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Sample records for escape mutants homology

  1. Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay

    International Nuclear Information System (INIS)

    Morton, Craig J.; Cameron, Rachel; Lawrence, Lynne J.; Lin Bo; Lowe, Melinda; Luttick, Angela; Mason, Anthony; McKimm-Breschkin, Jenny; Parker, Michael W.; Ryan, Jane; Smout, Michael; Sullivan, Jayne; Tucker, Simon P.; Young, Paul R.

    2003-01-01

    Respiratory syncytial virus (RSV) is a ubiquitous human pathogen and the leading cause of lower respiratory tract infections in infants. Infection of cells and subsequent formation of syncytia occur through membrane fusion mediated by the RSV fusion protein (RSV-F). A novel in vitro assay of recombinant RSV-F function has been devised and used to characterize a number of escape mutants for three known inhibitors of RSV-F that have been isolated. Homology modeling of the RSV-F structure has been carried out on the basis of a chimera derived from the crystal structures of the RSV-F core and a fragment from the orthologous fusion protein from Newcastle disease virus (NDV). The structure correlates well with the appearance of RSV-F in electron micrographs, and the residues identified as contributing to specific binding sites for several monoclonal antibodies are arranged in appropriate solvent-accessible clusters. The positions of the characterized resistance mutants in the model structure identify two promising regions for the design of fusion inhibitors

  2. Modelling the evolution and spread of HIV immune escape mutants.

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    Helen R Fryer

    2010-11-01

    Full Text Available During infection with human immunodeficiency virus (HIV, immune pressure from cytotoxic T-lymphocytes (CTLs selects for viral mutants that confer escape from CTL recognition. These escape variants can be transmitted between individuals where, depending upon their cost to viral fitness and the CTL responses made by the recipient, they may revert. The rates of within-host evolution and their concordant impact upon the rate of spread of escape mutants at the population level are uncertain. Here we present a mathematical model of within-host evolution of escape mutants, transmission of these variants between hosts and subsequent reversion in new hosts. The model is an extension of the well-known SI model of disease transmission and includes three further parameters that describe host immunogenetic heterogeneity and rates of within host viral evolution. We use the model to explain why some escape mutants appear to have stable prevalence whilst others are spreading through the population. Further, we use it to compare diverse datasets on CTL escape, highlighting where different sources agree or disagree on within-host evolutionary rates. The several dozen CTL epitopes we survey from HIV-1 gag, RT and nef reveal a relatively sedate rate of evolution with average rates of escape measured in years and reversion in decades. For many epitopes in HIV, occasional rapid within-host evolution is not reflected in fast evolution at the population level.

  3. Genetic interactions among homologous recombination mutants in Candida albicans.

    Science.gov (United States)

    Bellido, Alberto; Andaluz, Encarnación; Gómez-Raja, Jonathan; Álvarez-Barrientos, Alberto; Larriba, Germán

    2015-01-01

    rad52-ΔΔ and, to a lesser extent, rad51-ΔΔ deletants of Candidaalbicans displayed slow growth and aberrant filamentous morphology whereas rad59-ΔΔ mutants, both by growth rate and morphology resembled wild type. In this study, we have constructed pair-wise double deletants to analyze genetic interactions among these homologous recombination (HR) proteins that affect growth and morphology traits. When grown in liquid YPD medium, double mutant rad51-ΔΔ rad59-ΔΔ exhibited growth rates, cell and colony morphologies, and plating efficiencies that were not significantly different from those observed for rad51-ΔΔ. The same was true for rad52-ΔΔ rad59-ΔΔ compared to rad52-ΔΔ. Slow growth and decreased plating efficiency were caused, at least in part, by a decreased viability, as deduced from FUN1 staining. Flow cytometry and microscopic studies of filamentous mutant populations revealed major changes in cell ploidy, size and morphology, whereas DAPI staining identified complex nuclear rearrangements in yeast and filamentous cells. These phenotypes were not observed in the rad59-ΔΔ mutant populations. Our results show that abolishing Rad51 functions induces the appearance of a subpopulation of aberrant yeast and filamentous forms with increased cell size and ploidy. The size of this complex subpopulation was exacerbated in rad52-ΔΔ mutants. The combination of filamentous cell morphology and viability phenotypes was reflected on the colony morphology of the respective mutants. We conclude that the rad52 mutation is epistatic to rad51 for all the morphological traits analyzed. We discuss these results in the light of the several functions of these recombination genes. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants

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    Rudneva, Irina A.; Timofeeva, Tatiana A.; Ignatieva, Anna V.; Shilov, Aleksandr A.; Krylov, Petr S. [D.I. Ivanovsky Institute of Virology, 123098 Moscow (Russian Federation); Ilyushina, Natalia A., E-mail: Natalia.Ilyushina@fda.hhs.gov [FDA CDER, 29 Lincoln Drive, Bethesda, MD 20892 (United States); Kaverin, Nikolai V., E-mail: nik.kaverin@gmail.com [D.I. Ivanovsky Institute of Virology, 123098 Moscow (Russian Federation)

    2013-12-15

    In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability (P<0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential. - Highlights: • HA1 N142K mutation significantly lowered the pH of fusion optimum. • Mutations located in the HA lateral loop significantly affected H5 HA thermostability. • HA changes at positions 131, 142, 144, 145, and 156 affected the replicative ability of H5 mutants. • Acquisition of glycosylation site could lead to the emergence of multiple pleiotropic effects.

  5. Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants

    International Nuclear Information System (INIS)

    Rudneva, Irina A.; Timofeeva, Tatiana A.; Ignatieva, Anna V.; Shilov, Aleksandr A.; Krylov, Petr S.; Ilyushina, Natalia A.; Kaverin, Nikolai V.

    2013-01-01

    In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability (P<0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential. - Highlights: • HA1 N142K mutation significantly lowered the pH of fusion optimum. • Mutations located in the HA lateral loop significantly affected H5 HA thermostability. • HA changes at positions 131, 142, 144, 145, and 156 affected the replicative ability of H5 mutants. • Acquisition of glycosylation site could lead to the emergence of multiple pleiotropic effects

  6. Viral Escape Mutant Epitope Maintains TCR Affinity for Antigen yet Curtails CD8 T Cell Responses.

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    Shayla K Shorter

    Full Text Available T cells have the remarkable ability to recognize antigen with great specificity and in turn mount an appropriate and robust immune response. Critical to this process is the initial T cell antigen recognition and subsequent signal transduction events. This antigen recognition can be modulated at the site of TCR interaction with peptide:major histocompatibility (pMHC or peptide interaction with the MHC molecule. Both events could have a range of effects on T cell fate. Though responses to antigens that bind sub-optimally to TCR, known as altered peptide ligands (APL, have been studied extensively, the impact of disrupting antigen binding to MHC has been highlighted to a lesser extent and is usually considered to result in complete loss of epitope recognition. Here we present a model of viral evasion from CD8 T cell immuno-surveillance by a lymphocytic choriomeningitis virus (LCMV escape mutant with an epitope for which TCR affinity for pMHC remains high but where the antigenic peptide binds sub optimally to MHC. Despite high TCR affinity for variant epitope, levels of interferon regulatory factor-4 (IRF4 are not sustained in response to the variant indicating differences in perceived TCR signal strength. The CD8+ T cell response to the variant epitope is characterized by early proliferation and up-regulation of activation markers. Interestingly, this response is not maintained and is characterized by a lack in IL-2 and IFNγ production, increased apoptosis and an abrogated glycolytic response. We show that disrupting the stability of peptide in MHC can effectively disrupt TCR signal strength despite unchanged affinity for TCR and can significantly impact the CD8+ T cell response to a viral escape mutant.

  7. Homologous Recombination Defective Arabidopsis Mutants Exhibit Enhanced Sensitivity to Abscisic Acid.

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    Sujit Roy

    Full Text Available Abscisic acid (ABA acts as an important plant hormone in regulating various aspects of plant growth and developmental processes particularly under abiotic stress conditions. An increased ABA level in plant cells inhibits DNA replication and cell division, causing plant growth retardation. In this study, we have investigated the effects of ABA on the growth responses of some major loss-of-function mutants of DNA double-stand break (DSB repair genes in Arabidopsis during seed germination and early stages of seedling growth for understanding the role of ABA in the induction of genome instability in plants. A comparative analysis of ABA sensitivity of wild-type Arabidopsis and the knockout mutant lines related to DSB sensors, including atatm, atatr, the non-homologous end joining (NHEJ pathway genes, and mutants related to homologous recombination (HR pathway genes showed relatively enhanced sensitivity of atatr and HR-related mutants to ABA treatment. The expression levels of HR-related genes were increased in wild-type Arabidopsis (Col-0 during seed germination and early stages of seedling growth. Immunoblotting experiments detected phosphorylation of histone H2AX in wild-type (Col-0 and DSB repair gene mutants after ABA treatment, indicating the activation of DNA damage response due to ABA treatment. Analyses of DSB repair kinetics using comet assay under neutral condition have revealed comparatively slower DSB repair activity in HR mutants. Overall, our results have provided comprehensive information on the possible effect of ABA on DNA repair machinery in plants and also indicated potential functional involvement of HR pathway in repairing ABA induced DNA damage in Arabidopsis.

  8. ISOLATION OF ANTIGENIC MUTANTS OF TYPE 1 POLIOVIRUS : GROWING THE VIRUS IN THE PRESENCE OF HOMOLOGOUS ANTISERUM

    OpenAIRE

    HASHIMOTO, Nobuo

    1980-01-01

    The antigenic mutants, which were significantly different intra-typically from the parental Mahoney-1709 type 1 poliovirus, were repeatedly isolated after a number of serial virus passages in the presence of homologous anti-Mahoney sera. The levels of the antigenic variation of those mutant viruses varied, depending on the individual antiserum employed for mutant selection and the passage numbers with same antiserum. The susceptibility to certain serum inhibitors of the antigenic mutants vari...

  9. Germline progenitors escape the widespread phenomenon of homolog pairing during Drosophila development.

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    Eric F Joyce

    Full Text Available Homolog pairing, which plays a critical role in meiosis, poses a potential risk if it occurs in inappropriate tissues or between nonallelic sites, as it can lead to changes in gene expression, chromosome entanglements, and loss-of-heterozygosity due to mitotic recombination. This is particularly true in Drosophila, which supports organismal-wide pairing throughout development. Discovered over a century ago, such extensive pairing has led to the perception that germline pairing in the adult gonad is an extension of the pairing established during embryogenesis and, therefore, differs from the mechanism utilized in most species to initiate pairing specifically in the germline. Here, we show that, contrary to long-standing assumptions, Drosophila meiotic pairing in the gonad is not an extension of pairing established during embryogenesis. Instead, we find that homologous chromosomes are unpaired in primordial germ cells from the moment the germline can be distinguished from the soma in the embryo and remain unpaired even in the germline stem cells of the adult gonad. We further establish that pairing originates immediately after the stem cell stage. This pairing occurs well before the initiation of meiosis and, strikingly, continues through the several mitotic divisions preceding meiosis. These discoveries indicate that the spatial organization of the Drosophila genome differs between the germline and the soma from the earliest moments of development and thus argue that homolog pairing in the germline is an active process as versus a passive continuation of pairing established during embryogenesis.

  10. Immune escape mutants of Highly Pathogenic Avian Influenza H5N1 selected using polyclonal sera: identification of key amino acids in the HA protein.

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    Ioannis Sitaras

    Full Text Available Evolution of Avian Influenza (AI viruses--especially of the Highly Pathogenic Avian Influenza (HPAI H5N1 subtype--is a major issue for the poultry industry. HPAI H5N1 epidemics are associated with huge economic losses and are sometimes connected to human morbidity and mortality. Vaccination (either as a preventive measure or as a means to control outbreaks is an approach that splits the scientific community, due to the risk of it being a potential driving force in HPAI evolution through the selection of mutants able to escape vaccination-induced immunity. It is therefore essential to study how mutations are selected due to immune pressure. To this effect, we performed an in vitro selection of mutants from HPAI A/turkey/Turkey/1/05 (H5N1, using immune pressure from homologous polyclonal sera. After 42 rounds of selection, we identified 5 amino acid substitutions in the Haemagglutinin (HA protein, most of which were located in areas of antigenic importance and suspected to be prone to selection pressure. We report that most of the mutations took place early in the selection process. Finally, our antigenic cartography studies showed that the antigenic distance between the selected isolates and their parent strain increased with passage number.

  11. IDH mutant gliomas escape natural killer cell immune surveillance by downregulation of NKG2D ligand expression.

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    Zhang, Xiaoran; Rao, Aparana; Sette, Paola; Deibert, Christopher; Pomerantz, Alexander; Kim, Wi Jin; Kohanbash, Gary; Chang, Yigang; Park, Yongseok; Engh, Johnathan; Choi, Jaehyuk; Chan, Timothy; Okada, Hideho; Lotze, Michael; Grandi, Paola; Amankulor, Nduka

    2016-10-01

    Diffuse gliomas are poorly immunogenic, fatal brain tumors. The basis for insufficient antitumor immunity in diffuse gliomas is unknown. Gain-of-function mutations in isocitrate dehydrogenases (IDH1 and IDH2) promote diffuse glioma formation through epigenetic reprogramming of a number of genes, including immune-related genes. Here, we identify epigenetic dysregulation of natural killer (NK) cell ligand genes as significant contributors to immune escape in glioma. We analyzed the database of The Cancer Genome Atlas for immune gene expression patterns in IDH mutant or wild-type gliomas and identified differentially expressed immune genes. NKG2D ligand expression levels and NK cell-mediated lysis were measured in IDH mutant and wild-type patient-derived glioma stem cells and genetically engineered astrocytes. Finally, we assessed the impact of hypomethylating agent 5-aza-2'deoxycytodine (decitabine) as a potential NK cell sensitizing agent in IDH mutant cells. IDH mutant glioma stemlike cell lines exhibited significantly lower expression of NKG2D ligands compared with IDH wild-type cells. Consistent with these findings, IDH mutant glioma cells and astrocytes are resistant to NK cell-mediated lysis. Decitabine increases NKG2D ligand expression and restores NK-mediated lysis of IDH mutant cells in an NKG2D-dependent manner. IDH mutant glioma cells acquire resistance to NK cells through epigenetic silencing of NKG2D ligands ULBP1 and ULBP3. Decitabine-mediated hypomethylation restores ULBP1 and ULBP3 expression in IDH mutant glioma cells and may provide a clinically useful method to sensitize IDH mutant gliomas to NK cell-mediated immune surveillance in patients with IDH mutated diffuse gliomas. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Rapid selection of escape mutants by the first CD8 T cell responses in acute HIV-1 infection

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    Korber, Bette Tina Marie [Los Alamos National Laboratory

    2008-01-01

    The recent failure of a vaccine that primes T cell responses to control primary HIV-1 infection has raised doubts about the role of CD8+ T cells in early HIV-1 infection. We studied four patients who were identified shortly after HIV-1 infection and before seroconversion. In each patient there was very rapid selection of multiple HIV-1 escape mutants in the transmitted virus by CD8 T cells, including examples of complete fixation of non-synonymous substitutions within 2 weeks. Sequencing by single genome amplification suggested that the high rate of virus replication in acute infection gave a selective advantage to virus molecules that contained simultaneous and gained sequential T cell escape mutations. These observations show that whilst early HIV-1 specific CD8 T cells can act against virus, rapid escape means that these T cell responses are unlikely to benefit the patient and may in part explain why current HIV-1 T cell vaccines may not be protective.

  13. Homologous expression of aspartokinase (ask) gene in Streptomyces clavuligerus and its hom-deleted mutant

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    Okay, Sezer; Ünsaldı, Eser; Taşkın, Bilgin; Liras, Paloma; Piret, Jacqueline

    2010-01-01

    In this study, the effect of homologous multiple copies of the ask gene, which encodes aspartokinase catalyzing the first step of the aspartate pathway, on cephamycin C biosynthesis in S. clavuligerus NRRL 3585 and its hom mutant was investigated. The intracellular pool levels of aspartate pathway amino acids accorded well with the Ask activity levels in TB3585 and AK39. When compared with the control strain carrying vector alone without any gene insert, amplification of the ask gene in the wild strain resulted in a maximum of 3.1- and 3.3-fold increase in specific, 1.7- and 1.9-fold increase in volumetric cephamycin C production when grown in trypticase soy broth (TSB) and a modified chemically defined medium (mCDM), respectively. However, expression of multicopy ask gene in a hom-deleted background significantly decreased cephamycin C yields when the cells were grown in either TSB or mCDM, most probably due to physiological disturbance resulting from enzyme overexpression and high copy number plasmid burden in an auxotrophic host, respectively. PMID:21326925

  14. CEP-1, the Caenorhabditis elegans p53 homolog, mediates opposing longevity outcomes in mitochondrial electron transport chain mutants.

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    Aiswarya Baruah

    2014-02-01

    Full Text Available Caenorhabditis elegans CEP-1 and its mammalian homolog p53 are critical for responding to diverse stress signals. In this study, we found that cep-1 inactivation suppressed the prolonged lifespan of electron transport chain (ETC mutants, such as isp-1 and nuo-6, but rescued the shortened lifespan of other ETC mutants, such as mev-1 and gas-1. We compared the CEP-1-regulated transcriptional profiles of the long-lived isp-1 and the short-lived mev-1 mutants and, to our surprise, found that CEP-1 regulated largely similar sets of target genes in the two mutants despite exerting opposing effects on their longevity. Further analyses identified a small subset of CEP-1-regulated genes that displayed distinct expression changes between the isp-1 and mev-1 mutants. Interestingly, this small group of differentially regulated genes are enriched for the "aging" Gene Ontology term, consistent with the hypothesis that they might be particularly important for mediating the distinct longevity effects of CEP-1 in isp-1 and mev-1 mutants. We further focused on one of these differentially regulated genes, ftn-1, which encodes ferritin in C. elegans, and demonstrated that it specifically contributed to the extended lifespan of isp-1 mutant worms but did not affect the mev-1 mutant lifespan. We propose that CEP-1 responds to different mitochondrial ETC stress by mounting distinct compensatory responses accordingly to modulate animal physiology and longevity. Our findings provide insights into how mammalian p53 might respond to distinct mitochondrial stressors to influence cellular and organismal responses.

  15. Genetic reconstitution of the human Adenovirus type 2 temperature-sensitive 1 mutant defective in endosomal escape

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    Gastaldelli Michele

    2009-10-01

    Full Text Available Abstract Human Adenoviruses infect the upper and lower respiratory tracts, the urinary and digestive tracts, lymphoid systems and heart, and give rise to epidemic conjunctivitis. More than 51 human serotypes have been identified to-date, and classified into 6 species A-F. The species C Adenoviruses Ad2 and Ad5 (Ad2/5 cause upper and lower respiratory disease, but how viral structure relates to the selection of particular infectious uptake pathways is not known. An adenovirus mutant, Ad2-ts1 had been isolated upon chemical mutagenesis in the past, and shown to have unprocessed capsid proteins. Ad2-ts1 fails to package the viral protease L3/p23, and Ad2-ts1 virions do not efficiently escape from endosomes. It had been suggested that the C22187T point mutation leading to the substitution of the conserved proline 137 to leucine (P137L in the L3/p23 protease was at least in part responsible for this phenotype. To clarify if the C22187T mutation is necessary and sufficient for the Ad2-ts1 phenotype, we sequenced the genes encoding the structural proteins of Ad2-ts1, and confirmed that the Ad2-ts1 DNA carries the point mutation C22187T. Introduction of C22187T to the wild-type Ad2 genome in a bacterial artificial chromosome (Ad2-BAC gave Ad2-BAC46 virions with the full Ad2-ts1 phenotype. Reversion of Ad2-BAC46 gave wild-type Ad2 particles indicating that P137L is necessary and sufficient for the Ad2-ts1 phenotype. The kinetics of Ad2-ts1 uptake into cells were comparable to Ad2 suggesting similar endocytic uptake mechanisms. Surprisingly, infectious Ad2 or Ad5 but not Ad2-ts1 uptake required CALM (clathrin assembly lymphoid myeloid protein, which controls clathrin-mediated endocytosis and membrane transport between endosomes and the trans-Golgi-network. The data show that no other mutations than P137L in the viral protease are necessary to give rise to particles that are defective in capsid processing and endosomal escape. This provides a basis for

  16. [Construction and characterization of a recombinant mutant homolog of the CheW protein from Thermotoga petrophila RKU-1].

    Science.gov (United States)

    Grishin, D V; Zhdanov, D D; Gladilina, Ju A; Pokrovsky, V S; Podobed, O V; Pokrovskaya, M V; Aleksandrova, S S; Milyushkina, A L; Vigovskiy, M A; Sokolov, N N

    2018-01-01

    In the work a recombinant chemotaxis protein CheW from Thermotoga petrophila RKU-1 (TpeCheW) and its mutant homolog (TpeCheW-mut) were created. It was shown that, despite the low homology with CheW prototypes from intestinal bacteria, these proteins didn't cause metabolic overload and were well expressed by cells of E. coli laboratory strains. We have discovered a broad spectrum of industrial valuable properties of the TpeCheW-mut protein such as stability in a wide range of temperatures and pH, high expression level, solubility and possibility of the application of a simple low-stage purification methodology with the use of preliminary heat treatment. Possible directions of the scientific and industrial application of this protein were claimed.

  17. Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants.

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    Chia Yin Lee

    2011-12-01

    Full Text Available Chikungunya virus (CHIKV is an alphavirus responsible for numerous epidemics throughout Africa and Asia, causing infectious arthritis and reportedly linked with fatal infections in newborns and elderly. Previous studies in animal models indicate that humoral immunity can protect against CHIKV infection, but despite the potential efficacy of B-cell-driven intervention strategies, there are no virus-specific vaccines or therapies currently available. In addition, CHIKV has been reported to elicit long-lasting virus-specific IgM in humans, and to establish long-term persistence in non-human primates, suggesting that the virus might evade immune defenses to establish chronic infections in man. However, the mechanisms of immune evasion potentially employed by CHIKV remain uncharacterized. We previously described two human monoclonal antibodies that potently neutralize CHIKV infection. In the current report, we have characterized CHIKV mutants that escape antibody-dependent neutralization to identify the CHIKV E2 domain B and fusion loop "groove" as the primary determinants of CHIKV interaction with these antibodies. Furthermore, for the first time, we have also demonstrated direct CHIKV cell-to-cell transmission, as a mechanism that involves the E2 domain A and that is associated with viral resistance to antibody-dependent neutralization. Identification of CHIKV sub-domains that are associated with human protective immunity, will pave the way for the development of CHIKV-specific sub-domain vaccination strategies. Moreover, the clear demonstration of CHIKV cell-to-cell transmission and its possible role in the establishment of CHIKV persistence, will also inform the development of future anti-viral interventions. These data shed new light on CHIKV-host interactions that will help to combat human CHIKV infection and inform future studies of CHIKV pathogenesis.

  18. PTEN Redundancy: Overexpressing lpten, a Homolog of Dictyostelium discoideum ptenA, the Ortholog of Human PTEN, Rescues All Behavioral Defects of the Mutant ptenA−

    OpenAIRE

    Lusche, Daniel F.; Wessels, Deborah; Richardson, Nicole A.; Russell, Kanoe B.; Hanson, Brett M.; Soll, Benjamin A.; Lin, Benjamin H.; Soll, David R.

    2014-01-01

    Mutations in the tumor suppressor gene PTEN are associated with a significant proportion of human cancers. Because the human genome also contains several homologs of PTEN, we considered the hypothesis that if a homolog, functionally redundant with PTEN, can be overexpressed, it may rescue the defects of a PTEN mutant. We have performed an initial test of this hypothesis in the model system Dictyostelium discoideum, which contains an ortholog of human PTEN, ptenA. Deletion of ptenA results in ...

  19. Homologous expression of aspartokinase (ask) gene in Streptomyces clavuligerus and its hom-deleted mutant: effects on cephamycin C production.

    Science.gov (United States)

    Özcengiz, Gülay; Okay, Sezer; Ünsaldı, Eser; Taşkın, Bilgin; Liras, Paloma; Piret, Jacqueline

    2010-01-01

    In this study, the effect of homologous multiple copies of the ask gene, which encodes aspartokinase catalyzing the first step of the aspartate pathway, on cephamycin C biosynthesis in S. clavuligerus NRRL 3585 and its hom mutant was investigated. The intracellular pool levels of aspartate pathway amino acids accorded well with the Ask activity levels in TB3585 and AK39. When compared with the control strain carrying vector alone without any gene insert, amplification of the ask gene in the wild strain resulted in a maximum of 3.1- and 3.3-fold increase in specific, 1.7- and 1.9-fold increase in volumetric cephamycin C production when grown in trypticase soy broth (TSB) and a modified chemically defined medium (mCDM), respectively. However, expression of multicopy ask gene in a hom-deleted background significantly decreased cephamycin C yields when the cells were grown in either TSB or mCDM, most probably due to physiological disturbance resulting from enzyme overexpression and high copy number plasmid burden in an auxotrophic host, respectively. © 2010 Landes Bioscience

  20. CARMA2sh and ULK2 control pathogen-associated molecular patterns recognition in human keratinocytes: psoriasis-linked CARMA2sh mutants escape ULK2 censorship.

    Science.gov (United States)

    Scudiero, Ivan; Mazzone, Pellegrino; D'Andrea, Luca E; Ferravante, Angela; Zotti, Tiziana; Telesio, Gianluca; De Rubis, Gabriele; Reale, Carla; Pizzulo, Maddalena; Muralitharan, Shanmugakonar; Vito, Pasquale; Stilo, Romania

    2017-02-23

    The molecular complexes formed by specific members of the family of CARMA proteins, the CARD domain-containing adapter molecule BCL10 and MALT1 (CBM complex) represent a central hub in regulating activation of the pleiotropic transcription factor NF-κB. Recently, missense mutations in CARMA2sh have been shown to cause psoriasis in a dominant manner and with high penetrancy. Here, we demonstrate that in human keratinocytes CARMA2sh plays an essential role in the signal transduction pathway that connects pathogen-associated molecular patterns recognition to NF-κB activation. We also find that the serine/threonine kinase ULK2 binds to and phosphorylates CARMA2sh, thereby inhibiting its capacity to activate NF-κB by promoting lysosomal degradation of BCL10, which is essential for CARMA2sh-mediated NF-κB signaling. Remarkably, CARMA2sh mutants associated with psoriasis escape ULK2 inhibition. Finally, we show that a peptide blocking CARD-mediated BCL10 interactions reduces the capacity of psoriasis-linked CARMA2sh mutants to activate NF-κB. Our work elucidates a fundamental signaling mechanism operating in human keratinocytes and opens to novel potential tools for the therapeutical treatment of human skin disorders.

  1. Agrobacterium tumefaciens T-DNA Integration and Gene Targeting in Arabidopsis thaliana Non-Homologous End-Joining Mutants

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    Qi Jia

    2012-01-01

    Full Text Available In order to study the role of AtKu70 and AtKu80 in Agrobacterium-mediated transformation and gene targeting, plant lines with a T-DNA insertion in AtKu80 or AtKu70 genes were functionally characterized. Such plant lines lacked both subunits, indicating that heterodimer formation between AtKu70 and AtKu80 is needed for the stability of the proteins. Homozygous mutants were phenotypically indistinguishable from wild-type plants and were fertile. However, they were hypersensitive to the genotoxic agent bleomycin, resulting in more DSBs as quantified in comet assays. They had lower end-joining efficiency, suggesting that NHEJ is a critical pathway for DSB repair in plants. Both Atku mutants and a previously isolated Atmre11 mutant were impaired in Agrobacterium T-DNA integration via floral dip transformation, indicating that AtKu70, AtKu80, and AtMre11 play an important role in T-DNA integration in Arabidopsis. The frequency of gene targeting was not significantly increased in the Atku80 and Atku70 mutants, but it was increased at least 10-fold in the Atmre11 mutant compared with the wild type.

  2. The tropical cedar tree (Cedrela fissilis Vell., Meliaceae) homolog of the Arabidopsis LEAFY gene is expressed in reproductive tissues and can complement Arabidopsis leafy mutants.

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    Dornelas, Marcelo Carnier; Rodriguez, Adriana Pinheiro Martinelli

    2006-01-01

    A homolog of FLORICAULA/LEAFY, CfLFY (for Cedrela fissilis LFY), was isolated from tropical cedar. The main stages of the reproductive development in C. fissilis were documented by scanning electron microscopy and the expression patterns of CfLFY were studied during the differentiation of the floral meristems. Furthermore, the biological role of the CfLFY gene was assessed using transgenic Arabidopsis plants. CfLFY showed a high degree of similarity to other plant homologs of FLO/LFY. Southern analysis showed that CfLFY is a single-copy gene in the tropical cedar genome. Northern blot analysis and in situ hybridization results showed that CfLFY was expressed in the reproductive buds during the transition from vegetative to reproductive growth, as well as in floral meristems and floral organs but was excluded from the vegetative apex and leaves. Transgenic Arabidopsis lfy26 mutant lines expressing the CfLFY coding region, under the control of the LFY promoter, showed restored wild-type phenotype. Taken together, our results suggest that CfLFY is a FLO/LFY homolog probably involved in the control of tropical cedar reproductive development.

  3. Molecular and antigenic traits on hemagglutinin gene of avian influenza H9N2 viruses: Evidence of a new escape mutant in Egypt adapted in quails.

    Science.gov (United States)

    Adel, Amany; Arafa, Abdelsatar; Hussein, Hussein A; El-Sanousi, Ahmed A

    2017-06-01

    The LPAI viruses of H9N2 subtype became widely distributed in Middle Eastern countries, causing great economic losses in poultry industry especially when complicated with other pathogens. The H9N2 viruses in Egypt have a wide spread nature since its first occurrence in 2011. In this study, we collected cloacal and tracheal samples from 19 flocks for detection and propagation of H9N2 virus using real-time RT-PCR and egg inoculation. We studied the molecular evolution of the Hemagglutinin gene of H9N2 viruses by full HA gene sequencing, then the antigenic characterization was implemented using the cross HI assay and analyzed using 3D Bioinformatics cartography software. The phylogenetic analysis of the HA gene of Egyptian H9N2 viruses clearly points out the presence of only one group (Egy/G1) of originally introduced viruses in 2011 related to the G1 lineage within group B, with the presence of multiple minor clusters includes viruses from 2011 to 2015. However, a new variant (Egy/G1var) cluster was detected in quails since 2012. Genetically, Egy/G1var viruses characterized by presence of 20 amino acid substitutions within and adjacent to the antigenic sites in comparison to other Egyptian viruses. In addition, two glycosylation sites at amino acid residues 127 and 189 were determined in close to the receptor binding and antigenic sites. The antigenic analysis based on 3D antigenic mapping showed that the Egy/G1var cluster was clearly distinct from the original Egy/G1 viruses. In conclusion, Egy/G1var is shown to be a new escape mutant variant cluster with an adaptive evolution in quails. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Down-regulation of the strawberry Bet v 1-homologous allergen in concert with the flavonoid biosynthesis pathway in colorless strawberry mutant

    DEFF Research Database (Denmark)

    Hjernø, Karin; Alm, Rikard; Canbäck, Björn

    2006-01-01

    Proteomic screening of strawberry (Fragaria ananassa) yielded a 58% success rate in protein identification in spite of the fact that no genomic sequence is available for this species. This was achieved by a combination of MALDI-MS/MS de novo sequencing of double-derivatized peptides and indel......-tolerant searching against local protein databases built on both EST and full-length nucleotide sequences. The amino acid sequence of a strawberry allergen, homologous to the well-known major birch pollen allergen Bet v 1, was partially determined. This strawberry allergen, named Fra a 1 according...... to the nomenclature for allergen proteins, showed sequence identity of 54 and 77%, respectively, with corresponding allergens from birch and apple. Differential expression, as evaluated by 2-D DIGE, occurred in 10% of protein spots when red strawberries were compared to a colorless (white) strawberry mutant. White...

  5. Complementation of a yeast cell cycle mutant by an alfalfa cDNA encoding a protein kinase homologous to p34cdc2.

    Science.gov (United States)

    Hirt, H; Páy, A; Györgyey, J; Bakó, L; Németh, K; Bögre, L; Schweyen, R J; Heberle-Bors, E; Dudits, D

    1991-03-01

    The cdc2 protein kinase plays a central role in control of the eukaryotic cell cycle of animals and yeasts. We have isolated a cDNA clone (cdc2Ms) from alfalfa (Medicago sativa L.) that is homologous to the yeast cdc2/CDC28 genes. The encoded protein is 64% identical to the yeast and mammalian counterparts and shows all the prominent structural features known from these organisms. Antibody raised against a 16-amino acid synthetic peptide with crossreactivity against p34 proteins recognized a 34-kilodalton protein in extracts of alfalfa cells. When transferred into a fission yeast, the plant cdc2 homolog can complement a temperature-sensitive cdc2 mutant. Northern analysis revealed higher transcript levels in shoots and suspension cultures than in roots. In addition to the dominant transcript of 1.4 kilobases detected in the poly(A)+fraction, 2.5- and 1.2-kilobase transcripts were detected in total RNA preparations from shoots or somatic embryos. Suspension cultures that were induced to form somatic embryos by an auxin (2,4-dichlorophenoxyacetic acid) showed fluctuations in transcription pattern during the induction period and embryogenesis.

  6. Pacemaker-neuron–dependent disturbance of the molecular clockwork by a Drosophila CLOCK mutant homologous to the mouse Clock mutation

    Science.gov (United States)

    Lee, Euna; Cho, Eunjoo; Kang, Doo Hyun; Jeong, Eun Hee; Chen, Zheng; Yoo, Seung-Hee; Kim, Eun Young

    2016-01-01

    Circadian clocks are composed of transcriptional/translational feedback loops (TTFLs) at the cellular level. In Drosophila TTFLs, the transcription factor dCLOCK (dCLK)/CYCLE (CYC) activates clock target gene expression, which is repressed by the physical interaction with PERIOD (PER). Here, we show that amino acids (AA) 657–707 of dCLK, a region that is homologous to the mouse Clock exon 19-encoded region, is crucial for PER binding and E-box–dependent transactivation in S2 cells. Consistently, in transgenic flies expressing dCLK with an AA657–707 deletion in the Clock (Clkout) genetic background (p{dClk-Δ};Clkout), oscillation of core clock genes’ mRNAs displayed diminished amplitude compared with control flies, and the highly abundant dCLKΔ657–707 showed significantly decreased binding to PER. Behaviorally, the p{dClk-Δ};Clkout flies exhibited arrhythmic locomotor behavior in the photic entrainment condition but showed anticipatory activities of temperature transition and improved free-running rhythms in the temperature entrainment condition. Surprisingly, p{dClk-Δ};Clkout flies showed pacemaker-neuron–dependent alterations in molecular rhythms; the abundance of dCLK target clock proteins was reduced in ventral lateral neurons (LNvs) but not in dorsal neurons (DNs) in both entrainment conditions. In p{dClk-Δ};Clkout flies, however, strong but delayed molecular oscillations in temperature cycle-sensitive pacemaker neurons, such as DN1s and DN2s, were correlated with delayed anticipatory activities of temperature transition. Taken together, our study reveals that the LNv molecular clockwork is more sensitive than the clockwork of DNs to dysregulation of dCLK by AA657–707 deletion. Therefore, we propose that the dCLK/CYC-controlled TTFL operates differently in subsets of pacemaker neurons, which may contribute to their specific functions. PMID:27489346

  7. Viral suppression of multiple escape mutants by de novo CD8+ T cell responses in a human immunodeficiency virus-1 Infected elite suppressor

    Directory of Open Access Journals (Sweden)

    Siliciano Robert F

    2011-08-01

    Full Text Available Abstract Elite suppressors or controllers (ES are HIV-1 infected patients who maintain undetectable viral loads without treatment. While HLA-B*57-positive ES are usually infected with virus that is unmutated at CTL epitopes, a single, dominant variant containing CTL escape mutations is typically seen in plasma during chronic infection. We describe an ES who developed seven distinct and rare escape variants at an HLA-B*57-restricted Gag epitope over a five year period. Interestingly, he developed proliferative, de novo CTL responses that suppressed replication of each of these variants. These responses, in combination with low viral fitness of each variant, may contribute to sustained elite control in this ES.

  8. mRNA processing in mutant zebrafish lines generated by chemical and CRISPR-mediated mutagenesis produces unexpected transcripts that escape nonsense-mediated decay.

    Directory of Open Access Journals (Sweden)

    Jennifer L Anderson

    2017-11-01

    Full Text Available As model organism-based research shifts from forward to reverse genetics approaches, largely due to the ease of genome editing technology, a low frequency of abnormal phenotypes is being observed in lines with mutations predicted to lead to deleterious effects on the encoded protein. In zebrafish, this low frequency is in part explained by compensation by genes of redundant or similar function, often resulting from the additional round of teleost-specific whole genome duplication within vertebrates. Here we offer additional explanations for the low frequency of mutant phenotypes. We analyzed mRNA processing in seven zebrafish lines with mutations expected to disrupt gene function, generated by CRISPR/Cas9 or ENU mutagenesis methods. Five of the seven lines showed evidence of altered mRNA processing: one through a skipped exon that did not lead to a frame shift, one through nonsense-associated splicing that did not lead to a frame shift, and three through the use of cryptic splice sites. These results highlight the need for a methodical analysis of the mRNA produced in mutant lines before making conclusions or embarking on studies that assume loss of function as a result of a given genomic change. Furthermore, recognition of the types of adaptations that can occur may inform the strategies of mutant generation.

  9. Localization of the homolog of a mouse craniofacial mutant to human chromosome 18q11 and evaluation of linkage to human CLP and CPO

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, A.J.; Burgess, D.L.; Kohrman, D.C.; Yu, J. [Univ. of Michigan, Ann Arbor, MI (United States)] [and others

    1996-06-15

    The transgene-induced mutation 9257 and the spontaneous mutation twirler cause craniofacial and inner ear malformations and are located on mouse chromosome 18 near the ataxia locus ax. To map the human homolog of 9257, a probe from the transgene insertion site was used to screen a human genomic library. Analysis of a cross-hybridizing human clone identified a 3-kb conserved sequence block that does not appear to contain protein coding sequence. Analysis of somatic cell hybrid panels assigned the human locus to 18q11. The polymorphic microsatellite markers D18S1001 and D18S1002 were isolated from the human locus and mapped by linkage analysis using the CEPH pedigrees. The 9257 locus maps close to the centromeres of human chromosome 18q and mouse chromosome 18 at the proximal end of a conserved linkage group. To evaluate the role of this locus in human craniofacial disorders, linkage to D18S1002 was tested in 11 families with autosomal dominant nonsyndromic cleft lip and palate and 3 families with autosomal dominant cleft palate only. Obligatory recombinants were observed in 8 of the families, and negative lod scores from the other families indicated that these disorders are not linked to the chromosome 18 loci. 23 refs., 4 figs., 2 tabs.

  10. Computational analysis of Amsacrine resistance in human topoisomerase II alpha mutants (R487K and E571K) using homology modeling, docking and all-atom molecular dynamics simulation in explicit solvent.

    Science.gov (United States)

    Sader, Safaa; Wu, Chun

    2017-03-01

    Amsacrine is an effective topoisomerase II enzyme inhibitor in acute lymphatic leukemia. Previous experimental studies have successfully identified two important mutations (R487K and E571K) conferring 100 and 25 fold resistance to Amsacrine respectively. Although the reduction of the cleavage ligand-DNA-protein ternary complex has been well thought as the major cause of drug resistance, the detailed energetic, structural and dynamic mechanisms remain to be elusive. In this study, we constructed human topoisomerase II alpha (hTop2α) homology model docked with Amsacrine based on crystal structure of human Top2β in complex with etoposide. This wild type complex was used to build the ternary complex with R487K and E571K mutants. Three 500ns molecular dynamics simulations were performed on complex systems of wild type and two mutants. The detailed energetic, structural and dynamic analysis were performed on the simulation data. Our binding data indicated a significant impairment of Amsacrine binding energy in the two mutants compared with the wild type. The order of weakening (R487K>E571K) was in agreement with the order of experimental drug resistance fold (R489K>E571K). Our binding energy decomposition further indicated that weakening of the ligand-protein interaction rather than the ligand-DNA interaction was the major contributor of the binding energy difference between R487K and E571K. In addition, key residues contributing to the binding energy (ΔG) or the decrease of the binding energy (ΔΔG) were identified through the energy decomposition analysis. The change in ligand binding pose, dynamics of protein, DNA and ligand upon the mutations were thoroughly analyzed and discussed. Deciphering the molecular basis of drug resistance is crucial to overcome drug resistance using rational drug design. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Directed homology

    DEFF Research Database (Denmark)

    Fahrenberg, Uli

    2004-01-01

    We introduce a new notion of directed homology for semicubical sets. We show that it respects directed homotopy and is functorial, and that it appears to enjoy some good algebraic properties. Our work has applications to higher-dimensional automata.......We introduce a new notion of directed homology for semicubical sets. We show that it respects directed homotopy and is functorial, and that it appears to enjoy some good algebraic properties. Our work has applications to higher-dimensional automata....

  12. The polyclonal CD8 T cell response to influenza M158-66 generates a fully connected network of cross-reactive clonotypes to structurally related peptides: a paradigm for memory repertoire coverage of novel epitopes or escape mutants.

    Science.gov (United States)

    Petrova, Galina V; Naumova, Elena N; Gorski, Jack

    2011-06-01

    Cross-reactivity of T cells is defined as recognition of two or more peptide-MHC complexes by the same T cell. Although examples of cross-reactivity have been reported, a detailed examination of cross-reactivity has not been performed. In this study, we took advantage of the high degree of polyclonality in the BV19 T cell repertoire responding to influenza M1(58-66) in HLA-A2 individuals to obtain a measure of simple cross-reactivity. We used substitutions that incrementally change the structure of the M1(58-66) peptide to measure how the HLA-A2-restricted response adapts to these changes. In three HLA-A2 adult subjects, we identified the BV19 clonotypes in the recall response to the influenza epitope M1(58-66) and 12 M1 peptides substituted at TCR contact position 63 or 65. The fraction of cross-reactive clonotypes in the M1(58-66) repertoire varied from 45-58% in the three donors. The extent of cross-reactivity, which is the additional number of peptides recognized by a single clonotype, is as high as six. We summarized the data using graph theory, with the cross-reactive clonotypes connecting the different HLA-A2 peptides recognized. The cross-reactive clonotypes form a well-connected network that could provide protection from virus-escape variants. We predict that any new pathogen with an epitope whose shape corresponds to that of the peptides that we studied would find a pre-existing repertoire ready to respond to it. We propose that in adult memory repertoires, previously encountered epitopes may have generated similar cross-reactive repertoires.

  13. Restricting wolves risks escape

    Science.gov (United States)

    Mech, L. David; Ballard, Warren; Bangs, Ed; Ream, Bob

    2010-01-01

    Implementing the proposal set forth by Licht and colleagues (BioScience 60: 147–153) requires restricting wolves to tiny "islands," areas that are magnitudes smaller than the ranges of most wolf populations. Wolves naturally have large ranges; restricting their spatial needs increases the risk of wolves escaping, exacerbating public relations and political and legal problems.

  14. Writing E/scapes

    Directory of Open Access Journals (Sweden)

    Jasmine Ulmer

    2017-12-01

    Full Text Available scape. 1 a brief ‘escape or means of escape’ 2 ‘a scenic view, whether of sea, land, or sky’ 3 ‘in its various senses’ 4 ‘a long flower-stalk rising directly from the root or rhizome’ 5 a theoretical approach to writing

  15. Escape From Cultural Isolation

    Science.gov (United States)

    Umesao, Tadao

    1975-01-01

    On the premise that the fundamental character of international interchange lies in a cruel and merciless collision of mutually suspicious and distrustful cultures, the historical resistance of the Japanese to cultural interchange is examined, the consequences of international trade without interchange noted, and the means of escape outlined. (JT)

  16. Escape from planetary neighbourhoods

    NARCIS (Netherlands)

    Waalkens, H.; Burbanks, A.; Wiggins, S.

    2005-01-01

    In this paper we use recently developed phase-space transport theory coupled with a so-called classical spectral theorem to develop a dynamically exact and computationally efficient procedure for studying escape from a planetary neighbourhood. The ‘planetary neighbourhood’ is a bounded region of

  17. Escape from the Alternative

    Directory of Open Access Journals (Sweden)

    Marin Dinu

    2006-12-01

    Full Text Available This paper sets out to elaborate on Romania’s specific agenda regarding the approach to the integration process in the EU as a project of modernization. The focus is on the functional aspects, the type of strategic solutions destined to consolidate the specific transformations belonging to post-communist transition seen as an internal transition, on the one hand and on the other hand to push convergence as the essence of integration, marked by the vision of EU integration as a continuation of change, which is the stage of external transition. Identifying the prominent factors and the pragmatic priorities of the escape from the peripheries of development by engaging in evolution by way of the second modernization constitutes as well a target for analysis. One particularity of the method of analysis is the review if the value-set of the bobsled effect of path dependency – the path of the peripheries – as well as of the set of values of the escape from the peripheries.

  18. Vaccination and timing influence SIV immune escape viral dynamics in vivo.

    Directory of Open Access Journals (Sweden)

    Liyen Loh

    2008-01-01

    Full Text Available CD8+ cytotoxic T lymphocytes (CTL can be effective at controlling HIV-1 in humans and SIV in macaques, but their utility is partly offset by mutational escape. The kinetics of CTL escape and reversion of escape mutant viruses upon transmission to MHC-mismatched hosts can help us understand CTL-mediated viral control and the fitness cost extracted by immune escape mutation. Traditional methods for following CTL escape and reversion are, however, insensitive to minor viral quasispecies. We developed sensitive quantitative real-time PCR assays to track the viral load of SIV Gag164-172 KP9 wild-type (WT and escape mutant (EM variants in pigtail macaques. Rapid outgrowth of EM virus occurs during the first few weeks of infection. However, the rate of escape plateaued soon after, revealing a prolonged persistence of WT viremia not detectable by standard cloning and sequencing methods. The rate of escape of KP9 correlated with levels of vaccine-primed KP9-specific CD8+ T cells present at that time. Similarly, when non-KP9 responder (lacking the restricting Mane-A*10 allele macaques were infected with SHIVmn229 stock containing a mixture of EM and WT virus, rapid reversion to WT was observed over the first 2 weeks following infection. However, the rate of reversion to WT slowed dramatically over the first month of infection. The serial quantitation of escape mutant viruses evolving during SIV infection shows that rapid dynamics of immune escape and reversion can be observed in early infection, particularly when CD8 T cells are primed by vaccination. However, these early rapid rates of escape and reversion are transient and followed by a significant slowing in these rates later during infection, highlighting that the rate of escape is significantly influenced by the timing of its occurrence.

  19. ATM mutants

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. ATM mutants. ATM (Ataxia Telangiectasia Mutated). AT2BE and AT5B1 cells – fibroblast cell lines from Ataxia telangiectasia patients. Deletion mutants expressing truncated ATM protein which is inactive. Have been used in studies looking at the role of ATM in DNA damage ...

  20. Antibody escape kinetics of equine infectious anemia virus infection of horses.

    Science.gov (United States)

    Schwartz, Elissa J; Nanda, Seema; Mealey, Robert H

    2015-07-01

    Lentivirus escape from neutralizing antibodies (NAbs) is not well understood. In this work, we quantified antibody escape of a lentivirus, using antibody escape data from horses infected with equine infectious anemia virus. We calculated antibody blocking rates of wild-type virus, fitness costs of mutant virus, and growth rates of both viruses. These quantitative kinetic estimates of antibody escape are important for understanding lentiviral control by antibody neutralization and in developing NAb-eliciting vaccine strategies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. Reconstructing the Alcatraz escape

    Science.gov (United States)

    Baart, F.; Hoes, O.; Hut, R.; Donchyts, G.; van Leeuwen, E.

    2014-12-01

    In the night of June 12, 1962 three inmates used a raft made of raincoatsto escaped the ultimate maximum security prison island Alcatraz in SanFrancisco, United States. History is unclear about what happened tothe escapees. At what time did they step into the water, did theysurvive, if so, where did they reach land? The fate of the escapees has been the subject of much debate: did theymake landfall on Angel Island, or did the current sweep them out ofthe bay and into the cold pacific ocean? In this presentation, we try to shed light on this historic case using avisualization of a high-resolution hydrodynamic simulation of the San Francisco Bay, combined with historical tidal records. By reconstructing the hydrodynamic conditions and using a particle based simulation of the escapees we show possible scenarios. The interactive model is visualized using both a 3D photorealistic and web based visualization. The "Escape from Alcatraz" scenario demonstrates the capabilities of the 3Di platform. This platform is normally used for overland flooding (1D/2D). The model engine uses a quad tree structure, resulting in an order of magnitude speedup. The subgrid approach takes detailed bathymetry information into account. The inter-model variability is tested by comparing the results with the DFlow Flexible Mesh (DFlowFM) San Francisco Bay model. Interactivity is implemented by converting the models from static programs to interactive libraries, adhering to the Basic ModelInterface (BMI). Interactive models are more suitable for answeringexploratory research questions such as this reconstruction effort. Although these hydrodynamic simulations only provide circumstantialevidence for solving the mystery of what happened during the foggy darknight of June 12, 1962, it can be used as a guidance and provides aninteresting testcase to apply interactive modelling.

  2. Real Topological Cyclic Homology

    DEFF Research Database (Denmark)

    Høgenhaven, Amalie

    The main topics of this thesis are real topological Hochschild homology and real topological cyclic homology. If a ring or a ring spectrum is equipped with an anti-involution, then it induces additional structure on the topological Hochschild homology spectrum. The group O(2) acts on the spectrum......, where O(2) is the semi-direct product of T, the multiplicative group of complex number of modulus 1, by the group G=Gal(C/R). We refer to this O(2)-spectrum as the real topological Hochschild homology. This generalization leads to a G-equivariant version of topological cyclic homology, which we call...... real topological cyclic homology. The first part of the thesis computes the G-equivariant homotopy type of the real topological cyclic homology of spherical group rings at a prime p with anti-involution induced by taking inverses in the group. The second part of the thesis investigates the derived G...

  3. Dynamics of immune escape during HIV/SIV infection.

    Directory of Open Access Journals (Sweden)

    Christian L Althaus

    Full Text Available Several studies have shown that cytotoxic T lymphocytes (CTLs play an important role in controlling HIV/SIV infection. Notably, the observation of escape mutants suggests a selective pressure induced by the CTL response. However, it remains difficult to assess the definite role of the cellular immune response. We devise a computational model of HIV/SIV infection having a broad cellular immune response targeting different viral epitopes. The CTL clones are stimulated by viral antigen and interact with the virus population through cytotoxic killing of infected cells. Consequently, the virus population reacts through the acquisition of CTL escape mutations. Our model provides realistic virus dynamics and describes several experimental observations. We postulate that inter-clonal competition and immunodominance may be critical factors determining the sequential emergence of escapes. We show that even though the total killing induced by the CTL response can be high, escape rates against a single CTL clone are often slow and difficult to estimate from infrequent sequence measurements. Finally, our simulations show that a higher degree of immunodominance leads to more frequent escape with a reduced control of viral replication but a substantially impaired replicative capacity of the virus. This result suggests two strategies for vaccine design: Vaccines inducing a broad CTL response should decrease the viral load, whereas vaccines stimulating a narrow but dominant CTL response are likely to induce escape but may dramatically reduce the replicative capacity of the virus.

  4. Lectures on functor homology

    CERN Document Server

    Touzé, Antoine

    2015-01-01

    This book features a series of lectures that explores three different fields in which functor homology (short for homological algebra in functor categories) has recently played a significant role. For each of these applications, the functor viewpoint provides both essential insights and new methods for tackling difficult mathematical problems. In the lectures by Aurélien Djament, polynomial functors appear as coefficients in the homology of infinite families of classical groups, e.g. general linear groups or symplectic groups, and their stabilization. Djament’s theorem states that this stable homology can be computed using only the homology with trivial coefficients and the manageable functor homology. The series includes an intriguing development of Scorichenko’s unpublished results. The lectures by Wilberd van der Kallen lead to the solution of the general cohomological finite generation problem, extending Hilbert’s fourteenth problem and its solution to the context of cohomology. The focus here is o...

  5. Human GLTP and mutant forms of ACD11 suppress cell death in the Arabidopsis acd11 mutant

    DEFF Research Database (Denmark)

    Petersen, Nikolaj H T; McKinney, Lea V; Pike, Helen

    2008-01-01

    The Arabidopsis acd11 mutant exhibits runaway, programmed cell death due to the loss of a putative sphingosine transfer protein (ACD11) with homology to mammalian GLTP. We demonstrate that transgenic expression in Arabidopsis thaliana of human GLTP partially suppressed the phenotype of the acd11...... null mutant, resulting in delayed programmed cell death development and plant survival. Surprisingly, a GLTP mutant form impaired in glycolipid transfer activity also complemented the acd11 mutants. To understand the relationship between functional complementarity and transfer activity, we generated...... site-specific mutants in ACD11 based on homologous GLTP residues required for glycolipid transfer. We show that these ACD11 mutant forms are impaired in their in vitro transfer activity of sphingolipids. However, transgenic expression of these mutant forms fully complemented acd11 mutant cell death...

  6. Evidence for soft selective sweeps in the evolution of pneumococcal multidrug resistance and vaccine escape.

    Science.gov (United States)

    Croucher, Nicholas J; Chewapreecha, Claire; Hanage, William P; Harris, Simon R; McGee, Lesley; van der Linden, Mark; Song, Jae-Hoon; Ko, Kwan Soo; de Lencastre, Herminia; Turner, Claudia; Yang, Fan; Sá-Leão, Raquel; Beall, Bernard; Klugman, Keith P; Parkhill, Julian; Turner, Paul; Bentley, Stephen D

    2014-06-10

    The multidrug-resistant Streptococcus pneumoniae Taiwan(19F)-14, or PMEN14, clone was first observed with a 19F serotype, which is targeted by the heptavalent polysaccharide conjugate vaccine (PCV7). However, "vaccine escape" PMEN14 isolates with a 19A serotype became an increasingly important cause of disease post-PCV7. Whole genome sequencing was used to characterize the recent evolution of 173 pneumococci of, or related to, PMEN14. This suggested that PMEN14 is a single lineage that originated in the late 1980s in parallel with the acquisition of multiple resistances by close relatives. One of the four detected serotype switches to 19A generated representatives of the sequence type (ST) 320 isolates that have been highly successful post-PCV7. A second produced an ST236 19A genotype with reduced resistance to β-lactams owing to alteration of pbp1a and pbp2x sequences through the same recombination that caused the change in serotype. A third, which generated a mosaic capsule biosynthesis locus, resulted in serotype 19A ST271 isolates. The rapid diversification through homologous recombination seen in the global collection was similarly observed in the absence of vaccination in a set of isolates from the Maela refugee camp in Thailand, a collection that also allowed variation to be observed within carriage through longitudinal sampling. This suggests that some pneumococcal genotypes generate a pool of standing variation that is sufficiently extensive to result in "soft" selective sweeps: The emergence of multiple mutants in parallel upon a change in selection pressure, such as vaccine introduction. The subsequent competition between these mutants makes this phenomenon difficult to detect without deep sampling of individual lineages. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  7. Creating Engaging Escape Rooms for the Classroom

    Science.gov (United States)

    Nicholson, Scott

    2018-01-01

    Escape rooms are "live-action team-based games where players discover clues, solve puzzles, and accomplish tasks in one or more rooms in order to accomplish a specific goal (usually escaping from the room) in a limited amount of time." Escape Rooms are one type of Escape Game, which are narrative-based challenges that use puzzles, tasks,…

  8. Automated Escape Guidance Algorithms for An Escape Vehicle

    Science.gov (United States)

    Flanary, Ronald; Hammen, David; Ito, Daigoro; Rabalais, Bruce; Rishikof, Brian; Siebold, Karl

    2002-01-01

    An escape vehicle was designed to provide an emergency evacuation for crew members living on a space station. For maximum escape capability, the escape vehicle needs to have the ability to safely evacuate a station in a contingency scenario such as an uncontrolled (e.g., tumbling) station. This emergency escape sequence will typically be divided into three events: The fust separation event (SEP1), the navigation reconstruction event, and the second separation event (SEP2). SEP1 is responsible for taking the spacecraft from its docking port to a distance greater than the maximum radius of the rotating station. The navigation reconstruction event takes place prior to the SEP2 event and establishes the orbital state to within the tolerance limits necessary for SEP2. The SEP2 event calculates and performs an avoidance burn to prevent station recontact during the next several orbits. This paper presents the tools and results for the whole separation sequence with an emphasis on the two separation events. The fust challenge includes collision avoidance during the escape sequence while the station is in an uncontrolled rotational state, with rotation rates of up to 2 degrees per second. The task of avoiding a collision may require the use of the Vehicle's de-orbit propulsion system for maximum thrust and minimum dwell time within the vicinity of the station vicinity. The thrust of the propulsion system is in a single direction, and can be controlled only by the attitude of the spacecraft. Escape algorithms based on a look-up table or analytical guidance can be implemented since the rotation rate and the angular momentum vector can be sensed onboard and a-priori knowledge of the position and relative orientation are available. In addition, crew intervention has been provided for in the event of unforeseen obstacles in the escape path. The purpose of the SEP2 burn is to avoid re-contact with the station over an extended period of time. Performing this maneuver properly

  9. Productive homologous and non-homologous recombination of hepatitis C virus in cell culture

    DEFF Research Database (Denmark)

    Scheel, Troels K H; Galli, Andrea; Li, Yi-Ping

    2013-01-01

    Genetic recombination is an important mechanism for increasing diversity of RNA viruses, and constitutes a viral escape mechanism to host immune responses and to treatment with antiviral compounds. Although rare, epidemiologically important hepatitis C virus (HCV) recombinants have been reported......) lacking functional envelope genes and strain J6 (2a), which has functional envelope genes but does not replicate in culture. After an initial decrease in the number of HCV positive cells, infection spread after 13-36 days. Sequencing of recovered viruses revealed non-homologous recombinants with J6...

  10. Lise Meitner's escape from Germany

    Science.gov (United States)

    Sime, Ruth Lewin

    1990-03-01

    Lise Meitner (1878-1968) achieved prominence as a nuclear physicist in Germany; although of Jewish origin, her Austrian citizenship exempted her from Nazi racial laws until the annexation of Austria in 1938 precipitated her dismissal. Forbidden to emigrate, she narrowly escaped to the Netherlands with the help of concerned friends in the international physics community.

  11. Gorenstein homological dimensions

    DEFF Research Database (Denmark)

    Holm, Henrik Granau

    2004-01-01

    In basic homological algebra, the projective, injective and 2at dimensions of modules play an important and fundamental role. In this paper, the closely related Gorenstein projective, Gorenstein injective and Gorenstein 2at dimensions are studied. There is a variety of nice results about Gorenstein...... dimensions over special commutative noetherian rings; very often local Cohen–Macaulay rings with a dualizing module. These results are done by Avramov, Christensen, Enochs, Foxby, Jenda, Martsinkovsky and Xu among others. The aim of this paper is to generalize these results, and to give homological...... descriptions of the Gorenstein dimensions over arbitrary associative rings....

  12. Escaping carbon lock-in

    International Nuclear Information System (INIS)

    Unruh, G.C.

    2002-01-01

    This article explores the climate policy implications of the arguments made in ''Understanding carbon lock-in'' (Unruh, 2000), which posited that industrial countries have become locked-into fossil fuel-based energy systems through path dependent processes driven by increasing returns to scale. Carbon lock-in arises through technological, organizational, social and institutional co-evolution, ''culminating'' in what was termed as techno-institutional complex (TIC). In order to resolve the climate problem, an escape from the lock-in condition is required. However, due to the self-referential nature of TIC, escape conditions are unlikely to be generated internally and it is argued here that erogenous forces are probably required. (author)

  13. The escape gated proportional counter

    International Nuclear Information System (INIS)

    Bibbo, G.; Sanford, P.W.

    1981-01-01

    Proportional counters, designed to detect hard X-rays, are generally filled with Xe or Kr or a mixture of Xe and Kr. In a large multichamber proportional counter the K-fluorescent radiation of these gases, which escapes the cell of origin, but is absorbed in other cells of the counter, provides an additional signal. A coincidence technique, which makes use of this signal to reduce the charged particle background and to correct the energy spectrum for the escape peak, has been evaluated. The detector has an improved energy resolution over that of the conventional proportional counter and preliminary results indicate that a reduction in the background by a factor of about 1000 can be obtained. Its combined properties of very efficient background reduction and improved energy resolution make this type of instrument most suitable for spectroscopic studies of astronomical X-ray sources in the energy range of 15-100 keV. (orig.)

  14. EscapED: A Framework for Creating Educational Escape Rooms and Interactive Games to For Higher/Further Education.

    Directory of Open Access Journals (Sweden)

    Samantha Jane Clarke

    2017-09-01

    Full Text Available Game-based learning (GBL is often found to be technologically driven and more often than not, serious games for instance, are conceptualised and designed solely for digital platforms and state of the art technologies. To encourage a greater discussion on the potential benefits and challenges of a more holistic approach to developing GBL that promote human centered interactions and play for learning, the authors present the escapED programme. The escapED programme was conceived following the recent entertainment trend of escape rooms and is used for developing non-digital GBL approaches within education. escapED aids the design and creation of educational Escape Rooms and Interactive Gaming Experiences for staff and students in further/higher education settings. The paper first presents a pilot study that was used to assess the feasibility and acceptance of University teaching staff of embedding interactive GBL into a higher education environment. The authors then present the escapED theoretical framework that was used to create the prototype game for the pilot study as a tool to aid future design and development of on-site interactive experiences. The paper also presents an external developer report of using the escapED framework to develop a prototype game for teaching research methods to Southampton University students. Finally, the authors present a discussion on the use of the escapED framework so far and plans for future work and evaluation in order to provide engaging alternatives for learning and soft skills development amongst higher education staff andstudents.

  15. Reporter Assay for Endo/Lysosomal Escape of Toxin-Based Therapeutics

    Directory of Open Access Journals (Sweden)

    Roger Gilabert-Oriol

    2014-05-01

    Full Text Available Protein-based therapeutics with cytosolic targets are capable of exhibiting their therapeutic effect once they have escaped from the endosomes or lysosomes. In this study, the reporters—horseradish peroxidase (HRP, Alexa Fluor 488 (Alexa and ricin A-chain (RTA—were investigated for their capacity to monitor the endo/lysosomal escape of the ribosome-inactivating protein, saporin. The conjugates—saporin-HRP, Alexasaporin and saporin-KQ-RTA—were constructed, and the endo/lysosomal escape of these conjugates alone (lack of endo/lysosomal release or in combination with certain structurally-specific triterpenoidal saponins (efficient endo/lysosomal escape was characterized. HRP failed in reporting the endo/lysosomal escape of saporin. Contrastingly, Alexa Fluor 488 successfully allowed the report of the process at a toxin concentration of 1000 nM. In addition, single endo/lysosome analysis facilitated the determination of the amount of Alexasaporin released from each vesicle. RTA was also successful in reporting the endo/lysosomal escape of the enzymatically inactive mutant, saporin-KQ, but in this case, the sensitivity of the method reached a toxin concentration of 10 nM. In conclusion, the simultaneous usage of Alexa Fluor 488 and RTA as reporters may provide the possibility of monitoring the endo/lysosomal escape of protein-based therapeutics in the concentration range of 10–1000 nM.

  16. Malaria parasites: the great escape

    Directory of Open Access Journals (Sweden)

    Laurent Rénia

    2016-11-01

    Full Text Available Parasites of the genus Plasmodium have a complex life cycle. They alternate between their final mosquito host and their intermediate hosts. The parasite can be either extra- or intracellular, depending on the stage of development. By modifying their shape, motility, and metabolic requirements, the parasite adapts to the different environments in their different hosts. The parasite has evolved to escape the multiple immune mechanisms in the host that try to block parasite development at the different stages of their development. In this article, we describe the mechanisms reported thus far that allow the Plasmodium parasite to evade innate and adaptive immune responses.

  17. Equivariant elliptic homology

    International Nuclear Information System (INIS)

    Devoto, J.A.

    1992-05-01

    In a previous paper we studied the modular properties of indices of elliptic operators on twisted loop spaces of manifolds with finite group actions. This motivates the introduction of the universal twisted elliptic genus. This genus can be interpreted as a ring homomorphism from the equivariant bordism ring MU * G to a ring Ell * G . It is shown that the functor X→Ell * G =MU * G (X)x MU * G Ell * G defines an equivariant homology theory, and that the associated cohomology theory satisfies a conjecture of Atiyah and Segal about generalized Lefchetz formulas. (author). 24 refs

  18. The PIKE homolog Centaurin gamma regulates developmental timing in Drosophila.

    Directory of Open Access Journals (Sweden)

    Anna Lisa Gündner

    Full Text Available Phosphoinositide-3-kinase enhancer (PIKE proteins encoded by the PIKE/CENTG1 gene are members of the gamma subgroup of the Centaurin superfamily of small GTPases. They are characterized by their chimeric protein domain architecture consisting of a pleckstrin homology (PH domain, a GTPase-activating (GAP domain, Ankyrin repeats as well as an intrinsic GTPase domain. In mammals, three PIKE isoforms with variations in protein structure and subcellular localization are encoded by the PIKE locus. PIKE inactivation in mice results in a broad range of defects, including neuronal cell death during brain development and misregulation of mammary gland development. PIKE -/- mutant mice are smaller, contain less white adipose tissue, and show insulin resistance due to misregulation of AMP-activated protein kinase (AMPK and insulin receptor/Akt signaling. here, we have studied the role of PIKE proteins in metabolic regulation in the fly. We show that the Drosophila PIKE homolog, ceng1A, encodes functional GTPases whose internal GAP domains catalyze their GTPase activity. To elucidate the biological function of ceng1A in flies, we introduced a deletion in the ceng1A gene by homologous recombination that removes all predicted functional PIKE domains. We found that homozygous ceng1A mutant animals survive to adulthood. In contrast to PIKE -/- mouse mutants, genetic ablation of Drosophila ceng1A does not result in growth defects or weight reduction. Although metabolic pathways such as insulin signaling, sensitivity towards starvation and mobilization of lipids under high fed conditions are not perturbed in ceng1A mutants, homozygous ceng1A mutants show a prolonged development in second instar larval stage, leading to a late onset of pupariation. In line with these results we found that expression of ecdysone inducible genes is reduced in ceng1A mutants. Together, we propose a novel role for Drosophila Ceng1A in regulating ecdysone signaling-dependent second to

  19. RpoS controls the Vibrio cholerae mucosal escape response.

    Directory of Open Access Journals (Sweden)

    Alex Toftgaard Nielsen

    2006-10-01

    Full Text Available Vibrio cholerae causes a severe diarrhoeal disease by secreting a toxin during colonization of the epithelium in the small intestine. Whereas the initial steps of the infectious process have been intensively studied, the last phases have received little attention. Confocal microscopy of V. cholerae O1-infected rabbit ileal loops captured a distinctive stage in the infectious process: 12 h post-inoculation, bacteria detach from the epithelial surface and move into the fluid-filled lumen. Designated the "mucosal escape response," this phenomenon requires RpoS, the stationary phase alternative sigma factor. Quantitative in vivo localization assays corroborated the rpoS phenotype and showed that it also requires HapR. Expression profiling of bacteria isolated from ileal loop fluid and mucus demonstrated a significant RpoS-dependent upregulation of many chemotaxis and motility genes coincident with the emigration of bacteria from the epithelial surface. In stationary phase cultures, RpoS was also required for upregulation of chemotaxis and motility genes, for production of flagella, and for movement of bacteria across low nutrient swarm plates. The hapR mutant produced near-normal numbers of flagellated cells, but was significantly less motile than the wild-type parent. During in vitro growth under virulence-inducing conditions, the rpoS mutant produced 10- to 100-fold more cholera toxin than the wild-type parent. Although the rpoS mutant caused only a small over-expression of the genes encoding cholera toxin in the ileal loop, it resulted in a 30% increase in fluid accumulation compared to the wild-type. Together, these results show that the mucosal escape response is orchestrated by an RpoS-dependent genetic program that activates chemotaxis and motility functions. This may furthermore coincide with reduced virulence gene expression, thus preparing the organism for the next stage in its life cycle.

