Sample records for ha1 globular domain

  1. Glycosylation Focuses Sequence Variation in the Influenza A Virus H1 Hemagglutinin Globular Domain

    PubMed Central

    Hensley, Scott E.; Hurt, Darrell E.; Bennink, Jack R.; Yewdell, Jonathan W.

    2010-01-01

    Antigenic drift in the influenza A virus hemagglutinin (HA) is responsible for seasonal reformulation of influenza vaccines. Here, we address an important and largely overlooked issue in antigenic drift: how does the number and location of glycosylation sites affect HA evolution in man? We analyzed the glycosylation status of all full-length H1 subtype HA sequences available in the NCBI influenza database. We devised the “flow index” (FI), a simple algorithm that calculates the tendency for viruses to gain or lose consensus glycosylation sites. The FI predicts the predominance of glycosylation states among existing strains. Our analyses show that while the number of glycosylation sites in the HA globular domain does not influence the overall magnitude of variation in defined antigenic regions, variation focuses on those regions unshielded by glycosylation. This supports the conclusion that glycosylation generally shields HA from antibody-mediated neutralization, and implies that fitness costs in accommodating oligosaccharides limit virus escape via HA hyperglycosylation. PMID:21124818

  2. Interdependence of the rad50 hook and globular domain functions.

    PubMed

    Hohl, Marcel; Kochańczyk, Tomasz; Tous, Cristina; Aguilera, Andrés; Krężel, Artur; Petrini, John H J

    2015-02-05

    Rad50 contains a conserved Zn(2+) coordination domain (the Rad50 hook) that functions as a homodimerization interface. Hook ablation phenocopies Rad50 deficiency in all respects. Here, we focused on rad50 mutations flanking the Zn(2+)-coordinating hook cysteines. These mutants impaired hook-mediated dimerization, but recombination between sister chromatids was largely unaffected. This may reflect that cohesin-mediated sister chromatid interactions are sufficient for double-strand break repair. However, Mre11 complex functions specified by the globular domain, including Tel1 (ATM) activation, nonhomologous end joining, and DNA double-strand break end resection were affected, suggesting that dimerization exerts a broad influence on Mre11 complex function. These phenotypes were suppressed by mutations within the coiled-coil and globular ATPase domains, suggesting a model in which conformational changes in the hook and globular domains are transmitted via the extended coils of Rad50. We propose that transmission of spatial information in this manner underlies the regulation of Mre11 complex functions. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Homology modeling study toward identifying structural properties in the HA2 B-loop that would influence the HA1 receptor-binding site.

    PubMed

    Cueno, Marni E; Imai, Kenichi; Shimizu, Kazufumi; Ochiai, Kuniyasu

    2013-07-01

    Influenza hemagglutinin (HA) consists of a fibrous globular stem (HA2) inserted into the viral membrane supporting a globular head (HA1). HA1 receptor-binding has been hypothesized to be structurally correlated to the HA2 B-loop, however, this was never fully understood. Here, we elucidated the structural relationship between the HA2 B-loop and the HA1 receptor-binding site (RBS). Throughout this study, we analyzed 2486 H1N1 HA homology models obtained from human, swine and avian strains during 1976-2012. Quality of all homology models were verified before further analyses. We established that amino acid residue 882 is putatively strain-conserved and differs in the human (K882), swine (H882) and avian (N882) strains. Moreover, we observed that the amino acid at residue 882 and, similarly, its orientation has the potential to influence the HA1 RBS diameter measurements which we hypothesize may consequentially affect influenza H1N1 viral infectivity, immune escape, transmissibility, and evolution. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Crystal structures of the coil 2B fragment and the globular tail domain of human lamin B1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ruan, Jianbin; Xu, Chao; Bian, Chuanbing

    2012-07-18

    We present here the crystal structures of human lamin B1 globular tail domain and coiled 2B domain, which adopt similar folds to Ig-like domain and coiled-coil domain of lamin A, respectively. Despite the overall similarity, we found an extra intermolecular disulfide bond in the lamin B1 coil 2B domain, which does not exist in lamin A/C. In addition, the structural analysis indicates that interactions at the lamin B1 homodimer interface are quite different from those of lamin A/C. Thus our research not only reveals the diversely formed homodimers among lamin family members, but also sheds light on understanding the importantmore » roles of lamin B1 in forming the nuclear lamina matrix.« less

  5. Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains.

