yersinia pestis have been analyzed in detail. The individual bacterial TIR domains from these pathogenic bacteria seem to differ in their modes of action and their roles in virulence. Here, we review the current state of knowledge on the possible roles and mechanisms of action of the bacterial TIR domains.

  3. Interaction network of tobacco etch potyvirus NIa protein with the host proteome during infection.

    PubMed

    Martínez, Fernando; Rodrigo, Guillermo; Aragonés, Verónica; Ruiz, Marta; Lodewijk, Iris; Fernández, Unai; Elena, Santiago F; Daròs, José-Antonio

    2016-02-01

    The genomes of plant viruses have limited coding capacity, and to complete their infectious cycles, viral factors must target, direct or indirectly, many host elements. However, the interaction networks between viruses and host factors are poorly understood. The genus Potyvirus is the largest group of plus-strand RNA viruses infecting plants. Potyviral nuclear inclusion a (NIa) plays many roles during infection. NIa is a polyprotein consisting of two domains, viral protein genome-linked (VPg) and protease (NIaPro), separated by an inefficiently utilized self-proteolytic site. To gain insights about the interaction between potyviral NIa and the host cell during infection, we constructed Tobacco etch virus (TEV, genus Potyvirus) infectious clones in which the VPg or the NIaPro domains of NIa were tagged with the affinity polypeptide Twin-Strep-tag and identified the host proteins targeted by the viral proteins by affinity purification followed by mass spectrometry analysis (AP-MS). We identified 232 different Arabidopsis thaliana proteins forming part of complexes in which TEV NIa products were also involved. VPg and NIaPro specifically targeted 89 and 76 of these proteins, respectively, whereas 67 proteins were targeted by both domains and considered full-length NIa targets. Taking advantage of the currently known A. thaliana interactome, we constructed a protein interaction network between TEV NIa domains and 516 host proteins. The most connected elements specifically targeted by VPg were G-box regulating factor 6 and mitochondrial ATP synthase δ subunit; those specifically targeted by NIaPro were plasma membrane aquaporin PIP2;7 and actin 7, whereas those targeted by full-length NIa were heat shock protein 70-1 and photosystem protein LHCA3. Moreover, a contextualization in the global A. thaliana interactome showed that NIa targets are not more connected with other host proteins than expected by chance, but are in a position that allows them to connect with other

  4. Yersinia type III effectors perturb host innate immune responses

    PubMed Central

    Pha, Khavong; Navarro, Lorena

    2016-01-01

    The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type III secretion system (T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The three human pathogenic Yersinia spp. (Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) are Gram-negative bacteria that share in common a 70 kb virulence plasmid which encodes the T3SS. Translocation of the Yersinia effector proteins (YopE, YopH, YopT, YopM, YpkA/YopO, and YopP/J) into the target host cell results in disruption of the actin cytoskeleton to inhibit phagocytosis, downregulation of proinflammatory cytokine/chemokine production, and induction of cellular apoptosis of the target cell. Over the past 25 years, studies on the Yersinia effector proteins have unveiled tremendous knowledge of how the effectors enhance Yersinia virulence. Recently, the long awaited crystal structure of YpkA has been solved providing further insights into the activation of the YpkA kinase domain. Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia

  5. Fractional diffusion on bounded domains

    DOE PAGES

    Defterli, Ozlem; D'Elia, Marta; Du, Qiang; ...

    2015-03-13

    We found that the mathematically correct specification of a fractional differential equation on a bounded domain requires specification of appropriate boundary conditions, or their fractional analogue. In this paper we discuss the application of nonlocal diffusion theory to specify well-posed fractional diffusion equations on bounded domains.

  6. Parallel pseudospectral domain decomposition techniques

    NASA Technical Reports Server (NTRS)

    Gottlieb, David; Hirsh, Richard S.

    1988-01-01

    The influence of interface boundary conditions on the ability to parallelize pseudospectral multidomain algorithms is investigated. Using the properties of spectral expansions, a novel parallel two domain procedure is generalized to an arbitrary number of domains each of which can be solved on a separate processor. This interface boundary condition considerably simplifies influence matrix techniques.

  7. Parallel pseudospectral domain decomposition techniques

    NASA Technical Reports Server (NTRS)

    Gottlieb, David; Hirsch, Richard S.

    1989-01-01

    The influence of interface boundary conditions on the ability to parallelize pseudospectral multidomain algorithms is investigated. Using the properties of spectral expansions, a novel parallel two domain procedure is generalized to an arbitrary number of domains each of which can be solved on a separate processor. This interface boundary condition considerably simplifies influence matrix techniques.

  8. Optimal Transport for Domain Adaptation.

    PubMed

    Courty, Nicolas; Flamary, Remi; Tuia, Devis; Rakotomamonjy, Alain

    2017-09-01

    Domain adaptation is one of the most challenging tasks of modern data analytics. If the adaptation is done correctly, models built on a specific data representation become more robust when confronted to data depicting the same classes, but described by another observation system. Among the many strategies proposed, finding domain-invariant representations has shown excellent properties, in particular since it allows to train a unique classifier effective in all domains. In this paper, we propose a regularized unsupervised optimal transportation model to perform the alignment of the representations in the source and target domains. We learn a transportation plan matching both PDFs, which constrains labeled samples of the same class in the source domain to remain close during transport. This way, we exploit at the same time the labeled samples in the source and the distributions observed in both domains. Experiments on toy and challenging real visual adaptation examples show the interest of the method, that consistently outperforms state of the art approaches. In addition, numerical experiments show that our approach leads to better performances on domain invariant deep learning features and can be easily adapted to the semi-supervised case where few labeled samples are available in the target domain.

  9. Fractional diffusion on bounded domains

    SciTech Connect

    Defterli, Ozlem; D'Elia, Marta; Du, Qiang; Gunzburger, Max Donald; Lehoucq, Richard B.; Meerschaert, Mark M.

    2015-03-13

    We found that the mathematically correct specification of a fractional differential equation on a bounded domain requires specification of appropriate boundary conditions, or their fractional analogue. In this paper we discuss the application of nonlocal diffusion theory to specify well-posed fractional diffusion equations on bounded domains.

  10. Structure of a two-CAP-domain protein from the human hookworm parasite Necator americanus

    SciTech Connect

    Asojo, Oluwatoyin A.

    2011-05-01

    The first structure of a two-CAP-domain protein, Na-ASP-1, from the major human hookworm parasite N. americanus refined to a resolution limit of 2.2 Å is presented. Major proteins secreted by the infective larval stage hookworms upon host entry include Ancylostoma secreted proteins (ASPs), which are characterized by one or two CAP (cysteine-rich secretory protein/antigen 5/pathogenesis related-1) domains. The CAP domain has been reported in diverse phylogenetically unrelated proteins, but has no confirmed function. The first structure of a two-CAP-domain protein, Na-ASP-1, from the major human hookworm parasite Necator americanus was refined to a resolution limit of 2.2 Å. The structure was solved by molecular replacement (MR) using Na-ASP-2, a one-CAP-domain ASP, as the search model. The correct MR solution could only be obtained by truncating the polyalanine model of Na-ASP-2 and removing several loops. The structure reveals two CAP domains linked by an extended loop. Overall, the carboxyl-terminal CAP domain is more similar to Na-ASP-2 than to the amino-terminal CAP domain. A large central cavity extends from the amino-terminal CAP domain to the carboxyl-terminal CAP domain, encompassing the putative CAP-binding cavity. The putative CAP-binding cavity is a characteristic cavity in the carboxyl-terminal CAP domain that contains a His and Glu pair. These residues are conserved in all single-CAP-domain proteins, but are absent in the amino-terminal CAP domain. The conserved His residues are oriented such that they appear to be capable of directly coordinating a zinc ion as observed for CAP proteins from reptile venoms. This first structure of a two-CAP-domain ASP can serve as a template for homology modeling of other two-CAP-domain proteins.

  11. Ability of a Generalist Seed Beetle to Colonize an Exotic Host: Effects of Host Plant Origin and Oviposition Host.

    PubMed

    Amarillo-Suárez, A; Repizo, A; Robles, J; Diaz, J; Bustamante, S

    2017-08-01

    The colonization of an exotic species by native herbivores is more likely to occur if that herbivore is a generalist. There is little information on the life-history mechanisms used by native generalist insects to colonize exotic hosts and how these mechanisms are affected by host properties. We examined the ability of the generalist seed beetle Stator limbatus Horn to colonize an exotic species. We compared its host preference, acceptability, performance, and egg size when ovipositing and developing on two native (Pithecellobium dulce (Roxb.) Benth and Senegalia riparia (Kunth)) and one exotic legume species (Leucaena leucocephala (Lam.)). We also analyzed the seed chemistry. We found that females recognize the exotic species as an unfavorable host for larval development and that they delayed oviposition and laid fewer and larger eggs on the exotic species than on the native species. Survivorship on the exotic host was 0%. Additionally, seeds of the native species contain five chemical compounds that are absent in the exotic species, and the exotic species contains three sterols, which are absent in the native legumes. Genetically based differences between beetles adapted to different hosts, plastic responses toward new hosts, and chemical differences among seeds are important in host colonization and recognition of the exotic host. In conclusion, the generalist nature of S. limbatus does not influence its ability to colonize L. leucocephala. Explanations for the colonization of exotic hosts by generalist native species and for the success of invasive species must be complemented with studies measuring local adaptation and plasticity.

  12. Phase-domain photoacoustic sensing

    NASA Astrophysics Data System (ADS)

    Gao, Fei; Zhang, Ruochong; Feng, Xiaohua; Liu, Siyu; Ding, Ran; Kishor, Rahul; Qiu, Lei; Zheng, Yuanjin

    2017-01-01

    As one of the fastest-growing imaging modalities in recent years, photoacoustic imaging has attracted tremendous research interest for various applications including anatomical, functional, and molecular imaging. The majority of the photoacoustic imaging systems are based on the time-domain pulsed photoacoustic method, which utilizes a pulsed laser source to induce a wideband photoacoustic signal, revealing optical absorption contrast. An alternative way is the frequency-domain photoacoustic method utilizing the chirping modulation of laser intensity to achieve lower system cost. In this paper, we report another way of the photoacoustic method, called phase-domain photoacoustic sensing, which explores the phase difference between two consequent intensity-modulated laser pulse induced photoacoustic measurements to reveal the optical properties. The basic principle is introduced, modeled, and experimentally validated in this paper, which opens another potential pathway to perform photoacoustic sensing and imaging, eliminating acoustic detection variations beyond the conventional time-domain and frequency-domain photoacoustic methods.

  13. Diversity in protein domain superfamilies

    PubMed Central

    Das, Sayoni; Dawson, Natalie L; Orengo, Christine A

    2015-01-01

    Whilst ∼93% of domain superfamilies appear to be relatively structurally and functionally conserved based on the available data from the CATH-Gene3D domain classification resource, the remainder are much more diverse. In this review, we consider how domains in some of the most ubiquitous and promiscuous superfamilies have evolved, in particular the plasticity in their functional sites and surfaces which expands the repertoire of molecules they interact with and actions performed on them. To what extent can we identify a core function for these superfamilies which would allow us to develop a ‘domain grammar of function’ whereby a protein's biological role can be proposed from its constituent domains? Clearly the first step is to understand the extent to which these components vary and how changes in their molecular make-up modifies function. PMID:26451979

  14. Microbial starch-binding domain.

    PubMed

    Rodríguez-Sanoja, Romina; Oviedo, Norma; Sánchez, Sergio

    2005-06-01

    Glucosidic bonds from different non-soluble polysaccharides such as starch, cellulose and xylan are hydrolyzed by amylases, cellulases and xylanases, respectively. These enzymes are produced by microorganisms. They have a modular structure that is composed of a catalytic domain and at least one non-catalytic domain that is involved in polysaccharide binding. Starch-binding modules are present in microbial enzymes that are involved in starch metabolism; these are classified into several different families on the basis of their amino acid sequence similarities. Such binding domains promote attachment to the substrate and increase its concentration at the active site of the enzyme, which allows microorganisms to degrade non-soluble starch. Fold similarities are better conserved than sequences; nevertheless, it is possible to notice two evolutionary clusters of microbial starch-binding domains. These domains have enormous potential as tags for protein immobilization, as well as for the tailoring of enzymes that play a part in polysaccharide metabolism.

  15. The monocyte binding domain(s) on human immunoglobulin G.

    PubMed

    Woof, J M; Nik Jaafar, M I; Jefferis, R; Burton, D R

    1984-06-01

    Monocyte binding has previously been assigned to the C gamma 3 domain of human immunoglobulin G (IgG) largely on the ability of the pFc' fragment to inhibit the monocyte-IgG interaction. This ability is markedly reduced compared to the intact parent IgG. We find this result with a conventional pFc' preparation but this preparation is found to contain trace contamination of parent IgG as demonstrated by reactivity with monoclonal antibodies directed against C gamma 2 domain and light-chain epitopes of human IgG. Extensive immunoaffinity purification of the pFc' preparation removes its inhibitory ability indicating that this originates in the trace contamination of parent IgG (or Fc). Neither of the human IgG1 paraproteins TIM, lacking the C gamma 2 domain, or SIZ, lacking the C gamma 3 domain, are found to inhibit the monocyte-IgG interaction. The hinge-deleted IgG1 Dob protein shows little or no inhibitory ability. Indirect evidence for the involvement of the C gamma 2 domain in monocyte binding is considered. We suggest finally that the site of interaction is found either on the C gamma 2 domain alone or between the C gamma 2 and C gamma 3 domains.

  16. Majorana Fermion Rides on a Magnetic Domain Wall

    NASA Astrophysics Data System (ADS)

    Kim, Se Kwon; Tewari, Sumanta; Tserkovnyak, Yaroslav

    Owing to the recent progress on endowing the electronic structure of magnetic nanowires with topological properties, the associated topological solitons in the magnetic texture--magnetic domain walls--appear as very natural hosts for exotic electronic excitations. Here, we propose to use the magnetic domain walls to engender Majorana fermions, which has several notable advantages compared to the existing approaches. First of all, the local tunneling density-of-states anomaly associated with the Majorana zero mode bound to a smooth magnetic soliton is immune to most of parasitic artifacts associated with the abrupt physical ends of a wire, which mar the existing experimental probes. Second, a viable route to move and braid Majorana fermions is offered by domain-wall motion. In particular, we envision the recently demonstrated heat-current induced motion of domain walls in insulating ferromagnets as a promising tool for nonintrusive displacement of Majorana modes. This leads us to propose a feasible scheme for braiding domain walls within a magnetic nanowire network, which manifests the nob-Abelian exchange statistics within the Majorana subspace. This work has been supported in part by the U.S. DOE-BES, FAME, and AFOSR grants.

  17. Separated matter and antimatter domains with vanishing domain walls

    SciTech Connect

    Dolgov, A.D.; Godunov, S.I.; Rudenko, A.S.; Tkachev, I.I. E-mail: sgodunov@itep.ru E-mail: tkachev@ms2.inr.ac.ru

    2015-10-01

    We present a model of spontaneous (or dynamical) C and CP violation where it is possible to generate domains of matter and antimatter separated by cosmologically large distances. Such C(CP) violation existed only in the early universe and later it disappeared with the only trace of generated baryonic and/or antibaryonic domains. So the problem of domain walls in this model does not exist. These features are achieved through a postulated form of interaction between inflaton and a new scalar field, realizing short time C(CP) violation.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24733922

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

    PubMed

    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.

  20. Genetic architecture underlying host choice differentiation in the sympatric host races of Lochmaea capreae leaf beetles.

    PubMed

    Soudi, Shaghayegh; Reinhold, Klaus; Engqvist, Leif

    2016-04-01

    Speciation in herbivorous insects has received considerable attention during the last few decades. Much of this group's diversity originates from adaptive population divergence onto different host plants, which often involves the evolution of specialized patterns of host choice behaviour. Differences in host choice often translates directly into divergence in mating sites, and therefore positive assortative mating will be created which will act as a strong barrier to gene flow. In this study, we first explored whether host choice is a genetically determined trait in the sympatric willow and birch host races of the leaf feeding beetle Lochmaea capreae, or whether larval experience influences adult host choice. Once we had established that host choice is a genetically based trait we determined its genetic architecture. To achieve this, we employed a reciprocal transplant design in which offspring from pure willow and birch cross-types, F1, F2 and backcrosses were raised on each host plant and their preference was determined upon reaching adulthood. We then applied joint-scaling analysis to uncover the genetic architecture of host preference. Our results suggest that rearing host does not have a pronounced effect on adult's host choice; rather the segregation pattern implies the existence of genetic loci affecting host choice in these host races. The joint-scaling analysis revealed that population differences in host choice are mainly influenced by the contribution of additive genetic effects and also maternally inherited cytoplasmic effects. We explore the implications of our findings for evolutionary dynamics of sympatric host race formation and speciation.

  1. Host defenses in subcutaneous mycoses.

    PubMed

    Vera-Cabrera, Lucio; Salinas-Carmona, Mario Cesar; Waksman, Noemi; Messeguer-Pérez, Jonathan; Ocampo-Candiani, Jorge; Welsh, Oliverio

    2012-01-01

    Subcutaneous mycoses include diverse clinical syndromes, characterized by invasion of the skin and subcutaneous tissue by saprobic fungi. Individuals living in rural areas constantly suffer lesions or trauma; however, only a few of them develop disease. In this contribution, we describe recent advances in the understanding of the virulence of these organisms, focusing on the most prevalent infections, sporotrichosis, chromoblastomycosis, and mycetoma. Although these infectious diseases are considered neglected tropical diseases, modern molecular techniques have been able to identify the etiologic agents and observe variations in the former monolithic concept of the species, which was based mostly on morphologic characteristics. The complete genetic characterization of the causative agents, along with that of their host, will help in the understanding of the factors on which the development of these infections depends.

  2. HOST structural analysis program overview

    NASA Technical Reports Server (NTRS)

    Thompson, Robert L.

    1986-01-01

    Hot-section components of aircraft gas turbine engines are subjected to severe thermal structural loading conditions, especially during the startup and takeoff portions of the engine cycle. The most severe and damaging stresses and strains are those induced by the steep thermal gradients induced during the startup transient. These transient stresses and strains are also the most difficult to predict, in part because the temperature gradients and distributions are not well known or readily predictable and, in part, because the cyclic elastic-viscoplastic behavior of the materials at these extremes of temperature and strain are not well known or readily predictable. A broad spectrum of structures related technology programs is underway to address these deficiencies at the basic as well as the applied level. The three key program elements in the HOST structural analysis program are computations, constitutive modeling, and experiments for each research activity. Also shown are tables summarizing each of the activities.

  3. Domain walls riding the wave.

    SciTech Connect

    Karapetrov, G.; Novosad, V.; Materials Science Division

    2010-11-01

    Recent years have witnessed a rapid proliferation of electronic gadgets around the world. These devices are used for both communication and entertainment, and it is a fact that they account for a growing portion of household energy consumption and overall world consumption of electricity. Increasing the energy efficiency of these devices could have a far greater and immediate impact than a gradual switch to renewable energy sources. The advances in the area of spintronics are therefore very important, as gadgets are mostly comprised of memory and logic elements. Recent developments in controlled manipulation of magnetic domains in ferromagnet nanostructures have opened opportunities for novel device architectures. This new class of memories and logic gates could soon power millions of consumer electronic devices. The attractiveness of using domain-wall motion in electronics is due to its inherent reliability (no mechanical moving parts), scalability (3D scalable architectures such as in racetrack memory), and nonvolatility (retains information in the absence of power). The remaining obstacles in widespread use of 'racetrack-type' elements are the speed and the energy dissipation during the manipulation of domain walls. In their recent contribution to Physical Review Letters, Oleg Tretiakov, Yang Liu, and Artem Abanov from Texas A&M University in College Station, provide a theoretical description of domain-wall motion in nanoscale ferromagnets due to the spin-polarized currents. They find exact conditions for time-dependent resonant domain-wall movement, which could speed up the motion of domain walls while minimizing Ohmic losses. Movement of domain walls in ferromagnetic nanowires can be achieved by application of external magnetic fields or by passing a spin-polarized current through the nanowire itself. On the other hand, the readout of the domain state is done by measuring the resistance of the wire. Therefore, passing current through the ferromagnetic wire is

  4. Lipid rafts, caveolae, caveolin-1, and entry by Chlamydiae into host cells.

    PubMed

    Stuart, Elizabeth S; Webley, Wilmore C; Norkin, Leonard C

    2003-07-01

    Obligate intracellular bacterial pathogens of the genus Chlamydia are reported to enter host cells by both clathrin-dependent and clathrin-independent processes. C. trachomatis serovar K recently was shown to enter cells via caveolae-like lipid raft domains. We asked here how widespread raft-mediated entry might be among the Chlamydia. We show that C. pneumoniae, an important cause of respiratory infections in humans that additionally is associated with cardiovascular disease, and C. psittaci, an important pathogen in domestic mammals and birds that also infects humans, each enter host cells via cholesterol-rich lipid raft microdomains. Further, we show that C. trachomatis serovars E and F also use these domains to enter host cells. The involvement of these membrane domains in the entry of these organisms was indicated by the sensitivity of their entry to the raft-disrupting agents Nystatin and filipin, and by their intracellular association with caveolin-1, a 22-kDa protein associated with the formation of caveolae in rafts. In contrast, caveolin-marked lipid raft domains do not mediate entry of C. trachomatis serovars A, 36B, and C, nor of LGV serovar L2 and MoPn. Finally, we show that entry of each of these chlamydial strains is independent of cellular expression of caveolin-1. Thus, entry via the Nystatin and filipin-sensitive pathway is dependent on lipid rafts containing cholesterol, rather than invaginated caveolae per se.

  5. VLA Hosts "Flag Across America"

    NASA Astrophysics Data System (ADS)

    2001-11-01

    The National Radio Astronomy Observatory (NRAO) hosted the runners and support personnel of the "Americans United Flag Across America" run as the transcontinental memorial and fundraising effort came through New Mexico. The flag run arrived at NRAO's Very Large Array (VLA) radio telescope west of Socorro, NM, early in the post-Midnight morning of Monday, November 5, and departed after sunrise that morning en route to the Arizona border. Drivers, runners and support personnel stayed overnight at the VLA. During the night, a "VLA Night Owl Run" kept the flag moving around the VLA area until the westward trek resumed after dawn. The run began Oct. 11, one month after the terrorist attacks on New York and Washington. Organized by employees of American and United Airlines to honor the flight crews lost in those attacks, to show support for U.S. troops and to raise funds to help the victims' families, the run will take an American flag from Boston Logan Airport to Los Angeles International Airport. The Boston-to-Los Angeles trip represents the intended journey of American Flight 11 and United Flight 175, both of which were crashed by terrorists into the World Trade Center. "Our observatory was proud to host this group and honored that they brought this flag through our facility," said Miller Goss, NRAO's director of VLA operations. The runners carried a flag that flew in a U.S. F-16 over Iraq in support of Operation Southern Watch on Oct. 2, and has visited Ground Zero in Manhattan. The flag is scheduled to arrive in Los Angeles on Veterans Day, Nov. 11. The National Radio Astronomy Observatory is a facility of the National Science Foundation, operated under cooperative agreement by Associated Universities, Inc.

  6. MHC polymorphism under host-pathogen coevolution.

    PubMed

    Borghans, José A M; Beltman, Joost B; De Boer, Rob J

    2004-02-01

    The genes encoding major histocompatibility (MHC) molecules are among the most polymorphic genes known for vertebrates. Since MHC molecules play an important role in the induction of immune responses, the evolution of MHC polymorphism is often explained in terms of increased protection of hosts against pathogens. Two selective pressures that are thought to be involved are (1) selection favoring MHC heterozygous hosts, and (2) selection for rare MHC alleles by host-pathogen coevolution. We have developed a computer simulation of coevolving hosts and pathogens to study the relative impact of these two mechanisms on the evolution of MHC polymorphism. We found that heterozygote advantage per se is insufficient to explain the high degree of polymorphism at the MHC, even in very large host populations. Host-pathogen coevolution, on the other hand, can easily account for realistic polymorphisms of more than 50 alleles per MHC locus. Since evolving pathogens mainly evade presentation by the most common MHC alleles in the host population, they provide a selective pressure for a large variety of rare MHC alleles. Provided that the host population is sufficiently large, a large set of MHC alleles can persist over many host generations under host-pathogen coevolution, despite the fact that allele frequencies continuously change.

  7. Toxocara spp. infections in paratenic hosts.

    PubMed

    Strube, Christina; Heuer, Lea; Janecek, Elisabeth

    2013-04-15

    The zoonotic roundworms Toxocara canis and T. cati are not only present worldwide in their definitive hosts; they also frequently occur in other animal species, including humans. In those so-called paratenic hosts, the larvae do not develop into the adult stage, but rather migrate throughout the somatic tissue and persist as infectious L3 stage for extensive periods. Those arrested larvae may lead to severe inflammatory reactions and consequently to a wide range of pathological and clinical manifestations. However, the infected paratenic hosts also constitute a potential source of infection for the definitive hosts or humans who may also function as paratenic hosts. In the present review, current knowledge of larval migration in a variety of possible paratenic hosts is summarized including variations of migration routes and susceptibilities. Furthermore, information about the clinical and pathological changes for the presented species and possible consequences of the somatic migration of larvae, i.e. the resulting tissue damage as well as adverse host reactions to arrested larvae are reviewed. There are still many questions unanswered regarding larval behaviour in hosts other than their definitive host. Therefore, it is of great importance to continue further elaboration on the biology of Toxocara spp. to prevent further spreading of larvae in both the paratenic and the definitive host.

  8. Understanding Host-Switching by Ecological Fitting

    PubMed Central

    Araujo, Sabrina B. L.; Braga, Mariana Pires; Brooks, Daniel R.; Agosta, Salvatore J.; Hoberg, Eric P.; von Hartenthal, Francisco W.; Boeger, Walter A.

    2015-01-01

    Despite the fact that parasites are highly specialized with respect to their hosts, empirical evidence demonstrates that host switching rather than co-speciation is the dominant factor influencing the diversification of host-parasite associations. Ecological fitting in sloppy fitness space has been proposed as a mechanism allowing ecological specialists to host-switch readily. That proposal is tested herein using an individual-based model of host switching. The model considers a parasite species exposed to multiple host resources. Through time host range expansion can occur readily without the prior evolution of novel genetic capacities. It also produces non-linear variation in the size of the fitness space. The capacity for host colonization is strongly influenced by propagule pressure early in the process and by the size of the fitness space later. The simulations suggest that co-adaptation may be initiated by the temporary loss of less fit phenotypes. Further, parasites can persist for extended periods in sub-optimal hosts, and thus may colonize distantly related hosts by a "stepping-stone" process. PMID:26431199

  9. Shifting Preference between Oviposition vs. Host-Feeding under Changing Host Densities in Two Aphelinid Parasitoids

    PubMed Central

    Yang, Nian-Wan; Ji, Lu-Lu; Lövei, Gabor L.; Wan, Fang-Hao

    2012-01-01

    Destructive host-feeding is common in hymenopteran parasitoids. Such feeding may be restricted to host stages not preferred for oviposition. However, whether this is a fixed strategy or can vary according to resource levels or parasitoid needs is less clear. We tested the trade-off between host feeding and oviposition on two whitefly parasitoids under varying host densities. Females of two aphelinid parasitoids, Eretmocerus hayati and Encarsia sophia were exposed to nine different densities of their whitefly host, Bemisia tabaci, in single-instar tests to identify their functional response. Mixed-instar host choice tests were also conducted by exposing whiteflies at four densities to the parasitoids. We hypothesized that the parasitoid females can detect different host densities, and decide on oviposition vs. host-feeding accordingly. The results showed that both Er. hayati and En. sophia females tended to increase both oviposition and host-feeding with increased host density within a certain range. Oviposition reached a plateau at lower host density than host-feeding in Er. hayati, while En. sophia reached its oviposition plateau at higher densities. At low densities, Er. hayati parasitized most on first and second (the optimal ones), and fed most on third nymphal instars (the suboptimal one) of the whitefly host as theory predicts, while at high densities, both parasitism and host-feeding occurred on first and second instars which are preferred for oviposition. En. sophia parasitized most on third and fourth (the optimal ones), while fed on first instars (the suboptimal one) at low densities, and utilized third and fourth instars for both at high densities. In conclusion, oviposition vs. host-feeding strategy of parasitoid females was found to vary at different host densities. The balance between reserving optimal hosts for oviposition or using them for host-feeding depended on parasitoid life history and the availability of host resources. PMID:22815964

  10. Shifting preference between oviposition vs. host-feeding under changing host densities in two aphelinid parasitoids.

    PubMed

    Yang, Nian-Wan; Ji, Lu-Lu; Lövei, Gabor L; Wan, Fang-Hao

    2012-01-01

    Destructive host-feeding is common in hymenopteran parasitoids. Such feeding may be restricted to host stages not preferred for oviposition. However, whether this is a fixed strategy or can vary according to resource levels or parasitoid needs is less clear. We tested the trade-off between host feeding and oviposition on two whitefly parasitoids under varying host densities. Females of two aphelinid parasitoids, Eretmocerus hayati and Encarsia sophia were exposed to nine different densities of their whitefly host, Bemisia tabaci, in single-instar tests to identify their functional response. Mixed-instar host choice tests were also conducted by exposing whiteflies at four densities to the parasitoids. We hypothesized that the parasitoid females can detect different host densities, and decide on oviposition vs. host-feeding accordingly. The results showed that both Er. hayati and En. sophia females tended to increase both oviposition and host-feeding with increased host density within a certain range. Oviposition reached a plateau at lower host density than host-feeding in Er. hayati, while En. sophia reached its oviposition plateau at higher densities. At low densities, Er. hayati parasitized most on first and second (the optimal ones), and fed most on third nymphal instars (the suboptimal one) of the whitefly host as theory predicts, while at high densities, both parasitism and host-feeding occurred on first and second instars which are preferred for oviposition. En. sophia parasitized most on third and fourth (the optimal ones), while fed on first instars (the suboptimal one) at low densities, and utilized third and fourth instars for both at high densities. In conclusion, oviposition vs. host-feeding strategy of parasitoid females was found to vary at different host densities. The balance between reserving optimal hosts for oviposition or using them for host-feeding depended on parasitoid life history and the availability of host resources.

  11. Mutation of domain III and domain VI in L gene conserved domain of Nipah virus

    NASA Astrophysics Data System (ADS)

    Jalani, Siti Aishah; Ibrahim, Nazlina

    2016-11-01

    Nipah virus (NiV) is the etiologic agent responsible for the respiratory illness and causes fatal encephalitis in human. NiV L protein subunit is thought to be responsible for the majority of enzymatic activities involved in viral transcription and replication. The L protein which is the viral RNA dependent RNA polymerase has high sequence homology among negative sense RNA viruses. In negative stranded RNA viruses, based on sequence alignment six conserved domain (domain I-IV) have been determined. Each domain is separated on variable regions that suggest the structure to consist concatenated functional domain. To directly address the roles of domains III and VI, site-directed mutations were constructed by the substitution of bases at sequences 2497, 2500, 5528 and 5532. Each mutated L gene can be used in future studies to test the ability for expression on in vitro translation.

  12. Modeling software systems by domains

    NASA Technical Reports Server (NTRS)

    Dippolito, Richard; Lee, Kenneth

    1992-01-01

    The Software Architectures Engineering (SAE) Project at the Software Engineering Institute (SEI) has developed engineering modeling techniques that both reduce the complexity of software for domain-specific computer systems and result in systems that are easier to build and maintain. These techniques allow maximum freedom for system developers to apply their domain expertise to software. We have applied these techniques to several types of applications, including training simulators operating in real time, engineering simulators operating in non-real time, and real-time embedded computer systems. Our modeling techniques result in software that mirrors both the complexity of the application and the domain knowledge requirements. We submit that the proper measure of software complexity reflects neither the number of software component units nor the code count, but the locus of and amount of domain knowledge. As a result of using these techniques, domain knowledge is isolated by fields of engineering expertise and removed from the concern of the software engineer. In this paper, we will describe kinds of domain expertise, describe engineering by domains, and provide relevant examples of software developed for simulator applications using the techniques.

  13. Discussion summary: Fictitious domain methods

    NASA Technical Reports Server (NTRS)

    Glowinski, Rowland; Rodrigue, Garry

    1991-01-01

    Fictitious Domain methods are constructed in the following manner: Suppose a partial differential equation is to be solved on an open bounded set, Omega, in 2-D or 3-D. Let R be a rectangle domain containing the closure of Omega. The partial differential equation is first solved on R. Using the solution on R, the solution of the equation on Omega is then recovered by some procedure. The advantage of the fictitious domain method is that in many cases the solution of a partial differential equation on a rectangular region is easier to compute than on a nonrectangular region. Fictitious domain methods for solving elliptic PDEs on general regions are also very efficient when used on a parallel computer. The reason is that one can use the many domain decomposition methods that are available for solving the PDE on the fictitious rectangular region. The discussion on fictitious domain methods began with a talk by R. Glowinski in which he gave some examples of a variational approach to ficititious domain methods for solving the Helmholtz and Navier-Stokes equations.

  14. HIV-1 and hijacking of the host immune system: the current scenario.

    PubMed

    Imran, Muhammad; Manzoor, Sobia; Saalim, Muhammad; Resham, Saleha; Ashraf, Javed; Javed, Aneela; Waqar, Ahmed Bilal

    2016-10-01

    Human immunodeficiency virus (HIV) infection is a major health burden across the world which leads to the development of acquired immune deficiency syndrome (AIDS). This review article discusses the prevalence of HIV, its major routes of transmission, natural immunity, and evasion from the host immune system. HIV is mostly prevalent in Sub-Saharan Africa and low income countries. It is mostly transmitted by sharing syringe needles, blood transfusion, and sexual routes. The host immune system is categorized into three main types; the innate, the adaptive, and the intrinsic immune system. Regarding the innate immune system against HIV, the key players are mucosal membrane, dendritic cells (DCs), complement system, interferon, and host Micro RNAs. The major components of the adaptive immune system exploited by HIV are T cells mainly CD4+ T cells and B cells. The intrinsic immune system confronted by HIV involves (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) APOBEC3G, tripartite motif 5-α (TRIM5a), terherin, and (SAM-domain HD-domain containing protein) SAMHD1. HIV-1 efficiently interacts with the host immune system, exploits the host machinery, successfully replicates and transmits from one cell to another. Further research is required to explore evasion strategies of HIV to develop novel therapeutic approaches against HIV.

  15. Structural and evolutionary divergence of cyclic nucleotide binding domains in eukaryotic pathogens: Implications for drug design☆

    PubMed Central

    Mohanty, Smita; Kennedy, Eileen J.; Herberg, Friedrich W.; Hui, Raymond; Taylor, Susan S.; Langsley, Gordon; Kannan, Natarajan

    2015-01-01

    Many cellular functions in eukaryotic pathogens are mediated by the cyclic nucleotide binding (CNB) domain, which senses second messengers such as cyclic AMP and cyclic GMP. Although CNB domain-containing proteins have been identified in many pathogenic organisms, an incomplete understanding of how CNB domains in pathogens differ from other eukaryotic hosts has hindered the development of selective inhibitors for CNB domains associated with infectious diseases. Here, we identify and classify CNB domain-containing proteins in eukaryotic genomes to understand the evolutionary basis for CNB domain functional divergence in pathogens. We identify 359 CNB domain-containing proteins in 31 pathogenic organisms and classify them into distinct subfamilies based on sequence similarity within the CNB domain as well as functional domains associated with the CNB domain. Our study reveals novel subfamilies with pathogen-specific variations in the phosphate-binding cassette. Analyzing these variations in light of existing structural and functional data provides new insights into ligand specificity and promiscuity and clues for drug design. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases. PMID:25847873

  16. Structural and evolutionary divergence of cyclic nucleotide binding domains in eukaryotic pathogens: Implications for drug design.