  20. Grid diagrams and Khovanov homology

    DEFF Research Database (Denmark)

    Droz, Jean-Marie; Wagner, Emmanuel

    2009-01-01

    We explain how to compute the Jones polynomial of a link from one of its grid diagrams and we observe a connection between Bigelow’s homological definition of the Jones polynomial and Kauffman’s definition of the Jones polynomial. Consequently, we prove that the Maslov grading on the Seidel–Smith...... symplectic link invariant coincides with the difference between the homological grading on Khovanov homology and the Jones grading on Khovanov homology. We give some evidence for the truth of the Seidel–Smith conjecture....

  1. Submarine 'safe to escape' studies in man.

    Science.gov (United States)

    Jurd, K M; Seddon, F M; Thacker, J C; Blogg, S L; Stansfield, M R D; White, M G; Loveman, G A M

    2014-01-01

    The Royal Navy requires reliable advice on the safe limits of escape from a distressed submarine (DISSUB). Flooding in a DISSUB may cause a rise in ambient pressure, increasing the risk of decompression sickness (DCS) and decreasing the maximum depth from which it is safe to escape. The aim of this study was to investigate the pressure/depth limits to escape following saturation at raised ambient pressure. Exposure to saturation pressures up to 1.6 bar (a) (160 kPa) (n = 38); escapes from depths down to 120 meters of sea water (msw) (n = 254) and a combination of saturation followed by escape (n = 90) was carried out in the QinetiQ Submarine Escape Simulator, Alverstoke, United Kingdom. Doppler ultrasound monitoring was used to judge the severity of decompression stress. The trials confirmed the previously untested advice, in the Guardbook, that if a DISSUB was lying at a depth of 90 msw, then it was safe to escape when the pressure in the DISSUB was 1.5 bar (a), but also indicated that this advice may be overly conservative. This study demonstrated that the upper DISSUB saturation pressure limit to safe escape from 90 msw was 1.6 bar (a), resulting in two cases of DCS.

  2. Escape of atmospheric gases from the Moon

    Indian Academy of Sciences (India)

    The escape rate of atmospheric molecules on the Moon is calculated.Based on the assumption that the rates of emission and escape of gases attain equilibrium, the ratio of molecular number densities during day and night, 0/0, can be explained. The plausible emission rate of helium and radioactive elements present ...

  3. Escape of atmospheric gases from the Moon

    Indian Academy of Sciences (India)

    its weak gravity, the atmospheric molecules gradu- ally escaped, resulting in the very thin atmosphere existing now. To see if a thick atmosphere could be retained or not, we assume that the air hav- ing pressure of 1atmosphere (as exists on Earth now) existed on the Moon initially and calculate the escape life times for ...

  4. Two examples of escaping harmonic maps

    International Nuclear Information System (INIS)

    Pereira do Valle, A.; Verjovsky, A.

    1988-12-01

    This paper is part of a study on the existence of special harmonic maps on complete non-compact Riemannian manifolds. We generalize the notion of escaping geodesic and prove some results on the existence of escaping harmonic maps. 11 refs, 6 figs

  5. Escaping Homelessness: Anticipated and Perceived Facilitators

    Science.gov (United States)

    Patterson, Allisha; Tweed, Roger

    2009-01-01

    One study with two distinct sections was conducted to identify factors facilitating escape from homelessness. In Section 1, 58 homeless individuals rated possible facilitators of escape (factors they believed would help them become more independent and self-sufficient). In Section 2, 80 participants who had already exited homelessness rated the…

  6. Learning from escaped prescribed fire reviews [Abstract

    Science.gov (United States)

    Anne Black; Dave Thomas; James Saveland

    2011-01-01

    Over the past decade, the wildland fire community has developed a number of innovative methods for conducting a review following escape of a prescribed fire. The stated purpose been to identify methods that not only meet policy requirements, but to reduce future escapes. Implicit is the assumption that a review leads to learning. Yet, as organizational learning expert...

  7. On S3-equivariant homology

    Directory of Open Access Journals (Sweden)

    Mohamed Elhamdadi

    2001-01-01

    Full Text Available We prove that the group S3 (norm 1 quaternions cannot be a geometric realization of a crossed simplicial group and construct an exact sequence connecting S3-equivariant homology of an S3-space with its Pin(2-equivariant homology.

  8. Physics escape room as an educational tool

    Science.gov (United States)

    Vörös, Alpár István Vita; Sárközi, Zsuzsa

    2017-12-01

    Escape rooms have flourished in the last decade. These are adventure games in which players work together to solve puzzles using hints, clues and a strategy to escape from a locked room. In many cases they use different phenomena related to physics. Hence the idea of using escape rooms in science centers or even in classroom activities. Escape rooms are designed for one single team of players, the method is more suitable for activities in a science centre. In our paper, we show that escape rooms' puzzle solving methods could be used in physics classroom activities as well, taking into account that several teams have to work together in the same room/place. We have developed an educational escape game for physics of fluids, as this topic is left out from the Romanian high-school curriculum. We have tried out our game during the project week called "Şcoala altfel" ("school in a different way") and in a physics camp for gifted students. We present the designed physics escape game and the results.

  9. A Model for SEP Escape

    Science.gov (United States)

    Antiochos, S. K.; Masson, S.; DeVore, C. R.

    2012-01-01

    Magnetic reconnection in the solar atmosphere is believed to be the driver of most solar explosive phenomena. Therefore, the topology of the coronal magnetic field is central to understanding the solar drivers of space weather. Of particular importance to space weather are the impulsive Solar Energetic particles that are associated with some CME/eruptive flare events. Observationally, the magnetic configuration of active regions where solar eruptions originate appears to agree with the standard eruptive flare model. According to this model, particles accelerated at the flare reconnection site should remain trapped in the corona and the ejected plasmoid. However, flare-accelerated particles frequently reach the Earth long before the CME does. We present a model that may account for the injection of energetic particles onto open magnetic flux tubes connecting to the Earth. Our model is based on the well-known 2.5D breakout topology, which has a coronal null point (null line) and a four-flux system. A key new addition, however, is that we include an isothermal solar wind with open-flux regions. Depending on the location of the open flux with respect to the null point, we find that the flare reconnection can consist of two distinct phases. At first, the flare reconnection involves only closed field, but if the eruption occurs close to the open field, we find a second phase involving interchange reconnection between open and closed. We argue that this second reconnection episode is responsible for the injection of flare-accelerated particles into the interplanetary medium. We will report on our recent work toward understanding how flare particles escape to the heliosphere. This work uses high-resolution 2.5D MHD numerical simulations performed with the Adaptively Refined MHD Solver (ARMS).

  10. Homology theory on algebraic varieties

    CERN Document Server

    Wallace, Andrew H

    1958-01-01

    Homology Theory on Algebraic Varieties, Volume 6 deals with the principles of homology theory in algebraic geometry and includes the main theorems first formulated by Lefschetz, one of which is interpreted in terms of relative homology and another concerns the Poincaré formula. The actual details of the proofs of these theorems are introduced by geometrical descriptions, sometimes aided with diagrams. This book is comprised of eight chapters and begins with a discussion on linear sections of an algebraic variety, with emphasis on the fibring of a variety defined over the complex numbers. The n

  11. Escape dynamics: a continuous-time approximation

    Czech Academy of Sciences Publication Activity Database

    Kolyuzhnov, D.; Bogomolova, A.; Slobodyan, Sergey

    2014-01-01

    Roč. 38, January (2014), s. 161-183 ISSN 0165-1889 Institutional support: RVO:67985998 Keywords : constant gain adaptive learning * escape dynamics * recursive least squares Subject RIV: AH - Economics Impact factor: 1.018, year: 2014

  12. Chromosome movements promoted by the mitochondrial protein SPD-3 are required for homology search during Caenorhabditis elegans meiosis.

    Directory of Open Access Journals (Sweden)

    Leticia Labrador

    2013-05-01

    Full Text Available Pairing of homologous chromosomes during early meiosis is essential to prevent the formation of aneuploid gametes. Chromosome pairing includes a step of homology search followed by the stabilization of homolog interactions by the synaptonemal complex (SC. These events coincide with dramatic changes in nuclear organization and rapid chromosome movements that depend on cytoskeletal motors and are mediated by SUN-domain proteins on the nuclear envelope, but how chromosome mobility contributes to the pairing process remains poorly understood. We show that defects in the mitochondria-localizing protein SPD-3 cause a defect in homolog pairing without impairing nuclear reorganization or SC assembly, which results in promiscuous installation of the SC between non-homologous chromosomes. Preventing SC assembly in spd-3 mutants does not improve homolog pairing, demonstrating that SPD-3 is required for homology search at the start of meiosis. Pairing center regions localize to SUN-1 aggregates at meiosis onset in spd-3 mutants; and pairing-promoting proteins, including cytoskeletal motors and polo-like kinase 2, are normally recruited to the nuclear envelope. However, quantitative analysis of SUN-1 aggregate movement in spd-3 mutants demonstrates a clear reduction in mobility, although this defect is not as severe as that seen in sun-1(jf18 mutants, which also show a stronger pairing defect, suggesting a correlation between chromosome-end mobility and the efficiency of pairing. SUN-1 aggregate movement is also impaired following inhibition of mitochondrial respiration or dynein knockdown, suggesting that mitochondrial function is required for motor-driven SUN-1 movement. The reduced chromosome-end mobility of spd-3 mutants impairs coupling of SC assembly to homology recognition and causes a delay in meiotic progression mediated by HORMA-domain protein HTP-1. Our work reveals how chromosome mobility impacts the different early meiotic events that promote

  13. St.Petersburg Escape Experience Tour

    OpenAIRE

    Palagina, Mariia; Zhak, Svetlana

    2017-01-01

    The growing popularity of Russia as a tourist destination and the high interest towards escape rooms and quests opens new business opportunities and market niches. The aim of this thesis is to develop a tourist product based on the new escape room tourism concept combining the historical, cultural and game experiences. The choice of the theme and destination was determined by the authors’ personal backgrounds and the destination proximity to Finland. The theoretical research was implement...

  14. The escape problem for mortal walkers

    OpenAIRE

    Grebenkov, D. S.; Rupprecht, J. -F.

    2016-01-01

    We introduce and investigate the escape problem for random walkers that may eventually die, decay, bleach, or lose activity during their diffusion towards an escape or reactive region on the boundary of a confining domain. In the case of a first-order kinetics (i.e., exponentially distributed lifetimes), we study the effect of the associated death rate onto the survival probability, the exit probability, and the mean first passage time. We derive the upper and lower bounds and some approximat...

  15. Combining Evidence from Homologous Datasets

    National Research Council Canada - National Science Library

    Feng, Ao; Allan, James

    2006-01-01

    .... We argue that combining evidence from these "homologous" datasets can give us better representation of the original data, and our experiments show that a model combining all sources outperforms each...

  16. Fivebranes and 3-manifold homology

    Science.gov (United States)

    Gukov, Sergei; Putrov, Pavel; Vafa, Cumrun

    2017-07-01

    Motivated by physical constructions of homological knot invariants, we study their analogs for closed 3-manifolds. We show that fivebrane compactifications provide a universal description of various old and new homological invariants of 3-manifolds. In terms of 3d/3d correspondence, such invariants are given by the Q-cohomology of the Hilbert space of partially topologically twisted 3d N=2 theory T[ M 3] on a Riemann surface with defects. We demonstrate this by concrete and explicit calculations in the case of monopole/Heegaard Floer homology and a 3-manifold analog of Khovanov-Rozansky link homology. The latter gives a categorification of Chern-Simons partition function. Some of the new key elements include the explicit form of the S-transform and a novel connection between categorification and a previously mysterious role of Eichler integrals in Chern-Simons theory.

  17. Submarine tower escape decompression sickness risk estimation.

    Science.gov (United States)

    Loveman, G A M; Seddon, E M; Thacker, J C; Stansfield, M R; Jurd, K M

    2014-01-01

    Actions to enhance survival in a distressed submarine (DISSUB) scenario may be guided in part by knowledge of the likely risk of decompression sickness (DCS) should the crew attempt tower escape. A mathematical model for DCS risk estimation has been calibrated against DCS outcome data from 3,738 exposures of either men or goats to raised pressure. Body mass was used to scale DCS risk. The calibration data included more than 1,000 actual or simulated submarine escape exposures and no exposures with substantial staged decompression. Cases of pulmonary barotrauma were removed from the calibration data. The calibrated model was used to estimate the likelihood of DCS occurrence following submarine escape from the United Kingdom Royal Navy tower escape system. Where internal DISSUB pressure remains at - 0.1 MPa, escape from DISSUB depths 60% DCS risk predicted for a 200-meter escape from saturation at 0.21 MPa. Using the calibrated model to predict DCS for direct ascent from saturation gives similar risk estimates to other published models.

  18. Polymer escape from a confining potential

    International Nuclear Information System (INIS)

    Mökkönen, Harri; Ikonen, Timo; Jónsson, Hannes; Ala-Nissila, Tapio

    2014-01-01

    The rate of escape of polymers from a two-dimensionally confining potential well has been evaluated using self-avoiding as well as ideal chain representations of varying length, up to 80 beads. Long timescale Langevin trajectories were calculated using the path integral hyperdynamics method to evaluate the escape rate. A minimum is found in the rate for self-avoiding polymers of intermediate length while the escape rate decreases monotonically with polymer length for ideal polymers. The increase in the rate for long, self-avoiding polymers is ascribed to crowding in the potential well which reduces the free energy escape barrier. An effective potential curve obtained using the centroid as an independent variable was evaluated by thermodynamic averaging and Kramers rate theory then applied to estimate the escape rate. While the qualitative features are well reproduced by this approach, it significantly overestimates the rate, especially for the longer polymers. The reason for this is illustrated by constructing a two-dimensional effective energy surface using the radius of gyration as well as the centroid as controlled variables. This shows that the description of a transition state dividing surface using only the centroid fails to confine the system to the region corresponding to the free energy barrier and this problem becomes more pronounced the longer the polymer is. A proper definition of a transition state for polymer escape needs to take into account the shape as well as the location of the polymer

  19. Contribution of Candida albicans cell wall components to recognition by and escape from murine macrophages.

    Science.gov (United States)

    McKenzie, C G J; Koser, U; Lewis, L E; Bain, J M; Mora-Montes, H M; Barker, R N; Gow, N A R; Erwig, L P

    2010-04-01

    The pathogenicity of the opportunistic human fungal pathogen Candida albicans depends on its ability to escape destruction by the host immune system. Using mutant strains that are defective in cell surface glycosylation, cell wall protein synthesis, and yeast-hypha morphogenesis, we have investigated three important aspects of C. albicans innate immune interactions: phagocytosis by primary macrophages and macrophage cell lines, hyphal formation within macrophage phagosomes, and the ability to escape from and kill macrophages. We show that cell wall glycosylation is critically important for the recognition and ingestion of C. albicans by macrophages. Phagocytosis was significantly reduced for mutants deficient in phosphomannan biosynthesis (mmn4Delta, pmr1Delta, and mnt3 mnt5Delta), whereas O- and N-linked mannan defects (mnt1Delta mnt2Delta and mns1Delta) were associated with increased ingestion, compared to the parent wild-type strains and genetically complemented controls. In contrast, macrophage uptake of mutants deficient in cell wall proteins such as adhesins (ece1Delta, hwp1Delta, and als3Delta) and yeast-locked mutants (clb2Delta, hgc1Delta, cph1Delta, efg1Delta, and efg1Delta cph1Delta), was similar to that observed for wild-type C. albicans. Killing of macrophages was abrogated in hypha-deficient strains, significantly reduced in all glycosylation mutants, and comparable to wild type in cell wall protein mutants. The diminished ability of glycosylation mutants to kill macrophages was not a consequence of impaired hyphal formation within macrophage phagosomes. Therefore, cell wall composition and the ability to undergo yeast-hypha morphogenesis are critical determinants of the macrophage's ability to ingest and process C. albicans.

  20. Object-oriented Persistent Homology.

    Science.gov (United States)

    Wang, Bao; Wei, Guo-Wei

    2016-01-15

    Persistent homology provides a new approach for the topological simplification of big data via measuring the life time of intrinsic topological features in a filtration process and has found its success in scientific and engineering applications. However, such a success is essentially limited to qualitative data classification and analysis. Indeed, persistent homology has rarely been employed for quantitative modeling and prediction. Additionally, the present persistent homology is a passive tool, rather than a proactive technique, for classification and analysis. In this work, we outline a general protocol to construct object-oriented persistent homology methods. By means of differential geometry theory of surfaces, we construct an objective functional, namely, a surface free energy defined on the data of interest. The minimization of the objective functional leads to a Laplace-Beltrami operator which generates a multiscale representation of the initial data and offers an objective oriented filtration process. The resulting differential geometry based object-oriented persistent homology is able to preserve desirable geometric features in the evolutionary filtration and enhances the corresponding topological persistence. The cubical complex based homology algorithm is employed in the present work to be compatible with the Cartesian representation of the Laplace-Beltrami flow. The proposed Laplace-Beltrami flow based persistent homology method is extensively validated. The consistence between Laplace-Beltrami flow based filtration and Euclidean distance based filtration is confirmed on the Vietoris-Rips complex for a large amount of numerical tests. The convergence and reliability of the present Laplace-Beltrami flow based cubical complex filtration approach are analyzed over various spatial and temporal mesh sizes. The Laplace-Beltrami flow based persistent homology approach is utilized to study the intrinsic topology of proteins and fullerene molecules. Based on a

  1. Radon escape from New Zealand speleothems

    International Nuclear Information System (INIS)

    Lyons, R.G.; Crossley, P.C.; Ditchburn, R.G.; McCabe, W.J.; Whitehead, N.

    1989-01-01

    When calculating the environment radiation absorbed dose rate in ESR or TL dating, it is usual to allow for the possibility of disequilibrium in the uranium-series decay chain, due to the escape of radon from the sample. A number of speleothems from a temperate climate, varying in age have been analysed for thorium and polonium isotopes. A comparison of thorium and polonium activities with the expected values, derived from the age of the sample and the initial concentrations, gives an estimate of the radon escape. The recovery rates of uranium and thorium were monitored by spiking but the recovery rate of polonium must be regarded as a minimum; estimates of radon escape are therefore likely to be overestimates. Of 19 speleothems studied, only two gave results inconsistent with values predicted on the basis of no radon loss one, a relatively young sample, showed evidence of radium coprecipitation with uranium, and one, a dog-tooth spar with an open crystal structure and a high porosity showed evidence for radon escape. A third sample, also a flowstone/spar with a higher porosity than normal, was marginally significant. As the degree of radon escape will vary from sample to sample, the environment dose rate must be regarded as having a high level of uncertainty for samples of this type, unless radon escape is determined experimentally. The remaining samples (12 stalagmites, 3 stalactites and 1 flowstone), of a more massive structure, showed no significant radon escape and therefore the environment dose rate for such samples should be calculated on the basis of radon retention. (author)

  2. Radon escape from New Zealand speleothems

    Energy Technology Data Exchange (ETDEWEB)

    Lyons, R.G.; Crossley, P.C. (Auckland Univ. (New Zealand). Dept. of Geography); Ditchburn, R.G.; McCabe, W.J.; Whitehead, N. (Department of Scientific and Industrial Research, Lower Hutt (New Zealand). Inst. of Nuclear Sciences)

    1989-01-01

    When calculating the environment radiation absorbed dose rate in ESR or TL dating, it is usual to allow for the possibility of disequilibrium in the uranium-series decay chain, due to the escape of radon from the sample. A number of speleothems from a temperate climate, varying in age have been analysed for thorium and polonium isotopes. A comparison of thorium and polonium activities with the expected values, derived from the age of the sample and the initial concentrations, gives an estimate of the radon escape. The recovery rates of uranium and thorium were monitored by spiking but the recovery rate of polonium must be regarded as a minimum; estimates of radon escape are therefore likely to be overestimates. Of 19 speleothems studied, only two gave results inconsistent with values predicted on the basis of no radon loss one, a relatively young sample, showed evidence of radium coprecipitation with uranium, and one, a dog-tooth spar with an open crystal structure and a high porosity showed evidence for radon escape. A third sample, also a flowstone/spar with a higher porosity than normal, was marginally significant. As the degree of radon escape will vary from sample to sample, the environment dose rate must be regarded as having a high level of uncertainty for samples of this type, unless radon escape is determined experimentally. The remaining samples (12 stalagmites, 3 stalactites and 1 flowstone), of a more massive structure, showed no significant radon escape and therefore the environment dose rate for such samples should be calculated on the basis of radon retention. (author).

  3. A novel mutation in TFL1 homolog affecting determinacy in cowpea (Vigna unguiculata).

    Science.gov (United States)

    Dhanasekar, P; Reddy, K S

    2015-02-01

    Mutations in the widely conserved Arabidopsis Terminal Flower 1 (TFL1) gene and its homologs have been demonstrated to result in determinacy across genera, the knowledge of which is lacking in cowpea. Understanding the molecular events leading to determinacy of apical meristems could hasten development of cowpea varieties with suitable ideotypes. Isolation and characterization of a novel mutation in cowpea TFL1 homolog (VuTFL1) affecting determinacy is reported here for the first time. Cowpea TFL1 homolog was amplified using primers designed based on conserved sequences in related genera and sequence variation was analysed in three gamma ray-induced determinate mutants, their indeterminate parent "EC394763" and two indeterminate varieties. The analyses of sequence variation exposed a novel SNP distinguishing the determinate mutants from the indeterminate types. The non-synonymous point mutation in exon 4 at position 1,176 resulted from transversion of cytosine (C) to adenine (A) leading to an amino acid change (Pro-136 to His) in determinate mutants. The effect of the mutation on protein function and stability was predicted to be detrimental using different bioinformatics/computational tools. The functionally significant novel substitution mutation is hypothesized to affect determinacy in the cowpea mutants. Development of suitable regeneration protocols in this hitherto recalcitrant crop and subsequent complementation assay in mutants or over-expressing assay in parents could decisively conclude the role of the SNP in regulating determinacy in these cowpea mutants.

  4. Dynamic escape of pre-existing raltegravir-resistant HIV-1 from raltegravir selection pressure.

    Science.gov (United States)

    Codoñer, Francisco M; Pou, Christian; Thielen, Alexander; García, Federico; Delgado, Rafael; Dalmau, David; Santos, José Ramon; Buzón, Maria José; Martínez-Picado, Javier; Alvarez-Tejado, Miguel; Clotet, Bonaventura; Ruiz, Lidia; Paredes, Roger

    2010-12-01

    Using quantitative deep HIV-1 sequencing in a subject who developed virological failure to deep salvage therapy with raltegravir, we found that most Q148R and N155H mutants detected at the time of virological failure originated from pre-existing minority Q148R and N155H variants through independent evolutionary clusters. Double 148R+N155H mutants were also detected in 1.7% of viruses at virological failure in association with E138K and/or G163R. Our findings illustrate the ability of HIV-1 to escape from suboptimal antiretroviral drug pressure through selection of pre-existing drug-resistant mutants, underscoring the importance of using fully active antiretroviral regimens to treat all HIV-1-infected subjects. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Thermal escape from extrasolar giant planets.

    Science.gov (United States)

    Koskinen, Tommi T; Lavvas, Panayotis; Harris, Matthew J; Yelle, Roger V

    2014-04-28

    The detection of hot atomic hydrogen and heavy atoms and ions at high altitudes around close-in extrasolar giant planets (EGPs) such as HD209458b implies that these planets have hot and rapidly escaping atmospheres that extend to several planetary radii. These characteristics, however, cannot be generalized to all close-in EGPs. The thermal escape mechanism and mass loss rate from EGPs depend on a complex interplay between photochemistry and radiative transfer driven by the stellar UV radiation. In this study, we explore how these processes change under different levels of irradiation on giant planets with different characteristics. We confirm that there are two distinct regimes of thermal escape from EGPs, and that the transition between these regimes is relatively sharp. Our results have implications for thermal mass loss rates from different EGPs that we discuss in the context of currently known planets and the detectability of their upper atmospheres.

  6. Persistent homology of complex networks

    International Nuclear Information System (INIS)

    Horak, Danijela; Maletić, Slobodan; Rajković, Milan

    2009-01-01

    Long-lived topological features are distinguished from short-lived ones (considered as topological noise) in simplicial complexes constructed from complex networks. A new topological invariant, persistent homology, is determined and presented as a parameterized version of a Betti number. Complex networks with distinct degree distributions exhibit distinct persistent topological features. Persistent topological attributes, shown to be related to the robust quality of networks, also reflect the deficiency in certain connectivity properties of networks. Random networks, networks with exponential connectivity distribution and scale-free networks were considered for homological persistency analysis

  7. Promising rice mutants

    International Nuclear Information System (INIS)

    Hakim, L.; Azam, M.A.; Miah, A.J.; Mansur, M.A.; Akanda, H.R.

    1988-01-01

    Two induced mutants namely, Mut NS 1 (tall) and Mut NS 5 (semi-dwarf) derived from rice variety Nizersail were evaluated for various agronomic characters at four locations in Bangladesh. Both the mutants matured about three weeks earlier and yielded significantly higher than the parent variety Nizersail. (author). 3 tabs., 9 refs

  8. Mutant heterosis in rice

    International Nuclear Information System (INIS)

    1987-01-01

    In the variety TKM6 a high yielding semidwarf mutant has been induced. This TKM6 mutant was used in test crosses with a number of other varieties and mutants to examine the extent of heterosis of dwarfs in rice and to select superior crosses. An excerpt of the published data is given. It appears from the backcross of the mutant with its original variety, that an increase in number of productive tillers occurs in the hybrid, leading to a striking grain yield increase, while the semi-dwarf culm length (the main mutant character) reverts to the normal phenotype. In the cross with IR8 on the other hand, there is only a minimal increase in tiller number but a substantial increase in TGW leading to more than 30% yield increase over the better parent

  9. A wheat cold resistance mutant derived from space mutagenesis

    International Nuclear Information System (INIS)

    Li Peng; Sun Mingzhu; Zhang Fengyun; Gao Guoqiang; Qiu Denglin; Li Xinhua

    2012-01-01

    A cold resistance mutant, obtained by spaceflight mutagenesis on the seeds of wheat variety Han6172, and the DNA of cold resistance mutant and contrast Han6172 were compared by SRAP technique. 380 pairs of primers were screened, 6 pairs of them had polymorphisms between mutant and contrast, the rate was 1.58%, and this data indicated that there are no obvious DNA differences between mutant and contrast Six specific fragments were obtained, 3 fragments of them were amplified in mutant. Homology analysis in GenBank showed that Me3-Em7-Mt, Me4-Em11-CK, Me7-Em19-CK and Me6-Em9-Mt all had homologous sequences with wheat chromosome 3B-specific BAC library, and this result indicated that the gene and regulator sequences associated with mutant cold resistance might locate on 3B chromosome. It was speculated that space mutation induced the mutation of 3B chromosome primary structure, and influenced the expressions of cold resistance genes, which resulted in the mutation of cold resistance ability. (authors)

  10. Martian Atmospheric and Ionospheric plasma Escape

    Science.gov (United States)

    Lundin, Rickard

    2016-04-01

    Solar forcing is responsible for the heating, ionization, photochemistry, and erosion processes in the upper atmosphere throughout the lifetime of the terrestrial planets. Of the four terrestrial planets, the Earth is the only one with a fully developed biosphere, while our kin Venus and Mars have evolved into arid inhabitable planets. As for Mars, there are ample evidences for an early Noachian, water rich period on Mars. The question is, what made Mars evolve so differently compared to the Earth? Various hydrosphere and atmospheric evolution scenarios for Mars have been forwarded based on surface morphology, chemical composition, simulations, semi-empiric (in-situ data) models, and the long-term evolution of the Sun. Progress has been made, but the case is still open regarding the changes that led to the present arid surface and tenuous atmosphere at Mars. This presentation addresses the long-term variability of the Sun, the solar forcing impact on the Martian atmosphere, and its interaction with the space environment - an electromagnetic wave and particle interaction with the upper atmosphere that has implications for its photochemistry, composition, and energization that governs thermal and non-thermal escape. Non-thermal escape implies an electromagnetic upward energization of planetary ions and molecules to velocities above escape velocity, a process governed by a combination of solar EUV radiation (ionization), and energy and momentum transfer by the solar wind. The ion escape issue dates back to the early Soviet and US-missions to Mars, but the first more accurate estimates of escape rates came with the Phobos-2 mission in 1989. Better-quality ion composition measurement results of atmospheric/ionospheric ion escape from Mars, obtained from ESA Mars Express (MEX) instruments, have improved our understanding of the ion escape mechanism. With the NASA MAVEN spacecraft orbiting Mars since Sept. 2014, dual in-situ measurement with plasma instruments are now

  11. Cyclic homology and group actions

    Science.gov (United States)

    Ponge, Raphaël

    2018-01-01

    In this paper we present the construction of explicit quasi-isomorphisms that compute the cyclic homology and periodic cyclic homology of crossed-product algebras associated with (discrete) group actions. In the first part we deal with algebraic crossed-products associated with group actions on unital algebras over any ring k ⊃ Q. In the second part, we extend the results to actions on locally convex algebras. We then deal with crossed-products associated with group actions on manifolds and smooth varieties. For the finite order components, the results are expressed in terms of what we call "mixed equivariant cohomology". This "mixed" theory mediates between group homology and de Rham cohomology. It is naturally related to equivariant cohomology, and so we obtain explicit constructions of cyclic cycles out of equivariant characteristic classes. For the infinite order components, we simplify and correct the misidentification of Crainic (1999). An important new homological tool is the notion of "triangular S-module". This is a natural generalization of the cylindrical complexes of Getzler-Jones. It combines the mixed complexes of Burghelea-Kassel and parachain complexes of Getzler-Jones with the S-modules of Kassel-Jones. There are spectral sequences naturally associated with triangular S-modules. In particular, this allows us to recover spectral sequences of Feigin-Tsygan and Getzler-Jones and leads us to a new spectral sequence.

  12. Nociception and escape behavior in planarians

    Science.gov (United States)

    Schoetz Collins, Eva-Maria

    2015-03-01

    Planarians are famous and widely studied for their regenerative capabilities. When a moving planarian is cut through the middle, the resulting head and tail pieces instantaneously retract and exhibit a characteristic escape response that differs from normal locomotion. In asexual animals, a similar reaction is observed when the planarian undergoes fission, suggesting that reproduction through self-tearing is a rather traumatic event for the animal. Using a multiscale approach, we unravel the dynamics, mechanics, and functional aspects of the planarian escape response. This musculature-driven gait was found to be a dominating response that supersedes the urge to feed or reproduce and quantitatively differs from other modes of planarian locomotion (gliding, peristalsis). We show that this escape gait constitutes the animal's pain response mediated by TRP like receptors and the neurotransmitter histamine, and that it can be induced through adverse thermal, mechanical, electrical or chemical stimuli. Ultimately, we will examine the neuronal subpopulations involved in mediating escape reflexes in planarians and how they are functionally restored during regeneration, thereby gaining mechanistic insight into the neuronal circuits required for specific behaviors. Supported by BWF CASI and Sloan Foundation.

  13. Pade approximant calculations for neutron escape probability

    International Nuclear Information System (INIS)

    El Wakil, S.A.; Saad, E.A.; Hendi, A.A.

    1984-07-01

    The neutron escape probability from a non-multiplying slab containing internal source is defined in terms of a functional relation for the scattering function for the diffuse reflection problem. The Pade approximant technique is used to get numerical results which compare with exact results. (author)

  14. How do biological systems escape 'chaotic' state?

    Indian Academy of Sciences (India)

    B J Rao

    2018-02-13

    Feb 13, 2018 ... triggering 'escape from homeostasis' (Nijhout et al. 2014) where phenotypes begin to become less stable and eventually turn into fully unstable state, the start of 'chaos' in a system. Therefore, the key to biological designs is to stay close to or within the 'homeostatic plateau' and resist drifting into 'chaos'.

  15. Escape dynamics: a continuous-time approximation

    Czech Academy of Sciences Publication Activity Database

    Kolyuzhnov, Dmitri; Bogomolova, Anna; Slobodyan, S.

    2014-01-01

    Roč. 38, January (2014), s. 161-183 ISSN 0165-1889 R&D Projects: GA ČR(CZ) GBP402/12/G097 Institutional support: PRVOUK-P23 Keywords : constant gain adaptive learning * escape dynamics * recursive least squares Subject RIV: AH - Economics Impact factor: 1.018, year: 2014

  16. Net escapement of Antartic krill in trawls

    DEFF Research Database (Denmark)

    Krafft, B.A.; Krag, Ludvig Ahm; Herrmann, Bent

    This document describes the aims and methodology of a three year project (commenced in 2012) entitled Net Escapement of Antarctic krill in Trawls (NEAT). The study will include a morphology based mathematical modeling (FISHSELECT) of different sex and maturity groups of Antarctic krill (Euphausia...

  17. Escape dynamics: a continuous-time approximation

    Czech Academy of Sciences Publication Activity Database

    Kolyuzhnov, Dmitri; Bogomolova, Anna; Slobodyan, Sergey

    -, č. 285 (2006), s. 1-42 ISSN 1211-3298 Institutional research plan: CEZ:AV0Z70850503 Keywords : escape dynamics * constant gain adaptive learning * large deviations theory Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp285.pdf

  18. Centrifugally Stimulated Exospheric Ion Escape at Mercury

    Science.gov (United States)

    Delcourt, Dominique; Seki, K.; Terada, N.; Moore, Thomas E.

    2012-01-01

    We investigate the transport of ions in the low-altitude magnetosphere magnetosphere of Mercury. We show that, because of small spatial scales, the centrifugal effect due to curvature of the E B drift paths can lead to significant particle energization in the parallel direction. We demonstrate that because of this effect, ions with initial speed smaller than the escape speed such as those produced via thermal desorption can overcome gravity and escape into the magnetosphere. The escape route of this low-energy exosphere originating material is largely controlled by the magnetospheric convection rate. This escape route spreads over a narrower range of altitudes when the convection rate increases. Bulk transport of low-energy planetary material thus occurs within a limited region of space once moderate magnetospheric convection is established. These results suggest that, via release of material otherwise gravitationally trapped, the E B related centrifugal acceleration is an important mechanism for the net supply of plasma to the magnetosphere of Mercury.

  19. Learning from escaped prescribed fire reviews

    Science.gov (United States)

    Anne E. Black; Dave Thomas; James Saveland; Jennifer D. Ziegler

    2011-01-01

    The U.S. wildland fire community has developed a number of innovative methods for conducting a review following escape of a prescribed fire (expanding on the typical regional or local reviews, to include more of a learning focus - expanded After Action Reviews, reviews that incorporate High Reliability Organizing, Facilitated Learning Analyses, etc). The stated purpose...

  20. The adiponectin receptor homologs in C. elegans promote energy utilization and homeostasis

    DEFF Research Database (Denmark)

    Svensson, Emma; Olsen, Louise Cathrine Braun; Mörck, Catarina

    2011-01-01

    Adiponectin is an adipokine with insulin-sensitising actions in vertebrates. Its receptors, AdipoR1 and AdipoR2, are PAQR-type proteins with 7-transmembrane domains and topologies reversed that of GPCR's, i.e. their C-termini are extracellular. We identified three adiponectin receptor homologs...... when combined with the paqr-1 mutation. paqr-2 mutants are also synthetic lethal with mutations in nhr-49, sbp-1 and fat-6, which are C. elegans homologs of nuclear hormone receptors, SREBP and FAT-6 (a Δ9 desaturase), respectively. Like paqr-2, paqr-1 is also synthetic lethal with sbp-1. Mutations...... in aak-2, the C. elegans homolog of AMPK, or nhr-80, another nuclear hormone receptor gene, suppress the growth phenotype of paqr-2 mutants, probably because they restore the balance between energy expenditure and storage. We conclude that paqr-1 and paqr-2 are receptors that regulate fatty acid...

  1. Escape driven by α -stable white noises

    Science.gov (United States)

    Dybiec, B.; Gudowska-Nowak, E.; Hänggi, P.

    2007-02-01

    We explore the archetype problem of an escape dynamics occurring in a symmetric double well potential when the Brownian particle is driven by white Lévy noise in a dynamical regime where inertial effects can safely be neglected. The behavior of escaping trajectories from one well to another is investigated by pointing to the special character that underpins the noise-induced discontinuity which is caused by the generalized Brownian paths that jump beyond the barrier location without actually hitting it. This fact implies that the boundary conditions for the mean first passage time (MFPT) are no longer determined by the well-known local boundary conditions that characterize the case with normal diffusion. By numerically implementing properly the set up boundary conditions, we investigate the survival probability and the average escape time as a function of the corresponding Lévy white noise parameters. Depending on the value of the skewness β of the Lévy noise, the escape can either become enhanced or suppressed: a negative asymmetry parameter β typically yields a decrease for the escape rate while the rate itself depicts a non-monotonic behavior as a function of the stability index α that characterizes the jump length distribution of Lévy noise, exhibiting a marked discontinuity at α=1 . We find that the typical factor of 2 that characterizes for normal diffusion the ratio between the MFPT for well-bottom-to-well-bottom and well-bottom-to-barrier-top no longer holds true. For sufficiently high barriers the survival probabilities assume an exponential behavior versus time. Distinct non-exponential deviations occur, however, for low barrier heights.

  2. Life events and escape in conversion disorder.

    Science.gov (United States)

    Nicholson, T R; Aybek, S; Craig, T; Harris, T; Wojcik, W; David, A S; Kanaan, R A

    2016-09-01

    Psychological models of conversion disorder (CD) traditionally assume that psychosocial stressors are identifiable around symptom onset. In the face of limited supportive evidence such models are being challenged. Forty-three motor CD patients, 28 depression patients and 28 healthy controls were assessed using the Life Events and Difficulties Schedule in the year before symptom onset. A novel 'escape' rating for events was developed to test the Freudian theory that physical symptoms of CD could provide escape from stressors, a form of 'secondary gain'. CD patients had significantly more severe life events and 'escape' events than controls. In the month before symptom onset at least one severe event was identified in 56% of CD patients - significantly more than 21% of depression patients [odds ratio (OR) 4.63, 95% confidence interval (CI) 1.56-13.70] and healthy controls (OR 5.81, 95% CI 1.86-18.2). In the same time period 53% of CD patients had at least one 'high escape' event - again significantly higher than 14% in depression patients (OR 6.90, 95% CI 2.05-23.6) and 0% in healthy controls. Previous sexual abuse was more commonly reported in CD than controls, and in one third of female patients was contextually relevant to life events at symptom onset. The majority (88%) of life events of potential aetiological relevance were not identified by routine clinical assessments. Nine per cent of CD patients had no identifiable severe life events. Evidence was found supporting the psychological model of CD, the Freudian notion of escape and the potential aetiological relevance of childhood traumas in some patients. Uncovering stressors of potential aetiological relevance requires thorough psychosocial evaluation.

  3. Lifespan and Glucose Metabolism in Insulin Receptor Mutant Mice

    Directory of Open Access Journals (Sweden)

    Takahiko Shimizu

    2011-01-01

    Full Text Available Insulin/insulin-like growth factor type 1 signaling regulates lifespan and resistance to oxidative stress in worms, flies, and mammals. In a previous study, we revealed that insulin receptor (IR mutant mice, which carry a homologous mutation found in the long-lived daf-2 mutant of Caenorhabditis elegans, showed enhanced resistance to oxidative stress cooperatively modulated by sex hormones and dietary signals (Baba et al., (2005. We herein investigated the lifespan of IR mutant mice to evaluate the biological significance of insulin signaling in mice. Under normoxia, mutant male mice had a lifespan comparable to that of wild-type male mice. IR mutant female mice also showed a lifespan similar to that of wild-type female mice, in spite of the fact that the IR mutant female mice acquired more resistance to oxidative stress than IR mutant male mice. On the other hand, IR mutant male and female mice both showed insulin resistance with hyperinsulinemia, but they did not develop hyperglycemia throughout their entire lifespan. These data indicate that the IR mutation does not impact the lifespan in mice, thus suggesting that insulin signaling might have a limited effect on the lifespan of mice.

  4. Indy mutants: live long and prosper

    Directory of Open Access Journals (Sweden)

    Stewart eFrankel

    2012-02-01

    Full Text Available Indy encodes the fly homologue of a mammalian transporter of di and tricarboxylatecomponents of the Krebs cycle. Reduced expression of fly Indy or two of the C. elegansIndy homologs leads to an increase in life span. Fly and worm tissues that play key roles inintermediary metabolism are also the places where Indy genes are expressed. One of themouse homologs of Indy (mIndy is mainly expressed in the liver. It has been hypothesizedthat decreased INDY activity creates a state similar to caloric restriction (CR. Thishypothesis is supported by the physiological similarities between Indy mutant flies on highcalorie food and control flies on CR, such as increased physical activity and decreases inweight, egg production, triglyceride levels, starvation resistance, and insulin signaling. Inaddition, Indy mutant flies undergo changes in mitochondrial biogenesis also observed inCR animals. Recent findings with mIndy knockout mice support and extend the findingsfrom flies. mIndy-/- mice display an increase in hepatic mitochondrial biogenesis, lipidoxidation and decreased hepatic lipogenesis. When mIndy-/- mice are fed high calorie foodthey are protected from adiposity and insulin resistance. These findings point to INDY as apotential drug target for the treatment of metabolic syndrome, type 2 diabetes and obesity.

  5. Plasticity of Escape Responses: Prior Predator Experience Enhances Escape Performance in a Coral Reef Fish.

    Directory of Open Access Journals (Sweden)

    Ryan A Ramasamy

    Full Text Available Teleost and amphibian prey undertake fast-start escape responses during a predatory attack in an attempt to avoid being captured. Although previously viewed as a reflex reaction controlled by the autonomic nervous system, the escape responses of individuals when repeatedly startled are highly variable in their characteristics, suggesting some behavioural mediation of the response. Previous studies have shown that fishes are able to learn from past experiences, but few studies have assessed how past experience with predators affect the fast-start response. Here we determined whether prior experience with the smell or sight of a predator (the Dottyback, Pseudochromis fuscus affected the escape response of juveniles of the Spiny Chromis (Acanthochromis polyacanthus. Results show that individuals exposed to any of the predator cues prior to being startled exhibited a stronger escape response (i.e., reduced latency, increased escape distance, mean response speed, maximum response speed and maximum acceleration when compared with controls. This study demonstrates the plasticity of escape responses and highlights the potential for naïve reef fish to take into account both visual and olfactory threat cues simultaneously to optimise the amplitude of their kinematic responses to perceived risk.

  6. Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation.

    Science.gov (United States)

    Liu, Donglai; Zuo, Tao; Hora, Bhavna; Song, Hongshuo; Kong, Wei; Yu, Xianghui; Goonetilleke, Nilu; Bhattacharya, Tanmoy; Perelson, Alan S; Haynes, Barton F; McMichael, Andrew J; Gao, Feng

    2014-11-19

    Fitness costs and slower disease progression are associated with a cytolytic T lymphocyte (CTL) escape mutation T242N in Gag in HIV-1-infected individuals carrying HLA-B*57/5801 alleles. However, the impact of different context in diverse HIV-1 strains on the fitness costs due to the T242N mutation has not been well characterized. To better understand the extent of fitness costs of the T242N mutation and the repair of fitness loss through compensatory amino acids, we investigated its fitness impact in different transmitted/founder (T/F) viruses. The T242N mutation resulted in various levels of fitness loss in four different T/F viruses. However, the fitness costs were significantly compromised by preexisting compensatory amino acids in (Isoleucine at position 247) or outside (glutamine at position 219) the CTL epitope. Moreover, the transmitted T242N escape mutant in subject CH131 was as fit as the revertant N242T mutant and the elimination of the compensatory amino acid I247 in the T/F viral genome resulted in significant fitness cost, suggesting the fitness loss caused by the T242N mutation had been fully repaired in the donor at transmission. Analysis of the global circulating HIV-1 sequences in the Los Alamos HIV Sequence Database showed a high prevalence of compensatory amino acids for the T242N mutation and other T cell escape mutations. Our results show that the preexisting compensatory amino acids in the majority of circulating HIV-1 strains could significantly compromise the fitness loss due to CTL escape mutations and thus increase challenges for T cell based vaccines.

  7. Homologous radioimmunoassay for human prolactin

    International Nuclear Information System (INIS)

    Reuter, A.M.; Kennes, F.; Gevaert, Y.; Franchimont, P.

    1976-01-01

    Although thee are descriptions of a range of radioimmunoassays for human prolactin in various biological fluids, only one of these is an homologous assay using human prolactin as the reference standard and tracer as well and an anti-human prolactin antiserum (Sinha, Y.N., Selby, F.W.; Lewis, U.; and Vanderlaan, W.P., 1973, J. Clin. Endocr., Vol. 36, 509). A homologous radioimmunoassay using human putuitary prolactin has been developed. The separation method is based on the double antibody solid phase system. Cross reactivity with human growth hormone (GH), placental lactogen (HPL), the pituitary protein hormones and prolactins of various species were studied as were values found in normal subjects in basal conditions and after a TRH injection. (author)

  8. Persistent Homology of Collaboration Networks

    Directory of Open Access Journals (Sweden)

    C. J. Carstens

    2013-01-01

    Full Text Available Over the past few decades, network science has introduced several statistical measures to determine the topological structure of large networks. Initially, the focus was on binary networks, where edges are either present or not. Thus, many of the earlier measures can only be applied to binary networks and not to weighted networks. More recently, it has been shown that weighted networks have a rich structure, and several generalized measures have been introduced. We use persistent homology, a recent technique from computational topology, to analyse four weighted collaboration networks. We include the first and second Betti numbers for the first time for this type of analysis. We show that persistent homology corresponds to tangible features of the networks. Furthermore, we use it to distinguish the collaboration networks from similar random networks.

  9. Enhanced Symbiotic Performance by Rhizobium tropici Glycogen Synthase Mutants

    Science.gov (United States)

    Marroquí, Silvia; Zorreguieta, Angeles; Santamaría, Carmen; Temprano, Francisco; Soberón, Mario; Megías, Manuel; Downie, J. Allan

    2001-01-01

    We isolated a Tn5-induced Rhizobium tropici mutant that has enhanced capacity to oxidize N,N-dimethyl-p-phenylendiamine (DMPD) and therefore has enhanced respiration via cytochrome oxidase. The mutant had increased levels of the cytochromes c1 and CycM and a small increase in the amount of cytochrome aa3. In plant tests, the mutant increased the dry weight of Phaseolus vulgaris plants by 20 to 38% compared with the control strain, thus showing significantly enhanced symbiotic performance. The predicted product of the mutated gene is homologous to glycogen synthases from several bacteria, and the mutant lacked glycogen. The DNA sequence of the adjacent gene region revealed six genes predicted to encode products homologous to the following gene products from Escherichia coli: glycogen phosphorylase (glgP), glycogen branching enzyme (glgB), ADP glucose pyrophosphorylase (glgC), glycogen synthase (glgA), phosphoglucomutase (pgm), and glycogen debranching enzyme (glgX). All six genes are transcribed in the same direction, and analysis with lacZ gene fusions suggests that the first five genes are organized in one operon, although pgm appears to have an additional promoter; glgX is transcribed independently. Surprisingly, the glgA mutant had decreased levels of high-molecular-weight exopolysaccharide after growth on glucose, but levels were normal after growth on galactose. A deletion mutant was constructed in order to generate a nonpolar mutation in glgA. This mutant had a phenotype similar to that of the Tn5 mutant, indicating that the enhanced respiration and symbiotic nitrogen fixation and decreased exopolysaccharide were due to mutation of glgA and not to a polar effect on a downstream gene. PMID:11208782

  10. Homological algebra in -abelian categories

    Indian Academy of Sciences (India)

    Deren Luo

    2017-08-16

    Aug 16, 2017 ... Homological algebra, as a connected system of notions and results, was first developed ..... monomorphism. Thus di−1. C( fg) is a weak kernel of di. C( fg) for i = 0,..., n −1 (we consider. X. −1, Y−1, Y−1, Xn+1, Yn+1, Yn+1 as 0 objects). Indeed, let. ( ui+1 vi. ) ..... Theorem 3.5 ((n + 2) × (n + 2)-lemma). Let A be a ...

  11. Asymmetric Effects on Escape Rates of Bistable System

    International Nuclear Information System (INIS)

    Wang Canjun; Mei Dongcheng; Dai Zucheng

    2011-01-01

    The asymmetric effects on the escape rates from the stable states x ± in the bistable system are analyzed. The results indicate that the multiplicative noise and the additive noise always enhance the particle escape from stable states x ± of bistable. However, the asymmetric parameter r enhances the particle escape from stable state x + , and holds back the particle escape from stable state x - . (general)

  12. Measurement of the resonance escape probability

    International Nuclear Information System (INIS)

    Anthony, J.P.; Bacher, P.; Lheureux, L.; Moreau, J.; Schmitt, A.P.

    1957-01-01

    The average cadmium ratio in natural uranium rods has been measured, using equal diameter natural uranium disks. These values correlated with independent measurements of the lattice buckling, enabled us to calculate values of the resonance escape probability for the G1 reactor with one or the other of two definitions. Measurements were performed on 26 mm and 32 mm rods, giving the following values for the resonance escape probability p: 0.8976 ± 0.005 and 0.912 ± 0.006 (d. 26 mm), 0.8627 ± 0.009 and 0.884 ± 0.01 (d. 32 mm). The influence of either definition on the lattice parameters is discussed, leading to values of the effective integral. Similar experiments have been performed with thorium rods. (author) [fr

  13. How does ionizing radiation escape from galaxies?

    Science.gov (United States)

    Orlitova, Ivana

    2016-10-01

    Search for sources that reionized the Universe from z 15 to z 6 is one of the main drivers of present-day astronomy. Low-mass star-forming galaxies are the most favoured sources of ionizing photons, but the searches of escaping Lyman continuum (LyC) have not been extremely successful. Our team has recently detected prominent LyC escape from five Green Pea galaxies at redshift 0.3, using the HST/COS spectrograph, which represents a significant breakthrough. We propose here to study the LyC escape of the strongest among these leakers, J1152, with spatial resolution. From the comparison of the ionizing and non-ionizing radiation maps, and surface brightness profiles, we will infer the major mode in which LyC is escaping: from the strongest starburst, from the galaxy edge, through a hole along our line-of-sight, through clumpy medium, or directly from all the production sites due to highly ionized medium in the entire galaxy. In parallel, we will test the predictive power of two highly debated indirect indicators of LyC leakage: the [OIII]5007/[OII]3727 ratio, and Lyman-alpha. We predict that their spatial distribution should closely follow that of the ionizing continuum if column densities of the neutral gas are low. This combined study, which relies on the HST unique capabilities, will bring crucial information on the structure of the leaking galaxies, provide constraints for hydrodynamic simulations, and will lead to efficient future searches for LyC leakers across a large range of redshifts.

  14. Scrunching: a novel escape gait in planarians

    Science.gov (United States)

    Cochet-Escartin, Olivier; Mickolajczyk, Keith J.; Collins, Eva-Maria S.

    2015-10-01

    The ability to escape a predator or other life-threatening situations is central to animal survival. Different species have evolved unique strategies under anatomical and environmental constraints. In this study, we describe a novel musculature-driven escape gait in planarians, ‘scrunching’, which is quantitatively different from other planarian gaits, such as gliding and peristalsis. We show that scrunching is a conserved gait among different flatworm species, underlying its importance as an escape mechanism. We further demonstrate that it can be induced by a variety of physical stimuli, including amputation, high temperature, electric shock and low pH. We discuss the functional basis for scrunching as the preferential gait when gliding is impaired due to a disruption of mucus production. Finally, we show that the key mechanical features of scrunching are adequately captured by a simple biomechanical model that is solely based on experimental data from traction force microscopy and tissue rheology without fit parameters. Together, our results form a complete description of this novel form of planarian locomotion. Because scrunching has distinct dynamics, this gait can serve as a robust behavioral readout for studies of motor neuron and muscular functions in planarians and in particular the restoration of these functions during regeneration.

  15. Escape probabilities for fluorescent x-rays

    International Nuclear Information System (INIS)

    Dance, D.R.; Day, G.J.

    1985-01-01

    Computation of the energy absorption efficiency of an x-ray photon detector involves consideration of the histories of the secondary particles produced in any initial or secondary interaction which may occur within the detector. In particular, the K or higher shell fluorescent x-rays which may be emitted following a photoelectric interaction can carry away a large fraction of the energy of the incident photon, especially if this energy is just above an absorption edge. The effects of such photons cannot be ignored and a correction term, depending upon the probability that the fluorescent x-rays will escape from the detector, must be applied to the energy absorption efficiency. For detectors such as x-ray intensifying screens, it has been usual to calculate this probability by numerical integration. In this note analytic expressions are derived for the escape probability of fluorescent photons from planar detectors in terms of exponential integral functions. Rational approximations for these functions are readily available and these analytic expressions therefore facilitate the computation of photon absorption efficiencies. A table is presented which should obviate the need for calculating the escape probability for most cases of interest. (author)

  16. HTP-1-dependent constraints coordinate homolog pairing and synapsis and promote chiasma formation during C. elegans meiosis

    OpenAIRE

    Martinez-Perez, Enrique; Villeneuve, Anne M.

    2005-01-01

    Synaptonemal complex (SC) assembly must occur between correctly paired homologous chromosomes to promote formation of chiasmata. Here, we identify the Caenorhabditis elegans HORMA-domain protein HTP-1 as a key player in coordinating establishment of homolog pairing and synapsis in C. elegans and provide evidence that checkpoint-like mechanisms couple these early meiotic prophase events. htp-1 mutants are defective in the establishment of pairing, but in contrast with the pairing-defective chk...

  17. Better understanding of homologous recombination through a 12-week laboratory course for undergraduates majoring in biotechnology.

    Science.gov (United States)

    Li, Ming; Shen, Xiaodong; Zhao, Yan; Hu, Xiaomei; Hu, Fuquan; Rao, Xiancai

    2017-07-08

    Homologous recombination, a central concept in biology, is defined as the exchange of DNA strands between two similar or identical nucleotide sequences. Unfortunately, undergraduate students majoring in biotechnology often experience difficulties in understanding the molecular basis of homologous recombination. In this study, we developed and implemented a 12-week laboratory course for biotechnology undergraduates in which gene targeting in Streptococcus suis was used to facilitate their understanding of the basic concept and process of homologous recombination. Students worked in teams of two to select a gene of interest to create a knockout mutant using methods that relied on homologous recombination. By integrating abstract knowledge and practice in the process of scientific research, students gained hands-on experience in molecular biology techniques while learning about the principle and process of homologous recombination. The learning outcomes and survey-based assessment demonstrated that students substantially enhanced their understanding of how homologous recombination could be used to study gene function. Overall, the course was very effective for helping biotechnology undergraduates learn the theory and application of homologous recombination, while also yielding positive effects in developing confidence and scientific skills for future work in research. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(4):329-335, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

  18. Identification and analysis of Ku70 and Ku80 homologs in the koji molds Aspergillus sojae and Aspergillus oryzae.

    Science.gov (United States)

    Takahashi, Tadashi; Masuda, Tsutomu; Koyama, Yasuji

    2006-01-01

    Ku genes play a key role in the non-homologous end-joining pathway. We have identified Ku70 and Ku80 homologs in the koji molds Aspergillus sojae and Aspergillus oryzae, and have constructed the disruption mutants of Ku70, Ku80, and Ku70-80 to characterize the phenotypic change in these mutants. Neither Ku70- nor Ku80-disrupted strains show hypersensitivity to the DNA damaging agents methylmethane sulfonate (MMS) and phleomycin. Moreover, undesirable phenotypes, such as poor growth or repressed conidiospore formation, were not observed in the Ku-disrupted A. sojae and A. oryzae.

  19. Productive mutants of niger

    International Nuclear Information System (INIS)

    Misra, R.C.

    2001-01-01

    Seeds of six niger (Guizotia abyssinica Cass.) varieties ('GA-10', 'ONS-8', 'IGP-72', 'N-71', 'NB-9' and 'UN-4') were treated with 0.5, 0.75 and 1% ethyl methanesulphonate. After four generations of selection, 29 mutant lines were developed and those were evaluated from 1990-92 during Kharif (July to October) and Rabi (December to March) seasons. Average plant characteristics and yield data of four high yielding mutants along with 'IGP-76' (National Check), GA-10 (Zonal Check) and 'Semiliguda Local' (Local Check) are presented

  20. Catching homologies by geometric entropy

    Science.gov (United States)

    Felice, Domenico; Franzosi, Roberto; Mancini, Stefano; Pettini, Marco

    2018-02-01

    A geometric entropy is defined in terms of the Riemannian volume of the parameter space of a statistical manifold associated with a given network. As such it can be a good candidate for measuring networks complexity. Here we investigate its ability to single out topological features of networks proceeding in a bottom-up manner: first we consider small size networks by analytical methods and then large size networks by numerical techniques. Two different classes of networks, the random graphs and the scale-free networks, are investigated computing their Betti numbers and then showing the capability of geometric entropy of detecting homologies.

  1. Kuranishi homology and Kuranishi cohomology

    OpenAIRE

    Joyce, Dominic

    2007-01-01

    A Kuranishi space is a topological space with a Kuranishi structure, defined by Fukaya and Ono. Kuranishi structures occur naturally on moduli spaces of J-holomorphic curves in symplectic geometry. Let Y be an orbifold and R a commutative ring or Q-algebra. We define two kinds of Kuranishi homology KH_*(Y;R). The chain complex KC_*(Y;R) defining KH_*(Y;R) is spanned over R by [X,f,G], for X a compact oriented Kuranishi space with corners, f : X --> Y smooth, and G "gauge-fixing data" which ma...

  2. The cost of the sword: escape performance in male swordtails.

    Directory of Open Access Journals (Sweden)

    Alex Baumgartner

    2011-01-01

    Full Text Available The handicap theory of sexual selection posits that male display traits that are favored in mate choice come at a significant cost to performance. We tested one facet of this hypothesis in the green swordtail (Xiphophorus helleri. In this species, the lower ray of male caudal fin is extended into a 'sword', which serves to attract potential mates. However, bearing a long sword may increase drag and thus compromise a male's ability to swim effectively. We tested escape performance in this species by eliciting C-start escape responses, an instinctive escape behavior, in males with various sword lengths. We then removed males' swords and retested escape performance. We found no relationship between escape performance and sword length and no effect of sword removal on escape performance. While having a large sword may attract a predator's attention, our results suggest that sword size does not compromise a male's escape performance.

  3. Escaping Underground Nets: Extracellular DNases Degrade Plant Extracellular Traps and Contribute to Virulence of the Plant Pathogenic Bacterium Ralstonia solanacearum.

    Directory of Open Access Journals (Sweden)

    Tuan Minh Tran

    2016-06-01

    Full Text Available Plant root border cells have been recently recognized as an important physical defense against soil-borne pathogens. Root border cells produce an extracellular matrix of protein, polysaccharide and DNA that functions like animal neutrophil extracellular traps to immobilize pathogens. Exposing pea root border cells to the root-infecting bacterial wilt pathogen Ralstonia solanacearum triggered release of DNA-containing extracellular traps in a flagellin-dependent manner. These traps rapidly immobilized the pathogen and killed some cells, but most of the entangled bacteria eventually escaped. The R. solanacearum genome encodes two putative extracellular DNases (exDNases that are expressed during pathogenesis, suggesting that these exDNases contribute to bacterial virulence by enabling the bacterium to degrade and escape root border cell traps. We tested this hypothesis with R. solanacearum deletion mutants lacking one or both of these nucleases, named NucA and NucB. Functional studies with purified proteins revealed that NucA and NucB are non-specific endonucleases and that NucA is membrane-associated and cation-dependent. Single ΔnucA and ΔnucB mutants and the ΔnucA/B double mutant all had reduced virulence on wilt-susceptible tomato plants in a naturalistic soil-soak inoculation assay. The ΔnucA/B mutant was out-competed by the wild-type strain in planta and was less able to stunt root growth or colonize plant stems. Further, the double nuclease mutant could not escape from root border cells in vitro and was defective in attachment to pea roots. Taken together, these results demonstrate that extracellular DNases are novel virulence factors that help R. solanacearum successfully overcome plant defenses to infect plant roots and cause bacterial wilt disease.

  4. Strange culinary encounters::stranger fetichism in "Jamie's Italian escape" and "Gordon's great escape"

    OpenAIRE

    Leer, Jonatan; Kjær, Katrine Meldgaard

    2015-01-01

    In this article, we examine the ways in which the encountering of 'other' food cultures is played out in the two travelogue cooking shows Gordon's Great Escape and Jamie's Italian Escape. We investigate how the two protagonist chefs Jamie Oliver and Gordon Ramsay imagine, meet and evaluate the ‘other’ food cultures in these programs, paying special attention to how the encounter with the local Indian and Italian is imagined to be a gateway to an authentic and/or primitive experience. Our main...

  5. Room escape at class: Escape games activities to facilitate the motivation and learning in computer science

    Directory of Open Access Journals (Sweden)

    Carlos Borrego

    2017-06-01

    Full Text Available Real-life room-escape games are ludic activities in which participants enter a room in order to get out of it only after solving some riddles. In this paper, we explain a Room Escape teaching experience developed in the Engineering School at Universitat Autònoma de Barcelona. The goal of this activity is to increase student’s motivation and to improve their learning on two courses of the second year in the Computer Engineering degree: Computer Networksand Information and Security.

  6. Pathways for Holliday Junction Processing during Homologous Recombination in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Ashton, Thomas M; Mankouri, Hocine W; Heidenblut, Anna

    2011-01-01

    The Saccharomyces cerevisiae Rmi1 protein is a component of the highly conserved Sgs1-Top3-Rmi1 complex. Deletion of SGS1, TOP3, or RMI1 is synthetically lethal when combined with the loss of the Mus81-Mms4 or Slx1-Slx4 endonucleases, which have been implicated in Holliday junction (HJ) resolution....... To investigate the causes of this synthetic lethality, we isolated a temperature-sensitive mutant of the RMI1 strain, referred to as the rmi1-1 mutant. At the restrictive temperature, this mutant phenocopies an rmi1¿ strain but behaves like the wild type at the permissive temperature. Following a transient...... exposure to methyl methanesulfonate, rmi1-1 mutants accumulate unprocessed homologous recombination repair (HRR) intermediates. These intermediates are slowly resolved at the restrictive temperature, revealing a redundant resolution activity when Rmi1 is impaired. This resolution depends on Mus81-Mms4...

  7. Arduino adventures escape from Gemini station

    CERN Document Server

    Kelly, James Floyd

    2013-01-01

    Arduino Adventures: Escape from Gemini Station provides a fun introduction to the Arduino microcontroller by putting you (the reader) into the action of a science fiction adventure story.  You'll find yourself following along as Cade and Elle explore Gemini Station-an orbiting museum dedicated to preserving and sharing technology throughout the centuries. Trouble ensues. The station is evacuated, including Cade and Elle's class that was visiting the station on a field trip. Cade and Elle don't make it aboard their shuttle and are trapped on the station along with a friendly artificial intellig

  8. Suicide as escape from psychotic panic.

    Science.gov (United States)

    Goldblatt, Mark J; Ronningstam, Elsa; Schechter, Mark; Herbstman, Benjamin; Maltsberger, John T

    2016-01-01

    Suicides of patients in states of acute persecutory panic may be provoked by a subjective experience of helpless terror threatening imminent annihilation or dismemberment. These patients are literally scared to death and try to run away. They imagine suicide is survivable and desperately attempt to escape from imaginary enemies. These states of terror occur in a wide range of psychotic illnesses and are often associated with command hallucinations and delusions. In this article, the authors consider the subjective experience of persecutory panic and the suicide response as an attempt to flee from danger.

  9. HTP-1-dependent constraints coordinate homolog pairing and synapsis and promote chiasma formation during C. elegans meiosis.

    Science.gov (United States)

    Martinez-Perez, Enrique; Villeneuve, Anne M

    2005-11-15

    Synaptonemal complex (SC) assembly must occur between correctly paired homologous chromosomes to promote formation of chiasmata. Here, we identify the Caenorhabditis elegans HORMA-domain protein HTP-1 as a key player in coordinating establishment of homolog pairing and synapsis in C. elegans and provide evidence that checkpoint-like mechanisms couple these early meiotic prophase events. htp-1 mutants are defective in the establishment of pairing, but in contrast with the pairing-defective chk-2 mutant, SC assembly is not inhibited and generalized nonhomologous synapsis occurs. Extensive nonhomologous synapsis in htp-1; chk-2 double mutants indicates that HTP-1 is required for the inhibition of SC assembly observed in chk-2 gonads. htp-1 mutants show a decreased abundance of nuclei exhibiting a polarized organization that normally accompanies establishment of pairing; analysis of htp-1; syp-2 double mutants suggests that HTP-1 is needed to prevent premature exit from this polarized nuclear organization and that this exit stops homology search. Further, based on experiments monitoring the formation of recombination intermediates and crossover products, we suggest that htp-1 mutants are defective in preventing the use of sister chromatids as recombination partners. We propose a model in which HTP-1 functions to establish or maintain multiple constraints that operate to ensure coordination of events leading to chiasma formation.

  10. Overcoming viral escape with vaccines that generate and display antigen diversity in vivo

    Directory of Open Access Journals (Sweden)

    García-Quintanilla Albert

    2007-11-01

    Full Text Available Abstract Background Viral diversity is a key problem for the design of effective and universal vaccines. Virtually, a vaccine candidate including most of the diversity for a given epitope would force the virus to create escape mutants above the viability threshold or with a high fitness cost. Presentation of the hypothesis Therefore, I hypothesize that priming the immune system with polyvalent vaccines where each single vehicle generates and displays multiple antigen variants in vivo, will elicit a broad and long-lasting immune response able to avoid viral escape. Testing the hypothesis To this purpose, I propose the use of yeasts that carry virus-like particles designed to pack the antigen-coding RNA inside and replicate it via RNA-dependent RNA polymerase. This would produce diversity in vivo limited to the target of interest and without killing the vaccine vehicle. Implications of the hypothesis This approach is in contrast with peptide cocktails synthesized in vitro and polyvalent strategies where every cell or vector displays a single or definite number of mutants; but similarly to all them, it should be able to overcome original antigenic sin, avoid major histocompatibility complex restriction, and elicit broad cross-reactive immune responses. Here I discuss additional advantages such as minimal global antagonism or those derived from using a yeast vehicle, and potential drawbacks like autoimmunity. Diversity generated by this method could be monitored both genotypically and phenotypically, and therefore selected or discarded before use if needed.