    PubMed

    Azizyan, Rafayel A; Garro, Adriana; Radkova, Zinaida; Anikeenko, Alexey; Bakulina, Anastasia; Dumas, Christian; Kajava, Andrey V

    2018-06-01

    In many disease-related and functional amyloids, the amyloid-forming regions of proteins are flanked by globular domains. When located in close vicinity of the amyloid regions along the chain, the globular domains can prevent the formation of amyloids because of the steric repulsion. Experimental tests of this effect are few in number and non-systematic, and their interpretation is hampered by polymorphism of amyloid structures. In this situation, modeling approaches that use such a clear-cut criterion as the steric tension can give us highly trustworthy results. In this work, we evaluated this steric effect by using molecular modeling and dynamics. As an example, we tested hybrid proteins containing an amyloid-forming fragment of Aβ peptide (17-42) linked to one or two globular domains of GFP. Searching for the shortest possible linker, we constructed models with pseudo-helical arrangements of the densely packed GFPs around the Aβ amyloid core. The molecular modeling showed that linkers of 7 and more residues allow fibrillogenesis of the Aβ-peptide flanked by GFP on one side and 18 and more residues when Aβ-peptide is flanked by GFPs on both sides. Furthermore, we were able to establish a more general relationship between the size of the globular domains and the length of the linkers by using analytical expressions and rigid body simulations. Our results will find use in planning and interpretation of experiments, improvement of the prediction of amyloidogenic regions in proteins, and design of new functional amyloids carrying globular domains. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. The globular domain of histone H5 is internally located in the 30 nm chromatin fiber: an immunochemical study.

    PubMed Central

    Dimitrov, S I; Russanova, V R; Pashev, I G

    1987-01-01

    The location of the globular domain of histone H5 relative to the axis of the 30 nm chromatin fiber was investigated by following the accessibility of this region of the molecule in chicken erythrocyte chromatin to specific antibodies as a function of chromatin structure. Antibodies to the globular domain of H5 as well as their Fab fragments were found to react with chromatin at ionic strengths ranging from 1-80 mM NaCl, the reaction gradually decreasing upon increase of salt concentration. If, however, Fab fragments were conjugated to ferritin, no reaction of the complex with chromatin was observed at salt concentrations higher than 20 mM. The accessibility of the globular part of H5 in unfolded chromatin to the Fab-ferritin complex was also demonstrated with trypsin-digested chromatin. The experiments were carried out by both solid-phase immunoassay and inhibition experiments. The data obtained are consistent with a structure in which the globular domain of H5 is internally located in the 30 nm chromatin fiber. Images Fig. 1. Fig. 2. PMID:2444434

  7. Phylogeny-Based Systematization of Arabidopsis Proteins with Histone H1 Globular Domain1[OPEN

    PubMed Central

    Knizewski, Lukasz; Schmidt, Anja; Ginalski, Krzysztof

    2017-01-01

    H1 (or linker) histones are basic nuclear proteins that possess an evolutionarily conserved nucleosome-binding globular domain, GH1. They perform critical functions in determining the accessibility of chromatin DNA to trans-acting factors. In most metazoan species studied so far, linker histones are highly heterogenous, with numerous nonallelic variants cooccurring in the same cells. The phylogenetic relationships among these variants as well as their structural and functional properties have been relatively well established. This contrasts markedly with the rather limited knowledge concerning the phylogeny and structural and functional roles of an unusually diverse group of GH1-containing proteins in plants. The dearth of information and the lack of a coherent phylogeny-based nomenclature of these proteins can lead to misunderstandings regarding their identity and possible relationships, thereby hampering plant chromatin research. Based on published data and our in silico and high-throughput analyses, we propose a systematization and coherent nomenclature of GH1-containing proteins of Arabidopsis (Arabidopsis thaliana [L.] Heynh) that will be useful for both the identification and structural and functional characterization of homologous proteins from other plant species. PMID:28298478