    PubMed

    Mohanty, Smita; Kennedy, Eileen J; Herberg, Friedrich W; Hui, Raymond; Taylor, Susan S; Langsley, Gordon; Kannan, Natarajan

    2015-10-01

    Many cellular functions in eukaryotic pathogens are mediated by the cyclic nucleotide binding (CNB) domain, which senses second messengers such as cyclic AMP and cyclic GMP. Although CNB domain-containing proteins have been identified in many pathogenic organisms, an incomplete understanding of how CNB domains in pathogens differ from other eukaryotic hosts has hindered the development of selective inhibitors for CNB domains associated with infectious diseases. Here, we identify and classify CNB domain-containing proteins in eukaryotic genomes to understand the evolutionary basis for CNB domain functional divergence in pathogens. We identify 359 CNB domain-containing proteins in 31 pathogenic organisms and classify them into distinct subfamilies based on sequence similarity within the CNB domain as well as functional domains associated with the CNB domain. Our study reveals novel subfamilies with pathogen-specific variations in the phosphate-binding cassette. Analyzing these variations in light of existing structural and functional data provides new insights into ligand specificity and promiscuity and clues for drug design. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases. Copyright © 2015. Published by Elsevier B.V.

  17. Systematic analyses reveal uniqueness and origin of the CFEM domain in fungi

    PubMed Central

    Zhang, Zhen-Na; Wu, Qin-Yi; Zhang, Gui-Zhi; Zhu, Yue-Yan; Murphy, Robert W.; Liu, Zhen; Zou, Cheng-Gang

    2015-01-01

    CFEM domain commonly occurs in fungal extracellular membrane proteins. To provide insights for understanding putative functions of CFEM, we investigate the evolutionary dynamics of CFEM domains by systematic comparative genomic analyses among diverse animals, plants, and more than 100 fungal species, which are representative across the entire group of fungi. We here show that CFEM domain is unique to fungi. Experiments using tissue culture demonstrate that the CFEM-containing ESTs in some plants originate from endophytic fungi. We also find that CFEM domain does not occur in all fungi. Its single origin dates to the most recent common ancestors of Ascomycota and Basidiomycota, instead of multiple origins. Although the length and architecture of CFEM domains are relatively conserved, the domain-number varies significantly among different fungal species. In general, pathogenic fungi have a larger number of domains compared to other species. Domain-expansion across fungal genomes appears to be driven by domain duplication and gene duplication via recombination. These findings generate a clear evolutionary trajectory of CFEM domains and provide novel insights into the functional exchange of CFEM-containing proteins from cell-surface components to mediators in host-pathogen interactions. PMID:26255557

  18. Predicting domain-domain interaction based on domain profiles with feature selection and support vector machines

    PubMed Central

    2010-01-01

    Background Protein-protein interaction (PPI) plays essential roles in cellular functions. The cost, time and other limitations associated with the current experimental methods have motivated the development of computational methods for predicting PPIs. As protein interactions generally occur via domains instead of the whole molecules, predicting domain-domain interaction (DDI) is an important step toward PPI prediction. Computational methods developed so far have utilized information from various sources at different levels, from primary sequences, to molecular structures, to evolutionary profiles. Results In this paper, we propose a computational method to predict DDI using support vector machines (SVMs), based on domains represented as interaction profile hidden Markov models (ipHMM) where interacting residues in domains are explicitly modeled according to the three dimensional structural information available at the Protein Data Bank (PDB). Features about the domains are extracted first as the Fisher scores derived from the ipHMM and then selected using singular value decomposition (SVD). Domain pairs are represented by concatenating their selected feature vectors, and classified by a support vector machine trained on these feature vectors. The method is tested by leave-one-out cross validation experiments with a set of interacting protein pairs adopted from the 3DID database. The prediction accuracy has shown significant improvement as compared to InterPreTS (Interaction Prediction through Tertiary Structure), an existing method for PPI prediction that also uses the sequences and complexes of known 3D structure. Conclusions We show that domain-domain interaction prediction can be significantly enhanced by exploiting information inherent in the domain profiles via feature selection based on Fisher scores, singular value decomposition and supervised learning based on support vector machines. Datasets and source code are freely available on the web at http

  19. Predicting domain-domain interaction based on domain profiles with feature selection and support vector machines.

    PubMed

    González, Alvaro J; Liao, Li

    2010-10-29

    Protein-protein interaction (PPI) plays essential roles in cellular functions. The cost, time and other limitations associated with the current experimental methods have motivated the development of computational methods for predicting PPIs. As protein interactions generally occur via domains instead of the whole molecules, predicting domain-domain interaction (DDI) is an important step toward PPI prediction. Computational methods developed so far have utilized information from various sources at different levels, from primary sequences, to molecular structures, to evolutionary profiles. In this paper, we propose a computational method to predict DDI using support vector machines (SVMs), based on domains represented as interaction profile hidden Markov models (ipHMM) where interacting residues in domains are explicitly modeled according to the three dimensional structural information available at the Protein Data Bank (PDB). Features about the domains are extracted first as the Fisher scores derived from the ipHMM and then selected using singular value decomposition (SVD). Domain pairs are represented by concatenating their selected feature vectors, and classified by a support vector machine trained on these feature vectors. The method is tested by leave-one-out cross validation experiments with a set of interacting protein pairs adopted from the 3DID database. The prediction accuracy has shown significant improvement as compared to InterPreTS (Interaction Prediction through Tertiary Structure), an existing method for PPI prediction that also uses the sequences and complexes of known 3D structure. We show that domain-domain interaction prediction can be significantly enhanced by exploiting information inherent in the domain profiles via feature selection based on Fisher scores, singular value decomposition and supervised learning based on support vector machines. Datasets and source code are freely available on the web at http

  20. An archaeal origin of eukaryotes supports only two primary domains of life.

    PubMed

    Williams, Tom A; Foster, Peter G; Cox, Cymon J; Embley, T Martin

    2013-12-12

    The discovery of the Archaea and the proposal of the three-domains 'universal' tree, based on ribosomal RNA and core genes mainly involved in protein translation, catalysed new ideas for cellular evolution and eukaryotic origins. However, accumulating evidence suggests that the three-domains tree may be incorrect: evolutionary trees made using newer methods place eukaryotic core genes within the Archaea, supporting hypotheses in which an archaeon participated in eukaryotic origins by founding the host lineage for the mitochondrial endosymbiont. These results provide support for only two primary domains of life--Archaea and Bacteria--because eukaryotes arose through partnership between them.

  1. Anatomy of Mammalian Replication Domains

    PubMed Central

    Takebayashi, Shin-ichiro; Ogata, Masato; Okumura, Katsuzumi

    2017-01-01

    Genetic information is faithfully copied by DNA replication through many rounds of cell division. In mammals, DNA is replicated in Mb-sized chromosomal units called “replication domains.” While genome-wide maps in multiple cell types and disease states have uncovered both dynamic and static properties of replication domains, we are still in the process of understanding the mechanisms that give rise to these properties. A better understanding of the molecular basis of replication domain regulation will bring new insights into chromosome structure and function. PMID:28350365

  2. Protein domain connectivity and essentiality

    NASA Astrophysics Data System (ADS)

    da F. Costa, L.; Rodrigues, F. A.; Travieso, G.

    2006-10-01

    Protein-protein interactions can be properly modeled as scale-free complex networks, while the lethality of proteins has been correlated with the node degrees, therefore defining a lethality-centrality rule. In this work the authors revisit this relevant problem by focusing attention not on proteins as a whole, but on their functional domains, which are ultimately responsible for their binding potential. Four networks are considered: the original protein-protein interaction network, its randomized version, and two domain networks assuming different lethality hypotheses. By using formal statistical analysis, they show that the correlation between connectivity and essentiality is higher for domains than for proteins.

  3. Local host specialization, host-switching, and dispersal shape the regional distributions of avian haemosporidian parasites

    PubMed Central

    Ellis, Vincenzo A.; Collins, Michael D.; Medeiros, Matthew C. I.; Sari, Eloisa H. R.; Coffey, Elyse D.; Dickerson, Rebecca C.; Lugarini, Camile; Stratford, Jeffrey A.; Henry, Donata R.; Merrill, Loren; Matthews, Alix E.; Hanson, Alison A.; Roberts, Jackson R.; Joyce, Michael; Kunkel, Melanie R.; Ricklefs, Robert E.

    2015-01-01

    The drivers of regional parasite distributions are poorly understood, especially in comparison with those of free-living species. For vector-transmitted parasites, in particular, distributions might be influenced by host-switching and by parasite dispersal with primary hosts and vectors. We surveyed haemosporidian blood parasites (Plasmodium and Haemoproteus) of small land birds in eastern North America to characterize a regional parasite community. Distributions of parasite populations generally reflected distributions of their hosts across the region. However, when the interdependence between hosts and parasites was controlled statistically, local host assemblages were related to regional climatic gradients, but parasite assemblages were not. Moreover, because parasite assemblage similarity does not decrease with distance when controlling for host assemblages and climate, parasites evidently disperse readily within the distributions of their hosts. The degree of specialization on hosts varied in some parasite lineages over short periods and small geographic distances independently of the diversity of available hosts and potentially competing parasite lineages. Nonrandom spatial turnover was apparent in parasite lineages infecting one host species that was well-sampled within a single year across its range, plausibly reflecting localized adaptations of hosts and parasites. Overall, populations of avian hosts generally determine the geographic distributions of haemosporidian parasites. However, parasites are not dispersal-limited within their host distributions, and they may switch hosts readily. PMID:26305975

  4. Host-to-host variation of ecological interactions in polymicrobial infections

    PubMed Central

    Mukherjee, Sayak; Weimer, Kristin E.; Seok, Sang-Cheol; Ray, Will C.; Jayaprakash, C.; Vieland, Veronica J.; Swords, W. Edward

    2014-01-01

    Host-to-host variability with respect to interactions between microorganisms and multicellular hosts are commonly observed in infection and in homeostasis. However, the majority of mechanistic models used to analyze host-microorganism relationships, as well as most of the ecological theories proposed to explain coevolution of hosts and microbes, are based on averages across a host population. By assuming that observed variations are random and independent, these models overlook the role of differences between hosts. Here, we analyze mechanisms underlying host-to-host variations of bacterial infection kinetics, using the well characterized experimental infection model of polymicrobial otitis media (OM) in chinchillas, in combination with population dynamic models and a Maximum Entropy (MaxEnt) based inference scheme. We find that the nature of the interactions between bacterial species critically regulates host-to-host variations in these interactions. Surprisingly, seemingly unrelated phenomena, such as the efficiency of individual bacterial species in utilizing nutrients for growth, and the microbe-specific host immune response, can become interdependent in a host population. The latter finding suggests a potential mechanism that could lead to selection of specific strains of bacterial species during the coevolution of the host immune response and the bacterial species. PMID:25473880

  5. Local host specialization, host-switching, and dispersal shape the regional distributions of avian haemosporidian parasites.

    PubMed

    Ellis, Vincenzo A; Collins, Michael D; Medeiros, Matthew C I; Sari, Eloisa H R; Coffey, Elyse D; Dickerson, Rebecca C; Lugarini, Camile; Stratford, Jeffrey A; Henry, Donata R; Merrill, Loren; Matthews, Alix E; Hanson, Alison A; Roberts, Jackson R; Joyce, Michael; Kunkel, Melanie R; Ricklefs, Robert E

    2015-09-08

    The drivers of regional parasite distributions are poorly understood, especially in comparison with those of free-living species. For vector-transmitted parasites, in particular, distributions might be influenced by host-switching and by parasite dispersal with primary hosts and vectors. We surveyed haemosporidian blood parasites (Plasmodium and Haemoproteus) of small land birds in eastern North America to characterize a regional parasite community. Distributions of parasite populations generally reflected distributions of their hosts across the region. However, when the interdependence between hosts and parasites was controlled statistically, local host assemblages were related to regional climatic gradients, but parasite assemblages were not. Moreover, because parasite assemblage similarity does not decrease with distance when controlling for host assemblages and climate, parasites evidently disperse readily within the distributions of their hosts. The degree of specialization on hosts varied in some parasite lineages over short periods and small geographic distances independently of the diversity of available hosts and potentially competing parasite lineages. Nonrandom spatial turnover was apparent in parasite lineages infecting one host species that was well-sampled within a single year across its range, plausibly reflecting localized adaptations of hosts and parasites. Overall, populations of avian hosts generally determine the geographic distributions of haemosporidian parasites. However, parasites are not dispersal-limited within their host distributions, and they may switch hosts readily.

  6. Host-to-host variation of ecological interactions in polymicrobial infections

    NASA Astrophysics Data System (ADS)

    Mukherjee, Sayak; Weimer, Kristin E.; Seok, Sang-Cheol; Ray, Will C.; Jayaprakash, C.; Vieland, Veronica J.; Swords, W. Edward; Das, Jayajit

    2015-02-01

    Host-to-host variability with respect to interactions between microorganisms and multicellular hosts are commonly observed in infection and in homeostasis. However, the majority of mechanistic models used to analyze host-microorganism relationships, as well as most of the ecological theories proposed to explain coevolution of hosts and microbes, are based on averages across a host population. By assuming that observed variations are random and independent, these models overlook the role of differences between hosts. Here, we analyze mechanisms underlying host-to-host variations of bacterial infection kinetics, using the well characterized experimental infection model of polymicrobial otitis media (OM) in chinchillas, in combination with population dynamic models and a maximum entropy (MaxEnt) based inference scheme. We find that the nature of the interactions between bacterial species critically regulates host-to-host variations in these interactions. Surprisingly, seemingly unrelated phenomena, such as the efficiency of individual bacterial species in utilizing nutrients for growth, and the microbe-specific host immune response, can become interdependent in a host population. The latter finding suggests a potential mechanism that could lead to selection of specific strains of bacterial species during the coevolution of the host immune response and the bacterial species.

  7. Host cell invasion by medically important fungi.

    PubMed

    Sheppard, Donald C; Filler, Scott G

    2014-11-03

    To infect the host and cause disease, many medically important fungi invade normally nonphagocytic host cells, such as endothelial cells and epithelial cells. Host cell invasion is a two-step process consisting of adherence followed by invasion. There are two general mechanisms of host cell invasion, induced endocytosis and active penetration. Furthermore, fungi can traverse epithelial or endothelial cell barriers either by proteolytic degradation of intercellular tight junctions or via a Trojan horse mechanism in which they are transported by leukocytes. Although these mechanisms of host cell invasion have been best studied using Candida albicans and Cryptococcus neoformans, it is probable that other invasive fungi also use one or more of these mechanisms to invade host cells. Identification of these invasion mechanisms holds promise to facilitate the development of new approaches to inhibit fungal invasion and thereby prevent disease. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  8. Host shifts and evolutionary radiations of butterflies.

    PubMed

    Fordyce, James A

    2010-12-22

    Ehrlich and Raven proposed a model of coevolution where major host plant shifts of butterflies facilitate a burst of diversification driven by their arrival to a new adaptive zone. One prediction of this model is that reconstructions of historical diversification of butterflies should indicate an increase in diversification rate following major host shifts. Using reconstructed histories of 15 butterfly groups, I tested this prediction and found general agreement with Ehrlich and Raven's model. Butterfly lineages with an inferred major historical host shift showed evidence of diversification rate variation, with a significant acceleration following the host shift. Lineages without an inferred major host shift generally agreed with a constant-rate model of diversification. These results are consistent with the view that host plant associations have played a profound role in the evolutionary history of butterflies, and show that major shifts to chemically distinct plant groups leave a historical footprint that remains detectable today.

  9. Salmonella - at home in the host cell.

    PubMed

    Malik-Kale, Preeti; Jolly, Carrie E; Lathrop, Stephanie; Winfree, Seth; Luterbach, Courtney; Steele-Mortimer, Olivia

    2011-01-01

    The Gram-negative bacterium Salmonella enterica has developed an array of sophisticated tools to manipulate the host cell and establish an intracellular niche, for successful propagation as a facultative intracellular pathogen. While Salmonella exerts diverse effects on its host cell, only the cell biology of the classic "trigger"-mediated invasion process and the subsequent development of the Salmonella-containing vacuole have been investigated extensively. These processes are dependent on cohorts of effector proteins translocated into host cells by two type III secretion systems (T3SS), although T3SS-independent mechanisms of entry may be important for invasion of certain host cell types. Recent studies into the intracellular lifestyle of Salmonella have provided new insights into the mechanisms used by this pathogen to modulate its intracellular environment. Here we discuss current knowledge of Salmonella-host interactions including invasion and establishment of an intracellular niche within the host.

  10. Trypanosoma cruzi Infection and Host Lipid Metabolism

    PubMed Central

    Miao, Qianqian

    2014-01-01

    Trypanosoma cruzi is the causative agent of Chagas disease. Approximately 8 million people are thought to be affected worldwide. Several players in host lipid metabolism have been implicated in T. cruzi-host interactions in recent research, including macrophages, adipocytes, low density lipoprotein (LDL), low density lipoprotein receptor (LDLR), and high density lipoprotein (HDL). All of these factors are required to maintain host lipid homeostasis and are intricately connected via several metabolic pathways. We reviewed the interaction of T. cruzi with each of the relevant host components, in order to further understand the roles of host lipid metabolism in T. cruzi infection. This review sheds light on the potential impact of T. cruzi infection on the status of host lipid homeostasis. PMID:25276058

  11. Host-microbiota interactions: epigenomic regulation.

    PubMed

    Woo, Vivienne; Alenghat, Theresa

    2017-01-16

    The coevolution of mammalian hosts and their commensal microbiota has led to the development of complex symbiotic relationships between resident microbes and mammalian cells. Epigenomic modifications enable host cells to alter gene expression without modifying the genetic code, and therefore represent potent mechanisms by which mammalian cells can transcriptionally respond, transiently or stably, to environmental cues. Advances in genome-wide approaches are accelerating our appreciation of microbial influences on host physiology, and increasing evidence highlights that epigenomics represent a level of regulation by which the host integrates and responds to microbial signals. In particular, bacterial-derived short chain fatty acids have emerged as one clear link between how the microbiota intersects with host epigenomic pathways. Here we review recent findings describing crosstalk between the microbiota and epigenomic pathways in multiple mammalian cell populations. Further, we discuss interesting links that suggest that the scope of our understanding of epigenomic regulation in the host-microbiota relationship is still in its infancy.

  12. Hitchhiking on Host Chromatin: how Papillomaviruses Persist

    PubMed Central

    McBride, Alison A.; Sakakibara, Nozomi; Stepp, Wesley H.; Jang, Moon Kyoo

    2012-01-01

    Persistent viruses need mechanisms to protect their genomes from cellular defenses and to ensure that they are efficiently propagated to daughter host cells. One mechanism by which papillomaviruses achieve this is through the association of viral genomes with host chromatin, mediated by the viral E2 tethering protein. Association of viral DNA with regions of active host chromatin ensures that the virus remains transcriptionally active and is not relegated to repressed heterochromatin. In addition, viral genomes are tethered to specific regions of host mitotic chromosomes to efficiently partition their DNA to daughter cells. Vegetative viral DNA replication also initiates at specific regions of host chromatin, where the viral E1 and E2 proteins initiate a DNA damage response that recruits cellular DNA damage and repair proteins to viral replication foci for efficient viral DNA synthesis. Thus, these small viruses have capitalized on interactions with chromatin to efficiently target their genomes to beneficial regions of the host nucleus. PMID:22306660

  13. Host Cell Invasion by Medically Important Fungi

    PubMed Central

    Sheppard, Donald C.; Filler, Scott G.

    2015-01-01

    To infect the host and cause disease, many medically important fungi invade normally nonphagocytic host cells, such as endothelial cells and epithelial cells. Host cell invasion is a two-step process consisting of adherence followed by invasion. There are two general mechanisms of host cell invasion, induced endocytosis and active penetration. Furthermore, fungi can traverse epithelial or endothelial cell barriers either by proteolytic degradation of intercellular tight junctions or via a Trojan horse mechanism in which they are transported by leukocytes. Although these mechanisms of host cell invasion have been best studied using Candida albicans and Cryptococcus neoformans, it is probable that other invasive fungi also use one or more of these mechanisms to invade host cells. Identification of these invasion mechanisms holds promise to facilitate the development of new approaches to inhibit fungal invasion and thereby prevent disease. PMID:25367974

  14. The role of the polymer host on reversible photodegradation in Disperse Orange 11 dye

    NASA Astrophysics Data System (ADS)

    Hung, Sheng-Ting; Ramini, Shiva K.; Wyrick, David G.; Clays, Koen; Kuzyk, Mark G.

    2012-10-01

    The photodegradation and recovery process in anthraquinone chromophores have been characterized using am­ plified spontaneous emission (ASE) in several Anthraquinone derivatives doped in poly(methyl methacrylate) (PMMA). To understand the mechanisms of self healing in disperse orange 11 (DOll) doped in PMMA and the role of the host polymer, we investigated reversible photodegradation in DOll doped in copolymer composed of different percentages of methyl methacrylate (MMA) and Styrene. The results suggest that the host polymer is an important factor in determining the distribution of domain sizes of dye molecules.

  15. PHIDIAS: a pathogen-host interaction data integration and analysis system

    PubMed Central

    Xiang, Zuoshuang; Tian, Yuying; He, Yongqun

    2007-01-01

    The Pathogen-Host Interaction Data Integration and Analysis System (PHIDIAS) is a web-based database system that serves as a centralized source to search, compare, and analyze integrated genome sequences, conserved domains, and gene expression data related to pathogen-host interactions (PHIs) for pathogen species designated as high priority agents for public health and biological security. In addition, PHIDIAS allows submission, search and analysis of PHI genes and molecular networks curated from peer-reviewed literature. PHIDIAS is publicly available at . PMID:17663773

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

    PubMed Central

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

    2015-01-01

    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. PMID:26578811

  17. Domain Walls in Bent Nanowires

    NASA Astrophysics Data System (ADS)

    Lofink, F.; Philippi-Kobs, A.; Rahbar Azad, M. R.; Hankemeier, S.; Hoffmann, G.; Frömter, R.; Oepen, H. P.

    2017-08-01

    The influence of geometric parameters on the magnetic fine structure of domain walls in bent nanowires is investigated. The domain pattern in the soft-magnetic Co39Fe54Si7 alloy is studied via scanning electron microscopy with polarization analysis and modeled via micromagnetic simulations. It is demonstrated that the bending angle affects details of the microstructure as well as the preponderant domain-wall type. A phenomenological model is developed that provides the global energy minimum of individual types of domain walls as a function of the geometric parameters of the wire. The results can be directly transferred to permalloy wires, as permalloy and Co39Fe54Si7 alloy have a comparable magnetostatic exchange length.

  18. Structure of axionic domain walls

    NASA Astrophysics Data System (ADS)

    Huang, M. C.; Sikivie, P.

    1985-09-01

    The structure of axionic domain walls is investigated using the low-energy effective theory of axions and pions. We derive the spatial dependence of the phases of the Peccei-Quinn scalar field and the QCD quark-antiquark condensates inside an axionic domain wall. Thence an accurate estimate of the wall surface energy density is obtained. The equations of motion for axions, photons, leptons, and baryons in the neighborhood of axionic domain walls are written down and estimates are given for the wall reflection and transmission coefficients of these particles. Finally, we discuss the energy dissipation by axionic domain walls oscillating in the early universe due to the reflection of particles in the primordial soup.

  19. Affective Domain Measuring Scale (ADMS).

    ERIC Educational Resources Information Center

    Downs, Gary E.

    The development, validation, and reliability of the Affective Domain Measuring Scale are described. Values are presented with the techniques used in calculations. The scale is included with the scale value (the median or 50th percentile) for each item. (SA)

  20. Ferroelectric domain states of a tetragonal BiFeO3 thin film investigated by second harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Roh, Chang Jae; Hamh, Sun Young; Woo, Chang-Soo; Kim, Kwang-Eun; Yang, Chan-Ho; Lee, Jong Seok

    2017-05-01

    We investigate the ferroelectric state of a tetragonal BiFeO3 thin film grown on a LaAlO3 (001) substrate using an optical second harmonic generation (SHG) microscope. Whereas the ferroelectric state of this material hosts nanometer-sized domains which again form micrometer-sized domains of four different configurations, we could figure out the characteristic features of each domain from the SHG mapping with various sizes of the probe beam, i.e., from 0.7 to 3.9 μm in its diameter. In particular, we demonstrate that a single micrometer-sized domain contributes to the SHG as a coherent summation of the constituent nanometer-sized domains, and multi-micrometer-sized domains contribute to the SHG as an incoherent summation of each micro-domain.

  1. Coevolution of parasitic fungi and insect hosts.

    PubMed

    Joop, Gerrit; Vilcinskas, Andreas

    2016-08-01

    Parasitic fungi and their insect hosts provide an intriguing model system for dissecting the complex co-evolutionary processes, which result in Red Queen dynamics. To explore the genetic basis behind host-parasite coevolution we chose two parasitic fungi (Beauveria bassiana and Metarhizium anisopliae, representing the most important entomopathogenic fungi used in the biological control of pest or vector insects) and two established insect model hosts (the greater wax moth Galleria mellonella and the red flour beetle Tribolium castaneum) for which sequenced genomes or comprehensive transcriptomes are available. Focusing on these model organisms, we review the knowledge about the interactions between fungal molecules operating as virulence factors and insect host-derived defense molecules mediating antifungal immunity. Particularly the study of the intimate interactions between fungal proteinases and corresponding host-derived proteinase inhibitors elucidated novel coevolutionary mechanisms such as functional shifts or diversification of involved effector molecules. Complementarily, we compared the outcome of coevolution experiments using the parasitic fungus B. bassiana and two different insect hosts which were initially either susceptible (Galleria mellonella) or resistant (Tribolium castaneum). Taking a snapshot of host-parasite coevolution, we show that parasitic fungi can overcome host barriers such as external antimicrobial secretions just as hosts can build new barriers, both within a relatively short time of coevolution. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

  2. Host Galaxy Identification for Supernova Surveys

    SciTech Connect

    Gupta, Ravi R.; Kuhlmann, Steve; Kovacs, Eve; Spinka, Harold; Kessler, Richard; Goldstein, Daniel A.; Liotine, Camille; Pomian, Katarzyna; D’Andrea, Chris B.; Sullivan, Mark; Carretero, Jorge; Castander, Francisco J.; Nichol, Robert C.; Finley, David A.; Fischer, John A.; Foley, Ryan J.; Kim, Alex G.; Papadopoulos, Andreas; Sako, Masao; Scolnic, Daniel M.; Smith, Mathew; Tucker, Brad E.; Uddin, Syed; Wolf, Rachel C.; Yuan, Fang; Abbott, Tim M. C.; Abdalla, Filipe B.; Benoit-Lévy, Aurélien; Bertin, Emmanuel; Brooks, David; Rosell, Aurelio Carnero; Kind, Matias Carrasco; Cunha, Carlos E.; Costa, Luiz N. da; Desai, Shantanu; Doel, Peter; Eifler, Tim F.; Evrard, August E.; Flaugher, Brenna; Fosalba, Pablo; Gaztañaga, Enrique; Gruen, Daniel; Gruendl, Robert; James, David J.; Kuehn, Kyler; Kuropatkin, Nikolay; Maia, Marcio A. G.; Marshall, Jennifer L.; Miquel, Ramon; Plazas, Andrés A.; Romer, A. Kathy; Sánchez, Eusebio; Schubnell, Michael; Sevilla-Noarbe, Ignacio; Sobreira, Flávia; Suchyta, Eric; Swanson, Molly E. C.; Tarle, Gregory; Walker, Alistair R.; Wester, William

    2016-11-08

    Host galaxy identification is a crucial step for modern supernova (SN) surveys such as the Dark Energy Survey (DES) and the Large Synoptic Survey Telescope (LSST), which will discover SNe by the thousands. Spectroscopic resources are limited, so in the absence of real-time SN spectra these surveys must rely on host galaxy spectra to obtain accurate redshifts for the Hubble diagram and to improve photometric classification of SNe. In addition, SN luminosities are known to correlate with host-galaxy properties. Therefore, reliable identification of host galaxies is essential for cosmology and SN science. We simulate SN events and their locations within their host galaxies to develop and test methods for matching SNe to their hosts. We use both real and simulated galaxy catalog data from the Advanced Camera for Surveys General Catalog and MICECATv2.0, respectively. We also incorporate "hostless" SNe residing in undetected faint hosts into our analysis, with an assumed hostless rate of 5%. Our fully automated algorithm is run on catalog data and matches SNe to their hosts with 91% accuracy. We find that including a machine learning component, run after the initial matching algorithm, improves the accuracy (purity) of the matching to 97% with a 2% cost in efficiency (true positive rate). Although the exact results are dependent on the details of the survey and the galaxy catalogs used, the method of identifying host galaxies we outline here can be applied to any transient survey.

  3. Host galaxy identification for supernova surveys

    SciTech Connect

    Gupta, Ravi R.; Kuhlmann, Steve; Kovacs, Eve; Spinka, Harold; Kessler, Richard; Goldstein, Daniel A.; Liotine, Camille; Pomian, Katarzyna; D’Andrea, Chris B.; Sullivan, Mark; Carretero, Jorge; Castander, Francisco J.; Nichol, Robert C.; Finley, David A.; Fischer, John A.; Foley, Ryan J.; Kim, Alex G.; Papadopoulos, Andreas; Sako, Masao; Scolnic, Daniel M.; Smith, Mathew; Tucker, Brad E.; Uddin, Syed; Wolf, Rachel C.; Yuan, Fang; Abbott, Tim M. C.; Abdalla, Filipe B.; Benoit-Lévy, Aurélien; Bertin, Emmanuel; Brooks, David; Rosell, Aurelio Carnero; Kind, Matias Carrasco; Cunha, Carlos E.; Costa, Luiz N. da; Desai, Shantanu; Doel, Peter; Eifler, Tim F.; Evrard, August E.; Flaugher, Brenna; Fosalba, Pablo; Gaztañaga, Enrique; Gruen, Daniel; Gruendl, Robert; James, David J.; Kuehn, Kyler; Kuropatkin, Nikolay; Maia, Marcio A. G.; Marshall, Jennifer L.; Miquel, Ramon; Plazas, Andrés A.; Romer, A. Kathy; Sánchez, Eusebio; Schubnell, Michael; Sevilla-Noarbe, Ignacio; Sobreira, Flávia; Suchyta, Eric; Swanson, Molly E. C.; Tarle, Gregory; Walker, Alistair R.; Wester, William

    2016-11-10

    Host galaxy identification is a crucial step for modern supernova (SN) surveys such as the Dark Energy Survey and the Large Synoptic Survey Telescope, which will discover SNe by the thousands. Spectroscopic resources are limited, and so in the absence of real-time SN spectra these surveys must rely on host galaxy spectra to obtain accurate redshifts for the Hubble diagram and to improve photometric classification of SNe. In addition, SN luminosities are known to correlate with host-galaxy properties. Therefore, reliable identification of host galaxies is essential for cosmology and SN science. We simulate SN events and their locations within their host galaxies to develop and test methods for matching SNe to their hosts. We use both real and simulated galaxy catalog data from the Advanced Camera for Surveys General Catalog and MICECATv2.0, respectively. We also incorporate "hostless" SNe residing in undetected faint hosts into our analysis, with an assumed hostless rate of 5%. Our fully automated algorithm is run on catalog data and matches SNe to their hosts with 91% accuracy. Here, we find that including a machine learning component, run after the initial matching algorithm, improves the accuracy (purity) of the matching to 97% with a 2% cost in efficiency (true positive rate). Although the exact results are dependent on the details of the survey and the galaxy catalogs used, the method of identifying host galaxies we outline here can be applied to any transient survey.

  4. Host galaxy identification for supernova surveys

    DOE PAGES

    Gupta, Ravi R.; Kuhlmann, Steve; Kovacs, Eve; ...

    2016-11-10

    Host galaxy identification is a crucial step for modern supernova (SN) surveys such as the Dark Energy Survey and the Large Synoptic Survey Telescope, which will discover SNe by the thousands. Spectroscopic resources are limited, and so in the absence of real-time SN spectra these surveys must rely on host galaxy spectra to obtain accurate redshifts for the Hubble diagram and to improve photometric classification of SNe. In addition, SN luminosities are known to correlate with host-galaxy properties. Therefore, reliable identification of host galaxies is essential for cosmology and SN science. We simulate SN events and their locations within theirmore » host galaxies to develop and test methods for matching SNe to their hosts. We use both real and simulated galaxy catalog data from the Advanced Camera for Surveys General Catalog and MICECATv2.0, respectively. We also incorporate "hostless" SNe residing in undetected faint hosts into our analysis, with an assumed hostless rate of 5%. Our fully automated algorithm is run on catalog data and matches SNe to their hosts with 91% accuracy. Here, we find that including a machine learning component, run after the initial matching algorithm, improves the accuracy (purity) of the matching to 97% with a 2% cost in efficiency (true positive rate). Although the exact results are dependent on the details of the survey and the galaxy catalogs used, the method of identifying host galaxies we outline here can be applied to any transient survey.« less

  5. Host Plant Adaptation in Drosophila mettleri Populations

    PubMed Central

    Castrezana, Sergio; Bono, Jeremy M.

    2012-01-01

    The process of local adaptation creates diversity among allopatric populations, and may eventually lead to speciation. Plant-feeding insect populations that specialize on different host species provide an excellent opportunity to evaluate the causes of ecological specialization and the subsequent consequences for diversity. In this study, we used geographically separated Drosophila mettleri populations that specialize on different host cacti to examine oviposition preference for and larval performance on an array of natural and non-natural hosts (eight total). We found evidence of local adaptation in performance on saguaro cactus (Carnegiea gigantea) for populations that are typically associated with this host, and to chemically divergent prickly pear species (Opuntia spp.) in a genetically isolated population on Santa Catalina Island. Moreover, each population exhibited reduced performance on the alternative host. This finding is consistent with trade-offs associated with adaptation to these chemically divergent hosts, although we also discuss alternative explanations for this pattern. For oviposition preference, Santa Catalina Island flies were more likely to oviposit on some prickly pear species, but all populations readily laid eggs on saguaro. Experiments with non-natural hosts suggest that factors such as ecological opportunity may play a more important role than host plant chemistry in explaining the lack of natural associations with some hosts. PMID:22493678

  6. Host plant adaptation in Drosophila mettleri populations.

    PubMed

    Castrezana, Sergio; Bono, Jeremy M

    2012-01-01

    The process of local adaptation creates diversity among allopatric populations, and may eventually lead to speciation. Plant-feeding insect populations that specialize on different host species provide an excellent opportunity to evaluate the causes of ecological specialization and the subsequent consequences for diversity. In this study, we used geographically separated Drosophila mettleri populations that specialize on different host cacti to examine oviposition preference for and larval performance on an array of natural and non-natural hosts (eight total). We found evidence of local adaptation in performance on saguaro cactus (Carnegiea gigantea) for populations that are typically associated with this host, and to chemically divergent prickly pear species (Opuntia spp.) in a genetically isolated population on Santa Catalina Island. Moreover, each population exhibited reduced performance on the alternative host. This finding is consistent with trade-offs associated with adaptation to these chemically divergent hosts, although we also discuss alternative explanations for this pattern. For oviposition preference, Santa Catalina Island flies were more likely to oviposit on some prickly pear species, but all populations readily laid eggs on saguaro. Experiments with non-natural hosts suggest that factors such as ecological opportunity may play a more important role than host plant chemistry in explaining the lack of natural associations with some hosts.

  7. Host Galaxy Identification for Supernova Surveys

    NASA Astrophysics Data System (ADS)

    Gupta, Ravi R.; Kuhlmann, Steve; Kovacs, Eve; Spinka, Harold; Kessler, Richard; Goldstein, Daniel A.; Liotine, Camille; Pomian, Katarzyna; D'Andrea, Chris B.; Sullivan, Mark; Carretero, Jorge; Castander, Francisco J.; Nichol, Robert C.; Finley, David A.; Fischer, John A.; Foley, Ryan J.; Kim, Alex G.; Papadopoulos, Andreas; Sako, Masao; Scolnic, Daniel M.; Smith, Mathew; Tucker, Brad E.; Uddin, Syed; Wolf, Rachel C.; Yuan, Fang; Abbott, Tim M. C.; Abdalla, Filipe B.; Benoit-Lévy, Aurélien; Bertin, Emmanuel; Brooks, David; Carnero Rosell, Aurelio; Carrasco Kind, Matias; Cunha, Carlos E.; da Costa, Luiz N.; Desai, Shantanu; Doel, Peter; Eifler, Tim F.; Evrard, August E.; Flaugher, Brenna; Fosalba, Pablo; Gaztañaga, Enrique; Gruen, Daniel; Gruendl, Robert; James, David J.; Kuehn, Kyler; Kuropatkin, Nikolay; Maia, Marcio A. G.; Marshall, Jennifer L.; Miquel, Ramon; Plazas, Andrés A.; Romer, A. Kathy; Sánchez, Eusebio; Schubnell, Michael; Sevilla-Noarbe, Ignacio; Sobreira, Flávia; Suchyta, Eric; Swanson, Molly E. C.; Tarle, Gregory; Walker, Alistair R.; Wester, William

    2016-12-01

    Host galaxy identification is a crucial step for modern supernova (SN) surveys such as the Dark Energy Survey and the Large Synoptic Survey Telescope, which will discover SNe by the thousands. Spectroscopic resources are limited, and so in the absence of real-time SN spectra these surveys must rely on host galaxy spectra to obtain accurate redshifts for the Hubble diagram and to improve photometric classification of SNe. In addition, SN luminosities are known to correlate with host-galaxy properties. Therefore, reliable identification of host galaxies is essential for cosmology and SN science. We simulate SN events and their locations within their host galaxies to develop and test methods for matching SNe to their hosts. We use both real and simulated galaxy catalog data from the Advanced Camera for Surveys General Catalog and MICECATv2.0, respectively. We also incorporate “hostless” SNe residing in undetected faint hosts into our analysis, with an assumed hostless rate of 5%. Our fully automated algorithm is run on catalog data and matches SNe to their hosts with 91% accuracy. We find that including a machine learning component, run after the initial matching algorithm, improves the accuracy (purity) of the matching to 97% with a 2% cost in efficiency (true positive rate). Although the exact results are dependent on the details of the survey and the galaxy catalogs used, the method of identifying host galaxies we outline here can be applied to any transient survey.