  11. Establishment of screening technique for mutant cell and analysis of base sequence in the mutation

    International Nuclear Information System (INIS)

    Sofuni, Toshio; Nomi, Takehiko; Yamada, Masami; Masumura, Kenichi

    2000-01-01

    This research project aimed to establish an easy and quick detection method for radiation-induced mutation using molecular-biological techniques and an effective analyzing method for the molecular changes in base sequence. In this year, Spi mutants derived from γ-radiation exposed mouse were analyzed by PCR method and DNA sequence method. Male transgenic mice were exposed to γ-ray at 5,10, 50 Gy and the transgene was taken out from the genome DNA from the spleen in vivo packaging method. Spi mutant plaques were obtained by infecting the recovered phage to E. coli. Sequence analysis for the mutants was made using ALFred DNA sequencer and SequiTherm TM Long-Red Cycle sequencing kit. Sequence analysis was carried out for 41 of 50 independent Spi mutants obtained. The deletions were classified into 4 groups; Group 1 included 15 mutants that were characterized with a large deletion (43 bp-10 kb) with a short homologous sequence. Group 2 included 11 mutants of a large deletion having no homologous sequence at the connecting region. Group 3 included 11 mutants having a short deletion of less than 20 bp, which occurred in the non-repetitive sequence of gam gene and possibly caused by oxidative breakage of DNA or recombination of DNA fragment produced by the breakage. Group 4 included 4 mutants having deletions as short as 20 bp or less in the repetitive sequence of gam gene, resulting in an alteration of the reading frame. Thus, the synthesis of Gam protein was terminated by the appearance of TGA between code 13 and 14 of redB gene, leading to inactivation of gam gene and redBA gene. These results indicated that most of Spi mutants had a deletion in red/gam region and the deletions in more than half mutants occurred in homologous sequences as short as 8 bp. (M.N.)

  12. Persistent homology and string vacua

    Energy Technology Data Exchange (ETDEWEB)

    Cirafici, Michele [Center for Mathematical Analysis, Geometry and Dynamical Systems,Instituto Superior Técnico, Universidade de Lisboa,Av. Rovisco Pais, 1049-001 Lisboa (Portugal); Institut des Hautes Études Scientifiques,Le Bois-Marie, 35 route de Chartres, F-91440 Bures-sur-Yvette (France)

    2016-03-08

    We use methods from topological data analysis to study the topological features of certain distributions of string vacua. Topological data analysis is a multi-scale approach used to analyze the topological features of a dataset by identifying which homological characteristics persist over a long range of scales. We apply these techniques in several contexts. We analyze N=2 vacua by focusing on certain distributions of Calabi-Yau varieties and Landau-Ginzburg models. We then turn to flux compactifications and discuss how we can use topological data analysis to extract physical information. Finally we apply these techniques to certain phenomenologically realistic heterotic models. We discuss the possibility of characterizing string vacua using the topological properties of their distributions.

  13. Equivariant ordinary homology and cohomology

    CERN Document Server

    Costenoble, Steven R

    2016-01-01

    Filling a gap in the literature, this book takes the reader to the frontiers of equivariant topology, the study of objects with specified symmetries. The discussion is motivated by reference to a list of instructive “toy” examples and calculations in what is a relatively unexplored field. The authors also provide a reading path for the first-time reader less interested in working through sophisticated machinery but still desiring a rigorous understanding of the main concepts. The subject’s classical counterparts, ordinary homology and cohomology, dating back to the work of Henri Poincaré in topology, are calculational and theoretical tools which are important in many parts of mathematics and theoretical physics, particularly in the study of manifolds. Similarly powerful tools have been lacking, however, in the context of equivariant topology. Aimed at advanced graduate students and researchers in algebraic topology and related fields, the book assumes knowledge of basic algebraic topology and group act...

  14. Molecular Dications in Planetary Atmospheric Escape

    Directory of Open Access Journals (Sweden)

    Stefano Falcinelli

    2016-08-01

    Full Text Available Fundamental properties of multiply charged molecular ions, such as energetics, structure, stability, lifetime and fragmentation dynamics, are relevant to understand and model the behavior of gaseous plasmas as well as ionosphere and astrophysical environments. Experimental determinations of the Kinetic Energy Released (KER for ions originating from dissociations reactions, induced by Coulomb explosion of doubly charged molecular ions (molecular dications produced by double photoionization of CO2, N2O and C2H2 molecules of interest in planetary atmospheres, are reported. The KER measurement as a function of the ultraviolet (UV photon energy in the range of 28–65 eV was extracted from the electron-ion-ion coincidence spectra obtained by using tunable synchrotron radiation coupled with ion imaging techniques at the ELETTRA Synchrotron Light Laboratory Trieste, Italy. These experiments, coupled with a computational analysis based on a Monte Carlo trajectory simulation, allow assessing the probability of escape for simple ionic species in the upper atmosphere of Mars, Venus and Titan. The measured KER in the case of H+, C+, CH+, CH2+, N+, O+, CO+, N2+ and NO+ fragment ions range between 1.0 and 5.5 eV, being large enough to allow these ionic species to participate in the atmospheric escape from such planets into space. In the case of Mars, we suggest a possible explanation for the observed behavior of the O+ and CO22+ ion density profiles.

  15. The escape problem for mortal walkers

    Science.gov (United States)

    Grebenkov, D. S.; Rupprecht, J.-F.

    2017-02-01

    We introduce and investigate the escape problem for random walkers that may eventually die, decay, bleach, or lose activity during their diffusion towards an escape or reactive region on the boundary of a confining domain. In the case of a first-order kinetics (i.e., exponentially distributed lifetimes), we study the effect of the associated death rate onto the survival probability, the exit probability, and the mean first passage time. We derive the upper and lower bounds and some approximations for these quantities. We reveal three asymptotic regimes of small, intermediate, and large death rates. General estimates and asymptotics are compared to several explicit solutions for simple domains and to numerical simulations. These results allow one to account for stochastic photobleaching of fluorescent tracers in bio-imaging, degradation of mRNA molecules in genetic translation mechanisms, or high mortality rates of spermatozoa in the fertilization process. Our findings provide a mathematical ground for optimizing storage containers and materials to reduce the risk of leakage of dangerous chemicals or nuclear wastes.

  16. Pavlovian Control of Escape and Avoidance.

    Science.gov (United States)

    Millner, Alexander J; Gershman, Samuel J; Nock, Matthew K; den Ouden, Hanneke E M

    2017-12-15

    To survive in complex environments, animals need to have mechanisms to select effective actions quickly, with minimal computational costs. As perhaps the computationally most parsimonious of these systems, Pavlovian control accomplishes this by hardwiring specific stereotyped responses to certain classes of stimuli. It is well documented that appetitive cues initiate a Pavlovian bias toward vigorous approach; however, Pavlovian responses to aversive stimuli are less well understood. Gaining a deeper understanding of aversive Pavlovian responses, such as active avoidance, is important given the critical role these behaviors play in several psychiatric conditions. The goal of the current study was to establish a behavioral and computational framework to examine aversive Pavlovian responses (activation vs. inhibition) depending on the proximity of an aversive state (escape vs. avoidance). We introduce a novel task in which participants are exposed to primary aversive (noise) stimuli and characterized behavior using a novel generative computational model. This model combines reinforcement learning and drift-diffusion models so as to capture effects of invigoration/inhibition in both explicit choice behavior as well as changes in RT. Choice and RT results both suggest that escape is associated with a bias for vigorous action, whereas avoidance is associated with behavioral inhibition. These results lay a foundation for future work seeking insights into typical and atypical aversive Pavlovian responses involved in psychiatric disorders, allowing us to quantify both implicit and explicit indices of vigorous choice behavior in the context of aversion.

  17. UNESCO TO BLAME: Reality or Easy Escape?

    Directory of Open Access Journals (Sweden)

    Anna Pereira Roders

    2015-03-01

    Full Text Available “UNESCO to blame” is a trend often observed in scholarly works. In those studies UNESCO is accused to privilege Eurocentric standards on heritage conservation. Is this reality or an easy escape? Can this trend be noted in other UNESCO reference texts? This article seeks to answer this question by studying the two main inscription-based conventions and their contribution to heritage management, while performing a data analysis on the countries behind these conventions, and their roles over time. The 1972 World Heritage Convention and the 2003 Convention for the Safeguarding of the Intangible Cultural Heritage are, therefore, taken as case studies. Based on the results, this paper elaborates on a critical analysis, distinguishing what UNESCO, as well as, Europe can eventually be blamed for and what may be used by the countries as an easy escape. This paper ends setting a research agenda to raise awareness and generate factual knowledge on the role of supranational governance in setting standards in global ethics, in particular, to guideline heritage conservation.

  18. Factors affecting escape distance in birds

    Directory of Open Access Journals (Sweden)

    Augusto J. Piratelli

    2015-12-01

    Full Text Available ABSTRACT The flight initiation distance has been used either to understand the cost-benefit trade-offs related to the risk of predation or as an important tool for wildlife managers. Although this variable is well-discussed for temperate regions, it is still poorly known in the Neotropics. Here we analyze the escape behavior of birds from southeastern Brazil, comparing an urban to a non-urban area. We tested for the influence of sites (urban vs. non-urban area, approaching (by one vs. two people, daytime (morning vs. afternoon, seasons (breeding vs. non-breeding and body mass on the determination of the initial (FID and final (FFD flight distances across different bird species. We predict that FID will be greater in rural areas and under a greater threat (higher number of predators approaching in the afternoon and in the non-breeding season. We also expect a direct relationship between body mass and FID and between FID and FFD. We sampled 11 species after measuring 331 escape behaviors, and we confirmed our predictions for sites (five species, daytime (one species and rejected our premise about seasons for one species. Mean FID was strongly affected by body mass, and directly affected FFD. Adjustments in FID are, most likely, an important adaptive trait in urban habitats and may partially explain the predominance of species with higher ecological plasticity in cities.

  19. Escape from viscosity : the kinematics and hydrodynamics of copepod foraging and escape swimming

    NARCIS (Netherlands)

    van Duren, LA; Videler, JJ

    Feeding and escape swimming in adult females of the calanoid copepod. Temora lopgicornis Muller were investigated and compared. Swimming velocities were calculated using a 3-D filming setup., Foraging velocities ranged between 2 and 6 min s(-1), while maximum velocities of up to 80 mm s(-1) were

  20. Dissecting the Mechanisms of Drug Resistance in BRCA1/2-Mutant Breast Cancers

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0600 TITLE: Dissecting the Mechanisms of Drug Resistance in BRCA1/2-Mutant Breast Cancers PRINCIPAL INVESTIGATOR: Dr...2017 4. TITLE AND SUBTITLE Dissecting the Mechanisms of Drug Resistance in BRCA1/2- Mutant Breast Cancers 5a. CONTRACT NUMBER W81XWH-16-1-0600 5b...therapeutic modality for targeting homologous recombination (HR) deficient tumors such as BRCA1 and BRCA2-mutated triple negative breast cancers

  1. Homology in Electromagnetic Boundary Value Problems

    Directory of Open Access Journals (Sweden)

    Matti Pellikka

    2010-01-01

    Full Text Available We discuss how homology computation can be exploited in computational electromagnetism. We represent various cellular mesh reduction techniques, which enable the computation of generators of homology spaces in an acceptable time. Furthermore, we show how the generators can be used for setting up and analysis of an electromagnetic boundary value problem. The aim is to provide a rationale for homology computation in electromagnetic modeling software.

  2. Some Possible Cases of Escape Mimicry in Neotropical Butterflies.

    Science.gov (United States)

    Pinheiro, C E G; Freitas, A V L

    2014-10-01

    The possibility that escape or evasive mimicry evolved in butterflies and other prey insects in a similar fashion to classical Batesian and Müllerian mimicry has long been advanced in the literature. However, there is a general disagreement among lepidopterists and evolutionary biologists on whether or not escape mimicry exists, as well as in which mimicry rings this form of mimicry has evolved. Here, we review some purported cases of escape mimicry in Neotropical butterflies and suggest new mimicry rings involving several species of Archaeoprepona, Prepona, and Doxocopa (the "bright blue bands" ring) and species of Colobura and Hypna (the "creamy bands" ring) where the palatability of butterflies, their ability to escape predator attacks, geographic distribution, relative abundance, and co-occurrence in the same habitats strongly suggest that escape mimicry is involved. In addition, we also indicate other butterfly taxa whose similarities of coloration patterns could be due to escape mimicry and would constitute important case studies for future investigation.

  3. Directed mutagenesis in Candida albicans: one-step gene disruption to isolate ura3 mutants

    International Nuclear Information System (INIS)

    Kelly, R.; Miller, S.M.; Kurtz, M.B.; Kirsch, D.R.

    1987-01-01

    A method for introducing specific mutations into the diploid Candida albicans by one-step gene disruption and subsequent UV-induced recombination was developed. The cloned C. albicans URA3 gene was disrupted with the C. albicans ADE2 gene, and the linearized DNA was used for transformation of two ade2 mutants, SGY-129 and A81-Pu. Both an insertional inactivation of the URA3 gene and a disruption which results in a 4.0-kilobase deletion were made. Southern hybridization analyses demonstrated that the URA3 gene was disrupted on one of the chromosomal homologs in 15 of the 18 transformants analyzed. These analyses also revealed restriction site dimorphism of EcoRI at the URA3 locus which provides a unique marker to distinguish between chromosomal homologs. This enabled us to show that either homolog could be disrupted and that disrupted transformants of SGY-129 contained more than two copies of the URA3 locus. The A81-Pu transformants heterozygous for the ura3 mutations were rendered homozygous and Ura- by UV-induced recombination. The homozygosity of a deletion mutant and an insertion mutant was confirmed by Southern hybridization. Both mutants were transformed to Ura+ with plasmids containing the URA3 gene and in addition, were resistant to 5-fluoro-orotic acid, a characteristic of Saccharomyces cerevisiae ura3 mutants as well as of orotidine-5'-phosphate decarboxylase mutants of other organisms

  4. Effect of Orbital Distance on the Atmospheric Escape of Exoplanets

    Science.gov (United States)

    Mo, Yang; Jian-heng, Guo

    2018-01-01

    Atmospheric escape is an important sector in the evolution of planetary atmosphere, and its energy is mainly originated from the radiation of the host star at the high energy band. The radiation flux drops dramatically with the increase of orbital distance, there is a large difference of planetary atmospheric escape in different orbits, so it is necessary to study the impact of orbital distance on the atmospheric escape of an exoplanet. We consider the radiation transfer and the photochemical reactions of multiple kinds of particles to study the variation of planetary atmospheric escape with the orbital distance by using a 1-D hydrodynamic model. Due to the large differences of the spectra of host stars in different evolution stages, the Astrophysical Plasma Emission Code (APEC) in the X-Ray Spectral Fitting Package (XSPEC) is used to obtain the spectra of solar-type stars with different ages as the input spectra of the model. The results indicate that the escape rates of the exoplanets in different orbits are different significantly, and the escape mechanism is converted from the drastic hydrodynamic escape into the moderate Jeans escape as the orbital distance increases, the smaller the planetary gravitational potential, the younger the star-planet system, the larger the distance of this conversion. The correlation between the escape rate and the radiation flux decreases for the short-period exoplanets in a younger star-planet system. It is shown that the classical energy-limited escape theory is not suitable for this kind of exoplanets. These results have enriched the studies on the atmospheric escape of exoplanets, especially, extended the studies on the escape mechanism and energy conversion under different orbital distances and stellar ages.

  5. Construction and expression of hepatitis B surface antigen escape variants within the "a" determinant by site directed mutagenesis.

    Science.gov (United States)

    Golsaz Shirazi, Forough; Amiri, Mohammad Mehdi; Mohammadi, Hamed; Bayat, Ali Ahmad; Roohi, Azam; Khoshnoodi, Jalal; Zarnani, Amir Hassan; Jeddi-Tehrani, Mahmood; Kardar, Gholam Ali; Shokri, Fazel

    2013-09-01

    The antibody response to hepatitis B surface antigen (HBsAg) controls hepatitis B virus infection. The "a" determinant of HBsAg is the most important target for protective antibody response, diagnosis and immunoprophylaxis. Mutations in this area may induce immune escape mutants and affect the performance of HBsAg assays. To construct clinically relevant recombinant mutant forms of HBsAg and assessment of their reactivity with anti-HBs monoclonal antibodies (MAbs). Wild type (wt) and mutant (mt) HBsAg genes were constructed by site directed mutagenesis and SEOing PCR. The amplified genes were inserted into pCMV6-neo plasmid and transfected in CHO cell line. The expression of wt- and mtHBsAg was assessed by commercial ELISA assays and stable cells were established and cloned by limiting dilution. The recombinant mutants were further characterized using a panel of anti-HBs monoclonal antibodies (MAbs) and the pattern of their reactivity was assessed by ELISA. Ten HBsAg mutants having single mutation within the "a" determinant including P120E, T123N, Q129H, M133L, K141E, P142S, D144A, G145R, N146S and C147S together with a wt form were successfully constructed and expressed in CHO cells. Reactivity of anti-HBs MAbs with mtHBsAgs displayed different patterns. The effect of mutations on antibody binding differed depending on the amino acid involved and its location within the ''a'' determinant. Mutation at amino acids 123 and 145 resulted in either complete loss or significant reduction of binding to all anti-HBs MAbs. Our panel of mtHBsAgs is a valuable tool for assessment of the antibody response to HBV escape mutants and may have substantial implications in HBV immunological diagnostics.

  6. Escape response of planktonic protists to fluid mechanical signals

    DEFF Research Database (Denmark)

    Jakobsen, Hans Henrik

    2001-01-01

    The escape response to fluid mechanical signals was examined in 6 protists, 4 ciliates and 2 dinoflagellates. When exposed to a siphon flow. 3 species of ciliates, Balanion comatum, Strobilidium sp., and Mesodinium pulex, responded with escape jumps. The threshold deformation rates required...... to elicit an escape ranged between 1.8 and 3 s(-1). Escape speeds varied between 100 to 150 body length s(-1). Jump directions were non- random in all jumping species and had a negative geotactic component. In a grazing experiment with copepods, the predation mortality of a jumping ciliate was about 15...

  7. Shu proteins promote the formation of homologous recombination intermediates that are processed by Sgs1-Rmi1-Top3

    DEFF Research Database (Denmark)

    Mankouri, Hocine W; Ngo, Hien-Ping; Hickson, Ian D

    2007-01-01

    CSM2, PSY3, SHU1, and SHU2 (collectively referred to as the SHU genes) were identified in Saccharomyces cerevisiae as four genes in the same epistasis group that suppress various sgs1 and top3 mutant phenotypes when mutated. Although the SHU genes have been implicated in homologous recombination...

  8. Escape of Black Holes from the Brane

    International Nuclear Information System (INIS)

    Flachi, Antonino; Tanaka, Takahiro

    2005-01-01

    TeV-scale gravity theories allow the possibility of producing small black holes at energies that soon will be explored at the CERN LHC or at the Auger observatory. One of the expected signatures is the detection of Hawking radiation that might eventually terminate if the black hole, once perturbed, leaves the brane. Here, we study how the 'black hole plus brane' system evolves once the black hole is given an initial velocity that mimics, for instance, the recoil due to the emission of a graviton. The results of our dynamical analysis show that the brane bends around the black hole, suggesting that the black hole eventually escapes into the extra dimensions once two portions of the brane come in contact and reconnect. This gives a dynamical mechanism for the creation of baby branes

  9. The fastest saccadic responses escape visual masking

    DEFF Research Database (Denmark)

    Crouzet, Sébastien M.; Overgaard, Morten; Busch, Niko A.

    2014-01-01

    visual processing while the initial feedforward processing is thought to be left intact. We tested a prediction derived from this hypothesis: the fastest responses, being triggered before the beginning of reentrant processing, should escape the OSM interference. In a saccadic choice reaction time task......, which gives access to very early stages of visual processing, target visibility was reduced either by OSM, conventional backward masking, or low stimulus contrast. A general reduction of performance was observed in all three conditions. However, the fastest saccades did not show any sign of interference...... under either OSM or backward masking, as they did under the low-contrast condition. This finding supports the hypothesis that masking interferes mostly with reentrant processing at later stages, while leaving early feedforward processing largely intact....

  10. Homotopic Chain Maps Have Equal s-Homology and d-Homology

    Directory of Open Access Journals (Sweden)

    M. Z. Kazemi-Baneh

    2016-01-01

    Full Text Available The homotopy of chain maps on preabelian categories is investigated and the equality of standard homologies and d-homologies of homotopic chain maps is established. As a special case, if X and Y are the same homotopy type, then their nth d-homology R-modules are isomorphic, and if X is a contractible space, then its nth d-homology R-modules for n≠0 are trivial.

  11. Escape Burrowing of Modern Freshwater Bivalves as a Paradigm for Escape Behavior in the Devonian Bivalve Archanodon catskillensis

    Directory of Open Access Journals (Sweden)

    Katja Knoll

    2017-10-01

    Full Text Available Many freshwater bivalves restore themselves to the sediment water interface after burial by upward escape burrowing. We studied the escape burrowing capacity of two modern unionoids, Elliptio complanata and Pyganodon cataracta and the invasive freshwater venerid Corbicula fluminea, in a controlled laboratory setting varying sediment grain size and burial depth. We found that the relatively streamlined E. complanata is a better escape burrower than the more obese P. cataracta. E. complanata is more likely to escape burial in both fine and coarse sand, and at faster rates than P. cataracta. However, successful escape from 10 cm burial, especially in fine sand, is unlikely for both unionoids. The comparatively small and obese C. fluminea outperforms both unionoids in terms of escape probability and escape time, especially when body size is taken into consideration. C. fluminea can escape burial depths many times its own size, while the two unionoids rarely escape from burial equivalent to the length of their shells. E. complanata, and particularly P. cataracta, are morphological paradigms for the extinct Devonian unionoid bivalve Archanodon catskillensis, common in riverine facies of the Devonian Catskill Delta Complex of the eastern United States. Our observations suggest that the escape burrowing capability of A. catskillensis was no better than that of P. cataracta. Archanodon catskillensis was likely unable to escape burial of more than a few centimeters of anastrophically deposited sediment. The long (up to 1 meter, vertical burrows that are associated with A. catskillensis, and interpreted to be its escape burrows, represent a response to episodic, small-scale sedimentation events due to patterns of repetitive hydrologic or weather-related phenomena. They are not a response to a single anastrophic event involving the influx of massive volumes of sediment.

  12. Relative K-homology and normal operators

    DEFF Research Database (Denmark)

    Manuilov, Vladimir; Thomsen, Klaus

    2009-01-01

    -term exact sequence which generalizes the excision six-term exact sequence in the first variable of KK-theory. Subsequently we investigate the relative K-homology which arises from the group of relative extensions by specializing to abelian $C^*$-algebras. It turns out that this relative K-homology carries...

  13. Managing Pacific salmon escapements: The gaps between theory and reality

    Science.gov (United States)

    Knudsen, E. Eric; Knudsen, E. Eric; Steward, Cleveland R.; MacDonald, Donald D.; Williams, Jack E.; Reiser, Dudley W.

    1999-01-01

    There are myriad challenges to estimating intrinsic production capacity for Pacific salmon populations that are heavily exploited and/or suffering from habitat alteration. Likewise, it is difficult to determine whether perceived decreases in production are due to harvest, habitat, or hatchery influences, natural variation, or some combination of all four. There are dramatic gaps between the true nature of the salmon spawner/recruit relationship and the theoretical basis for describing and understanding the relationship. Importantly, there are also extensive practical difficulties associated with gathering and interpreting accurate escapement and run-size information and applying it to population management. Paradoxically, certain aspects of salmon management may well be contributing to losses in abundance and biodiversity, including harvesting salmon in mixed population fisheries, grouping populations into management units subject to a common harvest rate, and fully exploiting all available hatchery fish at the expense of wild fish escapements. Information on U.S. Pacific salmon escapement goal-setting methods, escapement data collection methods and estimation types, and the degree to which stocks are subjected to mixed stock fisheries was summarized and categorized for 1,025 known management units consisting of 9,430 known populations. Using criteria developed in this study, only 1% of U.S. escapement goals are by methods rated as excellent. Escapement goals for 16% of management units were rated as good. Over 60% of escapement goals have been set by methods rated as either fair or poor and 22% of management units have no escapement goals at all. Of the 9,430 populations for which any information was available, 6,614 (70%) had sufficient information to categorize the method by which escapement data are collected. Of those, data collection methods were rated as excellent for 1%, good for 1%, fair for 2%, and poor for 52%. Escapement estimates are not made for 44

  14. Lectures on homology with internal symmetries

    International Nuclear Information System (INIS)

    Solovyov, Yu.

    1993-09-01

    Homology with internal symmetries is a natural generalization of cyclic homology introduced, independently, by Connes and Tsygan, which has turned out to be a very useful tool in a number of problems of algebra, geometry topology, analysis and mathematical physics. It suffices to say cycling homology and cohomology are successfully applied in the index theory of elliptic operators on foliations, in the description of the homotopy type of pseudoisotopy spaces, in the theory of characteristic classes in algebraic K-theory. They are also applied in noncommutative differential geometry and in the cohomology of Lie algebras, the branches of mathematics which brought them to life in the first place. Essentially, we consider dihedral homology, which was successfully applied for the description of the homology type of groups of homeomorphisms and diffeomorphisms of simply connected manifolds. (author). 27 refs

  15. Homology Groups of a Pipeline Petri Net

    Directory of Open Access Journals (Sweden)

    A. A. Husainov

    2013-01-01

    Full Text Available Petri net is said to be elementary if every place can contain no more than one token. In this paper, it is studied topological properties of the elementary Petri net for a pipeline consisting of n functional devices. If the work of the functional devices is considered continuous, we can come to some topological space of “intermediate” states. In the paper, it is calculated the homology groups of this topological space. By induction on n, using the Addition Sequence for homology groups of semicubical sets, it is proved that in dimension 0 and 1 the integer homology groups of these nets are equal to the group of integers, and in the remaining dimensions are zero. Directed homology groups are studied. A connection of these groups with deadlocks and newsletters is found. This helps to prove that all directed homology groups of the pipeline elementary Petri nets are zeroth.

  16. Function of Rad51 paralogs in eukaryotic homologous recombinational repair

    International Nuclear Information System (INIS)

    Liu, N.; Skowronek, K.

    2003-01-01

    Full text: Homologous recombinational repair (HRR) is an important mechanism for maintaining genetic integrity and cancer prevention by accurately repair of DNA double strand breaks induced by environmental insults or occurred in DNA replication. A critical step in HRR is the polymerization of Rad51 on single stranded DNA to form nuclear protein filaments, the later conduct DNA strand paring and exchange between homologous strands. A number of proteins, including replication protein A (RPA), Rad52 and Rad51 paralogs, are suggested to modulate or facilitate the process of Rad51 filament formation. Five Rad51 paralogs, namely XRCC2, XRCC3, Rad51B, Rad51C and Rad51D have been identified in eucaryotic cells. These proteins show distant protein sequence identity to Rad51, to yeast Rad51 paralogs (Rad55 and Rad57) and to each other. Hamster or chicken mutants of Rad51 paralogs exhibit hypersensitivity to a variety of DNA damaging agents, especially cross-linking agents, and are defective in assembly of Rad51 onto HRR site after DNA damage. Recent data from our and other labs showed that Rad51 paralogs constitute two distinct complexes in cell extracts, one contains XRCC2, Rad51B, Rad51C and Rad51D, and the other contains Rad51C and XRCC3. Rad51C is involved in both complexes. Our results also showed that XRCC3-Rad51C complex interacts with Rad51 in vivo. Furthermore, overexpression of Rad52 can partially suppress the hypersensitivity of XRCC2 mutant irs1 to ionizing radiation and corrected the defects in Rad51 focus formation. These results suggest that XRCC2 and other Rad51 paralogs play a mediator function to Rad51 in the early stage of HRR

  17. Reliable reconstruction of HIV-1 whole genome haplotypes reveals clonal interference and genetic hitchhiking among immune escape variants

    Science.gov (United States)

    2014-01-01

    Background Following transmission, HIV-1 evolves into a diverse population, and next generation sequencing enables us to detect variants occurring at low frequencies. Studying viral evolution at the level of whole genomes was hitherto not possible because next generation sequencing delivers relatively short reads. Results We here provide a proof of principle that whole HIV-1 genomes can be reliably reconstructed from short reads, and use this to study the selection of immune escape mutations at the level of whole genome haplotypes. Using realistically simulated HIV-1 populations, we demonstrate that reconstruction of complete genome haplotypes is feasible with high fidelity. We do not reconstruct all genetically distinct genomes, but each reconstructed haplotype represents one or more of the quasispecies in the HIV-1 population. We then reconstruct 30 whole genome haplotypes from published short sequence reads sampled longitudinally from a single HIV-1 infected patient. We confirm the reliability of the reconstruction by validating our predicted haplotype genes with single genome amplification sequences, and by comparing haplotype frequencies with observed epitope escape frequencies. Conclusions Phylogenetic analysis shows that the HIV-1 population undergoes selection driven evolution, with successive replacement of the viral population by novel dominant strains. We demonstrate that immune escape mutants evolve in a dependent manner with various mutations hitchhiking along with others. As a consequence of this clonal interference, selection coefficients have to be estimated for complete haplotypes and not for individual immune escapes. PMID:24996694

  18. Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import.

    Science.gov (United States)

    Götz, Veronika; Magar, Linda; Dornfeld, Dominik; Giese, Sebastian; Pohlmann, Anne; Höper, Dirk; Kong, Byung-Whi; Jans, David A; Beer, Martin; Haller, Otto; Schwemmle, Martin

    2016-03-18

    To establish a new lineage in the human population, avian influenza A viruses (AIV) must overcome the intracellular restriction factor MxA. Partial escape from MxA restriction can be achieved when the viral nucleoprotein (NP) acquires the critical human-adaptive amino acid residues 100I/V, 283P, and 313Y. Here, we show that introduction of these three residues into the NP of an avian H5N1 virus renders it genetically unstable, resulting in viruses harboring additional single mutations, including G16D. These substitutions restored genetic stability yet again yielded viruses with varying degrees of attenuation in mammalian and avian cells. Additionally, most of the mutant viruses lost the capacity to escape MxA restriction, with the exception of the G16D virus. We show that MxA escape is linked to attenuation by demonstrating that the three substitutions promoting MxA escape disturbed intracellular trafficking of incoming viral ribonucleoprotein complexes (vRNPs), thereby resulting in impaired nuclear import, and that the additional acquired mutations only partially compensate for this import block. We conclude that for adaptation to the human host, AIV must not only overcome MxA restriction but also an associated block in nuclear vRNP import. This inherent difficulty may partially explain the frequent failure of AIV to become pandemic.

  19. Fast neutron mutants database and web displays at SoyBase

    Science.gov (United States)

    SoyBase, the USDA-ARS soybean genetics and genomics database, has been expanded to include data for the fast neutron mutants produced by Bolon, Vance, et al. In addition to the expected text and sequence homology searches and visualization of the indels in the context of the genome sequence viewer, ...

  20. Photorepair mutants of Arabidopsis

    International Nuclear Information System (INIS)

    Jiang, C.Z.; Yee, J.; Mitchell, D.L.; Britt, A.B.

    1997-01-01

    UV radiation induces two major DNA damage products, the cyclobutane pyrimidine dimer (CPD) and, at a lower frequency, the pyrimidine (6-4) pyrimidinone dimer (6-4 product). Although Escherichia coli and Saccharomyces cerevisiae produce a CPD-specific photolyase that eliminates only this class of dimer, Arabidopsis thaliana, Drosophila melanogaster, Crotalus atrox, and Xenopus laevis have recently been shown to photoreactivate both CPDs and 6-4 products. We describe the isolation and characterization of two new classes of mutants of Arabidopsis, termed uvr2 and uvr3, that are defective in the photoreactivation of CPDs and 6-4 products, respectively. We demonstrate that the CPD photolyase mutation is genetically linked to a DNA sequence encoding a type II (metazoan) CPD photolyase. In addition, we are able to generate plants in which only CPDs or 6-4 products are photoreactivated in the nuclear genome by exposing these mutants to UV light and then allowing them to repair one or the other class of dimers. This provides us with a unique opportunity to study the biological consequences of each of these two major UV-induced photoproducts in an intact living system

  1. Buying to blunt negative feelings : Materialistic escape from the self

    NARCIS (Netherlands)

    Donnelly, Grant E.; Ksendzova, Masha; Howell, Ryan T.; Vohs, Kathleen D.; Baumeister, Roy F.

    2016-01-01

    We propose that escape theory, which describes how individuals seek to free themselves from aversive states of self-awareness, helps explain key patterns of materialistic people's behavior. As predicted by escape theory, materialistic individuals may feel dissatisfied with their standard of living,

  2. Escape of protists in predator-generated feeding currents

    DEFF Research Database (Denmark)

    Jakobsen, Hans Henrik

    2002-01-01

    The ciliate Strobilidium sp. and 2 flagellates, Chrysochromulina simplex and Gymnodinium sp., were exposed to predator-generated feeding currents, and their escape responses were quantified using 2- and 3-dimensional video techniques. All 3 studied organisms responded by escaping at a defined...

  3. 30 CFR 75.382 - Mechanical escape facilities.

    Science.gov (United States)

    2010-07-01

    ... with brakes that can stop the fully loaded platform, cage, or other device. (c) Mechanical escape facilities, including automatic elevators, shall be examined weekly. The weekly examination of this equipment... cages, platforms, or elevators. (e) Mechanical escape facilities shall have rated capacities consistent...

  4. Escape rate scaling in infinite measure preserving systems

    International Nuclear Information System (INIS)

    Munday, Sara; Knight, Georgie

    2016-01-01

    We investigate the scaling of the escape rate from piecewise linear dynamical systems displaying intermittency due to the presence of an indifferent fixed point. Strong intermittent behaviour in the dynamics can result in the system preserving an infinite measure. We define a neighbourhood of the indifferent fixed point to be a hole through which points escape and investigate the scaling of the rate of this escape as the length of the hole decreases, both in the finite measure preserving case and infinite measure preserving case. In the infinite measure preserving systems we observe logarithmic corrections to and polynomial scaling of the escape rate with hole length. Finally we conjecture a relationship between the wandering rate and the observed scaling of the escape rate. (paper)

  5. Entrapment and escape of liquid lubricant in metal forming

    DEFF Research Database (Denmark)

    Bech, Jakob Ilsted; Bay, Niels; Eriksen, Morten

    1999-01-01

    Using a transparent tool entrapment, compression and eventual escape of liquid lubricant in surface pockets is observed in plane strip drawing. The two mechanisms of lubricant escape. Micro Plasto HydroDynamic and Hydrostatic Lubrication (MPHDL and MPHSL), are observed and quantified experimentally...... with Varying viscosity, speed, reduction, workpiece material, back tension and friction. The mechanisms are influenced by all these parameters in an explicable way. Theoretical models of the escape mechanisms are established combining continuum mechanic analyses of the die pressure distribution with a fluid...... mechanic analysis of the lubricant escape. Oscillations in the drawing force are caused by the local escape of lubricant. (C) 1999 Elsevier Science S.A. All rights reserved....

  6. Escape route simulator utilizing augmented reality

    Energy Technology Data Exchange (ETDEWEB)

    Mattos, Karen Salazar Ribeiro de; Mó, Antônio Carlos de A.; Santo, André Cotelli do E.; Silva, Marcio Henrique, E-mail: karensalazar.1190@gmail.com [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Centro Universitário Carioca (UniCarioca), Rio de Janeiro, RJ (Brazil)

    2017-07-01

    Due to increasing demand and interest in the interaction of technology platforms and integration of different types of systems and technologies, some tools are already providing practical ways to develop integrated applications. The tools explored by this article are Unity, a platform for game development, and Vuforia, an SDK, software development kit, for augmented reality creation. The coalition proposal of these resources is to create an intuitive escape route that can be used for the evacuation of buildings or open spaces in view of imminent danger, such as radiation leakage, and that can be accessed from a target available at the institution. It has also the intention of simulating situations that involve training of personnel in order to obtain methods that allow to save financial resources, and even to avoid that those who are involved are exposed to risks unnecessarily. The simulator is expected to help design, test, and improve ways to maintain the physical integrity of the facility and provide end users with a better sense of immersion and attractiveness. (author)

  7. Immune escape strategies of malaria parasites

    Directory of Open Access Journals (Sweden)

    Pollyanna Stephanie Gomes

    2016-10-01

    Full Text Available Malaria is one of the most life-threatening infectious diseases worldwide. Immunity to malaria is slow and short-lived despite the repeated parasite exposure in endemic areas. Malaria parasites have evolved refined machinery to evade the immune system based on a range of genetic changes that include allelic variation, biomolecular exposure of proteins and intracellular replication. All of these features increase the probability of survival in both mosquitoes and the vertebrate host. Plasmodium species escape from the first immunological trap in its invertebrate vector host, the Anopheles mosquitoes. The parasites have to pass through various immunological barriers within the mosquito such as anti-microbial molecules and the mosquito microbiota in order to achieve successful transmission to the vertebrate host. Within these hosts, Plasmodium species employ various immune evasion strategies during different life cycle stages. Parasite persistence against the vertebrate immune response depends on the balance among virulence factors, pathology, metabolic cost of the host immune response, and the parasites ability to evade the immune response. In this review we discuss the strategies that Plasmodium parasites use to avoid the vertebrate host immune system and how they promote successful infection and transmission.

  8. Escaping the resource curse in China.

    Science.gov (United States)

    Cao, Shixiong; Li, Shurong; Ma, Hua; Sun, Yutong

    2015-02-01

    Many societies face an income gap between rich regions with access to advanced technology and regions that are rich in natural resources but poorer in technology. This "resource curse" can lead to a Kuznets trap, in which economic inequalities between the rich and the poor increase during the process of socioeconomic development. This can also lead to depletion of natural resources, environmental degradation, social instability, and declining socioeconomic development. These problems will jeopardize China's achievements if the current path continues to be pursued without intervention by the government to solve the problems. To mitigate the socioeconomic development gap between western and eastern China, the government implemented its Western Development Program in 2000. However, recent data suggest that this program has instead worsened the resource curse. Because each region has its own unique strengths and weaknesses, China must escape the resource curse by accounting for this difference; in western China, this can be done by improving education, promoting high-tech industry, adjusting its economic strategy to balance regional development, and seeking more sustainable approaches to socioeconomic development.

  9. Escape route simulator utilizing augmented reality

    International Nuclear Information System (INIS)

    Mattos, Karen Salazar Ribeiro de; Mó, Antônio Carlos de A.; Santo, André Cotelli do E.; Silva, Marcio Henrique

    2017-01-01

    Due to increasing demand and interest in the interaction of technology platforms and integration of different types of systems and technologies, some tools are already providing practical ways to develop integrated applications. The tools explored by this article are Unity, a platform for game development, and Vuforia, an SDK, software development kit, for augmented reality creation. The coalition proposal of these resources is to create an intuitive escape route that can be used for the evacuation of buildings or open spaces in view of imminent danger, such as radiation leakage, and that can be accessed from a target available at the institution. It has also the intention of simulating situations that involve training of personnel in order to obtain methods that allow to save financial resources, and even to avoid that those who are involved are exposed to risks unnecessarily. The simulator is expected to help design, test, and improve ways to maintain the physical integrity of the facility and provide end users with a better sense of immersion and attractiveness. (author)

  10. Isozyme differences in barley mutants

    International Nuclear Information System (INIS)

    AI-Jibouri, A.A.M.; Dham, K.M.

    1990-01-01

    Full text: Thirty mutants (M 11 ) of barley (Hordeum vulgare L.) induced by physical and chemical mutagens were analysed for isozyme composition using polyacrylamide gel electrophoresis. Results show that these mutants were different in the isozymes leucine aminopeptidase, esterase and peroxidase. The differences included the number of forms of each enzyme, relative mobility value and their intensity on the gel. Glutamate oxaloacetate transaminase isozyme was found in six molecular forms and these forms were similar in all mutants. (author)

  11. The RecBCD and SbcCD DNases suppress homology-facilitated illegitimate recombination during natural transformation of Acinetobacter baylyi.

    Science.gov (United States)

    Harms, Klaus; Wackernagel, Wilfried

    2008-08-01

    During natural transformation of Acinetobacter baylyi, the genomic integration of foreign (non-homologous) DNA is possible when the DNA contains a single segment homologous to the recipient genome (anchor) through homologous recombination in the anchor facilitating illegitimate recombination in the neighbouring foreign DNA (homology-facilitated illegitimate recombination; HFIR). DNA integration by HFIR occurs about 10 000 times less frequently than fully homologous recombination, but at least 100 000-fold more frequently than integration in the absence of any homology. We investigated the influence of the RecBCD enzyme (DNase/helicase) and SbcCD DNase (DNA-structure-specific single-strand endonuclease and exonuclease) on HFIR. In a recBCD null mutant the acquisition of foreign DNA was elevated 11-fold relative to wild-type cells by a 6.9-fold increased HFIR frequency and by the integration of longer stretches of foreign DNA in each event. In an sbcCD null mutant, the foreign DNA acquisition was 4.5-fold higher than in the wild-type, while homologous transformation with large DNA molecules was unaffected and increased 3.2-fold with small DNA fragments. The sbcCD mutation partially suppressed the high UV sensitivity and low viability of the recBCD mutant and also decreased its foreign DNA acquisition by HFIR to the lower level of the sbcCD mutant. We propose that suppression of HFIR results from the elimination of double-stranded intermediates of the HFIR process during transformation by RecBCD, and by SbcCD interfering with branched molecules. Our results provide evidence that the homologous recombination enzymes RecBCD and SbcCD control the level of foreign DNA acquisition by HFIR.

  12. AtMND1 is required for homologous pairing during meiosis in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Marimuthu Mohan PA

    2006-07-01

    Full Text Available Abstract Background Pairing of homologous chromosomes at meiosis is an important requirement for recombination and balanced chromosome segregation among the products of meiotic division. Recombination is initiated by double strand breaks (DSBs made by Spo11 followed by interaction of DSB sites with a homologous chromosome. This interaction requires the strand exchange proteins Rad51 and Dmc1 that bind to single stranded regions created by resection of ends at the site of DSBs and promote interactions with uncut DNA on the homologous partner. Recombination is also considered to be dependent on factors that stabilize interactions between homologous chromosomes. In budding yeast Hop2 and Mnd1 act as a complex to promote homologous pairing and recombination in conjunction with Rad51 and Dmc1. Results We have analyzed the function of the Arabidopsis orthologue of the budding yeast MND1 gene (AtMND1. Loss of AtMND1 did not affect normal vegetative development but caused fragmentation and missegregation of chromosomes in male and female meiosis, formation of inviable gametes, and sterility. Analysis of the Atmnd1 Atspo11-1 double mutant indicated that chromosome fragmentation in Atmnd1 was suppressed by loss of Atspo11-1. Fluorescence in situ hybridization (FISH analysis showed that homologous pairing failed to occur and homologues remained apart throughout meiosis. AtMND1 showed strong expression in meiocytes as revealed by RNA in situs. Conclusion We conclude that AtMND1 is required for homologous pairing and is likely to play a role in the repair of DNA double strand breaks during meiosis in Arabidopsis, thus showing conservation of function with that of MND1 during meiosis in yeast.

  13. AtMND1 is required for homologous pairing during meiosis in Arabidopsis

    Science.gov (United States)

    Panoli, Aneesh P; Ravi, Maruthachalam; Sebastian, Jose; Nishal, Bindu; Reddy, Thamalampudi V; Marimuthu, Mohan PA; Subbiah, Veeraputhiran; Vijaybhaskar, Virupapuram; Siddiqi, Imran

    2006-01-01

    Background Pairing of homologous chromosomes at meiosis is an important requirement for recombination and balanced chromosome segregation among the products of meiotic division. Recombination is initiated by double strand breaks (DSBs) made by Spo11 followed by interaction of DSB sites with a homologous chromosome. This interaction requires the strand exchange proteins Rad51 and Dmc1 that bind to single stranded regions created by resection of ends at the site of DSBs and promote interactions with uncut DNA on the homologous partner. Recombination is also considered to be dependent on factors that stabilize interactions between homologous chromosomes. In budding yeast Hop2 and Mnd1 act as a complex to promote homologous pairing and recombination in conjunction with Rad51 and Dmc1. Results We have analyzed the function of the Arabidopsis orthologue of the budding yeast MND1 gene (AtMND1). Loss of AtMND1 did not affect normal vegetative development but caused fragmentation and missegregation of chromosomes in male and female meiosis, formation of inviable gametes, and sterility. Analysis of the Atmnd1 Atspo11-1 double mutant indicated that chromosome fragmentation in Atmnd1 was suppressed by loss of Atspo11-1. Fluorescence in situ hybridization (FISH) analysis showed that homologous pairing failed to occur and homologues remained apart throughout meiosis. AtMND1 showed strong expression in meiocytes as revealed by RNA in situs. Conclusion We conclude that AtMND1 is required for homologous pairing and is likely to play a role in the repair of DNA double strand breaks during meiosis in Arabidopsis, thus showing conservation of function with that of MND1 during meiosis in yeast. PMID:16872528

  14. Efficacy of hepatitis B vaccine against antiviral drug-resistant hepatitis B virus mutants in the chimpanzee model.

    Science.gov (United States)

    Kamili, Saleem; Sozzi, Vitini; Thompson, Geoff; Campbell, Katie; Walker, Christopher M; Locarnini, Stephen; Krawczynski, Krzysztof

    2009-05-01

    Hepatitis B virus (HBV) mutants resistant to treatment with nucleoside or nucleotide analogs and those with the ability to escape from HBV-neutralizing antibody have the potential to infect HBV-vaccinated individuals. To address this potential serious public health challenge, we tested the efficacy of immunity induced by a commercial hepatitis B vaccine against a tissue culture-derived, clonal HBV polymerase mutant in HBV seronegative chimpanzees. The polymerase gene mutant contained a combination of three mutations (rtV173L, rtL180M, rtM204V), two of which resulted in changes to the overlapping viral envelope of the hepatitis B surface antigen (sE164D, sI195M). Prior to the HBV mutant challenge of vaccinated chimpanzees, we established virologic, serologic, and pathologic characteristics of infections resulting from intravenous inoculation of the HBV polymerase gene mutant and the sG145R vaccine-escape surface gene mutant. Cloning and sequencing experiments determined that the three mutations in the polymerase gene mutant remained stable and that the single mutation in the surface gene mutant reverted to the wild-type sequence. Immunological evidence of HBV replication was observed in the vaccinated chimpanzees after challenge with the polymerase gene mutant as well as after rechallenge with serum-derived wild-type HBV (5,000 chimpanzee infectious doses administered intravenously), despite robust humoral and cellular anti-HBV immune responses after hepatitis B vaccination. Our data showing successful experimental infection by HBV mutants despite the presence of high anti-HBs levels considered protective in the vaccinated host are consistent with clinical reports on breakthrough infection in anti-HBs-positive patients infected with HBV mutants. In the absence of a protective humoral immunity, adaptive cellular immune responses elicited by infection may limit HBV replication and persistence.

  15. Dualities in Persistent (Co)Homology

    Energy Technology Data Exchange (ETDEWEB)

    de Silva, Vin; Morozov, Dmitriy; Vejdemo-Johansson, Mikael

    2011-09-16

    We consider sequences of absolute and relative homology and cohomology groups that arise naturally for a filtered cell complex. We establishalgebraic relationships between their persistence modules, and show that they contain equivalent information. We explain how one can use the existingalgorithm for persistent homology to process any of the four modules, and relate it to a recently introduced persistent cohomology algorithm. Wepresent experimental evidence for the practical efficiency of the latter algorithm.

  16. Srs2 and Mus81-Mms4 Prevent Accumulation of Toxic Inter-Homolog Recombination Intermediates.

    Directory of Open Access Journals (Sweden)

    Kenji Keyamura

    2016-07-01

    Full Text Available Homologous recombination is an evolutionally conserved mechanism that promotes genome stability through the faithful repair of double-strand breaks and single-strand gaps in DNA, and the recovery of stalled or collapsed replication forks. Saccharomyces cerevisiae ATP-dependent DNA helicase Srs2 (a member of the highly conserved UvrD family of helicases has multiple roles in regulating homologous recombination. A mutation (srs2K41A resulting in a helicase-dead mutant of Srs2 was found to be lethal in diploid, but not in haploid, cells. In diploid cells, Srs2K41A caused the accumulation of inter-homolog joint molecule intermediates, increased the levels of spontaneous Rad52 foci, and induced gross chromosomal rearrangements. Srs2K41A lethality and accumulation of joint molecules were suppressed by inactivating Rad51 or deleting the Rad51-interaction domain of Srs2, whereas phosphorylation and sumoylation of Srs2 and its interaction with sumoylated proliferating cell nuclear antigen (PCNA were not required for lethality. The structure-specific complex of crossover junction endonucleases Mus81 and Mms4 was also required for viability of diploid, but not haploid, SRS2 deletion mutants (srs2Δ, and diploid srs2Δ mus81Δ mutants accumulated joint molecule intermediates. Our data suggest that Srs2 and Mus81-Mms4 have critical roles in preventing the formation of (or in resolving toxic inter-homolog joint molecules, which could otherwise interfere with chromosome segregation and lead to genetic instability.

  17. Whole genome analysis of CRISPR Cas9 sgRNA off-target homologies via an efficient computational algorithm.

    Science.gov (United States)

    Zhou, Hong; Zhou, Michael; Li, Daisy; Manthey, Joseph; Lioutikova, Ekaterina; Wang, Hong; Zeng, Xiao

    2017-11-17

    The beauty and power of the genome editing mechanism, CRISPR Cas9 endonuclease system, lies in the fact that it is RNA-programmable such that Cas9 can be guided to any genomic loci complementary to a 20-nt RNA, single guide RNA (sgRNA), to cleave double stranded DNA, allowing the introduction of wanted mutations. Unfortunately, it has been reported repeatedly that the sgRNA can also guide Cas9 to off-target sites where the DNA sequence is homologous to sgRNA. Using human genome and Streptococcus pyogenes Cas9 (SpCas9) as an example, this article mathematically analyzed the probabilities of off-target homologies of sgRNAs and discovered that for large genome size such as human genome, potential off-target homologies are inevitable for sgRNA selection. A highly efficient computationl algorithm was developed for whole genome sgRNA design and off-target homology searches. By means of a dynamically constructed sequence-indexed database and a simplified sequence alignment method, this algorithm achieves very high efficiency while guaranteeing the identification of all existing potential off-target homologies. Via this algorithm, 1,876,775 sgRNAs were designed for the 19,153 human mRNA genes and only two sgRNAs were found to be free of off-target homology. By means of the novel and efficient sgRNA homology search algorithm introduced in this article, genome wide sgRNA design and off-target analysis were conducted and the results confirmed the mathematical analysis that for a sgRNA sequence, it is almost impossible to escape potential off-target homologies. Future innovations on the CRISPR Cas9 gene editing technology need to focus on how to eliminate the Cas9 off-target activity.

  18. Mouse Dach2 mutants do not exhibit gross defects in eye development or brain function.

    Science.gov (United States)

    Davis, Richard J; Pesah, Yakov I; Harding, Mark; Paylor, Richard; Mardon, Graeme

    2006-02-01

    Drosophila dachshund is a critical regulator of eye, brain, and limb formation. Vertebrate homologs, Dach1 and Dach2, are expressed in the developing retina, brain, and limbs, suggesting functional conservation of the dachshund/Dach gene family. Dach1 mutants die postnatally, but exhibit grossly normal development. Here we report the generation of Dach2 mutant mice. Although deletion of Dach2 exon 1 results in abrogation of RNA expression, Dach2 mutants are viable and fertile. Histochemical analysis reveals grossly normal Dach2 mutant eye development. In addition, a battery of neurological assays failed to yield significant differences in behavior between Dach2 mutants and controls. We discuss these findings in the light of published observations of DACH2 mutations in the human population. Finally, to test the functional conservation hypothesis, we generated Dach2; Dach1 double mutant mice. Dach double mutants die after birth, similar to Dach1 homozygotes. However, unlike Drosophila dachshund mutants that lack eyes and exhibit leg truncations, the eyes and limbs of Dach double mutants are present, suggesting differences between Dach and dachshund gene function during embryonic eye and limb formation.

  19. Escape to infinity under the action of a potential and a constant electromagnetic field

    CERN Document Server

    Gascon, F G

    2003-01-01

    Escape to infinity is proved for a great variety of potentials, including the potential created by an infinite number of sources. Relativistic escape is studied. Escape in the presence of a constant electromagnetic field and a potential is also considered.

  20. Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome

    Directory of Open Access Journals (Sweden)

    Song Hongshuo

    2012-10-01

    Full Text Available Abstract Background A modest change in HIV-1 fitness can have a significant impact on viral quasispecies evolution and viral pathogenesis, transmission and disease progression. To determine the impact of immune escape mutations selected by cytotoxic T lymphocytes (CTL on viral fitness in the context of the cognate transmitted/founder (T/F genome, we developed a new competitive fitness assay using molecular clones of T/F genomes lacking exogenous genetic markers and a highly sensitive and precise parallel allele-specific sequencing (PASS method. Results The T/F and mutant viruses were competed in CD4+ T-cell enriched cultures, relative proportions of viruses were assayed after repeated cell-free passage, and fitness costs were estimated by mathematical modeling. Naturally occurring HLA B57-restricted mutations involving the TW10 epitope in Gag and two epitopes in Tat/Rev and Env were assessed independently and together. Compensatory mutations which restored viral replication fitness were also assessed. A principal TW10 escape mutation, T242N, led to a 42% reduction in replication fitness but V247I and G248A mutations in the same epitope restored fitness to wild-type levels. No fitness difference was observed between the T/F and a naturally selected variant carrying the early CTL escape mutation (R355K in Env and a reversion mutation in the Tat/Rev overlapping region. Conclusions These findings reveal a broad spectrum of fitness costs to CTL escape mutations in T/F viral genomes, similar to recent findings reported for neutralizing antibody escape mutations, and highlight the extraordinary plasticity and adaptive potential of the HIV-1 genome. Analysis of T/F genomes and their evolved progeny is a powerful approach for assessing the impact of composite mutational events on viral fitness.

  1. Escape of Cosmic Rays from their Acceleration Sites

    Science.gov (United States)

    Malkov, Mikhail; Sagdeev, Roald; Diamond, Patrick

    2012-07-01

    The escape of cosmic rays (CR) from sites of their acceleration, such as supernova remnants (SNR), is calculated self-consistently with the CR transport suppression by self-excited Alfvén waves. The treatment uniformly applies both to the accelerator's nearby zone where intense CRs drive strong turbulence efficiently reducing their escape, and far zone where the CRs rapidly diffuse as test particles. To demonstrate the inseparability of the two zones in calculating the escape flux, an exact solution is obtained for the nonlinear spreading of a sharply localized CR cloud.

  2. Sequence homology at the breakpoint and clinical phenotype of mitochondrial DNA deletion syndromes.

    Directory of Open Access Journals (Sweden)

    Bekim Sadikovic

    2010-12-01

    Full Text Available Mitochondrial DNA (mtDNA deletions are a common cause of mitochondrial disorders. Large mtDNA deletions can lead to a broad spectrum of clinical features with different age of onset, ranging from mild mitochondrial myopathies (MM, progressive external ophthalmoplegia (PEO, and Kearns-Sayre syndrome (KSS, to severe Pearson syndrome. The aim of this study is to investigate the molecular signatures surrounding the deletion breakpoints and their association with the clinical phenotype and age at onset. MtDNA deletions in 67 patients were characterized using array comparative genomic hybridization (aCGH followed by PCR-sequencing of the deletion junctions. Sequence homology including both perfect and imperfect short repeats flanking the deletion regions were analyzed and correlated with clinical features and patients' age group. In all age groups, there was a significant increase in sequence homology flanking the deletion compared to mtDNA background. The youngest patient group (<6 years old showed a diffused pattern of deletion distribution in size and locations, with a significantly lower sequence homology flanking the deletion, and the highest percentage of deletion mutant heteroplasmy. The older age groups showed rather discrete pattern of deletions with 44% of all patients over 6 years old carrying the most common 5 kb mtDNA deletion, which was found mostly in muscle specimens (22/41. Only 15% (3/20 of the young patients (<6 years old carry the 5 kb common deletion, which is usually present in blood rather than muscle. This group of patients predominantly (16 out of 17 exhibit multisystem disorder and/or Pearson syndrome, while older patients had predominantly neuromuscular manifestations including KSS, PEO, and MM. In conclusion, sequence homology at the deletion flanking regions is a consistent feature of mtDNA deletions. Decreased levels of sequence homology and increased levels of deletion mutant heteroplasmy appear to correlate with earlier

  3. Sequence homology at the breakpoint and clinical phenotype of mitochondrial DNA deletion syndromes.

    Science.gov (United States)

    Sadikovic, Bekim; Wang, Jing; El-Hattab, Ayman W; Landsverk, Megan; Douglas, Ganka; Brundage, Ellen K; Craigen, William J; Schmitt, Eric S; Wong, Lee-Jun C

    2010-12-20

    Mitochondrial DNA (mtDNA) deletions are a common cause of mitochondrial disorders. Large mtDNA deletions can lead to a broad spectrum of clinical features with different age of onset, ranging from mild mitochondrial myopathies (MM), progressive external ophthalmoplegia (PEO), and Kearns-Sayre syndrome (KSS), to severe Pearson syndrome. The aim of this study is to investigate the molecular signatures surrounding the deletion breakpoints and their association with the clinical phenotype and age at onset. MtDNA deletions in 67 patients were characterized using array comparative genomic hybridization (aCGH) followed by PCR-sequencing of the deletion junctions. Sequence homology including both perfect and imperfect short repeats flanking the deletion regions were analyzed and correlated with clinical features and patients' age group. In all age groups, there was a significant increase in sequence homology flanking the deletion compared to mtDNA background. The youngest patient group (deletion distribution in size and locations, with a significantly lower sequence homology flanking the deletion, and the highest percentage of deletion mutant heteroplasmy. The older age groups showed rather discrete pattern of deletions with 44% of all patients over 6 years old carrying the most common 5 kb mtDNA deletion, which was found mostly in muscle specimens (22/41). Only 15% (3/20) of the young patients (deletion, which is usually present in blood rather than muscle. This group of patients predominantly (16 out of 17) exhibit multisystem disorder and/or Pearson syndrome, while older patients had predominantly neuromuscular manifestations including KSS, PEO, and MM. In conclusion, sequence homology at the deletion flanking regions is a consistent feature of mtDNA deletions. Decreased levels of sequence homology and increased levels of deletion mutant heteroplasmy appear to correlate with earlier onset and more severe disease with multisystem involvement.

  4. Fin-tail coordination during escape and predatory behavior in larval zebrafish.

    Directory of Open Access Journals (Sweden)

    Phil McClenahan

    Full Text Available Larval zebrafish innately perform a suite of behaviors that are tightly linked to their evolutionary past, notably escape from threatening stimuli and pursuit and capture of prey. These behaviors have been carefully examined in the past, but mostly with regard to the movements of the trunk and tail of the larvae. Here, we employ kinematics analyses to describe the movements of the pectoral fins during escape and predatory behavior. In accord with previous studies, we find roles for the pectoral fins in slow swimming and immediately after striking prey. We find novel roles for the pectoral fins in long-latency, but not in short-latency C-bends. We also observe fin movements that occur during orienting J-turns and S-starts that drive high-velocity predatory strikes. Finally, we find that the use of pectoral fins following a predatory strike is scaled to the velocity of the strike, supporting a role for the fins in braking. The implications of these results for central control of coordinated movements are discussed, and we hope that these results will provide baselines for future analyses of cross-body coordination using mutants, morphants, and transgenic approaches.

  5. A Nuclease from Streptococcus mutans Facilitates Biofilm Dispersal and Escape from Killing by Neutrophil Extracellular Traps.

    Science.gov (United States)

    Liu, Jia; Sun, Luping; Liu, Wei; Guo, Lihong; Liu, Zhaohui; Wei, Xi; Ling, Junqi

    2017-01-01

    Streptococcus mutans is the primary etiologic agent of dental caries and occasionally infective endocarditis, with the ability to form biofilms and disperse cells into distal sites to exacerbate and spread infection. In this study, we identified a nuclease (DeoC) as a S. mutans biofilm dispersal modulating factor through microarray analysis. In vitro assays revealed a dispersal defect of a deoC deletion mutant, and functional studies with purified protein were indicative of the biofilm dispersal activity of DeoC. Neutrophils are a key host response factor restraining bacterial spreading through the formation of neutrophil extracellular traps (NETs), which consist of a nuclear DNA backbone associated with antimicrobial peptides. Therefore, we hypothesized that the dispersed S. mutans might utilize DeoC to degrade NETs and escape killing by the immune system. It was found that S. mutans induced NET formation upon contact with neutrophils, while the presence of NETs in turn enhanced the deoC expression of S. mutans . Fluorescence microscopy inspection showed that deoC deletion resulted in a decreased NET degradation ability of S. mutans and enhanced susceptibility to neutrophil killing. Data obtained from this study assigned two important roles for DeoC in S. mutans : contributing to the spread of infection through mediating biofilm dispersal, and facilitating the escape of S. mutans from neutrophil killing through NET degradation.

  6. Evaluation of tall rice mutant

    International Nuclear Information System (INIS)

    Hakim, L.; Azam, M.A.; Miah, A.J.; Mansur, M.A.; Akanda, H.R.

    1989-01-01

    One tall mutant (Mut NS1) of rice variety Nizersail was put to multilocation on-farm trial. It showed improvement over the parent in respect of by earlier maturity and higher grain yield at all locations and thus it appears as an improved mutant of Nizersail. (author). 6 refs

  7. DNA apoptosis and stability in B-cell chronic lymphoid leukaemia: implication of the DNA double-strand breaks repair system by non homologous recombination

    International Nuclear Information System (INIS)

    Deriano, L.

    2005-01-01

    After an introduction presenting the diagnosis and treatment of chronic lymphoid leukaemia, its molecular and genetic characteristics, and its cellular origin and clonal evolution, this research thesis describes the apoptosis (definition and characteristics, cancer and chemotherapy, apoptotic ways induced by gamma irradiation), the genotoxic stresses, the different repair mechanisms for different damages, and the DNA repair processes. It reports how human chronic lymphocytic leukaemia B cells can escape DNA damage-induced apoptosis through the non-homologous end-joining DNA repair pathway, and presents non-homologous end-joining DNA repair as a potent mutagenic process in human chronic lymphocytic leukaemia B cells

  8. Autologous HIV-1 neutralizing antibodies: emergence of neutralization-resistant escape virus and subsequent development of escape virus neutralizing antibodies

    DEFF Research Database (Denmark)

    Arendrup, M; Nielsen, C; Hansen, J E

    1992-01-01

    The capacity of consecutive human sera to neutralize sequentially obtained autologous virus isolates was studied. HIV-1 was isolated three times over a 48-164-week period from three individuals immediately after seroconversion and from two individuals in later stages of infection. Development...... escape virus may be part of the explanation of the apparent failure of the immune system to control HIV infection....... of neutralizing antibodies to the primary virus isolates was detected 13-45 weeks after seroconversion. Emergence of escape virus with reduced sensitivity to neutralization by autologous sera was demonstrated. The patients subsequently developed neutralizing antibodies against the escape virus but after a delay...

  9. GREEN PEA GALAXIES REVEAL SECRETS OF Lyα ESCAPE

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Huan; Wang, Junxian [CAS Key Laboratory for Research in Galaxies and Cosmology, Department of Astronomy, University of Science and Technology of China (China); Malhotra, Sangeeta; Rhoads, James E. [Arizona State University, School of Earth and Space Exploration (United States); Gronke, Max; Dijkstra, Mark [Institute of Theoretical Astrophysics, University of Oslo (Norway); Jaskot, Anne [Smith College, Northampton, MA (United States); Zheng, Zhenya, E-mail: yanghuan@mail.ustc.edu.cn, E-mail: huan.y@asu.edu, E-mail: Sangeeta.Malhotra@asu.edu, E-mail: James.Rhoads@asu.edu [Pontificia Universidad Católica de Chile, Santiago (Chile)

    2016-04-01

    We analyze archival Lyα spectra of 12 “Green Pea” galaxies observed with the Hubble Space Telescope, model their Lyα profiles with radiative transfer models, and explore the dependence of the Lyα escape fraction on various properties. Green Pea galaxies are nearby compact starburst galaxies with [O iii] λ5007 equivalent widths (EWs) of hundreds of Å. All 12 Green Pea galaxies in our sample show Lyα lines in emission, with an Lyα EW distribution similar to high-redshift Lyα emitters. Combining the optical and UV spectra of Green Pea galaxies, we estimate their Lyα escape fractions and find correlations between Lyα escape fraction and kinematic features of Lyα profiles. The escape fraction of Lyα in these galaxies ranges from 1.4% to 67%. We also find that the Lyα escape fraction depends strongly on metallicity and moderately on dust extinction. We compare their high-quality Lyα profiles with single H i shell radiative transfer models and find that the Lyα escape fraction anticorrelates with the derived H i column densities. Single-shell models fit most Lyα profiles well, but not the ones with the highest escape fractions of Lyα. Our results suggest that low H i column density and low metallicity are essential for Lyα escape and make a galaxy an Lyα emitter.

  10. The influence of panic on the efficiency of escape

    Science.gov (United States)

    Shen, Jia-Quan; Wang, Xu-Wen; Jiang, Luo-Luo

    2018-02-01

    Whenever we (such as pedestrians) perceive a high density or imminent danger in a confined space, we tend to be panic, which can lead to severe injuries even in the absence of real dangers. Although it is difficult to measure panics in real conditions, we introduced a simple model to study the collective behaviors in condition of fire with dense smoke. Owing to blocking the sight with dense smoke, pedestrians in this condition have two strategies to escape: random-walking or walking along the wall. When the pedestrians are in moderate panic that mean the two types of behaviors are mixed(random-walking and walking along the wall). Our simulation results show that moderate panic, meaning that two escape strategies are mixed, reduces the escape time. In addition, the results indicate that moderate panic can improve the efficiency of escape, this theory also can be useful in a real escape situation. We hope that our research provides the theoretical understanding of underlying mechanisms of panic escape in the condition of poor sight.

  11. On the hodological criterion for homology

    Directory of Open Access Journals (Sweden)

    Macarena eFaunes

    2015-06-01

    Full Text Available Owen’s pre-evolutionary definition of a homologue as the same organ in different animals under every variety of form and function and its redefinition after Darwin as the same trait in different lineages due to common ancestry entail the same heuristic problem: how to establish sameness. Although different criteria for homology often conflict, there is currently a generalized acceptance of gene expression as the best criterion. This gene-centered view of homology results from a reductionist and preformationist concept of living beings. Here, we adopt an alternative organismic-epigenetic viewpoint, and conceive living beings as systems whose identity is given by the dynamic interactions between their components at their multiple levels of composition. We posit that there cannot be an absolute homology criterion, and instead, homology should be inferred from comparisons at the levels and developmental stages where the delimitation of the compared trait lies. In this line, we argue that neural connectivity, i.e., the hodological criterion, should prevail in the determination of homologies between brain supra-cellular structures, such as the vertebrate pallium.