  8. Phylogeny-Based Systematization of Arabidopsis Proteins with Histone H1 Globular Domain.

    PubMed

    Kotliński, Maciej; Knizewski, Lukasz; Muszewska, Anna; Rutowicz, Kinga; Lirski, Maciej; Schmidt, Anja; Baroux, Célia; Ginalski, Krzysztof; Jerzmanowski, Andrzej

    2017-05-01

    H1 (or linker) histones are basic nuclear proteins that possess an evolutionarily conserved nucleosome-binding globular domain, GH1. They perform critical functions in determining the accessibility of chromatin DNA to trans-acting factors. In most metazoan species studied so far, linker histones are highly heterogenous, with numerous nonallelic variants cooccurring in the same cells. The phylogenetic relationships among these variants as well as their structural and functional properties have been relatively well established. This contrasts markedly with the rather limited knowledge concerning the phylogeny and structural and functional roles of an unusually diverse group of GH1-containing proteins in plants. The dearth of information and the lack of a coherent phylogeny-based nomenclature of these proteins can lead to misunderstandings regarding their identity and possible relationships, thereby hampering plant chromatin research. Based on published data and our in silico and high-throughput analyses, we propose a systematization and coherent nomenclature of GH1-containing proteins of Arabidopsis ( Arabidopsis thaliana [L.] Heynh) that will be useful for both the identification and structural and functional characterization of homologous proteins from other plant species. © 2017 American Society of Plant Biologists. All Rights Reserved.

  9. Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain

    PubMed Central

    Steel, John; Lowen, Anice C.; Wang, Taia T.; Yondola, Mark; Gao, Qinshan; Haye, Kester; García-Sastre, Adolfo; Palese, Peter

    2010-01-01

    ABSTRACT Although highly effective in the general population when well matched to circulating influenza virus strains, current influenza vaccines are limited in their utility due to the narrow breadth of protection they provide. The strain specificity of vaccines presently in use mirrors the exquisite specificity of the neutralizing antibodies that they induce, that is, antibodies which bind to the highly variable globular head domain of hemagglutinin (HA). Herein, we describe the construction of a novel immunogen comprising the conserved influenza HA stalk domain and lacking the globular head. Vaccination of mice with this headless HA construct elicited immune sera with broader reactivity than those obtained from mice immunized with a full-length HA. Furthermore, the headless HA vaccine provided full protection against death and partial protection against disease following lethal viral challenge. Our results suggest that the response induced by headless HA vaccines is sufficiently potent to warrant their further development toward a universal influenza virus vaccine. PMID:20689752

  10. Cingulin Contains Globular and Coiled-Coil Domains and Interacts with Zo-1, Zo-2, Zo-3, and Myosin

    PubMed Central

    Cordenonsi, Michelangelo; D'Atri, Fabio; Hammar, Eva; Parry, David A.D.; Kendrick-Jones, John; Shore, David; Citi, Sandra

    1999-01-01

    We characterized the sequence and protein interactions of cingulin, an M r 140–160-kD phosphoprotein localized on the cytoplasmic surface of epithelial tight junctions (TJ). The derived amino acid sequence of a full-length Xenopus laevis cingulin cDNA shows globular head (residues 1–439) and tail (1,326–1,368) domains and a central α-helical rod domain (440–1,325). Sequence analysis, electron microscopy, and pull-down assays indicate that the cingulin rod is responsible for the formation of coiled-coil parallel dimers, which can further aggregate through intermolecular interactions. Pull-down assays from epithelial, insect cell, and reticulocyte lysates show that an NH2-terminal fragment of cingulin (1–378) interacts in vitro with ZO-1 (K d ∼5 nM), ZO-2, ZO-3, myosin, and AF-6, but not with symplekin, and a COOH-terminal fragment (377–1,368) interacts with myosin and ZO-3. ZO-1 and ZO-2 immunoprecipitates contain cingulin, suggesting in vivo interactions. Full-length cingulin, but not NH2-terminal and COOH-terminal fragments, colocalizes with endogenous cingulin in transfected MDCK cells, indicating that sequences within both head and rod domains are required for TJ localization. We propose that cingulin is a functionally important component of TJ, linking the submembrane plaque domain of TJ to the actomyosin cytoskeleton. PMID:10613913

  11. Precision Landing and Hazard Avoidance (PL&HA) Domain

    NASA Technical Reports Server (NTRS)

    Robertson, Edward A.; Carson, John M., III

    2016-01-01

    The Precision Landing and Hazard Avoidance (PL&HA) domain addresses the development, integration, testing, and spaceflight infusion of sensing, processing, and GN&C (Guidance, Navigation and Control) functions critical to the success and safety of future human and robotic exploration missions. PL&HA sensors also have applications to other mission events, such as rendezvous and docking.