  8. Host-gut microbiota metabolic interactions.

    PubMed

    Nicholson, Jeremy K; Holmes, Elaine; Kinross, James; Burcelin, Remy; Gibson, Glenn; Jia, Wei; Pettersson, Sven

    2012-06-08

    The composition and activity of the gut microbiota codevelop with the host from birth and is subject to a complex interplay that depends on the host genome, nutrition, and life-style. The gut microbiota is involved in the regulation of multiple host metabolic pathways, giving rise to interactive host-microbiota metabolic, signaling, and immune-inflammatory axes that physiologically connect the gut, liver, muscle, and brain. A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health.

  9. Adenovirus Early Proteins and Host Sumoylation

    PubMed Central

    Sohn, Sook-Young

    2016-01-01

    ABSTRACT The human adenovirus genome is transported into the nucleus, where viral gene transcription, viral DNA replication, and virion assembly take place. Posttranslational modifications by small ubiquitin-like modifiers (SUMOs) are implicated in the regulation of diverse cellular processes, particularly nuclear events. It is not surprising, therefore, that adenovirus modulates and utilizes the host sumoylation system. Adenovirus early proteins play an important role in establishing optimal host environments for virus replication within infected cells by stimulating the cell cycle and counteracting host antiviral defenses. Here, we review findings on the mechanisms and functional consequences of the interplay between human adenovirus early proteins and the host sumoylation system. PMID:27651358

  10. Engineered autonomous human variable domains

    PubMed Central

    Nilvebrant, Johan; Tessier, Peter M.; Sidhu, Sachdev S.

    2017-01-01

    The complex multi-chain architecture of antibodies has spurred interest in smaller derivatives that retain specificity but can be more easily produced in bacteria. Domain antibodies consisting of single variable domains are the smallest antibody fragments and have been shown to possess enhanced ability to target epitopes that are difficult to access using multidomain antibodies. However, in contrast to natural camelid antibody domains, human variable domains typically suffer from low stability and high propensity to aggregate. This review summarizes strategies to improve the biophysical properties of heavy chain variable domains from human antibodies with an emphasis on aggregation resistance. Several protein engineering approaches have targeted antibody frameworks and complementarity determining regions to stabilize the native state and prevent aggregation of the denatured state. Recent findings enable the construction of highly diverse libraries enriched in aggregation-resistant variants that are expected to provide binders to diverse antigens. Engineered domain antibodies possess unique advantages in expression, epitope preference and flexibility of formatting over conventional immunoreagents and are a promising class of antibody fragments for biomedical development. PMID:27655414

  11. Unexpected hosts: imaging parasitic diseases.

    PubMed

    Rodríguez Carnero, Pablo; Hernández Mateo, Paula; Martín-Garre, Susana; García Pérez, Ángela; Del Campo, Lourdes

    2017-02-01

    Radiologists seldom encounter parasitic diseases in their daily practice in most of Europe, although the incidence of these diseases is increasing due to migration and tourism from/to endemic areas. Moreover, some parasitic diseases are still endemic in certain European regions, and immunocompromised individuals also pose a higher risk of developing these conditions. This article reviews and summarises the imaging findings of some of the most important and frequent human parasitic diseases, including information about the parasite's life cycle, pathophysiology, clinical findings, diagnosis, and treatment. We include malaria, amoebiasis, toxoplasmosis, trypanosomiasis, leishmaniasis, echinococcosis, cysticercosis, clonorchiasis, schistosomiasis, fascioliasis, ascariasis, anisakiasis, dracunculiasis, and strongyloidiasis. The aim of this review is to help radiologists when dealing with these diseases or in cases where they are suspected. Teaching Points • Incidence of parasitic diseases is increasing due to migratory movements and travelling. • Some parasitic diseases are still endemic in certain regions in Europe. • Parasitic diseases can have complex life cycles often involving different hosts. • Prompt diagnosis and treatment is essential for patient management in parasitic diseases. • Radiologists should be able to recognise and suspect the most relevant parasitic diseases.

  12. Noncentrosymmetric Magnets Hosting Magnetic Skyrmions.

    PubMed

    Kanazawa, Naoya; Seki, Shinichiro; Tokura, Yoshinori

    2017-03-17

    The concept of a skyrmion, which was first introduced by Tony Skyrme in the field of particle physics, has become widespread in condensed matter physics to describe various topological orders. Skyrmions in magnetic materials have recently received particular attention; they represent vortex-like spin structures with the character of nanometric particles and produce fascinating physical properties rooted in their topological nature. Here, a series of noncentrosymmetric ferromagnets hosting skyrmions is reviewed: B20 metals, Cu2 OSeO3 , Co-Zn-Mn alloys, and GaV4 S8 , where Dzyaloshinskii-Moriya interaction plays a key role in the stabilization of skyrmion spin texture. Their topological spin arrangements and consequent emergent electromagnetic fields give rise to striking features in transport and magnetoelectric properties in metals and insulators, such as the topological Hall effect, efficient electric-drive of skyrmions, and multiferroic behavior. Such electric controllability and nanometric particle natures highlight magnetic skyrmions as a potential information carrier for high-density magnetic storage devices with excellent energy efficiency.

  13. Quality of life of residents living in a city hosting mega-sport events: a longitudinal study.

    PubMed

    Pfitzner, Rebecca; Koenigstorfer, Joerg

    2016-10-21

    It remains unknown whether and when the hosting of mega-sport events increases quality of life of host city residents. The aim of this study is to assess the changes in quality of life of host city residents over the course of hosting a mega-sport event until three months after the event, depending on residents' perception of the atmosphere during the event. The study was conducted in Rio de Janeiro, one of the host cities of the 2014 FIFA World Cup in soccer. Participants were recruited from a Brazilian market research agency's panel and surveyed online. The WHOQOL-BREF was used to measure quality of life of residents of Rio de Janeiro (n = 281) in three waves in the context of the 2014 FIFA World Cup. Perceived atmosphere at the event was measured via an established scale. Piecewise latent growth models were used to analyze individual changes in the four domains of quality of life per se and depending on perceived atmosphere. There was no change in quality of life with respect to physical, social, psychological, and environmental health for all participants during the course of the event. However, residents who perceived a positive atmosphere rated the social and environmental domains of quality of life more positively right after the end (vs. at the beginning) of the World Cup. This increase sustained until three months after the event. Physical health (particularly at high levels of perceived atmosphere) and psychological health decreased from right after the event until three months after. There was no positive effect of the hosting of the mega-sport event on the four quality of life domains of the panel members (who were residents of a city hosting a mega-sport event) per se. The individual changes in quality of life vary by perception of atmosphere and by domain of quality of life.

  14. Male hosts drive infracommunity structure of ectoparasites.

    PubMed

    Krasnov, Boris R; Stanko, Michal; Matthee, Sonja; Laudisoit, Anne; Leirs, Herwig; Khokhlova, Irina S; Korallo-Vinarskaya, Natalia P; Vinarski, Maxim V; Morand, Serge

    2011-08-01

    We studied the co-occurrence of flea species in infracommunities of 16 rodents from four regions (South Africa, Tanzania, central Europe and western Siberia) using null models, and predicted that flea co-occurrences will be expressed more strongly in male than in female hosts. We examined patterns of co-occurrence (measured as the C score) in infracommunities of fleas that are parasitic on male and female hosts by comparing co-occurrence frequencies with those expected by chance. When a significant degree of nonrandomness in flea co-occurrences was detected, it indicated aggregative infracommunity structure. In Tanzanian rodents, no significant flea co-occurrences were detected in either male or female hosts. In a South African rodent, significant flea co-occurrences were not detected in males, but were found in females in some localities. In Palaearctic rodents, significant nonrandomness was detected either equally for males and females or more frequently in males than in females. Meta-analyses demonstrated that the frequency of the detection of nonrandomness in flea co-occurrences was significantly higher in male than in female hosts. The values of the standardized effect size (SES) for the C score differed significantly among host species, but not between host genders. When the Palaearctic hosts were analyzed separately, the effects of both host gender and species appeared to be significant, with the SES values for the C score in males being smaller than those in females. The strength of the gender difference in the manifestation of flea community structure increased with increasing gender difference in flea species richness, and with decreasing gender difference in flea prevalence for the Palaearctic hosts. We conclude that male hosts are the main drivers of flea infracommunity structure. However, the manifestation of gender bias in flea community structure varies among host species, and is likely determined by the pattern of species-specific spatial behavior.

  15. In Vivo Crystallization of Three-Domain Cry Toxins

    PubMed Central

    Adalat, Rooma; Saleem, Faiza; Crickmore, Neil; Naz, Shagufta; Shakoori, Abdul Rauf

    2017-01-01

    Bacillus thuringiensis (Bt) is the most successful, environmentally-friendly, and intensively studied microbial insecticide. The major characteristic of Bt is the production of proteinaceous crystals containing toxins with specific activity against many pests including dipteran, lepidopteran, and coleopteran insects, as well as nematodes, protozoa, flukes, and mites. These crystals allow large quantities of the protein toxins to remain stable in the environment until ingested by a susceptible host. It has been previously established that 135 kDa Cry proteins have a crystallization domain at their C-terminal end. In the absence of this domain, Cry proteins often need helper proteins or other factors for crystallization. In this review, we classify the Cry proteins based on their requirements for crystallization. PMID:28282927

  16. Origin and structure of polar domains in doped molecular crystals

    PubMed Central

    Meirzadeh, E.; Azuri, I.; Qi, Y.; Ehre, D.; Rappe, A. M.; Lahav, M.; Kronik, L.; Lubomirsky, I.

    2016-01-01

    Doping is a primary tool for the modification of the properties of materials. Occlusion of guest molecules in crystals generally reduces their symmetry by the creation of polar domains, which engender polarization and pyroelectricity in the doped crystals. Here we describe a molecular-level determination of the structure of such polar domains, as created by low dopant concentrations (<0.5%). The approach comprises crystal engineering and pyroelectric measurements, together with dispersion-corrected density functional theory and classical molecular dynamics calculations of the doped crystals, using neutron diffraction data of the host at different temperatures. This approach is illustrated using centrosymmetric α-glycine crystals doped with minute amounts of different L-amino acids. The experimentally determined pyroelectric coefficients are explained by the structure and polarization calculations, thus providing strong support for the local and global understanding of how different dopants influence the properties of molecular crystals. PMID:27824050

  17. In Vivo Crystallization of Three-Domain Cry Toxins.

    PubMed

    Adalat, Rooma; Saleem, Faiza; Crickmore, Neil; Naz, Shagufta; Shakoori, Abdul Rauf

    2017-03-09

    Bacillus thuringiensis (Bt) is the most successful, environmentally-friendly, and intensively studied microbial insecticide. The major characteristic of Bt is the production of proteinaceous crystals containing toxins with specific activity against many pests including dipteran, lepidopteran, and coleopteran insects, as well as nematodes, protozoa, flukes, and mites. These crystals allow large quantities of the protein toxins to remain stable in the environment until ingested by a susceptible host. It has been previously established that 135 kDa Cry proteins have a crystallization domain at their C-terminal end. In the absence of this domain, Cry proteins often need helper proteins or other factors for crystallization. In this review, we classify the Cry proteins based on their requirements for crystallization.

  18. Induction of promyelocytic leukemia (PML) oncogenic domains (PODs) by papillomavirus

    SciTech Connect

    Nakahara, Tomomi; Lambert, Paul F.

    2007-09-30

    Promyelocytic leukemia oncogenic domains (PODs), also called nuclear domain 10 (ND10), are subnuclear structures that have been implicated in a variety of cellular processes as well as the life cycle of DNA viruses including papillomaviruses. In order to investigate the interplay between papillomaviruses and PODs, we analyzed the status of PODs in organotypic raft cultures of human keratinocytes harboring HPV genome that support the differentiation-dependent HPV life cycle. The number of PODs per nucleus was increased in the presence of HPV genomes selectively within the poorly differentiated layers but was absent in the terminally differentiated layers of the stratified epithelium. This increase in PODs was correlated with an increase in abundance of post-translationally modified PML protein. Neither the E2-dependent transcription nor viral DNA replication was reliant upon the presence of PML. Implications of these findings in terms of HPV's interaction with its host are discussed.

  19. Domain-to-domain coupling in voltage-sensing phosphatase

    PubMed Central

    Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi

    2017-01-01

    Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain. PMID:28744425

  20. Chloroplast targeting factor AKR2 evolved from an ankyrin repeat domain coincidentally binds two chloroplast lipids

    PubMed Central

    Kim, Dae Heon; Park, Mi-Jeong; Gwon, Gwang Hyeon; Silkov, Antonina; Xu, Zheng-Yi; Yang, Eun Chan; Song, Seohyeon; Song, Kyungyoung; Kim, Younghyun; Yoon, Hwan Su; Honig, Barry; Cho, Wonhwa; Cho, Yunje; Hwang, Inhwan

    2014-01-01

    SUMMARY In organellogenesis of the chloroplast from endosymbiotic cyanobacterium, the establishment of protein targeting mechanisms to the chloroplast should have been pivotal. However, it is still mysterious how these mechanisms were established and how they work in plant cells. Here, we show that AKR2A, the cytosolic targeting factor for chloroplast outer membrane (COM) proteins, evolved from the ankyrin repeat domain (ARD) of the host cell by stepwise extensions of its N-terminal domain, and two lipids monogalactosyldiacylglycerol (MGDG) and phosphatidylglycerol (PG) of the endosymbiont were selected to function as the AKR2A receptor. Structural analysis, molecular modeling and mutational analysis of the ARD identified two adjacent sites for coincidental and synergistic binding of MGDG and PG. Based on these findings, we propose that the targeting mechanism of COM proteins was established using components from both the endosymbiont and host cell through a modification of the protein-protein interacting ARD into a lipid binding domain. PMID:25203210

  1. The VSG C-terminal domain is inaccessible to antibodies on live trypanosomes.

    PubMed

    Schwede, Angela; Jones, Nicola; Engstler, Markus; Carrington, Mark

    2011-02-01

    In the mammalian host, the Trypanosoma brucei cell surface is covered with a densely packed protein coat of a single protein, the variant surface glycoprotein (VSG). The VSG is believed to shield invariant surface proteins from host antibodies but there is limited information on how far antibodies can penetrate into the VSG monolayer. Here, the VSG surface coat was probed to determine whether it acts as a barrier to binding of antibodies to the membrane proximal VSG C-terminal domain. The binding of C-terminal domain antibodies to VSG221 or VSG118 was compared with antibodies recognising the cognate whole VSGs. The C-terminal VSG domain was inaccessible to antibodies on live cells but not on fixed cells. This provides further evidence that the VSG coat acts as a barrier and protects the cell from antibodies that would otherwise bind to some of the other externally disposed proteins.

  2. Functional characterization of Ebola virus L-domains using VSV recombinants

    PubMed Central

    Irie, Takashi; Licata, Jillian M.; Harty, Ronald N.

    2010-01-01

    VSV recombinants containing the overlapping L-domain sequences from Ebola virus VP40 (PTAPPEY) were recovered by reverse-genetics. Replication kinetics of M40-WT, M40-P24L, and M40-Y30A were indistinguishable from VSV-WT in BHK-21 cells, whereas the double mutant (M40-P2728A) was defective in budding. Insertion of the Ebola L-domain region into VSV M protein was sufficient to alter the dependence on host proteins for efficient budding. Indeed, M40 recombinants containing a functional PTAP motif specifically incorporated endogenous tsg101 into budding virions and were dependent on tsg101 expression for efficient budding. Thus, VSV represents an excellent negative-sense RNA virus model for elucidating the functional aspects and diverse host interactions associated with the L-domains of Ebola virus. PMID:15892969

  3. Predictability of helminth parasite host range using information on geography, host traits and parasite community structure.

    PubMed

    Dallas, Tad; Park, Andrew W; Drake, John M

    2017-02-01

    Host-parasite associations are complex interactions dependent on aspects of hosts (e.g. traits, phylogeny or coevolutionary history), parasites (e.g. traits and parasite interactions) and geography (e.g. latitude). Predicting the permissive host set or the subset of the host community that a parasite can infect is a central goal of parasite ecology. Here we develop models that accurately predict the permissive host set of 562 helminth parasites in five different parasite taxonomic groups. We developed predictive models using host traits, host taxonomy, geographic covariates, and parasite community composition, finding that models trained on parasite community variables were more accurate than any other covariate group, even though parasite community covariates only captured a quarter of the variance in parasite community composition. This suggests that it is possible to predict the permissive host set for a given parasite, and that parasite community structure is an important predictor, potentially because parasite communities are interacting non-random assemblages.

  4. Domain and Specification Models for Software Engineering

    NASA Technical Reports Server (NTRS)

    Iscoe, Neil; Liu, Zheng-Yang; Feng, Guohui

    1992-01-01

    This paper discusses our approach to representing application domain knowledge for specific software engineering tasks. Application domain knowledge is embodied in a domain model. Domain models are used to assist in the creation of specification models. Although many different specification models can be created from any particular domain model, each specification model is consistent and correct with respect to the domain model. One aspect of the system-hierarchical organization is described in detail.

  5. The Crystal Structures of EAP Domains from Staphylococcus aureus Reveal an Unexpected Homology to Bacterial Superantigens

    SciTech Connect

    Geisbrecht, B V; Hamaoka, B Y; Perman, B; Zemla, A; Leahy, D J

    2005-10-14

    The Eap (extracellular adherence protein) of Staphylococcus aureus functions as a secreted virulence factor by mediating interactions between the bacterial cell surface and several extracellular host proteins. Eap proteins from different Staphylococcal strains consist of four to six tandem repeats of a structurally uncharacterized domain (EAP domain). We have determined the three-dimensional structures of three different EAP domains to 1.8, 2.2, and 1.35 {angstrom} resolution, respectively. These structures reveal a core fold that is comprised of an {alpha}-helix lying diagonally across a five-stranded, mixed {beta}-sheet. Comparison of EAP domains with known structures reveals an unexpected homology with the C-terminal domain of bacterial superantigens. Examination of the structure of the superantigen SEC2 bound to the {beta}-chain of a T-cell receptor suggests a possible ligand-binding site within the EAP domain (Fields, B. A., Malchiodi, E. L., Li, H., Ysern, X., Stauffacher, C. V., Schlievert, P. M., Karjalainen, K., and Mariuzza, R. (1996) Nature 384, 188-192). These results provide the first structural characterization of EAP domains, relate EAP domains to a large class of bacterial toxins, and will guide the design of future experiments to analyze EAP domain structure/function relationships.

  6. Host-Nation Operations: Soldier Training on Governance (HOST-G) Training Support Package

    DTIC Science & Technology

    2011-07-01

    The Brookings Institution. In addition, the team searched academic journals using EBSCO Host and incorporated a search of military journals such...Research Product 2011-05 Host -Nation Operations: Soldier Training on Governance ( HOST -G) Training Support Package...DATE (dd-mm-yy) July 2011 2. REPORT TYPE Final 3. DATES COVERED (from. . . to) August 2009 – August 2010 4. TITLE AND SUBTITLE Host

  7. Nestedness of Ectoparasite-Vertebrate Host Networks

    PubMed Central

    Graham, Sean P.; Hassan, Hassan K.; Burkett-Cadena, Nathan D.; Guyer, Craig; Unnasch, Thomas R.

    2009-01-01

    Determining the structure of ectoparasite-host networks will enable disease ecologists to better understand and predict the spread of vector-borne diseases. If these networks have consistent properties, then studying the structure of well-understood networks could lead to extrapolation of these properties to others, including those that support emerging pathogens. Borrowing a quantitative measure of network structure from studies of mutualistic relationships between plants and their pollinators, we analyzed 29 ectoparasite-vertebrate host networks—including three derived from molecular bloodmeal analysis of mosquito feeding patterns—using measures of nestedness to identify non-random interactions among species. We found significant nestedness in ectoparasite-vertebrate host lists for habitats ranging from tropical rainforests to polar environments. These networks showed non-random patterns of nesting, and did not differ significantly from published estimates of nestedness from mutualistic networks. Mutualistic and antagonistic networks appear to be organized similarly, with generalized ectoparasites interacting with hosts that attract many ectoparasites and more specialized ectoparasites usually interacting with these same “generalized” hosts. This finding has implications for understanding the network dynamics of vector-born pathogens. We suggest that nestedness (rather than random ectoparasite-host associations) can allow rapid transfer of pathogens throughout a network, and expand upon such concepts as the dilution effect, bridge vectors, and host switching in the context of nested ectoparasite-vertebrate host networks. PMID:19924299

  8. Endosymbiont Tolerance and Control within Insect Hosts

    PubMed Central

    Ratzka, Carolin; Gross, Roy; Feldhaar, Heike

    2012-01-01

    Bacterial endosymbioses are very common in insects and can range from obligate to facultative as well as from mutualistic to pathogenic associations. Several recent studies provide new insight into how endosymbionts manage to establish chronic infections of their hosts without being eliminated by the host immune system. Endosymbiont tolerance may be achieved either by specific bacterial adaptations or by host measurements shielding bacteria from innate defense mechanisms. Nevertheless, insect hosts also need to sustain control mechanisms to prevent endosymbionts from unregulated proliferation. Emerging evidence indicates that in some cases the mutual adaptations of the two organisms may have led to the integration of the endosymbionts as a part of the host immune system. In fact, endosymbionts may provide protective traits against pathogens and predators and may even be required for the proper development of the host immune system during host ontogeny. This review gives an overview of current knowledge of molecular mechanisms ensuring maintenance of chronic infections with mutualistic endosymbionts and the impact of endosymbionts on host immune competence. PMID:26466544

  9. Mycobacterium tuberculosis and the host response

    PubMed Central

    Kaufmann, Stefan H.E.; Cole, Stewart T.; Mizrahi, Valerie; Rubin, Eric; Nathan, Carl

    2005-01-01

    Mycobacterium tuberculosis remains a leading cause of morbidity and mortality worldwide. Advances reported at a recent international meeting highlight insights and controversies in the genetics of M. tuberculosis and the infected host, the nature of protective immune responses, adaptation of the bacillus to host-imposed stresses, animal models, and new techniques. PMID:15939785

  10. Children and Host-Selling Television Commercials.

    ERIC Educational Resources Information Center

    Kunkel, Dale

    This study explores children's understanding of television commercials that feature the same primary characters as those in the adjacent program content, a commercial technique known as "host-selling." Responses of children 4 to 5 and 7 to 8 years of age to identical commercials presented in both a host-selling and normal viewing…

  11. Host tree resistance against the polyphagous

    Treesearch

    W. D. Morewood; K. Hoover; P. R. Neiner; J.R. McNeil; J. C. Sellmer

    2004-01-01

    Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae: Lamiini) is an invasive wood-boring beetle with an unusually broad host range and a proven ability to increase its host range as it colonizes new areas and encounters new tree species. The beetle is native to eastern Asia and has become an invasive pest in North America and Europe,...

  12. Warfare between Host Immunity and Bacterial Weapons.

    PubMed

    Yu, Manda; Lai, Erh-Min

    2017-01-11

    Bacterial pathogens deploy protein secretion systems to facilitate infection and colonization of their hosts. In this issue of Cell Host & Microbe, Chen et al. (2017) report a new role for a type VI secretion effector in promoting bacterial colonization by preventing inflammasome activation induced by a type III secretion system. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Social Host Ordinances and Policies. Prevention Update

    ERIC Educational Resources Information Center

    Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2011

    2011-01-01

    Social host liability laws (also known as teen party ordinances, loud or unruly gathering ordinances, or response costs ordinances) target the location in which underage drinking takes place. Social host liability laws hold noncommercial individuals responsible for underage drinking events on property they own, lease, or otherwise control. They…

  14. Host selection by the shiny cowbird

    USGS Publications Warehouse

    Wiley, J.W.

    1988-01-01

    Factors important in Shiny Cowbird (Molothrus bonariensis) host selection were examined within the mangrove community in Puerto Rico. Cowbirds did not parasitize birds in proportion to their abundance. The cowbird breeding season coincided with those of its major hosts, which were 'high-quality' foster species (i.e., species that fledge .gtoreq. 55% of cowbirds hatched: Yellow Warbler, Dendroica petechia; Yellow-shouldered Blackbird, Agelaius xanthomus; Black-whiskered Vireo, Vireo altiloquus; Black-cowled Oriole, Icterus dominicensis; Peurto Rican Flycatcher, Myiarchus antillarum; Troupial, Icterus icterus), and did not extend into other periods even though nests of 'low-quality: species (i.e., species that fledge < 55% of cowbird chicks that hatched: Bronze Mannikin, Lonchura cucullata; Greater Antillean Grackle, Quiscalus niger; Gray Kingbird, Tyrannus dominicensis; Northern Mockingbird, Mimus polyglottos; Red-legged Thrush, Turdus plumbeus) were available. Shiny Cowbird food habits and egg size were similar to those of their hosts, suggesting that cowbirds choose hosts partly on the basis of this combination. Cowbirds located host nests primarily by cryptically watching activities of birds in likely habitats. Other nest locating strategies were active searching of suitable habitat and 'flushing' of hosts by the cowbird's noisy approach. Cowbirds closely monitored nest status with frequent visits that peaked on the host's first day of egg laying. Hosts using covered nests (e.g., cavities, domed nests) were as vulnerable to cowbird parasitism as those building open nests.

  15. Seasonal and spatial heterogeneities in host and vector abundances impact the spatiotemporal spread of bluetongue.

    PubMed

    Charron, Maud V P; Kluiters, Georgette; Langlais, Michel; Seegers, Henri; Baylis, Matthew; Ezanno, Pauline

    2013-06-19

    Bluetongue (BT) can cause severe livestock losses and large direct and indirect costs for farmers. To propose targeted control strategies as alternative to massive vaccination, there is a need to better understand how BT virus spread in space and time according to local characteristics of host and vector populations. Our objective was to assess, using a modelling approach, how spatiotemporal heterogeneities in abundance and distribution of hosts and vectors impact the occurrence and amplitude of local and regional BT epidemics. We built a reaction-diffusion model accounting for the seasonality in vector abundance and the active dispersal of vectors. Because of the scale chosen, and movement restrictions imposed during epidemics, host movements and wind-induced passive vector movements were neglected. Four levels of complexity were addressed using a theoretical approach, from a homogeneous to a heterogeneous environment in abundance and distribution of hosts and vectors. These scenarios were illustrated using data on abundance and distribution of hosts and vectors in a real geographical area. We have shown that local epidemics can occur earlier and be larger in scale far from the primary case rather than close to it. Moreover, spatial heterogeneities in hosts and vectors delay the epidemic peak and decrease the infection prevalence. The results obtained on a real area confirmed those obtained on a theoretical domain. Although developed to represent BTV spatiotemporal spread, our model can be used to study other vector-borne diseases of animals with a local to regional spread by vector diffusion.

  16. Supramolecular effects and molecular discrimination by macrocyclic hosts embedded in synthetic bilayer membranes.

    PubMed Central

    Murakami, Y; Hayashida, O

    1993-01-01

    Hybrid assemblies were prepared in combinations of a synthetic lipid, involving an L-alanine residue interposed between an anionic head group and a hydrophobic double-chain segment, with cage-type cyclophanes having a three-dimensionally extended hydrophobic cavity. Incorporation behavior of the cage-type hosts into the multi- and single-walled vesicules was characterized by highly sensitive differential scanning calorimetry and dynamic light-scattering measurements as well as by gel-filtration chromatography and electronic absorption spectroscopy. Both hosts were found to be completely incorporated into a relatively polar domain close to the vesicular surface. Anionic guest molecules, such as naphthol yellow S, dimethylsulfonazo III, bromopyrogallol red, and orange G, were effectively incorporated into the hydrophobic cavities provided by the cage-type cyclophanes embedded in the single-walled bilayer membrane, as confirmed by circular dichroism spectroscopy; the formation constants for 1:1 host-guest complexes were in the order of 10(4)-10(5) mol.dm-3. This means that the binding affinities of the cage-type hosts are largely retained even when the hosts are incorporated into the vesicle. Moreover, the pyridinium moieties bound to the chiral L-valine residues in the bridging components of the hosts underwent conformational changes upon inclusion of the guest, as confirmed by circular dichroism spectroscopy and molecular mechanics and dynamics calculations. Images PMID:8433975

  17. Complex oxide ferroelectrics: Electrostatic doping by domain walls

    DOE PAGES

    Maksymovych, Petro

    2015-06-19

    Electrically conducting interfaces can form, rather unexpectedly, by breaking the translational symmetry of electrically insulating complex oxides. For example, a nanometre-thick heteroepitaxial interface between electronically insulating LaAlO3 and SrTiO3 supports a 2D electron gas1 with high mobility of >1,000 cm2 V-1 s-1 (ref. 2). Such interfaces can exhibit magnetism, superconductivity and phase transitions that may form the functional basis of future electronic devices2. A peculiar conducting interface can be created within a polar ferroelectric oxide by breaking the translational symmetry of the ferroelectric order parameter and creating a so-called ferroelectric domain wall (Fig. 1a,b). If the direction of atomic displacementsmore » changes at the wall in such a way as to create a discontinuity in the polarization component normal to the wall (Fig. 1a), the domain wall becomes electrostatically charged. It may then attract compensating mobile charges of opposite sign produced by dopant ionization, photoexcitation or other effects, thereby locally, electrostatically doping the host ferroelectric film. In contrast to conductive interfaces between epitaxially grown oxides, domain walls can be reversibly created, positioned and shaped by electric fields, enabling reconfigurable circuitry within the same volume of the material. Now, writing in Nature Nanotechnology, Arnaud Crassous and colleagues at EPFL and University of Geneva demonstrate control and stability of charged conducting domain walls in ferroelectric thin films of BiFeO3 down to the nanoscale.« less

  18. Subatomic movements of a domain wall in the Peierls potential

    NASA Astrophysics Data System (ADS)

    Novoselov, K. S.; Geim, A. K.; Dubonos, S. V.; Hill, E. W.; Grigorieva, I. V.

    2003-12-01

    The discrete nature of crystal lattices plays a role in virtually every material property. But it is only when the size of entities hosted by a crystal becomes comparable to the lattice period-as occurs for dislocations, vortices in superconductors and domain walls-that this discreteness is manifest explicitly. The associated phenomena are usually described in terms of a background Peierls `atomic washboard' energy potential, which was first introduced for the case of dislocation motion in the 1940s. This concept has subsequently been invoked in many situations to describe certain features in the bulk behaviour of materials, but has to date eluded direct detection and experimental scrutiny at a microscopic level. Here we report observations of the motion of a single magnetic domain wall at the scale of the individual peaks and troughs of the atomic energy landscape. Our experiments reveal that domain walls can become trapped between crystalline planes, and that they propagate by distinct jumps that match the lattice periodicity. The jumps between valleys are found to involve unusual dynamics that shed light on the microscopic processes underlying domain-wall propagation. Such observations offer a means for probing experimentally the physics of topological defects in discrete lattices-a field rich in phenomena that have been subject to extensive theoretical study.

  19. In defence of the three-domains of life paradigm.

    PubMed

    van der Gulik, P T S; Hoff, W D; Speijer, D

    2017-09-19

    Recently, important discoveries regarding the archaeon that functioned as the "host" in the merger with a bacterium that led to the eukaryotes, its "complex" nature, and its phylogenetic relationship to eukaryotes, have been reported. Based on these new insights proposals have been put forward to get rid of the three-domain Model of life, and replace it with a two-domain model. We present arguments (both regarding timing, complexity, and chemical nature of specific evolutionary processes, as well as regarding genetic structure) to resist such proposals. The three-domain Model represents an accurate description of the differences at the most fundamental level of living organisms, as the eukaryotic lineage that arose from this unique merging event is distinct from both Archaea and Bacteria in a myriad of crucial ways. We maintain that "a natural system of organisms", as proposed when the three-domain Model of life was introduced, should not be revised when considering the recent discoveries, however exciting they may be.

  20. Subatomic movements of a domain wall in the Peierls potential.

    PubMed

    Novoselov, K S; Geim, A K; Dubonos, S V; Hill, E W; Grigorieva, I V

    2003-12-18

    The discrete nature of crystal lattices plays a role in virtually every material property. But it is only when the size of entities hosted by a crystal becomes comparable to the lattice period--as occurs for dislocations, vortices in superconductors and domain walls--that this discreteness is manifest explicitly. The associated phenomena are usually described in terms of a background Peierls 'atomic washboard' energy potential, which was first introduced for the case of dislocation motion in the 1940s. This concept has subsequently been invoked in many situations to describe certain features in the bulk behaviour of materials, but has to date eluded direct detection and experimental scrutiny at a microscopic level. Here we report observations of the motion of a single magnetic domain wall at the scale of the individual peaks and troughs of the atomic energy landscape. Our experiments reveal that domain walls can become trapped between crystalline planes, and that they propagate by distinct jumps that match the lattice periodicity. The jumps between valleys are found to involve unusual dynamics that shed light on the microscopic processes underlying domain-wall propagation. Such observations offer a means for probing experimentally the physics of topological defects in discrete lattices--a field rich in phenomena that have been subject to extensive theoretical study.

  1. Localization of resistive domains in inhomogeneous superconductors

    SciTech Connect

    Gurevich, A.V.; Mints, R.G.

    1981-01-01

    The properties of resistive domains due to the Joule heating in inhomogeneous superconductors with transport currents are studied. The equilibrium of a domain at an inhomogeneity of arbitrary type and with dimensions much smaller than the dimensions of the domain is investigated. It is shown that resistive domains can become localized at inhomogeneities. The temperature distribution in a domain and the current--voltage characteristic of the domain are determined. The stability of localized domains is discussed. It is shown that such domains give rise to a hysteresis in the destruction (recovery) of the superconductivity by the transport current.

  2. The Role of Within-Host Competition for Coexistence in Multiparasitoid-Host Systems.

    PubMed

    van Velzen, Ellen; Pérez-Vila, Saleta; Etienne, Rampal S

    2016-01-01

    Multiparasitism (females of multiple species parasitizing the same host) is a ubiquitous phenomenon in parasitoids, yet the role of within-host competition has been mostly ignored in multiparasitoid-host models. Here we study the effect of varying the degree of competition at different life stages: competition over oviposition sites (between-adult competition) and larval competition over resources within the host (within-host competition). We adapt a Nicholson-Bailey model to allow for varying levels of between-adult competition (varying the overlap in species distributions) and within-host competition (varying the number of offspring that can successfully emerge from a host). Surprisingly, while stronger between-adult competition reduces coexistence, stronger within-host competition promotes it. Asymmetric between-adult competition (a fecundity difference between the two species) reduces coexistence when compared to symmetric competition; this can be counteracted by asymmetric within-host competition (within-host competitive advantage of the lower-fecundity species), but only when within-host competition is strong and the correlation between the parasitoids' distributions is intermediate. We discuss our results in the context of the interaction between two parasitoid species, Nasonia vitripennis and Nasonia giraulti, which have strongly correlated distributions and high levels of multiparasitism in the field. We conclude that either low or asymmetric within-host competition is unlikely to explain their coexistence.