  12. The Swedish mutant barley collection

    International Nuclear Information System (INIS)

    1989-01-01

    Full text: The Swedish mutation research programme in barley began about 50 years ago and has mainly been carried out at Svaloev in co-operation with the institute of Genetics at the University of Lund. The collection has been produced from different Swedish high-yielding spring barley varieties, using the following mutagens: X-rays, neutrons, several organic chemical compounds such as ethyleneimine, several sulfonate derivatives and the inorganic chemical mutagen sodium azide. Nearly 10,000 barley mutants are stored in the Nordic Gene Bank and documented in databases developed by Udda Lundquist, Svaloev AB. The collection consists of the following nine categories with 94 different types of mutants: 1. Mutants with changes in the spike and spikelets; 2. Changes in culm length and culm composition; 3. Changes in growth types; 4. Physiological mutants; 5. Changes in awns; 6. Changes in seed size and shape; 7. Changes in leaf blades; 8. Changes in anthocyanin and colour; 9. Resistance to barley powdery mildew. Barley is one of the most thoroughly investigated crops in terms of induction of mutations and mutation genetics. So far, about half of the mutants stored at the Nordic Gene Bank, have been analysed genetically; They constitute, however, only a minority of the 94 different mutant types. The genetic analyses have given valuable insights into the mutation process but also into the genetic architecture of various characters. A number of mutants of two-row barley have been registered and commercially released. One of the earliest released, Mari, an early maturing, daylength neutral, straw stiff mutant, is still grown in Iceland. The Swedish mutation material has been used in Sweden, but also in other countries, such as Denmark, Germany, and USA, for various studies providing a better understanding of the barley genome. The collection will be immensely valuable for future molecular genetical analyses of clone mutant genes. (author)

  13. Primary Cilia in the Murine Cerebellum and in Mutant Models of Medulloblastoma.

    Science.gov (United States)

    Di Pietro, Chiara; Marazziti, Daniela; La Sala, Gina; Abbaszadeh, Zeinab; Golini, Elisabetta; Matteoni, Rafaele; Tocchini-Valentini, Glauco P

    2017-01-01

    Cellular primary cilia crucially sense and transduce extracellular physicochemical stimuli. Cilium-mediated developmental signaling is tissue and cell type specific. Primary cilia are required for cerebellar differentiation and sonic hedgehog (Shh)-dependent proliferation of neuronal granule precursors. The mammalian G-protein-coupled receptor 37-like 1 is specifically expressed in cerebellar Bergmann glia astrocytes and participates in regulating postnatal cerebellar granule neuron proliferation/differentiation and Bergmann glia and Purkinje neuron maturation. The mouse receptor protein interacts with the patched 1 component of the cilium-associated Shh receptor complex. Mice heterozygous for patched homolog 1 mutations, like heterozygous patched 1 humans, have a higher incidence of Shh subgroup medulloblastoma (MB) and other tumors. Cerebellar cells bearing primary cilia were identified during postnatal development and in adulthood in two mouse strains with altered Shh signaling: a G-protein-coupled receptor 37-like 1 null mutant and an MB-susceptible, heterozygous patched homolog 1 mutant. In addition to granule and Purkinje neurons, primary cilia were also expressed by Bergmann glia astrocytes in both wild-type and mutant animals, from birth to adulthood. Variations in ciliary number and length were related to the different levels of neuronal and glial cell proliferation and maturation, during postnatal cerebellar development. Primary cilia were also detected in pre-neoplastic MB lesions in heterozygous patched homolog 1 mutant mice and they could represent specific markers for the development and analysis of novel cerebellar oncogenic models.

  14. ESCAPE to Reality, Post-Trial Outcomes in an ESCAPE Centre: A Retrospective Case-Control Study.

    Science.gov (United States)

    Nixon, Amy M; Jamison, Michael; Rennie, Ian M; Flynn, Peter A; Smyth, Graham; Wiggam, Ivan; Kerr, Enda; Fulton, Ailsa; Hunter, Annemarie; Burns, Paul A

    2018-01-01

    The Royal Victoria Hospital, Belfast provides the regional neuroendovascular service for Northern Ireland and was an enrolling centre for the ESCAPE endovascular stroke trial. Our aim was to assess outcomes for patients presenting with acute stroke following discontinuation of trial enrolment at our centre. We collected data on all patients presenting with acute stoke between Nov-1st-2014 and Oct-31st-2015 who received endovascular treatment or received IV thrombolysis (IV-tPA) alone. ESCAPE eligibility of each patient was assessed. Primary outcome was modified Rankin Score (mRS) at 3 months. 129 patients presented with acute stoke symptoms during the time period; 56/129 (43.4%) patients in the intervention group and 73/129 (56.5%) patients in the control group. In the interventional group, 42/56 (75%) were considered ESCAPE eligible and 14/56 (25%) were considered ESCAPE ineligible. 30/42 (71.4%) ESCAPE eligible patients had a positive functional outcome at 3 months compared to 9/14 (64.2%) ESCAPE ineligible patients. In the control group, 37 (50.7%) had identifiable thrombotic occlusion and 13/37 (35.1%) were considered eligible for intervention. 4/13 (30.8%) achieved functional independence (mRS<3) at 3 months.There was a statistically significant difference in functional independence in those who underwent endovascular therapy compared to the control group (p= 0.04). ESCAPE eligible patients in our centre had favourable outcome rates superior to the published trial data. ESCAPE ineligible patients tended to do slightly less well, but still better than the favourable outcome rates achieved with IVtPA alone. There is potentially a wide discordance between the threshold for futility and trial eligibility criteria when considering endovascular treatment for acute ischaemic stroke.

  15. The Drosophila HEM-2/NAP1 homolog KETTE controls axonal pathfinding and cytoskeletal organization.

    Science.gov (United States)

    Hummel, T; Leifker, K; Klämbt, C

    2000-04-01

    In Drosophila, the correct formation of the segmental commissures depends on neuron-glial interactions at the midline. The VUM midline neurons extend axons along which glial cells migrate in between anterior and posterior commissures. Here, we show that the gene kette is required for the normal projection of the VUM axons and subsequently disrupts glial migration. Axonal projection defects are also found for many other moto- and interneurons. In addition, kette affects the cell morphology of mesodermal and epidermal derivatives, which show an abnormal actin cytoskeleton. The KETTE protein is homologous to the transmembrane protein HEM-2/NAP1 evolutionary conserved from worms to vertebrates. In vitro analysis has shown a specific interaction of the vertebrate HEM-2/NAP1 with the SH2-SH3 adapter protein NCK and the small GTPase RAC1, which both have been implicated in regulating cytoskeleton organization and axonal growth. Hypomorphic kette mutations lead to axonal defects similar to mutations in the Drosophila NCK homolog dreadlocks. Furthermore, we show that kette and dock mutants genetically interact. NCK is thought to interact with the small G proteins RAC1 and CDC42, which play a role in axonal growth. In line with these observations, a kette phenocopy can be obtained following directed expression of mutant DCDC42 or DRAC1 in the CNS midline. In addition, the kette mutant phenotype can be partially rescued by expression of an activated DRAC1 transgene. Our data suggest an important role of the HEM-2 protein in cytoskeletal organization during axonal pathfinding.

  16. Homological methods, representation theory, and cluster algebras

    CERN Document Server

    Trepode, Sonia

    2018-01-01

    This text presents six mini-courses, all devoted to interactions between representation theory of algebras, homological algebra, and the new ever-expanding theory of cluster algebras. The interplay between the topics discussed in this text will continue to grow and this collection of courses stands as a partial testimony to this new development. The courses are useful for any mathematician who would like to learn more about this rapidly developing field; the primary aim is to engage graduate students and young researchers. Prerequisites include knowledge of some noncommutative algebra or homological algebra. Homological algebra has always been considered as one of the main tools in the study of finite-dimensional algebras. The strong relationship with cluster algebras is more recent and has quickly established itself as one of the important highlights of today’s mathematical landscape. This connection has been fruitful to both areas—representation theory provides a categorification of cluster algebras, wh...

  17. Parallelism, deep homology, and evo-devo.

    Science.gov (United States)

    Hall, Brian K

    2012-01-01

    Parallelism has been the subject of a number of recent studies that have resulted in reassessment of the term and the process. Parallelism has been aligned with homology leaving convergence as the only case of homoplasy, regarded as a transition between homologous and convergent characters, and defined as the independent evolution of genetic traits. Another study advocates abolishing the term parallelism and treating all cases of the independent evolution of characters as convergence. With the sophistication of modern genomics and genetic analysis, parallelism of characters of the phenotype is being discovered to reflect parallel genetic evolution. Approaching parallelism from developmental and genetic perspectives enables us to tease out the degree to which the reuse of pathways represent deep homology and is a major task for evolutionary developmental biology in the coming decades. © 2012 Wiley Periodicals, Inc.

  18. Either non-homologous ends joining or homologous recombination is required to repair double-strand breaks in the genome of macrophage-internalized Mycobacterium tuberculosis.

    Science.gov (United States)

    Brzostek, Anna; Szulc, Izabela; Klink, Magdalena; Brzezinska, Marta; Sulowska, Zofia; Dziadek, Jaroslaw

    2014-01-01

    The intracellular pathogen Mycobacterium tuberculosis (Mtb) is constantly exposed to a multitude of hostile conditions and is confronted by a variety of potentially DNA-damaging assaults in vivo, primarily from host-generated antimicrobial toxic radicals. Exposure to reactive nitrogen species and/or reactive oxygen species causes different types of DNA damage, including oxidation, depurination, methylation and deamination, that can result in single- or double-strand breaks (DSBs). These breaks affect the integrity of the whole genome and, when left unrepaired, can lead to cell death. Here, we investigated the role of the DSB repair pathways, homologous recombination (HR) and non-homologous ends joining (NHEJ), in the survival of Mtb inside macrophages. To this end, we constructed Mtb strains defective for HR (ΔrecA), NHEJ [Δ(ku,ligD)], or both DSB repair systems [Δ(ku,ligD,recA)]. Experiments using these strains revealed that either HR or NHEJ is sufficient for the survival and propagation of tubercle bacilli inside macrophages. Inhibition of nitric oxide or superoxide anion production with L-NIL or apocynin, respectively, enabled the Δ(ku,ligD,recA) mutant strain lacking both systems to survive intracellularly. Complementation of the Δ(ku,ligD,recA) mutant with an intact recA or ku-ligD rescued the ability of Mtb to propagate inside macrophages.

  19. Either non-homologous ends joining or homologous recombination is required to repair double-strand breaks in the genome of macrophage-internalized Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Anna Brzostek

    Full Text Available The intracellular pathogen Mycobacterium tuberculosis (Mtb is constantly exposed to a multitude of hostile conditions and is confronted by a variety of potentially DNA-damaging assaults in vivo, primarily from host-generated antimicrobial toxic radicals. Exposure to reactive nitrogen species and/or reactive oxygen species causes different types of DNA damage, including oxidation, depurination, methylation and deamination, that can result in single- or double-strand breaks (DSBs. These breaks affect the integrity of the whole genome and, when left unrepaired, can lead to cell death. Here, we investigated the role of the DSB repair pathways, homologous recombination (HR and non-homologous ends joining (NHEJ, in the survival of Mtb inside macrophages. To this end, we constructed Mtb strains defective for HR (ΔrecA, NHEJ [Δ(ku,ligD], or both DSB repair systems [Δ(ku,ligD,recA]. Experiments using these strains revealed that either HR or NHEJ is sufficient for the survival and propagation of tubercle bacilli inside macrophages. Inhibition of nitric oxide or superoxide anion production with L-NIL or apocynin, respectively, enabled the Δ(ku,ligD,recA mutant strain lacking both systems to survive intracellularly. Complementation of the Δ(ku,ligD,recA mutant with an intact recA or ku-ligD rescued the ability of Mtb to propagate inside macrophages.

  20. Homology Requirements and Competition between Gene Conversion and Break-Induced Replication during Double-Strand Break Repair.

    Science.gov (United States)

    Mehta, Anuja; Beach, Annette; Haber, James E

    2017-02-02

    Saccharomyces cerevisiae mating-type switching is initiated by a double-strand break (DSB) at MATa, leaving one cut end perfectly homologous to the HMLα donor, while the second end must be processed to remove a non-homologous tail before completing repair by gene conversion (GC). When homology at the matched end is ≤150 bp, efficient repair depends on the recombination enhancer, which tethers HMLα near the DSB. Thus, homology shorter than an apparent minimum efficient processing segment can be rescued by tethering the donor near the break. When homology at the second end is ≤150 bp, second-end capture becomes inefficient and repair shifts from GC to break-induced replication (BIR). But when pol32 or pif1 mutants block BIR, GC increases 3-fold, indicating that the steps blocked by these mutations are reversible. With short second-end homology, absence of the RecQ helicase Sgs1 promotes gene conversion, whereas deletion of the FANCM-related Mph1 helicase promotes BIR. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Mutants of alfalfa mosaic virus

    International Nuclear Information System (INIS)

    Roosien, J.

    1983-01-01

    In this thesis the isolation and characterization of a number of mutants of alfalfa mosaic virus, a plant virus with a coat protein dependent genome, is described. Thermo-sensitive (ts) mutants were selected since, at least theoretically, ts mutations can be present in all virus coded functions. It was found that a high percentage of spontaneous mutants, isolated because of their aberrant symptoms, were ts. The majority of these isolates could grow at the non-permissive temperature in the presence of a single wild type (wt) component. To increase the mutation rate virus preparations were treated with several mutagens. After nitrous acid treatment or irradiation with ultraviolet light, an increase in the level of mutations was observed. UV irradiation was preferred since it did not require large amounts of purified viral components. During the preliminary characterization of potential ts mutants the author also obtained one structural and several symptom mutants which were analysed further (chapter 7, 8 and 9). The properties of the ts mutants are described in chapter 3-7. (Auth.)

  2. To run or hide?: escape behaviour in a cryptic African snake | Maritz ...

    African Journals Online (AJOL)

    Optimal escape theory predicts that escape behaviour of an organism is best understood in terms of costs and benefits of escaping relative to risk of predation. However, risk of predation facing an organism is dependent on various biotic and abiotic factors. In order to better understand escape behaviour of an African snake, ...

  3. FBH1 helicase disrupts RAD51 filaments in vitro and modulates homologous recombination in mammalian cells

    DEFF Research Database (Denmark)

    Simandlova, Jitka; Zagelbaum, Jennifer; Payne, Miranda J

    2013-01-01

    Efficient repair of DNA double strand breaks and interstrand cross-links requires the homologous recombination (HR) pathway, a potentially error-free process that utilizes a homologous sequence as a repair template. A key player in HR is RAD51, the eukaryotic ortholog of bacterial RecA protein. RAD....... Using a combination of molecular genetic, biochemical, and single-molecule biophysical techniques, we provide mechanistic insight into the mode of action of the FBH1 helicase as a regulator of RAD51-dependent HR in mammalian cells. We show that FBH1 binds directly to RAD51 and is able to disrupt RAD51...... filaments on DNA through its ssDNA translocase function. Consistent with this, a mutant mouse embryonic stem cell line with a deletion in the FBH1 helicase domain fails to limit RAD51 chromatin association and shows hyper-recombination. Our data are consistent with FBH1 restraining RAD51 DNA binding under...

  4. Facilitation of Endosomal Recycling by an IRG Protein Homolog Maintains Apical Tubule Structure in Caenorhabditis elegans

    Science.gov (United States)

    Grussendorf, Kelly A.; Trezza, Christopher J.; Salem, Alexander T.; Al-Hashimi, Hikmat; Mattingly, Brendan C.; Kampmeyer, Drew E.; Khan, Liakot A.; Hall, David H.; Göbel, Verena; Ackley, Brian D.; Buechner, Matthew

    2016-01-01

    Determination of luminal diameter is critical to the function of small single-celled tubes. A series of EXC proteins, including EXC-1, prevent swelling of the tubular excretory canals in Caenorhabditis elegans. In this study, cloning of exc-1 reveals it to encode a homolog of mammalian IRG proteins, which play roles in immune response and autophagy and are associated with Crohn’s disease. Mutants in exc-1 accumulate early endosomes, lack recycling endosomes, and exhibit abnormal apical cytoskeletal structure in regions of enlarged tubules. EXC-1 interacts genetically with two other EXC proteins that also affect endosomal trafficking. In yeast two-hybrid assays, wild-type and putative constitutively active EXC-1 binds to the LIM-domain protein EXC-9, whose homolog, cysteine-rich intestinal protein, is enriched in mammalian intestine. These results suggest a model for IRG function in forming and maintaining apical tubule structure via regulation of endosomal recycling. PMID:27334269

  5. A rapid method for recombination and site-specific mutagenesis by placing homologous ends on DNA using polymerase chain reaction.

    Science.gov (United States)

    Jones, D H; Howard, B H

    1991-01-01

    We have developed a novel polymerase chain reaction (PCR) method that permits the rapid generation of site-specific mutants and recombinant DNA constructs with a minimum number of steps and primers. DNA segments are modified by using amplifying primers that add homologous ends to the polymerase chain reaction product(s). These homologous ends undergo recombination in vivo following transformation of recA-E. coli strains used routinely in cloning. In vivo circularization of PCR products containing plasmid sequences with a selective marker permits the rapid cloning of the desired mutant or recombinant. In the mutagenesis protocol, 7 of the 12 clones contained the product of interest, and 6 of these clones had no detected error (50% of the clones without detected errors). In each of several recombination protocols, at least 50% of the clones tested contained the insert of interest without detected errors.

  6. ESCAPE DYNAMICS AS A WAY TO DESCRIBE ECONOMIC PHENOMENA

    Directory of Open Access Journals (Sweden)

    Bogomolova A. S.

    2017-06-01

    Full Text Available This paper presents the review of issues and approaches to the analysis of escape dynamics in economic models with constant gain adaptive learning which is used to model and describe the behavior of various (macroeconomic as well as microeconomic variables in diverse economic phenomena such as currency crises, inflation episodes, endogenous collusion in oligopoly, and cycles of economic activity. This review considers and contrasts two currently existing approaches to the analysis of escape dynamics: the discrete-time approach employed, for example, by Cho, Williams and Sargent (2002, and the continuous-time approach proposed by Kasa (2004 and extended recently by Kolyuzhnov, Bogomolova and Slobodyan (2014, stressing the advantages of the latter. The continuous-time approach is based on the application of the results of the continuous-time version of the large deviations theory to the diffusion approximation of the original discrete-time dynamics under learning. Escape dynamics is characterized by analytically deriving the most probable escape point and mean escape time. The paper provides an example of the continuous-time approach applied to the Phelps problem of a government controlling inflation while adaptively learning the approximate Phillips curve.

  7. History of oxygen and carbon escape from the Martian atmosphere

    Science.gov (United States)

    Luhmann, J. G.; Zhang, M. H. G.; Johnson, R. E.; Bougher, S. W.; Nagy, A. F.

    1992-01-01

    A fraction of the oxygen in the Martian atmosphere continually escapes to space because dissociative recombination of the O2(+) ions in the ionosphere can impart sufficient energy to the product O atoms. In addition, ionization of the extended atomic oxygen corona resulting from the above process adds to escape since the solar wind can carry away O(+) ions born above a few hundred km altitude. A further by-product of this ion-pickup by the solar wind is an additional population of escaping oxygen atoms that are sputtered from the atmosphere near the exobase by pickup ions that are on reentry rather than escaping trajectories. This sputtering process can also remove carbon in the form of intact or dissociated CO2 since all atoms and molecules in the 'target' gas are subject to the collisional energy transfer that characterizes sputtering. We have estimated the present rates of escape of oxygen and carbon due to these mechanisms, as well as the rates at several epochs in the history of the solar system.

  8. GPCR Homology Model Generation for Lead Optimization.

    Science.gov (United States)

    Tautermann, Christofer S

    2018-01-01

    The vast increase of recently solved GPCR X-ray structures forms the basis for GPCR homology modeling to atomistic accuracy. Nowadays, homology models can be employed for GPCR-ligand optimization and have been reported as invaluable tools for drug design in the last few years. Elucidation of the complex GPCR pharmacology and the associated GPCR conformations made clear that different homology models have to be constructed for different activation states of the GPCRs. Therefore, templates have to be chosen accordingly to their sequence homology as well as to their activation state. The subsequent ligand placement is nontrivial, as some recent X-ray structures show very unusual ligand binding sites and solvent involvement, expanding the space of the putative ligand binding site from the generic retinal binding pocket to the whole receptor. In the present study, a workflow is presented starting from the selection of the target sequence, guiding through the GPCR modeling process, and finishing with ligand placement and pose validation.

  9. Threading homology through algebra selected patterns

    CERN Document Server

    Boffi, Giandomenico

    2006-01-01

    Aimed at graduate students and researchers in mathematics, this book takes homological themes, such as Koszul complexes and their generalizations, and shows how these can be used to clarify certain problems in selected parts of algebra, as well as their success in solving a number of them.

  10. Homological stability for unordered configuration spaces

    DEFF Research Database (Denmark)

    Randal-Williams, Oscar

    2013-01-01

    This paper consists of two related parts. In the first part we give a self-contained proof of homological stability for the spaces C_n(M;X) of configurations of n unordered points in a connected open manifold M with labels in a path-connected space X, with the best possible integral stability range...

  11. Homology modeling of γ-aminobutyrateaminotransferase, a ...

    African Journals Online (AJOL)

    γ-Aminobutyrate aminotransferase (GABA-AT) is a pyridoxal phosphate dependent homodimeric enzyme of 50-kD subunits. It is a potential drug target against epilepsy. The three-dimensional structure of GABA-AT is not experimentally known, and we thus resorted to homology modelling to build a model based on x-ray ...

  12. On the homology length spectrum of surfaces

    OpenAIRE

    Massart, Daniel; Parlier, Hugo

    2014-01-01

    On a surface with a Finsler metric, we investigate the asymptotic growth of the number of closed geodesics of length less than L which minimize length among all geodesic multicurves in the same homology class. An important class of surfaces which are of interest to us are hyperbolic surfaces.

  13. Homology and cohomology of Rees semigroup algebras

    DEFF Research Database (Denmark)

    Grønbæk, Niels; Gourdeau, Frédéric; White, Michael C.

    2011-01-01

    Let S by a Rees semigroup, and let 1¹(S) be its convolution semigroup algebra. Using Morita equivalence we show that bounded Hochschild homology and cohomology of l¹(S) is isomorphic to those of the underlying discrete group algebra....

  14. Nash equilibria via duality and homological selection

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Given a multifunction from to the -fold symmetric product Symk(X), we use the Dold–Thom theorem to establish a homological selection theorem. ... The domain part of the email address of all email addresses used by the office of Indian Academy of Sciences, including those of the staff, the journals, ...

  15. Cell biology of homologous recombination in yeast

    DEFF Research Database (Denmark)

    Eckert-Boulet, Nadine Valerie; Rothstein, Rodney; Lisby, Michael

    2011-01-01

    Homologous recombination is an important pathway for error-free repair of DNA lesions, such as single- and double-strand breaks, and for rescue of collapsed replication forks. Here, we describe protocols for live cell imaging of single-lesion recombination events in the yeast Saccharomyces...

  16. Parametric representation of centrifugal pump homologous curves

    International Nuclear Information System (INIS)

    Veloso, Marcelo A.; Mattos, Joao R.L. de

    2015-01-01

    Essential for any mathematical model designed to simulate flow transient events caused by pump operations is the pump performance data. The performance of a centrifugal pump is characterized by four basic quantities: the rotational speed, the volumetric flow rate, the dynamic head, and the hydraulic torque. The curves showing the relationships between these four variables are called the pump characteristic curves. The characteristic curves are empirically developed by the pump manufacturer and uniquely describe head and torque as functions of volumetric flow rate and rotation speed. Because of comprising a large amount of points, this configuration is not suitable for computational purposes. However, it can be converted to a simpler form by the development of the homologous curves, in which dynamic head and hydraulic torque ratios are expressed as functions of volumetric flow and rotation speed ratios. The numerical use of the complete set of homologous curves requires specification of sixteen partial curves, being eight for the dynamic head and eight for the hydraulic torque. As a consequence, the handling of homologous curves is still somewhat complicated. In solving flow transient problems that require the pump characteristic data for all the operation zones, the parametric form appears as the simplest way to deal with the homologous curves. In this approach, the complete characteristics of a pump can be described by only two closed curves, one for the dynamic head and other for the hydraulic torque, both in function of a single angular coordinate defined adequately in terms of the quotient between volumetric flow ratio and rotation speed ratio. The usefulness and advantages of this alternative method are demonstrated through a practical example in which the homologous curves for a pump of the type used in the main coolant loops of a pressurized water reactor (PWR) are transformed to the parametric form. (author)

  17. Polar representation of centrifugal pump homologous curves

    International Nuclear Information System (INIS)

    Veloso, Marcelo Antonio; Mattos, Joao Roberto Loureiro de

    2008-01-01

    Essential for any mathematical model designed to simulate flow transient events caused by pump operations is the pump performance data. The performance of a centrifugal pump is characterized by four basic parameters: the rotational speed, the volumetric flow rate, the dynamic head, and the hydraulic torque. Any one of these quantities can be expressed as a function of any two others. The curves showing the relationships between these four variables are called the pump characteristic curves, also referred to as four-quadrant curves. The characteristic curves are empirically developed by the pump manufacturer and uniquely describe head and torque as functions of volumetric flow rate and rotation speed. Because of comprising a large amount of points, the four-quadrant configuration is not suitable for computational purposes. However, it can be converted to a simpler form by the development of the homologous curves, in which dynamic head and hydraulic torque ratios are expressed as functions of volumetric flow and rotation speed ratios. The numerical use of the complete set of homologous curves requires specification of sixteen partial curves, being eight for the dynamic head and eight for the hydraulic torque. As a consequence, the handling of homologous curves is still somewhat complicated. In solving flow transient problems that require the pump characteristic data for all the operation zones, the polar form appears as the simplest way to represent the homologous curves. In the polar method, the complete characteristics of a pump can be described by only two closed curves, one for the dynamic head and other for the hydraulic torque, both in function of a single angular coordinate defined adequately in terms of the quotient between volumetric flow ratio and rotation speed ratio. The usefulness and advantages of this alternative method are demonstrated through a practical example in which the homologous curves for a pump of the type used in the main coolant loops of a

  18. Parametric representation of centrifugal pump homologous curves

    Energy Technology Data Exchange (ETDEWEB)

    Veloso, Marcelo A.; Mattos, Joao R.L. de, E-mail: velosom@cdtn.br, E-mail: jrmattos@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2015-07-01

    Essential for any mathematical model designed to simulate flow transient events caused by pump operations is the pump performance data. The performance of a centrifugal pump is characterized by four basic quantities: the rotational speed, the volumetric flow rate, the dynamic head, and the hydraulic torque. The curves showing the relationships between these four variables are called the pump characteristic curves. The characteristic curves are empirically developed by the pump manufacturer and uniquely describe head and torque as functions of volumetric flow rate and rotation speed. Because of comprising a large amount of points, this configuration is not suitable for computational purposes. However, it can be converted to a simpler form by the development of the homologous curves, in which dynamic head and hydraulic torque ratios are expressed as functions of volumetric flow and rotation speed ratios. The numerical use of the complete set of homologous curves requires specification of sixteen partial curves, being eight for the dynamic head and eight for the hydraulic torque. As a consequence, the handling of homologous curves is still somewhat complicated. In solving flow transient problems that require the pump characteristic data for all the operation zones, the parametric form appears as the simplest way to deal with the homologous curves. In this approach, the complete characteristics of a pump can be described by only two closed curves, one for the dynamic head and other for the hydraulic torque, both in function of a single angular coordinate defined adequately in terms of the quotient between volumetric flow ratio and rotation speed ratio. The usefulness and advantages of this alternative method are demonstrated through a practical example in which the homologous curves for a pump of the type used in the main coolant loops of a pressurized water reactor (PWR) are transformed to the parametric form. (author)

  19. Passive Facebook use, Facebook addiction, and associations with escapism: an experimental vignette study

    OpenAIRE

    Young, LN; Kuss, DJ; Griffiths, MD; Howard, CJ

    2017-01-01

    There is relatively little research considering motivations of passive Facebook use. However, research regarding motivations of general Facebook use indicates that people use Facebook to escape – and that escapism may motivate passive Facebook use. Research also suggests that using Facebook to escape is associated with Facebook addiction. Using an experimental vignette design, the present research investigated whether passive Facebook use is motivated by escapism and whether this escape motiv...

  20. Behavior of Ants Escaping from a Single-Exit Room.

    Directory of Open Access Journals (Sweden)

    Shujie Wang

    Full Text Available To study the rules of ant behavior and group-formation phenomena, we examined the behaviors of Camponotus japonicus, a species of large ant, in a range of situations. For these experiments, ants were placed inside a rectangular chamber with a single exit that also contained a filter paper soaked in citronella oil, a powerful repellent. The ants formed several groups as they moved toward the exit to escape. We measured the time intervals between individual escapes in six versions of the experiment, each containing an exit of a different width, to quantify the movement of the groups. As the ants exited the chamber, the time intervals between individual escapes changed and the frequency distribution of the time intervals exhibited exponential decay. We also investigated the relationship between the number of ants in a group and the group flow rate.

  1. Escaping and Falling into Poverty in India Today.

    Science.gov (United States)

    Thorat, Amit; Vanneman, Reeve; Desai, Sonalde; Dubey, Amaresh

    2017-05-01

    The study examines the dynamic nature of movements into and out of poverty over a period when poverty has fallen substantially in India. The analysis identifies people who escaped poverty and those who fell into it over the period 2005 to 2012. The analysis identifies people who escaped poverty and those who fell into it over the period 2005 to 2012. Using panel data from the India Human Development Survey for 2005 and 2012, we find that the risks of marginalized communities such as Dalits and Adivasis of falling into or remaining in poverty were higher than those for more privileged groups. Some, but not all of these higher risks are explained by educational, financial, and social disadvantages of these groups in 2005. Results from a logistic regression show that some factors that help people escape poverty differ from those that push people into it and that the strength of their effects varies.

  2. Escape panels in trawls – a consistent management tool?

    DEFF Research Database (Denmark)

    Krag, Ludvig Ahm; Herrmann, Bent; Feekings, Jordan P.

    2016-01-01

    gears are often developed in collaboration between scientists and fishers. Part of the development is a controlled scientific test documenting the selectivity effect. In this study, we compared two versions of a mandatory escape panel that were introduced into the mixed species fishery in the Skagerrak...... vertical distance between the upper panel (escape panel) and the bottom panel compared to the pre-version. Both designs are legal and considered identical. The results of this study showed significantly higher catches (lower selectivity) for the post-version for all five species examined; cod (Gadus morhua......), saithe (Pollachius virens), haddock (Melanogrammus aeglefinus), plaice (Pleuronectes platessa) and Norway lobster (Nephrops norvegicus). Thus the modification by fishers of certain gear properties not specified in the legislation can significantly influence the efficiency of an escape panel. We discuss...

  3. Feature Integration Drives Probabilistic Behavior in the Drosophila Escape Response.

    Science.gov (United States)

    von Reyn, Catherine R; Nern, Aljoscha; Williamson, W Ryan; Breads, Patrick; Wu, Ming; Namiki, Shigehiro; Card, Gwyneth M

    2017-06-21

    Animals rely on dedicated sensory circuits to extract and encode environmental features. How individual neurons integrate and translate these features into behavioral responses remains a major question. Here, we identify a visual projection neuron type that conveys predator approach information to the Drosophila giant fiber (GF) escape circuit. Genetic removal of this input during looming stimuli reveals that it encodes angular expansion velocity, whereas other input cell type(s) encode angular size. Motor program selection and timing emerge from linear integration of these two features within the GF. Linear integration improves size detection invariance over prior models and appropriately biases motor selection to rapid, GF-mediated escapes during fast looms. Our findings suggest feature integration, and motor control may occur as simultaneous operations within the same neuron and establish the Drosophila escape circuit as a model system in which these computations may be further dissected at the circuit level. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Eyes shut homolog is required for maintaining the ciliary pocket and survival of photoreceptors in zebrafish

    Directory of Open Access Journals (Sweden)

    Miao Yu

    2016-11-01

    Full Text Available Mutations in the extracellular matrix protein eyes shut homolog (EYS cause photoreceptor degeneration in patients with retinitis pigmentosa 25 (RP25. Functions of EYS remain poorly understood, due in part to the lack of an EYS gene in mouse. We investigated the localization of vertebrate EYS proteins and engineered loss-of-function alleles in zebrafish. Immunostaining indicated that EYS localized near the connecting cilium/transition zone in photoreceptors. EYS also strongly localized to the cone outer segments and weakly to the rod outer segments and cone terminals in primate retinas. Analysis of mutant EYS zebrafish revealed disruption of the ciliary pocket in cone photoreceptors, indicating that EYS is required for maintaining the integrity of the ciliary pocket lumen. Mutant zebrafish exhibited progressive loss of cone and rod photoreceptors. Our results indicate that EYS protein localization is species-dependent and that EYS is required for maintaining ciliary pocket morphology and survival of photoreceptors in zebrafish.

  5. Characterization of Brucella abortus mutant strain Δ22915, a potential vaccine candidate.

    Science.gov (United States)

    Bao, Yanqing; Tian, Mingxing; Li, Peng; Liu, Jiameng; Ding, Chan; Yu, Shengqing

    2017-04-04

    Brucellosis, caused by Brucella spp., is an important zoonosis worldwide. Vaccination is an effective strategy for protection against Brucella infection in livestock in developing countries and in wildlife in developed countries. However, current vaccine strains including S19 and RB51 are pathogenic to humans and pregnant animals, limiting their use. In this study, we constructed the Brucella abortus (B. abortus) S2308 mutant strain Δ22915, in which the putative lytic transglycosylase gene BAB_RS22915 was deleted. The biological properties of mutant strain Δ22915 were characterized and protection of mice against virulent S2308 challenge was evaluated. The mutant strain Δ22915 showed reduced survival within RAW264.7 cells and survival in vivo in mice. In addition, the mutant strain Δ22915 failed to escape fusion with lysosomes within host cells, and caused no observable pathological damage. RNA-seq analysis indicated that four genes associated with amino acid/nucleotide transport and metabolism were significantly upregulated in mutant strain Δ22915. Furthermore, inoculation of ∆22915 at 10 5 colony forming units induced effective host immune responses and long-term protection of BALB/c mice. Therefore, mutant strain ∆22915 could be used as a novel vaccine candidate in the future to protect animals against B. abortus infection.

  6. Genetic dissection of leukemia-associated IDH1 and IDH2 mutants and D-2-hydroxyglutarate in Drosophila

    Science.gov (United States)

    Reitman, Zachary J.; Sinenko, Sergey A.; Spana, Eric P.

    2015-01-01

    Gain-of-function mutations in nicotinamide adenine dinucleotide phosphate–dependent isocitrate dehydrogenase (IDH)1 and IDH2 frequently arise in human leukemias and other cancers and produce high levels of D-2-hydroxyglutarate (D-2HG). We expressed the R195H mutant of Drosophila Idh (CG7176), which is equivalent to the human cancer-associated IDH1-R132H mutant, in fly tissues using the UAS-Gal4 binary expression system. Idh-R195H caused a >25-fold elevation of D-2HG when expressed ubiquitously in flies. Expression of mutant Idh in larval blood cells (hemocytes) resulted in higher numbers of circulating blood cells. Mutant Idh expression in fly neurons resulted in neurologic and wing-expansion defects, and these phenotypes were rescued by genetic modulation of superoxide dismutase 2, p53, and apoptotic caspase cascade mediators. Idh-R163Q, which is homologous to the common leukemia-associated IDH2-R140Q mutant, resulted in moderately elevated D-2HG and milder phenotypes. We identified the fly homolog of D-2-hydroxyglutaric acid dehydrogenase (CG3835), which metabolizes D-2HG, and showed that coexpression of this enzyme with mutant Idh abolishes mutant Idh-associated phenotypes. These results provide a flexible model system to interrogate a cancer-related genetic and metabolic pathway and offer insights into the impact of IDH mutation and D-2HG on metazoan tissues. PMID:25398939

  7. SHY1, the yeast homolog of the mammalian SURF-1 gene, encodes a mitochondrial protein required for respiration.

    Science.gov (United States)

    Mashkevich, G; Repetto, B; Glerum, D M; Jin, C; Tzagoloff, A

    1997-05-30

    C173 and W125 are pet mutants of Saccharomyces cerevisiae, partially deficient in cytochrome oxidase but with elevated concentrations of cytochrome c. Assays of electron transport chain enzymes indicate that the mutations exert different effects on the terminal respiratory pathway, including an inefficient transfer of electrons between the bc1 and the cytochrome oxidase complexes. A cloned gene capable of restoring respiration in C173/U1 and W125 is identical to reading frame YGR112w of yeast chromosome VII (GenBank Z72897Z72897). The encoded protein is homologous to the product of the mammalian SURF-1 gene. In view of the homology, the yeast gene has been designated SHY1 (Surf Homolog of Yeast). An antibody against the carboxyl-terminal half of Shy1p has been used to localize the protein in the inner mitochondrial membrane. Deletion of part of SHY1 produces a phenotype similar to that of G91 mutants. Disruption of SHY1 at a BamHI site, located approximately 2/3 of the way into the gene, has no obvious phenotypic consequence. This evidence, together with the ability of a carboxyl-terminal coding sequence starting from the BamHI site to complement a shy1 mutant, suggests that the Shy1p contains two domains that can be separately expressed to form a functional protein.

  8. SOYUZ escape trajectory analysis from Space Station Freedom

    Science.gov (United States)

    Heck, Michael L.

    1993-01-01

    It has been proposed to utilize the Russian built SOYUZ as an assured crew return vehicle (ACRV) for Space Station Freedom. Three departure directions (nadir, zenith, minus velocity) are evaluated to determine escape path clearances. In addition, the effects of the following parameters were also evaluated: delta-V magnitude, configuration dependent ballistic coefficients, atmospheric density, Freedom attitude control, and canted docking adaptors. The primary factor influencing the escape trajectory was station contingency attitude rate. The nadir and zenith departures were preferable to minus velocity. The impact of atmospheric density and relative ballistic coefficients was minimal.

  9. Case of escape in cassava, Manihot esculenta Crantz.

    Science.gov (United States)

    Nassar, N M A; Mendonza, M

    2017-02-08

    Two cassava escapes where collected from cultivated fields near natural habitat in Bolivia. They are described morphologically and analyzed cytogenetically in this study. It is suggested that they are the product of backcrosses of cassava interspecific hybrids with the cultigen itself, and that selective conditions have developed in which certain forms of cassava segregates have adapted to grow wildly in natural habitats near cassava fields. These segregates may hybridize with cultivated cassava upon coming in contact with such varieties. Because these escapes have incorporated useful genes from the wild into their genetic structure, they could be used for cassava improvement since their genetic barriers with other forms of cassava are very weak.

  10. Rapid endosomal escape of prickly nanodiamonds: implications for gene delivery

    Science.gov (United States)

    Chu, Zhiqin; Miu, Kaikei; Lung, Pingsai; Zhang, Silu; Zhao, Saisai; Chang, Huan-Cheng; Lin, Ge; Li, Quan

    2015-06-01

    The prickly nanodiamonds easily entered cells via endocytosis followed by unique intracellular translocation characteristics—quick endosomal escape followed by stable residence in cytoplasm. Endosomal membrane rupturing is identified as the major route of nanodiamonds’ escaping the vesicle confinement and to the cytoplasm. Little cytotoxicity is observed to associate with the nanodiamonds’ cytosolic release. Such features enable its application for gene delivery, which requires both effective cellular uptake and cytosolic release of the gene. Taking green fluorescent protein gene as an example, we demonstrate the successful cytosolic delivery and expression of such a gene using the prickly nanodiamonds as carrier.

  11. Rapid endosomal escape of prickly nanodiamonds: implications for gene delivery.

    Science.gov (United States)

    Chu, Zhiqin; Miu, Kaikei; Lung, Pingsai; Zhang, Silu; Zhao, Saisai; Chang, Huan-Cheng; Lin, Ge; Li, Quan

    2015-06-30

    The prickly nanodiamonds easily entered cells via endocytosis followed by unique intracellular translocation characteristics—quick endosomal escape followed by stable residence in cytoplasm. Endosomal membrane rupturing is identified as the major route of nanodiamonds' escaping the vesicle confinement and to the cytoplasm. Little cytotoxicity is observed to associate with the nanodiamonds' cytosolic release. Such features enable its application for gene delivery, which requires both effective cellular uptake and cytosolic release of the gene. Taking green fluorescent protein gene as an example, we demonstrate the successful cytosolic delivery and expression of such a gene using the prickly nanodiamonds as carrier.

  12. The murine cytomegalovirus chemokine homolog, m131/129, is a determinant of viral pathogenicity.

    Science.gov (United States)

    Fleming, P; Davis-Poynter, N; Degli-Esposti, M; Densley, E; Papadimitriou, J; Shellam, G; Farrell, H

    1999-08-01

    Chemokines are important mediators of the early inflammatory response to infection and modify a wide range of host immune responses. Functional homologs of cellular chemokines have been identified in a number of herpesviruses, suggesting that the subversion of the host chemokine response contributes to the pathogenesis of these viruses. Transcriptional and reverse transcription-PCR analyses demonstrated that the murine cytomegalovirus (MCMV) chemokine homolog, m131, was spliced at the 3' end to the adjacent downstream open reading frame, m129, resulting in a predicted product of 31 kDa, which is significantly larger than most known chemokines. The in vivo impact of m131/129 was investigated by comparing the replication of MCMV mutants having m131/129 deleted (Deltam131/129) with that of wild-type (wt) MCMV. Our studies demonstrate that both wt and Deltam131/129 viruses replicated to equivalent levels during the first 2 to 3 days following in vivo infection. However, histological studies demonstrated that the early inflammatory response elicited by Deltam131/129 was reduced compared with that of wt MCMV. Furthermore, the Deltam131/129 mutants failed to establish a high-titer infection in the salivary glands. These results suggest that m131/129 possesses proinflammatory properties in vivo and is important for the dissemination of MCMV to or infection of the salivary gland. Notably, the Deltam131/129 mutants were cleared more rapidly from the spleen and liver during acute infection compared with wt MCMV. The accelerated clearance of the mutants was dependent on NK cells and cells of the CD4(+) CD8(+) phenotype. These data suggest that m131/129 may also contribute to virus mechanisms of immune system evasion during early infection, possibly through the interference of NK cells and T cells.

  13. Recombination Phenotypes of Escherichia coli greA Mutants

    Directory of Open Access Journals (Sweden)

    Poteete Anthony R

    2011-03-01

    Full Text Available Abstract Background The elongation factor GreA binds to RNA polymerase and modulates transcriptional pausing. Some recent research suggests that the primary role of GreA may not be to regulate gene expression, but rather, to promote the progression of replication forks which collide with RNA polymerase, and which might otherwise collapse. Replication fork collapse is known to generate dsDNA breaks, which can be recombinogenic. It follows that GreA malfunction could have consequences affecting homologous recombination. Results Escherichia coli mutants bearing substitutions of the active site acidic residues of the transcription elongation factor GreA, D41N and E44K, were isolated as suppressors of growth inhibition by a toxic variant of the bacteriophage lambda Red-beta recombination protein. These mutants, as well as a D41A greA mutant and a greA deletion, were tested for proficiency in recombination events. The mutations were found to increase the efficiency of RecA-RecBCD-mediated and RecA-Red-mediated recombination, which are replication-independent, and to decrease the efficiency of replication-dependent Red-mediated recombination. Conclusion These observations provide new evidence for a role of GreA in resolving conflicts between replication and transcription.

  14. LEUNIG_HOMOLOG and LEUNIG regulate seed mucilage extrusion in Arabidopsis.

    Science.gov (United States)

    Bui, Minh; Lim, Nathan; Sijacic, Paja; Liu, Zhongchi

    2011-05-01

    LEUNIG (LUG) and LEUNIG_HOMOLOG (LUH) encode two closely related Arabidopsis proteins, belonging to the Gro/TLE family of transcriptional co-repressors. These two genes were previously shown to exhibit partially overlapping functions in embryo and flower development. In this report, the role of both LUH and LUG on seed mucilage extrusion was examined. Seed mucilage extrusion occurs after the seeds are imbibed, serving as functional aid in seed hydration, germination, and dispersal. While luh-1 mutants exhibited strong defects in seed mucilage extrusion, lug-3 mutants exhibited a minor phenotype in mucilage extrusion. Further characterization indicates that luh-1 does not exhibit any obvious defect in seed epidermal cell differentiation, mucilage synthesis, or mucilage deposition, suggesting a specific role of LUH in mucilage extrusion. This seed mucilage phenotype of luh-1 is identical to that of mucilage modified 2 (mum2) mutants. MUM2 encodes a β-galactosidase required for the modification of the mucilage. Quantitative reverse transcription polymerase chain reaction of RNA extracted from siliques detected a slight decrease of MUM2 mRNA in the luh-1 mutant compared to the wild type. Together, LUH and possibly LUG may specifically regulate mucilage extrusion by promoting the expression of genes required for mucilage maturation. © 2011 Institute of Botany, Chinese Academy of Sciences.

  15. Autologous HIV-1 neutralizing antibodies: emergence of neutralization-resistant escape virus and subsequent development of escape virus neutralizing antibodies

    DEFF Research Database (Denmark)

    Arendrup, M; Nielsen, C; Hansen, J E

    1992-01-01

    The capacity of consecutive human sera to neutralize sequentially obtained autologous virus isolates was studied. HIV-1 was isolated three times over a 48-164-week period from three individuals immediately after seroconversion and from two individuals in later stages of infection. Development of ...... escape virus may be part of the explanation of the apparent failure of the immune system to control HIV infection.......The capacity of consecutive human sera to neutralize sequentially obtained autologous virus isolates was studied. HIV-1 was isolated three times over a 48-164-week period from three individuals immediately after seroconversion and from two individuals in later stages of infection. Development...... of neutralizing antibodies to the primary virus isolates was detected 13-45 weeks after seroconversion. Emergence of escape virus with reduced sensitivity to neutralization by autologous sera was demonstrated. The patients subsequently developed neutralizing antibodies against the escape virus but after a delay...

  16. HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag.

    Directory of Open Access Journals (Sweden)

    Esther F Gijsbers

    Full Text Available Expression of HLA-B*57 and the closely related HLA-B*58:01 are associated with prolonged survival after HIV-1 infection. However, large differences in disease course are observed among HLA-B*57/58:01 patients. Escape mutations in CTL epitopes restricted by these HLA alleles come at a fitness cost and particularly the T242N mutation in the TW10 CTL epitope in Gag has been demonstrated to decrease the viral replication capacity. Additional mutations within or flanking this CTL epitope can partially restore replication fitness of CTL escape variants. Five HLA-B*57/58:01 progressors and 5 HLA-B*57/58:01 long-term nonprogressors (LTNPs were followed longitudinally and we studied which compensatory mutations were involved in the restoration of the viral fitness of variants that escaped from HLA-B*57/58:01-restricted CTL pressure. The Sequence Harmony algorithm was used to detect homology in amino acid composition by comparing longitudinal Gag sequences obtained from HIV-1 patients positive and negative for HLA-B*57/58:01 and from HLA-B*57/58:01 progressors and LTNPs. Although virus isolates from HLA-B*57/58:01 individuals contained multiple CTL escape mutations, these escape mutations were not associated with disease progression. In sequences from HLA-B*57/58:01 progressors, 5 additional mutations in Gag were observed: S126N, L215T, H219Q, M228I and N252H. The combination of these mutations restored the replication fitness of CTL escape HIV-1 variants. Furthermore, we observed a positive correlation between the number of escape and compensatory mutations in Gag and the replication fitness of biological HIV-1 variants isolated from HLA-B*57/58:01 patients, suggesting that the replication fitness of HLA-B*57/58:01 escape variants is restored by accumulation of compensatory mutations.

  17. Targeting ESR1-Mutant Breast Cancer

    Science.gov (United States)

    2015-09-01

    we have developed models of mutant ER driven cancer in which to characterize gene expression. Specifically, tetracycline inducible MCF7 cells that...expression profiling. Figure 1: Degradation of WT and mutant ER with ARN810. MCF7 cells stably transfected with tet-inducible WT and mutant...mutant ER. MCF7 cells stably transfected with tet- inducible WT and mutant ER are treated for 24 hours with estradiol and gene expression profiling

  18. Homological mirror symmetry and tropical geometry

    CERN Document Server

    Catanese, Fabrizio; Kontsevich, Maxim; Pantev, Tony; Soibelman, Yan; Zharkov, Ilia

    2014-01-01

    The relationship between Tropical Geometry and Mirror Symmetry goes back to the work of Kontsevich and Y. Soibelman (2000), who applied methods of non-archimedean geometry (in particular, tropical curves) to Homological Mirror Symmetry. In combination with the subsequent work of Mikhalkin on the “tropical” approach to Gromov-Witten theory, and the work of Gross and Siebert, Tropical Geometry has now become a powerful tool. Homological Mirror Symmetry is the area of mathematics concentrated around several categorical equivalences connecting symplectic and holomorphic (or algebraic) geometry. The central ideas first appeared in the work of Maxim Kontsevich (1993). Roughly speaking, the subject can be approached in two ways: either one uses Lagrangian torus fibrations of Calabi-Yau manifolds (the so-called Strominger-Yau-Zaslow picture, further developed by Kontsevich and Soibelman) or one uses Lefschetz fibrations of symplectic manifolds (suggested by Kontsevich and further developed by Seidel). Tropical Ge...

  19. Homology and phylogeny and their automated inference.

    Science.gov (United States)

    Fuellen, Georg

    2008-06-01

    The analysis of the ever-increasing amount of biological and biomedical data can be pushed forward by comparing the data within and among species. For example, an integrative analysis of data from the genome sequencing projects for various species traces the evolution of the genomes and identifies conserved and innovative parts. Here, I review the foundations and advantages of this "historical" approach and evaluate recent attempts at automating such analyses. Biological data is comparable if a common origin exists (homology), as is the case for members of a gene family originating via duplication of an ancestral gene. If the family has relatives in other species, we can assume that the ancestral gene was present in the ancestral species from which all the other species evolved. In particular, describing the relationships among the duplicated biological sequences found in the various species is often possible by a phylogeny, which is more informative than homology statements. Detecting and elaborating on common origins may answer how certain biological sequences developed, and predict what sequences are in a particular species and what their function is. Such knowledge transfer from sequences in one species to the homologous sequences of the other is based on the principle of 'my closest relative looks and behaves like I do', often referred to as 'guilt by association'. To enable knowledge transfer on a large scale, several automated 'phylogenomics pipelines' have been developed in recent years, and seven of these will be described and compared. Overall, the examples in this review demonstrate that homology and phylogeny analyses, done on a large (and automated) scale, can give insights into function in biology and biomedicine.

  20. Mismatch Repair during Homologous and Homeologous Recombination

    Science.gov (United States)

    Spies, Maria; Fishel, Richard

    2015-01-01

    Homologous recombination (HR) and mismatch repair (MMR) are inextricably linked. HR pairs homologous chromosomes before meiosis I and is ultimately responsible for generating genetic diversity during sexual reproduction. HR is initiated in meiosis by numerous programmed DNA double-strand breaks (DSBs; several hundred in mammals). A characteristic feature of HR is the exchange of DNA strands, which results in the formation of heteroduplex DNA. Mismatched nucleotides arise in heteroduplex DNA because the participating parental chromosomes contain nonidentical sequences. These mismatched nucleotides may be processed by MMR, resulting in nonreciprocal exchange of genetic information (gene conversion). MMR and HR also play prominent roles in mitotic cells during genome duplication; MMR rectifies polymerase misincorporation errors, whereas HR contributes to replication fork maintenance, as well as the repair of spontaneous DSBs and genotoxic lesions that affect both DNA strands. MMR suppresses HR when the heteroduplex DNA contains excessive mismatched nucleotides, termed homeologous recombination. The regulation of homeologous recombination by MMR ensures the accuracy of DSB repair and significantly contributes to species barriers during sexual reproduction. This review discusses the history, genetics, biochemistry, biophysics, and the current state of studies on the role of MMR in homologous and homeologous recombination from bacteria to humans. PMID:25731766

  1. Language evolution: neural homologies and neuroinformatics.

    Science.gov (United States)

    Arbib, Michael; Bota, Mihail

    2003-11-01

    This paper contributes to neurolinguistics by grounding an evolutionary account of the readiness of the human brain for language in the search for homologies between different cortical areas in macaque and human. We consider two hypotheses for this grounding, that of Aboitiz and Garci;a [Brain Res. Rev. 25 (1997) 381] and the Mirror System Hypothesis of Rizzolatti and Arbib [Trends Neurosci. 21 (1998) 188] and note the promise of computational modeling of neural circuitry of the macaque and its linkage to analysis of human brain imaging data. In addition to the functional differences between the two hypotheses, problems arise because they are grounded in different cortical maps of the macaque brain. In order to address these divergences, we have developed several neuroinformatics tools included in an on-line knowledge management system, the NeuroHomology Database, which is equipped with inference engines both to relate and translate information across equivalent cortical maps and to evaluate degrees of homology for brain regions of interest in different species.

  2. Homology among divergent Paleozoic tetrapod clades.

    Science.gov (United States)

    Carroll, R L

    1999-01-01

    A stringent definition of homology is necessary to establish phylogenetic relationships among Paleozoic amphibians. Many derived characters exhibited by divergent clades of Carboniferous lepospondyls resemble those achieved convergently among Cenozoic squamates that have elongate bodies and reduced limbs, and by lineages of modern amphibians that have undergone miniaturization. Incongruent character distribution, poorly resolved cladograms and functionally improbable character transformations determined by phylogenetic analysis suggest that convergence was also common among Paleozoic amphibians with a skull length under 3 cm, including lepospondyls, early amniotes and the putative ancestors of modern amphibians. For this reason, it is injudicious to equate apparent synapomorphy (perceived common presence of a particular derived character in two putative sister-taxa) with strict homology of phylogenetic origin. Identification of homology by the similarity of structure, anatomical position and pattern of development is insufficient to establish the synapomorphy of bone and limb loss or precocial ossification of vertebral centra, which are common among small Paleozoic amphibians. The only way in which synapomorphies can be established definitively is through the discovery and recognition of the trait in question in basal members of each of the clades under study, and in their immediate common ancestors.

  3. Applying antibody-sensitive hypervariable region 1-deleted hepatitis C virus to the study of escape pathways of neutralizing human monoclonal antibody AR5A

    DEFF Research Database (Denmark)

    Velazquez-Moctezuma, Rodrigo; Law, Mansun; Bukh, Jens

    2017-01-01

    isolates with high antibody resistance, or antibodies with moderate potency, it remains challenging to induce escape mutations in vitro. Here, as proof-of-concept, we used antibody-sensitive HVR1-deleted (ΔHVR1) viruses to generate escape mutants for a human monoclonal antibody, AR5A, targeting a rare...... effect but sensitized the virus to AR5A. Of note, H77/JFH1L665S was non-viable. The resistance mutations did not affect cell-to-cell spread or E1/E2 interactions. Finally, introducing L665W, identified in genotype 1, into genotypes 2–6 parental and HVR1-deleted variants (not available for genotype 4a) we...... observed diverse effects on viral fitness and a universally pronounced reduction in AR5A sensitivity. Thus, we were able to take advantage of the neutralization-sensitive HVR1-deleted viruses to rapidly generate escape viruses aiding our understanding of the divergent escape pathways used by HCV to evade...

  4. Predator escape tactics in birds : linking ecology and aerodynamics

    NARCIS (Netherlands)

    van den Hout, Piet J.; Mathot, Kimberley J.; Maas, Leo R. M.; Piersma, Theunis

    2010-01-01

    In most birds, flight is the most important means of escape from predators. Impaired flight abilities due to increased wing loading may increase vulnerability to predation. To compensate for an increase in wing loading, birds are able to independently decrease body mass (BM) or increase pectoral

  5. Escape angles in bulk chi((2)) soliton interactions

    DEFF Research Database (Denmark)

    Johansen, Steffen Kjær; Bang, Ole; Sørensen, Mads Peter

    2002-01-01

    We develop a theory for nonplanar interaction between two identical type I spatial solitons propagating at opposite, but arbitrary transverse angles in quadratic nonlinear (or so-called chi((2))) bulk, media. We predict quantitatively the outwards escape angle, below which the solitons turn around...

  6. Molecular strategies to design an escape-proof antiviral therapy

    NARCIS (Netherlands)

    Berkhout, Ben; Sanders, Rogier W.

    2011-01-01

    Two antiviral approaches against the human immunodeficiency virus type 1 (HIV-1) were presented at the Antivirals Congress in Amsterdam. The common theme among these two separate therapeutic research lines is the wish to develop a durable therapy that prevents viral escape. We will present a brief

  7. Determination of forage escape protein value with in situ and ...

    African Journals Online (AJOL)

    This study was carried out to compare in situ and in vitro enzyme techniques for determining estimates of forage escape proteins. Eight forages (vetch hay, wheat silage, corn silage, wheat hay, grass hay, lentil straw, triticale hay and alfalfa hay) were used as feed materials. During 70 h, incubation with enzyme method had ...

  8. Escaping Embarrassment: Face-Work in the Rap Cipher

    Science.gov (United States)

    Lee, Jooyoung

    2009-01-01

    How do individuals escape embarrassing moments in interaction? Drawing from ethnographic fieldwork, in-depth interviews, and video recordings of weekly street corner ciphers (impromptu rap sessions), this paper expands Goffman's theory of defensive and protective face-work. The findings reveal formulaic and indirect dimensions of face-work. First,…

  9. 46 CFR 169.313 - Means of escape.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Means of escape. 169.313 Section 169.313 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Construction... apart, uniform for the length of the ladder; (3) At least 3 inches from the nearest permanent object in...

  10. A Structural Soundness Proof for Shivers's Escape Technique

    DEFF Research Database (Denmark)

    Midtgaard, Jan; Adams, Michael D.; Matthew, Might

    2012-01-01

    Shivers’s escape technique enables one to analyse the control flow of higher-order program fragments. It is widely used, but its soundness has never been proven. In this paper, we present the first soundness proof for the technique. Our proof is structured as a composition of Galois connections...

  11. 46 CFR 108.445 - Alarm and means of escape.

    Science.gov (United States)

    2010-10-01

    ... AND EQUIPMENT Fire Extinguishing Systems Fixed Carbon Dioxide Fire Extinguishing Systems § 108.445 Alarm and means of escape. (a) Each CO2 system that has a supply of more than 136 kilograms (300 pounds) of CO2, except a system that protects a tank, must have an alarm that sounds for at least 20 seconds...

  12. The great escape - AIDS viruses and immune control.

    Science.gov (United States)

    Goulder, P J; Walker, B D

    1999-11-01

    Many studies have been designed to address the role of CTL immune escape in HIV-1 infection, but have not given conclusive answers. Now, an elegant longitudinal analysis clearly demonstrates that progression to disease in SIV-infected macaques is associated with evasion of the CTL response (pages 1270-1276).

  13. Mutants dissecting development and behaviour in drosophila

    International Nuclear Information System (INIS)

    Joshi, Adita; Chandrashekaran, Shanti; Sharma, R.P.

    2005-01-01

    We have traced in this paper the progress in Drosophila genetics research from the 1960s, at the IARI, spearheaded by the visionary insight of M. S. Swaminathan. The work started with the study of indirect effect of radiation and the synergistic interaction of physical and chemical mutagens on chromosomal and genetic changes. This paved the way for the study of single gene mutants in dissecting developmental and behavioural processes. New genes discovered by us have been shown to encode conserved cell signalling molecules controlling developmental and behavioural pathways. With the complete sequencing of the Drosophila genome, in the year 2000, mounting evidence for the homology between Drosophila and human genes controlling genetic disorders became available. This has led to the fly becoming an indispensable tool for studying human diseases as well as a model to test for drugs and pharmaceuticals against human diseases and complex behavioural processes. For example wingless in Drosophila belongs to the conserved Wnt gene family and aberrant WNT signalling is linked to a range of human diseases, most notably cancer. Inhibition as well as activation of WNT signalling form the basis of an effective therapy for some cancers as well as several other clinical conditions. Recent experiments have shown that WNTs might also normally participate in self-renewal, proliferation or differentiation of stem cells and altering WNT signalling might be beneficial to the use of stem cells for therapeutic means. Likewise, the stambhA mutant of Drosophila which was discovered for its temperature-dependent paralytic behaviour is the fly homologue of Phospholipase Cβ. Phospholipase C mediated G protein signalling plays a central role in vital processes controlling epilepsy, vision, taste, and olfaction in animals. Proteins of the G-signalling pathway are of intense research interest since many human diseases involve defects in G-protein signalling pathways. In fact, approximately 50

  14. Several aspects of some techniques avoiding homologous blood transfusions

    NARCIS (Netherlands)

    E.C.S.M. van Woerkens (Liesbeth)

    1998-01-01

    textabstractThe use of homologous blood products during anesthesia and surgery is not without risks. Complications due to homologous blood transfusions include transfusion reactions, isosensitization, transmission of infections (including HIV, hepatitis, CMV) and immunosuppression (resuiting in

  15. Danger detection and escape behaviour in wood crickets.

    Science.gov (United States)

    Dupuy, Fabienne; Casas, Jérôme; Body, Mélanie; Lazzari, Claudio R

    2011-07-01

    The wind-sensitive cercal system of Orthopteroid insects that mediates the detection of the approach of a predator is a very sensitive sensory system. It has been intensively analysed from a behavioural and neurobiological point of view, and constitutes a classical model system in neuroethology. The escape behaviour is triggered in orthopteroids by the detection of air-currents produced by approaching objects, allowing these insects to keep away from potential dangers. Nevertheless, escape behaviour has not been studied in terms of success. Moreover, an attacking predator is more than "air movement", it is also a visible moving entity. The sensory basis of predator detection is thus probably more complex than the perception of air movement by the cerci. We have used a piston mimicking an attacking running predator for a quantitative evaluation of the escape behaviour of wood crickets Nemobius sylvestris. The movement of the piston not only generates air movement, but it can be seen by the insect and can touch it as a natural predator. This procedure allowed us to study the escape behaviour in terms of detection and also in terms of success. Our results showed that 5-52% of crickets that detected the piston thrust were indeed touched. Crickets escaped to stimulation from behind better than to a stimulation from the front, even though they detected the approaching object similarly in both cases. After cerci ablation, 48% crickets were still able to detect a piston approaching from behind (compared with 79% of detection in intact insects) and 24% crickets escaped successfully (compared with 62% in the case of intact insects). So, cerci play a major role in the detection of an approaching object but other mechanoreceptors or sensory modalities are implicated in this detection. It is not possible to assure that other sensory modalities participate (in the case of intact animals) in the behaviour; rather, than in the absence of cerci other sensory modalities can

  16. Novel rabies virus-neutralizing epitope recognized by human monoclonal antibody: Fine mapping and escape mutant analysis

    NARCIS (Netherlands)

    Marissen, W.E.; Kramer, R.A.; Rice, A.; Weldon, W.C.; Niezgoda, M.; Faber, M.; Slootstra, J.W.; Meloen, R.H.; Clijsters-van der Horst, M.; Visser, T.J.; Jongeneelen, M.; Thijsse, S.; Throsby, M.; Kruif, de J.; Rupprecht, C.E.; Dietzschold, B.; Goudsmit, J.; Bakker, A.B.H.

    2005-01-01

    Anti-rabies virus immunoglobulin combined with rabies vaccine protects humans from lethal rabies infections. For cost and safety reasons, replacement of the human or equine polyclonal immunoglobulin is advocated, and the use of rabies virus-specific monoclonal antibodies (MAbs) is recommended. We

  17. Novel rabies virus-neutralizing epitope recognized by human monoclonal antibody: fine mapping and escape mutant analysis

    NARCIS (Netherlands)

    Marissen, Wilfred E.; Kramer, R. Arjen; Rice, Amy; Weldon, William C.; Niezgoda, Michael; Faber, Milosz; Slootstra, Jerry W.; Meloen, Rob H.; Clijsters-van der Horst, Marieke; Visser, Therese J.; Jongeneelen, Mandy; Thijsse, Sandra; Throsby, Mark; de Kruif, John; Rupprecht, Charles E.; Dietzschold, Bernhard; Goudsmit, Jaap; Bakker, Alexander B. H.

    2005-01-01

    Anti-rabies virus immunoglobulin combined with rabies vaccine protects humans from lethal rabies infections. For cost and safety reasons, replacement of the human or equine polyclonal immunoglobulin is advocated, and the use of rabies virus-specific monoclonal antibodies (MAbs) is recommended. We

  18. Computing Homology Group Generators of Images Using Irregular Graph Pyramids

    OpenAIRE

    Peltier , Samuel; Ion , Adrian; Haxhimusa , Yll; Kropatsch , Walter; Damiand , Guillaume

    2007-01-01

    International audience; We introduce a method for computing homology groups and their generators of a 2D image, using a hierarchical structure i.e. irregular graph pyramid. Starting from an image, a hierarchy of the image is built, by two operations that preserve homology of each region. Instead of computing homology generators in the base where the number of entities (cells) is large, we first reduce the number of cells by a graph pyramid. Then homology generators are computed efficiently on...

  19. Wild Accessions and Mutant Resources

    DEFF Research Database (Denmark)

    Kawaguchi, Masayoshi; Sandal, Niels Nørgaard

    2014-01-01

    Lotus japonicus, Lotus burttii, and Lotus filicaulis are species of Lotus genus that are utilized for molecular genetic analysis such as the construction of a linkage map and QTL analysis. Among them, a number of mutants have been isolated from two wild accessions: L. japonicus Gifu B-129...

  20. components in induced sorghum mutants

    African Journals Online (AJOL)

    (1984) evaluated induced mutation and hybridisation methods for producing genetic variability in 15 quantitative characters of sorghum. Their results showed large variability in grain yield, plant maturity, plant height and panicles length. Selected mutants with favorable properties can be directly combined in varietal hybrids.

  1. The influence of Mars' magnetic topology on atmospheric escape

    Science.gov (United States)

    Curry, S.; Luhmann, J. G.; DiBraccio, G. A.; Dong, C.; Xu, S.; Mitchell, D.; Gruesbeck, J.; Espley, J. R.; Connerney, J. E. P.; McFadden, J. P.; Ma, Y. J.; Brain, D.

    2017-12-01

    At weakly magnetized planets such as Mars and Venus, the solar wind directly interacts with the upper atmosphere where ions can be picked up and swept away by the background convection electric field. These pick-up ions have a gyroradius on the planetary scale that is largely dominated by the interplanetary magnetic field (IMF). But at Mars, their trajectory is also influenced by the existence of remanent crustal magnetic fields, which are thought to create a shielding effect for escaping planetary ions when they are on the dayside. Consequently, the magnetic topology changes at Mars as magnetic reconnection occurs between the draped (IMF) and the crustal magnetic fields (closed). The resulting topology includes open field lines in the solar wind with one footprint attached to the planet. Using magnetohydrodynamic (MHD) and test particle simulations, we will explore the influence of the magnetic topology on ion escape. We will present escape rates for planetary ions for different crustal field positions during different IMF configurations, with +/-BY and +/-BZ components in the Mars Sun Orbit (MSO) coordinate system. We will also compare global maps of ion outflow and escape with open / closed magnetic field line maps and compare our results with ion fluxes and magnetic field data from the Mars Atmospheric and Volatile EvolutioN (MAVEN) mission. Our results relating the dynamic magnetic field topology at Mars and planetary ion escape are an important aspect of magnetospheric physics and planetary evolution, both of which have applications to our own solar system and the increasing number of exoplanets discovered every year.

  2. CRISPR/Cas9-Derived Mutations Both Inhibit HIV-1 Replication and Accelerate Viral Escape

    Directory of Open Access Journals (Sweden)

    Zhen Wang

    2016-04-01

    Full Text Available Cas9 cleaves specific DNA sequences with the assistance of a programmable single guide RNA (sgRNA. Repairing this broken DNA by the cell’s error-prone non-homologous end joining (NHEJ machinery leads to insertions and deletions (indels that often impair DNA function. Using HIV-1, we have now demonstrated that many of these indels are indeed lethal for the virus, but that others lead to the emergence of replication competent viruses that are resistant to Cas9/sgRNA. This unexpected contribution of Cas9 to the development of viral resistance is facilitated by some indels that are not deleterious for viral replication, but that are refractory to recognition by the same sgRNA as a result of changing the target DNA sequences. This observation illustrates two opposite outcomes of Cas9/sgRNA action, i.e., inactivation of HIV-1 and acceleration of viral escape, thereby potentially limiting the use of Cas9/sgRNA in HIV-1 therapy.