  12. The structure of the Myo4p globular tail and its function in ASH1 mRNA localization.

    PubMed

    Heuck, Alexander; Fetka, Ingrid; Brewer, Daniel N; Hüls, Daniela; Munson, Mary; Jansen, Ralf-Peter; Niessing, Dierk

    2010-05-03

    Type V myosin (MyoV)-dependent transport of cargo is an essential process in eukaryotes. Studies on yeast and vertebrate MyoV showed that their globular tails mediate binding to the cargo complexes. In Saccharomyces cerevisiae, the MyoV motor Myo4p interacts with She3p to localize asymmetric synthesis of HO 1 (ASH1) mRNA into the bud of dividing cells. A recent study showed that localization of GFP-MS2-tethered ASH1 particles does not require the Myo4p globular tail, challenging the supposed role of this domain. We assessed ASH1 mRNA and Myo4p distribution more directly and found that their localization is impaired in cells expressing globular tail-lacking Myo4p. In vitro studies further show that the globular tail together with a more N-terminal linker region is required for efficient She3p binding. We also determined the x-ray structure of the Myo4p globular tail and identify a conserved surface patch important for She3p binding. The structure shows pronounced similarities to membrane-tethering complexes and indicates that Myo4p may not undergo auto-inhibition of its motor domain.

  13. Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease.

    PubMed

    Khurana, Surender; Loving, Crystal L; Manischewitz, Jody; King, Lisa R; Gauger, Phillip C; Henningson, Jamie; Vincent, Amy L; Golding, Hana

    2013-08-28

    Vaccine-induced disease enhancement has been described in connection with several viral vaccines in animal models and in humans. We investigated a swine model to evaluate mismatched influenza vaccine-associated enhanced respiratory disease (VAERD) after pH1N1 infection. Vaccinating pigs with whole inactivated H1N2 (human-like) virus vaccine (WIV-H1N2) resulted in enhanced pneumonia and disease after pH1N1 infection. WIV-H1N2 immune sera contained high titers of cross-reactive anti-pH1N1 hemagglutinin (HA) antibodies that bound exclusively to the HA2 domain but not to the HA1 globular head. No hemagglutination inhibition titers against pH1N1 (challenge virus) were measured. Epitope mapping using phage display library identified the immunodominant epitope recognized by WIV-H1N2 immune sera as amino acids 32 to 77 of pH1N1-HA2 domain, close to the fusion peptide. These cross-reactive anti-HA2 antibodies enhanced pH1N1 infection of Madin-Darby canine kidney cells by promoting virus membrane fusion activity. The enhanced fusion activity correlated with lung pathology in pigs. This study suggests a role for fusion-enhancing anti-HA2 antibodies in VAERD, in the absence of receptor-blocking virus-neutralizing antibodies. These findings should be considered during the evaluation of universal influenza vaccines designed to elicit HA2 stem-targeting antibodies.

  14. Temperature-accelerated molecular dynamics gives insights into globular conformations sampled in the free state of the AC catalytic domain.

    PubMed

    Selwa, Edithe; Huynh, Tru; Ciccotti, Giovanni; Maragliano, Luca; Malliavin, Thérèse E

    2014-10-01

    The catalytic domain of the adenyl cyclase (AC) toxin from Bordetella pertussis is activated by interaction with calmodulin (CaM), resulting in cAMP overproduction in the infected cell. In the X-ray crystallographic structure of the complex between AC and the C terminal lobe of CaM, the toxin displays a markedly elongated shape. As for the structure of the isolated protein, experimental results support the hypothesis that more globular conformations are sampled, but information at atomic resolution is still lacking. Here, we use temperature-accelerated molecular dynamics (TAMD) simulations to generate putative all-atom models of globular conformations sampled by CaM-free AC. As collective variables, we use centers of mass coordinates of groups of residues selected from the analysis of standard molecular dynamics (MD) simulations. Results show that TAMD allows extended conformational sampling and generates AC conformations that are more globular than in the complexed state. These structures are then refined via energy minimization and further unrestrained MD simulations to optimize inter-domain packing interactions, thus resulting in the identification of a set of hydrogen bonds present in the globular conformations. © 2014 Wiley Periodicals, Inc.