  3. Host Sexual Dimorphism and Parasite Adaptation

    PubMed Central

    Duneau, David; Ebert, Dieter

    2012-01-01

    In species with separate sexes, parasite prevalence and disease expression is often different between males and females. This effect has mainly been attributed to sex differences in host traits, such as immune response. Here, we make the case for how properties of the parasites themselves can also matter. Specifically, we suggest that differences between host sexes in many different traits, such as morphology and hormone levels, can impose selection on parasites. This selection can eventually lead to parasite adaptations specific to the host sex more commonly encountered, or to differential expression of parasite traits depending on which host sex they find themselves in. Parasites adapted to the sex of the host in this way can contribute to differences between males and females in disease prevalence and expression. Considering those possibilities can help shed light on host–parasite interactions, and impact epidemiological and medical science. PMID:22389630

  4. Magnetism and activity of planet hosting stars

    NASA Astrophysics Data System (ADS)

    Wright, Jason T.; Miller, Brendan P.

    The magnetic activity levels of planet host stars may differ from that of stars not known to host planets in several ways. Hot Jupiters may induce activity in their hosts through magnetic interactions, or through tidal interactions by affecting their host's rotation or convection. Measurements of photospheric, chromospheric, or coronal activity might then be abnormally high or low compared to control stars that do not host hot Jupiters, or might be modulated at the planet's orbital period. Such detections are complicated by the small amplitude of the expected signal, by the fact that the signals may be transient, and by the difficulty of constructing control samples due to exoplanet detection biases and the uncertainty of field star ages. We review these issues, and discuss avenues for future progress in the field.

  5. Evolution of Protein Domain Repeats in Metazoa

    PubMed Central

    Schüler, Andreas; Bornberg-Bauer, Erich

    2016-01-01

    Repeats are ubiquitous elements of proteins and they play important roles for cellular function and during evolution. Repeats are, however, also notoriously difficult to capture computationally and large scale studies so far had difficulties in linking genetic causes, structural properties and evolutionary trajectories of protein repeats. Here we apply recently developed methods for repeat detection and analysis to a large dataset comprising over hundred metazoan genomes. We find that repeats in larger protein families experience generally very few insertions or deletions (indels) of repeat units but there is also a significant fraction of noteworthy volatile outliers with very high indel rates. Analysis of structural data indicates that repeats with an open structure and independently folding units are more volatile and more likely to be intrinsically disordered. Such disordered repeats are also significantly enriched in sites with a high functional potential such as linear motifs. Furthermore, the most volatile repeats have a high sequence similarity between their units. Since many volatile repeats also show signs of recombination, we conclude they are often shaped by concerted evolution. Intriguingly, many of these conserved yet volatile repeats are involved in host-pathogen interactions where they might foster fast but subtle adaptation in biological arms races. Key Words: protein evolution, domain rearrangements, protein repeats, concerted evolution. PMID:27671125

  6. Prediction of Interactions between Viral and Host Proteins Using Supervised Machine Learning Methods

    PubMed Central

    Barman, Ranjan Kumar; Saha, Sudipto; Das, Santasabuj

    2014-01-01

    Background Viral-host protein-protein interaction plays a vital role in pathogenesis, since it defines viral infection of the host and regulation of the host proteins. Identification of key viral-host protein-protein interactions (PPIs) has great implication for therapeutics. Methods In this study, a systematic attempt has been made to predict viral-host PPIs by integrating different features, including domain-domain association, network topology and sequence information using viral-host PPIs from VirusMINT. The three well-known supervised machine learning methods, such as SVM, Naïve Bayes and Random Forest, which are commonly used in the prediction of PPIs, were employed to evaluate the performance measure based on five-fold cross validation techniques. Results Out of 44 descriptors, best features were found to be domain-domain association and methionine, serine and valine amino acid composition of viral proteins. In this study, SVM-based method achieved better sensitivity of 67% over Naïve Bayes (37.49%) and Random Forest (55.66%). However the specificity of Naïve Bayes was the highest (99.52%) as compared with SVM (74%) and Random Forest (89.08%). Overall, the SVM and Random Forest achieved accuracy of 71% and 72.41%, respectively. The proposed SVM-based method was evaluated on blind dataset and attained a sensitivity of 64%, specificity of 83%, and accuracy of 74%. In addition, unknown potential targets of hepatitis B virus-human and hepatitis E virus-human PPIs have been predicted through proposed SVM model and validated by gene ontology enrichment analysis. Our proposed model shows that, hepatitis B virus “C protein” binds to membrane docking protein, while “X protein” and “P protein” interacts with cell-killing and metabolic process proteins, respectively. Conclusion The proposed method can predict large scale interspecies viral-human PPIs. The nature and function of unknown viral proteins (HBV and HEV), interacting partners of host protein

  7. Functional domain walls in multiferroics.

    PubMed

    Meier, Dennis

    2015-11-25

    During the last decade a wide variety of novel and fascinating correlation phenomena has been discovered at domain walls in multiferroic bulk systems, ranging from unusual electronic conductance to inseparably entangled spin and charge degrees of freedom. The domain walls represent quasi-2D functional objects that can be induced, positioned, and erased on demand, bearing considerable technological potential for future nanoelectronics. Most of the challenges that remain to be solved before turning related device paradigms into reality, however, still fall in the field of fundamental condensed matter physics and materials science. In this topical review seminal experimental findings gained on electric and magnetic domain walls in multiferroic bulk materials are addressed. A special focus is put on the physical properties that emerge at so-called charged domain walls and the added functionality that arises from coexisting magnetic order. The research presented in this review highlights that we are just entering a whole new world of intriguing nanoscale physics that is yet to be explored in all its details. The goal is to draw attention to the persistent challenges and identify future key directions for the research on functional domain walls in multiferroics.

  8. Codivergence of Mycoviruses with Their Hosts

    PubMed Central

    Göker, Markus; Scheuner, Carmen; Klenk, Hans-Peter; Stielow, J. Benjamin; Menzel, Wulf

    2011-01-01

    Background The associations between pathogens and their hosts are complex and can result from any combination of evolutionary events such as codivergence, switching, and duplication of the pathogen. Mycoviruses are RNA viruses which infect fungi and for which natural vectors are so far unknown. Thus, lateral transfer might be improbable and codivergence their dominant mode of evolution. Accordingly, mycoviruses are a suitable target for statistical tests of virus-host codivergence, but inference of mycovirus phylogenies might be difficult because of low sequence similarity even within families. Methodology We analyzed here the evolutionary dynamics of all mycovirus families by comparing virus and host phylogenies. Additionally, we assessed the sensitivity of the co-phylogenetic tests to the settings for inferring virus trees from their genome sequences and approximate, taxonomy-based host trees. Conclusions While sequence alignment filtering modes affected branch support, the overall results of the co-phylogenetic tests were significantly influenced only by the number of viruses sampled per family. The trees of the two largest families, Partitiviridae and Totiviridae, were significantly more similar to those of their hosts than expected by chance, and most individual host-virus links had a significant positive impact on the global fit, indicating that codivergence is the dominant mode of virus diversification. However, in this regard mycoviruses did not differ from closely related viruses sampled from non-fungus hosts. The remaining virus families were either dominated by other evolutionary modes or lacked an apparent overall pattern. As this negative result might be caused by insufficient taxon sampling, the most parsimonious hypothesis still is that host-parasite evolution is basically the same in all mycovirus families. This is the first study of mycovirus-host codivergence, and the results shed light not only on how mycovirus biology affects their co

  9. Uncovering Wolbachia diversity upon artificial host transfer.

    PubMed

    Schneider, Daniela I; Riegler, Markus; Arthofer, Wolfgang; Merçot, Hervé; Stauffer, Christian; Miller, Wolfgang J

    2013-01-01

    The common endosymbiotic Wolbachia bacteria influence arthropod hosts in multiple ways. They are mostly recognized for their manipulations of host reproduction, yet, more recent studies demonstrate that Wolbachia also impact host behavior, metabolic pathways and immunity. Besides their biological and evolutionary roles, Wolbachia are new potential biological control agents for pest and vector management. Importantly, Wolbachia-based control strategies require controlled symbiont transfer between host species and predictable outcomes of novel Wolbachia-host associations. Theoretically, this artificial horizontal transfer could inflict genetic changes within transferred Wolbachia populations. This could be facilitated through de novo mutations in the novel recipient host or changes of haplotype frequencies of polymorphic Wolbachia populations when transferred from donor to recipient hosts. Here we show that Wolbachia resident in the European cherry fruit fly, Rhagoletis cerasi, exhibit ancestral and cryptic sequence polymorphism in three symbiont genes, which are exposed upon microinjection into the new hosts Drosophila simulans and Ceratitis capitata. Our analyses of Wolbachia in microinjected D. simulans over 150 generations after microinjection uncovered infections with multiple Wolbachia strains in trans-infected lines that had previously been typed as single infections. This confirms the persistence of low-titer Wolbachia strains in microinjection experiments that had previously escaped standard detection techniques. Our study demonstrates that infections by multiple Wolbachia strains can shift in prevalence after artificial host transfer driven by either stochastic or selective processes. Trans-infection of Wolbachia can claim fitness costs in new hosts and we speculate that these costs may have driven the shifts of Wolbachia strains that we saw in our model system.

  10. Effect of Intermediate Hosts on Emerging Zoonoses.

    PubMed

    Cui, Jing-An; Chen, Fangyuan; Fan, Shengjie

    2017-08-01

    Most emerging zoonotic pathogens originate from animals. They can directly infect humans through natural reservoirs or indirectly through intermediate hosts. As a bridge, an intermediate host plays different roles in the transmission of zoonotic pathogens. In this study, we present three types of pathogen transmission to evaluate the effect of intermediate hosts on emerging zoonotic diseases in human epidemics. These types are identified as follows: TYPE 1, pathogen transmission without an intermediate host for comparison; TYPE 2, pathogen transmission with an intermediate host as an amplifier; and TYPE 3, pathogen transmission with an intermediate host as a vessel for genetic variation. In addition, we established three mathematical models to elucidate the mechanisms underlying zoonotic disease transmission according to these three types. Stability analysis indicated that the existence of intermediate hosts increased the difficulty of controlling zoonotic diseases because of more difficult conditions to satisfy for the disease to die out. The human epidemic would die out under the following conditions: TYPE 1: [Formula: see text] and [Formula: see text]; TYPE 2: [Formula: see text], [Formula: see text], and [Formula: see text]; and TYPE 3: [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] Simulation with similar parameters demonstrated that intermediate hosts could change the peak time and number of infected humans during a human epidemic; intermediate hosts also exerted different effects on controlling the prevalence of a human epidemic with natural reservoirs in different periods, which is important in addressing problems in public health. Monitoring and controlling the number of natural reservoirs and intermediate hosts at the right time would successfully manage and prevent the prevalence of emerging zoonoses in humans.

  11. Are three colonies of Neostromboceros albicomus, a candidate biological control agent for Lygodium microphyllum, the same host biotype?

    USDA-ARS?s Scientific Manuscript database

    Three colonies of Neostromboceros albicomus, a candidate biological control agent of Lygodium microphyllum, were barcoded using the D2 expansion domain, to determine which of two biotypes they represented. The first colony, collected in 2005 & 2007, was used for the initial host range testing. Colon...

  12. Cloning, expression, purification, crystallization and preliminary X-ray crystallographic analysis of the TIR domain from the Brucella melitensis TIR-domain-containing protein TcpB.

    PubMed

    Alaidarous, Mohammed; Ve, Thomas; Ullah, M Obayed; Valkov, Eugene; Mansell, Ashley; Schembri, Mark A; Sweet, Matthew J; Kobe, Bostjan

    2013-10-01

    In mammals, Toll-like receptors (TLRs) recognize conserved microbial molecular signatures and induce an early innate immune response in the host. TLR signalling is mediated by interactions between the cytosolic TIR (Toll/interleukin-1 receptor) domains of the receptor and the adaptor proteins. Increasingly, it is apparent that pathogens target this interaction via pathogen-expressed TIR-domain-containing proteins to modulate immune responses. A TIR-domain-containing protein TcpB has been reported in the pathogenic bacterium Brucella melitensis. Studies have shown that TcpB interferes with the TLR2 and TLR4 signalling pathways to inhibit TLR-mediated inflammatory responses. Such interference may involve TIR-TIR-domain interactions between bacterial and mammalian proteins, but there is a lack of information about these interactions at the molecular level. In this study, the cloning, expression, purification, crystallization and preliminary X-ray crystallographic analysis of the protein construct corresponding to the TIR domain of TcpB (residues 120-250) are reported. The crystals diffracted to 2.6 Å resolution, have the symmetry of the monoclinic space group P2₁ and are most likely to contain four molecules in the asymmetric unit. The structure should help in understanding the molecular basis of how TcpB affects the innate immunity of the host.

  13. The C domain in the surface envelope glycoprotein of subgroup C feline leukemia virus is a second receptor-binding domain.

    PubMed

    Rey, Michelle A; Prasad, Rati; Tailor, Chetankumar S

    2008-01-20

    The receptor-binding domain (RBD) in the surface (SU) subunit of gammaretrovirus envelope glycoprotein is critical for determining the host receptor specificity of the virus. This domain is separated from the carboxy terminal C domain (Cdom) of SU by a proline-rich region. In this study, we show that the Cdom region in the SU from subgroup C feline leukemia virus (FeLV-C) forms a second receptor-binding domain that is distinct from its RBD, and which can independently bind to its host receptor FLVCR1, in the absence of RBD. Furthermore, our results suggest that residues located in the C2 disulfide-bonded loop in FeLV-C Cdom are critical for SU binding to FLVCR1 and for virus infection. We propose that binding of FeLV-C SU to FLVCR1 involves interaction of two receptor-binding domains (RBD and Cdom) with FLVCR1, and that this mechanism of interaction is conserved for other gammaretroviruses. Our results could have important implications for designing gammaretrovirus vectors that can efficiently infect specific target cells.

  14. Fungal Hybrid B heme peroxidases - unique fusions of a heme peroxidase domain with a carbohydrate-binding domain.

    PubMed

    Zámocký, Marcel; Janeček, Štefan; Obinger, Christian

    2017-08-24

    Heme peroxidases, essential peroxide converting oxidoreductases are divided into four independently evolved superfamilies. Within the largest one - the peroxidase-catalase superfamily - two hybrid lineages were described recently. Whereas Hybrid A heme peroxidases represent intermediate enzymes between ascorbate peroxidases and cytochrome c peroxidases, Hybrid B heme peroxidases are unique fusion proteins comprised of a conserved N-terminal heme peroxidase domain and a C-terminal domain of various sugar binding motifs. So far these peculiar peroxidases are only found in the kingdom of Fungi. Here we present a phylogenetic reconstruction of the whole superfamily with focus on Hybrid B peroxidases. We analyse the domain assembly and putative structure and function of the newly discovered oligosaccharide binding domains. Two distinct carbohydrate binding modules (CBM21 and CBM34) are shown to occur in phytopathogenic ascomycetous orthologs of Hybrid B heme peroxidases only. Based on multiple sequence alignment and homology modeling the structure-function relationships are discussed with respect to physiological function. A concerted action of peroxide cleavage with specific cell-wall carbohydrate binding can support phytopathogens survival within the plant host.

  15. Mosquito host selection varies seasonally with host availability and mosquito density.

    PubMed

    Thiemann, Tara C; Wheeler, Sarah S; Barker, Christopher M; Reisen, William K

    2011-12-01

    Host selection by vector mosquitoes is a critical component of virus proliferation, particularly for viruses such as West Nile (WNV) that are transmitted enzootically to a variety of avian hosts, and tangentially to dead-end hosts such as humans. Culex tarsalis is a principal vector of WNV in rural areas of western North America. Based on previous work, Cx. tarsalis utilizes a variety of avian and mammalian hosts and tends to feed more frequently on mammals in the late summer than during the rest of the year. To further explore this and other temporal changes in host selection, bloodfed females were collected at a rural farmstead and heron nesting site in Northern California from May 2008 through May 2009, and bloodmeal hosts identified using either a microsphere-based array or by sequencing of the mitochondrial cytochrome c oxidase I (COI) gene. Host composition during summer was dominated by four species of nesting Ardeidae. In addition, the site was populated with various passerine species as well as domestic farm animals and humans. When present, Cx. tarsalis fed predominantly (>80%) upon the ardeids, with Black-crowned Night-Herons, a highly competent WNV host, the most prevalent summer host. As the ardeids fledged and left the area and mosquito abundance increased in late summer, Cx. tarsalis feeding shifted to include more mammals, primarily cattle, and a high diversity of avian species. In the winter, Yellow-billed Magpies and House Sparrows were the predominant hosts, and Yellow-billed Magpies and American Robins were fed upon more frequently than expected given their relative abundance. These data demonstrated that host selection was likely based both on host availability and differences in utilization, that the shift of bloodfeeding to include more mammalian hosts was likely the result of both host availability and increased mosquito abundance, and that WNV-competent hosts were fed upon by Cx. tarsalis throughout the year.

  16. Ectoparasitism and stress hormones: strategy of host exploitation, common host-parasite history and energetics matter.

    PubMed

    St Juliana, Justin R; Khokhlova, Irina S; Wielebnowski, Nadja; Kotler, Burt P; Krasnov, Boris R

    2014-09-01

    Parasites are thought to have numerous negative effects on their hosts. These negative effects may be associated with stress in a host. We evaluated the effects of four species of flea ectoparasites (Parapulex chephrenis, Synosternus cleopatrae, Xenopsylla conformis and Xenopsylla ramesis) on non-specific responses of eight species of rodents (Meriones crassus, Gerbillus dasyurus, Gerbillus andersoni, Gerbillus pyramidum, Gerbillus nanus, Acomys cahirinus, Acomys russatus and Mesocricetus auratus) and measured faecal glucocorticoid metabolites concentrations (FGMC) produced by the hosts. We found no effect of body mass of an individual rodent on FGMCs. Parasitism by fleas with a 'stay on the host body' exploitation strategy was associated with higher host FGMCs than parasitism by fleas that spent most of their life 'off-host'. FGMCs among rodents infested by the same flea species were correlated positively with the phylogenetic distance of a given rodent from the principal host of this flea; changes in FGMCs were lower in the host species more closely related to the flea's principal host. Changes in FMGCs of a host while parasitized were correlated with a host's change in body mass, where hosts that lost more body mass had higher FGMCs. Our results suggest that ectoparasitism can be stressful to their hosts. However, the occurrence of parasite-induced stress seems to depend on the identity of both host and parasite species and the evolutionary history of a host-parasite association. To our knowledge, this is the first multispecies study to evaluate the effect of ectoparasites on glucocorticoid hormones in small mammals. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

  17. Emergence of host-adapted Salmonella Enteritidis through rapid evolution in an immunocompromised host

    PubMed Central

    Klemm, Elizabeth J; Gkrania-Klotsas, Effrossyni; Hadfield, James; Forbester, Jessica L; Harris, Simon R; Hale, Christine; Heath, Jennifer N; Wileman, Thomas; Clare, Simon; Kane, Leanne; Goulding, David; Otto, Thomas D; Kay, Sally; Doffinger, Rainer; Cooke, Fiona J; Carmichael, Andrew; Lever, Andrew ML; Parkhill, Julian; MacLennan, Calman A; Kumararatne, Dinakantha

    2016-01-01

    Summary Host adaptation is a key factor contributing to the emergence of new bacterial, viral and parasitic pathogens. Many pathogens are considered promiscuous because they cause disease across a range of host species, while others are host-adapted, infecting particular hosts1. Host adaptation can potentially progress to host restriction where the pathogen is strictly limited to a single host species and is frequently associated with more severe symptoms. Host-adapted and host-restricted bacterial clades evolve from within a broader host-promiscuous species and sometimes target different niches within their specialist hosts, such as adapting from a mucosal to a systemic lifestyle. Genome degradation, marked by gene inactivation and deletion, is a key feature of host adaptation, although the triggers initiating genome degradation are not well understood. Here, we show that a chronic systemic non-typhoidal Salmonella infection in an immunocompromised human patient resulted in genome degradation targeting genes that are expendable for a systemic lifestyle. We present a genome-based investigation of a recurrent blood-borne Salmonella enterica serotype Enteritidis (S. Enteritidis) infection covering 15 years in an interleukin (IL)-12 β-1 receptor-deficient individual that developed into an asymptomatic chronic infection. The infecting S. Enteritidis harbored a mutation in the mismatch repair gene mutS that accelerated the genomic mutation rate. Phylogenetic analysis and phenotyping of multiple patient isolates provides evidence for a remarkable level of within-host evolution that parallels genome changes present in successful host-restricted bacterial pathogens but never before observed on this timescale. Our analysis identifies common pathways of host adaptation and demonstrates the role that immunocompromised individuals can play in this process. PMID:27127642

  18. Mosquito Host Selection Varies Seasonally with Host Availability and Mosquito Density

    PubMed Central

    Thiemann, Tara C.; Wheeler, Sarah S.; Barker, Christopher M.; Reisen, William K.

    2011-01-01

    Host selection by vector mosquitoes is a critical component of virus proliferation, particularly for viruses such as West Nile (WNV) that are transmitted enzootically to a variety of avian hosts, and tangentially to dead-end hosts such as humans. Culex tarsalis is a principal vector of WNV in rural areas of western North America. Based on previous work, Cx. tarsalis utilizes a variety of avian and mammalian hosts and tends to feed more frequently on mammals in the late summer than during the rest of the year. To further explore this and other temporal changes in host selection, bloodfed females were collected at a rural farmstead and heron nesting site in Northern California from May 2008 through May 2009, and bloodmeal hosts identified using either a microsphere-based array or by sequencing of the mitochondrial cytochrome c oxidase I (COI) gene. Host composition during summer was dominated by four species of nesting Ardeidae. In addition, the site was populated with various passerine species as well as domestic farm animals and humans. When present, Cx. tarsalis fed predominantly (>80%) upon the ardeids, with Black-crowned Night-Herons, a highly competent WNV host, the most prevalent summer host. As the ardeids fledged and left the area and mosquito abundance increased in late summer, Cx. tarsalis feeding shifted to include more mammals, primarily cattle, and a high diversity of avian species. In the winter, Yellow-billed Magpies and House Sparrows were the predominant hosts, and Yellow-billed Magpies and American Robins were fed upon more frequently than expected given their relative abundance. These data demonstrated that host selection was likely based both on host availability and differences in utilization, that the shift of bloodfeeding to include more mammalian hosts was likely the result of both host availability and increased mosquito abundance, and that WNV-competent hosts were fed upon by Cx. tarsalis throughout the year. PMID:22206038

  19. Faraday instability in deformable domains

    NASA Astrophysics Data System (ADS)

    Pucci, Giuseppe; Ben Amar, Martine; Couder, Yves

    2014-11-01

    We investigate the Faraday instability in floating liquid lenses, as an example of hydrodynamic instability that develops in a domain with flexible boundaries. We show that a mutual adaptation of the instability pattern and the domain shape occurs, as a result of the competition between the wave radiation pressure and the capillary response of the lens border. Two archetypes of behaviour are observed. In the first, stable shapes are obtained experimentally and predicted theoretically as the exact solutions of a Riccati equation, and they result from the equilibrium between wave radiation pressure and capillarity. In the second, the radiation pressure exceeds the capillary response of the lens border and leads to non-equilibrium behaviours, with breaking into smaller domains that have a complex dynamics including spontaneous propagation. The authors are grateful to Université Franco-Italienne (UFI) for financial support.

  20. The Luminosity Function of QSO Host Galaxies

    NASA Technical Reports Server (NTRS)

    Hamilton, Timothy S.; Casertano, Stefano; Turnshek, David A.; White, Nicholas E. (Technical Monitor)

    2002-01-01

    We present some results from our HST archival image study of 71 QSO host galaxies. The objects are selected to have z less than or equal to 0.46 and total absolute magnitude M(sub v) less than or equal to -23 in our adopted cosmology (H(sub 0) = 50 kilometers per second Mpc(sup-1), q(sub 0) = 0.5, lambda = 0)). The aim of this initial study is to investigate the composition of the sample with respect to host morphology and radio loudness, as well as derive the QSO host galaxy luminosity function. We have analyzed available WFPC2 images in R or I band (U in one case), using a uniform set of procedures. The host galaxies span a narrow range of luminosities and are exceptionally bright, much more so than normal galaxies, usually L greater than L*(sub v). The QSOs are almost equally divided among three subclasses: radio-loud QSOs with elliptical hosts, radio-quiet QSOs with elliptical hosts, and radio-quiet QSOs with spiral hosts. Radio-loud QSOs with spiral hosts are extremely rare. Using a weighting procedure, we derive the combined luminosity function of QSO host galaxies. We find that the luminosity function of QSO hosts differs in shape from that of normal galaxies but that they coincide at the highest luminosities. The ratio of the number of quasar hosts to the number of normal galaxies at a luminosity L*(sub v) is R = (Lv/11.48L*(sub v))(sup 2.46), where L*(sub v) corresponds to M*(sub v)= -22.35, and a QSO is defined to be an object with total nuclear plus host light M(sub v) less than or equal to -23. This ratio can be interpreted as the probability that a galaxy with luminosity L(sub V) will host a QSO at redshift z approximately equal to 0.26.

  1. Function of Nod-like Receptors in Microbial Recognition and Host Defense

    PubMed Central

    Franchi, Luigi; Warner, Neil; Viani, Kyle; Nuñez, Gabriel

    2009-01-01

    Summary Nucleotide oligomerization domain (NOD)-like receptors (NLRs) are a specialized group of intracellular proteins that play a critical role in the regulation of the host innate immune response. NLRs act as scaffolding proteins that assemble signaling platforms that trigger nuclear factor-κB and mitogen-activated protein kinase signaling pathways and control the activation of inflammatory caspases. Importantly, mutations in several members of the NLR family have been linked to a variety of inflammatory diseases consistent with these molecules playing an important role in host-pathogen interactions and the inflammatory response. In this review, we focus on the role of Nod1 and Nod2 in host defense and in particular discuss recent finding regarding the role of Nlrc4, Nlpr1, and Nlrp3 inflammasomes in caspase-1 activation and subsequent release of proinflammatory cytokines such as interleukin-1β. PMID:19120480

  2. Domain similarity based orthology detection.

    PubMed

    Bitard-Feildel, Tristan; Kemena, Carsten; Greenwood, Jenny M; Bornberg-Bauer, Erich

    2015-05-13

    Orthologous protein detection software mostly uses pairwise comparisons of amino-acid sequences to assert whether two proteins are orthologous or not. Accordingly, when the number of sequences for comparison increases, the number of comparisons to compute grows in a quadratic order. A current challenge of bioinformatic research, especially when taking into account the increasing number of sequenced organisms available, is to make this ever-growing number of comparisons computationally feasible in a reasonable amount of time. We propose to speed up the detection of orthologous proteins by using strings of domains to characterize the proteins. We present two new protein similarity measures, a cosine and a maximal weight matching score based on domain content similarity, and new software, named porthoDom. The qualities of the cosine and the maximal weight matching similarity measures are compared against curated datasets. The measures show that domain content similarities are able to correctly group proteins into their families. Accordingly, the cosine similarity measure is used inside porthoDom, the wrapper developed for proteinortho. porthoDom makes use of domain content similarity measures to group proteins together before searching for orthologs. By using domains instead of amino acid sequences, the reduction of the search space decreases the computational complexity of an all-against-all sequence comparison. We demonstrate that representing and comparing proteins as strings of discrete domains, i.e. as a concatenation of their unique identifiers, allows a drastic simplification of search space. porthoDom has the advantage of speeding up orthology detection while maintaining a degree of accuracy similar to proteinortho. The implementation of porthoDom is released using python and C++ languages and is available under the GNU GPL licence 3 at http://www.bornberglab.org/pages/porthoda .

  3. The Garrison Domain: Civil Military Relations in the Cyberspace Domain

    DTIC Science & Technology

    2015-04-01

    through the creation of the Advanced Research Projects Agency Network ( ARPANET ), and was not codified as a domain until the early part of the 21st...therefore viewed as less important . The powers of the legislative and judicial branches of government become weak in relation to the executive branch

  4. The Bordetella Adenylate Cyclase Repeat-in-Toxin (RTX) Domain Is Immunodominant and Elicits Neutralizing Antibodies*

    PubMed Central

    Wang, Xianzhe; Maynard, Jennifer A.

    2015-01-01

    The adenylate cyclase toxin (ACT) is a multifunctional virulence factor secreted by Bordetella species. Upon interaction of its C-terminal hemolysin moiety with the cell surface receptor αMβ2 integrin, the N-terminal cyclase domain translocates into the host cell cytosol where it rapidly generates supraphysiological cAMP concentrations, which inhibit host cell anti-bacterial activities. Although ACT has been shown to induce protective immunity in mice, it is not included in any current acellular pertussis vaccines due to protein stability issues and a poor understanding of its role as a protective antigen. Here, we aimed to determine whether any single domain could recapitulate the antibody responses induced by the holo-toxin and to characterize the dominant neutralizing antibody response. We first immunized mice with ACT and screened antibody phage display libraries for binding to purified ACT. The vast majority of unique antibodies identified bound the C-terminal repeat-in-toxin (RTX) domain. Representative antibodies binding two nonoverlapping, neutralizing epitopes in the RTX domain prevented ACT association with J774A.1 macrophages and soluble αMβ2 integrin, suggesting that these antibodies inhibit the ACT-receptor interaction. Sera from mice immunized with the RTX domain showed similar neutralizing activity as ACT-immunized mice, indicating that this domain induced an antibody response similar to that induced by ACT. These data demonstrate that RTX can elicit neutralizing antibodies and suggest it may present an alternative to ACT. PMID:25505186

  5. Antigenicity of peptides comprising the immunosuppressive domain of the retroviral envelope glycoprotein

    PubMed Central

    2016-01-01

    To achieve persistent infection of the host, viruses often subvert or suppress host immunity through mechanisms that are not entirely understood. The envelope glycoprotein of several retroviruses is thought to possess potent immunosuppressive activity, mapped to a 17-amino acid residue conserved domain. Synthetic peptides corresponding to this immunosuppressive domain can inhibit lymphocyte activation, whereas mutation of key domain residues can increase the lymphocyte response to linked antigenic epitopes. Using three T cell receptors (TCRs) of defined specificity, we examine the effect of the immunosuppressive domain on the T cell response to their respective antigenic peptides. We find that fusion of a T cell epitope to the immunosuppressive domain can greatly modulate its potency. However, the effects heavily depend on the particular combination of TCR and peptide-major histocompatibility complex class II (pMHC II), and are mimicked by sequence-scrambled peptides of similar length, suggesting they operate at the level of TCR-pMHC interaction. These results offer an alternative explanation for the immunogenicity of T cell epitopes comprising the putative immunosuppressive domain, which is more consistent with an effect on peptide antigenicity than true immunosuppressive activity. PMID:28111636

  6. Sinh-domain complex integrators

    NASA Astrophysics Data System (ADS)

    Skotis, George-Drosos; Khanday, Farooq A.; Psychalinos, Costas

    2015-07-01

    The basic building blocks for performing complex signal processing in the Sinh-domain are introduced in this article. Attractive offered benefits are the capabilities for achieving resistorless realisations with electronic adjustment of their frequency characteristics, independent tuning of centre frequency and bandwidth and operating in a low-voltage environment. In addition, the inherent class-AB operation of Sinh-domain filters allows the handling of signals greater than the bias current, leading to a power saving. The aforementioned benefits have been evaluated through simulation results, using the Analog Design Environment of the Cadence software.

  7. Strong host resistance targeted against a viral suppressor of the plant gene silencing defence mechanism.

    PubMed Central

    Li, H W; Lucy, A P; Guo, H S; Li, W X; Ji, L H; Wong, S M; Ding, S W

    1999-01-01

    The 2b protein encoded by cucumber mosaic cucumovirus (Cmv2b) acts as an important virulence determinant by suppressing post-transcriptional gene silencing (PTGS), a natural plant defence mechanism against viruses. We report here that the tomato aspermy cucumovirus 2b protein (Tav2b), when expressed from the unrelated tobacco mosaic tobamovirus (TMV) RNA genome, activates strong host resistance responses to TMV in tobacco which are typical of the gene-for-gene disease resistance mechanism. Domain swapping between Cmv2b, which does not elicit these responses, and Tav2b, revealed functional domains in Tav2b critical for triggering virus resistance and hypersensitive cell death. Furthermore, substitution of two amino acids from Tav2b by those found at the same positions in Cmv2b, Lys21-->Val and Arg28-->Ser, abolished the ability to induce hypersensitive cell death and virus resistance. However, in Nicotiana benthamiana, a species related to tobacco, Tav2b functions as a virulence determinant and suppresses PTGS. Thus, a viral suppressor of the host gene silencing defence mechanism is the target of another independent host resistance mechanism. Our results provide new insights into the complex molecular strategies employed by viruses and their hosts for defence, counter-defence and counter counter-defence. PMID:10329615

  8. Bacteriophage adhering to mucus provide a non–host-derived immunity

    PubMed Central

    Barr, Jeremy J.; Auro, Rita; Furlan, Mike; Whiteson, Katrine L.; Erb, Marcella L.; Pogliano, Joe; Stotland, Aleksandr; Wolkowicz, Roland; Cutting, Andrew S.; Doran, Kelly S.; Salamon, Peter; Youle, Merry; Rohwer, Forest

    2013-01-01

    Mucosal surfaces are a main entry point for pathogens and the principal sites of defense against infection. Both bacteria and phage are associated with this mucus. Here we show that phage-to-bacteria ratios were increased, relative to the adjacent environment, on all mucosal surfaces sampled, ranging from cnidarians to humans. In vitro studies of tissue culture cells with and without surface mucus demonstrated that this increase in phage abundance is mucus dependent and protects the underlying epithelium from bacterial infection. Enrichment of phage in mucus occurs via binding interactions between mucin glycoproteins and Ig-like protein domains exposed on phage capsids. In particular, phage Ig-like domains bind variable glycan residues that coat the mucin glycoprotein component of mucus. Metagenomic analysis found these Ig-like proteins present in the phages sampled from many environments, particularly from locations adjacent to mucosal surfaces. Based on these observations, we present the bacteriophage adherence to mucus model that provides a ubiquitous, but non–host-derived, immunity applicable to mucosal surfaces. The model suggests that metazoan mucosal surfaces and phage coevolve to maintain phage adherence. This benefits the metazoan host by limiting mucosal bacteria, and benefits the phage through more frequent interactions with bacterial hosts. The relationships shown here suggest a symbiotic relationship between phage and metazoan hosts that provides a previously unrecognized antimicrobial defense that actively protects mucosal surfaces. PMID:23690590

  9. Host allometry influences the evolution of parasite host-generalism: theory and meta-analysis

    PubMed Central

    Hurford, Amy; Ellison, Amy R.

    2017-01-01

    Parasites vary widely in the diversity of hosts they infect: some parasite species are specialists—infecting just a single host species, while others are generalists, capable of infecting many. Understanding the factors that drive parasite host-generalism is of basic biological interest, but also directly relevant to predicting disease emergence in new host species, identifying parasites that are likely to have unidentified additional hosts, and assessing transmission risk. Here, we use mathematical models to investigate how variation in host body size and environmental temperature affect the evolution of parasite host-generalism. We predict that parasites are more likely to evolve a generalist strategy when hosts are large-bodied, when variation in host body size is large, and in cooler environments. We then explore these predictions using a newly updated database of over 20 000 fish–macroparasite associations. Within the database we see some evidence supporting these predictions, but also highlight mismatches between theory and data. By combining these two approaches, we establish a theoretical basis for interpreting empirical data on parasites' host specificity and identify key areas for future work that will help untangle the drivers of parasite host-generalism. This article is part of the themed issue ‘Opening the black box: re-examining the ecology and evolution of parasite transmission’. PMID:28289257

  10. Host allometry influences the evolution of parasite host-generalism: theory and meta-analysis.

    PubMed

    Walker, Josephine G; Hurford, Amy; Cable, Jo; Ellison, Amy R; Price, Stephen J; Cressler, Clayton E

    2017-05-05

    Parasites vary widely in the diversity of hosts they infect: some parasite species are specialists-infecting just a single host species, while others are generalists, capable of infecting many. Understanding the factors that drive parasite host-generalism is of basic biological interest, but also directly relevant to predicting disease emergence in new host species, identifying parasites that are likely to have unidentified additional hosts, and assessing transmission risk. Here, we use mathematical models to investigate how variation in host body size and environmental temperature affect the evolution of parasite host-generalism. We predict that parasites are more likely to evolve a generalist strategy when hosts are large-bodied, when variation in host body size is large, and in cooler environments. We then explore these predictions using a newly updated database of over 20 000 fish-macroparasite associations. Within the database we see some evidence supporting these predictions, but also highlight mismatches between theory and data. By combining these two approaches, we establish a theoretical basis for interpreting empirical data on parasites' host specificity and identify key areas for future work that will help untangle the drivers of parasite host-generalism.This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'.