  3. Phenotypic changes in Cyprinus carpiovar var. Jian introduced by sperm-mediated transgenesis of rearranged homologous DNA fragments.

    Science.gov (United States)

    Cao, Zheming; Ding, Weidong; Ren, Hongtao

    2013-09-01

    Common carp, specifically the Jian variety (Cyprinus carpiovar var. Jian), is an important Chinese and global aquatic stock for commercial foodstuff. Homologous recombination of carp gene sequences has been widely used in population genetics to broadly screen for beneficial phenotypical variations, thus optimizing artificially engineered carp stocks with Jian variety and native stock varieties. Random rearrangement of homologous DNA fragments from parent specimens of C. carpiovar var. Jian were attained by digestion of genomic DNA with MspI followed by religation and redigestion with EcoR I to specifically rearrange homologous DNA fragments of myostatin and microsatellite genes. Based on known characteristics of myostatin gene function, growth pattern changes in resultant carp mutant varieties was expected. DNA fragments were introduced into metaphase-II oocytes, resulting in one to several dozen insertions of homologous fragments into the host genome by sperm-mediated transgenesis. Introduction of rearranged homologous DNA fragments often resulted in phenotypic changes in C. carpiovar var. Jian, including significant phenotypic changes linked to growth rate at 4 months.

  4. A Dominant Mutation in Human RAD51 Reveals Its Function in DNA Interstrand Crosslink Repair Independent of Homologous Recombination.

    Science.gov (United States)

    Wang, Anderson T; Kim, Taeho; Wagner, John E; Conti, Brooke A; Lach, Francis P; Huang, Athena L; Molina, Henrik; Sanborn, Erica M; Zierhut, Heather; Cornes, Belinda K; Abhyankar, Avinash; Sougnez, Carrie; Gabriel, Stacey B; Auerbach, Arleen D; Kowalczykowski, Stephen C; Smogorzewska, Agata

    2015-08-06

    Repair of DNA interstrand crosslinks requires action of multiple DNA repair pathways, including homologous recombination. Here, we report a de novo heterozygous T131P mutation in RAD51/FANCR, the key recombinase essential for homologous recombination, in a patient with Fanconi anemia-like phenotype. In vitro, RAD51-T131P displays DNA-independent ATPase activity, no DNA pairing capacity, and a co-dominant-negative effect on RAD51 recombinase function. However, the patient cells are homologous recombination proficient due to the low ratio of mutant to wild-type RAD51 in cells. Instead, patient cells are sensitive to crosslinking agents and display hyperphosphorylation of Replication Protein A due to increased activity of DNA2 and WRN at the DNA interstrand crosslinks. Thus, proper RAD51 function is important during DNA interstrand crosslink repair outside of homologous recombination. Our study provides a molecular basis for how RAD51 and its associated factors may operate in a homologous recombination-independent manner to maintain genomic integrity. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Regulation of the insulin-like developmental pathway of Caenorhabditis elegans by a homolog of the PTEN tumor suppressor gene.

    Science.gov (United States)

    Gil, E B; Malone Link, E; Liu, L X; Johnson, C D; Lees, J A

    1999-03-16

    The human PTEN tumor suppressor gene is mutated in a wide variety of sporadic tumors. To determine the function of PTEN in vivo we have studied a PTEN homolog in Caenorhabditis elegans. We have generated a strong loss-of-function allele of the PTEN homolog and shown that the deficient strain is unable to enter dauer diapause. An insulin-like phosphatidylinositol 3-OH kinase (PI3'K) signaling pathway regulates dauer-stage entry. Mutations in either the daf-2 insulin receptor-like (IRL) gene or the age-1 encoded PI3'K catalytic subunit homolog cause constitutive dauer formation and also affect the life span, brood size, and metabolism of nondauer animals. Strikingly, loss-of-function mutations in the age-1 PI3'K and daf-2 IRL genes are suppressed by loss-of-function mutations in the PTEN homolog. We establish that the PTEN homolog is encoded by daf-18, a previously uncloned gene that has been shown to interact genetically with the DAF-2 IRL AGE-1 PI3'K signaling pathway. This interaction provides clear genetic evidence that PTEN acts to antagonize PI3'K function in vivo. Given the conservation of the PI3'K signaling pathway between C. elegans and mammals, the analysis of daf-18 PTEN mutant nematodes should shed light on the role of human PTEN in the etiology of metabolic disease, aging, and cancer.

  6. TRPM7 is required within zebrafish sensory neurons for the activation of touch-evoked escape behaviors

    Science.gov (United States)

    Low, Sean E.; Amburgey, Kimberly; Horstick, Eric; Linsley, Jeremy; Sprague, Shawn M.; Cui, Wilson W.; Zhou, Weibin; Hirata, Hiromi; Saint-Amant, Louis; Hume, Richard I.; Kuwada, John Y.

    2011-01-01

    Mutations in the gene encoding TRPM7 (trpm7), a member of the TRP superfamily of cation channels that possesses an enzymatically active kinase at its carboxyl terminus, cause the touch-unresponsive zebrafish mutant touchdown. We identified and characterized a new allele of touchdown, as well as two previously reported alleles, and found that all three alleles harbor mutations which abolish channel activity. Through the selective restoration of TRPM7 expression in sensory neurons we found that TRPM7’s kinase activity, and selectivity for divalent cations over monovalent cations, were dispensable for touch-evoked activation of escape behaviors in zebrafish. Additional characterization revealed that sensory neurons were present and capable of responding to tactile stimuli in touchdown mutants, indicating that TRPM7 is not required for sensory neuron survival or mechanosensation. Finally, exposure to elevated concentrations of divalent cations was found to restore touch-evoked behaviors in touchdown mutants. Collectively these findings are consistent with a role for zebrafish TRPM7 within sensory neurons in the modulation of neurotransmitter release at central synapses, similar to that proposed for mammalian TRPM7 at peripheral synapses. PMID:21832193

  7. The Sac10b homolog in Methanococcus maripaludis binds DNA at specific sites.

    Science.gov (United States)

    Liu, Yuchen; Guo, Li; Guo, Rong; Wong, Richard L; Hernandez, Hilda; Hu, Jinchuan; Chu, Yindi; Amster, I Jonathan; Whitman, William B; Huang, Li

    2009-04-01

    The Sac10b protein family, also known as Alba, is widely distributed in Archaea. Sac10b homologs in thermophilic Sulfolobus species are very abundant. They bind both DNA and RNA with high affinity and without sequence specificity, and their physiological functions are still not fully understood. Mma10b from the euryarchaeote Methanococcus maripaludis is a mesophilic member of the Sac10b family. Mma10b is not abundant and constitutes only approximately 0.01% of the total cellular protein. Disruption of mma10b resulted in poor growth of the mutant in minimal medium at near the optimal growth temperature but had no detectable effect on growth in rich medium. Quantitative proteomics, real time reverse transcription-PCR, and enzyme assays revealed that the expression levels of some genes involved in CO(2) assimilation and other activities were changed in the Deltamma10b mutant. Chromatin immunoprecipitation suggested a direct association of Mma10b with an 18-bp DNA binding motif in vivo. Electrophoretic mobility shift assays and DNase I footprinting confirmed that Mma10b preferentially binds specific sequences of DNA with an apparent Kd in the 100 nM range. These results suggested that the physiological role of Mma10b in the mesophilic methanococci is greatly diverged from that of homologs in thermophiles.

  8. A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus

    Science.gov (United States)

    McGregor, Alistair

    2016-01-01

    In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenital CMV. Guinea pig cytomegalovirus (GPCMV) potentially encodes a UL128-131 HCMV PC homolog locus (GP128-GP133). In transient expression studies, GPCMV gH and gL glycoproteins interacted with UL128, UL130 and UL131 homolog proteins (designated GP129 and GP131 and GP133 respectively) to form PC or subcomplexes which were determined by immunoprecipitation reactions directed to gH or gL. A natural GP129 C-terminal deletion mutant (aa 107–179) and a chimeric HCMV UL128 C-terminal domain swap GP129 mutant failed to form PC with other components. GPCMV infection of a newly established guinea pig epithelial cell line required a complete PC and a GP129 mutant virus lacked epithelial tropism and was attenuated in the guinea pig for pathogenicity and had a low congenital transmission rate. Individual knockout of GP131 or 133 genes resulted in loss of viral epithelial tropism. A GP128 mutant virus retained epithelial tropism and GP128 was determined not to be a PC component. A series of GPCMV mutants demonstrated that gO was not strictly essential for epithelial infection whereas gB and the PC were essential. Ectopic expression of a GP129 cDNA in a GP129 mutant virus restored epithelial tropism, pathogenicity and congenital infection. Overall, GPCMV forms a PC similar to HCMV which enables evaluation of PC based vaccine strategies in the guinea pig model. PMID:27387220

  9. An Empirical Investigation of Time-Out with and without Escape Extinction to Treat Escape-Maintained Noncompliance

    Science.gov (United States)

    Everett, Gregory E.; Olmi, D. Joe; Edwards, Ron P.; Tingstrom, Daniel H.; Sterling-Turner, Heather E.; Christ, Theodore J.

    2007-01-01

    The present study evaluates the effectiveness of two time-out (TO) procedures in reducing escape-maintained noncompliance of 4 children. Noncompliant behavioral function was established via a functional assessment (FA), including indirect and direct descriptive procedures and brief confirmatory experimental analyses. Following FA, parents were…

  10. Induced High Lysine Mutants in Barley

    DEFF Research Database (Denmark)

    Doll, Hans; Køie, B.; Eggum, B. O.

    1974-01-01

    variety. Comparisons of six high lysine mutants with the parent variety showed that grain yield and seed size of the mutants are reduced between 10 and 30 per cent. However, the most promising mutant had the lowest reduction in grain yield, and the absolute lysine yield of this mutant was some 30 per cent...... above that of the parent variety. Feeding tests with rats revealed substantial increases in the biological value of the high lysine mutant protein. Also the net protein utilization was improved but less so because of a somewhat reduced digestibility of the mutant protein....

  11. HTP-1 coordinates synaptonemal complex assembly with homolog alignment during meiosis in C. elegans.

    Science.gov (United States)

    Couteau, Florence; Zetka, Monique

    2005-11-15

    During meiosis, the mechanisms responsible for homolog alignment, synapsis, and recombination are precisely coordinated to culminate in the formation of crossovers capable of directing accurate chromosome segregation. An outstanding question is how the cell ensures that the structural hallmark of meiosis, the synaptonemal complex (SC), forms only between aligned pairs of homologous chromosomes. In the present study, we find that two closely related members of the him-3 gene family in Caenorhabditis elegans function as regulators of synapsis. HTP-1 functionally couples homolog alignment to its stabilization by synapsis by preventing the association of SC components with unaligned and immature chromosome axes; in the absence of the protein, nonhomologous contacts between chromosomes are inappropriately stabilized, resulting in extensive nonhomologous synapsis and a drastic decline in chiasma formation. In the absence of both HTP-1 and HTP-2, synapsis is abrogated per se and the early association of SC components with chromosomes observed in htp-1 mutants does not occur, suggesting a function for the proteins in licensing SC assembly. Furthermore, our results suggest that early steps of recombination occur in a narrow window of opportunity in early prophase that ends with SC assembly, resulting in a mechanistic coupling of the two processes to promote crossing over.

  12. The C. elegans Crumbs family contains a CRB3 homolog and is not essential for viability

    Directory of Open Access Journals (Sweden)

    Selma Waaijers

    2015-02-01

    Full Text Available Crumbs proteins are important regulators of epithelial polarity. In C. elegans, no essential role for the two described Crumbs homologs has been uncovered. Here, we identify and characterize an additional Crumbs family member in C. elegans, which we termed CRB-3 based on its similarity in size and sequence to mammalian CRB3. We visualized CRB-3 subcellular localization by expressing a translational GFP fusion. CRB-3::GFP was expressed in several polarized tissues in the embryo and larval stages, and showed apical localization in the intestine and pharynx. To identify the function of the Crumbs family in C. elegans development, we generated a triple Crumbs deletion mutant by sequentially removing the entire coding sequence for each crumbs homolog using a CRISPR/Cas9-based approach. Remarkably, animals lacking all three Crumbs homologs are viable and show normal epithelial polarity. Thus, the three C. elegans Crumbs family members do not appear to play an essential role in epithelial polarity establishment.

  13. Resolving RAD51C function in late stages of homologous recombination

    Directory of Open Access Journals (Sweden)

    Kuznetsov Sergey G

    2007-06-01

    Full Text Available Abstract DNA double strand breaks are efficiently repaired by homologous recombination. One of the last steps of this process is resolution of Holliday junctions that are formed at the sites of genetic exchange between homologous DNA. Although various resolvases with Holliday junctions processing activity have been identified in bacteriophages, bacteria and archaebacteria, eukaryotic resolvases have been elusive. Recent biochemical evidence has revealed that RAD51C and XRCC3, members of the RAD51-like protein family, are involved in Holliday junction resolution in mammalian cells. However, purified recombinant RAD51C and XRCC3 proteins have not shown any Holliday junction resolution activity. In addition, these proteins did not reveal the presence of a nuclease domain, which raises doubts about their ability to function as a resolvase. Furthermore, oocytes from infertile Rad51C mutant mice exhibit precocious separation of sister chromatids at metaphase II, a phenotype that reflects a defect in sister chromatid cohesion, not a lack of Holliday junction resolution. Here we discuss a model to explain how a Holliday junction resolution defect can lead to sister chromatid separation in mouse oocytes. We also describe other recent in vitro and in vivo evidence supporting a late role for RAD51C in homologous recombination in mammalian cells, which is likely to be resolution of the Holliday junction.

  14. Molecular landscape of acquired resistance to targeted therapy combinations in BRAF mutant colorectal cancer

    Science.gov (United States)

    Oddo, Daniele; Sennott, Erin M.; Barault, Ludovic; Valtorta, Emanuele; Arena, Sabrina; Cassingena, Andrea; Filiciotto, Genny; Marzolla, Giulia; Elez, Elena; van Geel, Robin M.J.M.; Bartolini, Alice; Crisafulli, Giovanni; Boscaro, Valentina; Godfrey, Jason T.; Buscarino, Michela; Cancelliere, Carlotta; Linnebacher, Michael; Corti, Giorgio; Truini, Mauro; Siravegna, Giulia; Grasselli, Julieta; Gallicchio, Margherita; Bernards, René; Schellens, Jan H.M.; Tabernero, Josep; Engelman, Jeffrey A.; Sartore-Bianchi, Andrea; Bardelli, Alberto; Siena, Salvatore; Corcoran, Ryan B.; Di Nicolantonio, Federica

    2016-01-01

    Summary Although recent clinical trials of BRAF inhibitor combinations have demonstrated improved efficacy in BRAF mutant colorectal cancer, emergence of acquired resistance limits clinical benefit. Here, we undertook a comprehensive effort to define mechanisms underlying drug resistance with the goal of guiding development of therapeutic strategies to overcome this limitation. We generated a broad panel of BRAF mutant resistant cell line models across seven different clinically-relevant drug combinations. Combinatorial drug treatments were able to abrogate ERK1/2 phosphorylation in parental sensitive cells, but not in their resistant counterparts, indicating that resistant cells escaped drug treatments through one or more mechanisms leading to biochemical reactivation of the MAPK signaling pathway. Genotyping of resistant cells identified gene amplification of EGFR, KRAS and mutant BRAF, as well as acquired mutations in KRAS, EGFR, and MAP2K1. These mechanisms were clinically relevant, as we identified emergence of a KRAS G12C mutation and increase of mutant BRAF V600E allele frequency in the circulating tumor DNA of a patient at relapse from combined treatment with BRAF and MEK inhibitors. In order to identify therapeutic combinations capable of overcoming drug resistance, we performed a systematic assessment of candidate therapies across the panel of resistant cell lines. Independent of the molecular alteration acquired upon drug pressure, most resistant cells retained sensitivity to vertical MAPK pathway suppression when combinations of ERK, BRAF, and EGFR inhibitors were applied. These therapeutic combinations represent promising strategies for future clinical trials in BRAF mutant colorectal cancer. PMID:27312529

  15. PXA1, a putative S. cerevisiae homolog of the human adrenoleukyodystrophy gene

    Energy Technology Data Exchange (ETDEWEB)

    Shani, N.; Watkins, P.A.; Valle, D. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)

    1994-09-01

    The adrenoleukodystrophy protein (ALDP) and the 70 kD peroxisomal membrane protein (PMP70) are ATP-binding cassette transporters in the peroxisome membrane. The former is defective in X-linked adrenoleukodystrophy (ALD), a neurodegenerative disorder with defective peroxisome oxidation of very long chain fatty acids; the latter is implicated in Zellweger syndrome, a defect in peroxisome biogenesis. The functions and interactions of ALDP and PMP70 in the peroxisomal membrane are not known. To develop a system in which these questions could be addressed, we sought to clone their yeast homologs. Using RT/PCR with degenerate primers and oleic acid (C18:1) induced yeast RNA as template, we amplified a cDNA segment corresponding to a conserved region of ALDP and PMP70. By sequencing amplified products, we found one with homology to both proteins and used it to clone the corresponding full length yeast gene (PXA1). PXA1 encodes a 758 amino acid protein with 28% and 21% overall identity to ALDP and PMP70, respectively which increases to 47% and 39% in a C terminal region of 178 amino acids. The PXA1 protein precipitates with peroxisomes as shown by immunoblot analysis of cell fractionation gradients. Disruption of PXA1 by homologous recombination results in impaired growth on oleic acid and reduced ability to oxidize oleate. The growth phenotype can be corrected by expression of the wild type PXA1 in the mutant strain. Peroxisomes in the PXA1 mutant yeast strain are intact as judged by catalase distribution and electron microscopy. Given the amino acid similarity, fatty acid oxidation defect and lack of an effect on peroxisomal integrity, we hypothesize that PXA1 may be the yeast ortholog of ALDP. Complementation studies to examine this hypothesis are in progress.

  16. A PHF8 homolog in C. elegans promotes DNA repair via homologous recombination.

    Directory of Open Access Journals (Sweden)

    Changrim Lee

    Full Text Available PHF8 is a JmjC domain-containing histone demethylase, defects in which are associated with X-linked mental retardation. In this study, we examined the roles of two PHF8 homologs, JMJD-1.1 and JMJD-1.2, in the model organism C. elegans in response to DNA damage. A deletion mutation in either of the genes led to hypersensitivity to interstrand DNA crosslinks (ICLs, while only mutation of jmjd-1.1 resulted in hypersensitivity to double-strand DNA breaks (DSBs. In response to ICLs, JMJD-1.1 did not affect the focus formation of FCD-2, a homolog of FANCD2, a key protein in the Fanconi anemia pathway. However, the dynamic behavior of RPA-1 and RAD-51 was affected by the mutation: the accumulations of both proteins at ICLs appeared normal, but their subsequent disappearance was retarded, suggesting that later steps of homologous recombination were defective. Similar changes in the dynamic behavior of RPA-1 and RAD-51 were seen in response to DSBs, supporting a role of JMJD-1.1 in homologous recombination. Such a role was also supported by our finding that the hypersensitivity of jmjd-1.1 worms to ICLs was rescued by knockdown of lig-4, a homolog of Ligase 4 active in nonhomologous end-joining. The hypersensitivity of jmjd-1.1 worms to ICLs was increased by rad-54 knockdown, suggesting that JMJD-1.1 acts in parallel with RAD-54 in modulating chromatin structure. Indeed, the level of histone H3 Lys9 tri-methylation, a marker of heterochromatin, was higher in jmjd-1.1 cells than in wild-type cells. We conclude that the histone demethylase JMJD-1.1 influences homologous recombination either by relaxing heterochromatin structure or by indirectly regulating the expression of multiple genes affecting DNA repair.

  17. Antibodies with higher bactericidal activity induced by a Neisseria gonorrhoeae Rmp deletion mutant strain.

    Directory of Open Access Journals (Sweden)

    Guocai Li

    Full Text Available Neisseria gonorrhoeae (N. gonorrhoeae outer membrane protein reduction modifiable protein (Rmp has strong immunogenicity. However, anti-Rmp antibodies block rather than preserve the antibacterial effects of protective antibodies, which hampers the development of vaccines for gonococcal infections. We herein constructed an Rmp deletion mutant strain of N. gonorrhoeae by gene homologous recombination. The 261-460 nucleotide residues of Rmp gene amplified from N. gonorrhoeae WHO-A strain were replaced with a kanamycin-resistant Kan gene amplified from pET-28a. The resultant hybridized DNA was transformed into N. gonorrhoeae WHO-A strain. PCR was used to screen the colonies in which wild-type Rmp gene was replaced with a mutant gene fragment. Western blotting revealed that the Rmp deletion mutant strain did not express Rmp protein. Rmp deletion did not alter the morphological and Gram staining properties of the mutant strain that grew slightly more slowly than the wild-type one. Rmp gene mutated stably throughout 25 generations of passage. Antibody-mediated complement-dependent cytotoxicity assay indicated that the antibodies induced by the mutant strain had evidently higher bactericidal activities than those induced by the wild-type strain. Further modification of the Rmp deletion mutant strain is still required in the development of novel live attenuated vaccines for gonorrhea by Opa genes deletion or screening of phenotypic variant strains that do not express Opa proteins.

  18. Homological Perturbation Theory for Nonperturbative Integrals

    Science.gov (United States)

    Johnson-Freyd, Theo

    2015-11-01

    We use the homological perturbation lemma to produce explicit formulas computing the class in the twisted de Rham complex represented by an arbitrary polynomial. This is a non-asymptotic version of the method of Feynman diagrams. In particular, we explain that phenomena usually thought of as particular to asymptotic integrals in fact also occur exactly: integrals of the type appearing in quantum field theory can be reduced in a totally algebraic fashion to integrals over an Euler-Lagrange locus, provided this locus is understood in the scheme-theoretic sense, so that imaginary critical points and multiplicities of degenerate critical points contribute.

  19. An apoptotic cell cycle mutant in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Villadsen, Ingrid

    1996-01-01

    The simple eukaryote Saccharomyces cerevisiae has proved to be a useful organism for elucidating the mechanisms that govern cell cycle progression in eukaryotic cells. The excellent in vivo system permits a cell cycle study using temperature sensitive mutants. In addition, it is possible to study...... many genes and gene products from higher eukaryotes in Saccharomyces cerevisiae because many genes and biological processes are homologous or similar in lower and in higher eukaryotes. The highly developed methods of genetics and molecular biology greatly facilitates studies of higher eukaryotic...... processes.Programmmed cell death with apoptosis plays a major role in development and homeostatis in most, if not all, animal cells. Apoptosis is a morphologically distinct form of death, that requires the activation of a highly regulated suicide program. Saccharomyces cerevisiae provides a new system...

  20. Environmental T4-Family Bacteriophages Evolve to Escape Abortive Infection via Multiple Routes in a Bacterial Host Employing "Altruistic Suicide" through Type III Toxin-Antitoxin Systems.

    Science.gov (United States)

    Chen, Bihe; Akusobi, Chidiebere; Fang, Xinzhe; Salmond, George P C

    2017-01-01

    Abortive infection is an anti-phage mechanism employed by a bacterium to initiate its own death upon phage infection. This reduces, or eliminates, production of viral progeny and protects clonal siblings in the bacterial population by an act akin to an "altruistic suicide." Abortive infection can be mediated by a Type III toxin-antitoxin system called ToxIN Pa consisting of an endoribonuclease toxin and RNA antitoxin. ToxIN Pa is a heterohexameric quaternary complex in which pseudoknotted RNA inhibits the toxicity of the toxin until infection by certain phages causes destabilization of ToxIN Pa , leading to bacteriostasis and, eventually, lethality. However, it is still unknown why only certain phages are able to activate ToxIN Pa . To try to address this issue we first introduced ToxIN Pa into the Gram-negative enterobacterium, Serratia sp. ATCC 39006 ( S 39006) and then isolated new environmental S 39006 phages that were scored for activation of ToxIN Pa and abortive infection capacity. We isolated three T4-like phages from a sewage treatment outflow point into the River Cam, each phage being isolated at least a year apart. These phages were susceptible to ToxIN Pa -mediated abortive infection but produced spontaneous "escape" mutants that were insensitive to ToxIN Pa . Analysis of these resistant mutants revealed three different routes of escaping ToxIN Pa , namely by mutating asiA (the product of which is a phage transcriptional co-activator); by mutating a conserved, yet functionally unknown, orf84 ; or by deleting a 6.5-10 kb region of the phage genome. Analysis of these evolved escape mutants may help uncover the nature of the corresponding phage product(s) involved in activation of ToxIN Pa .

  1. Mutant genes in pea breeding

    International Nuclear Information System (INIS)

    Swiecicki, W.K.

    1990-01-01

    Full text: Mutations of genes Dpo (dehiscing pods) and A (anthocyanin synthesis) played a role in pea domestication. A number of other genes were important in cultivar development for 3 types of usage (dry seeds, green vegetable types, fodder), e.g. fn, fna, le, p, v, fas and af. New genes (induced and spontaneous), are important for present ideotypes and are registered by the Pisum Genetics Association (PGA). Comparison of a pea variety ideotype with the variation available in gene banks shows that breeders need 'new' features. In mutation induction experiments, genotype, mutagen and method of treatment (e.g. combined or fractionated doses) are varied for broadening the mutation spectrum and selecting more genes of agronomic value. New genes are genetically analysed. In Poland, some mutant varieties with the gene afila were registered, controlling lodging by a shorter stem and a higher number of internodes. Really non-lodging pea varieties could strongly increase seed yield. But the probability of detecting a major gene for lodging resistance is low. Therefore, mutant genes with smaller influence on plant architecture are sought, to combine their effect by crossing. Promising seem to be the genes rogue, reductus and arthritic as well as a number of mutant genes not yet genetically identified. The gene det for terminal inflorescence - similarly to Vicia faba - changes plant development. Utilisation of assimilates and ripening should be better. Improvement of harvest index should give higher seed yield. A number of genes controlling disease resistance are well known (eg. Fw, Fnw, En, mo and sbm). Important in mass screening of resistance are closely linked gene markers. Pea gene banks collect respective lines, but mutants induced in highly productive cultivars would be better. Inducing gene markers sometimes seems to be easier than transfer by crossing. Mutation induction in pea breeding is probably more important because a high number of monogenic features are

  2. ESCAP holds training workshop to improve monitoring of reproductive health.

    Science.gov (United States)

    1998-01-01

    While governments in the ESCAP region have made significant efforts toward meeting the 1994 International Conference on Population and Development (ICPD) Program of Action recommendations to reorient and broaden reproductive health programs, obstacles related to the limited capacity of statistical systems for monitoring and evaluating progress in meeting ICPD goals have been problematic. With the goal of strengthening national capacities to monitor and evaluate comprehensive reproductive health programs, the Training Workshop on Improving the National Capacity for Monitoring Reproductive Health Programs was organized by ESCAP, with the financial support of the Netherlands. The workshop was held in Bangkok from November 23 to December 4, 1998, and attended by 15 participants from Cambodia, Laos, Mongolia, Myanmar, Nepal, Pakistan, and Vietnam. Participants were drawn from countries' ministries of health and national statistical agencies. Workshop participants valued the experience and look forward to receiving additional training in the field.

  3. Behavioral analysis of the escape response in larval zebrafish

    Science.gov (United States)

    Feng, Ruopei; Girdhar, Kiran; Chemla, Yann; Gruebele, Martin

    The behavior of larval zebrafish is of great interest because the limited number of locomotor neurons in larval zebrafish couples with its rich repertoire of movements as a vertebrate animal. Current research uses a priori-selected parameters to describe their swimming behavior while our lab has built a parameter-free model based on singular value decomposition analysis to characterize it. Our previous work has analyzed the free swimming of larval zebrafish and presented a different picture from the current classification of larval zebrafish locomotion. Now we are extending this work to the studies of their escape response to acoustic stimulus. Analysis has shown intrinsic difference in the locomotion between escape response and free swimming.

  4. Quantum and thermal phase escape in extended Josephson systems

    Energy Technology Data Exchange (ETDEWEB)

    Kemp, A.

    2006-07-12

    In this work I examine phase escape in long annular Josephson tunnel junctions. The sine-Gordon equation governs the dynamics of the phase variable along the junction. This equation supports topological soliton solutions, which correspond to quanta of magnetic flux trapped in the junction barrier. For such Josephson vortices an effective potential is formed by an external magnetic field, while a bias current acts as a driving force. Both together form a metastable potential well, which the vortex is trapped in. When the driving force exceeds the pinning force of the potential, the vortex escapes and the junction switches to the voltage state. At a finite temperature the driving force fluctuates. If the junction's energy scale is small, the phase variable can undergo a macroscopic quantum tunneling (MQT) process at temperatures below the crossover temperature. Without a vortex trapped, the metastable state is not a potential minimum in space, but a potential minimum at zero phase difference. (orig.)

  5. Fixation and escape times in stochastic game learning

    International Nuclear Information System (INIS)

    Realpe-Gomez, John; Szczesny, Bartosz; Galla, Tobias; Dall’Asta, Luca

    2012-01-01

    Evolutionary dynamics in finite populations is known to fixate eventually in the absence of mutation. We here show that a similar phenomenon can be found in stochastic game dynamical batch learning, and investigate fixation in learning processes in a simple 2×2 game, for two-player games with cyclic interaction, and in the context of the best-shot network game. The analogues of finite populations in evolution are here finite batches of observations between strategy updates. We study when and how such fixation can occur, and present results on the average time-to-fixation from numerical simulations. Simple cases are also amenable to analytical approaches and we provide estimates of the behaviour of so-called escape times as a function of the batch size. The differences and similarities with escape and fixation in evolutionary dynamics are discussed. (paper)

  6. Fractionation of noble gases by thermal escape from accreting planetesimals

    International Nuclear Information System (INIS)

    Donahue, T.M.

    1986-01-01

    Assuming solar initial elemental and isotopic ratios and a determination of the degree of fractionation occurring by competition between gravitational binding and escape, a model is developed for selective noble gas loss through escape during the growth of planetesimals to form the terrestrial planets. Of the two classes of planetesimals that can form on a time scale that is consistent with modern accretion models, one is depleted in neon while the other is neon-rich. The mechanism is noted to be capable of accounting for all known properties of the noble gas volatiles on the terrestrial planets, with only one exception, namely the Ar-36/Ar-38 ratios for Mars and the earth, which are much lower than observed. 11 references

  7. Library Lockdown: An escape room by kids for the community

    Directory of Open Access Journals (Sweden)

    Jennifer Thoegersen

    2016-11-01

    Full Text Available In Brief Hoping to bring the unexpected to Nebraska City, the Morton-James Public Library applied for an ALA Association for Library Service to Children Curiosity Creates grant to undertake an ambitious project: build an escape room. In a library storage room. With children. The hope was  by trying something completely different, we could increase interest in the library throughout the community and build a sense of ownership in the participants, while encouraging creativity and having a lot of fun. Library Lockdown was a four-month program that brought several dozen kids together—age 8 to 13—to build a fully-functioning escape room. Their creation, the Lab of Dr. Morton McBrains, is now open for business.

  8. Escape of Mars atmospheric carbon through time by photochemical means

    Science.gov (United States)

    Luhmann, J. G.; Kim, J.; Nagy, A. F.

    1993-01-01

    Luhmann et al. recently suggested that sputtering of the Martian atmosphere by re-entering O(+) pickup ions could have provided a significant route of escape for CO2 and its products throughout Mars' history. They estimated that the equivalent of C in an approximately 140-mbar CO2 atmosphere should have been lost this way if the Sun and solar wind evolved according to available models. Another source of escaping C (and O) that is potentially important is the dissociative recombination of ionospheric CO(+) near the exobase. We have evaluated the loss rates due to this process for 'ancient' solar EUV radiation fluxes of 1, 3, and 6 times the present flux in order to calculate the possible cumulative loss over the last 3.5 Gyr.

  9. State may be liable for HIV exposure from inmate's escape.

    Science.gov (United States)

    1999-09-03

    The Louisiana Court of Appeal is reviewing a case on whether the Louisiana prison system is liable to a private citizen who was exposed to HIV as a consequence of an inmate escape. The case questions whether the Department of Public Safety and Corrections had a duty to inform the local prison, where the inmate was transferred to, about his HIV infection and propensity to escape. The department requested a summary judgment stating that no such duty existed. This motion was rejected by the trial court. Affidavits were presented that questioned the facts and circumstances of the case. The department's duty to the prisoner and jail are in dispute and the trial court's denial has been deemed proper.

  10. Mutation in Torenia fournieri Lind. UFO homolog confers loss of TfLFY interaction and results in a petal to sepal transformation.

    Science.gov (United States)

    Sasaki, Katsutomo; Yamaguchi, Hiroyasu; Aida, Ryutaro; Shikata, Masahito; Abe, Tomoko; Ohtsubo, Norihiro

    2012-09-01

    We identified a Torenia fournieri Lind. mutant (no. 252) that exhibited a sepaloid phenotype in which the second whorls were changed to sepal-like organs. This mutant had no stamens, and the floral organs consisted of sepals and carpels. Although the expression of a torenia class B MADS-box gene, GLOBOSA (TfGLO), was abolished in the 252 mutant, no mutation of TfGLO was found. Among torenia homologs such as APETALA1 (AP1), LEAFY (LFY), and UNUSUAL FLORAL ORGANS (UFO), which regulate expression of class B genes in Arabidopsis, only accumulation of the TfUFO transcript was diminished in the 252 mutant. Furthermore, a missense mutation was found in the coding region of the mutant TfUFO. Intact TfUFO complemented the mutant phenotype whereas mutated TfUFO did not; in addition, the transgenic phenotype of TfUFO-knockdown torenias coincided with the mutant phenotype. Yeast two-hybrid analysis revealed that the mutated TfUFO lost its ability to interact with TfLFY protein. In situ hybridization analysis indicated that the transcripts of TfUFO and TfLFY were partially accumulated in the same region. These results clearly demonstrate that the defect in TfUFO caused the sepaloid phenotype in the 252 mutant due to the loss of interaction with TfLFY. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

  11. The Endocannabinoid System Differentially Regulates Escape Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Andreas J. Genewsky

    2017-10-01

    Full Text Available Among the hardwired behaviors, fear or survival responses certainly belong to the most evolutionary conserved ones. However, higher animals possess the ability to adapt to certain environments (e.g., novel foraging grounds, and, therefore, those responses need to be plastic. Previous studies revealed a cell-type specific role of the endocannabinoid system in novelty fear, conditioned fear and active vs. passive avoidance in a shuttle box paradigm. In this study we aim to investigate, whether knocking-out the cannabinoid receptor type-1 (CB1 on cortical glutamatergic (Glu-CB1−/− or GABAergic (GABA-CB1−/− neurons differentially affects the level of behavioral inhibition, which could ultimately lead to differences in escape behavior. In this context, we developed a novel behavioral paradigm, the Moving Wall Box (MWB. Using the MWB task we could show that Glu-CB1−/− mice have higher levels of behavioral inhibition over the course of repeated testing. GABA-CB1−/− mice, in contrast, showed significantly lower levels of behavioral inhibition compared to wild-type controls and more escape behavior. These changes in behavioral inhibition and escape behavior cannot be explained by altered levels of arousal, as repeated startle measurements revealed general habituation irrespective of the line and genotype of the animals. Taken together, we could show that CB1 on cortical glutamatergic terminals is important for the acquisition of active avoidance, as the absence of CB1 on these neurons creates a bias toward inhibitory avoidance. This is the case in situations without punishment such as electric footshocks. On the contrary CB1 receptors on GABAergic neurons mediate the acquisition of passive avoidance, as the absence of CB1 on those neurons establishes a strong bias toward escape behavior.

  12. UNESCO to blame:Reality or easy escape?

    OpenAIRE

    Pereira Roders, A Ana; Grigolon, AB Anna

    2015-01-01

    “UNESCO to blame” is a trend often observed in scholarly works. In those studies UNESCO is accused to privilege Eurocentric standards on heritage conservation. Is this reality or an easy escape? Can this trend be noted in other UNESCO reference texts? This article seeks to answer this question by studying the two main inscription-based conventions and their contribution to heritage management, while performing a data analysis on the countries behind these conventions, and their roles over tim...

  13. The escape of natural satellites from Mercury and Venus

    International Nuclear Information System (INIS)

    Kumar, S.S.

    1977-01-01

    It is suggested that the slow rotations of Mercury and Venus may be connected with the absence of natural satellites around them. If Mercury or Venus possessed a satellite at the time of formation, the tidal evolution would have caused the satellite to recede. At a sufficiently large distance from the planet, the Sun's gravitational influence makes the satellite orbit unstable. The natural satellites of Mercury and Venus might have escaped as a consequence of this instability. (Auth.)

  14. Saint Louis Encephalitis Temperature-Sensitive Mutants.

    Science.gov (United States)

    1981-01-01

    group II contains two mutants and group III contains three mutants. Examination of the ability of mutants to grow at 300C, 40 C or 37 C indicates that...importance. Information from studies with Poliovirus has shown that the use of live attenuated virus vaccines result in longer lasting, more effec- tive...sensitive mutant to grow at internal body temperature may have a significant effect on the ability of the virus to induce a protective immune response or

  15. Escape of Tick-Borne Flavivirus from 2'-C-Methylated Nucleoside Antivirals Is Mediated by a Single Conservative Mutation in NS5 That Has a Dramatic Effect on Viral Fitness

    Czech Academy of Sciences Publication Activity Database

    Eyer, Luděk; Kondo, H.; Zouharová, D.; Hirano, M.; Valdés, James J.; Muto, M.; Kastl, T.; Kobayashi, S.; Haviernik, J.; Igarashi, K.; Kariwa, H.; Vaculovicova, M.; Černý, Jiří; Kizek, R.; Kroeger, A.; Lienenklaus, S.; Dejmek, Milan; Nencka, Radim; Palus, Martin; Salát, J.; De Clercq, E.; Yoshii, K.; Růžek, Daniel

    2017-01-01

    Roč. 91, č. 21 (2017), č. článku e01028-17. ISSN 0022-538X R&D Projects: GA MZd(CZ) NV16-34238A Institutional support: RVO:60077344 ; RVO:61388963 Keywords : antiviral agents * antiviral therapy * escape mutant * tick-borne * encephalitis virus * tick-borne pathogens Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 4.663, year: 2016

  16. Human monoclonal antibodies to a novel cluster of conformational epitopes on HCV E2 with resistance to neutralization escape in a genotype 2a isolate

    DEFF Research Database (Denmark)

    Keck, Zhen-yong; Xia, Jinming; Wang, Yong

    2012-01-01

    regions that will be relevant for vaccine design, we employed yeast surface display of antibodies that bound to genotype 1a H77C E2 mutant proteins containing a substitution either at Y632A (to avoid selecting non-neutralizing antibodies) or D535A. A panel of nine human monoclonal antibodies (HMAbs......, when HCVcc were passaged in the presence of each of these antibodies, virus escape was not observed. Thus, the cluster of HC-84 epitopes, designated as antigenic domain D, is relevant for vaccine design for this highly diverse virus....

  17. Oxygen and carbogen breathing following simulated submarine escape.

    Science.gov (United States)

    Gennser, Mikael; Loveman, Geoff; Seddon, Fiona; Thacker, Julian; Blogg, S Lesley

    2014-01-01

    Escape from a disabled submarine exposes escapers to a high risk of decompression sickness (DCS). The initial bubble load is thought to emanate from the fast tissues; it is this load that should be lowered to reduce risk of serious neurological DCS. The breathing of oxygen or carbogen (5% CO2, 95% O2) post-surfacing was investigated with regard to its ability to reduce the initial bubble load in comparison to air breathing. Thirty-two goats were subject to a dry simulated submarine escape profile to and from 240 meters (2.5 MPa). On surfacing, they breathed air (control), oxygen or carbogen for 30 minutes. Regular Doppler audio bubble grading was carried out, using the Kisman Masurel (KM) scale. One suspected case of DCS was noted. No oxygen toxicity or arterial gas embolism occurred. No significant difference was found between the groups in terms of the median peak KM grade or the period before the KM grade dropped below III. Time to disappearance of bubbles was significantly different between groups; oxygen showed faster bubble resolution than carbogen and air. This reduction in time to bubble resolution may be beneficial in reducing decompression stress, but probably does not affect the risk of fast-tissue DCS.

  18. Effective climate-energy solutions, escape routes and peak oil

    International Nuclear Information System (INIS)

    Bergh, Jeroen C.J.M. van den

    2012-01-01

    Many well-intended climate-energy strategies are ineffective in the absence of serious environmental regulation. This holds, among others, for direct support of clean energy, voluntary energy conservation, technical standards on a limited set of products, unilateral stringent carbon pricing, and awaiting peak oil as a climate strategy. All of these suffer from “escape routes” that indirectly increase CO 2 emissions and thus make the original strategy ineffective. On the other hand, environmental regulation alone may lead to a myopia-bias, stimulating early dominance of cost-effective technologies and a focus on incremental innovations associated with such technologies rather than on radical innovations. Although adopting a partial viewpoint keeps the analysis simple, we urgently need a more inclusive systems perspective on climate solutions. This will allow the formulation of an effective climate policy package that addresses the various escape routes. - Highlights: ► Many well-intended climate-energy strategies are ineffective because of escape routes. ► In this context the relationship between peak oil and climate policy receives attention. ► Environmental regulation alone creates myopia-bias, the resolution of which requires technology-specific policies. ► To formulate an effective climate policy package an inclusive systems perspective is needed.

  19. Transitions between three swimming gaits in Paramecium escape.

    Science.gov (United States)

    Hamel, Amandine; Fisch, Cathy; Combettes, Laurent; Dupuis-Williams, Pascale; Baroud, Charles N

    2011-05-03

    Paramecium and other protists are able to swim at velocities reaching several times their body size per second by beating their cilia in an organized fashion. The cilia beat in an asymmetric stroke, which breaks the time reversal symmetry of small scale flows. Here we show that Paramecium uses three different swimming gaits to escape from an aggression, applied in the form of a focused laser heating. For a weak aggression, normal swimming is sufficient and produces a steady swimming velocity. As the heating amplitude is increased, a higher acceleration and faster swimming are achieved through synchronized beating of the cilia, which begin by producing oscillating swimming velocities and later give way to the usual gait. Finally, escape from a life-threatening aggression is achieved by a "jumping" gait, which does not rely on the cilia but is achieved through the explosive release of a group of trichocysts in the direction of the hot spot. Measurements through high-speed video explain the role of trichocysts in defending against aggressions while showing unexpected transitions in the swimming of microorganisms. These measurements also demonstrate that Paramecium optimizes its escape pattern by taking advantage of its inertia.

  20. Variable processing and cross-presentation of HIV by dendritic cells and macrophages shapes CTL immunodominance and immune escape.

    Directory of Open Access Journals (Sweden)

    Jens Dinter

    2015-03-01

    Full Text Available Dendritic cells (DCs and macrophages (Møs internalize and process exogenous HIV-derived antigens for cross-presentation by MHC-I to cytotoxic CD8⁺ T cells (CTL. However, how degradation patterns of HIV antigens in the cross-presentation pathways affect immunodominance and immune escape is poorly defined. Here, we studied the processing and cross-presentation of dominant and subdominant HIV-1 Gag-derived epitopes and HLA-restricted mutants by monocyte-derived DCs and Møs. The cross-presentation of HIV proteins by both DCs and Møs led to higher CTL responses specific for immunodominant epitopes. The low CTL responses to subdominant epitopes were increased by pretreatment of target cells with peptidase inhibitors, suggestive of higher intracellular degradation of the corresponding peptides. Using DC and Mø cell extracts as a source of cytosolic, endosomal or lysosomal proteases to degrade long HIV peptides, we identified by mass spectrometry cell-specific and compartment-specific degradation patterns, which favored the production of peptides containing immunodominant epitopes in all compartments. The intracellular stability of optimal HIV-1 epitopes prior to loading onto MHC was highly variable and sequence-dependent in all compartments, and followed CTL hierarchy with immunodominant epitopes presenting higher stability rates. Common HLA-associated mutations in a dominant epitope appearing during acute HIV infection modified the degradation patterns of long HIV peptides, reduced intracellular stability and epitope production in cross-presentation-competent cell compartments, showing that impaired epitope production in the cross-presentation pathway contributes to immune escape. These findings highlight the contribution of degradation patterns in the cross-presentation pathway to HIV immunodominance and provide the first demonstration of immune escape affecting epitope cross-presentation.

  1. Variable Processing and Cross-presentation of HIV by Dendritic Cells and Macrophages Shapes CTL Immunodominance and Immune Escape

    Science.gov (United States)

    Dinter, Jens; Duong, Ellen; Lai, Nicole Y.; Berberich, Matthew J.; Kourjian, Georgio; Bracho-Sanchez, Edith; Chu, Duong; Su, Hang; Zhang, Shao Chong; Le Gall, Sylvie

    2015-01-01

    Dendritic cells (DCs) and macrophages (Møs) internalize and process exogenous HIV-derived antigens for cross-presentation by MHC-I to cytotoxic CD8+ T cells (CTL). However, how degradation patterns of HIV antigens in the cross-presentation pathways affect immunodominance and immune escape is poorly defined. Here, we studied the processing and cross-presentation of dominant and subdominant HIV-1 Gag-derived epitopes and HLA-restricted mutants by monocyte-derived DCs and Møs. The cross-presentation of HIV proteins by both DCs and Møs led to higher CTL responses specific for immunodominant epitopes. The low CTL responses to subdominant epitopes were increased by pretreatment of target cells with peptidase inhibitors, suggestive of higher intracellular degradation of the corresponding peptides. Using DC and Mø cell extracts as a source of cytosolic, endosomal or lysosomal proteases to degrade long HIV peptides, we identified by mass spectrometry cell-specific and compartment-specific degradation patterns, which favored the production of peptides containing immunodominant epitopes in all compartments. The intracellular stability of optimal HIV-1 epitopes prior to loading onto MHC was highly variable and sequence-dependent in all compartments, and followed CTL hierarchy with immunodominant epitopes presenting higher stability rates. Common HLA-associated mutations in a dominant epitope appearing during acute HIV infection modified the degradation patterns of long HIV peptides, reduced intracellular stability and epitope production in cross-presentation-competent cell compartments, showing that impaired epitope production in the cross-presentation pathway contributes to immune escape. These findings highlight the contribution of degradation patterns in the cross-presentation pathway to HIV immunodominance and provide the first demonstration of immune escape affecting epitope cross-presentation. PMID:25781895

  2. Mutants of Agrobacterium tumefaciens with elevated vir gene expression

    International Nuclear Information System (INIS)

    Pazour, G.J.; Ta, C.N.; Das, A.

    1991-01-01

    Expression of Agrobacterium tumefaciens virulence (vir) genes requires virA, virG, and a plant-derived inducing compound such as acetosyringone. To identify the critical functional domains of virA and virG, a mutational approach was used. Agrobacterium A136 harboring plasmid pGP159, which contains virA, virG, and a reporter virB:lacZ gene fusion, was mutagenized with UV light or nitrosoguanidine. Survivors that formed blue colonies on a plate containing 5-bromo-4-chloro-3-indolyl beta-D-galactoside were isolated and analyzed. Quantification of beta-galactosidase activity in liquid assays identified nine mutant strains. By plasmid reconstruction and other procedures, all mutations mapped to the virA locus. These mutations caused an 11- to 560-fold increase in the vegetative level of virB:lacZ reporter gene expression. DNA sequence analysis showed that the mutations are located in four regions of VirA: transmembrane domain one, the active site, a glycine-rich region with homology to ATP-binding sites, and a region at the C terminus that has homology to the N terminus of VirG

  3. An extra early mutant of pigeonpea

    International Nuclear Information System (INIS)

    Ravikesavan, R.; Kalaimagal, T.; Rathnaswamy, R.

    2001-01-01

    The redgram (Cajanus cajan (L.) Huth) variety 'Prabhat DT' was gamma irradiated with 100, 200, 300 and 400 Gy doses. Several mutants have been identified viz., extra early mutants, monostem mutants, obcordifoliate mutants and bi-stigmatic mutants. The extra early mutant was obtained when treated with 100 Gy dose. The mutant was selfed and forwarded from M 2 to M 4 generation. In the M 4 generation the mutant line was raised along with the parental variety. Normal cultural practices were followed and the biometrical observations were recorded. It was observed that for the characters viz., total number of branches per plant, number of pods per plants, seeds per pod, 100 seed weight and seed yield per plant there was no difference between the mutant and parent variety. Whereas, regarding the days to flowering and maturity the mutants were earlier than the parents. The observation was recorded from two hundred plants each. The mutant gives the same yield in 90 days as that of the parent variety in 107 days, which make it an economic mutant

  4. Problem-Solving Test: Tryptophan Operon Mutants

    Science.gov (United States)

    Szeberenyi, Jozsef

    2010-01-01

    This paper presents a problem-solving test that deals with the regulation of the "trp" operon of "Escherichia coli." Two mutants of this operon are described: in mutant A, the operator region of the operon carries a point mutation so that it is unable to carry out its function; mutant B expresses a "trp" repressor protein unable to bind…

  5. The K Domain Mediates Homologous and Heterologous Interactions Between FLC and SVP Proteins of Brassica juncea

    Directory of Open Access Journals (Sweden)

    Ma Guanpeng

    2015-07-01

    Full Text Available The transcription factors FLOWERING LOCUS C (FLC and SHORT VEGETATIVE PHASE (SVP can interact to form homologous and heterologous protein complexes that regulate flowering time in Brassica juncea Coss. (Mustard.Previous studies showed that protein interactions were mediated by the K domain, which contains the subdomains K1, K2 and K3. However, it remains unknown how the subdomains mediate the interactions between FLC and SVP. In the present study, we constructed several mutants of subdomains K1–K3 and investigated the mechanisms involved in the heterologous interaction of BjFLC/BjSVP and in the homologous interaction of BjFLC/BjFLC or BjSVP/BjSVP. Yeast two-hybrid and β-Galactosidase activity assays showed that the 19 amino acids of the K1 subdomain in BjSVP and the 17 amino acids of the K1 subdomain in BjFLC were functional subdomains that interact with each other to mediate hetero-dimerization. The heterologous interaction was enhanced by the K2 subdomain of BjSVP protein, but weakened by its interhelical domain L2. The heterologous interaction was also enhanced by the K2 subdomain of BjFLC protein, but weakened by its K3 subdomain. The homologous interaction of BjSVP was mediated by the full K-domain. However, the homologous interaction of BjFLC was regulated only by its K1 and weakened by its K2 and K3 subdomains. The results provided new insights into the interactions between FLC and SVP, which will be valuable for further studies on the molecular regulation mechanisms of the regulation of flowering time in B. juncea and other Brassicaceae.

  6. The Legionella pneumophila Dps homolog is regulated by iron and involved in multiple stress tolerance.

    Science.gov (United States)

    Yu, Ming-Jia; Ren, Jun; Zeng, Yong-Lun; Zhou, Shi-Ning; Lu, Yong-Jun

    2009-09-01

    Iron homeostasis is essential to almost all organisms. In this study, we identified the putative homolog of the iron-storage protein-encoding gene, dpsL, in the intracellular pathogen Legionella pneumophila and demonstrated its expression under iron-limited conditions and its responses to multiple stresses. Quantitative real-time PCR analysis indicated that the expression of dpsL was enhanced under iron limitation regardless of the growth phase. Compared with the wild-type cells, the cells devoid of dpsL were heat and H(2)O(2)-sensitive. In contrast to the dps mutants of other bacteria, the growth of the dpsL mutant in an iron-deprived medium was delayed but finally reached the same cell density as wild-type cells during the stationary phase of growth. The finding that the dpsL mutant is salt resistant suggested the involvement of DpsL in virulence. Copyright 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. MutT Homolog 1 (MTH1) maintains multiple KRAS-driven pro-malignant pathways.

    Science.gov (United States)

    Patel, A; Burton, D G A; Halvorsen, K; Balkan, W; Reiner, T; Perez-Stable, C; Cohen, A; Munoz, A; Giribaldi, M G; Singh, S; Robbins, D J; Nguyen, D M; Rai, P

    2015-05-14

    Oncogenic RAS promotes production of reactive oxygen species (ROS), which mediate pro-malignant signaling but can also trigger DNA damage-induced tumor suppression. Thus RAS-driven tumor cells require redox-protective mechanisms to mitigate the damaging aspects of ROS. Here, we show that MutT Homolog 1 (MTH1), the mammalian 8-oxodGTPase that sanitizes oxidative damage in the nucleotide pool, is important for maintaining several KRAS-driven pro-malignant traits in a nonsmall cell lung carcinoma (NSCLC) model. MTH1 suppression in KRAS-mutant NSCLC cells impairs proliferation and xenograft tumor formation. Furthermore, MTH1 levels modulate KRAS-induced transformation of immortalized lung epithelial cells. MTH1 expression is upregulated by oncogenic KRAS and correlates positively with high KRAS levels in NSCLC human tumors. At a molecular level, in p53-competent KRAS-mutant cells, MTH1 loss provokes DNA damage and induction of oncogene-induced senescence. In p53-nonfunctional KRAS-mutant cells, MTH1 suppression does not produce DNA damage but reduces proliferation and leads to an adaptive decrease in KRAS expression levels. Thus, MTH1 not only enables evasion of oxidative DNA damage and its consequences, but can also function as a molecular rheostat for maintaining oncogene expression at optimal levels. Accordingly, our results indicate MTH1 is a novel and critical component of oncogenic KRAS-associated malignancy and its inhibition is likely to yield significant tumor-suppressive outcomes in KRAS-driven tumors.

  8. The transcriptional regulator LEUNIG_HOMOLOG regulates mucilage release from the Arabidopsis testa.

    Science.gov (United States)

    Walker, Murray; Tehseen, Muhammad; Doblin, Monika S; Pettolino, Filomena A; Wilson, Sarah M; Bacic, Antony; Golz, John F

    2011-05-01

    Exposure of the mature Arabidopsis (Arabidopsis thaliana) seed to water results in the rapid release of pectinaceous mucilage from the outer cells of the testa. Once released, mucilage completely envelops the seed in a gel-like capsule. The physical force required to rupture the outer cell wall of the testa comes from the swelling of the mucilage as it expands rapidly following hydration. In this study, we show that mutations in the transcriptional regulator LEUNIG_HOMOLOG (LUH) cause a mucilage extrusion defect due to altered mucilage swelling. Based on sugar linkage and immunomicroscopic analyses, we show that the structure of luh mucilage is altered, having both an increase in substituted rhamnogalacturonan I and in methyl-esterified homogalacturonan. Also correlated with the structural modification of luh mucilage is a significant decrease in MUCILAGE MODIFIED2 (MUM2; a β-galactosidase) expression in the luh seed coat, raising the possibility that reduced activity of this glycosidase is directly responsible for the luh mucilage defects. Consistent with this is the structural similarity between mum2 and luh mucilage as well as the observation that elevating MUM2 expression in luh mutants completely suppresses the mucilage extrusion defect. Suppression of the luh mutant phenotype was also observed when LEUNIG, a transcriptional corepressor closely related to LUH, was introduced in luh mutants under the control of the LUH promoter. Based on these data, we propose a new model for the regulation of pectin biosynthesis during plant growth and development.

  9. LPA19, a Psb27 Homolog in Arabidopsis thaliana, Facilitates D1 Protein Precursor Processing during PSII Biogenesis*

    Science.gov (United States)

    Wei, Lili; Guo, Jinkui; Ouyang, Min; Sun, Xuwu; Ma, Jinfang; Chi, Wei; Lu, Congming; Zhang, Lixin

    2010-01-01

    The biogenesis and assembly of photosystem II (PSII) are mainly regulated by the nuclear-encoded factors. To further identify the novel components involved in PSII biogenesis, we isolated and characterized a high chlorophyll fluorescence low psii accumulation19 (lpa19) mutant, which is defective in PSII biogenesis. LPA19 encodes a Psb27 homolog (At1g05385). Interestingly, another Psb27 homolog (At1g03600) in Arabidopsis was revealed to be required for the efficient repair of photodamaged PSII. These results suggest that the Psb27 homologs play distinct functions in PSII biogenesis and repair in Arabidopsis. Chloroplast protein labeling assays showed that the C-terminal processing of D1 in the lpa19 mutant was impaired. Protein overlay assays provided evidence that LPA19 interacts with D1, and coimmunoprecipitation analysis demonstrated that LPA19 interacts with mature D1 (mD1) and precursor D1 (pD1). Moreover, LPA19 protein was shown to specifically interact with the soluble C terminus present in the precursor and mature D1 through yeast two-hybrid analyses. Thus, these studies suggest that LPA19 is involved in facilitating the D1 precursor protein processing in Arabidopsis. PMID:20444695

  10. Calcium-Enhanced Twitching Motility in Xylella fastidiosa Is Linked to a Single PilY1 Homolog.

    Science.gov (United States)

    Cruz, Luisa F; Parker, Jennifer K; Cobine, Paul A; De La Fuente, Leonardo

    2014-12-01

    The plant-pathogenic bacterium Xylella fastidiosa is restricted to the xylem vessel environment, where mineral nutrients are transported through the plant host; therefore, changes in the concentrations of these elements likely impact the growth and virulence of this bacterium. Twitching motility, dependent on type IV pili (TFP), is required for movement against the transpiration stream that results in basipetal colonization. We previously demonstrated that calcium (Ca) increases the motility of X. fastidiosa, although the mechanism was unknown. PilY1 is a TFP structural protein recently shown to bind Ca and to regulate twitching and adhesion in bacterial pathogens of humans. Sequence analysis identified three pilY1 homologs in X. fastidiosa (PD0023, PD0502, and PD1611), one of which (PD1611) contains a Ca-binding motif. Separate deletions of PD0023 and PD1611 resulted in mutants that still showed twitching motility and were not impaired in attachment or biofilm formation. However, the response of increased twitching at higher Ca concentrations was lost in the pilY1-1611 mutant. Ca does not modulate the expression of any of the X. fastidiosa PilY1 homologs, although it increases the expression of the retraction ATPase pilT during active movement. The evidence presented here suggests functional differences between the PilY1 homologs, which may provide X. fastidiosa with an adaptive advantage in environments with high Ca concentrations, such as xylem sap. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  11. Imp2, the PSTPIP homolog in fission yeast, affects sensitivity to the immunosuppressant FK506 and membrane trafficking in fission yeast

    International Nuclear Information System (INIS)

    Kita, Ayako; Higa, Mari; Doi, Akira; Satoh, Ryosuke; Sugiura, Reiko

    2015-01-01

    Cytokinesis is a highly ordered process that divides one cell into two cells, which is functionally linked to the dynamic remodeling of the plasma membrane coordinately with various events such as membrane trafficking. Calcineurin is a highly conserved serine/threonine protein phosphatase, which regulates multiple biological functions, such as membrane trafficking and cytokinesis. Here, we isolated imp2-c3, a mutant allele of the imp2 + gene, encoding a homolog of the mouse PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1), using a genetic screen for mutations that are synthetically lethal with calcineurin deletion in fission yeast. The imp2-c3 mutants showed a defect in cytokinesis with multi-septated phenotypes, which was further enhanced upon treatment with the calcineurin inhibitor FK506. Notably, electron micrographs revealed that the imp2-c3 mutant cells accumulated aberrant multi-lamella Golgi structures and putative post-Golgi secretory vesicles, and exhibited fragmented vacuoles in addition to thickened septa. Consistently, imp2-c3 mutants showed a reduced secretion of acid phosphatase and defects in vacuole fusion. The imp2-c3 mutant cells exhibited a weakened cell wall, similar to the membrane trafficking mutants identified in the same genetic screen such as ypt3-i5. These findings implicate the PSTPIP1 homolog Imp2 in Golgi/vacuole function, thereby affecting various cellular processes, including cytokinesis and cell integrity. - Highlights: • We isolated imp2-c3, in a synthetic lethal screen with calcineurin in fission yeast. • The imp2 + gene encodes a component of the actin contractile ring similar to Cdc15. • The imp2-c3 mutants showed defects in cytokinesis, which were exacerbated by FK506. • The imp2-c3 mutants were defective in membrane trafficking and cell wall integrity. • Our study revealed a novel role for Imp2 in the Golgi/vacuolar membrane trafficking

  12. Imp2, the PSTPIP homolog in fission yeast, affects sensitivity to the immunosuppressant FK506 and membrane trafficking in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Kita, Ayako; Higa, Mari [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Doi, Akira [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472 (Japan); Satoh, Ryosuke [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Sugiura, Reiko, E-mail: sugiurar@phar.kindai.ac.jp [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan)

    2015-02-13

    Cytokinesis is a highly ordered process that divides one cell into two cells, which is functionally linked to the dynamic remodeling of the plasma membrane coordinately with various events such as membrane trafficking. Calcineurin is a highly conserved serine/threonine protein phosphatase, which regulates multiple biological functions, such as membrane trafficking and cytokinesis. Here, we isolated imp2-c3, a mutant allele of the imp2{sup +} gene, encoding a homolog of the mouse PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1), using a genetic screen for mutations that are synthetically lethal with calcineurin deletion in fission yeast. The imp2-c3 mutants showed a defect in cytokinesis with multi-septated phenotypes, which was further enhanced upon treatment with the calcineurin inhibitor FK506. Notably, electron micrographs revealed that the imp2-c3 mutant cells accumulated aberrant multi-lamella Golgi structures and putative post-Golgi secretory vesicles, and exhibited fragmented vacuoles in addition to thickened septa. Consistently, imp2-c3 mutants showed a reduced secretion of acid phosphatase and defects in vacuole fusion. The imp2-c3 mutant cells exhibited a weakened cell wall, similar to the membrane trafficking mutants identified in the same genetic screen such as ypt3-i5. These findings implicate the PSTPIP1 homolog Imp2 in Golgi/vacuole function, thereby affecting various cellular processes, including cytokinesis and cell integrity. - Highlights: • We isolated imp2-c3, in a synthetic lethal screen with calcineurin in fission yeast. • The imp2{sup +} gene encodes a component of the actin contractile ring similar to Cdc15. • The imp2-c3 mutants showed defects in cytokinesis, which were exacerbated by FK506. • The imp2-c3 mutants were defective in membrane trafficking and cell wall integrity. • Our study revealed a novel role for Imp2 in the Golgi/vacuolar membrane trafficking.

  13. Enhancers of Conidiation Mutants in Aspergillus Nidulans

    OpenAIRE

    Gems, D. H.; Clutterbuck, A. J.

    1994-01-01

    Mutants at a number of loci, designated sthenyo, have been isolated as enhancers of the oligoconidial mutations at the medA locus. Two loci have been mapped: sthA on linkage group I, and sthB on linkage group V. Two probable alleles have been identified at each locus but two further mutants were unlinked to either sthA or sthB. Neither sthA nor sthB mutants have conspicuous effects on morphology on their own, nor could the sthA1 sthB2 double mutant be distinguished from wild type. Mutants at ...

  14. Dwarf mutant of rice variety Seratus Malam

    International Nuclear Information System (INIS)

    Mugiono, P. S.; Soemanggono, A.M.R.

    1989-01-01

    Full text: Seeds of 'Seratus Malam', a local tall upland variety with long panicles and high yield potential were irradiated with 10-50 krad gamma rays in 1983. From 50,000 M 2 plants, 130 semidwarf mutants and 1 dwarf mutant were selected. The dwarf mutant M-362 was obtained from the 10 krad treatment. The mutant shows about 50% reduction in plant height, but also in number of productive tillers. Thus the yield per plant is also significantly less. However, the mutant gene is not allelic to DGWG and therefore may be useful in cross breeding. (author)

  15. Acetylcholine Receptor: Complex of Homologous Subunits

    Science.gov (United States)

    Raftery, Michael A.; Hunkapiller, Michael W.; Strader, Catherine D.; Hood, Leroy E.

    1980-06-01

    The acetylcholine receptor from the electric ray Torpedo californica is composed of five subunits; two are identical and the other three are structurally related to them. Microsequence analysis of the four polypeptides demonstrates amino acid homology among the subunits. Further sequence analysis of both membrane-bound and Triton-solubilized, chromatographically purified receptor gave the stoichiometry of the four subunits (40,000:50,000:60,000:65,000 daltons) as 2:1:1:1, indicating that this protein is a pentameric complex with a molecular weight of 255,000 daltons. Genealogical analysis suggests that divergence from a common ancestral gene occurred early in the evolution of the receptor. This shared ancestry argues that each of the four subunits plays a functional role in the receptor's physiological action.

  16. Regulation of Homologous Recombination by SUMOylation

    DEFF Research Database (Denmark)

    Pinela da Silva, Sonia Cristina

    , deletions, and genome rearrangements that can lead to cell death or cancer in humans. The post-translational modification by SUMO (small ubiquitinlike modifier) has proven to be an important regulator of HR and genome integrity, but the molecular mechanisms responsible for these roles are still unclear......Double-strand breaks (DSBs) are one of the most deleterious types of DNA lesions challenging genome integrity. The DNA damage response (DDR) promotes fast and effective detection and repair of the damaged DNA, leading to cell cycle arrest through checkpoint activation and the recruitment of repair...... factors such as the homologous recombination (HR) machinery. HR constitutes the main DSB repair pathway in Saccharomyces cerevisiae and despite being largely considered an error-free process and essential for genome stability, uncontrolled recombination can lead to loss of heterozygosity, translocations...

  17. Clustering evolving proteins into homologous families.

    Science.gov (United States)

    Chan, Cheong Xin; Mahbob, Maisarah; Ragan, Mark A

    2013-04-08

    Clustering sequences into groups of putative homologs (families) is a critical first step in many areas of comparative biology and bioinformatics. The performance of clustering approaches in delineating biologically meaningful families depends strongly on characteristics of the data, including content bias and degree of divergence. New, highly scalable methods have recently been introduced to cluster the very large datasets being generated by next-generation sequencing technologies. However, there has been little systematic investigation of how characteristics of the data impact the performance of these approaches. Using clusters from a manually curated dataset as reference, we examined the performance of a widely used graph-based Markov clustering algorithm (MCL) and a greedy heuristic approach (UCLUST) in delineating protein families coded by three sets of bacterial genomes of different G+C content. Both MCL and UCLUST generated clusters that are comparable to the reference sets at specific parameter settings, although UCLUST tends to under-cluster compositionally biased sequences (G+C content 33% and 66%). Using simulated data, we sought to assess the individual effects of sequence divergence, rate heterogeneity, and underlying G+C content. Performance decreased with increasing sequence divergence, decreasing among-site rate variation, and increasing G+C bias. Two MCL-based methods recovered the simulated families more accurately than did UCLUST. MCL using local alignment distances is more robust across the investigated range of sequence features than are greedy heuristics using distances based on global alignment. Our results demonstrate that sequence divergence, rate heterogeneity and content bias can individually and in combination affect the accuracy with which MCL and UCLUST can recover homologous protein families. For application to data that are more divergent, and exhibit higher among-site rate variation and/or content bias, MCL may often be the better

  18. More on homological supersymmetric quantum mechanics

    Science.gov (United States)

    Behtash, Alireza

    2018-03-01

    In this work, we first solve complex Morse flow equations for the simplest case of a bosonic harmonic oscillator to discuss localization in the context of Picard-Lefschetz theory. We briefly touch on the exact non-BPS solutions of the bosonized supersymmetric quantum mechanics on algebraic geometric grounds and report that their complex phases can be accessed through the cohomology of WKB 1-form of the underlying singular spectral curve subject to necessary cohomological corrections for nonzero genus. Motivated by Picard-Lefschetz theory, we write down a general formula for the index of N =4 quantum mechanics with background R -symmetry gauge fields. We conjecture that certain symmetries of the refined Witten index and singularities of the moduli space may be used to determine the correct intersection coefficients. A few examples, where this conjecture holds, are shown in both linear and closed quivers with rank-one quiver gauge groups. The R -anomaly removal along the "Morsified" relative homology cycles also called "Lefschetz thimbles" is shown to lead to the appearance of Stokes lines. We show that the Fayet-Iliopoulos parameters appear in the intersection coefficients for the relative homology of the quiver quantum mechanics resulting from dimensional reduction of 2 d N =(2 ,2 ) gauge theory on a circle and explicitly calculate integrals along the Lefschetz thimbles in N =4 C Pk -1 model. The Stokes jumping of coefficients and its relation to wall crossing phenomena is briefly discussed. We also find that the notion of "on-the-wall" index is related to the invariant Lefschetz thimbles under Stokes phenomena. An implication of the Lefschetz thimbles in constructing knots from quiver quantum mechanics is indicated.