  15. Mucosal and Systemic Immune Responses to Influenza H7N9 Antigen HA1-2 Co-Delivered Intranasally with Flagellin or Polyethyleneimine in Mice and Chickens.

    PubMed

    Song, Li; Xiong, Dan; Song, Hongqin; Wu, Lili; Zhang, Meihua; Kang, Xilong; Pan, Zhiming; Jiao, Xinan

    2017-01-01

    Consecutive cases of human infection with H7N9 influenza viruses since 2013 in China have prompted efforts to develop an effective treatment. Subunit vaccines introduced by intranasal administration can block an infection at its primary site; flagellin (fliC) and polyethyleneimine (PEI) have been shown to be potent adjuvants. We previously generated the hemagglutinin (HA)1-2-fliC fusion protein consisting of the globular head domain (HA1-2; amino acids 62-284) of HA fused with Salmonella typhimurium fliC. In the present study, we investigated its effectiveness of both flagellin and PEI as mucosal adjuvants for the H7N9 influenza subunit vaccine. Mice immunized intranasally with HA1-2-fliC and HA1-2-PEI showed higher HA1-2-specific immunoglobulin (Ig)G and IgA titers in serum, nasal wash, and bronchial alveolar lavage fluid. Moreover, splenocyte activation and proliferation and the number of HA1-2-specific interferon (IFN)-γ- and interleukin (IL)-4-producing splenocytes were markedly increased in the fliC and PEI groups; in the latter, there were more cells secreting IL-4 than IFN-γ, suggesting that fliC induced T helper type (Th)1 and Th2 immune responses, and PEI induced Th2-biased responses, consistent with the serum antibody isotype pattern (IgG1/IgG2a ratio). Furthermore, virus challenge was performed in a chicken model. The results showed that chickens receiving fliC and PEI adjuvant vaccine exhibited robust immune responses leading to a significant reduction in viral loads of throat and cloaca compared to chickens receiving only HA1-2. These findings provide a basis for the development of H7N9 influenza HA1-2 mucosal subunit vaccines.

  16. Mucosal and Systemic Immune Responses to Influenza H7N9 Antigen HA1–2 Co-Delivered Intranasally with Flagellin or Polyethyleneimine in Mice and Chickens

    PubMed Central

    Song, Li; Xiong, Dan; Song, Hongqin; Wu, Lili; Zhang, Meihua; Kang, Xilong; Pan, Zhiming; Jiao, Xinan

    2017-01-01

    Consecutive cases of human infection with H7N9 influenza viruses since 2013 in China have prompted efforts to develop an effective treatment. Subunit vaccines introduced by intranasal administration can block an infection at its primary site; flagellin (fliC) and polyethyleneimine (PEI) have been shown to be potent adjuvants. We previously generated the hemagglutinin (HA)1–2-fliC fusion protein consisting of the globular head domain (HA1–2; amino acids 62–284) of HA fused with Salmonella typhimurium fliC. In the present study, we investigated its effectiveness of both flagellin and PEI as mucosal adjuvants for the H7N9 influenza subunit vaccine. Mice immunized intranasally with HA1–2-fliC and HA1–2-PEI showed higher HA1–2-specific immunoglobulin (Ig)G and IgA titers in serum, nasal wash, and bronchial alveolar lavage fluid. Moreover, splenocyte activation and proliferation and the number of HA1–2-specific interferon (IFN)-γ- and interleukin (IL)-4-producing splenocytes were markedly increased in the fliC and PEI groups; in the latter, there were more cells secreting IL-4 than IFN-γ, suggesting that fliC induced T helper type (Th)1 and Th2 immune responses, and PEI induced Th2-biased responses, consistent with the serum antibody isotype pattern (IgG1/IgG2a ratio). Furthermore, virus challenge was performed in a chicken model. The results showed that chickens receiving fliC and PEI adjuvant vaccine exhibited robust immune responses leading to a significant reduction in viral loads of throat and cloaca compared to chickens receiving only HA1–2. These findings provide a basis for the development of H7N9 influenza HA1–2 mucosal subunit vaccines. PMID:28424686

  17. The crystal structure of the streptococcal collagen-like protein 2 globular domain from invasive M3-type group A Streptococcus shows significant similarity to immunomodulatory HIV protein gp41.