  11. Host-parasite associations and host-specificity in haemoparasites of reed bed passerines.

    PubMed

    Ventim, Rita; Morais, Joana; Pardal, Sara; Mendes, Luísa; Ramos, Jaime A; Pérez-Tris, Javier

    2012-03-01

    The host specificity and host sharing of avian haemoparasites (genera Haemoproteus and Plasmodium) is still poorly known, although they infect a large proportion of several studied bird populations. This study used molecular techniques to detect haemoparasites in marsh warblers and in other passerines that feed in reed beds, at 4 sites in Portugal. The host-specificity of the parasite lineages was analysed and compared with other cases described in the literature to assess whether apparent host specificity changes according to the studied system. Nine lineages of Haemoproteus and 15 of Plasmodium were found, of which only 10 Plasmodium were proven to have local transmission. Each lineage was confined to a distinct set of host species. The distribution of parasites in the host species was non-nested, meaning that specialist lineages did not always share hosts with generalists. The most prevalent lineages were those with a wider host range, indicating that the ability to infect more hosts will enhance a parasite's prevalence in its entire host range. We also found that in our areas, a specialist parasite (H. MW1) appears to have a more generalist character than described in the literature, suggesting that a parasite's apparent specialization can depend on the type of host species sampled.

  12. Host-dependent differences in abundance, composition and host range of cyanophages from the Red Sea.

    PubMed

    Dekel-Bird, Naama P; Sabehi, Gazalah; Mosevitzky, Bar; Lindell, Debbie

    2015-04-01

    Cyanobacteria coexist in the oceans with a wealth of phages that infect them. While numerous studies have investigated Synechococcus phages, much less data are available for Prochlorococcus phages. Furthermore, little is known about cyanophage composition. Here, we examined the abundance and relative composition of cyanophages on six cyanobacterial hosts in samples collected during spring and summer from the Red Sea. Maximal abundances found on Synechococcus of 35 000 phages/ml are within ranges found previously, whereas the 24 000 phages/ml found on Prochlorococcus are approximately 10-fold higher than previous findings. T7-like, T4-like and 'unknown' phages were isolated on all hosts, including many T4-like phages on high-light adapted Prochlorococcus strains, whereas TIM5-like phages were found only on Synechococcus. Large differences in cyanophage abundance and composition were found for different hosts on the same sampling date, as well as for the same host on different dates, with few predictable patterns discerned. Host range analyses showed that T7-like and TIM5-like phages were quite host-specific, whereas the breadth of hosts for T4-like phages was related to host type: those isolated on high-light adapted Prochlorococcus were considerably more host-specific than those on low-light adapted Prochlorococcus or Synechococcus. These host-related differences likely contribute to the complexity of host-phage interactions in the oceans. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  13. Host nutritive quality and host plant choice in two grass miners: primary roles for primary compounds?

    PubMed

    Scheirs, Jan; De Bruyn, Luc; Verhagen, Ron

    2003-06-01

    The relationship between host plant choice and plant nutritional quality was investigated in two oligophagous grass miners Chromatomyia milii and C. nigra (Diptera, Agromyzidae). We tested whether host choice is determined by chemically mediated host suitability for offspring performance and/or adult performance. A second goal was to relate the observed variation among the different fitness parameters to quantitative and qualitative variation in foliar food quality. Choice experiments illustrated that both miners discriminated among grass species, and that C. milii has a smaller host range than C. nigra, as observed under natural conditions. Oviposition preference was correlated with adult feeding preference and related adult performance (longevity and fecundity) for both miners. Offspring performance measures (survival and pupal size) of at least C. nigra were more weakly related to host preference. Nearly all variation in adult performance of both miners was explained by foliar protein content, which had a positive effect on adult longevity and fecundity. Pupal size of both miners was positively related to foliar water and amino acid content and negatively related to lignin content. No clear relationship between host chemistry and offspring survival was observed. These observations show that fitness parameters are differentially related to host chemistry. Secondly, they suggest that chemically mediated host suitability for adult performance is an important determinant of host choice in this species. Finally, the results suggest a primary role for foliar protein content in host choice of the study species in general and in shaping the host range of C. milii in particular.

  14. Exclusion and spatial segregation in the apparent competition between two hosts sharing macroparasites.

    PubMed

    Manica, Mattia; Rosà, Roberto; Pugliese, Andrea; Bolzoni, Luca

    2013-06-01

    In this paper we investigate the spatial dynamics of a deterministic model describing two host species that partially share a common spatial domain, experiencing apparent competition mediated by macroparasites. The aim of this work is to understand the mechanisms underlying apparent competition processes in a spatially structured environment, which have been generally overlooked up to now. First, we analyse the behaviour of a single-host macroparasite partial differential equation (PDE) model, both in the cases of uniform or spatially-dependent vital rates of the host, focusing on the role of spatial diffusion on parasite persistence and host abundance. We obtained the threshold condition for parasite persistence, and (in contrast to what occurs in reaction-diffusion models for an isolated population) we found that, in the case of spatially-dependent vital rates, increasing the host diffusion coefficient results in an increase of the overall host population. Then, a PDE model featuring spatial diffusion and apparent competition mediated via shared macroparasites between two species is analysed in order to understand the role of spatial heterogeneity in host coexistence. We assumed a partial overlap among the habitats of the two species and found that the shared parasites could cause, depending on the values of the diffusion coefficients and differences in induced mortality among host species, a decrease of the realized habitat and, eventually, the extinction of the species less tolerant to parasite infection. This shows that the presence of regulating parasites complicates the effect of dispersal on population dynamics and that the dynamics of apparent competition cannot be adequately understood from spatially-independent models.

  15. Host insulin stimulates Echinococcus multilocularis insulin signalling pathways and larval development

    PubMed Central

    2014-01-01

    Background The metacestode of the tapeworm Echinococcus multilocularis is the causative agent of alveolar echinococcosis, a lethal zoonosis. Infections are initiated through establishment of parasite larvae within the intermediate host’s liver, where high concentrations of insulin are present, followed by tumour-like growth of the metacestode in host organs. The molecular mechanisms determining the organ tropism of E. multilocularis or the influences of host hormones on parasite proliferation are poorly understood. Results Using in vitro cultivation systems for parasite larvae we show that physiological concentrations (10 nM) of human insulin significantly stimulate the formation of metacestode larvae from parasite stem cells and promote asexual growth of the metacestode. Addition of human insulin to parasite larvae led to increased glucose uptake and enhanced phosphorylation of Echinococcus insulin signalling components, including an insulin receptor-like kinase, EmIR1, for which we demonstrate predominant expression in the parasite’s glycogen storage cells. We also characterized a second insulin receptor family member, EmIR2, and demonstrated interaction of its ligand binding domain with human insulin in the yeast two-hybrid system. Addition of an insulin receptor inhibitor resulted in metacestode killing, prevented metacestode development from parasite stem cells, and impaired the activation of insulin signalling pathways through host insulin. Conclusions Our data indicate that host insulin acts as a stimulant for parasite development within the host liver and that E. multilocularis senses the host hormone through an evolutionarily conserved insulin signalling pathway. Hormonal host-parasite cross-communication, facilitated by the relatively close phylogenetic relationship between E. multilocularis and its mammalian hosts, thus appears to be important in the pathology of alveolar echinococcosis. This contributes to a closer understanding of organ tropism and

  16. Bartonella entry mechanisms into mammalian host cells.

    PubMed

    Eicher, Simone C; Dehio, Christoph

    2012-08-01

    The Gram-negative genus Bartonella comprises arthropod-borne pathogens that typically infect mammals in a host-specific manner. Bartonella bacilliformis and Bartonella quintana are human-specific pathogens, while several zoonotic bartonellae specific for diverse animal hosts infect humans as an incidental host. Clinical manifestations of Bartonella infections range from mild symptoms to life-threatening disease. Following transmission by blood-sucking arthropods or traumatic contact with infected animals, bartonellae display sequential tropisms towards endothelial and possibly other nucleated cells and erythrocytes, the latter in a host-specific manner. Attachment to the extracellular matrix (ECM) and to nucleated cells is mediated by surface-exposed bacterial adhesins, in particular trimeric autotransporter adhesins (TAAs). The subsequent engulfment of the pathogen into a vacuolar structure follows a unique series of events whereby the pathogen avoids the endolysosomal compartments. For Bartonella henselae and assumingly most other species, the infection process is aided at different steps by Bartonella effector proteins (Beps). They are injected into host cells through the type IV secretion system (T4SS) VirB/D4 and subvert host cellular functions to favour pathogen uptake. Bacterial binding to erythrocytes is mediated by Trw, another T4SS, in a strictly host-specific manner, followed by pathogen-forced uptake involving the IalB invasin and subsequent replication and persistence within a membrane-bound intra-erythrocytic compartment.

  17. Contrasting Lifestyles Within the Host Cell

    PubMed Central

    Case, Elizabeth Di Russo; Samuel, James E.

    2015-01-01

    CHAPTER SUMMARY Intracellular bacterial pathogens have evolved to exploit the protected niche provided within the boundaries of a eukaryotic host cell. Upon entering a host cell, some bacteria can evade the adaptive immune response of its host, and replicate in a relatively nutrient-rich environment devoid of competition from other host flora. Growth within a host cell is not without its hazards, however. Many pathogens enter their hosts through receptor-mediated endocytosis or phagocytosis, two intracellular trafficking pathways that terminate in a highly degradative organelle, the phagolysosome. This usually deadly compartment is maintained at a low pH, and contains degradative enzymes, and reactive oxygen species resulting in an environment to which few bacterial species are adapted. Some intracellular pathogens, like Shigella, Listeria, Francisella, and Rickettsia escape the phagosome to replicate within the cytosol of the host cell. Bacteria that remain within a vacuole either alter the trafficking of their initial phagosomal compartment or adapt to survive within the harsh environment it will soon become. In this chapter, we focus on the mechanisms by which different vacuolar pathogens either evade lysosomal fusion, as in the case of Mycobacterium and Chlamydia, or allow interaction with lysosomes to varying degrees, such as Brucella and Coxiella, and their specific adaptations to inhabit a replicative niche. PMID:26999394

  18. Mechanisms of host seeking by parasitic nematodes.

    PubMed

    Gang, Spencer S; Hallem, Elissa A

    2016-07-01

    The phylum Nematoda comprises a diverse group of roundworms that includes parasites of vertebrates, invertebrates, and plants. Human-parasitic nematodes infect more than one billion people worldwide and cause some of the most common neglected tropical diseases, particularly in low-resource countries [1]. Parasitic nematodes of livestock and crops result in billions of dollars in losses each year [1]. Many nematode infections are treatable with low-cost anthelmintic drugs, but repeated infections are common in endemic areas and drug resistance is a growing concern with increasing therapeutic and agricultural administration [1]. Many parasitic nematodes have an environmental infective larval stage that engages in host seeking, a process whereby the infective larvae use sensory cues to search for hosts. Host seeking is a complex behavior that involves multiple sensory modalities, including olfaction, gustation, thermosensation, and humidity sensation. As the initial step of the parasite-host interaction, host seeking could be a powerful target for preventative intervention. However, host-seeking behavior remains poorly understood. Here we review what is currently known about the host-seeking behaviors of different parasitic nematodes, including insect-parasitic nematodes, mammalian-parasitic nematodes, and plant-parasitic nematodes. We also discuss the neural bases of these behaviors. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Calling all hosts: Bacterial communication in situ.

    PubMed

    Cleary, Jessica L; Condren, Alanna R; Zink, Katherine E; Sanchez, Laura M

    2017-03-09

    Bacteria are cosmopolitan organisms that in recent years have demonstrated many roles in maintaining host equilibrium. In this review, we discuss three roles bacteria can occupy in a host: pathogenic, symbiotic, and transient, with a specific focus on how bacterial small molecules contribute to homeostasis or dysbiosis. First, we will dissect how small molecules produced by pathogenic bacteria can be used as a source for communication during colonization and as protection against host immune responses. The ability to achieve a higher level of organization through small molecule communication gives pathogenic bacteria an opportunity for increased virulence and fitness. Conversely, in symbiotic relationships with hosts, small molecules are used in the initial acquisition, colonization, and maintenance of this beneficial population. Chemical signals can come from both the host and symbiont, and it is often observed that these interKingdom symbioses result in coevolution of both species involved. Furthermore, the transition from transient to commensal or opportunistic likely relies on molecular mechanisms. The small molecules utilized and produced by transient bacteria are desirable for both the immune and nutritional benefits they provide to the host. Finally, the advantages and disadvantages of modern analytical techniques that are available to researchers in order to study small molecules in situ is an important aspect of this review. It is our opinion that small molecules produced by bacteria are central to many biological processes and a larger focus on uncovering the function and identity of these small molecules is required to gain a deeper understanding of host-microbe associations.

  20. Host specificity of the badger's flea (Paraceras melis) and first detection on a bat host.

    PubMed

    Ancillotto, Leonardo; Mazza, Giuseppe; Menchetti, Mattia; Mori, Emiliano

    2014-10-01

    Defining the whole spectrum of potential hosts of a parasite has large epidemiological and evolutionary implications in biology. Specialized parasites might be able to occasionally exploit a range of different host species, increasing the individual survival and the chances of successful dispersal. For long time Paraceras melis has been considered a specific flea of European badger Meles meles. Anyway, it has occasionally been reported on different hosts. In this work, we summarize the host spectrum of P. melis from literature and we report its first detection on a bat host. Ten species were identified as occasional hosts, man included, and the plasticity of this flea in host exploitation is noteworthy because of possible increase of pathogens transmission to humans and domestic species.

  1. Selecting soluble/foldable protein domains through single-gene or genomic ORF filtering: structure of the head domain of Burkholderia pseudomallei antigen BPSL2063.

    PubMed

    Gourlay, Louise J; Peano, Clelia; Deantonio, Cecilia; Perletti, Lucia; Pietrelli, Alessandro; Villa, Riccardo; Matterazzo, Elena; Lassaux, Patricia; Santoro, Claudio; Puccio, Simone; Sblattero, Daniele; Bolognesi, Martino

    2015-11-01

    The 1.8 Å resolution crystal structure of a conserved domain of the potential Burkholderia pseudomallei antigen and trimeric autotransporter BPSL2063 is presented as a structural vaccinology target for melioidosis vaccine development. Since BPSL2063 (1090 amino acids) hosts only one conserved domain, and the expression/purification of the full-length protein proved to be problematic, a domain-filtering library was generated using β-lactamase as a reporter gene to select further BPSL2063 domains. As a result, two domains (D1 and D2) were identified and produced in soluble form in Escherichia coli. Furthermore, as a general tool, a genomic open reading frame-filtering library from the B. pseudomallei genome was also constructed to facilitate the selection of domain boundaries from the entire ORFeome. Such an approach allowed the selection of three potential protein antigens that were also produced in soluble form. The results imply the further development of ORF-filtering methods as a tool in protein-based research to improve the selection and production of soluble proteins or domains for downstream applications such as X-ray crystallography.

  2. Host conservatism or host specialization? Patterns of fungal diversification are influenced by host specificity in Ophiognomonia (Gnomoniaceae, Diaporthales)

    USDA-ARS?s Scientific Manuscript database

    Species of Ophiognomonia (Gnomoniaceae) are perithecial fungi that occur as endophytes, pathogens, and latent saprobes on leaf and stem tissue of plants in the Betulaceae, Fagaceae, Juglandaceae, Lauraceae, Malvaceae, Platanaceae, Rosaceae, Salicaceae, and Sapindaceae. In this study host plant patte...

  3. Mesoscale spatiotemporal variability in a complex host-parasite system influenced by intermediate host body size.

    PubMed

    Rodríguez, Sara M; Valdivia, Nelson

    2017-01-01

    Parasites are essential components of natural communities, but the factors that generate skewed distributions of parasite occurrences and abundances across host populations are not well understood. Here, we analyse at a seascape scale the spatiotemporal relationships of parasite exposure and host body-size with the proportion of infected hosts (i.e., prevalence) and aggregation of parasite burden across ca. 150 km of the coast and over 22 months. We predicted that the effects of parasite exposure on prevalence and aggregation are dependent on host body-sizes. We used an indirect host-parasite interaction in which migratory seagulls, sandy-shore molecrabs, and an acanthocephalan worm constitute the definitive hosts, intermediate hosts, and endoparasite, respectively. In such complex systems, increments in the abundance of definitive hosts imply increments in intermediate hosts' exposure to the parasite's dispersive stages. Linear mixed-effects models showed a significant, albeit highly variable, positive relationship between seagull density and prevalence. This relationship was stronger for small (cephalothorax length >15 mm) than large molecrabs (<15 mm). Independently of seagull density, large molecrabs carried significantly more parasites than small molecrabs. The analysis of the variance-to-mean ratio of per capita parasite burden showed no relationship between seagull density and mean parasite aggregation across host populations. However, the amount of unexplained variability in aggregation was strikingly higher in larger than smaller intermediate hosts. This unexplained variability was driven by a decrease in the mean-variance scaling in heavily infected large molecrabs. These results show complex interdependencies between extrinsic and intrinsic population attributes on the structure of host-parasite interactions. We suggest that parasite accumulation-a characteristic of indirect host-parasite interactions-and subsequent increasing mortality rates over

  4. Female fecundity variation affects reproducibility of experiments on host plant preference and acceptance in a phytophagous insect.

    PubMed

    Schäpers, Alexander; Petrén, Hampus; Wheat, Christopher W; Wiklund, Christer; Friberg, Magne

    2017-02-22

    Reproducibility is a scientific cornerstone. Many recent studies, however, describe a reproducibility crisis and call for assessments of reproducibility across scientific domains. Here, we explore the reproducibility of a classic ecological experiment-that of assessing female host plant preference and acceptance in phytophagous insects, a group in which host specialization is a key driver of diversification. We exposed multiple cohorts of Pieris napi butterflies from the same population to traditional host acceptance and preference tests on three Brassicaceae host species. Whereas the host plant rank order was highly reproducible, the propensity to oviposit on low-ranked hosts varied significantly even among cohorts exposed to similar conditions. Much variation could be attributed to among-cohort variation in female fecundity, a trait strongly correlated both to female size and to the size of the nuptial gift a female receives during mating. Small males provide small spermatophores, and in our experiment small females that mated with small males had a disproportionally low propensity to oviposit on low-ranked hosts. Hence, our results provide empirical support to the theoretical prediction that female host utilization is strongly affected by non-genetic, environmental variation, and that such variation can affect the reproducibility of ecological experiments even under seemingly identical conditions. © 2017 The Author(s).

  5. Cowpox: reservoir hosts and geographic range.

    PubMed Central

    Chantrey, J.; Meyer, H.; Baxby, D.; Begon, M.; Bown, K. J.; Hazel, S. M.; Jones, T.; Montgomery, W. I.; Bennett, M.

    1999-01-01

    It is generally accepted that the reservoir hosts of cowpox virus are wild rodents, although direct evidence for this is lacking for much of the virus's geographic range. Here, through a combination of serology and PCR, we demonstrate conclusively that the main hosts in Great Britain are bank voles, wood mice and short-tailed field voles. However, we also suggest that wood mice may not be able to maintain infection alone, explaining the absence of cowpox from Ireland where voles are generally not found. Infection in wild rodents varies seasonally, and this variation probably underlies the marked seasonal incidence of infection in accidental hosts such as humans and domestic cats. PMID:10459650

  6. Use of lice to identify cowbird hosts

    USGS Publications Warehouse

    Hahn, D.C.; Price, R.D.; Osenton, P.C.

    2000-01-01

    The host specificity of avian lice (Phthiraptera) may be utilized by biologists to investigate the brood parasitism patterns of Brown-headed Cowbirds (Molothrus ater). As nestlings, brood parasites have a unique opportunity to encounter lice that are typically host specific. Lice are permanent hemimetabolic ectoparasites, a group found strictly on the body of the host, and they are transferred almost exclusively by bodily contact between hosts during care of young and at copulation. We investigated whether cowbird nestlings become infested with avian lice from their host parents and carry these lice away when they fledge, in effect bearing ectoparasite indicators of the species that raised them. The technique of examining the lice on cowbird fledglings to identify their foster parents would be much less costly than hiring a team of experts to determine parasitism patterns in the conventional way by finding hundreds of songbird nests. We examined 244 cowbird fledglings and found that they carried a rich fauna of lice representing 11 species and six genera, almost the entire spectrum of louse genera known to occur on passerines. We also examined 320 songbirds from 30 species, all known hosts of the Brown-headed Cowbird. As a group the host birds bore a diversity of louse species comparable to that on the fledgling cowbirds: 13 species of lice from seven genera. In contrast, most individual passerine host species yielded only 1 or 2 louse species, significantly fewer than the cowbird fledglings (p < 0.0001). Of 44 fledgling cowbirds carrying lice, 11 were linked to their probable avian foster parents via louse indicators, and these are the Wood Thrush and Red-winged Blackbird. Eighteen additional fledglings were linked to one of two possible foster parents. We concluded that cowbird fledglings do carry away host lice and this survey technique provides a partial assessment of local community parasitism patterns. The incomplete state of passerine louse taxonomy requires

  7. Use of lice to identify cowbird hosts

    USGS Publications Warehouse

    Hahn, D.C.; Price, R.D.; Osenton, P.C.

    2000-01-01

    The host specificity of avian lice (Phthiraptera) may be utilized by biologists to investigate the brood parasitism patterns of Brown-headed Cowbirds (Molothrus ater). As nestlings, brood parasites have a unique opportunity to encounter lice that are typically host specific. Lice are permanent hemimetabolic ectoparasites, a group found strictly on the body of the host, and they are transferred almost exclusively by bodily contact between hosts during care of young and at copulation. We investigated whether cowbird nestlings become infested with avian lice from their host parents and carry these lice away when they fledge, in effect bearing ectoparasite indicators of the species that raised them. The technique of examining the lice on cowbird fledglings to identify their foster parents would be much less costly than hiring a team of experts to determine parasitism patterns in the conventional way by finding hundreds of songbird nests. We examined 244 cowbird fledglings and found that they carried a rich fauna of lice representing 11 species and six genera, almost the entire spectrum of louse genera known to occur on passerines. We also examined 320 songbirds from 30 species, all known hosts of the Brown-headed Cowbird. As a group the host birds bore a diversity of louse species comparable to that on the fledgling cowbirds: 13 species of lice from seven genera. In contrast, most individual passerine host species yielded only 1 or 2 louse species, significantly fewer than the cowbird fledglings (p < 0.0001). Of 44 fledgling cowbirds carrying lice, 11 were linked to their probable avian foster parents via louse indicators, and these are the Wood Thrush and Red-winged Blackbird. Eighteen additional fledglings were linked to one of two possible foster parents. We concluded that cowbird fledglings do carry away host lice and this survey technique provides a partial assessment of local community parasitism patterns. The incomplete state of passerine louse taxonomy requires

  8. Treatment of candidiasis: insights from host genetics.

    PubMed

    Delsing, Corine E; Bleeker-Rovers, Chantal P; Kullberg, Bart-Jan; Netea, Mihai G

    2012-08-01

    Candida species are major causes of mucosal and invasive infections, leading to substantial morbidity and mortality. Despite the development of new classes of antifungal drugs, mortality in patients with systemic candidiasis remains high. Host-Candida interaction plays an important role in effective elimination of the pathogen. Genetic studies have rendered important insights into antifungal host defense and have identified potential targets for adjunctive therapy. In this article, the authors review the genetic variations in the host defense to Candida and their implications for the treatment of mucosal and systemic candidiasis.

  9. Protective host immune responses to Salmonella infection.

    PubMed

    Pham, Oanh H; McSorley, Stephen J

    2015-01-01

    Salmonella enterica serovars Typhi and Paratyphi are the causative agents of human typhoid fever. Current typhoid vaccines are ineffective and are not widely used in endemic areas. Greater understanding of host-pathogen interactions during Salmonella infection should facilitate the development of improved vaccines to combat typhoid and nontyphoidal Salmonellosis. This review will focus on our current understanding of Salmonella pathogenesis and the major host immune components that participate in immunity to Salmonella infection. In addition, recent findings regarding host immune mechanisms in response to Salmonella infection will be also discussed, providing a new perspective on the utility of improved tools to study the immune response to Salmonella infections.

  10. Iron homeostasis in host defence and inflammation

    PubMed Central

    Ganz, Tomas; Nemeth, Elizabeta

    2016-01-01

    Iron is an essential trace element for multicellular organisms and nearly all microorganisms. Although iron is abundant in the environment, common forms of iron are minimally soluble and therefore poorly accessible to biological organisms. Microorganisms entering a mammalian host face multiple mechanisms that further restrict their ability to obtain iron and thereby limit their pathogenicity. Iron levels also modulate host defence, as iron content in macrophages regulates their cytokine production. Here, we review recent advances that highlight the role of systemic and cellular iron-regulating mechanisms in protecting hosts from infection, emphasizing aspects that are applicable to human health and disease. PMID:26160612

  11. Inferring Domain-Domain Interactions from Protein-Protein Interactions with Formal Concept Analysis

    PubMed Central

    Khor, Susan

    2014-01-01

    Identifying reliable domain-domain interactions will increase our ability to predict novel protein-protein interactions, to unravel interactions in protein complexes, and thus gain more information about the function and behavior of genes. One of the challenges of identifying reliable domain-domain interactions is domain promiscuity. Promiscuous domains are domains that can occur in many domain architectures and are therefore found in many proteins. This becomes a problem for a method where the score of a domain-pair is the ratio between observed and expected frequencies because the protein-protein interaction network is sparse. As such, many protein-pairs will be non-interacting and domain-pairs with promiscuous domains will be penalized. This domain promiscuity challenge to the problem of inferring reliable domain-domain interactions from protein-protein interactions has been recognized, and a number of work-arounds have been proposed. This paper reports on an application of Formal Concept Analysis to this problem. It is found that the relationship between formal concepts provides a natural way for rare domains to elevate the rank of promiscuous domain-pairs and enrich highly ranked domain-pairs with reliable domain-domain interactions. This piggybacking of promiscuous domain-pairs onto less promiscuous domain-pairs is possible only with concept lattices whose attribute-labels are not reduced and is enhanced by the presence of proteins that comprise both promiscuous and rare domains. PMID:24586450

  12. The BID Domain of Type IV Secretion Substrates Forms a Conserved Four-Helix Bundle Topped with a Hook.

    PubMed

    Stanger, Frédéric V; de Beer, Tjaart A P; Dranow, David M; Schirmer, Tilman; Phan, Isabelle; Dehio, Christoph

    2017-01-03

    The BID (Bep intracellular delivery) domain functions as secretion signal in a subfamily of protein substrates of bacterial type IV secretion (T4S) systems. It mediates transfer of (1) relaxases and the attached DNA during bacterial conjugation, and (2) numerous Bartonella effector proteins (Beps) during protein transfer into host cells infected by pathogenic Bartonella species. Furthermore, BID domains of Beps have often evolved secondary effector functions within host cells. Here, we provide crystal structures for three representative BID domains and describe a novel conserved fold characterized by a compact, antiparallel four-helix bundle topped with a hook. The conserved hydrophobic core provides a rigid scaffold to a surface that, despite a few conserved exposed residues and similarities in charge distribution, displays significant variability. We propose that the genuine function of BID domains as T4S signal may primarily depend on their rigid structure, while the plasticity of their surface may facilitate adaptation to secondary effector functions.

  13. Comparative analysis of plant immune receptor architectures uncovers host proteins likely targeted by pathogens.

    PubMed

    Sarris, Panagiotis F; Cevik, Volkan; Dagdas, Gulay; Jones, Jonathan D G; Krasileva, Ksenia V

    2016-02-19

    Plants deploy immune receptors to detect pathogen-derived molecules and initiate defense responses. Intracellular plant immune receptors called nucleotide-binding leucine-rich repeat (NLR) proteins contain a central nucleotide-binding (NB) domain followed by a series of leucine-rich repeats (LRRs), and are key initiators of plant defense responses. However, recent studies demonstrated that NLRs with non-canonical domain architectures play an important role in plant immunity. These composite immune receptors are thought to arise from fusions between NLRs and additional domains that serve as "baits" for the pathogen-derived effector proteins, thus enabling pathogen recognition. Several names have been proposed to describe these proteins, including "integrated decoys" and "integrated sensors". We adopt and argue for "integrated domains" or NLR-IDs, which describes the product of the fusion without assigning a universal mode of action. We have scanned available plant genome sequences for the full spectrum of NLR-IDs to evaluate the diversity of integrations of potential sensor/decoy domains across flowering plants, including 19 crop species. We manually curated wheat and brassicas and experimentally validated a subset of NLR-IDs in wild and cultivated wheat varieties. We have examined NLR fusions that occur in multiple plant families and identified that some domains show re-occurring integration across lineages. Domains fused to NLRs overlap with previously identified pathogen targets confirming that they act as baits for the pathogen. While some of the integrated domains have been previously implicated in disease resistance, others provide new targets for engineering durable resistance to plant pathogens. We have built a robust reproducible pipeline for detecting variable domain architectures in plant immune receptors across species. We hypothesize that NLR-IDs that we revealed provide clues to the host proteins targeted by pathogens, and that this information can be

  14. AIDA: ab initio domain assembly server.

    PubMed

    Xu, Dong; Jaroszewski, Lukasz; Li, Zhanwen; Godzik, Adam

    2014-07-01

    AIDA: ab initio domain assembly server, available at http://ffas.burnham.org/AIDA/ is a tool that can identify domains in multi-domain proteins and then predict their 3D structures and relative spatial arrangements. The server is free and open to all users, and there is an option for a user to provide an e-mail to get the link to result page. Domains are evolutionary conserved and often functionally independent units in proteins. Most proteins, especially eukaryotic ones, consist of multiple domains while at the same time, most experimentally determined protein structures contain only one or two domains. As a result, often structures of individual domains in multi-domain proteins can be accurately predicted, but the mutual arrangement of different domains remains unknown. To address this issue we have developed AIDA program, which combines steps of identifying individual domains, predicting (separately) their structures and assembling them into multiple domain complexes using an ab initio folding potential to describe domain-domain interactions. AIDA server not only supports the assembly of a large number of continuous domains, but also allows the assembly of domains inserted into other domains. Users can also provide distance restraints to guide the AIDA energy minimization. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Exhaustive enumeration of protein domain families.

    PubMed

    Heger, Andreas; Holm, Liisa

    2003-05-02

    Domains are considered as the basic units of protein folding, evolution, and function. Decomposing each protein into modular domains is thus a basic prerequisite for accurate functional classification of biological molecules. Here, we present ADDA, an automatic algorithm for domain decomposition and clustering of all protein domain families. We use alignments derived from an all-on-all sequence comparison to define domains within protein sequences based on a global maximum likelihood model. In all, 90% of domain boundaries are predicted within 10% of domain size when compared with the manual domain definitions given in the SCOP database. A representative database of 249,264 protein sequences were decomposed into 450,462 domains. These domains were clustered on the basis of sequence similarities into 33,879 domain families containing at least two members with less than 40% sequence identity. Validation against family definitions in the manually curated databases SCOP and PFAM indicates almost perfect unification of various large domain families while contamination by unrelated sequences remains at a low level. The global survey of protein-domain space by ADDA confirms that most large and universal domain families are already described in PFAM and/or SMART. However, a survey of the complete set of mobile modules leads to the identification of 1479 new interesting domain families which shuffle around in multi-domain proteins. The data are publicly available at ftp://ftp.ebi.ac.uk/pub/contrib/heger/adda.

  16. A Method to Examine Content Domain Structures

    ERIC Educational Resources Information Center

    D'Agostino, Jerome; Karpinski, Aryn; Welsh, Megan

    2011-01-01

    After a test is developed, most content validation analyses shift from ascertaining domain definition to studying domain representation and relevance because the domain is assumed to be set once a test exists. We present an approach that allows for the examination of alternative domain structures based on extant test items. In our example based on…

  17. Domain Specificity and Variability in Cognitive Development.

    ERIC Educational Resources Information Center

    Gelman, Rochel

    2000-01-01

    Maintains that there are core-specific and non-core-specific domains of knowledge, but that only the core-specific domains benefit from innate skeletal structures. Asserts that core skeletal domains are universally shared, even though their particular foci may vary. Emphasizes that individuals vary in terms of the noncore domains they acquire.…

  18. Identification of potential molecular associations between chikungunya virus non-structural protein 2 and human host proteins.

    PubMed

    Rana, J; Gulati, S; Rajasekharan, S; Gupta, A; Chaudhary, V; Gupta, S

    2017-01-01

    Chikungunya virus (CHIKV) non-structural protein 2 (nsP2) is considered to be the master regulator of viral RNA replication and host responses generated during viral infection. This protein has two main functional domains: an N-terminal domain which exhibits NTPase, RNA triphosphatase and helicase activities and a C-terminal protease domain. Understanding how CHIKV nsP2 interacts with its host proteins is essential for elucidating all the required processes for viral replication and pathogenesis along with the identification of potential targets for antiviral therapy. In current study yeast two-hybrid (Y2H) screening of a human fetal brain cDNA library was performed using nsP2 protein as bait. The analysis identified seven host proteins (CCDC130, CPNE6, POLR2C, MAPK9, EIF4A2, EEF1A1 and EIF3I) as putative interactors of CHIKV nsP2 which were selected for further analysis based on their roles in host cellular machinery. The gene ontology analysis indicates that these proteins are mainly involved in apoptosis, transcription and translational mechanism of host cell. Domain mapping of nsP2 revealed that these associations are not random connections but instead they have functional significance. Further studies to identify the amino acid residues and their chemical interactions that may help in opening new possibilities for preventing these interactions, thus reducing chances of chikungunya infection were performed. This study expands the understanding of CHIKV-host interactions and is important for rational approaches of discovering new antiviral agents.

  19. A diverse host thrombospondin-type-1 repeat protein repertoire promotes symbiont colonization during establishment of cnidarian-dinoflagellate symbiosis.

    PubMed

    Neubauer, Emilie-Fleur; Poole, Angela Z; Neubauer, Philipp; Detournay, Olivier; Tan, Kenneth; Davy, Simon K; Weis, Virginia M

    2017-05-08

    The mutualistic endosymbiosis between cnidarians and dinoflagellates is mediated by complex inter-partner signaling events, where the host cnidarian innate immune system plays a crucial role in recognition and regulation of symbionts. To date, little is known about the diversity of thrombospondin-type-1 repeat (TSR) domain proteins in basal metazoans or their potential role in regulation of cnidarian-dinoflagellate mutualisms. We reveal a large and diverse repertoire of TSR proteins in seven anthozoan species, and show that in the model sea anemone Aiptasia pallida the TSR domain promotes colonization of the host by the symbiotic dinoflagellate Symbiodinium minutum. Blocking TSR domains led to decreased colonization success, while adding exogenous TSRs resulted in a 'super colonization'. Furthermore, gene expression of TSR proteins was highest at early time-points during symbiosis establishment. Our work characterizes the diversity of cnidarian TSR proteins and provides evidence that these proteins play an important role in the establishment of cnidarian-dinoflagellate symbiosis.

  20. Chemical similarity between historical and novel host plants promotes range and host expansion of the mountain pine beetle in a naïve host ecosystem.

    PubMed

    Erbilgin, Nadir; Ma, Cary; Whitehouse, Caroline; Shan, Bin; Najar, Ahmed; Evenden, Maya

    2014-02-01

    Host plant secondary chemistry can have cascading impacts on host and range expansion of herbivorous insect populations. We investigated the role of host secondary compounds on pheromone production by the mountain pine beetle (Dendroctonus ponderosae) (MPB) and beetle attraction in response to a historical (lodgepole pine, Pinus contorta var. latifolia) and a novel (jack pine, Pinus banksiana) hosts, as pheromones regulate the host colonization process. Beetles emit the same pheromones from both hosts, but more trans-verbenol, the primary aggregation pheromone, was emitted by female beetles on the novel host. The phloem of the novel host contains more α-pinene, a secondary compound that is the precursor for trans-verbenol production in beetle, than the historical host. Beetle-induced emission of 3-carene, another secondary compound found in both hosts, was also higher from the novel host. Field tests showed that the addition of 3-carene to the pheromone mixture mimicking the aggregation pheromones produced from the two host species increased beetle capture. We conclude that chemical similarity between historical and novel hosts has facilitated host expansion of MPB in jack pine forests through the exploitation of common host secondary compounds for pheromone production and aggregation on the hosts. Furthermore, broods emerging from the novel host were larger in terms of body size. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  1. Development in the Food Domain.