  19. Diversity of the Lyman continuum escape fractions of high-z galaxies and its origins

    Science.gov (United States)

    Sumida, Takumi; Kashino, Daichi; Hasegawa, Kenji

    2018-04-01

    The Lyman continuum (LyC) escape fraction is a key quantity to determine the contribution of galaxies to cosmic reionization. It has been known that the escape fractions estimated by observations and numerical simulations show a large diversity. However, the origins of the diversity are still uncertain. In this work, to understand what quantities of galaxies are responsible for controlling the escape fraction, we numerically evaluate the escape fraction by performing ray-tracing calculation with simplified disc galaxy models. With a smooth disc model, we explore the dependence of the escape fraction on the disposition of ionizing sources and find that the escape fraction varies up to ˜3 orders of magnitude. It is also found that the halo mass dependence of disc scale height determines whether the escape fraction increases or decreases with halo mass. With a clumpy disc model, it turns out that the escape fraction increases as the clump mass fraction increases because the density in the inter-clump region decreases. In addition, we find that clumpiness regulates the escape fraction via two ways when the total clump mass dominates the total gas mass; the escape fraction is controlled by the covering factor of clumps if the clumps are dense sufficient to block LyC photons, otherwise the clumpiness works to reduce the escape fraction by increasing the total number of recombination events in a galaxy.

  20. Heteromorphic Sex Chromosomes: Navigating Meiosis without a Homologous Partner

    OpenAIRE

    Checchi, Paula M.; Engebrecht, JoAnne

    2011-01-01

    Accurate chromosome segregation during meiosis relies on homology between the maternal and paternal chromosomes. Yet by definition, sex chromosomes of the heterogametic sex lack a homologous partner. Recent studies in a number of systems have shed light on the unique meiotic behavior of heteromorphic sex chromosomes, and highlight both the commonalities and differences in divergent species. During meiotic prophase, the homology-dependent processes of pairing, synapsis, and recombination have ...

  1. A local homology theory for linearly compact modules

    International Nuclear Information System (INIS)

    Nguyen Tu Cuong; Tran Tuan Nam

    2004-11-01

    We introduce a local homology theory for linearly modules which is in some sense dual to the local cohomology theory of A. Grothendieck. Some basic properties of local homology modules are shown such as: the vanishing and non-vanishing, the noetherianness of local homology modules. By using duality, we extend some well-known results in theory of local cohomology of A. Grothendieck. (author)

  2. A sialidase mutant displaying trans-sialidase activity.

    Science.gov (United States)

    Paris, Gastón; Ratier, Laura; Amaya, María Fernanda; Nguyen, Tong; Alzari, Pedro M; Frasch, Alberto Carlos C

    2005-01-28

    Trypanosoma cruzi, the agent of Chagas disease, expresses a modified sialidase, the trans-sialidase, which transfers sialic acid from host glycoconjugates to beta-galactose present in parasite mucins. Another American trypanosome, Trypanosoma rangeli, expresses a homologous protein that has sialidase activity but is devoid of transglycosidase activity. Based on the recently determined structures of T.rangeli sialidase (TrSA) and T.cruzi trans-sialidase (TcTS), we have now constructed mutants of TrSA with the aim of studying the relevant residues in transfer activity. Five mutations, Met96-Val, Ala98-Pro, Ser120-Tyr, Gly249-Tyr and Gln284-Pro, were enough to obtain a sialidase mutant (TrSA(5mut)) with trans-sialidase activity; and a sixth mutation increased the activity to about 10% that of wild-type TcTS. The crystal structure of TrSA(5mut) revealed the formation of a trans-sialidase-like binding site for the acceptor galactose, primarily defined by the phenol group of Tyr120 and the indole ring of Trp313, which adopts a new conformation, similar to that in TcTS, induced by the Gln284-Pro mutation. The transition state analogue 2,3-didehydro-2-deoxy-N-acetylneuraminic acid (DANA), which inhibits sialidases but is a poor inhibitor of trans-sialidase, was used to probe the active site conformation of mutant enzymes. The results show that the presence of a sugar acceptor binding-site, the fine-tuning of protein-substrate interactions and the flexibility of crucial active site residues are all important to achieve transglycosidase activity from the TrSA sialidase scaffold.

  3. Colored Kauffman homology and super-A-polynomials

    International Nuclear Information System (INIS)

    Nawata, Satoshi; Ramadevi, P.; Zodinmawia

    2014-01-01

    We study the structural properties of colored Kauffman homologies of knots. Quadruple-gradings play an essential role in revealing the differential structure of colored Kauffman homology. Using the differential structure, the Kauffman homologies carrying the symmetric tensor products of the vector representation for the trefoil and the figure-eight are determined. In addition, making use of relations from representation theory, we also obtain the HOMFLY homologies colored by rectangular Young tableaux with two rows for these knots. Furthermore, the notion of super-A-polynomials is extended in order to encompass two-parameter deformations of PSL(2,ℂ) character varieties

  4. PNRI mutant variety: Cordyline 'Afable'

    International Nuclear Information System (INIS)

    Aurigue, Fernando B.

    2012-01-01

    Cordyline 'Afable', registered by the Philippine Nuclear Research Institute as NSIC 2009 Or-83, is an induced mutant developed from Cordyline 'Kiwi' by treating stem cuttings with acute gamma radiation from a Cobalt-60 source. The new mutant is identical to Cordyline 'Kiwi' in growth habit but differs in foliage color, and exhibits field resistance to Phytophthora sp., a fungus that causes leaf blight and rot in Ti plants. Results of this mutation breeding experiment showed that leaf color was altered by gamma irradiation and resistance to fungal diseases was improved. It also demonstrated how mutations that occur in nature may be generated artificially. Propagation of cordyline 'Afable' is true-to-type by vegetative propagation methods, such as separation of suckers and offshoots, shoot tip cutting, and top cutting. Aside from landscaping material, terrarium or dish-garden plant, it is ideal as containerized plant for indoor and outdoor use. The leaves or shoots may be harvested as cut foliage for flower arrangements. (author)

  5. Three homologous genes encoding sn-glycerol-3-phosphate acyltransferase 4 exhibit different expression patterns and functional divergence in Brassica napus.

    Science.gov (United States)

    Chen, Xue; Truksa, Martin; Snyder, Crystal L; El-Mezawy, Aliaa; Shah, Saleh; Weselake, Randall J

    2011-02-01

    Brassica napus is an allotetraploid (AACC) formed from the fusion of two diploid progenitors, Brassica rapa (AA) and Brassica oleracea (CC). Polyploidy and genome-wide rearrangement during the evolution process have resulted in genes that are present as multiple homologs in the B. napus genome. In this study, three B. napus homologous genes encoding endoplasmic reticulum-bound sn-glycerol-3-phosphate acyltransferase 4 (GPAT4) were identified and characterized. Although the three GPAT4 homologs share a high sequence similarity, they exhibit different expression patterns and altered epigenetic features. Heterologous expression in yeast further revealed that the three BnGPAT4 homologs encoded functional GPAT enzymes but with different levels of polypeptide accumulation. Complementation of the Arabidopsis (Arabidopsis thaliana) gpat4 gpat8 double mutant line with individual BnGPAT4 homologs suggested their physiological roles in cuticle formation. Analysis of gpat4 RNA interference lines of B. napus revealed that the BnGPAT4 deficiency resulted in reduced cutin content and altered stomatal structures in leaves. Our results revealed that the BnGPAT4 homologs have evolved into functionally divergent forms and play important roles in cutin synthesis and stomatal development.

  6. Escaping the Self: Identity, Group Identification and Violence

    Directory of Open Access Journals (Sweden)

    James Hardie-Bick

    2016-12-01

    Full Text Available This article draws on the early work of Erich Fromm. In Escape from Freedom Fromm (1969 [1941] directly addressed the psychological mechanisms of escape modern individuals employ to protect themselves from feelings of ontological insecurity and existential estrangement. The article builds on Fromm’s analysis by discussing the significance of his escape mechanisms for understanding the dynamic psychological attractions of identifying with entitative groups. Fromm’s work will be discussed in relation to Hogg’s recent work on uncertainty-identity theory. The aim of the article is to examine the advantages of combining Fromm’s psychoanalytic analysis with Hogg’s uncertainty-identity theory and to highlight the potential this approach has for understanding why groups engage in violent and destructive behaviour. Este artículo se inspira en las primeras obras de Erich Fromm. En El miedo a la libertad, Fromm (1969 [1941] abordó directamente los mecanismos psicológicos de evasión que los individuos modernos emplean para protegerse de los sentimientos de inseguridad ontológica y distanciamiento existencial. Este artículo se basa en el análisis de Fromm exponiendo el significado de sus mecanismos de evasión para entender las atracciones psicológicas dinámicas de identificación con grupos entitativos. Se analizará la obra de Fromm en relación con la obra reciente de Hogg sobre la teoría de incertidumbre identitaria. El objetivo del artículo es examinar las ventajas de combinar el análisis psicoanalítico de Fromm con la teoría de incertidumbre identitaria de Hogg, y destacar el potencial que tiene esta aproximación para comprender por qué los grupos adoptan un comportamiento violento y destructivo. DOWNLOAD THIS PAPER FROM SSRN: https://ssrn.com/abstract=2875737

  7. Role of teh Rad52 Amino-terminal DNA Binding Activity in DNA Strand Capture in Homologous Recombination

    DEFF Research Database (Denmark)

    Shi, Idina; Hallwyl, Swee Chuang Lim; Seong, Changhyun

    2009-01-01

    Saccharomyces cerevisiae Rad52 protein promotes homologous recombination by nucleating the Rad51 recombinase onto replication protein A-coated single-stranded DNA strands and also by directly annealing such strands. We show that the purified rad52-R70A mutant protein, with a compromised amino......-terminal DNA binding domain, is capable of Rad51 delivery to DNA but is deficient in DNA annealing. Results from chromatin immunoprecipitation experiments find that rad52-R70A associates with DNA double-strand breaks and promotes recruitment of Rad51 as efficiently as wild-type Rad52. Analysis of gene...... conversion intermediates reveals that rad52-R70A cells can mediate DNA strand invasion but are unable to complete the recombination event. These results provide evidence that DNA binding by the evolutionarily conserved amino terminus of Rad52 is needed for the capture of the second DNA end during homologous...

  8. Phenotypical and biochemical characterisation of resistance for parasitic weed (Orobanche foetida Poir.) in radiation-mutagenised mutants of chickpea.

    Science.gov (United States)

    Brahmi, Ines; Mabrouk, Yassine; Brun, Guillaume; Delavault, Philippe; Belhadj, Omrane; Simier, Philippe

    2016-12-01

    Some radiation-mutagenised chickpea mutants potentially resistant to the broomrape, Orobanche foetida Poir., were selected through field trials. The objectives of this work were to confirm resistance under artificial infestation, in pots and mini-rhizotron systems, and to determine the developmental stages of broomrape affected by resistance and the relevant resistance mechanisms induced by radiation mutagenesis. Among 30 mutants tested for resistance to O. foetida, five shared strong resistance in both pot experiments and mini-rhizotron systems. Resistance was not complete, but the few individuals that escaped resistance displayed high disorders of shoot development. Results demonstrated a 2-3-fold decrease in stimulatory activity of root exudates towards broomrape seed germination in resistant mutants in comparison with non-irradiated control plants and susceptible mutants. Resistance was associated with an induction of broomrape necrosis early during infection. When infested, most of the resistant mutants shared enhanced levels of soluble phenolic contents, phenylalanine ammonia lyase activity, guaiacol peroxidase activity and polyphenol oxidase activity, in addition to glutathione and notably ascorbate peroxidase gene expression in roots. Results confirmed enhanced resistance in chickpea radiation-mutagenised mutants, and demonstrated that resistance is based on alteration of root exudation, presumed cell-wall reinforcement and change in root oxidative status in response to infection. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  9. Chases and escapes the mathematics of pursuit and evasion

    CERN Document Server

    Nahin, Paul J

    2012-01-01

    We all played tag when we were kids. What most of us don't realize is that this simple chase game is in fact an application of pursuit theory, and that the same principles of games like tag, dodgeball, and hide-and-seek are also at play in military strategy, high-seas chases by the Coast Guard, and even romantic pursuits. In Chases and Escapes, Paul Nahin gives us the first complete history of this fascinating area of mathematics, from its classical analytical beginnings to the present day. Drawing on game theory, geometry, linear algebra, target-tracking algorithms, and much

  10. Mechanisms of Pulmonary Escape and Dissemination by Cryptococcus neoformans

    Directory of Open Access Journals (Sweden)

    Steven T. Denham

    2018-02-01

    Full Text Available Cryptococcus neoformans is a common environmental saprophyte and human fungal pathogen that primarily causes disease in immunocompromised individuals. Similar to many environmentally acquired human fungal pathogens, C. neoformans initiates infection in the lungs. However, the main driver of mortality is invasive cryptococcosis leading to fungal meningitis. After C. neoformans gains a foothold in the lungs, a critical early step in invasion is transversal of the respiratory epithelium. In this review, we summarize current knowledge relating to pulmonary escape. We focus on fungal factors that allow C. neoformans to disseminate from the lungs via intracellular and extracellular routes.

  11. Diffusion escape through a cluster of small absorbing windows

    Energy Technology Data Exchange (ETDEWEB)

    Holcman, D [Department of Mathematics, Weizmann Institute of Science, Rehovot 76100 (Israel); Schuss, Z [Department of Mathematics, Tel-Aviv University, Tel-Aviv 69978 (Israel)

    2008-04-18

    We study the first eigenvalue of the Laplace equation in a bounded domain in R{sup d} (d=2,3) with mixed Neumann-Dirichlet (Zaremba) boundary conditions. The Neumann condition is imposed on most of the boundary and the Dirichlet boundary consists of a cluster of small windows. When the windows are well separated the first eigenvalue is asymptotically the sum of eigenvalues of mixed problems with a single Dirichlet window. However, when two or more Dirichlet windows cluster tightly together they interact nonlinearly. We compare our asymptotic approximation of the eigenvalue to the escape rate of simulated Brownian particles through the small windows.

  12. Dynamics of Periodic Impulsive Collision in Escapement Mechanism

    Directory of Open Access Journals (Sweden)

    Jian Mao

    2013-01-01

    Full Text Available Among various non-smooth dynamic systems, the periodically forced oscillation system with impact is perhaps the most common in engineering applications. The dynamical study becomes complicated due to the impact. This paper presents a systematic study on the periodically forced oscillation system with impact. A simplified model of the escapement mechanism is introduced. Impulsive differential equation and Poincare map are applied to describe the model and study the stability of the system. Numerical examples are given and the results show that the model is highly accurate in describing/predicting their dynamics.

  13. The mirror of the escaped God – Alejandra Pizarnik

    Directory of Open Access Journals (Sweden)

    Mariano Carou

    2015-04-01

    Full Text Available Alejandra Pizarnik (1936-1972 shows many different stands regarding to “God’s escape” in her poetry and his diaries: from the psalmist’s request to the more combative atheism. There is, however, a constant development of a symbolic constellation to speak about God’s mistery, and the certitude –inherited from German romanticism– that the poet has always something to say about God’s escape, searching for a new hope in which is maybe a new form of mysticism.

  14. The mirror of the escaped God – Alejandra Pizarnik

    OpenAIRE

    Carou, Mariano

    2015-01-01

    Alejandra Pizarnik (1936-1972) shows many different stands regarding to “God’s escape” in her poetry and his diaries: from the psalmist’s request to the more combative atheism. There is, however, a constant development of a symbolic constellation to speak about God’s mistery, and the certitude –inherited from German romanticism– that the poet has always something to say about God’s escape, searching for a new hope in which is maybe a new form of mysticism. Alejandra Pizarnik (1936-1972) mu...

  15. The mirror of the escaped God – Alejandra Pizarnik

    OpenAIRE

    Mariano Carou

    2015-01-01

    Alejandra Pizarnik (1936-1972) shows many different stands regarding to “God’s escape” in her poetry and his diaries: from the psalmist’s request to the more combative atheism. There is, however, a constant development of a symbolic constellation to speak about God’s mistery, and the certitude –inherited from German romanticism– that the poet has always something to say about God’s escape, searching for a new hope in which is maybe a new form of mysticism.

  16. Test of time: what if little Albert had escaped?

    Science.gov (United States)

    Field, Andy P; Nightingale, Zoë C

    2009-04-01

    Watson and Rayner's (1920) ;Little Albert' experiment has become one of the most famous studies in psychology. It is a staple of many general psychology textbooks and is part of the very fabric of the discipline's folklore. Despite this fame, the study has been widely criticized in the nearly 90 years since it was published for its lack of methodological rigour. This article attempts to evaluate the contribution of the ;little Albert' study to modern clinical psychology by speculating on what theories and treatments of child anxiety would look like in a parallel universe in which the study never took place because ;little Albert' escaped from the hospital in which Watson tested him.

  17. International Environmental Agreements: Emissions Trade, Safety Valves and Escape Clauses

    International Nuclear Information System (INIS)

    Karp, Larry; Zhao, Jinhua

    2010-01-01

    We explain how the structure of multi-national or multi-regional environmental agreements affect their chance of success. Trade in emissions permits has ambiguous and in some cases surprising effects on both the equilibrium level of abatement, and on the ability to persuade nations or regions to participate in environmental agreements. An escape clause policy and a safety valve policy have essentially the same properties when membership in environmental agreement is pre-determined, but they create markedly different effects on the incentives to join such an agreement. The two policies lead to a qualitative difference in the leverage that a potential member of the agreement exercises on other members

  18. Gamma ray induced mutants in Coleus

    International Nuclear Information System (INIS)

    Vasudevan, K.; Jos, J.S.

    1988-01-01

    The germplasm collection of Chinese potato (Coleus parviflorus Benth) contains almost no variation for yield contributing traits. The crop does not produce seeds. Treatment of underground tubers with 1 kR, 2 kR, 3 kR and 4 kR gamma rays resulted in 50 morphologically different mutants which are maintained as mutant clones. In the M 1 V 1 generation, suspected mutant sprouts, were carefully removed and grown separately. The most interesting mutant types are the following: (i) erect mutant with spoon shaped light green leaves, 30 cm long inflorescences against 20 cm in the control, cylindrical tubers measuring ca. 7.0 cm long and 3 cm girth against 4 cm and 2.5 cm in the control (ii) early mutants 1 and 2, one having less leaf serration, the other having light green small leaves and dwarf type (iii) fleshy leaf mutant, dark green, thick and smooth leaves. Control plants spread almost in 1 m 2 area and bear tubers from the nodes of branches. In the early mutants tuber formation is mainly restricted to the base of the plant, which makes harvest easier. The crop usually matures within 150 - 160 days, the early mutants are ready for harvest 100 days after planting. As the mutants are less spreading, the yield could be increased by closer spacing

  19. A mechanistic understanding of allosteric immune escape pathways in the HIV-1 envelope glycoprotein.

    Directory of Open Access Journals (Sweden)

    Anurag Sethi

    Full Text Available The HIV-1 envelope (Env spike, which consists of a compact, heterodimeric trimer of the glycoproteins gp120 and gp41, is the target of neutralizing antibodies. However, the high mutation rate of HIV-1 and plasticity of Env facilitates viral evasion from neutralizing antibodies through various mechanisms. Mutations that are distant from the antibody binding site can lead to escape, probably by changing the conformation or dynamics of Env; however, these changes are difficult to identify and define mechanistically. Here we describe a network analysis-based approach to identify potential allosteric immune evasion mechanisms using three known HIV-1 Env gp120 protein structures from two different clades, B and C. First, correlation and principal component analyses of molecular dynamics (MD simulations identified a high degree of long-distance coupled motions that exist between functionally distant regions within the intrinsic dynamics of the gp120 core, supporting the presence of long-distance communication in the protein. Then, by integrating MD simulations with network theory, we identified the optimal and suboptimal communication pathways and modules within the gp120 core. The results unveil both strain-dependent and -independent characteristics of the communication pathways in gp120. We show that within the context of three structurally homologous gp120 cores, the optimal pathway for communication is sequence sensitive, i.e. a suboptimal pathway in one strain becomes the optimal pathway in another strain. Yet the identification of conserved elements within these communication pathways, termed inter-modular hotspots, could present a new opportunity for immunogen design, as this could be an additional mechanism that HIV-1 uses to shield vulnerable antibody targets in Env that induce neutralizing antibody breadth.

  20. Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein

    International Nuclear Information System (INIS)

    Bates, John T.; Keefer, Christopher J.; Slaughter, James C.; Kulp, Daniel W.; Schief, William R.; Crowe, James E.

    2014-01-01

    The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (K on ) for binding to RSV F protein, while alteration of dissociation rate (K off ) did not significantly affect neutralizing activity. Interestingly, linkage of reduced K on with reduced potency mirrored the effect of increased K on found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants. - Highlights: • The relationship of affinity to neutralization for virus antibodies is uncertain. • Palivizumab binds to RSV escape mutant fusion proteins, but with reduced affinity. • Association rate (K on ) correlated well with the potency of neutralization

  1. Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein

    Energy Technology Data Exchange (ETDEWEB)

    Bates, John T. [The Vanderbilt Vaccine Center, Departments of Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Keefer, Christopher J. [The Vanderbilt Vaccine Center, Departments of Pediatrics, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Slaughter, James C. [The Vanderbilt Vaccine Center, Departments of Biostatistics and Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Kulp, Daniel W. [IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA (United States); Schief, William R. [IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA (United States); Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA (United States); Crowe, James E., E-mail: james.crowe@vanderbilt.edu [The Vanderbilt Vaccine Center, Departments of Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); The Vanderbilt Vaccine Center, Departments of Pediatrics, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States)

    2014-04-15

    The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (K{sub on}) for binding to RSV F protein, while alteration of dissociation rate (K{sub off}) did not significantly affect neutralizing activity. Interestingly, linkage of reduced K{sub on} with reduced potency mirrored the effect of increased K{sub on} found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants. - Highlights: • The relationship of affinity to neutralization for virus antibodies is uncertain. • Palivizumab binds to RSV escape mutant fusion proteins, but with reduced affinity. • Association rate (K{sub on}) correlated well with the potency of neutralization.

  2. Homology-dependent Gene Silencing in Paramecium

    Science.gov (United States)

    Ruiz, Françoise; Vayssié, Laurence; Klotz, Catherine; Sperling, Linda; Madeddu, Luisa

    1998-01-01

    Microinjection at high copy number of plasmids containing only the coding region of a gene into the Paramecium somatic macronucleus led to a marked reduction in the expression of the corresponding endogenous gene(s). The silencing effect, which is stably maintained throughout vegetative growth, has been observed for all Paramecium genes examined so far: a single-copy gene (ND7), as well as members of multigene families (centrin genes and trichocyst matrix protein genes) in which all closely related paralogous genes appeared to be affected. This phenomenon may be related to posttranscriptional gene silencing in transgenic plants and quelling in Neurospora and allows the efficient creation of specific mutant phenotypes thus providing a potentially powerful tool to study gene function in Paramecium. For the two multigene families that encode proteins that coassemble to build up complex subcellular structures the analysis presented herein provides the first experimental evidence that the members of these gene families are not functionally redundant. PMID:9529389

  3. Sharing mutants and experimental information prepublication using FgMutantDb (https://scabusa.org/FgMutantDb).

    Science.gov (United States)

    Baldwin, Thomas T; Basenko, Evelina; Harb, Omar; Brown, Neil A; Urban, Martin; Hammond-Kosack, Kim E; Bregitzer, Phil P

    2018-02-02

    There is no comprehensive storage for generated mutants of Fusarium graminearum or data associated with these mutants. Instead, researchers relied on several independent and non-integrated databases. FgMutantDb was designed as a simple spreadsheet that is accessible globally on the web that will function as a centralized source of information on F. graminearum mutants. FgMutantDb aids in the maintenance and sharing of mutants within a research community. It will serve also as a platform for disseminating prepublication results as well as negative results that often go unreported. Additionally, the highly curated information on mutants in FgMutantDb will be shared with other databases (FungiDB, Ensembl, PhytoPath, and PHI-base) through updating reports. Here we describe the creation and potential usefulness of FgMutantDb to the F. graminearum research community, and provide a tutorial on its use. This type of database could be easily emulated for other fungal species. Published by Elsevier Inc.

  4. T-Cell Lymphoma Caused by Herpesvirus Saimiri C488 Independently of ie14/vsag, a Viral Gene with Superantigen Homology

    Science.gov (United States)

    Knappe, Andrea; Thurau, Mathias; Niphuis, Henk; Hiller, Christian; Wittmann, Sabine; Kuhn, Eva-Maria; Rosenwirth, Brigitte; Fleckenstein, Bernhard; Heeney, Jonathan; Fickenscher, Helmut

    1998-01-01

    The immediate-early gene ie14/vsag of herpesvirus saimiri has homology with murine superantigens. We compared the pathogenesis of infection with either ie14/vsag deletion mutants or wild-type virus C488 in cottontop tamarin monkeys (Saguinus oedipus). Two weeks after infection, all animals developed acute T-cell lymphomas independently of the presence of the viral ie14/vsag gene. PMID:9525684

  5. T-Cell Lymphoma Caused by Herpesvirus Saimiri C488 Independently of ie14/vsag, a Viral Gene with Superantigen Homology

    OpenAIRE

    Knappe, Andrea; Thurau, Mathias; Niphuis, Henk; Hiller, Christian; Wittmann, Sabine; Kuhn, Eva-Maria; Rosenwirth, Brigitte; Fleckenstein, Bernhard; Heeney, Jonathan; Fickenscher, Helmut

    1998-01-01

    The immediate-early gene ie14/vsag of herpesvirus saimiri has homology with murine superantigens. We compared the pathogenesis of infection with either ie14/vsag deletion mutants or wild-type virus C488 in cottontop tamarin monkeys (Saguinus oedipus). Two weeks after infection, all animals developed acute T-cell lymphomas independently of the presence of the viral ie14/vsag gene.

  6. A single amino acid substitution in the S1 and S2 Spike protein domains determines the neutralization escape phenotype of SARS-CoV.

    Science.gov (United States)

    Mitsuki, Yu-ya; Ohnishi, Kazuo; Takagi, Hirotaka; Oshima, Masamichi; Yamamoto, Takuya; Mizukoshi, Fuminori; Terahara, Kazutaka; Kobayashi, Kazuo; Yamamoto, Naoki; Yamaoka, Shoji; Tsunetsugu-Yokota, Yasuko

    2008-07-01

    In response to SARS-CoV infection, neutralizing antibodies are generated against the Spike (S) protein. Determination of the active regions that allow viral escape from neutralization would enable the use of these antibodies for future passive immunotherapy. We immunized mice with UV-inactivated SARS-CoV to generate three anti-S monoclonal antibodies, and established several neutralization escape mutants with S protein. We identified several amino acid substitutions, including Y442F and V601G in the S1 domain and D757N and A834V in the S2 region. In the presence of each neutralizing antibody, double mutants with substitutions in both domains exhibited a greater growth advantage than those with only one substitution. Importantly, combining two monoclonal antibodies that target different epitopes effected almost complete suppression of wild type virus replication. Thus, for effective passive immunotherapy, it is important to use neutralizing antibodies that recognize both the S1 and S2 regions.

  7. ARABIDOPSIS HOMOLOG of TRITHORAX1 (ATX1) is required for cell production, patterning, and morphogenesis in root development

    OpenAIRE

    Napsucialy-Mendivil, Selene; Alvarez-Venegas, Raúl; Shishkova, Svetlana; Dubrovsky, Joseph G.

    2014-01-01

    ARABIDOPSIS HOMOLOG of TRITHORAX1 (ATX1/SDG27), a known regulator of flower development, encodes a H3K4histone methyltransferase that maintains a number of genes in an active state. In this study, the role of ATX1 in root development was evaluated. The loss-of-function mutant atx1-1 was impaired in primary root growth. The data suggest that ATX1 controls root growth by regulating cell cycle duration, cell production, and the transition from cell proliferation in the root apical meristem (RAM)...

  8. Mutants for plant height in hexaploid triticale

    International Nuclear Information System (INIS)

    Reddy, V.R.K.; Gupta, P.K.

    1988-01-01

    Full text: Four hexaploid triticale varieties namely Beagle, Coorong, TL 419 and Welsh were subjected to gamma rays (100 Gy, 200 Gy, 300 Gy) and to aqueous solution of EMS (0.5%, (8h, 12h, 16h). In all four varieties, three types of mutants for plant height were observed: Semidwarf - the mutant plants are 20-25 cm shorter than the shortest plant in the control. Dwarf - mutant plants grow up to 40-60 cm. Stunted - mutant plants grow up to 10-20 cm. The segregation pattern suggests that semidwarf mutants are quantitatively inherited, showing continuous segregation in M 3 , M 4 and M 5 , whereas dwarf and stunted are monogenic recessive. They showed true breeding in M 3 and later generations. The semi-dwarf, dwarf and stunted mutants can be used as initial material for development of new varieties with short straw and resistance to lodging. (author)

  9. Quantification of Nociceptive Escape Response in C.elegans

    Science.gov (United States)

    Leung, Kawai; Mohammadi, Aylia; Ryu, William; Nemenman, Ilya

    2013-03-01

    Animals cannot rank and communicate their pain consciously. Thus in pain studies on animal models, one must infer the pain level from high precision experimental characterization of behavior. This is not trivial since behaviors are very complex and multidimensional. Here we explore the feasibility of C.elegans as a model for pain transduction. The nematode has a robust neurally mediated noxious escape response, which we show to be partially decoupled from other sensory behaviors. We develop a nociceptive behavioral response assay that allows us to apply controlled levels of pain by locally heating worms with an IR laser. The worms' motions are captured by machine vision programming with high spatiotemporal resolution. The resulting behavioral quantification allows us to build a statistical model for inference of the experienced pain level from the behavioral response. Based on the measured nociceptive escape of over 400 worms, we conclude that none of the simple characteristics of the response are reliable indicators of the laser pulse strength. Nonetheless, a more reliable statistical inference of the pain stimulus level from the measured behavior is possible based on a complexity-controlled regression model that takes into account the entire worm behavioral output. This work was partially supported by NSF grant No. IOS/1208126 and HFSP grant No. RGY0084/2011.

  10. Naloxone facilitates appetitive extinction and eliminates escape from frustration.

    Science.gov (United States)

    Norris, Jacob N; Pérez-Acosta, Andrés M; Ortega, Leonardo A; Papini, Mauricio R

    2009-11-01

    Two experiments tested the effects of opioid receptor blockage on behavior. In Experiment 1, rats reinforced for lever pressing with either sucrose or food pellets received treatment with saline, 2, and 10 mg/kg naloxone, i.p. (within-subject design). Naloxone 10 mg/kg increased response latency, but 2 mg/kg had no effect. When shifted to extinction (between-group design), naloxone (2 and 10 mg/kg) facilitated extinction relative to saline animals, after reinforcement with either sucrose or food pellets. In Experiment 2, after 10 sessions of access to 32% sucrose or an empty tube (between-group design), all rats were exposed to the empty tube while allowing them to jump over a barrier into a different compartment. Escape latencies were shorter for downshifted saline than for saline rats always given access to the empty tube. This escape-from-frustration effect was eliminated by naloxone (2 mg/kg, i.p.). Opioid blockage appears to reduce the value of alternative incentives.

  11. Ultra-fast Escape of a Octopus-inspired Rocket

    Science.gov (United States)

    Weymouth, Gabriel; Triantafyllou, Michael

    2013-11-01

    The octopus, squid, and other cephalopods inflate with water and then release a jet to accelerate in the opposite direction. This escape mechanism is particularly interesting in the octopus because they become initially quite bluff, yet this does not hinder them in achieving impressive bursts of speed. We examine this somewhat paradoxical maneuver using a simple deflating spheroid model in both potential and viscous flow. We demonstrate that the dynamic reduction of the width of the body completely changes the flow and forces acting on the escaping rocket in three ways. First, a body which reduces in size can generate an added mass thrust which counteracts the added mass inertia. Second, the motion of the shrinking wall acts similar to suction on a static wall, reducing separation and drag forces in a viscous fluid, but that this effects depends on the rate of size change. Third, using a combination of these two features it is possible to initially load the fluid with kinetic energy when heavy and bluff and then recover that energy when streamlined and light, enabling ultra-fast accelerations. As a notable example, these mechanisms allow a shrinking spheroid rocket in a heavy inviscid fluid to achieve speeds greater than an identical rocket in the vacuum of space. Southampton Marine and Maritime Institute.

  12. Specific transcription of an Acanthamoeba castellanii 5S RNA gene in homologous nuclear extracts.

    Science.gov (United States)

    Zwick, M G; Imboden, M A; Paule, M R

    1991-01-01

    An RNA polymerase III in vitro transcription system has been developed from the protist Acanthamoeba castellanii. The system is dependent on a cloned 5S RNA gene and utilizes a nuclear extract which contains all the necessary protein components. The system is assembled from completely homologous components. Primer extension and RNA sequencing analysis confirm that the in vitro 5S RNA transcript is identical to the 5S RNA isolated from cells. The transcription complex forms unusually rapidly on the 5S RNA gene and is stable to challenge by excess competitor templates. Several 5' deletion mutants were constructed and indicate that the region upstream of -33 is dispensable. Deletion to +16 show the region between -33 and +16 to be required for transcription, a region outside the canonical internal control region. Images PMID:2027775

  13. Gamma ray induced mutants in Colocasia

    International Nuclear Information System (INIS)

    Vasudevan, K.; Jos, J.S.

    1988-01-01

    Presented are selected treatments with 250 r, 500 r and 1000 r gamma rays Colocasia mutants with changes in morphological and yield characters. Results from a preliminary yield trial of four mutants with its control variety C 9 are presented. The mutant's characteristics are (i) erect and narrow leaf (ii) cup shaped leaf, dwarf, matures within 120 days against 180 days in control (iii) narrow and thicker leaves, colour of lamina chalky and pale green (iv) vigorous

  14. The Causes of Quasi-homologous CMEs

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Lijuan; Wang, Yuming; Liu, Rui; Zhou, Zhenjun; Liu, Jiajia; Liu, Kai; Shen, Chenglong; Zhang, Quanhao [CAS Key Laboratory of Geospace Environment, Department of Geophysics and Planetary Sciences, University of Science and Technology of China, Hefei, Anhui, 230026 (China); Temmer, M.; Thalmann, J. K.; Veronig, A. M., E-mail: ymwang@ustc.edu.cn, E-mail: ljliu@mail.ustc.edu.cn [Institute of Physics/IGAM, University of Graz, Universitätsplatz 5/II, A-8010 Graz (Austria)

    2017-08-01

    In this paper, we identified the magnetic source locations of 142 quasi-homologous (QH) coronal mass ejections (CMEs), of which 121 are from solar cycle (SC) 23 and 21 from SC 24. Among those CMEs, 63% originated from the same source location as their predecessor (defined as S-type), while 37% originated from a different location within the same active region as their predecessor (defined as D-type). Their distinctly different waiting time distributions, peaking around 7.5 and 1.5 hr for S- and D-type CMEs, suggest that they might involve different physical mechanisms with different characteristic timescales. Through detailed analysis based on nonlinear force-free coronal magnetic field modeling of two exemplary cases, we propose that the S-type QH CMES might involve a recurring energy release process from the same source location (by magnetic free energy replenishment), whereas the D-type QH CMEs can happen when a flux tube system is disturbed by a nearby CME.

  15. Controlling PTEN (Phosphatase and Tensin Homolog) Stability

    Science.gov (United States)

    Gupta, Amit

    2016-01-01

    Phosphatase and tensin homolog (PTEN) is a phosphoinositide lipid phosphatase and one of the most frequently disrupted tumor suppressors in many forms of cancer, with even small reductions in the expression levels of PTEN promoting cancer development. Although the post-translational ubiquitination of PTEN can control its stability, activity, and localization, a detailed understanding of how PTEN ubiquitination integrates with other cellular regulatory processes and may be dysregulated in cancer has been hampered by a poor understanding of the significance of ubiquitination at individual sites. Here we show that Lys66 is not required for cellular activity, yet dominates over other PTEN ubiquitination sites in the regulation of protein stability. Notably, combined mutation of other sites (Lys13, Lys80, and Lys289) has relatively little effect on protein expression, protein stability, or PTEN polyubiquitination. The present work identifies a key role for Lys66 in the regulation of PTEN expression and provides both an opportunity to improve the stability of PTEN as a protein therapy and a mechanistic basis for efforts to stabilize endogenous PTEN. PMID:27405757

  16. High speed homology search with FPGAs.

    Science.gov (United States)

    Yamaguchi, Yoshiki; Maruyama, Tsutomu; Konagaya, Akihiko

    2002-01-01

    We will introduce a way how we can achieve high speed homology search by only adding one off-the-shelf PCI board with one Field Programmable Gate Array (FPGA) to a Pentium based computer system in use. FPGA is a reconfigurable device, and any kind of circuits, such as pattern matching program, can be realized in a moment. The performance is almost proportional to the size of FPGA which is used in the system, and FPGAs are becoming larger and larger following Moore's law. We can easily obtain latest/larger FPGAs in the form off-the-shelf PCI boards with FPGAs, at low costs. The result which we obtained is as follows. The performance is most comparable with small to middle class dedicated hardware systems when we use a board with one of the latest FPGAs and the performance can be furthermore accelerated by using more number of FPGA boards. The time for comparing a query sequence of 2,048 elements with a database sequence of 64 million elements by the Smith-Waterman algorithm is about 34 sec, which is about 330 times faster than a desktop computer with a 1 GHz Pentium III. We can also accelerate the performance of a laptop computer using a PC card with one smaller FPGA. The time for comparing a query sequence (1,024) with the database sequence (64 million) is about 185 sec, which is about 30 times faster than the desktop computer.

  17. Regulation of homologous recombination at telomeres in budding yeast

    DEFF Research Database (Denmark)

    Eckert-Boulet, Nadine; Lisby, Michael

    2010-01-01

    Homologous recombination is suppressed at normal length telomere sequences. In contrast, telomere recombination is allowed when telomeres erode in the absence of telomerase activity or as a consequence of nucleolytic degradation or incomplete replication. Here, we review the mechanisms...... that contribute to regulating mitotic homologous recombination at telomeres and the role of these mechanisms in signalling short telomeres in the budding yeast Saccharomyces cerevisiae....

  18. Dynamic protein assemblies in homologous recombination with single DNA molecules

    NARCIS (Netherlands)

    van der Heijden, A.H.

    2007-01-01

    What happens when your DNA breaks? This thesis describes experimental work on the single-molecule level focusing on the interaction between DNA and DNA-repair proteins, in particular bacterial RecA and human Rad51, involved in homologous recombination. Homologous recombination and its central event

  19. Induction of osteogenesis by demineralized homologous and xenograft bone matrix

    Directory of Open Access Journals (Sweden)

    Dall'Agnol Rosiris

    2003-01-01

    Full Text Available The osteogenesis induction by demineralized bone matrix grafts remains as a challenge in the reconstructions of the mandible through homologous and xenografts or in implants in abdominal muscle. PURPOSE: Observed the behaviour of implants of demineralized bone matrix at the mandible (right side with homologous graft and left side with xenograft of pig. METHODS: Experimental study with homologous and heterologous implants of demineralized bone matrix at the mandible and in ectopic muscle at the Center of Experimental Surgery of Heliopolis Hospital, Hosphel, São Paulo, Brazil. In 6 white New Zeland rabbits, 46 grafts were performed being 23 with homologous (rabbit and 23 with xenograft (pig. 12 homologous implants (6 at the right side of the mandible and 6 at abdominal muscle of the rabbit and 12 heterologous implants of pigs (6 at the left side of the mandible and 6 at abdominal muscle rabbit were performed with demineralized bone matrix. RESULTS: Osteogenesis was assessed through histologic features after 30 and 60 days. After 1 rabbit dead, osteogenesis (mandible were detected in 9 of 11 (82% rabbits that received homologous matrix, in spite of heterologous implants showed osteogenesis in 6 out of 11 (54% (p=0,18. The abdominal muscle showed induced osteogenesis in 3 out of 11(27% animals with homologous and 0% with heterologous implants (p=0,10. CONCLUSIONS: Osteogenesis induction through homologous grafts in rabbit mandible and abdominal muscle were more effective than xenografts.

  20. Synergistic interactions between RAD5, RAD16, and RAD54, three partially homologous yeast DNA repair genes each in a different repair pathway

    International Nuclear Information System (INIS)

    Glassner, B.J.; Mortimer, R.K.

    1994-01-01

    Considerable homology has recently been noted between the proteins encoded by the RAD5, RAD16 and RAD54 genes of Saccharomyces cerevisiae. These genes are members of the RAD6, RAD3 and RAD50 epistasis groups, respectively, which correspond to the three major DNA repair pathways in yeast. These proteins also share homology with other eucaryotic proteins, including those encoded by SNF2 and MO1 of yeast, brahma and lodestar of Drosophila and the human ERCC6 gene. The homology shares features with known helicases, suggesting a newly identified helicase subfamily. We have constructed a series of congenic single-, double- and triple-deletion mutants involving RAD5, RAD16 and RAD54 to examine the interactions between these genes. Each deletion mutation alone has only a moderate effect on survival after exposure to UV radiation. Each pairwise-double mutant exhibits marked synergism. The triple-deletion mutant displays further synergism. These results confirm the assignment of the RAD54 gene to the RAD50 epistasis group and suggest that the RAD16 gene plays a larger role in DNA repair after exposure to UV radiation than has been suggested previously. Additionally, the proteins encoded by RAD5, RAD16, and RAD54 may compete for the same substrate after damage induced by UV radiation, possibly at an early step in their respective pathways. 49 refs., 6 figs., 2 tabs

  1. Assessment of immunity against avian colibacillosis induced by an aroA mutant containing increased serum survival gene in broilers

    Directory of Open Access Journals (Sweden)

    Taghi Zahraei Salehi

    2012-03-01

    Full Text Available Colibacillosis is an important disease in the poultry industry which causes serious economic damages. As it is suggested that vaccination is one of the means to control colibacillosis, we tried to investigate the vaccine potential of a ΔaroA derivative of an O78:K80 avian pathogenic Escherichia coli containing increased serum survival gene. 490 chicks were selected as follows: For assessment of virulence of ΔaroA mutant, 30 chicks were divided into three groups and injected with 0.5ml of PBS or bacterial suspension containing either10(7colony forming units (CFU of mutant or parent strains via subcutaneous route. Macroscopic lesions and mortality rate were recorded in different groups during the week after challenge. For assessment of safety and immunogenicity of the ΔaroA mutant, three groups of 20 chicks were vaccinated by aerosol administration of 250 ml of suspension containing 10(8 CFU of mutant strain at days 1 and 14, while the two other groups received PBS or wild type strain. Macroscopic lesions and mortality rate were recorded in different groups until day 21. To determine whether the vaccination is protective against challenges or not, the chickens were vaccinated at days 1 and 14 and challenged intramuscularly with either a homologous or heterologous strains at day 21. Macroscopic lesions and mortality rate were recorded in different groups during the week after challenge. The results revealed that the ΔaroA mutant was slightly virulent, however it was safe and did not cause mortality, lesions or weight loss after vaccination. Antibody responses were similar in the control and mutant groups and vaccination did not induce a significant humoral immunity. The mutant could not protect chickens against both homologous and heterologous challenges. This could be due to several factors such as the high amount of maternal antibodies in the first two weeks of life, and the vaccination procedure.

  2. Statistical Inference for Porous Materials using Persistent Homology.

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Chul [Univ. of Georgia, Athens, GA (United States); Heath, Jason E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mitchell, Scott A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-12-01

    We propose a porous materials analysis pipeline using persistent homology. We rst compute persistent homology of binarized 3D images of sampled material subvolumes. For each image we compute sets of homology intervals, which are represented as summary graphics called persistence diagrams. We convert persistence diagrams into image vectors in order to analyze the similarity of the homology of the material images using the mature tools for image analysis. Each image is treated as a vector and we compute its principal components to extract features. We t a statistical model using the loadings of principal components to estimate material porosity, permeability, anisotropy, and tortuosity. We also propose an adaptive version of the structural similarity index (SSIM), a similarity metric for images, as a measure to determine the statistical representative elementary volumes (sREV) for persistence homology. Thus we provide a capability for making a statistical inference of the uid ow and transport properties of porous materials based on their geometry and connectivity.

  3. Sequence and functional analysis of a homolog of interleukin-10 encoded by the parapoxvirus orf virus.

    Science.gov (United States)

    Fleming, S B; Haig, D M; Nettleton, P; Reid, H W; McCaughan, C A; Wise, L M; Mercer, A

    2000-01-01

    Orf virus is a large DNA virus and is the type species of the Parapoxvirus genus of the family Poxviridae. Orf virus infects the epithelium of sheep and goats and is transmissible to humans. Recently we discovered a gene in orf virus that encodes a polypeptide with remarkable homology to mammalian interleukin (IL-10) and viral encoded IL-10s of herpes viruses. The predicted polypeptide sequence shows high levels of amino acid identity to IL-10 of sheep (80%), cattle (75%), humans (67%) and mice (64%), as well as IL-10-like proteins of Epstein-Barr virus (63%) and equine herpes virus (67%). The C-terminal region, comprising two-thirds of the orf virus protein, is identical to ovine IL-10 which suggests that this gene has been captured from its host sheep during the evolution of orf virus. In contrast the N-terminal region shows little homology with cellular IL10s and in this respect resembles other viral IL-10s. IL-10 is a pleiotrophic cytokine that can exert either immunostimulatory or immunosuppressive effects on many cell types. IL-10 is a potent anti-inflammatory cytokine with inhibitory effects on non-specific immunity in particular macrophage function and Thl effector function. Our studies so far, indicate, that the functional activities of orf virus IL-10 are the same as ovine IL-10. Orf virus IL-10 stimulates mouse thymocyte proliferation and inhibits cytokine synthesis in lipopolysaccharide-activated ovine macrophages, peripheral blood monocytes and keratinocytes. Infection of sheep with an IL-10 deletion mutant of orf virus has shown that interferon-gamma levels are higher in tissue infected with the mutant virus than the parent virus. The functional activities of IL-10 and our data on orf virus IL-10 suggest a role in immune evasion.

  4. Orbital and escape dynamics in barred galaxies - III. The 3D system: correlations between the basins of escape and the NHIMs

    Science.gov (United States)

    Zotos, Euaggelos E.; Jung, Christof

    2018-01-01

    The escape dynamics of the stars in a barred galaxy composed of a spherically symmetric central nucleus, a bar, a flat thin disc and a dark matter halo component is investigated by using a realistic three degrees of freedom (3-d.o.f.) dynamical model. Modern colour-coded diagrams are used for distinguishing between bounded and escaping motion. In addition, the smaller alignment index method is deployed for determining the regular, sticky or chaotic nature of bounded orbits. We reveal the basins of escape corresponding to the escape through the two symmetrical escape channels around the Lagrange points L2 and L3 and also we relate them with the corresponding distribution of the escape times of the orbits. Furthermore, we demonstrate how the stable manifolds, around the index-1 saddle points, accurately define the fractal basin boundaries observed in the colour-coded diagrams. The development scenario of the fundamental vertical Lyapunov periodic orbit is thoroughly explored for obtaining a more complete view of the unfolding of the singular behaviour of the dynamics at the cusp values of the parameters. Finally, we examine how the combination of the most important parameters of the bar (such as the semimajor axis and the angular velocity) influences the observed stellar structures (rings and spirals), which are formed by escaping stars guided by the invariant manifolds near the saddle points.

  5. Integrating geographical information and augmented reality techniques for mobile escape guidelines on nuclear accident sites

    International Nuclear Information System (INIS)

    Tsai, Ming-Kuan; Lee, Yung-Ching; Lu, Chung-Hsin; Chen, Mei-Hsin; Chou, Tien-Yin; Yau, Nie-Jia

    2012-01-01

    During nuclear accidents, when radioactive materials spread into the environment, the people in the affected areas should evacuate immediately. However, few information systems are available regarding escape guidelines for nuclear accidents. Therefore, this study constructs escape guidelines on mobile phones. This application is called Mobile Escape Guidelines (MEG) and adopts two techniques. One technique is the geographical information that offers multiple representations; the other is the augmented reality that provides semi-realistic information services. When this study tested the mobile escape guidelines, the results showed that this application was capable of identifying the correct locations of users, showing the escape routes, filtering geographical layers, and rapidly generating the relief reports. Users could evacuate from nuclear accident sites easily, even without relief personnel, since using slim devices to access the mobile escape guidelines is convenient. Overall, this study is a useful reference for a nuclear accident emergency response.

  6. Transformation of Aspergillus parasiticus with a homologous gene (pyrG) involved in pyrimidine biosynthesis

    International Nuclear Information System (INIS)

    Skory, C.D.; Horng, J.S.; Pestka, J.J.; Linz, J.E.

    1990-01-01

    The lack of efficient transformation methods for aflatoxigenic Aspergillus parasiticus has been a major constraint for the study of aflatoxin biosynthesis at the genetic level. A transformation system with efficiencies of 30 to 50 stable transformants per μg of DNA was developed for A. parasiticus by using homologous pyrG gene. The pyrG gene from A. parasiticus was isolated by in situ plaque hybridization of a lambda genomic DNA library. Uridine auxotrophs of A. parasiticus ATCC 36537, a mutant blocked in aflatoxin biosynthesis, were isolated by selection on 5-fluoroorotic acid following nitrosoguanidine mutagenesis. Isolates with mutations in the pyrG gene resulting in elimination of orotidine monophosphate (OMP) decarboxylase activity were detected by assaying cell extracts for their ability to convert [ 14 C]OMP to [ 14 C]UMP. Transformation of A. parasiticus pyrG protoplasts with the homologous pyrG gene restored the fungal cells to prototrophy. Enzymatic analysis of cell extracts of transformant clones demonstrated that these extracts had the ability to convert [ 14 C]OMP to [ 14 C]UMP. Southern analysis of DNA purified from transformant clones indicated that both pUC19 vector sequences and pyrG sequences were integrated into the genome. The development of this pyrG transformation system should allow cloning of the aflatoxin-biosynthetic genes, which will be useful in studying the regulation of aflatoxin biosynthesis and may ultimately provide a means for controlling aflatoxin production in the field

  7. Mutagenic Organized Recombination Process by Homologous IN vivo Grouping (MORPHING) for directed enzyme evolution.

    Science.gov (United States)

    Gonzalez-Perez, David; Molina-Espeja, Patricia; Garcia-Ruiz, Eva; Alcalde, Miguel

    2014-01-01

    Approaches that depend on directed evolution require reliable methods to generate DNA diversity so that mutant libraries can focus on specific target regions. We took advantage of the high frequency of homologous DNA recombination in Saccharomyces cerevisiae to develop a strategy for domain mutagenesis aimed at introducing and in vivo recombining random mutations in defined segments of DNA. Mutagenic Organized Recombination Process by Homologous IN vivo Grouping (MORPHING) is a one-pot random mutagenic method for short protein regions that harnesses the in vivo recombination apparatus of yeast. Using this approach, libraries can be prepared with different mutational loads in DNA segments of less than 30 amino acids so that they can be assembled into the remaining unaltered DNA regions in vivo with high fidelity. As a proof of concept, we present two eukaryotic-ligninolytic enzyme case studies: i) the enhancement of the oxidative stability of a H2O2-sensitive versatile peroxidase by independent evolution of three distinct protein segments (Leu28-Gly57, Leu149-Ala174 and Ile199-Leu268); and ii) the heterologous functional expression of an unspecific peroxygenase by exclusive evolution of its native 43-residue signal sequence.

  8. The homologous recombination machinery modulates the formation of RNA–DNA hybrids and associated chromosome instability

    Science.gov (United States)

    Wahba, Lamia; Gore, Steven K; Koshland, Douglas

    2013-01-01

    Genome instability in yeast and mammals is caused by RNA–DNA hybrids that form as a result of defects in different aspects of RNA biogenesis. We report that in yeast mutants defective for transcription repression and RNA degradation, hybrid formation requires Rad51p and Rad52p. These proteins normally promote DNA–DNA strand exchange in homologous recombination. We suggest they also directly promote the DNA–RNA strand exchange necessary for hybrid formation since we observed accumulation of Rad51p at a model hybrid-forming locus. Furthermore, we provide evidence that Rad51p mediates hybridization of transcripts to homologous chromosomal loci distinct from their site of synthesis. This hybrid formation in trans amplifies the genome-destabilizing potential of RNA and broadens the exclusive co-transcriptional models that pervade the field. The deleterious hybrid-forming activity of Rad51p is counteracted by Srs2p, a known Rad51p antagonist. Thus Srs2p serves as a novel anti-hybrid mechanism in vivo. DOI: http://dx.doi.org/10.7554/eLife.00505.001 PMID:23795288

  9. Homology directed repair is unaffected by the absence of siRNAs in Drosophila melanogaster.

    Science.gov (United States)

    Schmidts, Ines; Böttcher, Romy; Mirkovic-Hösle, Milijana; Förstemann, Klaus

    2016-09-30

    Small interfering RNAs (siRNAs) defend the organism against harmful transcripts from exogenous (e.g. viral) or endogenous (e.g. transposons) sources. Recent publications describe the production of siRNAs induced by DNA double-strand breaks (DSB) in Neurospora crassa, Arabidopsis thaliana, Drosophila melanogaster and human cells, which suggests a conserved function. A current hypothesis is that break-induced small RNAs ensure efficient homologous recombination (HR). However, biogenesis of siRNAs is often intertwined with other small RNA species, such as microRNAs (miRNAs), which complicates interpretation of experimental results. In Drosophila, siRNAs are produced by Dcr-2 while miRNAs are processed by Dcr-1. Thus, it is possible to probe siRNA function without miRNA deregulation. We therefore examined DNA double-strand break repair after perturbation of siRNA biogenesis in cultured Drosophila cells as well as mutant flies. Our assays comprised reporters for the single-strand annealing pathway, homologous recombination and sensitivity to the DSB-inducing drug camptothecin. We could not detect any repair defects caused by the lack of siRNAs derived from the broken DNA locus. Since production of these siRNAs depends on local transcription, they may thus participate in RNA metabolism-an established function of siRNAs-rather than DNA repair. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Disparate requirements for the Walker A and B ATPase motifs ofhuman RAD51D in homologous recombination

    Energy Technology Data Exchange (ETDEWEB)

    Wiese, Claudia; Hinz, John M.; Tebbs, Robert S.; Nham, Peter B.; Urbin, Salustra S.; Collins, David W.; Thompson, Larry H.; Schild, David

    2006-04-21

    In vertebrates, homologous recombinational repair (HRR) requires RAD51 and five RAD51 paralogs (XRCC2, XRCC3, RAD51B, RAD51C, and RAD51D) that all contain conserved Walker A and B ATPase motifs. In human RAD51D we examined the requirement for these motifs in interactions with XRCC2 and RAD51C, and for survival of cells in response to DNA interstrand crosslinks. Ectopic expression of wild type human RAD51D or mutants having a non-functional A or B motif was used to test for complementation of a rad51d knockout hamster CHO cell line. Although A-motif mutants complement very efficiently, B-motif mutants do not. Consistent with these results, experiments using the yeast two- and three-hybrid systems show that the interactions between RAD51D and its XRCC2 and RAD51C partners also require a functional RAD51D B motif, but not motif A. Similarly, hamster Xrcc2 is unable to bind to the non-complementing human RAD51D B-motif mutants in co-immunoprecipitation assays. We conclude that a functional Walker B motif, but not A motif, is necessary for RAD51D's interactions with other paralogs and for efficient HRR. We present a model in which ATPase sites are formed in a bipartite manner between RAD51D and other RAD51 paralogs.

  11. Cancer associated E17K mutation causes rapid conformational drift in AKT1 pleckstrin homology (PH domain.

    Directory of Open Access Journals (Sweden)

    Ambuj Kumar

    Full Text Available BACKGROUND: AKT1 (v-akt murine thymoma viral oncogene homologue 1 kinase is one of the most frequently activated proliferated and survival pathway of cancer. Recently it has been shown that E17K mutation in the Pleckstrin Homology (PH domain of AKT1 protein leads to cancer by amplifying the phosphorylation and membrane localization of protein. The mutant has shown resistance to AKT1/2 inhibitor VIII drug molecule. In this study we have demonstrated the detailed structural and molecular consequences associated with the activity regulation of mutant protein. METHODS: The docking score exhibited significant loss in the interaction affinity to AKT1/2 inhibitor VIII drug molecule. Furthermore, the molecular dynamics simulation studies presented an evidence of rapid conformational drift observed in mutant structure. RESULTS: There was no stability loss in mutant as compared to native structure and the major cation-π interactions were also shown to be retained. Moreover, the active residues involved in membrane localization of protein exhibited significant rise in NHbonds formation in mutant. The rise in NHbond formation in active residues accounts for the 4-fold increase in the membrane localization potential of protein. CONCLUSION: The overall result suggested that, although the mutation did not induce any stability loss in structure, the associated pathological consequences might have occurred due to the rapid conformational drifts observed in the mutant AKT1 PH domain. GENERAL SIGNIFICANCE: The methodology implemented and the results obtained in this work will facilitate in determining the core molecular mechanisms of cancer-associated mutations and in designing their potential drug inhibitors.

  12. Metazoan Scc4 homologs link sister chromatid cohesion to cell and axon migration guidance.

    Directory of Open Access Journals (Sweden)

    Vlad C Seitan

    2006-07-01

    Full Text Available Saccharomyces cerevisiae Scc2 binds Scc4 to form an essential complex that loads cohesin onto chromosomes. The prevalence of Scc2 orthologs in eukaryotes emphasizes a conserved role in regulating sister chromatid cohesion, but homologs of Scc4 have not hitherto been identified outside certain fungi. Some metazoan orthologs of Scc2 were initially identified as developmental gene regulators, such as Drosophila Nipped-B, a regulator of cut and Ultrabithorax, and delangin, a protein mutant in Cornelia de Lange syndrome. We show that delangin and Nipped-B bind previously unstudied human and fly orthologs of Caenorhabditis elegans MAU-2, a non-axis-specific guidance factor for migrating cells and axons. PSI-BLAST shows that Scc4 is evolutionarily related to metazoan MAU-2 sequences, with the greatest homology evident in a short N-terminal domain, and protein-protein interaction studies map the site of interaction between delangin and human MAU-2 to the N-terminal regions of both proteins. Short interfering RNA knockdown of human MAU-2 in HeLa cells resulted in precocious sister chromatid separation and in impaired loading of cohesin onto chromatin, indicating that it is functionally related to Scc4, and RNAi analyses show that MAU-2 regulates chromosome segregation in C. elegans embryos. Using antisense morpholino oligonucleotides to knock down Xenopus tropicalis delangin or MAU-2 in early embryos produced similar patterns of retarded growth and developmental defects. Our data show that sister chromatid cohesion in metazoans involves the formation of a complex similar to the Scc2-Scc4 interaction in the budding yeast. The very high degree of sequence conservation between Scc4 homologs in complex metazoans is consistent with increased selection pressure to conserve additional essential functions, such as regulation of cell and axon migration during development.

  13. Scarless and sequential gene modification in Pseudomonas using PCR product flanked by short homology regions

    Directory of Open Access Journals (Sweden)

    Liang Rubing

    2010-08-01

    Full Text Available Abstract Background The lambda Red recombination system has been used to inactivate chromosomal genes in various bacteria and fungi. The procedure consists of electroporating a polymerase chain reaction (PCR fragment containing antibiotic cassette flanked by homology regions to the target locus into a strain that can express the lambda Red proteins (Gam, Bet, Exo. Results Here a scarless gene modification strategy based on the Red recombination system has been developed to modify Pseudomonas genome DNA via sequential deletion of multiple targets. This process was mediated by plasmid pRKaraRed encoding the Red proteins regulated by PBAD promoter, which was functional in P. aeruginosa as well as in other bacteria. First the target gene was substituted for the sacB-bla cassette flanked by short homology regions (50 bp, and then this marker gene cassette could be replaced by the PCR fragment flanking itself, generating target-deleted genome without any remnants and no change happened to the surrounding region. Twenty genes involved in the synthesis and regulation pathways of the phenazine derivate, pyocyanin, were modified, including one single-point mutation and deletion of two large operons. The recombination efficiencies ranged from 88% to 98%. Multiple-gene modification was also achieved, generating a triple-gene deletion strain PCA (PAO1, ΔphzHΔphzMΔphzS, which could produce another phenazine derivate, phenazine-1-carboxylic acid (PCA, efficiently and exclusively. Conclusions This lambda Red-based technique can be used to generate scarless and sequential gene modification mutants of P. aeruginosa efficiently, using one-step PCR product flanked by short homology regions. Single-point mutation, scarless deletion of genes can be achieved easily in less than three days. This method may give a new way to construct genetically modified P. aeruginosa strains more efficiently and advance the regulatory network study of this organism.

  14. A Practical Guide to Molecular Docking and Homology Modelling for Medicinal Chemists.

    Science.gov (United States)

    Lohning, Anna E; Levonis, Stephan M; Williams-Noonan, Billy; Schweiker, Stephanie S

    2017-01-01

    Elucidating details of the relationship between molecular structure and a particular biological end point is essential for successful, rational drug discovery. Molecular docking is a widely accepted tool for lead identification however, navigating the intricacies of the software can be daunting. Our objective was therefore to provide a step-by-step guide for those interested in incorporating contemporary basic molecular docking and homology modelling into their design strategy. Three molecular docking programs, AutoDock4, SwissDock and Surflex-Dock, were compared in the context of a case study where a set of steroidal and non-steroidal ligands were docked into the human androgen receptor (hAR) using both rigid and flexible target atoms. Metrics for comparison included how well each program predicted the X-ray structure orientation via root mean square deviation (rmsd), predicting known actives via ligand ranking and comparison to biological data where available. Benchmarking metrics were discussed in terms of identifying accurate and reliable results. For cases where no three dimensional structure exists, we provided a practical example for creating a homology model using Swiss-Model. Results showed an rmsd between X-ray ligands from wild-type and mutant receptors and docked poses were 4.15Å and 0.83Å (SwissDock), 2.69Å and 8.80Å (AutoDock4) and 0.39Å and 0.71Å (Surflex-Dock) respectively. Surflex-Dock performed consistently well in pose prediction (less than 2Å) while Auto- Dock4 predicted known active non-steroidal antiandrogens most accurately. Introducing flexibility into target atoms produced the largest degree of change in ligand ranking in Surflex-Dock. We produced a viable homology model of the P2X1 purireceptor for subsequent docking analysis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Peridinialean dinoflagellate plate patterns, labels and homologies

    Science.gov (United States)

    Edwards, L.E.

    1990-01-01

    Tabulation patterns for peridinialean dinoflagellate thecae and cysts have been traditionally expressed using a plate labelling system described by C.A. Kofoid in the early 1900's. This system can obscure dinoflagellate plate homologies and has not always been strictly applied. The plate-labelling system presented here introduces new series labels but incorporates key features and ideas from the more recently proposed systems of G.L. Eaton and F.J.R. Taylor, as modified by W.R. Evitt. Plate-series recognition begins with the cingulum (C-series) and proceeds from the cingulum toward the apex for the three series of the epitheca/epicyst and proceeds from the cingulum toward the antapex for the two series of the hypotheca/hypocyst. The epithecal/epicystal model consists of eight plates that touch the anterior margin of the cingulum (E-series: plates E1-E7, ES), seven plates toward the apex that touch the E-series plates (M-series: R, M1-M6), and up to seven plates near the apex that do not touch E-series plates (D-series: Dp-Dv). The hypothecal/hypocystal model consists of eight plates that touch the posterior margin of the cingulum (H-series: H1-H6,HR,HS) and three plates toward the antapex (T1-T3). Epithecal/epicystal tabulation patterns come in both 8- and 7- models, corresponding to eight and seven plates, respectively, in the E-series. Hypothecal/hypocystal tabulation patterns also come in both 8- and 7-models, corresponding to eight and seven plates, respectively, in the H-series. By convention, the 7-model epitheca/epicyst has no plates E1 and M1; the 7-model hypotheca/hypocyst has no plate H6. Within an 8-model or 7-model, the system emphasizes plates that are presumed to be homologous by giving them identical labels. I introduce the adjectives "monothigmate", "dithigmate," and "trithigmate" to designate plates touching one, two, and three plates, respectively, of the adjacent series. The term "thigmation" applies to the analysis of plate contacts between

  16. Homology-dependent repair is involved in 45S rDNA loss in plant CAF-1 mutants

    Czech Academy of Sciences Publication Activity Database

    Muchová, V.; Amiard, S.; Mozgová, I.; Dvořáčková, Martina; Gallego, M.E.; White, C.; Fajkus, Jiří

    2015-01-01

    Roč. 81, č. 2 (2015), s. 198-209 ISSN 0960-7412 R&D Projects: GA ČR(CZ) GP13-11563P Institutional support: RVO:68081707 Keywords : DNA repair * genome instability * 45S rDNA Subject RIV: BO - Biophysics Impact factor: 5.468, year: 2015

  17. Role of AmiA in the morphological transition of Helicobacter pylori and in immune escape.

    Directory of Open Access Journals (Sweden)

    Catherine Chaput

    2006-09-01

    Full Text Available The human gastric pathogen Helicobacter pylori is responsible for peptic ulcers and neoplasia. Both in vitro and in the human stomach it can be found in two forms, the bacillary and coccoid forms. The molecular mechanisms of the morphological transition between these two forms and the role of coccoids remain largely unknown. The peptidoglycan (PG layer is a major determinant of bacterial cell shape, and therefore we studied H. pylori PG structure during the morphological transition. The transition correlated with an accumulation of the N-acetyl-D-glucosaminyl-beta(1,4-N-acetylmuramyl-L-Ala-D-Glu (GM-dipeptide motif. We investigated the molecular mechanisms responsible for the GM-dipeptide motif accumulation, and studied the role of various putative PG hydrolases in this process. Interestingly, a mutant strain with a mutation in the amiA gene, encoding a putative PG hydrolase, was impaired in accumulating the GM-dipeptide motif and transforming into coccoids. We investigated the role of the morphological transition and the PG modification in the biology of H. pylori. PG modification and transformation of H. pylori was accompanied by an escape from detection by human Nod1 and the absence of NF-kappaB activation in epithelial cells. Accordingly, coccoids were unable to induce IL-8 secretion by AGS gastric epithelial cells. amiA is, to our knowledge, the first genetic determinant discovered to be required for this morphological transition into the coccoid forms, and therefore contributes to modulation of the host response and participates in the chronicity of H. pylori infection.