    PubMed

    Squeglia, Flavia; Bachert, Beth; De Simone, Alfonso; Lukomski, Slawomir; Berisio, Rita

    2014-02-21

    The arsenal of virulence factors deployed by streptococci includes streptococcal collagen-like (Scl) proteins. These proteins, which are characterized by a globular domain and a collagen-like domain, play key roles in host adhesion, host immune defense evasion, and biofilm formation. In this work, we demonstrate that the Scl2.3 protein is expressed on the surface of invasive M3-type strain MGAS315 of Streptococcus pyogenes. We report the crystal structure of Scl2.3 globular domain, the first of any Scl. This structure shows a novel fold among collagen trimerization domains of either bacterial or human origin. Despite there being low sequence identity, we observed that Scl2.3 globular domain structurally resembles the gp41 subunit of the envelope glycoprotein from human immunodeficiency virus type 1, an essential subunit for viral fusion to human T cells. We combined crystallographic data with modeling and molecular dynamics techniques to gather information on the entire lollipop-like Scl2.3 structure. Molecular dynamics data evidence a high flexibility of Scl2.3 with remarkable interdomain motions that are likely instrumental to the protein biological function in mediating adhesive or immune-modulatory functions in host-pathogen interactions. Altogether, our results provide molecular tools for the understanding of Scl-mediated streptococcal pathogenesis and important structural insights for the future design of small molecular inhibitors of streptococcal invasion.

  18. The central globular domain of the nucleocapsid protein of human immunodeficiency virus type 1 is critical for virion structure and infectivity.

    PubMed

    Ottmann, M; Gabus, C; Darlix, J L

    1995-03-01

    The nucleocapsid protein NCp7 of human immunodeficiency virus type 1 (HIV-1) is a 72-amino-acid peptide containing two CCHC-type zinc fingers linked by a short basic sequence, 29RAPRKKG35, which is conserved in HIV-1 and simian immunodeficiency virus. The complete three-dimensional structure of NCp7 has been determined by 1H-nuclear magnetic resonance spectroscopy (N. Morellet, H. de Rocquigny, Y. Mely, N. Jullian, H. Demene, M. Ottmann, D. Gerard, J. L. Darlix, M. C. Fournié-Zaluski, and B. P. Roques, J. Mol. Biol. 235:287-301, 1994) and revealed a central globular domain where the two zinc fingers are brought in close proximity by the RAPRKKG linker. To examine the role of this globular structure and more precisely of the RAPRKKG linker in virion structure and infectivity, we generated HIV-1 DNA mutants in the RAPRKK sequence of NCp7 and analyzed the mutant virions produced by transfected cells. Mutations that probably alter the structure of NCp7 structure led to the formation of very poorly infectious virus (A30P) or noninfectious virus (P31L and R32G). In addition, the P31L mutant did not contain detectable amounts of reverse transcriptase and had an immature core morphology, as determined by electron microscopy. On the other hand, mutations changing the basic nature of NCp7 had poor effect. R29S had a wild-type phenotype, and the replacement of 32RKK34 by SSS (S3 mutant) resulted in a decrease by no more than 100-fold of the virus titer. These results clearly show that the RAPRKKG linker contains residues that are critical for virion structure and infectivity.

  19. The central globular domain of the nucleocapsid protein of human immunodeficiency virus type 1 is critical for virion structure and infectivity.