    ERIC Educational Resources Information Center

    Rozin, Paul

    1990-01-01

    Discusses problems of general interest in developmental psychology that can be successfully studied in the domain of food; these include (1) development of food likes and dislikes; (2) establishment of the edible/inedible distinction; (3) disgust and contagion; (4) transgenerational communication of preferences; and (5) transition to food…

  2. Cellulose binding domain fusion proteins

    DOEpatents

    Shoseyov, O.; Yosef, K.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1998-02-17

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  3. Cellulose binding domain fusion proteins

    SciTech Connect

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  4. Life sciences domain analysis model.

    PubMed

    Freimuth, Robert R; Freund, Elaine T; Schick, Lisa; Sharma, Mukesh K; Stafford, Grace A; Suzek, Baris E; Hernandez, Joyce; Hipp, Jason; Kelley, Jenny M; Rokicki, Konrad; Pan, Sue; Buckler, Andrew; Stokes, Todd H; Fernandez, Anna; Fore, Ian; Buetow, Kenneth H; Klemm, Juli D

    2012-01-01

    Meaningful exchange of information is a fundamental challenge in collaborative biomedical research. To help address this, the authors developed the Life Sciences Domain Analysis Model (LS DAM), an information model that provides a framework for communication among domain experts and technical teams developing information systems to support biomedical research. The LS DAM is harmonized with the Biomedical Research Integrated Domain Group (BRIDG) model of protocol-driven clinical research. Together, these models can facilitate data exchange for translational research. The content of the LS DAM was driven by analysis of life sciences and translational research scenarios and the concepts in the model are derived from existing information models, reference models and data exchange formats. The model is represented in the Unified Modeling Language and uses ISO 21090 data types. The LS DAM v2.2.1 is comprised of 130 classes and covers several core areas including Experiment, Molecular Biology, Molecular Databases and Specimen. Nearly half of these classes originate from the BRIDG model, emphasizing the semantic harmonization between these models. Validation of the LS DAM against independently derived information models, research scenarios and reference databases supports its general applicability to represent life sciences research. The LS DAM provides unambiguous definitions for concepts required to describe life sciences research. The processes established to achieve consensus among domain experts will be applied in future iterations and may be broadly applicable to other standardization efforts. The LS DAM provides common semantics for life sciences research. Through harmonization with BRIDG, it promotes interoperability in translational science.

  5. Protein structural domains: definition and prediction.

    PubMed

    Ezkurdia, Iakes; Tress, Michael L

    2011-11-01

    Recognition and prediction of structural domains in proteins is an important part of structure and function prediction. This unit lists the range of tools available for domain prediction, and describes sequence and structural analysis tools that complement domain prediction methods. Also detailed are the basic domain prediction steps, along with suggested strategies for different protein sequences and potential pitfalls in domain boundary prediction. The difficult problem of domain orientation prediction is also discussed. All the resources necessary for domain boundary prediction are accessible via publicly available Web servers and databases and do not require computational expertise.

  6. Beneficial and Deleterious Bacterial - Host Interactions in Chronic Wound Pathophysiology

    DTIC Science & Technology

    2015-04-02

    The presence of biofilm causes chronic inflammation , leading to impaired healing rates and host mortality. This review describes the deleterious... inflammation , leading to impaired healing rates and host mortality. This review describes the deleterious bacterial–host interactions, as well as the...biofilm causes chronic inflammation , leading to impaired healing rates and host mortality. This review describes the deleterious bacterial–host

  7. Host-Specific Parvovirus Evolution in Nature Is Recapitulated by In Vitro Adaptation to Different Carnivore Species

    PubMed Central

    Allison, Andrew B.; Kohler, Dennis J.; Ortega, Alicia; Hoover, Elizabeth A.; Grove, Daniel M.; Holmes, Edward C.; Parrish, Colin R.

    2014-01-01

    Canine parvovirus (CPV) emerged as a new pandemic pathogen of dogs in the 1970s and is closely related to feline panleukopenia virus (FPV), a parvovirus of cats and related carnivores. Although both viruses have wide host ranges, analysis of viral sequences recovered from different wild carnivore species, as shown here, demonstrated that >95% were derived from CPV-like viruses, suggesting that CPV is dominant in sylvatic cycles. Many viral sequences showed host-specific mutations in their capsid proteins, which were often close to sites known to control binding to the transferrin receptor (TfR), the host receptor for these carnivore parvoviruses, and which exhibited frequent parallel evolution. To further examine the process of host adaptation, we passaged parvoviruses with alternative backgrounds in cells from different carnivore hosts. Specific mutations were selected in several viruses and these differed depending on both the background of the virus and the host cells in which they were passaged. Strikingly, these in vitro mutations recapitulated many specific changes seen in viruses from natural populations, strongly suggesting they are host adaptive, and which were shown to result in fitness advantages over their parental virus. Comparison of the sequences of the transferrin receptors of the different carnivore species demonstrated that many mutations occurred in and around the apical domain where the virus binds, indicating that viral variants were likely selected through their fit to receptor structures. Some of the viruses accumulated high levels of variation upon passage in alternative hosts, while others could infect multiple different hosts with no or only a few additional mutations. Overall, these studies demonstrate that the evolutionary history of a virus, including how long it has been circulating and in which hosts, as well as its phylogenetic background, has a profound effect on determining viral host range. PMID:25375184

  8. Determination and augmentation of RNA sequence specificity of the Nova K-homology domains.

    PubMed

    Musunuru, Kiran; Darnell, Robert B

    2004-01-01

    The Nova onconeural antigens are implicated in the pathogenesis of paraneoplastic opsoclonus-myoclonus-ataxia (POMA). The Nova antigens are neuron-specific RNA-binding proteins harboring three repeats of the K-homology (KH) motif; they have been implicated in the regulation of alternative splicing of a host of genes involved in inhibitory synaptic transmission. Although the third Nova KH domain (KH3) has been extensively characterized using biochemical and crystallographic techniques, the roles of the KH1 and KH2 domains remain unclear. Furthermore, the specificity determinants that distinguish the Nova KH domains from those of the closely related hnRNP E and hnRNP K proteins are undefined. We demonstrate through the use of RNA selection and biochemical analysis that the sequence specificity of the Nova KH1/2 domains is similar to that of Nova KH3. We also show that the mutagenesis of a Nova KH domain to render it similar to the KH domains of the heterogeneous nuclear ribonucleoprotein E (hnRNP E) and hnRNP K allow it to recognize longer RNA sequences. These data yield important insights into KH domain function and suggest a strategy by which to engineer KH domains with novel sequence preferences.

  9. A conserved domain targets exported PHISTb family proteins to the periphery of Plasmodium infected erythrocytes

    PubMed Central

    Tarr, Sarah J.; Moon, Robert W.; Hardege, Iris; Osborne, Andrew R.

    2014-01-01

    During blood-stage infection, malaria parasites export numerous proteins to the host erythrocyte. The Poly-Helical Interspersed Sub-Telomeric (PHIST) proteins are an exported family that share a common ‘PRESAN’ domain, and include numerous members in Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi. In P. falciparum, PHIST proteins have been implicated in protein trafficking and intercellular communication. A number of PHIST proteins are essential for parasite survival. Here, we identify nine members of the PHISTb sub-class of PHIST proteins, including one protein known to be essential for parasite survival, that localise to the erythrocyte periphery. These proteins have solubility characteristics consistent with their association with the erythrocyte cytoskeleton. Together, an extended PRESAN domain, comprising the PRESAN domain and preceding sequence, form a novel targeting-domain that is sufficient to localise a protein to the erythrocyte periphery. We validate the role of this domain in RESA, thus identifying a cytoskeleton-binding domain in RESA that functions independently of its known spectrin-binding domain. Our data suggest that some PHISTb proteins may act as cross-linkers of the erythrocyte cytoskeleton. We also show for the first time that peripherally-localised PHISTb proteins are encoded in genomes of P. knowlesi and vivax indicating a conserved role for the extended PRESAN domain of these proteins in targeting to the erythrocyte periphery. PMID:25106850

  10. Domains of Awareness in Schizophrenia

    PubMed Central

    Gilleen, J.; Greenwood, K.; David, A. S.

    2011-01-01

    Patients with schizophrenia are often characterized as lacking insight or awareness into their illness and symptoms, yet despite considerable research, we still lack a full understanding of the factors involved in causing poor awareness. Within schizophrenia, there has been shown to be a fractionation across dimensions of awareness into mental illness: of being ill, of symptoms, and of treatment compliance. Recently, attention has turned to evidence of a fractionation between awareness of illness and of cognitive impairments and functioning. The current study investigated the degree of fractionation across a broad range of domains of function in schizophrenia and how each domain may be associated with neuropsychological functioning, clinical, mood, and demographic variables. Thirty-one mostly chronic stable patients with schizophrenia completed a battery of neuropsychological tests and measures of psychopathology, including mood. Cognitive insight and awareness of illness, symptoms, memory, and behavioral functioning were also measured. Insight and awareness were assessed using a combination of semistructured interview, observer-rated, self-rated, and objective measures, and included measures of the discrepancy between carer and self-ratings of impairment. Results revealed that awareness of functioning in each domain was largely independent and that awareness in each domain was predicted by different factors. Insight into symptoms was relatively poor while insight into cognitive deficits was preserved. Relative to neuropsychological variables, cognitive insight, comprising self-certainty and self-reflexivity, was a greater predictor of awareness. In conclusion, awareness is multiply fractionated and multiply determined. Therapeutic interventions could, therefore, produce beneficial changes within specific domains of awareness. PMID:20851850

  11. Domain relaxation in Langmuir films

    NASA Astrophysics Data System (ADS)

    Alexander, James C.; Bernoff, Andrew J.; Mann, Elizabeth K.; Mann, J. Adin; Wintersmith, Jacob R.; Zou, Lu

    We report on theoretical studies of molecularly thin Langmuir films on the surface of a quiescent subfluid and qualitatively compare the results to both new and previous experiments. The film covers the entire fluid surface, but domains of different phases are observed. In the absence of external forcing, the compact domains tend to relax to circles, driven by a line tension at the phase boundaries. When stretched (by a transient applied stagnation-point flow or by stirring), a compact domain elongates, creating a bola consisting of two roughly circular reservoirs connected by a thin tether. This shape will then relax slowly to the minimum-energy configuration of a circular domain. The tether is never observed to rupture, even when it is more than a hundred times as long as it is wide. We model these experiments by taking previous descriptions of the full hydrodynamics, identifying the dominant effects via dimensional analysis, and reducing the system to a more tractable form. The result is a free boundary problem for an inviscid Langmuir film whose motion is driven by the line tension of the domain and damped by the viscosity of the subfluid. Using this model we derive relaxation rates for perturbations of a uniform strip and a circular patch. We also derive a boundary integral formulation which allows an efficient numerical solution of the problem. Numerically this model replicates the formation of a bola and the subsequent relaxation observed in the experiments. Finally, we suggest physical properties of the system (such as line tension) that can be deduced by comparison of the theory and numerical simulations to the experiment. Two movies are available with the online version of the paper.

  12. Role of the PB2 627 Domain in Influenza A Virus Polymerase Function

    PubMed Central

    Nilsson, Benjamin E.; te Velthuis, Aartjan J. W.

    2017-01-01

    ABSTRACT The RNA genome of influenza A viruses is transcribed and replicated by the viral RNA-dependent RNA polymerase, composed of the subunits PA, PB1, and PB2. High-resolution structural data revealed that the polymerase assembles into a central polymerase core and several auxiliary highly flexible, protruding domains. The auxiliary PB2 cap-binding and the PA endonuclease domains are both involved in cap snatching, but the role of the auxiliary PB2 627 domain, implicated in host range restriction of influenza A viruses, is still poorly understood. In this study, we used structure-guided truncations of the PB2 subunit to show that a PB2 subunit lacking the 627 domain accumulates in the cell nucleus and assembles into a heterotrimeric polymerase with PB1 and PA. Furthermore, we showed that a recombinant viral polymerase lacking the PB2 627 domain is able to carry out cap snatching, cap-dependent transcription initiation, and cap-independent ApG dinucleotide extension in vitro, indicating that the PB2 627 domain of the influenza virus RNA polymerase is not involved in core catalytic functions of the polymerase. However, in a cellular context, the 627 domain is essential for both transcription and replication. In particular, we showed that the PB2 627 domain is essential for the accumulation of the cRNA replicative intermediate in infected cells. Together, these results further our understanding of the role of the PB2 627 domain in transcription and replication of the influenza virus RNA genome. IMPORTANCE Influenza A viruses are a major global health threat, not only causing disease in both humans and birds but also placing significant strains on economies worldwide. Avian influenza A virus polymerases typically do not function efficiently in mammalian hosts and require adaptive mutations to restore polymerase activity. These adaptations include mutations in the 627 domain of the PB2 subunit of the viral polymerase, but it still remains to be established how these

  13. Bacillus anthracis TIR Domain-Containing Protein Localises to Cellular Microtubule Structures and Induces Autophagy

    PubMed Central

    Carlsson, Emil; Thwaite, Joanne E.; Jenner, Dominic C.; Spear, Abigail M.; Flick-Smith, Helen; Atkins, Helen S.; Ding, Jeak Ling

    2016-01-01

    Toll-like receptors (TLRs) recognise invading pathogens and mediate downstream immune signalling via Toll/IL-1 receptor (TIR) domains. TIR domain proteins (Tdps) have been identified in multiple pathogenic bacteria and have recently been implicated as negative regulators of host innate immune activation. A Tdp has been identified in Bacillus anthracis, the causative agent of anthrax. Here we present the first study of this protein, designated BaTdp. Recombinantly expressed and purified BaTdp TIR domain interacted with several human TIR domains, including that of the key TLR adaptor MyD88, although BaTdp expression in cultured HEK293 cells had no effect on TLR4- or TLR2- mediated immune activation. During expression in mammalian cells, BaTdp localised to microtubular networks and caused an increase in lipidated cytosolic microtubule-associated protein 1A/1B-light chain 3 (LC3), indicative of autophagosome formation. In vivo intra-nasal infection experiments in mice showed that a BaTdp knockout strain colonised host tissue faster with higher bacterial load within 4 days post-infection compared to the wild type B. anthracis. Taken together, these findings indicate that BaTdp does not play an immune suppressive role, but rather, its absence increases virulence. BaTdp present in wild type B. anthracis plausibly interact with the infected host cell, which undergoes autophagy in self-defence. PMID:27391310

  14. Bacillus anthracis TIR Domain-Containing Protein Localises to Cellular Microtubule Structures and Induces Autophagy.

    PubMed

    Carlsson, Emil; Thwaite, Joanne E; Jenner, Dominic C; Spear, Abigail M; Flick-Smith, Helen; Atkins, Helen S; Byrne, Bernadette; Ding, Jeak Ling

    2016-01-01

    Toll-like receptors (TLRs) recognise invading pathogens and mediate downstream immune signalling via Toll/IL-1 receptor (TIR) domains. TIR domain proteins (Tdps) have been identified in multiple pathogenic bacteria and have recently been implicated as negative regulators of host innate immune activation. A Tdp has been identified in Bacillus anthracis, the causative agent of anthrax. Here we present the first study of this protein, designated BaTdp. Recombinantly expressed and purified BaTdp TIR domain interacted with several human TIR domains, including that of the key TLR adaptor MyD88, although BaTdp expression in cultured HEK293 cells had no effect on TLR4- or TLR2- mediated immune activation. During expression in mammalian cells, BaTdp localised to microtubular networks and caused an increase in lipidated cytosolic microtubule-associated protein 1A/1B-light chain 3 (LC3), indicative of autophagosome formation. In vivo intra-nasal infection experiments in mice showed that a BaTdp knockout strain colonised host tissue faster with higher bacterial load within 4 days post-infection compared to the wild type B. anthracis. Taken together, these findings indicate that BaTdp does not play an immune suppressive role, but rather, its absence increases virulence. BaTdp present in wild type B. anthracis plausibly interact with the infected host cell, which undergoes autophagy in self-defence.

  15. Host compounds for red phosphorescent OLEDs

    DOEpatents

    Xia, Chuanjun; Cheon, Kwang -Ohk

    2015-08-25

    Novel compounds containing a triphenylene moiety linked to an .alpha..beta. connected binaphthyl ring system are provided. These compounds have surprisingly good solubility in organic solvents and are useful as host compounds in red phosphorescent OLEDs.

  16. Communication between Bacteria and Their Hosts

    PubMed Central

    2013-01-01

    It is clear that a dialogue is occurring between microbes and their hosts and that chemical signals are the language of this interkingdom communication. Microbial endocrinology shows that, through their long coexistence with animals and plants, microorganisms have evolved sensors for detecting eukaryotic hormones, which the microbe uses to determine that they are within proximity of a suitable host and to optimally time the expression of genes needed for host colonisation. It has also been shown that some prokaryotic chemical communication signals are recognized by eukaryotes. Deciphering what is being said during the cross-talk between microbe and host is therefore important, as it could lead to new strategies for preventing or treating bacterial infections. PMID:24381789

  17. The virome in host health and disease

    PubMed Central

    Cadwell, Ken

    2015-01-01

    The mammalian virome includes diverse commensal and pathogenic viruses that evoke a broad range of immune responses from the host. Sustained viral immunomodulation is implicated in a variety of inflammatory diseases, but also confers unexpected benefits to the host. These outcomes of viral infections are often dependent on host genotype. Moreover, it is becoming clear that the virome is part of a dynamic network of microorganisms that inhabit the body. Therefore, viruses can be viewed as a component of the microbiome, and interactions with commensal bacteria and other microbial agents influence their behavior. In this article, our current understanding of how the virome, together with other components of the microbiome, affects the function of the host immune system to regulate health and disease is reviewed. PMID:25992857

  18. The virome in host health and disease.

    PubMed

    Cadwell, Ken

    2015-05-19

    The mammalian virome includes diverse commensal and pathogenic viruses that evoke a broad range of immune responses from the host. Sustained viral immunomodulation is implicated in a variety of inflammatory diseases, but also confers unexpected benefits to the host. These outcomes of viral infections are often dependent on host genotype. Moreover, it is becoming clear that the virome is part of a dynamic network of microorganisms that inhabit the body. Therefore, viruses can be viewed as a component of the microbiome, and interactions with commensal bacteria and other microbial agents influence their behavior. This piece is a review of our current understanding of how the virome, together with other components of the microbiome, affects the function of the host immune system to regulate health and disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Population Synthesis Modeling of QSO Host Galaxies

    NASA Astrophysics Data System (ADS)

    Wold, Isak; Sheinis, A.

    2007-12-01

    A strong connection between AGN activity and galaxy formation/evolution has emerged over the past few years. To obtain further insight into this important evolutionary phase we wish to analyze the properties of the host galaxies of AGN, using the tools of population synthesis. To this end, we investigate the utilization of simulated annealing and down-hill simplex method of optimization in the modeling of QSO host galaxy spectra. In this technique, subtraction of residual scattered quasar light in the observed spectra is performed while simultaneously modeling the constituent stellar populations of the host galaxy. The reliability of this method is tested by generating spectra with known parameters, adding noise, and measuring the correspondence between the known input and the output of the program. Preliminary results of the application of this program to data from off-nuclear host galaxy spectra via long-slit and integral field unit observations on the Keck and WIYN telescopes will be presented.

  20. Directional Selection from Host Plants Is a Major Force Driving Host Specificity in Magnaporthe Species

    PubMed Central

    Zhong, Zhenhui; Norvienyeku, Justice; Chen, Meilian; Bao, Jiandong; Lin, Lianyu; Chen, Liqiong; Lin, Yahong; Wu, Xiaoxian; Cai, Zena; Zhang, Qi; Lin, Xiaoye; Hong, Yonghe; Huang, Jun; Xu, Linghong; Zhang, Honghong; Chen, Long; Tang, Wei; Zheng, Huakun; Chen, Xiaofeng; Wang, Yanli; Lian, Bi; Zhang, Liangsheng; Tang, Haibao; Lu, Guodong; Ebbole, Daniel J.; Wang, Baohua; Wang, Zonghua

    2016-01-01

    One major threat to global food security that requires immediate attention, is the increasing incidence of host shift and host expansion in growing number of pathogenic fungi and emergence of new pathogens. The threat is more alarming because, yield quality and quantity improvement efforts are encouraging the cultivation of uniform plants with low genetic diversity that are increasingly susceptible to emerging pathogens. However, the influence of host genome differentiation on pathogen genome differentiation and its contribution to emergence and adaptability is still obscure. Here, we compared genome sequence of 6 isolates of Magnaporthe species obtained from three different host plants. We demonstrated the evolutionary relationship between Magnaporthe species and the influence of host differentiation on pathogens. Phylogenetic analysis showed that evolution of pathogen directly corresponds with host divergence, suggesting that host-pathogen interaction has led to co-evolution. Furthermore, we identified an asymmetric selection pressure on Magnaporthe species. Oryza sativa-infecting isolates showed higher directional selection from host and subsequently tends to lower the genetic diversity in its genome. We concluded that, frequent gene loss or gain, new transposon acquisition and sequence divergence are host adaptability mechanisms for Magnaporthe species, and this coevolution processes is greatly driven by directional selection from host plants. PMID:27151494

  1. Host Suitability of a Gregarious Parasitoid on Beetle Hosts: Flexibility between Fitness of Adult and Offspring

    PubMed Central

    Li, Li; Sun, Jianghua

    2011-01-01

    Behavioral tactics play a crucial role in the evolution of species and are likely to be found in host-parasitoid interactions where host quality may differ between host developmental stages. We investigated foraging decisions, parasitism and related fitness in a gregarious ectoparasitoid, Sclerodermus harmandi in relation to two distinct host developmental stages: larvae and pupae. Two colonies of parasitoids were reared on larvae of Monochamus alternatus and Saperda populnea (Cerambycidae: Lamiinae). Paired-choice and non-choice experiments were used to evaluate the preference and performance of S. harmandi on larvae and pupae of the two species. Foraging decisions and offspring fitness-related consequences of S. harmandi led to the selection of the most profitable host stage for parasitoid development. Adult females from the two colonies oviposited more quickly on pupae as compared to larvae of M. alternatus. Subsequently, their offspring development time was faster and they gained higher body weight on the pupal hosts. This study demonstrates optimal foraging of intraspecific détente that can occur during host-parasitoid interactions, of which the quality of the parasitism (highest fitness benefit and profitability) is related to the host developmental stage utilized. We conclude that S. harmandi is able to perfectly discriminate among host species or stages in a manner that maximizes its offspring fitness. The results indicated that foraging potential of adults may not be driven by its maternal effects, also induced flexibly with encountering prior host quality. PMID:21526176

  2. Temporal dynamics of outcrossing and host mortality rates in host-pathogen experimental coevolution.

    PubMed

    Morran, Levi T; Parrish, Raymond C; Gelarden, Ian A; Lively, Curtis M

    2013-07-01

    Cross-fertilization is predicted to facilitate the short-term response and the long-term persistence of host populations engaged in antagonistic coevolutionary interactions. Consistent with this idea, our previous work has shown that coevolving bacterial pathogens (Serratia marcescens) can drive obligately selfing hosts (Caenorhabditis elegans) to extinction, whereas the obligately outcrossing and partially outcrossing populations persisted. We focused the present study on the partially outcrossing (mixed mating) and obligately outcrossing hosts, and analyzed the changes in the host resistance/avoidance (and pathogen infectivity) over time. We found that host mortality rates increased in the mixed mating populations over the first 10 generations of coevolution when outcrossing rates were initially low. However, mortality rates decreased after elevated outcrossing rates evolved during the experiment. In contrast, host mortality rates decreased in the obligately outcrossing populations during the first 10 generations of coevolution, and remained low throughout the experiment. Therefore, predominant selfing reduced the ability of the hosts to respond to coevolving pathogens compared to outcrossing hosts. Thus, we found that host-pathogen coevolution can generate rapid evolutionary change, and that host mating system can influence the outcome of coevolution at a fine temporal scale. © 2012 The Author(s). Evolution © 2012 The Society for the Study of Evolution.

  3. Host suitability of a gregarious parasitoid on beetle hosts: flexibility between fitness of adult and offspring.

    PubMed

    Li, Li; Sun, Jianghua

    2011-04-19

    Behavioral tactics play a crucial role in the evolution of species and are likely to be found in host-parasitoid interactions where host quality may differ between host developmental stages. We investigated foraging decisions, parasitism and related fitness in a gregarious ectoparasitoid, Sclerodermus harmandi in relation to two distinct host developmental stages: larvae and pupae. Two colonies of parasitoids were reared on larvae of Monochamus alternatus and Saperda populnea (Cerambycidae: Lamiinae). Paired-choice and non-choice experiments were used to evaluate the preference and performance of S. harmandi on larvae and pupae of the two species. Foraging decisions and offspring fitness-related consequences of S. harmandi led to the selection of the most profitable host stage for parasitoid development. Adult females from the two colonies oviposited more quickly on pupae as compared to larvae of M. alternatus. Subsequently, their offspring development time was faster and they gained higher body weight on the pupal hosts. This study demonstrates optimal foraging of intraspecific détente that can occur during host-parasitoid interactions, of which the quality of the parasitism (highest fitness benefit and profitability) is related to the host developmental stage utilized. We conclude that S. harmandi is able to perfectly discriminate among host species or stages in a manner that maximizes its offspring fitness. The results indicated that foraging potential of adults may not be driven by its maternal effects, also induced flexibly with encountering prior host quality.

  4. Bayesian inference supports the host selection hypothesis in explaining adaptive host specificity by European bitterling.

    PubMed

    Smith, Carl

    2017-02-01

    Generalist parasites have the capacity to infect multiple hosts. The temporal pattern of host specificity by generalist parasites is rarely studied, but is critical to understanding what variables underpin infection and thereby the impact of parasites on host species and the way they impose selection on hosts. Here, the temporal dynamics of infection of four species of freshwater mussel by European bitterling fish (Rhodeus amarus) was investigated over three spawning seasons. Bitterling lay their eggs in the gills of freshwater mussels, which suffer reduced growth, oxygen stress, gill damage and elevated mortality as a result of parasitism. The temporal pattern of infection of mussels by European bitterling in multiple populations was examined. Using a Bernoulli Generalized Additive Mixed Model with Bayesian inference it was demonstrated that one mussel species, Unio pictorum, was exploited over the entire bitterling spawning season. As the season progressed, bitterling showed a preference for other mussel species, which were inferior hosts. Temporal changes in host use reflected elevated density-dependent mortality in preferred hosts that were already infected. Plasticity in host specificity by bitterling conformed with the predictions of the host selection hypothesis. The relationship between bitterling and their host mussels differs qualitatively from that of avian brood parasites.

  5. Host Reproductive Phenology Drives Seasonal Patterns of Host Use in Mosquitoes

    PubMed Central

    Burkett-Cadena, Nathan D.; McClure, Christopher J. W.; Ligon, Russell A.; Graham, Sean P.; Guyer, Craig; Hill, Geoffrey E.; Ditchkoff, Stephen S.; Eubanks, Micky D.; Hassan, Hassan K.; Unnasch, Thomas R.

    2011-01-01

    Seasonal shifts in host use by mosquitoes from birds to mammals drive the timing and intensity of annual epidemics of mosquito-borne viruses, such as West Nile virus, in North America. The biological mechanism underlying these shifts has been a matter of debate, with hypotheses falling into two camps: (1) the shift is driven by changes in host abundance, or (2) the shift is driven by seasonal changes in the foraging behavior of mosquitoes. Here we explored the idea that seasonal changes in host use by mosquitoes are driven by temporal patterns of host reproduction. We investigated the relationship between seasonal patterns of host use by mosquitoes and host reproductive phenology by examining a seven-year dataset of blood meal identifications from a site in Tuskegee National Forest, Alabama USA and data on reproduction from the most commonly utilized endothermic (white-tailed deer, great blue heron, yellow-crowned night heron) and ectothermic (frogs) hosts. Our analysis revealed that feeding on each host peaked during periods of reproductive activity. Specifically, mosquitoes utilized herons in the spring and early summer, during periods of peak nest occupancy, whereas deer were fed upon most during the late summer and fall, the period corresponding to the peak in births for deer. For frogs, however, feeding on early- and late-season breeders paralleled peaks in male vocalization. We demonstrate for the first time that seasonal patterns of host use by mosquitoes track the reproductive phenology of the hosts. Peaks in relative mosquito feeding on each host during reproductive phases are likely the result of increased tolerance and decreased vigilance to attacking mosquitoes by nestlings and brooding adults (avian hosts), quiescent young (avian and mammalian hosts), and mate-seeking males (frogs). PMID:21408172

  6. Host Density and Competency Determine the Effects of Host Diversity on Trematode Parasite Infection

    PubMed Central

    Wojdak, Jeremy M.; Edman, Robert M.; Wyderko, Jennie A.; Zemmer, Sally A.; Belden, Lisa K.

    2014-01-01

    Variation in host species composition can dramatically alter parasite transmission in natural communities. Whether diverse host communities dilute or amplify parasite transmission is thought to depend critically on species traits, particularly on how hosts affect each other’s densities, and their relative competency as hosts. Here we studied a community of potential hosts and/or decoys (i.e. non-competent hosts) for two trematode parasite species, Echinostoma trivolvis and Ribeiroia ondatrae, which commonly infect wildlife across North America. We manipulated the density of a focal host (green frog tadpoles, Rana clamitans), in concert with manipulating the diversity of alternative species, to simulate communities where alternative species either (1) replace the focal host species so that the total number of individuals remains constant (substitution) or (2) add to total host density (addition). For E. trivolvis, we found that total parasite transmission remained roughly equal (or perhaps decreased slightly) when alternative species replaced focal host individuals, but parasite transmission was higher when alternative species were added to a community without replacing focal host individuals. Given the alternative species were roughly equal in competency, these results are consistent with current theory. Remarkably, both total tadpole and per-capita tadpole infection intensity by E. trivolvis increased with increasing intraspecific host density. For R. ondatrae, alternative species did not function as effective decoys or hosts for parasite infective stages, and the diversity and density treatments did not produce clear changes in parasite transmission, although high tank to tank variation in R. ondatrae infection could have obscured patterns. PMID:25119568

  7. Mesoscale spatiotemporal variability in a complex host-parasite system influenced by intermediate host body size

    PubMed Central

    2017-01-01

    Background Parasites are essential components of natural communities, but the factors that generate skewed distributions of parasite occurrences and abundances across host populations are not well understood. Methods Here, we analyse at a seascape scale the spatiotemporal relationships of parasite exposure and host body-size with the proportion of infected hosts (i.e., prevalence) and aggregation of parasite burden across ca. 150 km of the coast and over 22 months. We predicted that the effects of parasite exposure on prevalence and aggregation are dependent on host body-sizes. We used an indirect host-parasite interaction in which migratory seagulls, sandy-shore molecrabs, and an acanthocephalan worm constitute the definitive hosts, intermediate hosts, and endoparasite, respectively. In such complex systems, increments in the abundance of definitive hosts imply increments in intermediate hosts’ exposure to the parasite’s dispersive stages. Results Linear mixed-effects models showed a significant, albeit highly variable, positive relationship between seagull density and prevalence. This relationship was stronger for small (cephalothorax length >15 mm) than large molecrabs (<15 mm). Independently of seagull density, large molecrabs carried significantly more parasites than small molecrabs. The analysis of the variance-to-mean ratio of per capita parasite burden showed no relationship between seagull density and mean parasite aggregation across host populations. However, the amount of unexplained variability in aggregation was strikingly higher in larger than smaller intermediate hosts. This unexplained variability was driven by a decrease in the mean-variance scaling in heavily infected large molecrabs. Conclusions These results show complex interdependencies between extrinsic and intrinsic population attributes on the structure of host-parasite interactions. We suggest that parasite accumulation—a characteristic of indirect host-parasite interactions

  8. Signaling in host-associated microbial communities

    PubMed Central

    Fischbach, Michael A.; Segre, Julia A.

    2016-01-01

    Human-associated microbiota form and stabilize communities based on interspecies interactions. We review how these microbe-microbe and microbe-host interactions are communicated to shape communities over a human’s lifespan, including periods of health and disease. Modeling and dissecting signaling in host-associated communities is crucial to understand their function, and will open the door to therapies that prevent or correct microbial community dysfunction to promote health and treat disease. PMID:26967294

  9. Ultramafic-Hosted Talc-Magnesite Deposits

    USGS Publications Warehouse

    Robinson,, Gilpin R.; Van Gosen, Bradley S.; Foley, Nora K.

    2006-01-01

    This presentation on the geology of ultramafic-hosted talc-magnesite deposits was given at the 42nd Forum on the Geology of Industrial Minerals, May 7-13, 2006, in Asheville, North Carolina (USA). Talc is a soft inert industrial mineral commodity commonly used as a component or filler in ceramic, paint, paper, plastic, roofing, and electrical applications. Ultramafic-hosted talc-magnesite deposits are important sources of talc.

  10. Apparent brightness distribution of GRB host galaxies

    NASA Astrophysics Data System (ADS)

    Bagoly, Zsolt; Racz, Istvan; Gyorgy Balazs, Lajos; Toth, Viktor; Horvath, Istvan

    2015-08-01

    We studied the relationship between the Swift GRB data and the optical brightness of the host galaxy measured by the Keck telescope. We calculated the unbiased distribution of the host's optical brightness by making use the survival analysis. Based on the sample obtained from merging the Swift GRB table and the Keck optical data we studied also the dependence of this distribution on the GRB's data.

  11. Summary of laser speckle photogrammetry for HOST

    NASA Technical Reports Server (NTRS)

    Pollack, Frank G.

    1986-01-01

    High temperature static strain measurement capability is important for the success of the HOST program. As part of the NASA Lewis effort to develop the technology for improved hot-section durability, the HOST instrumentation program has, as a major goal, the development of methods for measuring strain at high temperature. Development work includes both improvements in resistance strain-gauge technology and, as an alternative approach, the development of optical techniques for high temperature strain measurement.

  12. Protein Complex Production in Alternative Prokaryotic Hosts.

    PubMed

    Gómez, Sara; López-Estepa, Miguel; Fernández, Francisco J; Vega, M Cristina

    2016-01-01

    Research for multiprotein expression in nonconventional bacterial and archaeal expression systems aims to exploit particular properties of "alternative" prokaryotic hosts that might make them more efficient than E. coli for particular applications, especially in those areas where more conventional bacterial hosts traditionally do not perform well. Currently, a wide range of products with clinical or industrial application have to be isolated from their native source, often microorganisms whose growth present numerous problems owing to very slow growth phenotypes or because they are unculturable under laboratory conditions. In those cases, transfer of the gene pathway responsible for synthesizing the product of interest into a suitable recombinant host becomes an attractive alternative solution. Despite many efforts dedicated to improving E. coli systems due to low cost, ease of use, and its dominant position as a ubiquitous expression host model, many alternative prokaryotic systems have been developed for heterologous protein expression mostly for biotechnological applications. Continuous research has led to improvements in expression yield through these non-conventional models, including Pseudomonas, Streptomyces and Mycobacterium as alternative bacterial expression hosts. Advantageous properties shared by these systems include low costs, high levels of secreted protein products and their safety of use, with non-pathogenic strains been commercialized. In addition, the use of extremophilic and halotolerant archaea as expression hosts has to be considered as a potential tool for the production of mammalian membrane proteins such as GPCRs.