  18. Sharks modulate their escape behavior in response to predator size, speed and approach orientation.

    Science.gov (United States)

    Seamone, Scott; Blaine, Tristan; Higham, Timothy E

    2014-12-01

    Escape responses are often critical for surviving predator-prey interactions. Nevertheless, little is known about how predator size, speed and approach orientation impact escape performance, especially in larger prey that are primarily viewed as predators. We used realistic shark models to examine how altering predatory behavior and morphology (size, speed and approach orientation) influences escape behavior and performance in Squalus acanthias, a shark that is preyed upon by apex marine predators. Predator models induced C-start escape responses, and increasing the size and speed of the models triggered a more intense response (increased escape turning rate and acceleration). In addition, increased predator size resulted in greater responsiveness from the sharks. Among the responses, predator approach orientation had the most significant impact on escapes, such that the head-on approach, as compared to the tail-on approach, induced greater reaction distances and increased escape turning rate, speed and acceleration. Thus, the anterior binocular vision in sharks renders them less effective at detecting predators approaching from behind. However, it appears that sharks compensate by performing high-intensity escapes, likely induced by the lateral line system, or by a sudden visual flash of the predator entering their field of view. Our study reveals key aspects of escape behavior in sharks, highlighting the modulation of performance in response to predator approach. Copyright © 2014 Elsevier GmbH. All rights reserved.

  19. Improving escape panel selectivity in Nephrops directed fisheries by actively stimulating fish behaviour

    DEFF Research Database (Denmark)

    Krag, Ludvig Ahm; Herrmann, Bent; Feekings, Jordan P.

    2017-01-01

    with it. To increase the efficiency of such panels, the contact probability needs to be improved. In this study, we investigate to what extent the efficiency of escape panels can be improved by actively stimulating the escape behaviour of fish. The performance of two identical panel sections was compared...... in a twin-trawl system, one with and one without a stimulation device. A new coupled analysis method was used to explicitly quantify the improvements in contact probability and release efficiency for the escape panel. The results demonstrate that by actively stimulating escape behaviour, the contact...

  20. Flocculation phenomenon of a mutant flocculent Saccharomyces ...

    African Journals Online (AJOL)

    The flocculation mechanism of a stable mutant flocculent yeast strain Saccharomyces cerevisiae KRM-1 was quantitatively investigated for potential industrial interest. It was found that the mutant flocculent strain was NewFlo phenotype by means of sugar inhibition test. The flocculation was completely inhibited by treatment ...

  1. Generation and characterization of pigment mutants of ...

    African Journals Online (AJOL)

    Compared to the wild CC-124, these mutants are characterized by a decrease in chlorophyll a & b content and an increase in carotenoids. The lowest decrease in chlorophyll a was 3 to 4 folds, while the highest increase in carotenoids was 2 to 4 folds. The result of bio-test, using the resulting pigment mutant of C. reinhardtii ...

  2. An Arabidopsis mutant resistant to thaxtomin A, a cellulose synthesis inhibitor from Streptomyces species.

    Science.gov (United States)

    Scheible, Wolf-Rüdiger; Fry, Barbara; Kochevenko, Andrej; Schindelasch, Dana; Zimmerli, Laurent; Somerville, Shauna; Loria, Rosemary; Somerville, Chris R

    2003-08-01

    Thaxtomin A is a phytotoxin produced by Streptomyces scabies and other Streptomyces species, the causative agents of common scab disease in potato and other taproot crops. At nanomolar concentrations, thaxtomin causes dramatic cell swelling, reduced seedling growth, and inhibition of cellulose synthesis in Arabidopsis. We identified a mutant of Arabidopsis, designated txr1, that exhibits increased resistance to thaxtomin as a result of a decrease in the rate of toxin uptake. The TXR1 gene was identified by map-based cloning and found to encode a novel, small protein with no apparent motifs or organelle-targeting signals. The protein, which has homologs in all fully sequenced eukaryotic genomes, is expressed in all tissues and during all developmental stages analyzed. Microarray transcript profiling of some 14,300 genes revealed two stomatin-like genes that were expressed differentially in the txr1 mutant and the wild type. We propose that TXR1 is a regulator of a transport mechanism.

  3. Construction of an Unmarked Zymomonas mobilis Mutant Using a Site-Specific FLP Recombinase

    Directory of Open Access Journals (Sweden)

    Shao-Lan Zou

    2012-01-01

    Full Text Available Flippase expression was carried out in Zymomonas mobilis strain ZM4. The FRT-flanked selection marker gene was first integrated into the ZM4 chromosome by homologous recombination. The Saccharomyces cerevisiae flp gene was then introduced under the control of the ZM4 gap gene promoter (Pgap, encoding glyceraldehyde-3-phosphate dehydrogenase or the λ bacteriophage cI857-pR contained in the broad-host-range cloning vector pBBR1-MCS-2. This study demonstrated that flp was expressed and that the deletion frequency of the FRT-flanked marker gene was very high (approx. 100 %. In addition, the flp gene expression vector could be conveniently removed from the resulting unmarked Z. mobilis mutants by serially transferring the cells three times into antibiotic-free medium, thereby establishing an efficient method for constructing unmarked Z. mobilis mutants.

  4. Cp/Heph mutant mice have iron-induced neurodegeneration diminished by deferiprone

    Science.gov (United States)

    Zhao, Liangliang; Hadziahmetovic, Majda; Wang, Chenguang; Xu, Xueying; Song, Ying; Jinnah, H.A.; Wodzinska, Jolanta; Iacovelli, Jared; Wolkow, Natalie; Krajacic, Predrag; Weissberger, Alyssa Cwanger; Connelly, John; Spino, Michael; Lee, Michael K.; Connor, James; Giasson, Benoit; Harris, Z. Leah; Dunaief, Joshua L.

    2016-01-01

    Brain iron accumulates in several neurodegenerative diseases and can cause oxidative damage, but mechanisms of brain iron homeostasis are incompletely understood. Patients with mutations in the cellular iron-exporting ferroxidase ceruloplasmin (Cp) have brain iron accumulation causing neurodegeneration. Here, we assessed the brains of mice with combined mutation of Cp and its homolog hephaestin. Compared to single mutants, brain iron accumulation was accelerated in double mutants in the cerebellum, substantia nigra, and hippocampus. Iron accumulated within glia, while neurons were iron deficient. There was loss of both neurons and glia. Mice developed ataxia and tremor, and most died by 9 months. Treatment with the oral iron chelator deferiprone diminished brain iron levels, protected against neuron loss, and extended lifespan. Ferroxidases play important, partially overlapping roles in brain iron homeostasis by facilitating iron export from glia, making iron available to neurons. PMID:26303407

  5. Will 3552 Don Quixote escape from the Solar System?

    Directory of Open Access Journals (Sweden)

    Suryadi Siregar

    2011-05-01

    Full Text Available Asteroid 1983 SA, well known as 3552 Don Quixote, is one of Near Earth Asteroids (NEAs which is the most probable candidate for the cometary origin, or otherwise as Jupiter-Family-Comets (JFCs. The aim of this study is to investigate the possibility of 3552 Don Quixote to be ejected from the Solar System. This paper presents an orbital evolution of 100 hypothetical asteroids generated by cloning 3552 Don Quixote. Investigation of its orbital evolution is conducted by using the SWIFT subroutine package, where the gravitational perturbations of eight major planets in the Solar System are considered. Over very short time scales (220 kyr relative to the Solar System life time (10 Gyr, the asteroid 3552 Don Quixote gave an example of chaotic motion that can cause asteroid to move outward and may be followed by escaping from the Solar System. Probability of ejection within the 220 kyr time scale is 50%.

  6. Escape and avoidance learning in the earthworm Eisenia hortensis

    Directory of Open Access Journals (Sweden)

    W. Jeffrey Wilson

    2014-01-01

    Full Text Available Interest in instrumental learning in earthworms dates back to 1912 when Yerkes concluded that they can learn a spatial discrimination in a T-maze. Rosenkoetter and Boice determined in the 1970s that the “learning” that Yerkes observed was probably chemotaxis and not learning at all. We examined a different form of instrumental learning: the ability to learn both to escape and to avoid an aversive stimulus. Freely moving “master” worms could turn off an aversive white light by increasing their movement; the behavior of yoked controls had no effect on the light. We demonstrate that in as few as 12 trials the behavior of the master worms comes under the control of this contingency.

  7. Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells

    Directory of Open Access Journals (Sweden)

    Mauricio P. Pinto

    2016-09-01

    Full Text Available Tumor angiogenesis is widely recognized as one of the “hallmarks of cancer”. Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic therapy escape: (1 upregulation of compensatory/alternative pathways for angiogenesis; (2 vasculogenic mimicry; and (3 vessel co-option. We suggest that an understanding of how a cancer cell adapts to antiangiogenic therapy may also parallel the mechanisms employed in the bourgeoning tumor and isolated metastatic cells delivering responsible for residual disease. Finally, we speculate on strategies to adapt antiangiogenic therapy for future clinical uses.

  8. Novel Anti-Melanoma Immunotherapies: Disarming Tumor Escape Mechanisms

    Directory of Open Access Journals (Sweden)

    Sivan Sapoznik

    2012-01-01

    Full Text Available The immune system fights cancer and sometimes temporarily eliminates it or reaches an equilibrium stage of tumor growth. However, continuous immunological pressure also selects poorly immunogenic tumor variants that eventually escape the immune control system. Here, we focus on metastatic melanoma, a highly immunogenic tumor, and on anti-melanoma immunotherapies, which recently, especially following the FDA approval of Ipilimumab, gained interest from drug development companies. We describe new immunomodulatory approaches currently in the development pipeline, focus on the novel CEACAM1 immune checkpoint, and compare its potential to the extensively described targets, CTLA4 and PD1. This paper combines multi-disciplinary approaches and describes anti-melanoma immunotherapies from molecular, medical, and business angles.

  9. The resonance escape probability during the neutron slowing down

    International Nuclear Information System (INIS)

    Jehouani, A.; Ghassoun, J.; Aboubeker, A.

    1994-01-01

    Three different methods were used to calculate the neutron resonance escape probability during neutron slowing down in homogeneous media : two Monte Carlo simulations and a determinist method. The first simulation is based on a natural process intervening in neutron transport, the second is a nonanalog simulation while the determinist method is based on an iterative solution of the neutron slowing down equation. The results are in a good agreement for the three methods . The second simulation was found to be more efficient than the first one for high dilutions . In fact we have attained a better figure of merite ( FOM = 1/ (sigma sup 2 ) T) by the second simulation than by the first one . 2 figs. ; 2 refs ( author )

  10. Initiating a watch list for Ebola virus antibody escape mutations

    Directory of Open Access Journals (Sweden)

    Craig R. Miller

    2016-02-01

    Full Text Available The 2014 Ebola virus (EBOV outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens.

  11. Los mutantes de la escuela

    Directory of Open Access Journals (Sweden)

    Diego Armando Jaramillo-Ocampo

    2013-01-01

    Full Text Available El presente artículo muestra los resultados parciales del estudio “Juegos en el recreo escolar: un escenario para la formación ciudadana”, cuya pretensión fue comprender los imaginarios sociales de juego en el recreo escolar y su relación con la convivencia social desde la proximidad del enfoque de complementariedad y el diseño de investigación emergente, planteado por Murcia y Jaramillo (2008. Se presentan los desarrollos logrados en dos categorías centrales del estudio: el patio y el cuerpo; dos categorías que mutan constantemente como entidades vivas en la escuela, hacia la configuración de sujetos que reconocen en el otro y lo otro su posibilidad. La escuela viva, donde es posible “ser en relación con”… se reduce a un espacio temporal y físico, limitado por la campana, “el recreo”. El texto muestra, desde la voz de los actores, esa vida que se da y se quita en la escuela y que se posiciona como una más de las imposiciones normalizadas para controlar. Reconoce, finalmente, una propuesta desde la posibilidad que estos dos mutantes propician para una escuela libre y dinámica.

  12. The role of DNA double-strand breaks in spontaneous homologous recombination in S. cerevisiae

    DEFF Research Database (Denmark)

    Lettier, Gaëlle; Feng, Q.; Mayolo, A.A. de

    2006-01-01

    Homologous recombination (HR) is a source of genomic instability and the loss of heterozygosity in mitotic cells. Since these events pose a severe health risk, it is important to understand the molecular events that cause spontaneous HR. In eukaryotes, high levels of HR are a normal feature of me...... mutants, supporting the view that DNA nicks and single-stranded gaps, rather than DSBs, are major sources of spontaneous HR in mitotic yeast cells....... of meiosis and result from the induction of a large number of DNA double-strand breaks (DSBs). By analogy, it is generally believed that the rare spontaneous mitotic HR events are due to repair of DNA DSBs that accidentally occur during mitotic growth. Here we provide the first direct evidence that most...... spontaneous mitotic HR in Saccharomyces cerevisiae is initiated by DNA lesions other than DSBs. Specifically, we describe a class of rad52 mutants that are fully proficient in inter- and intra-chromosomal mitotic HR, yet at the same time fail to repair DNA DSBs. The conclusions are drawn from genetic analyses...

  13. Structural and Mechanistic Studies of Pesticin, a Bacterial Homolog of Phage Lysozymes*

    Science.gov (United States)

    Patzer, Silke I.; Albrecht, Reinhard; Braun, Volkmar; Zeth, Kornelius

    2012-01-01

    Yersinia pestis produces and secretes a toxin named pesticin that kills related bacteria of the same niche. Uptake of the bacteriocin is required for activity in the periplasm leading to hydrolysis of peptidoglycan. To understand the uptake mechanism and to investigate the function of pesticin, we combined crystal structures of the wild type enzyme, active site mutants, and a chimera protein with in vivo and in vitro activity assays. Wild type pesticin comprises an elongated N-terminal translocation domain, the intermediate receptor binding domain, and a C-terminal activity domain with structural analogy to lysozyme homologs. The full-length protein is toxic to bacteria when taken up to the target site via the outer or the inner membrane. Uptake studies of deletion mutants in the translocation domain demonstrate their critical size for import. To further test the plasticity of pesticin during uptake into bacterial cells, the activity domain was replaced by T4 lysozyme. Surprisingly, this replacement resulted in an active chimera protein that is not inhibited by the immunity protein Pim. Activity of pesticin and the chimera protein was blocked through introduction of disulfide bonds, which suggests unfolding as the prerequisite to gain access to the periplasm. Pesticin, a muramidase, was characterized by active site mutations demonstrating a similar but not identical residue pattern in comparison with T4 lysozyme. PMID:22593569

  14. The K-homology of nets of C∗-algebras

    Science.gov (United States)

    Ruzzi, Giuseppe; Vasselli, Ezio

    2014-12-01

    Let X be a space, intended as a possibly curved space-time, and A a precosheaf of C∗-algebras on X. Motivated by algebraic quantum field theory, we study the Kasparov and Θ-summable K-homology of A interpreting them in terms of the holonomy equivariant K-homology of the associated C∗-dynamical system. This yields a characteristic class for K-homology cycles of A with values in the odd cohomology of X, that we interpret as a generalized statistical dimension.

  15. Colletotrichum orbiculare WHI2, a Yeast Stress-Response Regulator Homolog, Controls the Biotrophic Stage of Hemibiotrophic Infection Through TOR Signaling.

    Science.gov (United States)

    Harata, Ken; Nishiuchi, Takumi; Kubo, Yasuyuki

    2016-06-01

    The hemibiotrophic fungus Colletotrichum orbiculare first establishes a biotrophic infection stage in cucumber (Cucumber sativus) epidermal cells and subsequently transitions to a necrotrophic stage. Here, we found that C. orbiculare established hemibiotrophic infection via C. orbiculare WHI2, a yeast stress regulator homolog, and TOR (target of rapamycin) signaling. Plant defense responses such as callose deposition, H2O2, and antimicrobial proteins were strongly induced by the C. orbiculare whi2Δ mutant, resulting in defective pathogenesis. Expression analysis of biotrophy-specific genes evaluated by the promoter VENUS fusion gene indicated weaker VENUS signal intensity in the whi2Δ mutant, thereby suggesting that C. orbiculare WHI2 plays a key role in regulating biotrophic infection of C. orbiculare. The involvement of CoWHI2 in biotrophic infection was further explored with a DNA microarray. In the Cowhi2Δ mutant, TOR-dependent ribosomal protein-related genes were strikingly upregulated compared with the wild type. Moreover, callose deposition in the host plant after inoculation with the Cowhi2Δ mutant treated with rapamycin, which inhibits TOR activity, was reduced, and the mutant remained biotrophic in contrast to the untreated mutant. Thus, regulation of TOR by Whi2 is apparently crucial to the biotrophic stage of hemibiotrophic infection in C. orbiculare.

  16. Hybrid fluid/kinetic modeling of Pluto’s escaping atmosphere

    Science.gov (United States)

    Erwin, Justin; Tucker, O. J.; Johnson, Robert E.

    2013-09-01

    Predicting the rate of escape and thermal structure of Pluto’s upper atmosphere in preparation for the New Horizons Spacecraft encounter in 2015 is important for planning and interpreting the expected measurements. Having a moderate Jeans parameter Pluto’s atmosphere does not fit the classic definition of Jeans escape for light species escaping from the terrestrial planets, nor does it fit the hydrodynamic outflow from comets and certain exoplanets. It has been proposed for some time that Pluto lies in the region of slow hydrodynamic escape. Using a hybrid fluid/molecular-kinetic model, we previously demonstrated the typical implementation of this model fails to correctly describe the appropriate temperature structure for the upper atmosphere for solar minimum conditions. Here we use a time-dependent solver to allow us to extend those simulations to higher heating rates and we examine fluid models in which Jeans-like escape expressions are used for the upper boundary conditions. We compare these to hybrid simulations of the atmosphere under heating conditions roughly representative of solar minimum and mean conditions as these bracket conditions expected during the New Horizon encounter. Although we find escape rates comparable to those previously estimated by the slow hydrodynamic escape model, and roughly consistent with energy limited escape, our model produces a much more extended atmosphere with higher temperatures roughly consistent with recent observations of CO. Such an extended atmosphere will be affected by Charon and will affect Pluto’s interaction with the solar wind at the New Horizon encounter. For the parameter space covered, we also find an inverse relationship between exobase temperature and altitude and the Jeans escape rate that is consistent with the energy limited escape rate. Since we have previously shown that such models can be scaled, these results have implications for modeling exoplanet atmospheres for which the energy limited

  17. Altered gene regulation and synaptic morphology in Drosophila learning and memory mutants

    Science.gov (United States)

    Guan, Zhuo; Buhl, Lauren K.; Quinn, William G.; Littleton, J. Troy

    2011-01-01

    Genetic studies in Drosophila have revealed two separable long-term memory pathways defined as anesthesia-resistant memory (ARM) and long-lasting long-term memory (LLTM). ARM is disrupted in radish (rsh) mutants, whereas LLTM requires CREB-dependent protein synthesis. Although the downstream effectors of ARM and LLTM are distinct, pathways leading to these forms of memory may share the cAMP cascade critical for associative learning. Dunce, which encodes a cAMP-specific phosphodiesterase, and rutabaga, which encodes an adenylyl cyclase, both disrupt short-term memory. Amnesiac encodes a pituitary adenylyl cyclase-activating peptide homolog and is required for middle-term memory. Here, we demonstrate that the Radish protein localizes to the cytoplasm and nucleus and is a PKA phosphorylation target in vitro. To characterize how these plasticity pathways may manifest at the synaptic level, we assayed synaptic connectivity and performed an expression analysis to detect altered transcriptional networks in rutabaga, dunce, amnesiac, and radish mutants. All four mutants disrupt specific aspects of synaptic connectivity at larval neuromuscular junctions (NMJs). Genome-wide DNA microarray analysis revealed ∼375 transcripts that are altered in these mutants, suggesting defects in multiple neuronal signaling pathways. In particular, the transcriptional target Lapsyn, which encodes a leucine-rich repeat cell adhesion protein, localizes to synapses and regulates synaptic growth. This analysis provides insights into the Radish-dependent ARM pathway and novel transcriptional targets that may contribute to memory processing in Drosophila. PMID:21422168

  18. Enhanced hippocampal long-term potentiation and fear memory in Btbd9 mutant mice.

    Directory of Open Access Journals (Sweden)

    Mark P DeAndrade

    Full Text Available Polymorphisms in BTBD9 have recently been associated with higher risk of restless legs syndrome (RLS, a neurological disorder characterized by uncomfortable sensations in the legs at rest that are relieved by movement. The BTBD9 protein contains a BTB/POZ domain and a BACK domain, but its function is unknown. To elucidate its function and potential role in the pathophysiology of RLS, we generated a line of mutant Btbd9 mice derived from a commercial gene-trap embryonic stem cell clone. Btbd9 is the mouse homolog of the human BTBD9. Proteins that contain a BTB/POZ domain have been reported to be associated with synaptic transmission and plasticity. We found that Btbd9 is naturally expressed in the hippocampus of our mutant mice, a region critical for learning and memory. As electrophysiological characteristics of CA3-CA1 synapses of the hippocampus are well characterized, we performed electrophysiological recordings in this region. The mutant mice showed normal input-output relationship, a significant impairment in pre-synaptic activity, and an enhanced long-term potentiation. We further performed an analysis of fear memory and found the mutant mice had an enhanced cued and contextual fear memory. To elucidate a possible molecular basis for these enhancements, we analyzed proteins that have been associated with synaptic plasticity. We found an elevated level of dynamin 1, an enzyme associated with endocytosis, in the mutant mice. These results suggest the first identified function of Btbd9 as being involved in regulating synaptic plasticity and memory. Recent studies have suggested that enhanced synaptic plasticity, analogous to what we have observed, in other regions of the brain could enhance sensory perception similar to what is seen in RLS patients. Further analyses of the mutant mice will help shine light on the function of BTBD9 and its role in RLS.

  19. The Mitochondrial DNA (mtDNA)-Associated Protein SWIB5 Influences mtDNA Architecture and Homologous Recombination

    KAUST Repository

    Blomme, Jonas

    2017-04-19

    In addition to the nucleus, mitochondria and chloroplasts in plant cells also contain genomes. Efficient DNA repair pathways are crucial in these organelles to fix damage resulting from endogenous and exogenous factors. Plant organellar genomes are complex compared with their animal counterparts, and although several plant-specific mediators of organelle DNA repair have been reported, many regulators remain to be identified. Here, we show that a mitochondrial SWI/SNF (nucleosome remodeling) complex B protein, SWIB5, is capable of associating with mitochondrial DNA (mtDNA) in Arabidopsis thaliana. Gainand loss-of-function mutants provided evidence for a role of SWIB5 in influencing mtDNA architecture and homologous recombination at specific intermediate-sized repeats both under normal and genotoxic conditions. SWIB5 interacts with other mitochondrial SWIB proteins. Gene expression and mutant phenotypic analysis of SWIB5 and SWIB family members suggests a link between organellar genome maintenance and cell proliferation. Taken together, our work presents a protein family that influences mtDNA architecture and homologous recombination in plants and suggests a link between organelle functioning and plant development.

  20. Loss of Caenorhabditis elegans BRCA1 Promotes Genome Stability During Replication in smc-5 Mutants

    Science.gov (United States)

    Wolters, Stefanie; Ermolaeva, Maria A.; Bickel, Jeremy S.; Fingerhut, Jaclyn M.; Khanikar, Jayshree; Chan, Raymond C.; Schumacher, Björn

    2014-01-01

    DNA damage by ultraviolet (UV) light poses a risk for mutagenesis and a potential hindrance for cell cycle progression. Cells cope with UV-induced DNA damage through two general strategies to repair the damaged nucleotides and to promote cell cycle progression in the presence of UV-damaged DNA. Defining the genetic pathways and understanding how they function together to enable effective tolerance to UV remains an important area of research. The structural maintenance of chromosomes (SMC) proteins form distinct complexes that maintain genome stability during chromosome segregation, homologous recombination, and DNA replication. Using a forward genetic screen, we identified two alleles of smc-5 that exacerbate UV sensitivity in Caenorhabditis elegans. Germ cells of smc-5-defective animals show reduced proliferation, sensitivity to perturbed replication, chromatin bridge formation, and accumulation of RAD-51 foci that indicate the activation of homologous recombination at DNA double-strand breaks. Mutations in the translesion synthesis polymerase polh-1 act synergistically with smc-5 mutations in provoking genome instability after UV-induced DNA damage. In contrast, the DNA damage accumulation and sensitivity of smc-5 mutant strains to replication impediments are suppressed by mutations in the C. elegans BRCA1/BARD1 homologs, brc-1 and brd-1. We propose that SMC-5/6 promotes replication fork stability and facilitates recombination-dependent repair when the BRC-1/BRD-1 complex initiates homologous recombination at stalled replication forks. Our data suggest that BRC-1/BRD-1 can both promote and antagonize genome stability depending on whether homologous recombination is initiated during DNA double-strand break repair or during replication stalling. PMID:24424777

  1. On the homology and the cohomology of certain polycyclic groups

    International Nuclear Information System (INIS)

    Majumdar, S.

    1987-10-01

    The homology and the cohomology of infinite non-abelian split extensions of cyclic groups by cyclic groups have been computed through construction of nice free resolutions for these groups. (author). 16 refs

  2. Substrate and Cation Binding Mechanism of Glutamate Transporter Homologs

    NARCIS (Netherlands)

    Jensen, Sonja

    2017-01-01

    Glutamate transporters and their homologs are membrane proteins that transport glutamate and aspartate together with sodium ions and/or protons. Human glutamate transporters remove the neurotransmitter glutamate after signal transmission. Therefore, glutamate transporters play a great role in

  3. Homology of normal chains and cohomology of charges

    CERN Document Server

    Pauw, Th De; Pfeffer, W F

    2017-01-01

    The authors consider a category of pairs of compact metric spaces and Lipschitz maps where the pairs satisfy a linearly isoperimetric condition related to the solvability of the Plateau problem with partially free boundary. It includes properly all pairs of compact Lipschitz neighborhood retracts of a large class of Banach spaces. On this category the authors define homology and cohomology functors with real coefficients which satisfy the Eilenberg-Steenrod axioms, but reflect the metric properties of the underlying spaces. As an example they show that the zero-dimensional homology of a space in our category is trivial if and only if the space is path connected by arcs of finite length. The homology and cohomology of a pair are, respectively, locally convex and Banach spaces that are in duality. Ignoring the topological structures, the homology and cohomology extend to all pairs of compact metric spaces. For locally acyclic spaces, the authors establish a natural isomorphism between their cohomology and the �...

  4. Neurologic function during developmental and adult stages in Dab1(scm) (scrambler) mutant mice.

    Science.gov (United States)

    Jacquelin, C; Strazielle, C; Lalonde, R

    2012-01-01

    Homozygous Dab1(scm) mouse mutants with cell ectopias in cerebellar cortex, hippocampus, and neocortex were compared to non-ataxic controls on the SHIRPA primary screening battery on postnatal days 8, 15, and 22, as well as in the adult period. Dab1(scm) mutants were distinguished from non-ataxic controls as early as postnatal day 8 based on body tremor, gait anomalies, and body weight. On postnatal day 15, motor coordination deficits were evident on horizontal bar and inclined or vertical grid tests in association with a weaker grip strength. Likewise, mutants were distinguished from controls on drop righting and hindpaw clasping tests. Further differences were detected on postnatal day 22 in the form of fewer visual placing, touch escape, trunk curl, freezing, and vocalization responses, as well as squares traversed in the open-field. Evaluation at the adult age demonstrated similar impairments, indicative of permanent motor alterations. Neuronal metabolic activity was estimated by cytochrome oxidase histochemistry on cerebellar sections. Cerebellar cortical layers and efferent deep nuclei of Dab1(scm) mice appeared hypometabolic relative to non-ataxic mice despite normal metabolism in both regular and ectopic Purkinje cells. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Natural history of acute and chronic hepatitis B: The role of HBV genotypes and mutants.

    Science.gov (United States)

    Lin, Chih-Lin; Kao, Jia-Horng

    2017-06-01

    Molecular epidemiologic studies reveal remarkable differences in the geographical distribution of hepatitis B virus (HBV) genotypes. The frequency of mutants among HBV genotypes also varies. The role of HBV genotypes/mutants in the pathogenesis of HBV infection and natural history of HBV infection has been extensively investigated. The distribution of HBV genotypes in acute hepatitis B patients reflects the predominant genotypes in a given geographic area. In chronic hepatitis B patients, genotype C and D have a higher frequency of basal core promoter A1762T/G1764A mutations than genotype A and B. HBV genotypes C, D and F carry a higher lifetime risk of cirrhosis and HCC development than genotype A and B. HBV pre-S/S gene mutations were associated with immune escape of hepatitis B immunoglobulin or vaccine-induced immunity. Mutations in the pre-S, core promoter and X regions correlate with an increased risk of cirrhosis and HCC. In summary, HBV genotypes and mutants are associated with the disease progression and long-term outcome of HBV infection. They may serve as viral genetic markers for risk stratification of chronic hepatitis B patients in clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. The rate of immune escape vanishes when multiple immune responses control an HIV infection

    NARCIS (Netherlands)

    van Deutekom, Hanneke W. M.; Wijnker, Gilles; de Boer, Rob J.

    2013-01-01

    During the first months of HIV infection, the virus typically evolves several immune escape mutations. These mutations are found in epitopes in viral proteins and reduce the impact of the CD8⁺ T cells specific for these epitopes. Recent data show that only a subset of the epitopes escapes, that most

  7. Computer Self-Efficacy, Competitive Anxiety and Flow State: Escaping from Firing Online Game

    Science.gov (United States)

    Hong, Jon-Chao; Pei-Yu, Chiu; Shih, Hsiao-Feng; Lin, Pei-Shin; Hong, Jon-Chao

    2012-01-01

    Flow state in game playing affected by computer self-efficacy and game competitive anxiety was studied. In order to examine the effect of those constructs with high competition, this study select "Escaping from firing online game" which require college students to escape from fire and rescue people and eliminate the fire damage along the way of…

  8. Effects of Visual Information on Wind-Evoked Escape Behavior of the Cricket, Gryllus bimaculatus.

    Science.gov (United States)

    Kanou, Masamichi; Matsuyama, Akane; Takuwa, Hiroyuki

    2014-09-01

    We investigated the effects of visual information on wind-evoked escape behavior in the cricket, Gryllus bimaculatus. Most agitated crickets were found to retreat into a shelter made of cardboard installed in the test arena within a short time. As this behavior was thought to be a type of escape, we confirmed how a visual image of a shelter affected wind-evoked escape behavior. Irrespective of the brightness of the visual background (black or white) or the absence or presence of a shelter, escape jumps were oriented almost 180° opposite to the source of the air puff stimulus. Therefore, the direction of wind-evoked escape depends solely depended on the direction of the stimulus air puff. In contrast, the turning direction of the crickets during the escape was affected by the position of the visual image of the shelter. During the wind-evoked escape jump, most crickets turned in the direction in which a shelter was presented. This behavioral nature is presumably necessary for crickets to retreat into a shelter within a short time after their escape jump.

  9. Spoon Distance Fading with and without Escape Extinction as Treatment for Food Refusal

    Science.gov (United States)

    Rivas, Kristi D.; Piazza, Cathleen C.; Patel, Meeta R.; Bachmeyer, Melanie H.

    2010-01-01

    Little is known about the characteristics of meals that serve as motivating operations (MOs) for escape behavior. In the current investigation, we showed that the distance at which a therapist held a spoon from a child's lips served as an MO for escape behavior. Based on these results, we implemented spoon distance fading, compared fading with and…

  10. Evaluating the potential ecological effects of transgene escape and persistence in constructed plant communities

    Science.gov (United States)

    To date, published studies with herbicide tolerant transgenic crops have failed to demonstrate that transgene escape to wild relatives results in more competitive hybrids. However, it is important to consider transgene escape in the context of the types of traits, which will lik...

  11. Supraventricular escape rhythms during transient episodes of bradycardia in preterm infants

    NARCIS (Netherlands)

    Andriessen, P.; Koolen, A.M.P.; Bastin, F.H.; Lafeber, H.N.; Meijler, F.L.

    2001-01-01

    Objective: To evaluate the origin of transient episodes of sinus bradycardia, atrial escape rhythm, and atrioventricular nodal escape rhythm in preterm infants. Material and methods: The study was observational, and was carried out in a third level neonatal intensive care unit. We srudied 19

  12. Escapement of Cape hakes under the fishing line of the Namibian ...

    African Journals Online (AJOL)

    The objective of this study was to establish whether Cape hakes Merluccius capensis and M. paradoxus escape under the fishing line and to identify any species or length dependence of escape rates. Experiments were carried out in Namibian waters during two cruises in October 2002 and October 2003. A collection bag ...

  13. The Efficacy of Noncontingent Escape for Decreasing Children's Disruptive Behavior during Restorative Dental Treatment

    Science.gov (United States)

    O'Callaghan, Patrick M.; Allen, Keith D.; Powell, Shawn; Salama, Fouad

    2006-01-01

    We evaluated the effectiveness of a dentist-implemented behavioral intervention in which brief escape from dental treatment was provided on a regular basis, independent of the child's behavior. Within a multiple baseline design across subjects, 5 children, ages 4 to 7 years, were provided with temporary escape from dental treatment on a fixed-time…

  14. Zeroth Poisson Homology, Foliated Cohomology and Perfect Poisson Manifolds

    Science.gov (United States)

    Martínez-Torres, David; Miranda, Eva

    2018-01-01

    We prove that, for compact regular Poisson manifolds, the zeroth homology group is isomorphic to the top foliated cohomology group, and we give some applications. In particular, we show that, for regular unimodular Poisson manifolds, top Poisson and foliated cohomology groups are isomorphic. Inspired by the symplectic setting, we define what a perfect Poisson manifold is. We use these Poisson homology computations to provide families of perfect Poisson manifolds.

  15. Even with nonnative interactions, the updated folding transition states of the homologs Proteins G & L are extensive and similar.

    Science.gov (United States)

    Baxa, Michael C; Yu, Wookyung; Adhikari, Aashish N; Ge, Liang; Xia, Zhen; Zhou, Ruhong; Freed, Karl F; Sosnick, Tobin R

    2015-07-07

    Experimental and computational folding studies of Proteins L & G and NuG2 typically find that sequence differences determine which of the two hairpins is formed in the transition state ensemble (TSE). However, our recent work on Protein L finds that its TSE contains both hairpins, compelling a reassessment of the influence of sequence on the folding behavior of the other two homologs. We characterize the TSEs for Protein G and NuG2b, a triple mutant of NuG2, using ψ analysis, a method for identifying contacts in the TSE. All three homologs are found to share a common and near-native TSE topology with interactions between all four strands. However, the helical content varies in the TSE, being largely absent in Proteins G & L but partially present in NuG2b. The variability likely arises from competing propensities for the formation of nonnative β turns in the naturally occurring proteins, as observed in our TerItFix folding algorithm. All-atom folding simulations of NuG2b recapitulate the observed TSEs with four strands for 5 of 27 transition paths [Lindorff-Larsen K, Piana S, Dror RO, Shaw DE (2011) Science 334(6055):517-520]. Our data support the view that homologous proteins have similar folding mechanisms, even when nonnative interactions are present in the transition state. These findings emphasize the ongoing challenge of accurately characterizing and predicting TSEs, even for relatively simple proteins.

  16. Progesterone after Estradiol Modulates Shuttle-Cage Escape by Facilitating Volition

    Directory of Open Access Journals (Sweden)

    Darryl J. Mayeaux

    2015-01-01

    Full Text Available In animal models of depression, depression is defined as performance on a learning task. That task is typically escaping a mild electric shock in a shuttle cage by moving from one side of the cage to the other. Ovarian hormones influence learning in other kinds of tasks, and these hormones are associated with depressive symptoms in humans. The role of these hormones in shuttle-cage escape learning, however, is less clear. This study manipulated estradiol and progesterone in ovariectomized female rats to examine their performance in shuttle-cage escape learning without intentionally inducing a depressive-like state. Progesterone, not estradiol, within four hours of testing affected latencies to escape. The improvement produced by progesterone was in the decision to act, not in the speed of learning or speed of escaping. This parallels depression in humans in that depressed people are slower in volition, in their decisions to take action.

  17. Plasma Clouds and Snowplows: Bulk Plasma Escape from Mars Observed by MAVEN

    Science.gov (United States)

    Halekas, J. S.; Brain, D. A.; Ruhunusiri, S.; McFadden, J. P.; Mitchell, D. L.; Mazelle, C.; Connerney, J. E. P.; Harada, Y.; Hara, T.; Espley, J. R.; hide

    2016-01-01

    We present initial Mars Atmosphere and Volatile EvolutioN (MAVEN) observations and preliminary interpretation of bulk plasma loss from Mars. MAVEN particle and field measurements show that planetary heavy ions derived from the Martian atmosphere can escape in the form of discrete coherent structures or "clouds." The ions in these clouds are unmagnetized or weakly magnetized, have velocities well above the escape speed, and lie directly downstream from magnetic field amplifications, suggesting a "snowplow" effect. This postulated escape process, similar to that successfully used to explain the dynamics of active gas releases in the solar wind and terrestrial magnetosheath, relies on momentum transfer from the shocked solar wind protons to the planetary heavy ions, with the electrons and magnetic field acting as intermediaries. Fluxes of planetary ions on the order of 10(exp 7)/sq cm/s can escape by this process, and if it operates regularly, it could contribute 10-20% of the current ion escape from Mars.

  18. Hydrogen and deuterium loss from the terrestrial atmosphere - A quantitative assessment of nonthermal escape fluxes

    Science.gov (United States)

    Yung, Yuk L.; Wen, Jun-Shan; Moses, Julianne I.; Landry, Bridget M.; Allen, Mark; Hsu, Kuang-Jung

    1989-01-01

    A comprehensive one-dimensional photochemical model extending from the middle atmosphere (50 km) to the exobase (432 km) has been used to study the escape of hydrogen and deuterium from the earth's atmosphere. The model incorporates recent advances in chemical kinetics as well as atmospheric observations by satellites, especially the Atmosphere Explorer C satellite. The results suggest that the escape fluxes of both H and D are limited by the upward transport of total hydrogen and total deuterium at the homopause. About one fourth of total hydrogen escape is thermal, the rest being nonthermal. It is shown that escape of D is nonthermal and that charge exchange and polar wind are important mechanisms for the nonthermal escape of H and D.

  19. Escape windows to improve the size selectivity in the Baltic cod trawl fishery

    DEFF Research Database (Denmark)

    Madsen, Niels; Holst, René; Foldager, L.

    2002-01-01

    A rapid decrease of the stock of Baltic cod (Gadus morhua) has provided the incentive to improve the size selectivity in the trawl fishery. Use of escape windows is permitted in the legislation to give means of improving the size selectivity of cod as an alternative to a traditional standard codend....... The history of the use of escape windows in the Baltic Sea cod fishery is reviewed. The present escape windows do not function optimally. The objective of this new experiment was to compare an improved design of escape window, which is placed in the upper panel, with that of standard codend. Three standard...... (WMS) as that of a standard codend. The L50 of the standard codends decreased with catch weight. An unexplained port- starboard effect was found for the window codends where the L50 depended on which of the two trawls the codend was attached to. The potential of these escape windows as a management...

  20. Antarctic krill; assessment of mesh size selectivity and escape mortality from trawls

    DEFF Research Database (Denmark)

    Krafft, Bjørn A.; Krag, Ludvig Ahm; Herrmann, Bent

    2015-01-01

    This working paper presents the aims and methodology for a three-year-project (commenced in 2015) assessing size selectivity and escape mortality of Antarctic krill from trawl nets. The project is widely based on acquired experiences from a completed study Net Escapement of Antarctic krill......Marine AS. The project will examine krill escape mortality from the codend during a full scale field experiment, model size selectivity and escape mortality in codends including different designs and assess the size selectivity in the trawl body forward of the codend. Based on end results from the preceding...... examinations we will be able to predict size selectivity and escape mortality from the entire trawl body with the appurtenant mortality for different trawl designs...

  1. Isolating human DNA repair genes using rodent-cell mutants

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, L.H.; Weber, C.A.; Brookman, K.W.; Salazar, E.P.; Stewart, S.A.; Mitchell, D.L.

    1987-03-23

    The DNA repair systems of rodent and human cells appear to be at least as complex genetically as those in lower eukaryotes and bacteria. The use of mutant lines of rodent cells as a means of identifying human repair genes by functional complementation offers a new approach toward studying the role of repair in mutagenesis and carcinogenesis. In each of six cases examined using hybrid cells, specific human chromosomes have been identified that correct CHO cell mutations affecting repair of damage from uv or ionizing radiations. This finding suggests that both the repair genes and proteins may be virtually interchangeable between rodent and human cells. Using cosmid vectors, human repair genes that map to chromosome 19 have cloned as functional sequences: ERCC2 and XRCC1. ERCC1 was found to have homology with the yeast excision repair gene RAD10. Transformants of repair-deficient cell lines carrying the corresponding human gene show efficient correction of repair capacity by all criteria examined. 39 refs., 1 fig., 1 tab.

  2. X-rays sensitive mammalian cell mutant

    International Nuclear Information System (INIS)

    Utsumi, Hiroshi

    1982-01-01

    A phenomenon that in x-ray-sensitive mammalian-cell mutants, cellular death due to x-ray radiation was not increased by caffeine, but on the contrary, the dead cells were resuscitated by it was discussed. The survival rate of mutant cells increased by caffein in a low concentration. This suggested that caffeine may have induced some mechanism to produce x-ray resistant mutant cells. Postirradiation treatment with caffeine increased considerably the survival rate of the mutant cells, and this suggested the existence of latent caffeine-sensitive potentially lethal damage repair system. This system, after a few hours, is thought to be substituted by caffeine-resistant repair system which is induced by caffeine, and this may be further substituted by x-ray-resistant repair system. The repair system was also induced by adenine. (Ueda, J.)

  3. Semi-dwarf mutants for rice improvement

    International Nuclear Information System (INIS)

    Othman, Ramli; Osman, Mohammad; Ibrahim, Rusli

    1990-01-01

    Full text: MARDI and the National University of Malaysia embarked on a programme to induce resistance against blast in rice in 1978. MARDI also obtained semi dwarf mutants of cvs 'Mahsuri', 'Muda', 'Pongsu seribu' and 'Jarum Mas', which are under evaluation. The popular local rice variety 'Manik' was subjected to gamma irradiation (15-40 krad) and 101 promising semidwarf mutants have been obtained following selection in M 2 -M 6 . 29 of them show grain yields of 6.0-7.3 t/ha, compared with 5.7t for 'Manik'. Other valuable mutants were found showing long grain, less shattering, earlier maturity, and glutinous endosperm. One mutant, resistant to brown plant hopper yields 6.3t/ha. (author)

  4. Doxycyclin ameliorates a starvation-induced germline tumor in C. elegans daf-18/PTEN mutant background.

    Science.gov (United States)

    Wolf, Tim; Qi, Wenjing; Schindler, Verena; Runkel, Eva Diana; Baumeister, Ralf

    2014-08-01

    Managing available resources is a key necessity of each organism to cope with the environment. The nematode C. elegans responds to nutritional deprivation or harsh environmental conditions with a multitude of developmental adaptations, among them a starvation-induced quiescence at early larval development (L1). daf-18, the C. elegans homolog of the human tumor suppressor gene PTEN, is essential for the maintenance of survival and germline stem cell arrest during the L1 diapause. We show here that daf-18 mutants, independently to their failure to maintain G2 arrest of the primordial germ cells, develop a gonad phenotype after refeeding. This highly penetrant gonadal phenotype is further enhanced by a mutation in shc-1, encoding a protein homologous to the human adaptor ShcA. Features of this phenotype are a tumor-like phenotype encompassing hyper-proliferation of germ cell nuclei and disruption/invasion of the basement membrane surrounding the gonad. The penetrance of this phenotype is reduced by decreasing starvation temperature. In addition, it is also ameliorated in a dose-dependent way by exposure to the antibiotic doxycyclin either during starvation or during subsequent refeeding. Since, in eukaryotic cells, doxycyclin specifically blocks mitochondrial translation, our results suggest that daf-18 and shc-1;daf-18 mutants fail to adapt mitochondrial activity to reduced nutritional availability during early larval developing. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Robust mutant strain design by pessimistic optimization.

    Science.gov (United States)

    Apaydin, Meltem; Xu, Liang; Zeng, Bo; Qian, Xiaoning

    2017-10-03

    Flux Balance Analysis (FBA) based mathematical modeling enables in silico prediction of systems behavior for genome-scale metabolic networks. Computational methods have been derived in the FBA framework to solve bi-level optimization for deriving "optimal" mutant microbial strains with targeted biochemical overproduction. The common inherent assumption of these methods is that the surviving mutants will always cooperate with the engineering objective by overproducing the maximum desired biochemicals. However, it has been shown that this optimistic assumption may not be valid in practice. We study the validity and robustness of existing bi-level methods for strain optimization under uncertainty and non-cooperative environment. More importantly, we propose new pessimistic optimization formulations: P-ROOM and P-OptKnock, aiming to derive robust mutants with the desired overproduction under two different mutant cell survival models: (1) ROOM assuming mutants have the minimum changes in reaction fluxes from wild-type flux values, and (2) the one considered by OptKnock maximizing the biomass production yield. When optimizing for desired overproduction, our pessimistic formulations derive more robust mutant strains by considering the uncertainty of the cell survival models at the inner level and the cooperation between the outer- and inner-level decision makers. For both P-ROOM and P-OptKnock, by converting multi-level formulations into single-level Mixed Integer Programming (MIP) problems based on the strong duality theorem, we can derive exact optimal solutions that are highly scalable with large networks. Our robust formulations P-ROOM and P-OptKnock are tested with a small E. coli core metabolic network and a large-scale E. coli iAF1260 network. We demonstrate that the original bi-level formulations (ROOM and OptKnock) derive mutants that may not achieve the predicted overproduction under uncertainty and non-cooperative environment. The knockouts obtained by the

  6. Cellular Adhesion Promotes Prostate Cancer Cells Escape from Dormancy.

    Science.gov (United States)

    Ruppender, Nazanin; Larson, Sandy; Lakely, Bryce; Kollath, Lori; Brown, Lisha; Coleman, Ilsa; Coleman, Roger; Nguyen, Holly; Nelson, Peter S; Corey, Eva; Snyder, Linda A; Vessella, Robert L; Morrissey, Colm; Lam, Hung-Ming

    2015-01-01

    Dissemination of prostate cancer (PCa) cells to the bone marrow is an early event in the disease process. In some patients, disseminated tumor cells (DTC) proliferate to form active metastases after a prolonged period of undetectable disease known as tumor dormancy. Identifying mechanisms of PCa dormancy and reactivation remain a challenge partly due to the lack of in vitro models. Here, we characterized in vitro PCa dormancy-reactivation by inducing cells from three patient-derived xenograft (PDX) lines to proliferate through tumor cell contact with each other and with bone marrow stroma. Proliferating PCa cells demonstrated tumor cell-cell contact and integrin clustering by immunofluorescence. Global gene expression analyses on proliferating cells cultured on bone marrow stroma revealed a downregulation of TGFB2 in all of the three proliferating PCa PDX lines when compared to their non-proliferating counterparts. Furthermore, constitutive activation of myosin light chain kinase (MLCK), a downstream effector of integrin-beta1 and TGF-beta2, in non-proliferating cells promoted cell proliferation. This cell proliferation was associated with an upregulation of CDK6 and a downregulation of E2F4. Taken together, our data provide the first clinically relevant in vitro model to support cellular adhesion and downregulation of TGFB2 as a potential mechanism by which PCa cells may escape from dormancy. Targeting the TGF-beta2-associated mechanism could provide novel opportunities to prevent lethal PCa metastasis.

  7. Human embryo immune escape mechanisms rediscovered by the tumor.

    Science.gov (United States)

    Ridolfi, Laura; Petrini, Massimiliano; Fiammenghi, Laura; Riccobon, Angela; Ridolfi, Ruggero

    2009-01-01

    Towards the end of the 1990s, the two opposing theories on immunosurveillance and immunostimulation were extensively studied by researchers in an attempt to understand the complex mechanisms that regulate the relation between tumors and the host's immune system. Both theories probably have elements that would help us to comprehend how the host can induce anti-tumor clinical responses through stimulation of the immune system and which could also give us a deeper insight into the mechanisms of tumor immunosuppression. The model that most resembles the behavior of tumor cells in terms of growth, infiltration and suppression of the immune system of the environment in which they live is undoubtedly that of the embryonic cell. The fetus behaves like an allogenic transplant within the mother's body, using every means it has to escape from and defend itself against the mother's immune system. The majority of these mechanisms are the same as those found in tumor cells: antigenic loss, lack of expression of classic HLA-I molecules, production of immunosuppressive cytokines, induction of lack of expression of co-stimulatory molecules in antigen presenting cells, and induction of apoptosis in infiltrating lymphocytes, with activation of a type Th2 regulatory lymphocyte response. A careful and comparative study of key mechanisms capable of triggering tolerance or cytotoxicity in both embryonic and tumor cells could prove immensely valuable in designing new strategies for anti-tumor immunotherapy.

  8. Modified guidance laws to escape microbursts with turbulence

    Directory of Open Access Journals (Sweden)

    Atilla Dogan

    2002-01-01

    Full Text Available This paper introduces Modified Altitude- and Dive-Guidance laws for escaping a microburst with turbulence. The goal is to develop a procedure to estimate the highest altitude at which an aircraft can fly through a microburst without running into stall. First, a new metric is constructed that quantifies the aircraft upward force capability in a microburst encounter. In the absence of turbulence, the metric is shown to be a decreasing function of altitude. This suggests that descending to a low altitude may improve safety in the sense that the aircraft will have more upward force capability to maintain its altitude. In the presence of stochastic turbulence, the metric is treated as a random variable and its probability distribution function is analytically approximated as a function of altitude. This approximation allows us to determine the highest safe altitude at which the aircraft may descend, hence avoiding to descend too low. This highest safe altitude is used as the commanded altitude in Modified Altitude- and Dive-Guidance. Monte Carlo simulations show that these Modified Altitude- and Dive-Guidance strategies can decrease the probability of minimum altitude being lower than a given value without significantly increasing the probability of crash.

  9. EUROGAM: A high efficiency escape suppressed spectrometer array

    International Nuclear Information System (INIS)

    Nolan, P.J.

    1992-01-01

    EUROGAM is a UK-France collaboration to develop and build a high efficiency escape suppressed spectrometer array. The project has involved the development of both germanium (Ge) and bismuth germanate (BGO) detectors to produce crystals which are both bigger and have a more complex geometry. As a major investment for the future, the collaboration has developed a new electronics and data acquisition system based on the VXI and VME standards. The array will start its experimental programme in mid 1992 at the Nuclear Structure Facility at Daresbury, U.K. At this stage it will have a total photopeak efficiency (for 1.33 MeV gamma-rays) of ∼ 4.5%. This will give an improvement in sensitivity (relative to presently operating arrays) of a factor of about 10. When EUROGAM moves to France in mid 1993 its photopeak efficiency will have increased to about 8.5% which will result in an increase in sensitivity of a further factor of about 10. In this article I will concentrate on the array which will operate at Daresbury in 1992 and only briefly cover the developments which will take place for the full array before it is used in France in 1993. (author). 13 refs., 2 tabs., 10 figs

  10. My car is sinking: automobile submersion, lessons in vehicle escape.

    Science.gov (United States)

    Giesbrecht, Gordon G; McDonald, Gerren K

    2010-08-01

    In North America approximately 400 individuals per year die in submersed vehicles, accounting for 5-11% of all drownings. About half of people surveyed would let the vehicle fill with water before attempting exit. We used a crane and two passenger vehicles of the same make, model, and year-one with passenger compartment intact (I) and one with holes (H) in the floor (area approximately 2200 cm2)--to conduct occupied and unoccupied submersions. Three phases of submersion were identified: 1) FLOATING, vehicles floated for 15 s (H) to 63 s (I) before the water reached the bottom of the side windows; 2) SINKING, the subsequent period until the vehicle is completely under water, but before it fills completely; and 3) SUBMERGED, the vehicle was full of water and several feet below the surface. Total time to submersion was 150 s for I but only 37 s for H. Opening the door to exit Vehicle I decreased submersion time from 150 to 30 s. Even the most difficult exit strategy attempted (three men and a child manikin through one window) was quickly performed from Vehicle I (only 51 s). During one exit attempt, initiated during the sinking phase, it was impossible to open the doors or windows until the vehicle was completely full of water. A vehicle is most easily exited during the initial Floating Phase. We suggest the following escape procedure: SEATBELT(s) unfastened; WINDOWS open; CHILDREN released from restraints and brought close to an adult; and OUT, children should exit first.

  11. Intertextuality in Novel: An Escape from Patriarchal Soliloquy

    Directory of Open Access Journals (Sweden)

    Nargess Bagheri

    2015-12-01

    Full Text Available Hypertextuality is one of the intertextual relationships introduced by Gerard Genette. According to him, hypertextuality includes all the relationships which the hypertext has with the previous text, i.e. the hypotext. However, he does not consider the relationship between these two texts to be in such a way that the hypertext is the interpretation of the hypotext. On the other hand, other theorizers including Bakhtin, regard the conversation between texts a way to escape a one-voiced and dominant discourse. From this viewpoint, the intertextual relationships of Sadegh Hedayat’s The Blind Owl, with Shahrnoush Parsipour’s The Blue Mind and Abbas Maroufi’s The Body of Farhad are in such a way that The Blind Owl can be regarded as a hypotext for the other 2 novels but these two novels interpret the text differently. The present study aims to examine the intertextual relationships between these 3 novels and explore how a multiple-voiced conversation is formed between them.

  12. ESCAPE. Energy Security and ClimAte Policy Evaluation

    International Nuclear Information System (INIS)

    Kessels, J.R.; Bakker, S.J.A.

    2005-05-01

    Climate change and energy supply security policy are currently not integrated in most countries, despite possible synergies. The ESCAPE approach suggests that linking climate change policy with security of energy supply could improve climate change policy at both a national and international level. The report explores the interaction between policies of energy security and climate change and the options of inclusion of energy security issues into national and international post-2012 climate negotiations. It emphasises the importance of the US in this regard and takes a close look at US energy policy documents. It appears that current US energy policy is not directed towards reducing its reliance on imported fossil fuel, even though the government has a strong preference for this. This study shows that measures to reduce import dependency are mostly synergetic with climate policy and gives some options that can be implemented. On an international level, linkages of energy security into post-2012 climate policy may be possible in sectoral bottom-up approaches or technology frameworks. As well, inclusion of a security of supply criterion in international emission trading instruments may provide potential benefits

  13. Tests of escape theory of binge eating among Latinas.

    Science.gov (United States)

    Higgins Neyland, M K; Bardone-Cone, Anna M

    2017-07-01

    Despite comparable prevalence of some eating disorders (e.g., binge eating disorder) among Latinas compared with Caucasians, eating disorders are still thought of as primarily afflicting Caucasian women. This has led to a lag in research on eating disorders among Latinas. Our objective was to test 3 escape theory models involving the culturally specific independent variables of acculturative stress, family disconnection, and discriminatory stress; the mediator of negative affect; and the dependent variable of binge eating frequency. We recruited a female sample of 119 Latinas (78 who have suffered from an eating disorder, 41 who have never had an eating disorder). Results indicated that all of the relationships between culturally specific factors and binge eating were mediated by negative affect, and that there was a significant direct pathway from discriminatory stress to binge eating. Findings from this study can be used to tailor interventions to Latinas who engage in binge eating, targeting culturally specific factors and their relationships with negative affect and binge eating. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Mutant ribosomes can generate dominant kirromycin resistance.

    Science.gov (United States)

    Tubulekas, I; Buckingham, R H; Hughes, D

    1991-01-01

    Mutations in the two genes for EF-Tu in Salmonella typhimurium and Escherichia coli, tufA and tufB, can confer resistance to the antibiotic kirromycin. Kirromycin resistance is a recessive phenotype expressed when both tuf genes are mutant. We describe a new kirromycin-resistant phenotype dominant to the effect of wild-type EF-Tu. Strains carrying a single kirromycin-resistant tuf mutation and an error-restrictive, streptomycin-resistant rpsL mutation are resistant to high levels of kirromycin, even when the other tuf gene is wild type. This phenotype is dependent on error-restrictive mutations and is not expressed with nonrestrictive streptomycin-resistant mutations. Kirromycin resistance is also expressed at a low level in the absence of any mutant EF-Tu. These novel phenotypes exist as a result of differences in the interactions of mutant and wild-type EF-Tu with the mutant ribosomes. The restrictive ribosomes have a relatively poor interaction with wild-type EF-Tu and are thus more easily saturated with mutant kirromycin-resistant EF-Tu. In addition, the mutant ribosomes are inherently kirromycin resistant and support a significantly faster EF-Tu cycle time in the presence of the antibiotic than do wild-type ribosomes. A second phenotype associated with combinations of rpsL and error-prone tuf mutations is a reduction in the level of resistance to streptomycin. PMID:2050625

  15. Commercialization Of Orchid Mutants For Floriculture Industry

    International Nuclear Information System (INIS)

    Sakinah Ariffin; Zaiton Ahmad

    2014-01-01

    Orchids are the main contributors to cut flower industry in Malaysia with an existing good market and a huge business potential. Orchid industry has been established in Malaysia since 1960s but only started to develop and expand since 1980s. Continuous development of new orchid varieties is essential to meet customers' demands. Orchid mutagenesis research using gamma irradiation at Malaysian Nuclear Agency has successfully generated a number of new orchid varieties with commercial potentials. Therefore, Nuclear Malaysia has collaborated with an industrial partner, Hexagon Green Sdn Bhd (HGSB), to carry out commercialization research on these mutants under a Technofund project entitled 'Pre-Commercialization of Mutant Orchids for Cut Flowers Industry' from July 2011 to July 2014. Through this collaboration, Dendrobium orchid mutant plants developed by Nuclear Malaysia were transferred to HGSB's commercial orchid nursery at Bukit Changgang Agrotechnology Park, Banting, Selangor, for mass-propagation. The activities include evaluations on plant growth performance, flower quality, post harvest and market potential of these mutants. Mutants with good field performance have been identified and filed for Plant Variety Protection (PVP) with Department of Agriculture Malaysia. This paper describes outputs from this collaboration and activities undertaken in commercializing these mutants. (author)

  16. Comparison of a coq7 deletion mutant with other respiration-defective mutants in fission yeast.

    Science.gov (United States)

    Miki, Risa; Saiki, Ryoichi; Ozoe, Yoshihisa; Kawamukai, Makoto

    2008-11-01

    Among the steps in ubiquinone biosynthesis, that catalyzed by the product of the clk-1/coq7 gene has received considerable attention because of its relevance to life span in Caenorhabditis elegans. We analyzed the coq7 ortholog (denoted coq7) in Schizosaccharomyces pombe, to determine whether coq7 has specific roles that differ from those of other coq genes. We first confirmed that coq7 is necessary for the penultimate step in ubiquinone biosynthesis, from the observation that the deletion mutant accumulated the ubiquinone precursor demethoxyubiquinone-10 instead of ubiquinone-10. The coq7 mutant displayed phenotypes characteristic of other ubiquinone-deficient Sc. pombe mutants, namely, hypersensitivity to hydrogen peroxide, a requirement for antioxidants for growth on minimal medium, and an elevated production of sulfide. To compare these phenotypes with those of other respiration-deficient mutants, we constructed cytochrome c (cyc1) and coq3 deletion mutants. We also assessed accumulation of oxidative stress in various ubiquinone-deficient strains and in the cyc1 mutant by measuring mRNA levels of stress-inducible genes and the phosphorylation level of the Spc1 MAP kinase. Induction of ctt1, encoding catalase, and apt1, encoding a 25 kDa protein, but not that of gpx1, encoding glutathione peroxidase, was indistinguishable in four ubiquinone-deficient mutants, indicating that the oxidative stress response operates at similar levels in the tested strains. One new phenotype was observed, namely, loss of viability in stationary phase (chronological life span) in both the ubiquinone-deficient mutant and in the cyc1 mutant. Finally, Coq7 was found to localize in mitochondria, consistent with the possibility that ubiquinone biosynthesis occurs in mitochondria in yeasts. In summary, our results indicate that coq7 is required for ubiquinone biosynthesis and the coq7 mutant is not distinguishable from other ubiquinone-deficient mutants, except that its phenotypes are more

  17. Enhanced stimulation of chromosomal translocations and sister chromatid exchanges by either HO-induced double-strand breaks or ionizing radiation in Saccharomyces cerevisiae yku70 mutants

    Energy Technology Data Exchange (ETDEWEB)

    Fasullo, Michael [Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12209 (United States)]. E-mail: mfasullo@ordwayresearch.org; St Amour, Courtney [Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12209 (United States); Zeng Li [Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12209 (United States)

    2005-10-15

    DNA double-strand break (DSB) repair occurs by homologous recombination (HR) or non-homologous endjoining (NHEJ). In Saccharomyces cerevisiae, expression of both MAT a and MAT{alpha} inhibits NHEJ and facilitates DSB-initiated HR. We previously observed that DSB-initiated recombination between two his3 fragments, his3-{delta}5' and his3-{delta}3'::HOcs is enhanced in haploids and diploids expressing both MAT a and MAT{alpha} genes, regardless of the position or orientation of the his3 fragments. Herein, we measured frequencies of DNA damage-associated translocations and sister chromatid exchanges (SCEs) in yku70 haploid mutants, defective in NHEJ. Translocation and SCE frequencies were measured in strains containing the same his3 fragments after DSBs were made directly at trp1::his3-{delta}3'::HOcs. Wild type and yku70 cells were also exposed to ionizing radiation and radiomimetic agents methyl methanesulfonate (MMS), phleomycin, and 4-nitroquinolone-1-oxide (4-NQO). Frequencies of X-ray-associated and DSB-initiated translocations were five-fold higher in yku70 mutants compared to wild type; however, frequencies of phleomycin-associated translocations were lower in the yku70 haploid mutant. Frequencies of DSB-initiated SCEs were 1.8-fold higher in the yku70 mutant, compared to wild type. Thus, DSB-initiated HR between repeated sequences on non-homologous chromosomes and sister chromatids occurs at higher frequencies in yku70 haploid mutants; however, higher frequencies of DNA damage-associated HR in yku70 mutants depend on the DNA damaging agent.

  18. Enhanced stimulation of chromosomal translocations and sister chromatid exchanges by either HO-induced double-strand breaks or ionizing radiation in Saccharomyces cerevisiae yku70 mutants

    International Nuclear Information System (INIS)

    Fasullo, Michael; St Amour, Courtney; Zeng Li

    2005-01-01

    DNA double-strand break (DSB) repair occurs by homologous recombination (HR) or non-homologous endjoining (NHEJ). In Saccharomyces cerevisiae, expression of both MAT a and MATα inhibits NHEJ and facilitates DSB-initiated HR. We previously observed that DSB-initiated recombination between two his3 fragments, his3-Δ5' and his3-Δ3'::HOcs is enhanced in haploids and diploids expressing both MAT a and MATα genes, regardless of the position or orientation of the his3 fragments. Herein, we measured frequencies of DNA damage-associated translocations and sister chromatid exchanges (SCEs) in yku70 haploid mutants, defective in NHEJ. Translocation and SCE frequencies were measured in strains containing the same his3 fragments after DSBs were made directly at trp1::his3-Δ3'::HOcs. Wild type and yku70 cells were also exposed to ionizing radiation and radiomimetic agents methyl methanesulfonate (MMS), phleomycin, and 4-nitroquinolone-1-oxide (4-NQO). Frequencies of X-ray-associated and DSB-initiated translocations were five-fold higher in yku70 mutants compared to wild type; however, frequencies of phleomycin-associated translocations were lower in the yku70 haploid mutant. Frequencies of DSB-initiated SCEs were 1.8-fold higher in the yku70 mutant, compared to wild type. Thus, DSB-initiated HR between repeated sequences on non-homologous chromosomes and sister chromatids occurs at higher frequencies in yku70 haploid mutants; however, higher frequencies of DNA damage-associated HR in yku70 mutants depend on the DNA damaging agent

  19. The role of the Brr5/Ysh1 C-terminal domain and its homolog Syc1 in mRNA 3′-end processing in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Nasser, Tommy; Tacahashi, Zhelkovsky A.; He, X.

    2006-01-01

    subunit Pap1. Because of similarity to other nucleases in the metallo-beta-lactamase family, the Brr5/Ysh1 subunit has been proposed to be the endonuclease. The C-terminal domain of Brr5 lies outside of beta-lactamase homology, and its function has not been elucidated. We show here that this region of Brr......5 is necessary for cell viability and mRNA 3'-end processing. It is highly homologous to another CPF subunit, Syc1. Syc1 is not essential, but its removal improves the growth of other processing mutants at restrictive temperatures and restores in vitro processing activity to cleavage...

  20. The Transcriptional Regulator LEUNIG_HOMOLOG Regulates Mucilage Release from the Arabidopsis Testa1[W][OA

    Science.gov (United States)

    Walker, Murray; Tehseen, Muhammad; Doblin, Monika S.; Pettolino, Filomena A.; Wilson, Sarah M.; Bacic, Antony; Golz, John F.

    2011-01-01

    Exposure of the mature Arabidopsis (Arabidopsis thaliana) seed to water results in the rapid release of pectinaceous mucilage from the outer cells of the testa. Once released, mucilage completely envelops the seed in a gel-like capsule. The physical force required to rupture the outer cell wall of the testa comes from the swelling of the mucilage as it expands rapidly following hydration. In this study, we show that mutations in the transcriptional regulator LEUNIG_HOMOLOG (LUH) cause a mucilage extrusion defect due to altered mucilage swelling. Based on sugar linkage and immunomicroscopic analyses, we show that the structure of luh mucilage is altered, having both an increase in substituted rhamnogalacturonan I and in methyl-esterified homogalacturonan. Also correlated with the structural modification of luh mucilage is a significant decrease in MUCILAGE MODIFIED2 (MUM2; a β-galactosidase) expression in the luh seed coat, raising the possibility that reduced activity of this glycosidase is directly responsible for the luh mucilage defects. Consistent with this is the structural similarity between mum2 and luh mucilage as well as the observation that elevating MUM2 expression in luh mutants completely suppresses the mucilage extrusion defect. Suppression of the luh mutant phenotype was also observed when LEUNIG, a transcriptional corepressor closely related to LUH, was introduced in luh mutants under the control of the LUH promoter. Based on these data, we propose a new model for the regulation of pectin biosynthesis during plant growth and development. PMID:21402796

  1. The Cloning and Functional Characterization of Peach CONSTANS and FLOWERING LOCUS T Homologous Genes PpCO and PpFT.

    Directory of Open Access Journals (Sweden)

    Xiang Zhang

    Full Text Available Flowering is an essential stage of plant growth and development. The successful transition to flowering not only ensures the completion of plant life cycles, it also serves as the basis for the production of economically important seeds and fruits. CONSTANS (CO and FLOWERING LOCUS T (FT are two genes playing critical roles in flowering time control in Arabidopsis. Through homology-based cloning and rapid-amplifications of cDNA ends (RACE, we obtained full-lengths cDNA sequences of Prunus persica CO (PpCO and Prunus persica FT (PpFT from peach (Prunus persica (L. Batsch and investigated their functions in flowering time regulation. PpCO and PpFT showed high homologies to Arabidopsis CO and FT at DNA, mRNA and protein levels. We showed that PpCO and PpFT were nucleus-localized and both showed transcriptional activation activities in yeast cells, consistent with their potential roles as transcription activators. Moreover, we established that the over-expression of PpCO could restore the late flowering phenotype of the Arabidopsis co-2 mutant, and the late flowering defect of the Arabidopsis ft-1 mutant can be rescued by the over-expression of PpFT, suggesting functional conservations of CO and FT genes in peach and Arabidopsis. Our results suggest that PpCO and PpFT are homologous genes of CO and FT in peach and they may function in regulating plant flowering time.