    PubMed Central

    Ottmann, M; Gabus, C; Darlix, J L

    1995-01-01

    The nucleocapsid protein NCp7 of human immunodeficiency virus type 1 (HIV-1) is a 72-amino-acid peptide containing two CCHC-type zinc fingers linked by a short basic sequence, 29RAPRKKG35, which is conserved in HIV-1 and simian immunodeficiency virus. The complete three-dimensional structure of NCp7 has been determined by 1H-nuclear magnetic resonance spectroscopy (N. Morellet, H. de Rocquigny, Y. Mely, N. Jullian, H. Demene, M. Ottmann, D. Gerard, J. L. Darlix, M. C. Fournié-Zaluski, and B. P. Roques, J. Mol. Biol. 235:287-301, 1994) and revealed a central globular domain where the two zinc fingers are brought in close proximity by the RAPRKKG linker. To examine the role of this globular structure and more precisely of the RAPRKKG linker in virion structure and infectivity, we generated HIV-1 DNA mutants in the RAPRKK sequence of NCp7 and analyzed the mutant virions produced by transfected cells. Mutations that probably alter the structure of NCp7 structure led to the formation of very poorly infectious virus (A30P) or noninfectious virus (P31L and R32G). In addition, the P31L mutant did not contain detectable amounts of reverse transcriptase and had an immature core morphology, as determined by electron microscopy. On the other hand, mutations changing the basic nature of NCp7 had poor effect. R29S had a wild-type phenotype, and the replacement of 32RKK34 by SSS (S3 mutant) resulted in a decrease by no more than 100-fold of the virus titer. These results clearly show that the RAPRKKG linker contains residues that are critical for virion structure and infectivity. PMID:7853517

  20. Enhanced humoural and cellular immune responses to influenza H7N9 antigen HA1-2 fused with flagellin in chickens.

    PubMed

    Song, Li; Xiong, Dan; Hu, Maozhi; Kang, Xilong; Pan, Zhiming; Jiao, Xinan

    2017-06-21

    Sudden increases in the number of human A (H7N9) cases reported during December and January have been observed in previous years. Most reported infection cases are due to prior exposure to live poultry or potentially contaminated environments. Low pathogenicity of influenza A (H7N9) virus in avian species complicates timely discovery of infected birds. Therefore, there is a pressing need to develop safe and effective anti-H7N9 vaccines for poultry to reduce the risk of human infection and prevent the emergence of novel mutated strains. In addition to a good antigen, an effective vaccine also requires an appropriate adjuvant to enhance its immunogenicity. Previously, we generated an H7N9 influenza recombinant subunit vaccine (HA1-2-fliC), in which haemagglutinin globular head domain (HA1-2) was fused with flagellin (fliC), a potent TLR5 ligand, and demonstrated that HA1-2-fliC elicited effective HA1-2-specific immune responses in mice. In this study, we determined flagellin-induced expression profiles of cytokines and chemokines in different types of avian immune cells in vitro and ex vivo. We found that flagellin significantly increased the expression levels of CXCL inflammatory chemokines (CXCLi1 and CXCLi2) and CCL chemokines (MIP-1β and MCP-3) in avian macrophage HD11 cells. In addition, HA1-2-fliC induced significant upregulation of cytokines (IL-1β, IL-6, IL-18 and IFN-γ) and chemokines (CXCLi1, CXCLi2 and MIP-1β) in ex vivo splenic lymphocytes and peripheral blood mononuclear cells (PBMCs), suggesting that flagellin promoted immune responses of avian cells in vitro. We also evaluated specific humoural and cellular immune responses induced by HA1-2-fliC and found that chickens immunised intramuscularly with HA1-2-fliC showed significantly higher HA1-2-specific immunoglobulin (Ig)G titers in serum. Furthermore, HA1-2-fliC potentiated cellular immune responses, as reflected by an increase in CD4 + and CD8 + T cells and proliferation of PBMCs. Significantly