  13. Host immune responses accelerate pathogen evolution

    PubMed Central

    Trivedi, Pankaj; Wang, Nian

    2014-01-01

    Pathogens face a hostile and often novel environment when infecting a new host, and adaptation is likely to be an important determinant of the success in colonization and establishment. We hypothesized that resistant hosts will impose stronger selection on pathogens than susceptible hosts, which should accelerate pathogen evolution through selection biased toward effector genes. To test this hypothesis, we conducted an experimental evolution study on Xanthomonas citri subsp. citri (Xcc) in a susceptible plant species and a resistant plant species. We performed 55 rounds of repeated reinoculation of Xcc through susceptible host grapefruit (isolates G1, G2, G3) and resistant host kumquat (isolates K1, K2, K3). Consequently, only K1 and K3 isolates lost their ability to elicit a hypersensitive response (HR) in kumquat. Illumina sequencing of the parental and descendant strains P, G1, G2, G3, K1, K2 and K3 revealed that fixed mutations were biased toward type three secretion system effectors in isolates K1 and K3. Parallel evolution was observed in the K1 and K3 strains, suggesting that the mutations result from selection rather than by random drift. Our results support our hypothesis and suggest that repeated infection of resistant hosts by pathogens should be prevented to avoid selecting for adaptive pathogens. PMID:24304673

  14. Allelic variation contributes to bacterial host specificity

    SciTech Connect

    Yue, Min; Han, Xiangan; Masi, Leon De; Zhu, Chunhong; Ma, Xun; Zhang, Junjie; Wu, Renwei; Schmieder, Robert; Kaushik, Radhey S.; Fraser, George P.; Zhao, Shaohua; McDermott, Patrick F.; Weill, François-Xavier; Mainil, Jacques G.; Arze, Cesar; Fricke, W. Florian; Edwards, Robert A.; Brisson, Dustin; Zhang, Nancy R.; Rankin, Shelley C.; Schifferli, Dieter M.

    2015-10-30

    Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population and functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. In conclusion, together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.

  15. Allelic variation contributes to bacterial host specificity

    DOE PAGES

    Yue, Min; Han, Xiangan; Masi, Leon De; ...

    2015-10-30

    Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population andmore » functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. In conclusion, together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.« less

  16. Direct imaging of topological edge states at a bilayer graphene domain wall.

    PubMed

    Yin, Long-Jing; Jiang, Hua; Qiao, Jia-Bin; He, Lin

    2016-06-17

    The AB-BA domain wall in gapped graphene bilayers is a rare naked structure hosting topological electronic states. Although it has been extensively studied in theory, a direct imaging of its topological edge states is still missing. Here we image the topological edge states at the graphene bilayer domain wall by using scanning tunnelling microscope. The simultaneously obtained atomic-resolution images of the domain wall provide us unprecedented opportunities to measure the spatially varying edge states within it. The one-dimensional conducting channels are observed to be mainly located around the two edges of the domain wall, which is reproduced quite well by our theoretical calculations. Our experiment further demonstrates that the one-dimensional topological states are quite robust even in the presence of high magnetic fields. The result reported here may raise hopes of graphene-based electronics with ultra-low dissipation.

  17. The crystal structure of PD1, a Haemophilus surface fibril domain

    PubMed Central

    Wright, Jack; Thomsen, Maren; Kolodziejczyk, Robert; Ridley, Joshua; Carrington, Glenn; Singh, Birendra; Riesbeck, Kristian; Goldman, Adrian

    2017-01-01

    The Haemophilus surface fibril (Hsf) is an unusually large trimeric autotransporter adhesin (TAA) expressed by the most virulent strains of H. influenzae. Hsf is known to mediate adhesion between pathogen and host, allowing the establishment of potentially deadly diseases such as epiglottitis, meningitis and pneumonia. While recent research has suggested that this TAA might adopt a novel ‘hairpin-like’ architecture, the characterization of Hsf has been limited to in silico modelling and electron micrographs, with no high-resolution structural data available. Here, the crystal structure of Hsf putative domain 1 (PD1) is reported at 3.3 Å resolution. The structure corrects the previous domain annotation by revealing the presence of an unexpected N-terminal TrpRing domain. PD1 represents the first Hsf domain to be solved, and thus paves the way for further research on the ‘hairpin-like’ hypothesis. PMID:28177321

  18. Versatile TPR domains accommodate different modes of target protein recognition and function.

    PubMed

    Allan, Rudi Kenneth; Ratajczak, Thomas

    2011-07-01

    The tetratricopeptide repeat (TPR) motif is one of many repeat motifs that form structural domains in proteins that can act as interaction scaffolds in the formation of multi-protein complexes involved in numerous cellular processes such as transcription, the cell cycle, protein translocation, protein degradation and host defence against invading pathogens. The crystal structures of many TPR domain-containing proteins have been determined, showing TPR motifs as two anti-parallel α-helices packed in tandem arrays to form a structure with an amphipathic groove which can bind a target peptide. This is however not the only mode of target recognition by TPR domains, with short amino acid insertions and alternative TPR motif conformations also shown to contribute to protein interactions, highlighting diversity in TPR domains and the versatility of this structure in mediating biological events.

  19. Molecular characterization of host-parasite cell signalling in Schistosoma mansoni during early development

    PubMed Central

    Ressurreição, Margarida; Elbeyioglu, Firat; Kirk, Ruth S.; Rollinson, David; Emery, Aidan M.; Page, Nigel M.; Walker, Anthony J.

    2016-01-01

    During infection of their human definitive host, schistosomes transform rapidly from free-swimming infective cercariae in freshwater to endoparasitic schistosomules. The ‘somules’ next migrate within the skin to access the vasculature and are surrounded by host molecules that might activate intracellular pathways that influence somule survival, development and/or behaviour. However, such ‘transactivation’ by host factors in schistosomes is not well defined. In the present study, we have characterized and functionally localized the dynamics of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) activation during early somule development in vitro and demonstrate activation of these protein kinases by human epidermal growth factor, insulin, and insulin-like growth factor I, particularly at the parasite surface. Further, we provide evidence that support the existence of specialized signalling domains called lipid rafts in schistosomes and propose that correct signalling to ERK requires proper raft organization. Finally, we show that modulation of PKC and ERK activities in somules affects motility and reduces somule survival. Thus, PKC and ERK are important mediators of host-ligand regulated transactivation events in schistosomes, and represent potential targets for anti-schistosome therapy aimed at reducing parasite survival in the human host. PMID:27762399

  20. Accidental genetic engineers: horizontal sequence transfer from parasitoid wasps to their Lepidopteran hosts.

    PubMed

    Schneider, Sean E; Thomas, James H

    2014-01-01

    We show here that 105 regions in two Lepidoptera genomes appear to derive from horizontally transferred wasp DNA. We experimentally verified the presence of two of these sequences in a diverse set of silkworm (Bombyx mori) genomes. We hypothesize that these horizontal transfers are made possible by the unusual strategy many parasitoid wasps employ of injecting hosts with endosymbiotic polydnaviruses to minimize the host's defense response. Because these virus-like particles deliver wasp DNA to the cells of the host, there has been much interest in whether genetic information can be permanently transferred from the wasp to the host. Two transferred sequences code for a BEN domain, known to be associated with polydnaviruses and transcriptional regulation. These findings represent the first documented cases of horizontal transfer of genes between two organisms by a polydnavirus. This presents an interesting evolutionary paradigm in which host species can acquire new sequences from parasitoid wasps that attack them. Hymenoptera and Lepidoptera diverged ∼300 MYA, making this type of event a source of novel sequences for recipient species. Unlike many other cases of horizontal transfer between two eukaryote species, these sequence transfers can be explained without the need to invoke the sequences 'hitchhiking' on a third organism (e.g. retrovirus) capable of independent reproduction. The cellular machinery necessary for the transfer is contained entirely in the wasp genome. The work presented here is the first such discovery of what is likely to be a broader phenomenon among species affected by these wasps.

  1. An internal thioester in a pathogen surface protein mediates covalent host binding

    PubMed Central

    Walden, Miriam; Edwards, John M; Dziewulska, Aleksandra M; Bergmann, Rene; Saalbach, Gerhard; Kan, Su-Yin; Miller, Ona K; Weckener, Miriam; Jackson, Rosemary J; Shirran, Sally L; Botting, Catherine H; Florence, Gordon J; Rohde, Manfred; Banfield, Mark J; Schwarz-Linek, Ulrich

    2015-01-01

    To cause disease and persist in a host, pathogenic and commensal microbes must adhere to tissues. Colonization and infection depend on specific molecular interactions at the host-microbe interface that involve microbial surface proteins, or adhesins. To date, adhesins are only known to bind to host receptors non-covalently. Here we show that the streptococcal surface protein SfbI mediates covalent interaction with the host protein fibrinogen using an unusual internal thioester bond as a ‘chemical harpoon’. This cross-linking reaction allows bacterial attachment to fibrin and SfbI binding to human cells in a model of inflammation. Thioester-containing domains are unexpectedly prevalent in Gram-positive bacteria, including many clinically relevant pathogens. Our findings support bacterial-encoded covalent binding as a new molecular principle in host-microbe interactions. This represents an as yet unexploited target to treat bacterial infection and may also offer novel opportunities for engineering beneficial interactions. DOI: http://dx.doi.org/10.7554/eLife.06638.001 PMID:26032562

  2. Insights into the selective pressures restricting Pelargonium flower break virus genome variability: Evidence for host adaptation.

    PubMed

    Rico, Patricia; Ivars, Pilar; Elena, Santiago F; Hernández, Carmen

    2006-08-01

    The molecular diversity of Pelargonium flower break virus (PFBV) was assessed using a collection of isolates from different geographical origins, hosts, and collecting times. The genomic region examined was 1,828 nucleotides (nt) long and comprised the coding sequences for the movement (p7 and p12) and the coat (CP) proteins, as well as flanking segments including the entire 3' untranslated region (3' UTR). Some constraints limiting viral heterogeneity could be inferred from sequence analyses, such as the conservation of the amino acid sequences of p7 and of the shell domain of the CP, the maintenance of a leucine zipper motif in p12, and the preservation of a particular folding in the 3' UTR. A remarkable covariation, involving five specific amino acid sites, was found in the CP of isolates largely propagated in the local lesion host Chenopodium quinoa and in the progeny of a PFBV variant subjected to serial passages in this host. Concomitant with this covariation, up to 30 nucleotide substitutions in a 1,428-nt region of the viral RNA could be attributable to C. quinoa-specific adaptation, representing one of the most outstanding cases of host-driven genome variation for a plant virus. Globally, the results indicate that the selective pressures exerted by the host play a critical role in shaping PFBV populations and that these populations are likely being selected for at both protein and RNA levels.

  3. Phosphorylation state-dependent interactions of hepadnavirus core protein with host factors.

    PubMed

    Ludgate, Laurie; Adams, Christina; Hu, Jianming

    2011-01-01

    Dynamic phosphorylation and dephosphorylation of the hepadnavirus core protein C-terminal domain (CTD) are required for multiple steps of the viral life cycle. It remains unknown how the CTD phosphorylation state may modulate core protein functions but phosphorylation state-dependent viral or host interactions may play a role. In an attempt to identify host factors that may interact differentially with the core protein depending on its CTD phosphorylation state, pulldown assays were performed using the CTD of the duck hepatitis B virus (DHBV) and human hepatitis B virus (HBV) core protein, either with wild type (WT) sequences or with alanine or aspartic acid substitutions at the phosphorylation sites. Two host proteins, B23 and I2PP2A, were found to interact preferentially with the alanine-substituted CTD. Furthermore, the WT CTD became competent to interact with the host proteins upon dephosphorylation. Intriguingly, the binding site on the DHBV CTD for both B23 and I2PP2A was mapped to a region upstream of the phosphorylation sites even though B23 or I2PP2A binding to this site was clearly modulated by the phosphorylation state of the downstream and non-overlapping sequences. Together, these results demonstrate a novel mode of phosphorylation-regulated protein-protein interaction and provide new insights into virus-host interactions. © 2011 Ludgate et al.

  4. Phosphorylation State-Dependent Interactions of Hepadnavirus Core Protein with Host Factors

    PubMed Central

    Ludgate, Laurie; Adams, Christina; Hu, Jianming

    2011-01-01

    Dynamic phosphorylation and dephosphorylation of the hepadnavirus core protein C-terminal domain (CTD) are required for multiple steps of the viral life cycle. It remains unknown how the CTD phosphorylation state may modulate core protein functions but phosphorylation state-dependent viral or host interactions may play a role. In an attempt to identify host factors that may interact differentially with the core protein depending on its CTD phosphorylation state, pulldown assays were performed using the CTD of the duck hepatitis B virus (DHBV) and human hepatitis B virus (HBV) core protein, either with wild type (WT) sequences or with alanine or aspartic acid substitutions at the phosphorylation sites. Two host proteins, B23 and I2PP2A, were found to interact preferentially with the alanine-substituted CTD. Furthermore, the WT CTD became competent to interact with the host proteins upon dephosphorylation. Intriguingly, the binding site on the DHBV CTD for both B23 and I2PP2A was mapped to a region upstream of the phosphorylation sites even though B23 or I2PP2A binding to this site was clearly modulated by the phosphorylation state of the downstream and non-overlapping sequences. Together, these results demonstrate a novel mode of phosphorylation-regulated protein-protein interaction and provide new insights into virus-host interactions. PMID:22216318

  5. Interactions between the host innate immune system and microbes in inflammatory bowel disease.

    PubMed

    Abraham, Clara; Medzhitov, Ruslan

    2011-05-01

    The intestinal immune system defends against pathogens and entry of excessive intestinal microbes; simultaneously, a state of immune tolerance to resident intestinal microbes must be maintained. Perturbation of this balance is associated with intestinal inflammation in various mouse models and is thought to predispose humans to inflammatory bowel disease (IBD). The innate immune system senses microbes; dendritic cells, macrophages, and epithelial cells produce an initial, rapid response. The immune system continuously monitors resident microbiota and utilizes constitutive antimicrobial mechanisms to maintain immune homeostasis. associations between IBD and genes that regulate microbial recognition and innate immune pathways, such as nucleotide oligomerization domain 2 (Nod2), genes that control autophagy (eg, ATG16L1, IRGM), and genes in the interleukin-23-T helper cell 17 pathway indicate the important roles of host-microbe interactions in regulating intestinal immune homeostasis. There is increasing evidence that intestinal microbes influence host immune development, immune responses, and susceptibility to human diseases such as IBD, diabetes mellitus, and obesity. Conversely, host factors can affect microbes, which in turn modulate disease susceptibility. We review the cell populations and mechanisms that mediate interactions between host defense and tolerance and how the dysregulation of host-microbe interactions leads to intestinal inflammation and IBD.

  6. The Potential for Hosted Payloads at NASA

    NASA Technical Reports Server (NTRS)

    Andraschko, Mark; Antol, Jeffrey; Baize, Rosemary; Horan, Stephen; Neil, Doreen; Rinsland, Pamela; Zaiceva, Rita

    2012-01-01

    The 2010 National Space Policy encourages federal agencies to actively explore the use of inventive, nontraditional arrangements for acquiring commercial space goods and services to meet United States Government requirements, including...hosting government capabilities on commercial spacecraft. NASA's Science Mission Directorate has taken an important step towards this goal by adding an option for hosted payload responses to its recent Announcement of Opportunity (AO) for Earth Venture-2 missions. Since NASA selects a significant portion of its science missions through a competitive process, it is useful to understand the implications that this process has on the feasibility of successfully proposing a commercially hosted payload mission. This paper describes some of the impediments associated with proposing a hosted payload mission to NASA, and offers suggestions on how these impediments might be addressed. Commercially hosted payloads provide a novel way to serve the needs of the science and technology demonstration communities at a fraction of the cost of a traditional Geostationary Earth Orbit (GEO) mission. The commercial communications industry launches over 20 satellites to GEO each year. By exercising this repeatable commercial paradigm of privately financed access to space with proven vendors, NASA can achieve science goals at a significantly lower cost than the current dedicated spacecraft and launch vehicle approach affords. Commercial hosting could open up a new realm of opportunities for NASA science missions to make measurements from GEO. This paper also briefly describes two GEO missions recommended by the National Academies of Science Earth Science Decadal Survey, the Geostationary Coastal and Air Pollution Events (GEO-CAPE) mission and the Precipitation and All-weather Temperature and Humidity (PATH) mission. Hosted payload missions recently selected for implementation by the Office of the Chief Technologist are also discussed. Finally, there are

  7. Local host adaptation and use of a novel host in the seed beetle Megacerus eulophus.

    PubMed

    Stotz, Gisela C; Suárez, Lorena H; Gonzáles, Wilfredo L; Gianoli, Ernesto

    2013-01-01

    Spatial variation in host plant availability may lead to specialization in host use and local host adaptation in herbivorous insects, which may involve a cost in performance on other hosts. We studied two geographically separated populations of the seed beetle Megacerus eulophus (Coleoptera: Bruchidae) in central Chile: a population from the host Convolvulus chilensis (in Aucó) and a population from C. bonariensis (in Algarrobo). In Aucó C. chilensis is the only host plant, while in Algarrobo both C. bonariensis and C. chilensis are available. We tested local adaptation to these native host plants and its influence on the use of another, exotic host plant. We hypothesized that local adaptation would be verified, particularly for the one-host population (Aucó), and that the Aucó population would be less able to use an alternative, high-quality host. We found evidence of local adaptation in the population from C. chilensis. Thus, when reared on C. chilensis, adults from the C. chilensis population were larger and lived longer than individuals from the C. bonariensis population, while bruchids from the two populations had the same body size and longevity when reared on C. bonariensis. Overall, bruchids from the C. chilensis population showed greater performance traits than those from the C. bonariensis population. There were no differences between the bruchid populations in their ability to use the alternative, exotic host Calystegia sepium, as shown by body size and longevity patterns. Results suggest that differences in local adaptation might be explained by differential host availability in the study populations.

  8. [Relationships between host preference of Liriomyza huidobrensis (Blanchard) and nutrient and chlorophyll contents in host foliage].

    PubMed

    Gao, Jun-Ping; Pang, Bao-Ping; Meng, Rui-Xia; Wang, Juan

    2007-03-01

    The laboratory study with no free choice means showed that the host preference of Liriomyza huidobrensis (Blanchard) adult differed significantly with test plants. Phaseolus vulgaris, Chrysanthemum coronarium and Cucurbita pepo were the most preferred, while Lycopersicum esculenturn and Brassica oleracea were the least. Correlative analysis indicated that the host preference of L. huidobrensis adult had a significant positive correlation with the content of soluble sugar, but less correlation with soluble protein and chlorophyll contents in host foliage.

  9. Local Host Adaptation and Use of a Novel Host in the Seed Beetle Megacerus eulophus

    PubMed Central

    Stotz, Gisela C.; Suárez, Lorena H.; Gonzáles, Wilfredo L.; Gianoli, Ernesto

    2013-01-01

    Spatial variation in host plant availability may lead to specialization in host use and local host adaptation in herbivorous insects, which may involve a cost in performance on other hosts. We studied two geographically separated populations of the seed beetle Megacerus eulophus (Coleoptera: Bruchidae) in central Chile: a population from the host Convolvulus chilensis (in Aucó) and a population from C. bonariensis (in Algarrobo). In Aucó C. chilensis is the only host plant, while in Algarrobo both C. bonariensis and C. chilensis are available. We tested local adaptation to these native host plants and its influence on the use of another, exotic host plant. We hypothesized that local adaptation would be verified, particularly for the one-host population (Aucó), and that the Aucó population would be less able to use an alternative, high-quality host. We found evidence of local adaptation in the population from C. chilensis. Thus, when reared on C. chilensis, adults from the C. chilensis population were larger and lived longer than individuals from the C. bonariensis population, while bruchids from the two populations had the same body size and longevity when reared on C. bonariensis. Overall, bruchids from the C. chilensis population showed greater performance traits than those from the C. bonariensis population. There were no differences between the bruchid populations in their ability to use the alternative, exotic host Calystegia sepium, as shown by body size and longevity patterns. Results suggest that differences in local adaptation might be explained by differential host availability in the study populations. PMID:23326528

  10. DIMA 3.0: Domain Interaction Map.

    PubMed

    Luo, Qibin; Pagel, Philipp; Vilne, Baiba; Frishman, Dmitrij

    2011-01-01

    Domain Interaction MAp (DIMA, available at http://webclu.bio.wzw.tum.de/dima) is a database of predicted and known interactions between protein domains. It integrates 5807 structurally known interactions imported from the iPfam and 3did databases and 46,900 domain interactions predicted by four computational methods: domain phylogenetic profiling, domain pair exclusion algorithm correlated mutations and domain interaction prediction in a discriminative way. Additionally predictions are filtered to exclude those domain pairs that are reported as non-interacting by the Negatome database. The DIMA Web site allows to calculate domain interaction networks either for a domain of interest or for entire organisms, and to explore them interactively using the Flash-based Cytoscape Web software.

  11. Certifying Domain-Specific Policies

    NASA Technical Reports Server (NTRS)

    Lowry, Michael; Pressburger, Thomas; Rosu, Grigore; Koga, Dennis (Technical Monitor)

    2001-01-01

    Proof-checking code for compliance to safety policies potentially enables a product-oriented approach to certain aspects of software certification. To date, previous research has focused on generic, low-level programming-language properties such as memory type safety. In this paper we consider proof-checking higher-level domain -specific properties for compliance to safety policies. The paper first describes a framework related to abstract interpretation in which compliance to a class of certification policies can be efficiently calculated Membership equational logic is shown to provide a rich logic for carrying out such calculations, including partiality, for certification. The architecture for a domain-specific certifier is described, followed by an implemented case study. The case study considers consistency of abstract variable attributes in code that performs geometric calculations in Aerospace systems.

  12. Frequency domain optical parametric amplification

    PubMed Central

    Schmidt, Bruno E.; Thiré, Nicolas; Boivin, Maxime; Laramée, Antoine; Poitras, François; Lebrun, Guy; Ozaki, Tsuneyuki; Ibrahim, Heide; Légaré, François

    2014-01-01

    Today’s ultrafast lasers operate at the physical limits of optical materials to reach extreme performances. Amplification of single-cycle laser pulses with their corresponding octave-spanning spectra still remains a formidable challenge since the universal dilemma of gain narrowing sets limits for both real level pumped amplifiers as well as parametric amplifiers. We demonstrate that employing parametric amplification in the frequency domain rather than in time domain opens up new design opportunities for ultrafast laser science, with the potential to generate single-cycle multi-terawatt pulses. Fundamental restrictions arising from phase mismatch and damage threshold of nonlinear laser crystals are not only circumvented but also exploited to produce a synergy between increased seed spectrum and increased pump energy. This concept was successfully demonstrated by generating carrier envelope phase stable, 1.43 mJ two-cycle pulses at 1.8 μm wavelength. PMID:24805968

  13. Domain decomposition methods in aerodynamics

    NASA Technical Reports Server (NTRS)

    Venkatakrishnan, V.; Saltz, Joel

    1990-01-01

    Compressible Euler equations are solved for two-dimensional problems by a preconditioned conjugate gradient-like technique. An approximate Riemann solver is used to compute the numerical fluxes to second order accuracy in space. Two ways to achieve parallelism are tested, one which makes use of parallelism inherent in triangular solves and the other which employs domain decomposition techniques. The vectorization/parallelism in triangular solves is realized by the use of a recording technique called wavefront ordering. This process involves the interpretation of the triangular matrix as a directed graph and the analysis of the data dependencies. It is noted that the factorization can also be done in parallel with the wave front ordering. The performances of two ways of partitioning the domain, strips and slabs, are compared. Results on Cray YMP are reported for an inviscid transonic test case. The performances of linear algebra kernels are also reported.

  14. Gabor domain optical coherence microscopy

    NASA Astrophysics Data System (ADS)

    Murali, Supraja

    Time domain Optical Coherence Tomography (TD-OCT), first reported in 1991, makes use of the low temporal coherence properties of a NIR broadband laser to create depth sectioning of up to 2mm under the surface using optical interferometry and point to point scanning. Prior and ongoing work in OCT in the research community has concentrated on improving axial resolution through the development of broadband sources and speed of image acquisition through new techniques such as Spectral domain OCT (SD-OCT). In SD-OCT, an entire depth scan is acquired at once with a low numerical aperture (NA) objective lens focused at a fixed point within the sample. In this imaging geometry, a longer depth of focus is achieved at the expense of lateral resolution, which is typically limited to 10 to 20 mum. Optical Coherence Microscopy (OCM), introduced in 1994, combined the advantages of high axial resolution obtained in OCT with high lateral resolution obtained by increasing the NA of the microscope placed in the sample arm. However, OCM presented trade-offs caused by the inverse quadratic relationship between the NA and the DOF of the optics used. For applications requiring high lateral resolution, such as cancer diagnostics, several solutions have been proposed including the periodic manual re-focusing of the objective lens in the time domain as well as the spectral domain C-mode configuration in order to overcome the loss in lateral resolution outside the DOF. In this research, we report for the first time, high speed, sub-cellular imaging (lateral resolution of 2 mum) in OCM using a Gabor domain image processing algorithm with a custom designed and fabricated dynamic focus microscope interfaced to a Ti:Sa femtosecond laser centered at 800 nm within an SD-OCM configuration. It is envisioned that this technology will provide a non-invasive replacement for the current practice of multiple biopsies for skin cancer diagnosis. The research reported here presents three important advances

  15. Structure of Streptococcus agalactiae tip pilin GBS104: a model for GBS pili assembly and host interactions

    SciTech Connect

    Krishnan, Vengadesan; Dwivedi, Prabhat; Kim, Brandon J.; Samal, Alexandra; Macon, Kevin; Ma, Xin; Mishra, Arunima; Doran, Kelly S.; Ton-That, Hung; Narayana, Sthanam V. L.

    2013-06-01

    The crystal structure of a 75 kDa central fragment of GBS104, a tip pilin from the 2063V/R strain of Streptococcus agalactiae (group B streptococcus; GBS), is reported. The crystal structure of a 75 kDa central fragment of GBS104, a tip pilin from the 2063V/R strain of Streptococcus agalactiae (group B streptococcus; GBS), is reported. In addition, a homology model of the remaining two domains of GBS104 was built and a model of full-length GBS104 was generated by combining the homology model (the N1 and N4 domains) and the crystal structure of the 75 kDa fragment (the N2 and N3 domains). This rod-shaped GBS104 model is constructed of three IgG-like domains (the N1, N2 and N4 domains) and one vWFA-like domain (the N3 domain). The N1 and N2 domains of GBS104 are assembled with distinct and remote segments contributed by the N- and C-termini. The metal-binding site in the N3 domain of GBS104 is in the closed/low-affinity conformation. Interestingly, this domain hosts two long arms that project away from the metal-binding site. Using site-directed mutagenesis, two cysteine residues that lock the N3 domain of GBS104 into the open/high-affinity conformation were introduced. Both wild-type and disulfide-locked recombinant proteins were tested for binding to extracellular matrix proteins such as collagen, fibronectin, fibrinogen and laminin, and an increase in fibronectin binding affinity was identified for the disulfide-locked N3 domain, suggesting that induced conformational changes may play a possible role in receptor binding.

  16. Domain Processes in Ferroelectric Ceramics

    DTIC Science & Technology

    1994-04-14

    WALLS Electron holography utilizing the wave characteristics of electrons. Through a sharp emission tip, the emitted electron beam is largely coherent, or...mirostructural modulation at 25% doping. The strongly first order ferroelectric phase transition in PbTiO3 is also gradually changed to a nearly second...a new domain configuraton. 13 The end-member of the PZT solid solution, PbTiO3 , has the highest transition temperature (Tc = 490 °C) and the largest

  17. Flexible time domain averaging technique

    NASA Astrophysics Data System (ADS)

    Zhao, Ming; Lin, Jing; Lei, Yaguo; Wang, Xiufeng

    2013-09-01

    Time domain averaging(TDA) is essentially a comb filter, it cannot extract the specified harmonics which may be caused by some faults, such as gear eccentric. Meanwhile, TDA always suffers from period cutting error(PCE) to different extent. Several improved TDA methods have been proposed, however they cannot completely eliminate the waveform reconstruction error caused by PCE. In order to overcome the shortcomings of conventional methods, a flexible time domain averaging(FTDA) technique is established, which adapts to the analyzed signal through adjusting each harmonic of the comb filter. In this technique, the explicit form of FTDA is first constructed by frequency domain sampling. Subsequently, chirp Z-transform(CZT) is employed in the algorithm of FTDA, which can improve the calculating efficiency significantly. Since the signal is reconstructed in the continuous time domain, there is no PCE in the FTDA. To validate the effectiveness of FTDA in the signal de-noising, interpolation and harmonic reconstruction, a simulated multi-components periodic signal that corrupted by noise is processed by FTDA. The simulation results show that the FTDA is capable of recovering the periodic components from the background noise effectively. Moreover, it can improve the signal-to-noise ratio by 7.9 dB compared with conventional ones. Experiments are also carried out on gearbox test rigs with chipped tooth and eccentricity gear, respectively. It is shown that the FTDA can identify the direction and severity of the eccentricity gear, and further enhances the amplitudes of impulses by 35%. The proposed technique not only solves the problem of PCE, but also provides a useful tool for the fault symptom extraction of rotating machinery.

  18. InfoDOMAIN. Fall 2011

    DTIC Science & Technology

    2011-09-01

    magazine of Navy Cyber Forces that promotes the advancement of Information Dominance through an open exchange of better practices, tactics, and... Information Dominance Corps is central to that effort. For the Department of Defense and the Navy to operate freely within the cyber domain, we must...Officer (CIO) Division on the staff of the Deputy Chief of Naval Operations for Information Dominance (OPNAV N2/N6). Fleet assignments include combat

  19. Escalation of the Space Domain

    DTIC Science & Technology

    2015-04-01

    whether close or open . The close blockade for space operations equates to preventing the deployment of systems from launch facilities and to interfering...obliges the adversary either to submit or fight. In contrast, a more capable space power can impose an open blockade, occupying or interfering with the...other domains the aperture begins to open on how space fits within full spectrum dominance. Space and Full Spectrum Dominance Joint Vision 2020

  20. Building Credible Cross Domain Operators

    DTIC Science & Technology

    2010-04-01

    Clark (POL) AP-E290 C-IED Lecture (POL) Lunch Transition AFA Guest Speaker (POL) Tuskegee Airmen (POL) Transition Lunch Combined Operations Week...domain integration and operators. However, today‟s Airmen are being shortchanged the essential education to develop critical thinking skills necessary...Air Service leaders recognized the need to educate airmen in air doctrine and concepts of aviation. The first air-minded school was called the Air

  1. Maneuver from the Air Domain

    DTIC Science & Technology

    2016-05-26

    cognitive maneuver mechanisms developed in the 1980s as part of broader maneuver warfare theory. The result is a proposed definition of maneuver from the...air power employment and results from two case studies - Operation Rolling Thunder and Operation Iraqi Freedom - support that the proposed definition is...question – what is maneuver from the air domain? Simply placing the doctrinal definition of maneuver in an air power context is not enough. Ultimately

  2. Life sciences domain analysis model

    PubMed Central

    Freimuth, Robert R; Freund, Elaine T; Schick, Lisa; Sharma, Mukesh K; Stafford, Grace A; Suzek, Baris E; Hernandez, Joyce; Hipp, Jason; Kelley, Jenny M; Rokicki, Konrad; Pan, Sue; Buckler, Andrew; Stokes, Todd H; Fernandez, Anna; Fore, Ian; Buetow, Kenneth H

    2012-01-01

    Objective Meaningful exchange of information is a fundamental challenge in collaborative biomedical research. To help address this, the authors developed the Life Sciences Domain Analysis Model (LS DAM), an information model that provides a framework for communication among domain experts and technical teams developing information systems to support biomedical research. The LS DAM is harmonized with the Biomedical Research Integrated Domain Group (BRIDG) model of protocol-driven clinical research. Together, these models can facilitate data exchange for translational research. Materials and methods The content of the LS DAM was driven by analysis of life sciences and translational research scenarios and the concepts in the model are derived from existing information models, reference models and data exchange formats. The model is represented in the Unified Modeling Language and uses ISO 21090 data types. Results The LS DAM v2.2.1 is comprised of 130 classes and covers several core areas including Experiment, Molecular Biology, Molecular Databases and Specimen. Nearly half of these classes originate from the BRIDG model, emphasizing the semantic harmonization between these models. Validation of the LS DAM against independently derived information models, research scenarios and reference databases supports its general applicability to represent life sciences research. Discussion The LS DAM provides unambiguous definitions for concepts required to describe life sciences research. The processes established to achieve consensus among domain experts will be applied in future iterations and may be broadly applicable to other standardization efforts. Conclusions The LS DAM provides common semantics for life sciences research. Through harmonization with BRIDG, it promotes interoperability in translational science. PMID:22744959

  3. Dynamic optical frequency domain reflectometry.

    PubMed

    Arbel, Dror; Eyal, Avishay

    2014-04-21

    We describe a dynamic Optical Frequency Domain Reflectometry (OFDR) system which enables real time, long range, acoustic sensing at high sampling rate. The system is based on a fast scanning laser and coherent detection scheme. Distributed sensing is obtained by probing the Rayleigh backscattered light. The system was tested by interrogation of a 10 km communication type single mode fiber and successfully detected localized impulse and sinusoidal excitations.

  4. Host plant utilization, host range oscillations and diversification in nymphalid butterflies: a phylogenetic investigation.

    PubMed

    Nylin, Sören; Slove, Jessica; Janz, Niklas

    2014-01-01

    It has been suggested that phenotypic plasticity is a major factor in the diversification of life, and that variation in host range in phytophagous insects is a good model for investigating this claim. We explore the use of angiosperm plants as hosts for nymphalid butterflies, and in particular the evidence for past oscillations in host range and how they are linked to host shifts and to diversification. At the level of orders of plants, a relatively simple pattern of host use and host shifts emerges, despite the 100 million years of history of the family Nymphalidae. We review the evidence that these host shifts and the accompanying diversifications were associated with transient polyphagous stages, as suggested by the "oscillation hypothesis." In addition, we investigate all currently polyphagous nymphalid species and demonstrate that the state of polyphagy is rare, has a weak phylogenetic signal, and a very apical distribution in the phylogeny; we argue that these are signs of its transient nature. We contrast our results with data from the bark beetles Dendroctonus, in which a more specialized host use is instead the apical state. We conclude that plasticity in host use is likely to have contributed to diversification in nymphalid butterflies.

  5. Co-extinction in a host-parasite network: identifying key hosts for network stability.

    PubMed

    Dallas, Tad; Cornelius, Emily

    2015-08-17

    Parasites comprise a substantial portion of total biodiversity. Ultimately, this means that host extinction could result in many secondary extinctions of obligate parasites and potentially alter host-parasite network structure. Here, we examined a highly resolved fish-parasite network to determine key hosts responsible for maintaining parasite diversity and network structure (quantified here as nestedness and modularity). We evaluated four possible host extinction orders and compared the resulting co-extinction dynamics to random extinction simulations; including host removal based on estimated extinction risk, parasite species richness and host level contributions to nestedness and modularity. We found that all extinction orders, except the one based on realistic extinction risk, resulted in faster declines in parasite diversity and network structure relative to random biodiversity loss. Further, we determined species-level contributions to network structure were best predicted by parasite species richness and host family. Taken together, we demonstrate that a small proportion of hosts contribute substantially to network structure and that removal of these hosts results in rapid declines in parasite diversity and network structure. As network stability can potentially be inferred through measures of network structure, our findings may provide insight into species traits that confer stability.

  6. HOST PLANT UTILIZATION, HOST RANGE OSCILLATIONS AND DIVERSIFICATION IN NYMPHALID BUTTERFLIES: A PHYLOGENETIC INVESTIGATION

    PubMed Central

    Nylin, Sören; Slove, Jessica; Janz, Niklas

    2014-01-01

    It has been suggested that phenotypic plasticity is a major factor in the diversification of life, and that variation in host range in phytophagous insects is a good model for investigating this claim. We explore the use of angiosperm plants as hosts for nymphalid butterflies, and in particular the evidence for past oscillations in host range and how they are linked to host shifts and to diversification. At the level of orders of plants, a relatively simple pattern of host use and host shifts emerges, despite the 100 million years of history of the family Nymphalidae. We review the evidence that these host shifts and the accompanying diversifications were associated with transient polyphagous stages, as suggested by the “oscillation hypothesis.” In addition, we investigate all currently polyphagous nymphalid species and demonstrate that the state of polyphagy is rare, has a weak phylogenetic signal, and a very apical distribution in the phylogeny; we argue that these are signs of its transient nature. We contrast our results with data from the bark beetles Dendroctonus, in which a more specialized host use is instead the apical state. We conclude that plasticity in host use is likely to have contributed to diversification in nymphalid butterflies. PMID:24372598

  7. A parasite's modification of host behavior reduces predation on its host.

    PubMed

    Soghigian, John; Valsdottir, Linda R; Livdahl, Todd P

    2017-03-01

    Parasite modification of host behavior is common, and the literature is dominated by demonstrations of enhanced predation on parasitized prey resulting in transmission of parasites to their next host. We present a case in which predation on parasitized prey is reduced. Despite theoretical modeling suggesting that this phenomenon should be common, it has been reported in only a few host-parasite-predator systems. Using a system of gregarine endosymbionts in host mosquitoes, we designed experiments to compare the vulnerability of parasitized and unparasitized mosquito larvae to predation by obligate predatory mosquito larvae and then compared behavioral features known to change in the presence of predatory cues. We exposed Aedes triseriatus larvae to the parasite Ascogregarina barretti and the predator Toxohrynchites rutilus and assessed larval mortality rate under each treatment condition. Further, we assessed behavioral differences in larvae due to infection and predation stimuli by recording larvae and scoring behaviors and positions within microcosms. Infection with gregarines reduced cohort mortality in the presence of the predator, but the parasite did not affect mortality alone. Further, infection by parasites altered behavior such that infected hosts thrashed less frequently than uninfected hosts and were found more frequently on or in a refuge within the microcosm. By reducing predation on their host, gregarines may be acting as mutualists in the presence of predation on their hosts. These results illustrate a higher-order interaction, in which a relationship between a species pair (host-endosymbiont or predator-prey) is altered by the presence of a third species.