  2. Means of escape provisions and evacuation simulation of public building in Malaysia and Singapore

    Science.gov (United States)

    Samad, Muna Hanim Abdul; Taib, Nooriati; Ying, Choo Siew

    2017-10-01

    The Uniform Building By-law 1984 of Malaysia is the legal document governing fire safety requirements in buildings. Its prescriptive nature has made the requirements out dated from the viewpoint of current performance based approach in most developed countries. The means of escape provisions is a critical requirement to safeguard occupants' safety in fire especially in public buildings. As stipulated in the UBBL 1984, the means of escape provisions includes sufficient escape routes, travel distance, protection of escape routes, etc. designated as means to allow occupants to escape within a safe period of time. This research aims at investigating the effectiveness of those provisions in public buildings during evacuation process involving massive crowd during emergencies. This research includes a scenario-based study on evacuation processes using two software i.e. PyroSim, a crowd modelling software to conduct smoke study and Pathfinder to stimulate evacuation model of building in Malaysia and Singapore as comparative study. The results show that the buildings used as case study were designed according to Malaysian UBBL 1984 and Singapore Firecode, 2013 respectively provide relative safe means of escape. The simulations of fire and smoke and coupled with simulation of evacuation have demonstrated that although there are adequate exits designated according to fire requirements, the impact of the geometry of atriums on the behavior of fire and smoke have significant effect on escape time especially for unfamiliar user of the premises.

  3. Escape of quantum particles from an open nano-circular microcavity

    International Nuclear Information System (INIS)

    Liu, Sheng; Wang, De-hua

    2014-01-01

    When a laser is irradiated on a negative ion, it will provide a coherent, mono-energetic source of detached electrons propagating out from the location of the negative ion. The total escape probability density of the electrons when the negative ion is placed inside an open nano-circular microcavity has been studied on the basis of the semiclassical theory. It is shown that significant oscillations appear in the total escape probability density due to the quantum interference effects. Besides, our study suggests that the escape probability density depends on the laser polarization sensitively. In order to show the correspondence between the escaped probability density and the detached electron's escaped orbits clearly, we calculate the path length spectrum and find that each peak corresponds to the length of one detached electron's escaped orbit. This study provides an example where the quantum nature of the electron's wave function can be observed in the macroscopic world. Our study may guide the future experimental research on the escape and transport process of particles through semiconductor microjunctions.

  4. Multiscale analysis of nonlinear systems using computational homology

    Energy Technology Data Exchange (ETDEWEB)

    Konstantin Mischaikow, Rutgers University/Georgia Institute of Technology, Michael Schatz, Georgia Institute of Technology, William Kalies, Florida Atlantic University, Thomas Wanner,George Mason University

    2010-05-19

    This is a collaborative project between the principal investigators. However, as is to be expected, different PIs have greater focus on different aspects of the project. This report lists these major directions of research which were pursued during the funding period: (1) Computational Homology in Fluids - For the computational homology effort in thermal convection, the focus of the work during the first two years of the funding period included: (1) A clear demonstration that homology can sensitively detect the presence or absence of an important flow symmetry, (2) An investigation of homology as a probe for flow dynamics, and (3) The construction of a new convection apparatus for probing the effects of large-aspect-ratio. (2) Computational Homology in Cardiac Dynamics - We have initiated an effort to test the use of homology in characterizing data from both laboratory experiments and numerical simulations of arrhythmia in the heart. Recently, the use of high speed, high sensitivity digital imaging in conjunction with voltage sensitive fluorescent dyes has enabled researchers to visualize electrical activity on the surface of cardiac tissue, both in vitro and in vivo. (3) Magnetohydrodynamics - A new research direction is to use computational homology to analyze results of large scale simulations of 2D turbulence in the presence of magnetic fields. Such simulations are relevant to the dynamics of black hole accretion disks. The complex flow patterns from simulations exhibit strong qualitative changes as a function of magnetic field strength. Efforts to characterize the pattern changes using Fourier methods and wavelet analysis have been unsuccessful. (4) Granular Flow - two experts in the area of granular media are studying 2D model experiments of earthquake dynamics where the stress fields can be measured; these stress fields from complex patterns of 'force chains' that may be amenable to analysis using computational homology. (5) Microstructure

  5. Multiscale analysis of nonlinear systems using computational homology

    Energy Technology Data Exchange (ETDEWEB)

    Konstantin Mischaikow; Michael Schatz; William Kalies; Thomas Wanner

    2010-05-24

    This is a collaborative project between the principal investigators. However, as is to be expected, different PIs have greater focus on different aspects of the project. This report lists these major directions of research which were pursued during the funding period: (1) Computational Homology in Fluids - For the computational homology effort in thermal convection, the focus of the work during the first two years of the funding period included: (1) A clear demonstration that homology can sensitively detect the presence or absence of an important flow symmetry, (2) An investigation of homology as a probe for flow dynamics, and (3) The construction of a new convection apparatus for probing the effects of large-aspect-ratio. (2) Computational Homology in Cardiac Dynamics - We have initiated an effort to test the use of homology in characterizing data from both laboratory experiments and numerical simulations of arrhythmia in the heart. Recently, the use of high speed, high sensitivity digital imaging in conjunction with voltage sensitive fluorescent dyes has enabled researchers to visualize electrical activity on the surface of cardiac tissue, both in vitro and in vivo. (3) Magnetohydrodynamics - A new research direction is to use computational homology to analyze results of large scale simulations of 2D turbulence in the presence of magnetic fields. Such simulations are relevant to the dynamics of black hole accretion disks. The complex flow patterns from simulations exhibit strong qualitative changes as a function of magnetic field strength. Efforts to characterize the pattern changes using Fourier methods and wavelet analysis have been unsuccessful. (4) Granular Flow - two experts in the area of granular media are studying 2D model experiments of earthquake dynamics where the stress fields can be measured; these stress fields from complex patterns of 'force chains' that may be amenable to analysis using computational homology. (5) Microstructure

  6. RNA Viruses and RNAi: Quasispecies Implications for Viral Escape

    Directory of Open Access Journals (Sweden)

    John B. Presloid

    2015-06-01

    Full Text Available Due to high mutation rates, populations of RNA viruses exist as a collection of closely related mutants known as a quasispecies. A consequence of error-prone replication is the potential for rapid adaptation of RNA viruses when a selective pressure is applied, including host immune systems and antiviral drugs. RNA interference (RNAi acts to inhibit protein synthesis by targeting specific mRNAs for degradation and this process has been developed to target RNA viruses, exhibiting their potential as a therapeutic against infections. However, viruses containing mutations conferring resistance to RNAi were isolated in nearly all cases, underlining the problems of rapid viral evolution. Thus, while promising, the use of RNAi in treating or preventing viral diseases remains fraught with the typical complications that result from high specificity of the target, as seen in other antiviral regimens.

  7. Photonic reagent control of dynamically homologous quantum systems

    International Nuclear Information System (INIS)

    Beltrani, Vincent; Dominy, Jason; Ho, Tak-San; Rabitz, Herschel

    2007-01-01

    The general objective of quantum control is the manipulation of atomic scale physical and chemical phenomena through the application of external control fields. These tailored fields, or photonic reagents, exhibit systematic properties analogous to those of ordinary laboratory reagents. This analogous behavior is explored further here by considering the controlled response of a family of homologous quantum systems to a single common photonic reagent. A level set of dynamically homologous quantum systems is defined as the family that produces the same value(s) for a target physical observable(s) when controlled by a common photonic reagent. This paper investigates the scope of homologous quantum system control using the level set exploration technique (L-SET). L-SET enables the identification of continuous families of dynamically homologous quantum systems. Each quantum system is specified by a point in a hypercube whose edges are labeled by Hamiltonian matrix elements. Numerical examples are presented with simple finite level systems to illustrate the L-SET concepts. Both connected and disconnected families of dynamically homologous systems are shown to exist

  8. Primary homologies of the circumorbital bones of snakes.

    Science.gov (United States)

    Palci, Alessandro; Caldwell, Michael W

    2013-09-01

    Some snakes have two circumorbital ossifications that in the current literature are usually referred to as the postorbital and supraorbital. We review the arguments that have been proposed to justify this interpretation and provide counter-arguments that reject those conjectures of primary homology based on the observation of 32 species of lizards and 81 species of snakes (both extant and fossil). We present similarity arguments, both topological and structural, for reinterpretation of the primary homologies of the dorsal and posterior orbital ossifications of snakes. Applying the test of similarity, we conclude that the posterior orbital ossification of snakes is topologically consistent as the homolog of the lacertilian jugal, and that the dorsal orbital ossification present in some snakes (e.g., pythons, Loxocemus, and Calabaria) is the homolog of the lacertilian postfrontal. We therefore propose that the terms postorbital and supraorbital should be abandoned as reference language for the circumorbital bones of snakes, and be replaced with the terms jugal and postfrontal, respectively. The primary homology claim for the snake "postorbital" fails the test of similarity, while the term "supraorbital" is an unnecessary and inaccurate application of the concept of a neomorphic ossification, for an element that passes the test of similarity as a postfrontal. This reinterpretation of the circumorbital bones of snakes is bound to have important repercussions for future phylogenetic analyses and consequently for our understanding of the origin and evolution of snakes. Copyright © 2013 Wiley Periodicals, Inc.

  9. Quantifying the impact of human immunodeficiency virus-1 escape from cytotoxic T-lymphocytes.

    Directory of Open Access Journals (Sweden)

    Ulrich D Kadolsky

    2010-11-01

    Full Text Available HIV-1 escape from the cytotoxic T-lymphocyte (CTL response leads to a weakening of viral control and is likely to be detrimental to the patient. To date, the impact of escape on viral load and CD4(+ T cell count has not been quantified, primarily because of sparse longitudinal data and the difficulty of separating cause and effect in cross-sectional studies. We use two independent methods to quantify the impact of HIV-1 escape from CTLs in chronic infection: mathematical modelling of escape and statistical analysis of a cross-sectional cohort. Mathematical modelling revealed a modest increase in log viral load of 0.051 copies ml(-1 per escape event. Analysis of the cross-sectional cohort revealed a significant positive association between viral load and the number of "escape events", after correcting for length of infection and rate of replication. We estimate that a single CTL escape event leads to a viral load increase of 0.11 log copies ml(-1 (95% confidence interval: 0.040-0.18, consistent with the predictions from the mathematical modelling. Overall, the number of escape events could only account for approximately 6% of the viral load variation in the cohort. Our findings indicate that although the loss of the CTL response for a single epitope results in a highly statistically significant increase in viral load, the biological impact is modest. We suggest that this small increase in viral load is explained by the small growth advantage of the variant relative to the wildtype virus. Escape from CTLs had a measurable, but unexpectedly low, impact on viral load in chronic infection.

  10. Escape of H and D from Mars' Atmosphere and the Evolution of its Crustal Water Reservoirs

    Science.gov (United States)

    Hartle, Richard E.; Einaudi, Franco (Technical Monitor)

    2001-01-01

    The evolution of water on Mars involves preferential escape of hydrogen over deuterium, producing its deuterium rich atmosphere with a D/H ratio 5.2 times that of terrestrial water. In the past decade, several estimates have been made of the magnitudes of current and ancient crustal water reservoirs on Mars that freely exchange with its atmosphere. Some of the differences in the magnitudes of the reservoirs are influenced by differences in the following basic parameters: composition of H, D, H2 and HD at the exobase; thermal history of the atmosphere; escape mechanisms; and the D/H ratio of earlier epochs as inferred from meteorites. The dominant escape mechanism used in the estimates is Jeans escape. However, the Jeans escape flux is enhanced considerably when atmospheric winds and rotation are applied at the exobase . This constraint is of particular importance because the enhancement of the D escape flux can be an order of magnitude greater than the enhancement of the H escape flux. This preferential enhancement of the D escape flux over that of H means that a great deal more H must escape (than in the case without winds and rotation) to attain the same D/H ratio in the today's atmosphere. Another new constraint on reservoir magnitudes comes from the recent interpretation of Martian meteorite data, which suggests that the D/H ratio was 2 times that of terrestrial water at the end of the heavy bombardment period (1). These two constraints together lead to larger current and ancient crustal water reservoirs. Applying Rayleigh fractionation, new estimates of the sizes of the water reservoirs are made using the above constraints along with plausible values for hydrogen and deuterium densities, temperatures, wind speeds and rotation rates at the exobase.

  11. The cucumber long hypocotyl mutant lacks a light-stable PHYB-like phytochrome.

    Science.gov (United States)

    López-Juez, E; Nagatani, A; Tomizawa, K; Deak, M; Kern, R; Kendrick, R E; Furuya, M

    1992-01-01

    A novel cDNA sequence homologous to a phytochrome B (phyB) gene that was isolated in a library from tobacco tissue has been used in an Escherichia coli expression system to raise anti-phytochrome B (anti-PHYB) polypeptide-specific monoclonal antibodies. The specificity of these antibodies has been tested by cross-reactivity against purified pea light-labile type 1 and light-stable type 2 phytochromes, with some antibodies reacting with the type 2 and none with the type 1 phytochromes. One such antibody, monoclonal mAT1, has been employed to analyze the phytochrome molecular species present in a photomorphogenic long hypocotyl (lh) mutant of cucumber. The results indicated that the mutant contains wild-type levels of the light-labile type 1 phytochrome polypeptide (PHYA), which has an apparent molecular mass of approximately 120 kD, but shows less than 1% (detection limit) of a light-stable polypeptide recognized by mAT1 in wild-type seedlings. This protein, not detectable in the lh mutant, has the properties of light-stable type 2 phytochrome, has an apparent molecular mass of 116 to 117 kD, and remains at constant levels under continuous low-fluence-rate red light. Therefore, we conclude that the lh mutant lacks at least one type 2 phytochrome-like polypeptide, most probably a phyB gene product. The correlation between the lack of this protein and the deficiency or absence of physiological responses to a light-stable phytochrome species in this mutant helps to identify the physiological roles played by the products of different subfamilies within the phytochrome gene family. PMID:1498594

  12. Microevolution of Candida albicans in macrophages restores filamentation in a nonfilamentous mutant.

    Directory of Open Access Journals (Sweden)

    Anja Wartenberg

    2014-12-01

    Full Text Available Following antifungal treatment, Candida albicans, and other human pathogenic fungi can undergo microevolution, which leads to the emergence of drug resistance. However, the capacity for microevolutionary adaptation of fungi goes beyond the development of resistance against antifungals. Here we used an experimental microevolution approach to show that one of the central pathogenicity mechanisms of C. albicans, the yeast-to-hyphae transition, can be subject to experimental evolution. The C. albicans cph1Δ/efg1Δ mutant is nonfilamentous, as central signaling pathways linking environmental cues to hyphal formation are disrupted. We subjected this mutant to constant selection pressure in the hostile environment of the macrophage phagosome. In a comparatively short time-frame, the mutant evolved the ability to escape macrophages by filamentation. In addition, the evolved mutant exhibited hyper-virulence in a murine infection model and an altered cell wall composition compared to the cph1Δ/efg1Δ strain. Moreover, the transcriptional regulation of hyphae-associated, and other pathogenicity-related genes became re-responsive to environmental cues in the evolved strain. We went on to identify the causative missense mutation via whole genome- and transcriptome-sequencing: a single nucleotide exchange took place within SSN3 that encodes a component of the Cdk8 module of the Mediator complex, which links transcription factors with the general transcription machinery. This mutation was responsible for the reconnection of the hyphal growth program with environmental signals in the evolved strain and was sufficient to bypass Efg1/Cph1-dependent filamentation. These data demonstrate that even central transcriptional networks can be remodeled very quickly under appropriate selection pressure.

  13. Development of high yielding mutants in lentil

    International Nuclear Information System (INIS)

    Rajput, M.A.; Sarwar, G.; Siddiqui, K.A.

    2001-01-01

    Full text: Lentil (Lens culinaris Medik.) locally known as Masoor, is the second most important rabi pulse crop, after chickpea, in Pakistan. It is cultivated on an area of over 63,400 ha, which constitutes about 4.83% of the total area under pulses. The annual production of the crop is 28,200 tones with an average yield of 445 kg/ha. Yield at the national level is very low, about one-half of the world's yield, which is mainly due to non-availability of high yield potential genotypes. Keeping in view the importance of mutants in developing a large number of new varieties, an induced mutations programme was initiated at AEARC, Tandojam during 1987-88, to develop high yielding varieties in lentil. For this, seeds of two lentil varieties, 'Masoor-85' and 'ICARDA-8' had been irradiated with gamma-rays ranging from 100-600 Gy in NIAB, Faisalabad during 1990. Selections were made in M2 on the basis of earliness, plant height, branches/plant and 100 grain weight. After confirming these mutants in M3 they were promoted in station yield trials and studied continuously for three consecutive years (1993- 1995). Overall results revealed that these mutants have consistent improvement of earliness in flowering and maturity. Plant height also increased in all mutant lines except AEL 23/40/91 where reduction in this attribute was observed as compared to parent variety. Mutant lines AEL 49/20/91 and AEL 13/30/91 showed improvement in 100 grain weight. The improvement of some agronomic characters enhanced the yield of mutant lines in comparison to parent varieties (Masoor-85 and ICARDA-8). The diversity in yield over the respective parents was computed from 6.94 to 60.12%. From these encouraging results it is hoped that mutant lines like AEL 12/30/91 and AEL 49/20/91 may serve as potential lentil genotypes in future. (author)

  14. Officially released mutant varieties in China

    International Nuclear Information System (INIS)

    Liu, L.; Van Zanten, L.; Shu, Q.Y.; Maluszynski, M.

    2004-01-01

    The use of mutation techniques for crop improvement in China has a long and well-established tradition of more than 50 years. As the result of intensive research in many institutes dealing with application of nuclear technologies more than 620 cultivars of 44 crop species have been released. Numerous mutant varieties have been grown on a large scale bringing significant economic impact, sustaining crop production and greatly contributing to increase of food production also in stress prone areas of the country. However, there is still missing information not only on the number of mutant varieties released in particular crop species but also on mutagens applied, selection approaches and on the use of mutants in cross breeding. Numerous Chinese scientists collected and systematized this information. Results of their work were often published in local scientific journals in the Chinese language and as such were unavailable to breeders from other countries. Having this in mind, we requested Dr. Liu Luxiang, the Director of the Department of Plant Mutation Breeding and Genetics, Institute for Application of Atomic Energy, Chinese Academy of Agricultural Sciences in Beijing to help us in finding as much information as possible on mutant varieties officially released in China. The data has been collected in close collaboration with his colleagues from various institutions all over the country and then evaluated, edited and prepared for publication by our team responsible for the FAO/IAEA Database of Officially Released Mutant Varieties. We would like to thank all Chinese colleagues who contributed to this list of Chinese mutant varieties. We hope that this publication will stimulate plant breeders in China to collect more information on released mutant varieties and especially on the use of mutated genes in cross breeding. (author)

  15. Escaping 1 MeV tritons in TFTR

    International Nuclear Information System (INIS)

    Zweben, S.J.; Strachan, J.D.; Boivin, R.; Cavallo, A.; Fredrickson, E.D.; McGuire, K.; Mynick, H.E.; White, R.B.

    1989-01-01

    1 MeV tritons created by D-D reactions can simulate the 'single-particle' behavior expected with 3.5 MeV D-T alphas, since the gyroradii and slowing-down of these two particles are similar. This paper describes measurements of the flux of escaping 1 MeV tritons from the TFTR plasma during high power D 0 →D neutral beam injection, and shows that in most cases the observed triton loss is consistent with the classical (single-particle) first-orbit loss model. In this model tritons are lost if their first orbit intersects the wall due to their large banana width, while almost all tritons confined on their first orbit should stay confined until thermalized. The triton detectors are ZnS(Ag) scintillator screens housed in light-tight boxes located just outside the plasma boundary at the bottom of the TFTR vessel. They are particle 'pinhole' cameras which can resolve the triton flux vs. pitch angle (to ±5 o ), energy (to ±50 %), and time (to <20 μsec). The 2-D images of triton flux onto these scintillators are optically coupled to either an intensified TV camera or to photomultiplyer tubes for fast time resolution. The soft x-ray background in an earlier prototype has been eliminated. Although there are presently 8 such detectors in TFTR, this paper discusses results from only the detector located just below the vessel center (R=259 cm, r=102 cm). Note that the '1 MeV triton' signal discussed below also has about a 30 % contribution from 3 MeV protons; however, since these two particles have identical gyroradii they should behave alike. 5 refs., 5 figs

  16. A new model for estimation of the consequences of chemical hazards - ESCAPE for Windows; Uusi malli kemikaalionnettomuuksien seurausten arvioimiseen - ESCAPE for Windows

    Energy Technology Data Exchange (ETDEWEB)

    Nikmo, J.; Kukkonen, J.; Riikonen, K. [The Finnish Meteorological Institute, Helsinki (Finland)

    1999-07-01

    By the new computerized model 'ESCAPE for Windows' it is possible to estimate the emissions hazardous substance, the spreading and the impacts of them during chemical accidents. The software can best be used e.g. for rescue service if authorities and the industry, in inspections of industrial plants and post-accident impact analyses. The software has 100 users outside the Meteorological Institute. The model consists of a collection of flow and spreading models. The input data needed consist of the weather and emissions data. The more detailed information on the ESCAPE- model can be found in the English WWW-home page of the model in address http://www.fmi.fi/ENG/ILA/escape.html.

  17. Homology groups for particles on one-connected graphs

    Science.gov (United States)

    MaciÄ Żek, Tomasz; Sawicki, Adam

    2017-06-01

    We present a mathematical framework for describing the topology of configuration spaces for particles on one-connected graphs. In particular, we compute the homology groups over integers for different classes of one-connected graphs. Our approach is based on some fundamental combinatorial properties of the configuration spaces, Mayer-Vietoris sequences for different parts of configuration spaces, and some limited use of discrete Morse theory. As one of the results, we derive the closed-form formulae for ranks of the homology groups for indistinguishable particles on tree graphs. We also give a detailed discussion of the second homology group of the configuration space of both distinguishable and indistinguishable particles. Our motivation is the search for new kinds of quantum statistics.

  18. Lower bounds for homological dimensions of Banach algebras

    International Nuclear Information System (INIS)

    Selivanov, Yurii V

    2007-01-01

    Let A be a commutative unital Banach algebra with infinite spectrum. Then by Helemskii's global dimension theorem the global homological dimension of A is strictly greater than one. This estimate has no analogue for abstract algebras or non-normable topological algebras. It is proved in the present paper that for every unital Banach algebra B the global homological dimensions and the homological bidimensions of the Banach algebras A widehat-otimes B and B (assuming certain restrictions on A) are related by A widehat-otimes B≥2 + dg B and A widehat-otimes B≥2 + db B. Thus, a partial extension of Helemskii's theorem to tensor products is obtained. Bibliography: 28 titles.

  19. Using Persistent Homology to Describe Rayleigh-Bénard Convection

    Science.gov (United States)

    Tithof, Jeffrey; Suri, Balachandra; Xu, Mu; Kramar, Miroslav; Levanger, Rachel; Mischaikow, Konstantin; Paul, Mark; Schatz, Michael

    2015-11-01

    Complex spatial patterns that exhibit aperiodic dynamics commonly arise in a wide variety of systems in nature and technology. Describing, understanding, and predicting the behavior of such patterns is an open problem. We explore the use of persistent homology (a branch of algebraic topology) to characterize spatiotemporal dynamics in a canonical fluid mechanics problem, Rayleigh Bénard convection. Persistent homology provides a powerful mathematical formalism in which the topological characteristics of a pattern (e.g. the midplane temperature field) are encoded in a so-called persistence diagram. By applying a metric to measure the pairwise distances across multiple persistence diagrams, we can quantify the similarities between different states in a time series. Our results show that persistent homology yields new physical insights into the complex dynamics of large spatially extended systems that are driven far-from-equilibrium. This work is supported under NSF grant DMS-1125302.

  20. Functional and evolutionary characterization of Ohr proteins in eukaryotes reveals many active homologs among pathogenic fungi

    Directory of Open Access Journals (Sweden)

    D.A. Meireles

    2017-08-01

    Full Text Available Ohr and OsmC proteins comprise two subfamilies within a large group of proteins that display Cys-based, thiol dependent peroxidase activity. These proteins were previously thought to be restricted to prokaryotes, but we show here, using iterated sequence searches, that Ohr/OsmC homologs are also present in 217 species of eukaryotes with a massive presence in Fungi (186 species. Many of these eukaryotic Ohr proteins possess an N-terminal extension that is predicted to target them to mitochondria. We obtained recombinant proteins for four eukaryotic members of the Ohr/OsmC family and three of them displayed lipoyl peroxidase activity. Further functional and biochemical characterization of the Ohr homologs from the ascomycete fungus Mycosphaerella fijiensis Mf_1 (MfOhr, the causative agent of Black Sigatoka disease in banana plants, was pursued. Similarly to what has been observed for the bacterial proteins, we found that: (i the peroxidase activity of MfOhr was supported by DTT or dihydrolipoamide (dithiols, but not by β-mercaptoethanol or GSH (monothiols, even in large excess; (ii MfOhr displayed preference for organic hydroperoxides (CuOOH and tBOOH over hydrogen peroxide; (iii MfOhr presented extraordinary reactivity towards linoleic acid hydroperoxides (k=3.18 (±2.13×108 M−1 s−1. Both Cys87 and Cys154 were essential to the peroxidase activity, since single mutants for each Cys residue presented no activity and no formation of intramolecular disulfide bond upon treatment with hydroperoxides. The pKa value of the Cysp residue was determined as 5.7±0.1 by a monobromobimane alkylation method. Therefore, eukaryotic Ohr peroxidases share several biochemical features with prokaryotic orthologues and are preferentially located in mitochondria. Keywords: Ohr/OsmC, Thiol-dependent peroxidases, Phylogeny

  1. Functional and evolutionary characterization of Ohr proteins in eukaryotes reveals many active homologs among pathogenic fungi.

    Science.gov (United States)

    Meireles, D A; Domingos, R M; Gaiarsa, J W; Ragnoni, E G; Bannitz-Fernandes, R; da Silva Neto, J F; de Souza, R F; Netto, L E S

    2017-08-01

    Ohr and OsmC proteins comprise two subfamilies within a large group of proteins that display Cys-based, thiol dependent peroxidase activity. These proteins were previously thought to be restricted to prokaryotes, but we show here, using iterated sequence searches, that Ohr/OsmC homologs are also present in 217 species of eukaryotes with a massive presence in Fungi (186 species). Many of these eukaryotic Ohr proteins possess an N-terminal extension that is predicted to target them to mitochondria. We obtained recombinant proteins for four eukaryotic members of the Ohr/OsmC family and three of them displayed lipoyl peroxidase activity. Further functional and biochemical characterization of the Ohr homologs from the ascomycete fungus Mycosphaerella fijiensis Mf_1 (MfOhr), the causative agent of Black Sigatoka disease in banana plants, was pursued. Similarly to what has been observed for the bacterial proteins, we found that: (i) the peroxidase activity of MfOhr was supported by DTT or dihydrolipoamide (dithiols), but not by β-mercaptoethanol or GSH (monothiols), even in large excess; (ii) MfOhr displayed preference for organic hydroperoxides (CuOOH and tBOOH) over hydrogen peroxide; (iii) MfOhr presented extraordinary reactivity towards linoleic acid hydroperoxides (k=3.18 (±2.13)×10 8 M -1 s -1 ). Both Cys 87 and Cys 154 were essential to the peroxidase activity, since single mutants for each Cys residue presented no activity and no formation of intramolecular disulfide bond upon treatment with hydroperoxides. The pK a value of the Cys p residue was determined as 5.7±0.1 by a monobromobimane alkylation method. Therefore, eukaryotic Ohr peroxidases share several biochemical features with prokaryotic orthologues and are preferentially located in mitochondria. Copyright © 2017. Published by Elsevier B.V.

  2. CDK targets Sae2 to control DNA-end resection and homologous recombination.

    Science.gov (United States)

    Huertas, Pablo; Cortés-Ledesma, Felipe; Sartori, Alessandro A; Aguilera, Andrés; Jackson, Stephen P

    2008-10-02

    DNA double-strand breaks (DSBs) are repaired by two principal mechanisms: non-homologous end-joining (NHEJ) and homologous recombination (HR). HR is the most accurate DSB repair mechanism but is generally restricted to the S and G2 phases of the cell cycle, when DNA has been replicated and a sister chromatid is available as a repair template. By contrast, NHEJ operates throughout the cell cycle but assumes most importance in G1 (refs 4, 6). The choice between repair pathways is governed by cyclin-dependent protein kinases (CDKs), with a major site of control being at the level of DSB resection, an event that is necessary for HR but not NHEJ, and which takes place most effectively in S and G2 (refs 2, 5). Here we establish that cell-cycle control of DSB resection in Saccharomyces cerevisiae results from the phosphorylation by CDK of an evolutionarily conserved motif in the Sae2 protein. We show that mutating Ser 267 of Sae2 to a non-phosphorylatable residue causes phenotypes comparable to those of a sae2Delta null mutant, including hypersensitivity to camptothecin, defective sporulation, reduced hairpin-induced recombination, severely impaired DNA-end processing and faulty assembly and disassembly of HR factors. Furthermore, a Sae2 mutation that mimics constitutive Ser 267 phosphorylation complements these phenotypes and overcomes the necessity of CDK activity for DSB resection. The Sae2 mutations also cause cell-cycle-stage specific hypersensitivity to DNA damage and affect the balance between HR and NHEJ. These findings therefore provide a mechanistic basis for cell-cycle control of DSB repair and highlight the importance of regulating DSB resection.

  3. Agronomically valuable mutant lines of castor

    International Nuclear Information System (INIS)

    Bokhan, I.K.

    1990-01-01

    Dry seeds of four castor varieties (VNIIMK 165-improved, VNIIMK 18, Chervonnaya and Antika) were treated with six chemical mutagens, N-nitroso-N-methyl urea (NMU), N-nitroso-N-ethyl urea (NEU), dimethyl sulphate (DMS), diethyl sulphate (DES), ethylenimine (EI) and 1,4-bis-diazoacetyl-butane (DAB) in various doses during 18 hours. About 40,000 plants were studied in M 2 and 80 types of mutations were found, including a number of valuable mutants: short-stemmed, semi-dwarf, dwarf, early maturing, with female and interspersed types of racemes, highly productive etc. Based on trials in M 3 -M 4 , on small plots with two or three replications, the superior mutant lines were identified. The best mutants are presented in the table. Early maturation is very important for growing castor in the USSR, as it is the predecessor of winter wheat in crop rotation. The mutants M2-323 and Ml-83 are of great value as they show early maturation and high yield. Their productivity is mainly conditioned by a high percentage of interspersed plants. The reduction of plant height is of great importance for the successful combine harvesting of castor. Mutant lines M2-119 and Ml-284 characterised by low plant height and high yield are very interesting in this respect. The obtained initial material will be used in further breeding work

  4. Plasmodium berghei: in vivo generation and selection of karyotype mutants and non-gametocyte producer mutants

    NARCIS (Netherlands)

    Janse, C. J.; Ramesar, J.; van den Berg, F. M.; Mons, B.

    1992-01-01

    We previously reported that karyotype and gametocyte-producer mutants spontaneously arose during in vivo asexual multiplication of Plasmodium berghei. Here we studied the rate of selection of these mutants in vivo. Gametocyte production and karyotype pattern were established at regular intervals

  5. Growth and sporulation defects in Bacillus subtilis mutants with a single rrn operon can be suppressed by amplification of the rrn operon.

    Science.gov (United States)

    Yano, Koichi; Masuda, Kenta; Akanuma, Genki; Wada, Tetsuya; Matsumoto, Takashi; Shiwa, Yuh; Ishige, Taichiro; Yoshikawa, Hirofumi; Niki, Hironori; Inaoka, Takashi; Kawamura, Fujio

    2016-01-01

    The genome of Bacillus subtilis strain 168 encodes ten rRNA (rrn) operons. We previously reported that strains with only a single rrn operon had a decreased growth and sporulation frequency. We report here the isolation and characterization of suppressor mutants from seven strains that each have a single rrn operon (rrnO, A, J, I, E, D or B). The suppressor mutants for strain RIK656 with a single rrnO operon had a higher frequency of larger colonies. These suppressor mutants had not only increased growth rates, but also increased sporulation frequencies and ribosome levels compared to the parental mutant strain RIK656. Quantitative PCR analyses showed that all these suppressor mutants had an increased number of copies of the rrnO operon. Suppressor mutants were also isolated from the six other strains with single rrn operons (rrnA, J, I, E, D or B). Next generation and capillary sequencing showed that all of the suppressor mutants had tandem repeats of the chromosomal locus containing the remaining rrn operon (amplicon). These amplicons varied in size from approximately 9 to 179 kb. The amplifications were likely to be initiated by illegitimate recombination between non- or micro-homologous sequences, followed by unequal crossing-over during DNA replication. These results are consistent with our previous report that rrn operon copy number has a major role in cellular processes such as cell growth and sporulation.

  6. Khovanov-Rozansky Graph Homology and Composition Product

    DEFF Research Database (Denmark)

    Wagner, Emmanuel

    2008-01-01

    In analogy with a recursive formula for the HOMFLY-PT polynomial of links given by Jaeger, we give a recursive formula for the graph polynomial introduced by Kauffman and Vogel. We show how this formula extends to the Khovanov–Rozansky graph homology.......In analogy with a recursive formula for the HOMFLY-PT polynomial of links given by Jaeger, we give a recursive formula for the graph polynomial introduced by Kauffman and Vogel. We show how this formula extends to the Khovanov–Rozansky graph homology....

  7. The research progress on plant mutant germplasm resources in China

    International Nuclear Information System (INIS)

    He Cexi; Ji Linzhen; Zhao Shirong

    1991-07-01

    Mutants induced by nuclear radiation or other mutagens are new artificial germplasm resources. Some mutants have been applied in plant breeding and great achievements have been reached. The status and progress on the collection, identification and utilization of mutants in China are introduced. A proposal for developing mutant germplasm resources with good agronomic characters is suggested

  8. A new gcrR-deficient Streptococcus mutans mutant for replacement therapy of dental caries.

    Science.gov (United States)

    Pan, Wenting; Mao, Tiantian; Xu, Qing-an; Shao, Jin; Liu, Chang; Fan, Mingwen

    2013-01-01

    gcrR gene acts as a negative regulator related to sucrose-dependent adherence in S. mutans. It is constructive to test the potential capacity of mutans with gcrR gene deficient in bacteria replacement therapy. In this study, we constructed the mutant by homologous recombination. The morphological characteristics of biofilms were analyzed by confocal laser scanning microscopy. S. mutans UA159 and the mutant MS-gcrR-def were inoculated, respectively, or together for competitive testing in vitro and in rat model. Adhesion assay showed that the adhesion ability of the mutant increased relative to the wild type, especially in the early stage. MS-gcrR-def out-competed S. mutans UA159 in vitro biofilm, and correspondingly coinfection displayed significantly fewer caries in vivo. The former possessed both a lower level of acid production and a stronger colonization potential than S. mutans UA159. These findings demonstrate that MS-gcrR-def appears to be a good candidate for replacement therapy.

  9. A New gcrR-Deficient Streptococcus mutans Mutant for Replacement Therapy of Dental Caries

    Directory of Open Access Journals (Sweden)

    Wenting Pan

    2013-01-01

    Full Text Available Background. gcrR gene acts as a negative regulator related to sucrose-dependent adherence in S. mutans. It is constructive to test the potential capacity of mutans with gcrR gene deficient in bacteria replacement therapy. Methods. In this study, we constructed the mutant by homologous recombination. The morphological characteristics of biofilms were analyzed by confocal laser scanning microscopy. S. mutans UA159 and the mutant MS-gcrR-def were inoculated, respectively, or together for competitive testing in vitro and in rat model. Results. Adhesion assay showed that the adhesion ability of the mutant increased relative to the wild type, especially in the early stage. MS-gcrR-def out-competed S. mutans UA159 in vitro biofilm, and correspondingly coinfection displayed significantly fewer caries in vivo. The former possessed both a lower level of acid production and a stronger colonization potential than S. mutans UA159. Conclusion. These findings demonstrate that MS-gcrR-def appears to be a good candidate for replacement therapy.

  10. Target-directed discovery and production of pharmaceuticals in transgenic mutant plant cells

    Science.gov (United States)

    Brown, DP; Rogers, DT; Gunjan, SK; Gerhardt, GA; Littleton, JM

    2016-01-01

    Plants are a source of complex bioactive compounds, with value as pharmaceuticals, or leads for synthetic modification. Many of these secondary metabolites have evolved as defenses against competing organisms. and their pharmaceutical value is “accidental”, resulting from homology between target proteins in these competitors, and human molecular therapeutic targets. Here we show that it is possible to use mutation and selection of plant cells to re-direct their “evolution” toward metabolites that interact with the therapeutic target proteins themselves. This is achieved by expressing the human target protein in plant cells, and selecting mutants for survival based on the interaction of their metabolome with this target. This report describes the successful evolution of hairy root cultures of a Lobelia species toward increased biosynthesis of metabolites that inhibit the human dopamine transporter protein. Many of the resulting selected mutants are overproducing the active metabolite found in the wild-type plant, but others overproduce active metabolites that are not readily detectable in non-mutants. This technology can access the whole genomic capability of a plant species to biosynthesize metabolites with a specific target. It has potential value as a novel platform for plant drug discovery and production, or as a means of optimizing the therapeutic value of medicinal plant extracts. PMID:27637316

  11. Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1 Mutant Zebrafish.

    Directory of Open Access Journals (Sweden)

    Brian P Grone

    Full Text Available Mutations in the synaptic machinery gene syntaxin-binding protein 1, STXBP1 (also known as MUNC18-1, are linked to childhood epilepsies and other neurodevelopmental disorders. Zebrafish STXBP1 homologs (stxbp1a and stxbp1b have highly conserved sequence and are prominently expressed in the larval zebrafish brain. To understand the functions of stxbp1a and stxbp1b, we generated loss-of-function mutations using CRISPR/Cas9 gene editing and studied brain electrical activity, behavior, development, heart physiology, metabolism, and survival in larval zebrafish. Homozygous stxbp1a mutants exhibited a profound lack of movement, low electrical brain activity, low heart rate, decreased glucose and mitochondrial metabolism, and early fatality compared to controls. On the other hand, homozygous stxbp1b mutants had spontaneous electrographic seizures, and reduced locomotor activity response to a movement-inducing "dark-flash" visual stimulus, despite showing normal metabolism, heart rate, survival, and baseline locomotor activity. Our findings in these newly generated mutant lines of zebrafish suggest that zebrafish recapitulate clinical phenotypes associated with human syntaxin-binding protein 1 mutations.

  12. Escape and Capture from Deep Gravity Wells (Earth, Moon, Planets) Using Low Thrust Propulsion Systems

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA missions are increasingly looking to use low thrust propulsion to capture into planetary orbits and/or lunar orbits, and to escape from low earth orbit. This...

  13. Escape windows to improve the size selectivity in the Baltic cod trawl fishery

    DEFF Research Database (Denmark)

    Madsen, Niels; Holst, René; Foldager, L.

    2002-01-01

    . The history of the use of escape windows in the Baltic Sea cod fishery is reviewed. The present escape windows do not function optimally. The objective of this new experiment was to compare an improved design of escape window, which is placed in the upper panel, with that of standard codend. Three standard......A rapid decrease of the stock of Baltic cod (Gadus morhua) has provided the incentive to improve the size selectivity in the trawl fishery. Use of escape windows is permitted in the legislation to give means of improving the size selectivity of cod as an alternative to a traditional standard codend...... tool to improve the size selectivity in the Baltic cod fishery is discussed. (C) 2002 Elsevier Science B.V. All rights reserved....

  14. Unsteady motion: escape jumps in planktonic copepods, their kinematics and energetics

    DEFF Research Database (Denmark)

    Kiørboe, Thomas; Andersen, Anders Peter; Langlois, Vincent J.

    2010-01-01

    estimate the force and power output needed to accelerate and overcome drag. Both are very high compared with those of other organisms, as are the escape velocities in comparison to startle velocities of other aquatic animals. Thus, the maximum weight-specific force, which for muscle motors of other animals...... has been found to be near constant at 57 N (kg muscle)−1, is more than an order of magnitude higher for the escaping copepods. We argue that this is feasible because most copepods have different systems for steady propulsion (feeding appendages) and intensive escapes (swimming legs), with the muscular...... arrangement of the latter probably adapted for high force production during short-lasting bursts. The resulting escape velocities scale with body length to power 0.65, different from the size-scaling of both similar sized and larger animals moving at constant velocity, but similar to that found for startle...

  15. 78 FR 54585 - Safety Zone; Escape to Miami Triathlon, Biscayne Bay, Miami, FL

    Science.gov (United States)

    2013-09-05

    ... Road Sports and Entertainment Group are sponsoring the Publix Escape to Miami Triathlon. The event will... direct effect on the States, on the relationship between the national government and the States, or on... Coordination with Indian Tribal Governments, [[Page 54587

  16. Inward contaminant leakage tests of the S-Tron Corporation emergency escape breathing device.

    Science.gov (United States)

    1992-04-01

    At the request of S-Tron Corporation, to support their contract with the U.S. Navy, performance tests of the Emergency Escape Breathing Device (EEBD) were conducted in the Environmental Physiology Research Section contaminant leakage chamber. Sulfur ...

  17. High Persister Mutants in Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Heather L Torrey

    Full Text Available Mycobacterium tuberculosis forms drug-tolerant persister cells that are the probable cause of its recalcitrance to antibiotic therapy. While genetically identical to the rest of the population, persisters are dormant, which protects them from killing by bactericidal antibiotics. The mechanism of persister formation in M. tuberculosis is not well understood. In this study, we selected for high persister (hip mutants and characterized them by whole genome sequencing and transcriptome analysis. In parallel, we identified and characterized clinical isolates that naturally produce high levels of persisters. We compared the hip mutants obtained in vitro with clinical isolates to identify candidate persister genes. Genes involved in lipid biosynthesis, carbon metabolism, toxin-antitoxin systems, and transcriptional regulators were among those identified. We also found that clinical hip isolates exhibited greater ex vivo survival than the low persister isolates. Our data suggest that M. tuberculosis persister formation involves multiple pathways, and hip mutants may contribute to the recalcitrance of the infection.

  18. Identification and Characterization of Non-Cellulose-Producing Mutants of Gluconacetobacter hansenii Generated by Tn5 Transposon Mutagenesis

    Science.gov (United States)

    Deng, Ying; Nagachar, Nivedita; Xiao, Chaowen; Tien, Ming

    2013-01-01

    The acs operon of Gluconacetobacter is thought to encode AcsA, AcsB, AcsC, and AcsD proteins that constitute the cellulose synthase complex, required for the synthesis and secretion of crystalline cellulose microfibrils. A few other genes have been shown to be involved in this process, but their precise role is unclear. We report here the use of Tn5 transposon insertion mutagenesis to identify and characterize six non-cellulose-producing (Cel−) mutants of Gluconacetobacter hansenii ATCC 23769. The genes disrupted were acsA, acsC, ccpAx (encoding cellulose-complementing protein [the subscript “Ax” indicates genes from organisms formerly classified as Acetobacter xylinum]), dgc1 (encoding guanylate dicyclase), and crp-fnr (encoding a cyclic AMP receptor protein/fumarate nitrate reductase transcriptional regulator). Protein blot analysis revealed that (i) AcsB and AcsC were absent in the acsA mutant, (ii) the levels of AcsB and AcsC were significantly reduced in the ccpAx mutant, and (iii) the level of AcsD was not affected in any of the Cel− mutants. Promoter analysis showed that the acs operon does not include acsD, unlike the organization of the acs operon of several strains of closely related Gluconacetobacter xylinus. Complementation experiments confirmed that the gene disrupted in each Cel− mutant was responsible for the phenotype. Quantitative real-time PCR and protein blotting results suggest that the transcription of bglAx (encoding β-glucosidase and located immediately downstream from acsD) was strongly dependent on Crp/Fnr. A bglAx knockout mutant, generated via homologous recombination, produced only ∼16% of the wild-type cellulose level. Since the crp-fnr mutant did not produce any cellulose, Crp/Fnr may regulate the expression of other gene(s) involved in cellulose biosynthesis. PMID:24013627

  19. Spinster homolog 2 (spns2 deficiency causes early onset progressive hearing loss.

    Directory of Open Access Journals (Sweden)

    Jing Chen

    2014-10-01

    Full Text Available Spinster homolog 2 (Spns2 acts as a Sphingosine-1-phosphate (S1P transporter in zebrafish and mice, regulating heart development and lymphocyte trafficking respectively. S1P is a biologically active lysophospholipid with multiple roles in signalling. The mechanism of action of Spns2 is still elusive in mammals. Here, we report that Spns2-deficient mice rapidly lost auditory sensitivity and endocochlear potential (EP from 2 to 3 weeks old. We found progressive degeneration of sensory hair cells in the organ of Corti, but the earliest defect was a decline in the EP, suggesting that dysfunction of the lateral wall was the primary lesion. In the lateral wall of adult mutants, we observed structural changes of marginal cell boundaries and of strial capillaries, and reduced expression of several key proteins involved in the generation of the EP (Kcnj10, Kcnq1, Gjb2 and Gjb6, but these changes were likely to be secondary. Permeability of the boundaries of the stria vascularis and of the strial capillaries appeared normal. We also found focal retinal degeneration and anomalies of retinal capillaries together with anterior eye defects in Spns2 mutant mice. Targeted inactivation of Spns2 in red blood cells, platelets, or lymphatic or vascular endothelial cells did not affect hearing, but targeted ablation of Spns2 in the cochlea using a Sox10-Cre allele produced a similar auditory phenotype to the original mutation, suggesting that local Spns2 expression is critical for hearing in mammals. These findings indicate that Spns2 is required for normal maintenance of the EP and hence for normal auditory function, and support a role for S1P signalling in hearing.

  20. Native Mutant Huntingtin in Human Brain

    Science.gov (United States)

    Sapp, Ellen; Valencia, Antonio; Li, Xueyi; Aronin, Neil; Kegel, Kimberly B.; Vonsattel, Jean-Paul; Young, Anne B.; Wexler, Nancy; DiFiglia, Marian

    2012-01-01

    Huntington disease (HD) is caused by polyglutamine expansion in the N terminus of huntingtin (htt). Analysis of human postmortem brain lysates by SDS-PAGE and Western blot reveals htt as full-length and fragmented. Here we used Blue Native PAGE (BNP) and Western blots to study native htt in human postmortem brain. Antisera against htt detected a single band broadly migrating at 575–850 kDa in control brain and at 650–885 kDa in heterozygous and Venezuelan homozygous HD brains. Anti-polyglutamine antisera detected full-length mutant htt in HD brain. There was little htt cleavage even if lysates were pretreated with trypsin, indicating a property of native htt to resist protease cleavage. A soluble mutant htt fragment of about 180 kDa was detected with anti-htt antibody Ab1 (htt-(1–17)) and increased when lysates were treated with denaturants (SDS, 8 m urea, DTT, or trypsin) before BNP. Wild-type htt was more resistant to denaturants. Based on migration of in vitro translated htt fragments, the 180-kDa segment terminated ≈htt 670–880 amino acids. If second dimension SDS-PAGE followed BNP, the 180-kDa mutant htt was absent, and 43–50 kDa htt fragments appeared. Brain lysates from two HD mouse models expressed native full-length htt; a mutant fragment formed if lysates were pretreated with 8 m urea + DTT. Native full-length mutant htt in embryonic HD140Q/140Q mouse primary neurons was intact during cell death and when cell lysates were exposed to denaturants before BNP. Thus, native mutant htt occurs in brain and primary neurons as a soluble full-length monomer. PMID:22375012

  1. Inhibition of chaotic escape from a potential well using small parametric modulations

    International Nuclear Information System (INIS)

    Chacon, R.; Balibrea, F.; Lopez, M.A.

    1996-01-01

    It is shown theoretically for the first time that, depending on its period, amplitude, and initial phase, a periodic parametric modulation can suppress a chaotic escape from a potential well. The instance of the Helmholtz oscillator is used to demonstrate, by means of Melnikov close-quote s method, that parametric modulations of the linear or quadratic potential terms inhibit chaotic escape when certain resonance conditions are met. copyright 1996 American Institute of Physics

  2. Outlet strut fracture and leaflet escape of Bjork-Shiley convexo-concave valve.

    Science.gov (United States)

    Uchino, Gaku; Yoshida, Hideo; Sakoda, Naoya; Hattori, Shigeru; Kawabata, Takuya; Saiki, Munehiro; Fujita, Yasufumi; Yunoki, Keiji; Hisamochi, Kunikazu; Mine, Yoshinari

    2017-06-01

    Prosthetic valve fracture is a serious complication and may arise in patient post-valve replacement. We experienced an outlet strut fracture and leaflet escape of a Bjork-Shiley convexo-concave valve. We performed an emergency redo mitral valve replacement and successfully retrieved the fractured strut and escaped leaflet from superficial femoral artery and the abdominal aorta. The patient showed an uneventful postoperative recovery.

  3. The relationship between migration and development in the ESCAP region.

    Science.gov (United States)

    Skeldon, R

    1991-01-01

    The relationship between migration and development in the ESCAP region including southeast and south Asian countries and the Pacific island of Fiji, Papua New Guinea, Vanuatu, Kiribati, Samoa, and the Solomon Islands is discussed in terms of mobility transition and origin and destination factors. The changing patterns of mobility in Asia are further delineated in the discussion of internal movements and international movement. Emigration in the smaller countries of the Pacific are treated separately. Future predictions are that the Asia Pacific region will experience continued fertility decline and stabilization of low rates over the next 20 years. The declines will result in slow labor force growth, and increased demand for labor in traditional core and neocore countries as defined and presented in table form by Friedman will be heightened. International movements are likely to increase in large urban areas within destination countries. Tokyo and Singapore are the principal cities in Asia. Tokyo by restrictive government policy has limited immigration, but future labor shortages of unskilled labor from southeast Asia and China are expected. Singapore is already dependent on foreign labor by 10%. Current labor shortages have led to the creation of a growth triangle between Singapore, Indonesia, and Malaysia. Other cities expected to emerge as primary cities in international regional complexes with spillover into the hinterlands include the Hong Kong, Guangzhou, and Macau triangle in the Pearl River delta, Taipei and Seoul, and possibly Kuala Lumpur. Internal migration is expected to increase in the capital cities of Bangkok, Manila,j and centers such as Shanghai, Beijing, and other large cities of southeast Asia. These cities will be linked through the flows of skilled international migrants, which began in the 1960s and is expected to become a future major flow. Recreational and resource niches will be left in much of the Pacific, the Himalayan Kingdoms, and

  4. Enhancing usability of augmented-reality-based mobile escape guidelines for radioactive accidents

    International Nuclear Information System (INIS)

    Tsai, Ming-Kuan; Yau, Nie-Jia

    2013-01-01

    When radioactive accidents occur, modern tools in information technology for emergency response are good solutions to reduce the impact. Since few information-technology-based applications were developed for people during radioactive accidents, a previous study (Tsai et al., 2012) proposed augmented-reality-based mobile escape guidelines. However, because of the lack of transparent escape routes and indoor escape guidelines, the usability of the guidelines is limited. Therefore, this study introduces route planning and mobile three-dimensional (3D) graphics techniques to address the identified problems. The proposed approach could correctly present the geographical relationship from user locations to the anticipated shelters, and quickly show the floor-plan drawings as users are in the buildings. Based on the testing results, in contrast to the previous study, this study offered better escape routes, when the participants performed self-evacuation in outdoor and indoor environments. Overall, this study is not only a useful reference for similar studies, but also a beneficial tool for emergency response during radioactive accidents. -- Highlights: ► Enhancing the efficiency when people escape from radioactive accidents. ► The spatial relationship is transparently displayed in real time. ► In contrast to a previous study, this study offers better escape guidelines

  5. Scaling invariance for the escape of particles from a periodically corrugated waveguide

    Energy Technology Data Exchange (ETDEWEB)

    Leonel, Edson D., E-mail: edleonel@rc.unesp.br [Departamento de Estatística, Matemática Aplicada e Computação, UNESP – Univ Estadual Paulista, Av. 24A, 1515, CEP 13506-900, Rio Claro, SP (Brazil); Costa, Diogo R. da [Departamento de Estatística, Matemática Aplicada e Computação, UNESP – Univ Estadual Paulista, Av. 24A, 1515, CEP 13506-900, Rio Claro, SP (Brazil); Instituto de Física, Univ São Paulo, Rua do Matão, Cidade Universitária, CEP 05314-970, São Paulo, SP (Brazil); Dettmann, Carl P. [School of Mathematics, University of Bristol, Bristol BS8 1TW (United Kingdom)

    2012-01-09

    The escape dynamics of a classical light ray inside a corrugated waveguide is characterised by the use of scaling arguments. The model is described via a two-dimensional nonlinear and area preserving mapping. The phase space of the mapping contains a set of periodic islands surrounded by a large chaotic sea that is confined by a set of invariant tori. When a hole is introduced in the chaotic sea, letting the ray escape, the histogram of frequency of the number of escaping particles exhibits rapid growth, reaching a maximum value at n{sub p} and later decaying asymptotically to zero. The behaviour of the histogram of escape frequency is characterised using scaling arguments. The scaling formalism is widely applicable to critical phenomena and useful in characterisation of phase transitions, including transitions from limited to unlimited energy growth in two-dimensional time varying billiard problems. -- Highlights: ► Escape of light ray inside a corrugated waveguide ► Two-dimensional nonlinear and area preserving mapping ► Scaling for escaping particles.

  6. Effects of Serotonergic and Opioidergic Drugs on Escape Behaviors and Social Status of Male Crickets

    Science.gov (United States)

    Dyakonova, V. E.; Schürmann, F.-W.; Sakharov, D. A.

    We examined the effects of selective serotonin depletion and opioid ligands on social rank and related escape behavior of the cricket Gryllus bimaculatus. Establishment of social rank in a pair of males affected their escape reactions. Losers showed a lower and dominants a higher percentage of jumps in response to tactile cercal stimulation than before a fight. The serotonin-depleting drug α-methyltryptophan (AMTP) caused an activation of the escape reactivity in socially naive crickets. AMTP-treated animals also showed a lower ability to become dominants. With an initial 51.6+/-3.6% of wins in the AMTP group, the percentage decreased to 26+/-1.6% on day 5 after injection. The opiate receptor antagonist naloxone affected fight and escape similarly as AMTP. In contrast to naloxone, the opioid agonist [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin decreased escape responsiveness to cercal stimulation in naive and subordinate crickets. We suggest that serotonergic and opioid systems are involved in the dominance induced depression of escape behavior.

  7. An approximate analytic model of a star cluster with potential escapers

    Science.gov (United States)

    Daniel, Kathryne J.; Heggie, Douglas C.; Varri, Anna Lisa

    2017-06-01

    In the context of a star cluster moving on a circular galactic orbit, a 'potential escaper' is a cluster star that has orbital energy greater than the escape energy, and yet is confined within the Jacobi radius of the stellar system. On the other hand, analytic models of stellar clusters typically have a truncation energy equal to the cluster escape energy, and therefore explicitly exclude these energetically unbound stars. Starting from the landmark analysis performed by Hénon of periodic orbits of the circular Hill equations, we present a numerical exploration of the population of 'non-escapers', defined here as those stars that remain within two Jacobi radii for several galactic periods, with energy above the escape energy. We show that they can be characterized by the Jacobi integral and two further approximate integrals, which are based on perturbation theory and ideas drawn from Lidov-Kozai theory. Finally, we use these results to construct an approximate analytic model that includes a phase-space description of a population resembling that of potential escapers, in addition to the usual bound population.

  8. Scaling invariance for the escape of particles from a periodically corrugated waveguide

    International Nuclear Information System (INIS)

    Leonel, Edson D.; Costa, Diogo R. da; Dettmann, Carl P.

    2012-01-01

    The escape dynamics of a classical light ray inside a corrugated waveguide is characterised by the use of scaling arguments. The model is described via a two-dimensional nonlinear and area preserving mapping. The phase space of the mapping contains a set of periodic islands surrounded by a large chaotic sea that is confined by a set of invariant tori. When a hole is introduced in the chaotic sea, letting the ray escape, the histogram of frequency of the number of escaping particles exhibits rapid growth, reaching a maximum value at n p and later decaying asymptotically to zero. The behaviour of the histogram of escape frequency is characterised using scaling arguments. The scaling formalism is widely applicable to critical phenomena and useful in characterisation of phase transitions, including transitions from limited to unlimited energy growth in two-dimensional time varying billiard problems. -- Highlights: ► Escape of light ray inside a corrugated waveguide ► Two-dimensional nonlinear and area preserving mapping ► Scaling for escaping particles.

  9. Lobelia siphilitica plants that escape herbivory in time also have reduced latex production.

    Directory of Open Access Journals (Sweden)

    Amy L Parachnowitsch

    Full Text Available Flowering phenology is an important determinant of a plant's reproductive success. Both assortative mating and niche construction can result in the evolution of correlations between phenology and other reproductive, functional, and life history traits. Correlations between phenology and herbivore defence traits are particularly likely because the timing of flowering can allow a plant to escape herbivory. To test whether herbivore escape and defence are correlated, we estimated phenotypic and genetic correlations between flowering phenology and latex production in greenhouse-grown Lobelia siphilitica L. (Lobeliaceae. Lobelia siphilitica plants that flower later escape herbivory by a specialist pre-dispersal seed predator, and thus should invest fewer resources in defence. Consistent with this prediction, we found that later flowering was phenotypically and genetically correlated with reduced latex production. To test whether herbivore escape and latex production were costly, we also measured four fitness correlates. Flowering phenology was negatively genetically correlated with three out of four fitness estimates, suggesting that herbivore escape can be costly. In contrast, we did not find evidence for costs of latex production. Generally, our results suggest that herbivore escape and defence traits will not evolve independently in L. siphilitica.

  10. Lobelia siphilitica Plants That Escape Herbivory in Time Also Have Reduced Latex Production

    Science.gov (United States)

    Parachnowitsch, Amy L.; Caruso, Christina M.; Campbell, Stuart A.; Kessler, André

    2012-01-01

    Flowering phenology is an important determinant of a plant’s reproductive success. Both assortative mating and niche construction can result in the evolution of correlations between phenology and other reproductive, functional, and life history traits. Correlations between phenology and herbivore defence traits are particularly likely because the timing of flowering can allow a plant to escape herbivory. To test whether herbivore escape and defence are correlated, we estimated phenotypic and genetic correlations between flowering phenology and latex production in greenhouse-grown Lobelia siphilitica L. (Lobeliaceae). Lobelia siphilitica plants that flower later escape herbivory by a specialist pre-dispersal seed predator, and thus should invest fewer resources in defence. Consistent with this prediction, we found that later flowering was phenotypically and genetically correlated with reduced latex production. To test whether herbivore escape and latex production were costly, we also measured four fitness correlates. Flowering phenology was negatively genetically correlated with three out of four fitness estimates, suggesting that herbivore escape can be costly. In contrast, we did not find evidence for costs of latex production. Generally, our results suggest that herbivore escape and defence traits will not evolve independently in L. siphilitica. PMID:22662205

  11. Heat-induced symmetry breaking in ant (Hymenoptera: Formicidae) escape behavior.

    Science.gov (United States)

    Chung, Yuan-Kai; Lin, Chung-Chi

    2017-01-01

    The collective egress of social insects is important in dangerous situations such as natural disasters or enemy attacks. Some studies have described the phenomenon of symmetry breaking in ants, with two exits induced by a repellent. However, whether symmetry breaking occurs under high temperature conditions, which are a common abiotic stress, remains unknown. In our study, we deposited a group of Polyrhachis dives ants on a heated platform and counted the number of escaping ants with two identical exits. We discovered that ants asymmetrically escaped through two exits when the temperature of the heated platform was >32.75°C. The degree of asymmetry increased linearly with the temperature of the platform. Furthermore, the higher the temperature of heated platform was, the more ants escaped from the heated platform. However, the number of escaping ants decreased for 3 min when the temperature was higher than the critical thermal limit (39.46°C), which is the threshold for ants to endure high temperature without a loss of performance. Moreover, the ants tended to form small groups to escape from the thermal stress. A preparatory formation of ant grouping was observed before they reached the exit, indicating that the ants actively clustered rather than accidentally gathered at the exits to escape. We suggest that a combination of individual and grouping ants may help to optimize the likelihood of survival during evacuation.

  12. Heat-induced symmetry breaking in ant (Hymenoptera: Formicidae escape behavior.

    Directory of Open Access Journals (Sweden)

    Yuan-Kai Chung

    Full Text Available The collective egress of social insects is important in dangerous situations such as natural disasters or enemy attacks. Some studies have described the phenomenon of symmetry breaking in ants, with two exits induced by a repellent. However, whether symmetry breaking occurs under high temperature conditions, which are a common abiotic stress, remains unknown. In our study, we deposited a group of Polyrhachis dives ants on a heated platform and counted the number of escaping ants with two identical exits. We discovered that ants asymmetrically escaped through two exits when the temperature of the heated platform was >32.75°C. The degree of asymmetry increased linearly with the temperature of the platform. Furthermore, the higher the temperature of heated platform was, the more ants escaped from the heated platform. However, the number of escaping ants decreased for 3 min when the temperature was higher than the critical thermal limit (39.46°C, which is the threshold for ants to endure high temperature without a loss of performance. Moreover, the ants tended to form small groups to escape from the thermal stress. A preparatory formation of ant grouping was observed before they reached the exit, indicating that the ants actively clustered rather than accidentally gathered at the exits to escape. We suggest that a combination of individual and grouping ants may help to optimize the likelihood of survival during evacuation.

  13. Homology of the open moduli space of curves

    DEFF Research Database (Denmark)

    Madsen, Ib Henning

    2012-01-01

    This is a survey on the proof of a generalized version of the Mumford conjecture obtained in joint work with M. Weiss stating that a certain map between some classifying spaces which a priori have different natures induces an isomorphism at the level of integral homology. We also discuss our proo...

  14. On rationality of logarithmic Q-homology planes - I

    International Nuclear Information System (INIS)

    Pradeep, C.R.

    1995-09-01

    Normal surfaces over the complex plane are considered that are logarithmic (i.e., all its singularities are of the quotient type) and of which all reduced homology groups with rational coefficients vanish. It is proved that all such planes are rational. 16 refs

  15. Comparative homology modeling of human rhodopsin with several ...

    African Journals Online (AJOL)

    The molecular structure of rhodopsin has been studied by cryo-electron microscopic, Nuclear Magnetic Resonance (NMR) and X-ray crystallographic techniques in bovine. A humble effort has been ... Key words: Homology modeling, human rhodopsin, bovine templates, sequence alignment, model building, energy profiles.

  16. Monitoring homologous recombination in rice (Oryza sativa L.)

    Energy Technology Data Exchange (ETDEWEB)

    Yang Zhuanying; Tang Li [Guangdong Provincial Key Lab of Biotechnology for Plant Development, College of Life Sciences, South China Normal University, Guangzhou 510631 (China); Li Meiru [South China Botanic Garden, Chinese Academy of Sciences, Guangzhou 510650 (China); Chen Lei; Xu Jie [Guangdong Provincial Key Lab of Biotechnology for Plant Development, College of Life Sciences, South China Normal University, Guangzhou 510631 (China); Wu Goujiang [South China Botanic Garden, Chinese Academy of Sciences, Guangzhou 510650 (China); Li Hongqing, E-mail: hqli@scnu.edu.cn [Guangdong Provincial Key Lab of Biotechnology for Plant Development, College of Life Sciences, South China Normal University, Guangzhou 510631 (China)

    2010-09-10

    Here we describe a system to assay homologous recombination during the complete life cycle of rice (Oryza sativa L.). Rice plants were transformed with two copies of non-functional GUS reporter overlap fragments as recombination substrate. Recombination was observed in all plant organs examined, from the seed stage until the flowering stage of somatic plant development. Embryogenic cells exhibited the highest recombination ability with an average of 3 x 10{sup -5} recombination events per genome, which is about 10-fold of that observed in root cells, and two orders of that observed in leaf cells. Histological analysis revealed that recombination events occurred in diverse cell types, but preferentially in cells with small size. Examples of this included embryogenic cells in callus, phloem cells in the leaf vein, and cells located in the root apical meristem. Steady state RNA analysis revealed that the expression levels of rice Rad51 homologs are positively correlated with increased recombination rates in embryogenic calli, roots and anthers. Finally, radiation treatment of plantlets from distinct recombination lines increased the recombination frequency to different extents. These results showed that homologous recombination frequency can be effectively measured in rice using a transgene reporter assay. This system will facilitate the study of DNA damage signaling and homologous recombination in rice, a model monocot.

  17. Response of Sahel goats tp homologous PPR vaccine (Capripestovax

    African Journals Online (AJOL)

    The response of Sahel goats to homologous PPR vaccine (CapripestovaxR) under field conditions was investigated in Maiduguri, using virus neutralization test and haematology. The study showed that the Sahel goats seroconverted with geometric mean titres (GMT) of 18.5 and 130 on day zero and 28 days post ...

  18. Multiresolution persistent homology for excessively large biomolecular datasets

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Kelin; Zhao, Zhixiong [Department of Mathematics, Michigan State University, East Lansing, Michigan 48824 (United States); Wei, Guo-Wei, E-mail: wei@math.msu.edu [Department of Mathematics, Michigan State University, East Lansing, Michigan 48824 (United States); Department of Electrical and Computer Engineering, Michigan State University, East Lansing, Michigan 48824 (United States); Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824 (United States)

    2015-10-07

    Although persistent homology has emerged as a promising tool for the topological simplification of complex data, it is computationally intractable for large datasets. We introduce multiresolution persistent homology to handle excessively large datasets. We match the resolution with the scale of interest so as to represent large scale datasets with appropriate resolution. We utilize flexibility-rigidity index to access the topological connectivity of the data set and define a rigidity density for the filtration analysis. By appropriately tuning the resolution of the rigidity density, we are able to focus the topological lens on the scale of interest. The proposed multiresolution topological analysis is validated by a hexagonal fractal image which has three distinct scales. We further demonstrate the proposed method for extracting topological fingerprints from DNA molecules. In particular, the topological persistence of a virus capsid with 273 780 atoms is successfully analyzed which would otherwise be inaccessible to the normal point cloud method and unreliable by using coarse-grained multiscale persistent homology. The proposed method has also been successfully applied to the protein domain classification, which is the first time that persistent homology is used for practical protein domain analysis, to our knowledge. The proposed multiresolution topological method has potential applications in arbitrary data sets, such as social networks, biological networks, and graphs.

  19. Homology modeling of ɣ-aminobutyrate- aminotransferase, a ...

    African Journals Online (AJOL)

    Jane

    2011-06-29

    Jun 29, 2011 ... of GABA-AT is not experimentally known, and we thus resorted to homology modelling to build a model based on x-ray crystal ... MUSCLE programs. The model was further checked for its correctness by predicting the .... is an important step for the prediction of protein's tertiary structure. Secondary structure ...

  20. Efficacy of homologous peste des petits ruminants vaccine on sheep ...

    African Journals Online (AJOL)

    The effect of homologous peste des petits ruminants vaccine (HPPRV) on flock size, morbidity and mortality in sheep and goats was determined in five locations, Unguwan Goje, Bayan Fada, Lowcost, Kyamsangi, and Bagyar, in Dengi, Kanam Local Government Area of Plateau State. Enzyme-linked Immunosorbent Assay ...