  8. Subharmonic Fourier domain mode locking.

    PubMed

    Eigenwillig, Christoph M; Wieser, Wolfgang; Biedermann, Benjamin R; Huber, Robert

    2009-03-15

    We demonstrate a subharmonically Fourier domain mode-locked wavelength-swept laser source with a substantially reduced cavity fiber length. In contrast to a standard Fourier domain mode-locked configuration, light is recirculated repetitively in the delay line with the optical bandpass filter used as switch. The laser has a fundamental optical round trip frequency of 285 kHz and can be operated at integer fractions thereof (subharmonics). Sweep ranges up to 95 nm full width centred at 1317 nm are achieved at the 1/5th subharmonic. A maximum sensitivity of 116 dB and an axial resolution of 12 microm in air are measured at an average sweep power of 12 mW. A sensitivity roll-off of 11 dB over 4 mm and 25 dB over 10 mm is observed and optical coherence tomography imaging is demonstrated. Besides the advantage of a reduced fiber length, subharmonic Fourier domain mode locking (shFDML) enables simple scaling of the sweep speed by extracting light from the delay part of the resonator. A sweep rate of 570 kHz is achieved. Characteristic features of shFDML operation, such as power leakage during fly-back and cw breakthrough, are investigated.

  9. Mapping knowledge domains: Characterizing PNAS

    PubMed Central

    Boyack, Kevin W.

    2004-01-01

    A review of data mining and analysis techniques that can be used for the mapping of knowledge domains is given. Literature mapping techniques can be based on authors, documents, journals, words, and/or indicators. Most mapping questions are related to research assessment or to the structure and dynamics of disciplines or networks. Several mapping techniques are demonstrated on a data set comprising 20 years of papers published in PNAS. Data from a variety of sources are merged to provide unique indicators of the domain bounded by PNAS. By using funding source information and citation counts, it is shown that, on an aggregate basis, papers funded jointly by the U.S. Public Health Service (which includes the National Institutes of Health) and non-U.S. government sources outperform papers funded by other sources, including by the U.S. Public Health Service alone. Grant data from the National Institute on Aging show that, on average, papers from large grants are cited more than those from small grants, with performance increasing with grant amount. A map of the highest performing papers over the 20-year period was generated by using citation analysis. Changes and trends in the subjects of highest impact within the PNAS domain are described. Interactions between topics over the most recent 5-year period are also detailed. PMID:14963238

  10. Nicotinic Receptor Fourth Transmembrane Domain

    PubMed Central

    Bouzat, Cecilia; Barrantes, Francisco; Sine, Steven

    2000-01-01

    The fourth transmembrane domain (M4) of the nicotinic acetylcholine receptor (AChR) contributes to the kinetics of activation, yet its close association with the lipid bilayer makes it the outermost of the transmembrane domains. To investigate mechanistic and structural contributions of M4 to AChR activation, we systematically mutated αT422, a conserved residue that has been labeled by hydrophobic probes, and evaluated changes in rate constants underlying ACh binding and channel gating steps. Aromatic and nonpolar mutations of αT422 selectively affect the channel gating step, slowing the rate of opening two- to sevenfold, and speeding the rate of closing four- to ninefold. Additionally, kinetic modeling shows a second doubly liganded open state for aromatic and nonpolar mutations. In contrast, serine and asparagine mutations of αT422 largely preserve the kinetics of the wild-type AChR. Thus, rapid and efficient gating of the AChR channel depends on a hydrogen bond involving the side chain at position 422 of the M4 transmembrane domain. PMID:10779322

  11. Domain Relaxation in Langmuir Films

    NASA Astrophysics Data System (ADS)

    Bernoff, Andrew J.; Alexander, James C.; Mann, Elizabeth K.; Mann, J. Adin; Zou, Lu; Wintersmith, Jacob R.

    2007-11-01

    We report on an experimental, theoretical and computational study of a molecularly thin polymer Langmuir layer domain on the surface of a subfluid. When stretched (by a transient stagnation flow), the Langmuir layer takes the form of a bola consisting of two roughly circular reservoirs connected by a thin tether. This shape relaxes to the circular minimum energy configuration. The tether is never observed to rupture, even when it is more than a hundred times as long as it is thin. We model these experiments as a free boundary problem where motion is driven by the line tension of the domain and damped by the viscosity of the subfluid. We process the digital images of the experiment to extract the domain shape, use one of these shapes as an initial condition for the numerical solution of a boundary-integral model of the underlying hydrodynamics, and compare the subsequent images of the experiment to the numerical simulation. The numerical evolutions verify that our hydrodynamical model can reproduce the observed dynamics. They also allow us to deduce the magnitude of the line tension in the system, often to within 1%.

  12. [Parasite-host relationships and treatment].

    PubMed

    Vuitton, Dominique-Angèle; Mantion, Georges; Bartholomot, Brigitte; Giraudoux, Patrick; Bresson-Hadni, Solange

    2008-01-01

    Alveolar echinococcosis (AE) is a parasitic disease caused by intrahepatic growth of the larval stage of the cestode Echinococcus multilocularis. The main definitive host in Europe is the fox. The adult worms live in the fox intestine and their oncospheres are disseminated by faeces. Wolves, dogs and cats may also serve as definitive hosts. Small rodents--especially voles in Europe and small lagomorphs in Asia--are the natural intermediate hosts. The tumour-like larva is composed of multiple vesicles which produce protoscoleces, the fertile stage of the E. multilocularis metacestode. Carnivores are infected by preying on infected rodents. Like rodents, humans are intermediate hosts and are infected either by eating uncooked vegetables and berries contaminated by faeces of infected carnivores, or by touching such animals. Humans are naturally resistant to metacestode development. Genetic characteristics are involved in susceptibility/resistance to E. multilocularis metacestodes. In humans and other intermediate animal hosts, immune suppression enhances parasite growth, which is normally controlled by cytotoxic mechanisms and delayed-type hypersensitivity. Tolerance of E. multilocularis is due in part to parasite characteristics (especially carbohydrate antigens of the laminated layer) and in part to the "anti-inflammatory/tolerogenic" cytokines IL-10 and TGF-beta. Treatment with interferon-a restores a cytokine balance favorable to the host and might be a new therapeutic option for AE patients. Vaccination is a scientifically sound but economically and politically Utopian means of preventing the disease. Prevention thus relies on simple lifestyle measures: cooking potentially contaminated food, regular treatment of domestic animals with praziquantel, and precautions when touching potentially infected definitive hosts (foxes and dogs).

  13. The Case for GEO Hosted SSA Payloads

    NASA Astrophysics Data System (ADS)

    Welsch, C.; Armand, B.; Repp, M.; Robinson, A.

    2014-09-01

    Space situational awareness (SSA) in the geosynchronous earth orbit (GEO) belt presents unique challenges, and given the national importance and high value of GEO satellites, is increasingly critical as space becomes more congested and contested. Space situational awareness capabilities can serve as an effective deterrent against potential adversaries if they provide accurate, timely, and persistent information and are resilient to the threat environment. This paper will demonstrate how simple optical SSA payloads hosted on GEO commercial and government satellites can complement the SSA mission and data provided by Space-Based Space Surveillance (SBSS) and the Geosynchronous Space Situational Awareness Program (GSSAP). GSSAP is built by Orbital Sciences Corporation and launched on July 28, 2014. Analysis performed for this paper will show how GEO hosted SSA payloads, working in combination with SBSS and GSSAP, can increase persistence and timely coverage of high value assets in the GEO belt. The potential to further increase GEO object identification and tracking accuracy by integrating SSA data from multiple sources across different viewing angles including GEO hosted SSA sources will be addressed. Hosting SSA payloads on GEO platforms also increases SSA mission architecture resiliency as the sensors are by distributed across multiple platforms including commercial platforms. This distributed architecture presents a challenging target for an adversary to attempt to degrade or disable. We will present a viable concept of operations to show how data from hosted SSA sensors could be integrated with SBSS and GSSAP data to present a comprehensive and more accurate data set to users. Lastly, we will present an acquisition approach using commercial practices and building on lessons learned from the Commercially Hosted Infra Red Payload CHIRP to demonstrate the affordability of GEO hosted SSA payloads.

  14. Spectroscopy of Kepler Candidate Exoplanet Host Stars

    NASA Astrophysics Data System (ADS)

    Everett, Mark E.; Howell, Steve B.; Silva, David R.; Szkody, Paula

    2014-02-01

    Currently the NASA Kepler Mission has identified 3449 exoplanet candidates, one third with estimated radii R_p<2.5R_oplus and orbiting faint (m_Kep>14.5) host stars. The NASA sponsored Kepler Follow-up Program is focusing on small exoplanet candidates (R_p<2.5R_oplus) and those in habitable zone orbits. Planet radii estimates depend on estimates of host star radii. Based on spectra previously obtained at the KPNO Mayall 4-m for 220 stars with candidate exoplanets, Everett et al. (2013) have shown that many host stars are larger than originally assumed (up to factor of 2). Therefore, the exoplanet candidates they host must be larger than originally assumed, which conversely reduces the number of known Earth- sized exoplanet candidates. Determination of the frequency of such Earth-sized planets is a cornerstone Kepler mission objective and of keen general interest. These Mayall spectra were also used to confirm the Buchhave et al. (2012) result that exoplanet candidates larger than 4R_oplus in short-period orbits are preferentially associated with host stars with solar or higher metallicity, using a fainter and larger sample of stars than Buchhave et al. In short, followup Mayall optical spectroscopy is critical to confirming the detection of Earth-sized exoplanets, a Kepler cornerstone goal, as well as characterizing the relationship between host star properties and planetary system properties. Here, we propose to continue our reconnaissance survey with a focus on the smallest (most rare) exoplanet candidates orbiting the faintest Kepler host stars.

  15. Host Galaxies of z=4 Quasars

    NASA Astrophysics Data System (ADS)

    McLeod, Kim K.; Bechtold, J.

    2010-01-01

    We have undertaken a project to investigate the host galaxies and environments of a sample of quasars at z 4. In this paper, we describe deep near-infrared imaging of 34 targets using the Magellan I and Gemini North telescopes. We discuss in detail special challenges of distortion and nonlinearity that must be addressed when performing PSF subtraction with data from these telescopes and their IR cameras, especially in very good seeing. We derive black hole masses from emission-line spectroscopy, and we calculate accretion rates from our Ks-band photometry, which directly samples the rest-frame B for these objects. We introduce a new isophotal diameter technique for estimating host galaxy luminosities. We report the detection of four host galaxies on our deepest, sharpest images, and present upper limits for the others. We find that if host galaxies passively evolve such that they brighten by 2 magnitudes or more in the rest-frame B band between the present and z=4, then high-z hosts are less massive at a given black hole mass than are their low-z counterparts. We argue that the most massive hosts plateau at < 10L*. We estimate the importance of selection effects on this survey and the subsequent limitations of our conclusions. These results are in broad agreement with recent semi-analytical models for the formation of luminous quasars and their host spheroids by mergers of gas-rich galaxies, with significant dissipation, and self-regulation of black hole growth and star-formation by the burst of merger-induced quasar activity.

  16. BC-box protein domain-related mechanism for VHL protein degradation

    PubMed Central

    Pozzebon, Maria Elena; Varadaraj, Archana; Mattoscio, Domenico; Jaffray, Ellis G.; Miccolo, Claudia; Galimberti, Viviana; Tommasino, Massimo; Hay, Ronald T.; Chiocca, Susanna

    2013-01-01

    The tumor suppressor VHL (von Hippel–Lindau) protein is a substrate receptor for Ubiquitin Cullin Ring Ligase complexes (CRLs), containing a BC-box domain that associates to the adaptor Elongin B/C. VHL targets hypoxia-inducible factor 1α to proteasome-dependent degradation. Gam1 is an adenoviral protein, which also possesses a BC-box domain that interacts with the host Elongin B/C, thereby acting as a viral substrate receptor. Gam1 associates with both Cullin2 and Cullin5 to form CRL complexes targeting the host protein SUMO enzyme SAE1 for proteasomal degradation. We show that Gam1 protein expression induces VHL protein degradation leading to hypoxia-inducible factor 1α stabilization and induction of its downstream targets. We also characterize the CRL-dependent mechanism that drives VHL protein degradation via proteasome. Interestingly, expression of Suppressor of Cytokine Signaling (SOCS) domain-containing viral proteins and cellular BC-box proteins leads to VHL protein degradation, in a SOCS domain-containing manner. Our work underscores the exquisite ability of viral domains to uncover new regulatory mechanisms by hijacking key cellular proteins. PMID:24145437

  17. Cooperative folding of intrinsically disordered domains drives assembly of a strong elongated protein

    PubMed Central

    Gruszka, Dominika T.; Whelan, Fiona; Farrance, Oliver E.; Fung, Herman K. H.; Paci, Emanuele; Jeffries, Cy M.; Svergun, Dmitri I.; Baldock, Clair; Baumann, Christoph G.; Brockwell, David J.; Potts, Jennifer R.; Clarke, Jane

    2015-01-01

    Bacteria exploit surface proteins to adhere to other bacteria, surfaces and host cells. Such proteins need to project away from the bacterial surface and resist significant mechanical forces. SasG is a protein that forms extended fibrils on the surface of Staphylococcus aureus and promotes host adherence and biofilm formation. Here we show that although monomeric and lacking covalent cross-links, SasG maintains a highly extended conformation in solution. This extension is mediated through obligate folding cooperativity of the intrinsically disordered E domains that couple non-adjacent G5 domains thermodynamically, forming interfaces that are more stable than the domains themselves. Thus, counterintuitively, the elongation of the protein appears to be dependent on the inherent instability of its domains. The remarkable mechanical strength of SasG arises from tandemly arrayed ‘clamp' motifs within the folded domains. Our findings reveal an elegant minimal solution for the assembly of monomeric mechano-resistant tethers of variable length. PMID:26027519

  18. Cross-Domain Network Fault Localization

    DTIC Science & Technology

    2009-06-01

    digest, or simply digest, for Gi. • Gj = ( n ] i6=j f(Gi) ) ] Gj , where j is a domain performing cross-domain inference and ] is a model-specific union... Gj is the cross-domain model integrating the digests from all the other domains with domain j’s undigested graph. Now, domain j may use an existing...algorithm such as SHRINK to perform inference over Gj . Before a practical graph digest design can be implemented, interoperability standards must be

  19. Evidence for a Structural Relationship between BRCT Domains and the Helicase Domains of the Replication Initiators Encoded by the Polyomaviridae and Papillomaviridae Families of DNA Tumor Viruses▿ †

    PubMed Central

    Kumar, Anuradha; Joo, Woo S.; Meinke, Gretchen; Moine, Stephanie; Naumova, Elena N.; Bullock, Peter A.

    2008-01-01

    Studies of DNA tumor viruses have provided important insights into fundamental cellular processes and oncogenic transformation. They have revealed, for example, that upon expression of virally encoded proteins, cellular pathways involved in DNA repair and cell cycle control are disrupted. Herein, evidence is presented that BRCT-related regions are present in the helicase domains of the viral initiators encoded by the Polyomaviridae and Papillomaviridae viral families. Of interest, BRCT domains in cellular proteins recruit factors involved in diverse pathways, including DNA repair and the regulation of cell cycle progression. Therefore, the viral BRCT-related regions may compete with host BRCT domains for particular cellular ligands, a process that would help to explain the pleiotropic effects associated with infections with many DNA tumor viruses. PMID:18579587

  20. Crystal Structure of a Bacterial Albumin-Binding Domain at 1.4 Angstrom Resolution

    SciTech Connect

    Cramer, J.F.; Nordberg, P.A.; Hajdu, J.; Lejon, S.; /Uppsala U. /Aalborg U. /Astra Tech, Molndal /SLAC

    2007-11-26

    The albumin-binding domain, or GA module, of the peptostreptococcal albumin-binding protein expressed in pathogenic strains of Finegoldia magna is believed to be responsible for the virulence and increased growth rate of these strains. Here we present the 1.4 Angstrom crystal structure of this domain, and compare it with the crystal structure of the GA-albumin complex. An analysis of protein-protein interactions in the two crystals, and the presence of multimeric GA species in solution, indicate the GA module is 'sticky', and is capable of forming contacts with a range of protein surfaces. This might lead to interactions with different host proteins.

  1. Dengue Virus Subverts Host Innate Immunity by Targeting Adaptor Protein MAVS

    PubMed Central

    He, Zhenjian; Zhu, Xun; Wen, Weitao; Yuan, Jie; Hu, Yiwen; Chen, Jiahui; An, Shu; Dong, Xinhuai; Lin, Cuiji; Yu, Jianchen; Wu, Jueheng; Yang, Yi; Cai, Junchao; Li, Jun

    2016-01-01

    ABSTRACT Dengue virus (DENV) is the most common mosquito-borne virus infecting humans and is currently a serious global health challenge. To establish infection in its host cells, DENV must subvert the production and/or antiviral effects of interferon (IFN). The aim of this study was to understand the mechanisms by which DENV suppresses IFN production. We determined that DENV NS4A interacts with mitochondrial antiviral signaling protein (MAVS), which was previously found to activate NF-κB and IFN regulatory factor 3 (IRF3), thus inducing type I IFN in the mitochondrion-associated endoplasmic reticulum membranes (MAMs). We further demonstrated that NS4A is associated with the N-terminal CARD-like (CL) domain and the C-terminal transmembrane (TM) domain of MAVS. This association prevented the binding of MAVS to RIG-I, resulting in the repression of RIG-I-induced IRF3 activation and, consequently, the abrogation of IFN production. Collectively, our findings illustrate a new molecular mechanism by which DENV evades the host immune system and suggest new targets for anti-DENV strategies. IMPORTANCE Type I interferon (IFN) constitutes the first line of host defense against invading viruses. To successfully establish infection, dengue virus (DENV) must counteract either the production or the function of IFN. The mechanism by which DENV suppresses IFN production is poorly understood and characterized. In this study, we demonstrate that the DENV NS4A protein plays an important role in suppressing interferon production through binding MAVS and disrupting the RIG-I–MAVS interaction in mitochondrion-associated endoplasmic reticulum membranes (MAMs). Our study reveals that MAVS is a novel host target of NS4A and provides a molecular mechanism for DENV evasion of the host innate immune response. These findings have important implications for understanding the pathogenesis of DENV and may provide new insights into using NS4A as a therapeutic and/or prevention target. PMID

  2. Host-Parasitoid Dynamics and the Success of Biological Control When Parasitoids Are Prone to Allee Effects

    PubMed Central

    Bompard, Anaïs; Amat, Isabelle; Fauvergue, Xavier; Spataro, Thierry

    2013-01-01

    In sexual organisms, low population density can result in mating failures and subsequently yields a low population growth rate and high chance of extinction. For species that are in tight interaction, as in host-parasitoid systems, population dynamics are primarily constrained by demographic interdependences, so that mating failures may have much more intricate consequences. Our main objective is to study the demographic consequences of parasitoid mating failures at low density and its consequences on the success of biological control. For this, we developed a deterministic host-parasitoid model with a mate-finding Allee effect, allowing to tackle interactions between the Allee effect and key determinants of host-parasitoid demography such as the distribution of parasitoid attacks and host competition. Our study shows that parasitoid mating failures at low density result in an extinction threshold and increase the domain of parasitoid deterministic extinction. When proned to mate finding difficulties, parasitoids with cyclic dynamics or low searching efficiency go extinct; parasitoids with high searching efficiency may either persist or go extinct, depending on host intraspecific competition. We show that parasitoids suitable as biocontrol agents for their ability to reduce host populations are particularly likely to suffer from mate-finding Allee effects. This study highlights novel perspectives for understanding of the dynamics observed in natural host-parasitoid systems and improving the success of parasitoid introductions. PMID:24116153

  3. Identification of host proteins, Spata3 and Dkk2, interacting with Toxoplasma gondii micronemal protein MIC3.

    PubMed

    Wang, Yifan; Fang, Rui; Yuan, Yuan; Pan, Ming; Hu, Min; Zhou, Yanqin; Shen, Bang; Zhao, Junlong

    2016-07-01

    As an obligate intracellular protozoan, Toxoplasma gondii is a successful pathogen infecting a variety of animals, including humans. As an adhesin involving in host invasion, the micronemal protein MIC3 plays important roles in host cell attachment, as well as modulation of host EGFR signaling cascade. However, the specific host proteins that interact with MIC3 are unknown and the identification of such proteins will increase our understanding of how MIC3 exerts its functions. This study was designed to identify host proteins interacting with MIC3 by yeast two-hybrid screens. Using MIC3 as bait, a library expressing mouse proteins was screened, uncovering eight mouse proteins that showed positive interactions with MIC3. Two of which, spermatogenesis-associated protein 3 (Spata3) and dickkopf-related protein 2 (Dkk2), were further confirmed to interact with MIC3 by additional protein-protein interaction tests. The results also revealed that the tandem repeat EGF domains of MIC3 were critical in mediating the interactions with the identified host proteins. This is the first study to show that MIC3 interacts with host proteins that are involved in reproduction, growth, and development. The results will provide a clearer understanding of the functions of adhesion-associated micronemal proteins in T. gondii.

  4. Large-scale identification of Legionella pneumophila Dot/Icm substrates that modulate host cell vesicle trafficking pathways.

    PubMed

    Heidtman, Matthew; Chen, Emy J; Moy, Man-Yu; Isberg, Ralph R

    2009-02-01

    The bacterial pathogen Legionella pneumophila replicates in a specialized vacuole within host cells. Establishment of the replication vacuole depends on the Dot/Icm translocation system that delivers a large number of protein substrates into the host cell. The functions of most substrates are unknown. Here, we analysed a defined set of 127 confirmed or candidate Dot/Icm substrates for their effect on host cell processes using yeast as a model system. Expression of 79 candidates caused significant yeast growth defects, indicating that these proteins impact essential host cell pathways. Notably, a group of 21 candidates interfered with the trafficking of secretory proteins to the yeast vacuole. Three candidates that caused yeast secretory defects (SetA, Ceg19 and Ceg9) were investigated further. These proteins impinged upon vesicle trafficking at distinct stages and had signals that allowed translocation into host cells by the Dot/Icm system. Ectopically produced SetA, Ceg19 and Ceg9 localized to secretory organelles in mammalian cells, consistent with a role for these proteins in modulating host cell vesicle trafficking. Interestingly, the ability of SetA to cause yeast phenotypes was dependent upon a functional glycosyltransferase domain. We hypothesize that SetA may glycosylate a component of the host cell vesicle trafficking machinery during L. pneumophila infection.

  5. Large scale identification of Legionella pneumophila Dot/Icm substrates that modulate host cell vesicle trafficking pathways

    PubMed Central

    Heidtman, Matthew; Chen, Emy J.; Moy, Man-Yu; Isberg, Ralph R.

    2009-01-01

    The bacterial pathogen Legionella pneumophila replicates in a specialized vacuole within host cells. Establishment of the replication vacuole depends on the Dot/Icm translocation system that delivers a large number of protein substrates into the host cell. The functions of most substrates are unknown. Here, we analyzed a defined set of 127 confirmed or candidate Dot/Icm substrates for their effect on host cell processes using yeast as a model system. Expression of 79 candidates caused significant yeast growth defects, indicating these proteins impact essential host cell pathways. Notably, a group of 21 candidates interfered with the trafficking of secretory proteins to the yeast vacuole. Three candidates that caused yeast secretory defects (SetA, Ceg19 and Ceg9) were investigated further. These proteins impinged upon vesicle trafficking at distinct stages and had signals that allowed translocation into host cells by the Dot/Icm system. Ectopically produced SetA, Ceg19 and Ceg9 localized to secretory organelles in mammalian cells, consistent with a role for these proteins in modulating host cell vesicle trafficking. Interestingly, the ability of SetA to cause yeast phenotypes was dependent upon a functional glycosyltransferase domain. We hypothesize that SetA may glycosylate a component of the host cell vesicle trafficking machinery during L. pneumophila infection. PMID:19016775

  6. Virus-Host Coevolution: Common Patterns of Nucleotide Motif Usage in Flaviviridae and Their Hosts

    PubMed Central

    Lobo, Francisco P.; Mota, Bruno E. F.; Pena, Sérgio D. J.; Azevedo, Vasco; Macedo, Andréa M.; Tauch, Andreas; Machado, Carlos R.; Franco, Glória R.

    2009-01-01

    Virus-host biological interaction is a continuous coevolutionary process involving both host immune system and viral escape mechanisms. Flaviviridae family is composed of fast evolving RNA viruses that infects vertebrate (mammals and birds) and/or invertebrate (ticks and mosquitoes) organisms. These host groups are very distinct life forms separated by a long evolutionary time, so lineage-specific anti-viral mechanisms are likely to have evolved. Flaviviridae viruses which infect a single host lineage would be subjected to specific host-induced pressures and, therefore, selected by them. In this work we compare the genomic evolutionary patterns of Flaviviridae viruses and their hosts in an attempt to uncover coevolutionary processes inducing common features in such disparate groups. Especially, we have analyzed dinucleotide and codon usage patterns in the coding regions of vertebrate and invertebrate organisms as well as in Flaviviridae viruses which specifically infect one or both host types. The two host groups possess very distinctive dinucleotide and codon usage patterns. A pronounced CpG under-representation was found in the vertebrate group, possibly induced by the methylation-deamination process, as well as a prominent TpA decrease. The invertebrate group displayed only a TpA frequency reduction bias. Flaviviridae viruses mimicked host nucleotide motif usage in a host-specific manner. Vertebrate-infecting viruses possessed under-representation of CpG and TpA, and insect-only viruses displayed only a TpA under-representation bias. Single-host Flaviviridae members which persistently infect mammals or insect hosts (Hepacivirus and insect-only Flavivirus, respectively) were found to posses a codon usage profile more similar to that of their hosts than to related Flaviviridae. We demonstrated that vertebrates and mosquitoes genomes are under very distinct lineage-specific constraints, and Flaviviridae viruses which specifically infect these lineages appear to be

  7. Early-Season Host Switching in Adelphocoris spp. (Hemiptera: Miridae) of Differing Host Breadth

    PubMed Central

    Pan, Hongsheng; Lu, Yanhui; Wyckhuys, Kris A. G.

    2013-01-01

    The mirid bugs Adelphocoris suturalis (Jakovlev), Adelphocoris lineolatus (Goeze) and Adelphocoris fasciaticollis (Reuter) (Hemiptera: Miridae) are common pests of several agricultural crops. These three species have vastly different geographical distributions, phenologies and abundances, all of which are linked to their reliance on local plants. Previous work has shown notable differences in Adelphocoris spp. host use for overwintering. In this study, we assessed the extent to which each of the Adelphocoris spp. relies on some of its major overwinter hosts for spring development. Over the course of four consecutive years (2009–2012), we conducted population surveys on 77 different plant species from 39 families. During the spring, A. fasciaticollis used the broadest range of hosts, as it was found on 35 plant species, followed by A. suturalis (15 species) and A. lineolatus (7 species). Abundances of the species greatly differed between host plants, with A. fasciaticollis reaching the highest abundance on Chinese date (Ziziphus jujuba Mill.), whereas both A. suturalis and A. lineolatus preferred alfalfa (Medicago sativa L.). The host breadths of the three Adelphocoris spp. differed greatly between subsequent spring and winter seasons. The generalist species exhibited the least host fidelity, with A. suturalis and A. lineolatus using 8 of 22 and 4 of 12 overwinter host species for spring development, respectively. By contrast, the comparative specialist A. fasciaticollis relied on 9 of its 11 overwinter plants as early-season hosts. We highlight important seasonal changes in host breadth and interspecific differences in the extent of host switching behavior between the winter and spring seasons. These findings benefit our understanding of the evolutionary interactions between mirid bugs and their host plants and can be used to guide early-season population management. PMID:23527069

  8. Early-season host switching in Adelphocoris spp. (Hemiptera: Miridae) of differing host breadth.

    PubMed

    Pan, Hongsheng; Lu, Yanhui; Wyckhuys, Kris A G

    2013-01-01

    The mirid bugs Adelphocoris suturalis (Jakovlev), Adelphocoris lineolatus (Goeze) and Adelphocoris fasciaticollis (Reuter) (Hemiptera: Miridae) are common pests of several agricultural crops. These three species have vastly different geographical distributions, phenologies and abundances, all of which are linked to their reliance on local plants. Previous work has shown notable differences in Adelphocoris spp. host use for overwintering. In this study, we assessed the extent to which each of the Adelphocoris spp. relies on some of its major overwinter hosts for spring development. Over the course of four consecutive years (2009-2012), we conducted population surveys on 77 different plant species from 39 families. During the spring, A. fasciaticollis used the broadest range of hosts, as it was found on 35 plant species, followed by A. suturalis (15 species) and A. lineolatus (7 species). Abundances of the species greatly differed between host plants, with A. fasciaticollis reaching the highest abundance on Chinese date (Ziziphus jujuba Mill.), whereas both A. suturalis and A. lineolatus preferred alfalfa (Medicago sativa L.). The host breadths of the three Adelphocoris spp. differed greatly between subsequent spring and winter seasons. The generalist species exhibited the least host fidelity, with A. suturalis and A. lineolatus using 8 of 22 and 4 of 12 overwinter host species for spring development, respectively. By contrast, the comparative specialist A. fasciaticollis relied on 9 of its 11 overwinter plants as early-season hosts. We highlight important seasonal changes in host breadth and interspecific differences in the extent of host switching behavior between the winter and spring seasons. These findings benefit our understanding of the evolutionary interactions between mirid bugs and their host plants and can be used to guide early-season population management.

  9. Parasitism and phenotypic change in colonial hosts.

    PubMed

    Hartikainen, Hanna; Fontes, Inês; Okamura, Beth

    2013-09-01

    Changes in host phenotype are often attributed to manipulation that enables parasites to complete trophic transmission cycles. We characterized changes in host phenotype in a colonial host–endoparasite system that lacks trophic transmission (the freshwater bryozoan Fredericella sultana and myxozoan parasite Tetracapsuloides bryosalmonae). We show that parasitism exerts opposing phenotypic effects at the colony and module levels. Thus, overt infection (the development of infectious spores in the host body cavity) was linked to a reduction in colony size and growth rate, while colony modules exhibited a form of gigantism. Larger modules may support larger parasite sacs and increase metabolite availability to the parasite. Host metabolic rates were lower in overtly infected relative to uninfected hosts that were not investing in propagule production. This suggests a role for direct resource competition and active parasite manipulation (castration) in driving the expression of the infected phenotype. The malformed offspring (statoblasts) of infected colonies had greatly reduced hatching success. Coupled with the severe reduction in statoblast production this suggests that vertical transmission is rare in overtly infected modules. We show that although the parasite can occasionally infect statoblasts during overt infections, no infections were detected in the surviving mature offspring, suggesting that during overt infections, horizontal transmission incurs a trade-off with vertical transmission.

  10. Viral antibody dynamics in a chiropteran host.

    PubMed

    Baker, Kate S; Suu-Ire, Richard; Barr, Jennifer; Hayman, David T S; Broder, Christopher C; Horton, Daniel L; Durrant, Christopher; Murcia, Pablo R; Cunningham, Andrew A; Wood, James L N

    2014-03-01

    Bats host many viruses that are significant for human and domestic animal health, but the dynamics of these infections in their natural reservoir hosts remain poorly elucidated. In these, and other, systems, there is evidence that seasonal life-cycle events drive infection dynamics, directly impacting the risk of exposure to spillover hosts. Understanding these dynamics improves our ability to predict zoonotic spillover from the reservoir hosts. To this end, we followed henipavirus antibody levels of >100 individual E. helvum in a closed, captive, breeding population over a 30-month period, using a powerful novel antibody quantitation method. We demonstrate the presence of maternal antibodies in this system and accurately determine their longevity. We also present evidence of population-level persistence of viral infection and demonstrate periods of increased horizontal virus transmission associated with the pregnancy/lactation period. The novel findings of infection persistence and the effect of pregnancy on viral transmission, as well as an accurate quantitation of chiropteran maternal antiviral antibody half-life, provide fundamental baseline data for the continued study of viral infections in these important reservoir hosts.

  11. Using lice to identify cowbird hosts

    USGS Publications Warehouse

    Hahn, D.C.; Osenton, P.C.; Price, R.W.

    1995-01-01

    Avian lice may link fledgling Brown-headed Cowbirds to the host species that raised them. Lice, if host-specific and transferred to nestling cowbirds, could serve to identify the principal host species raising cowbirds in a local area. This approach of trapping cowbird fledglings in a feeding flock, then collecting and identifying the lice they carry is economical. The alternative requires a team of people to locate large numbers of parasitized host nests. We trapped 250 cowbird fledglings during June-August 1994 on Patuxent Research Center, and from them we collected 426 lice identified as representing 6 genera and 12 species. We. also collected and identified 347 lice from 30 known host species that were mist-netted on our Center. The lice found on cowbird fledglings in this population can be linked to Wood Thrush, Red-eyed Vireo, Common Yellowthroat, Rufous-sided Towhee, Red-winged Blackbird, Common Grackle, Song Sparrow, Field Sparrow, and Tree sparrow, based on this study and also on published reports.

  12. Proteinaceous Molecules Mediating Bifidobacterium-Host Interactions

    PubMed Central

    Ruiz, Lorena; Delgado, Susana; Ruas-Madiedo, Patricia; Margolles, Abelardo; Sánchez, Borja

    2016-01-01

    Bifidobacteria are commensal microoganisms found in the gastrointestinal tract. Several strains have been attributed beneficial traits at local and systemic levels, through pathogen exclusion or immune modulation, among other benefits. This has promoted a growing industrial and scientific interest in bifidobacteria as probiotic supplements. However, the molecular mechanisms mediating this cross-talk with the human host remain unknown. High-throughput technologies, from functional genomics to transcriptomics, proteomics, and interactomics coupled to the development of both in vitro and in vivo models to study the dynamics of the intestinal microbiota and their effects on host cells, have eased the identification of key molecules in these interactions. Numerous secreted or surface-associated proteins or peptides have been identified as potential mediators of bifidobacteria-host interactions and molecular cross-talk, directly participating in sensing environmental factors, promoting intestinal colonization, or mediating a dialogue with mucosa-associated immune cells. On the other hand, bifidobacteria induce the production of proteins in the intestine, by epithelial or immune cells, and other gut bacteria, which are key elements in orchestrating interactions among bifidobacteria, gut microbiota, and host cells. This review aims to give a comprehensive overview on proteinaceous molecules described and characterized to date, as mediators of the dynamic interplay between bifidobacteria and the human host, providing a framework to identify knowledge gaps and future research needs. PMID:27536282

  13. Nocardia species: host-parasite relationships.

    PubMed Central

    Beaman, B L; Beaman, L

    1994-01-01

    The nocardiae are bacteria belonging to the aerobic actinomycetes. They are an important part of the normal soil microflora worldwide. The type species, Nocardia asteroides, and N. brasiliensis, N. farcinica, N. otitidiscaviarum, N. nova, and N. transvalensis cause a variety of diseases in both normal and immunocompromised humans and animals. The mechanisms of pathogenesis are complex, not fully understood, and include the capacity to evade or neutralize the myriad microbicidal activities of the host. The relative virulence of N. asteroides correlates with the ability to inhibit phagosome-lysosome fusion in phagocytes; to neutralize p