  1. Measles virus fusion machinery activated by sialic acid binding globular domain.

    PubMed

    Talekar, Aparna; Moscona, Anne; Porotto, Matteo

    2013-12-01

    Paramyxoviruses, including the human pathogen measles virus (MV) and the avian Newcastle disease virus (NDV), enter host cells through fusion of the viral envelope with the target cell membrane. This fusion is driven by the concerted action of two viral envelope glycoproteins: the receptor binding protein and the fusion protein (F). The MV receptor binding protein (hemagglutinin [H]) attaches to proteinaceous receptors on host cells, while the receptor binding protein of NDV (hemagglutinin-neuraminidase [HN]) interacts with sialic acid-containing receptors. The receptor-bound HN/H triggers F to undergo conformational changes that render it competent to mediate fusion of the viral and cellular membranes. The mechanism of fusion activation has been proposed to be different for sialic acid-binding viruses and proteinaceous receptor-binding viruses. We report that a chimeric protein containing the NDV HN receptor binding region and the MV H stalk domain can activate MV F to fuse, suggesting that the signal to the stalk of a protein-binding receptor binding molecule can be transmitted from a sialic acid binding domain. By engineering the NDV HN globular domain to interact with a proteinaceous receptor, the fusion activation signal was preserved. Our findings are consistent with a unified mechanism of fusion activation, at least for the Paramyxovirinae subfamily, in which the receptor binding domains of the receptor binding proteins are interchangeable and the stalk determines the specificity of F activation.

  2. Structural and biochemical characterization of the protease domain of the mosaic botulinum neurotoxin type HA.

    PubMed

    Lam, Kwok-Ho; Sikorra, Stefan; Weisemann, Jasmin; Maatsch, Hannah; Perry, Kay; Rummel, Andreas; Binz, Thomas; Jin, Rongsheng

    2018-04-23

    The extreme toxicity of botulinum neurotoxins (BoNTs) relies on their specific cleavage of SNARE proteins, which eventually leads to muscle paralysis. One newly identified mosaic toxin, BoNT/HA (aka H or FA), cleaves VAMP-2 at a unique position between residues L54 and E55, but the molecular basis underlying VAMP-2-recognition of BoNT/HA remains poorly characterized. Here, we report a ∼2.09 Å resolution crystal structure of the light chain protease domain of BoNT/HA (LC/HA). Structural comparison between LC/HA and LC of BoNT/F1 (LC/F1) reveals distinctive hydrophobic and electrostatic features near the active sites, which may explain their different VAMP-2 cleavage sites. When compared to BoNT/F5 that cleaves VAMP-2 at the same site as BoNT/HA, LC/HA displays higher affinity for VAMP-2, which could be caused by their different surface charge properties surrounding a VAMP-2 exosite-binding cleft. Furthermore, systematic mutagenesis studies on VAMP-2 and structural modeling demonstrate that residues R47 to K59 spanning the cleavage site in VAMP-2 may adopt a novel extended conformation when interacting with LC/HA and LC/F5. Taken together, our structure provides new insights into substrate-recognition of BoNT/HA and paves the way for rational design of small molecule or peptide inhibitors against LC/HA.

  3. Structure, function and tissue forms of the C-terminal globular domain of collagen XVIII containing the angiogenesis inhibitor endostatin.

    PubMed Central

    Sasaki, T; Fukai, N; Mann, K; Göhring, W; Olsen, B R; Timpl, R

    1998-01-01

    The C-terminal domain NC1 of mouse collagen XVIII (38 kDa) and the shorter mouse and human endostatins (22 kDa) were prepared in recombinant form from transfected mammalian cells. The NC1 domain aggregated non-covalently into a globular trimer which was partially cleaved by endogenous proteolysis into several monomers (25-32 kDa) related to endostatin. Endostatins were obtained in a highly soluble, monomeric form and showed a single N-terminal sequence which, together with other data, indicated a compact folding. Endostatins and NC1 showed a comparable binding activity for the microfibrillar fibulin-1 and fibulin-2, and for heparin. Domain NC1, however, was a distinctly stronger ligand than endostatin for sulfatides and the basement membrane proteins laminin-1 and perlecan. Immunological assays demonstrated endostatin epitopes on several tissue components (22-38 kDa) and in serum (120-300 ng/ml), the latter representing the smaller variants. The data indicated that the NC1 domain consists of an N-terminal association region (approximately 50 residues), a central protease-sensitive hinge region (approximately 70 residues) and a C-terminal stable endostatin domain (approximately 180 residues). They also demonstrated that proteolytic release of endostatin can occur through several pathways, which may lead to a switch from a matrix-associated to a more soluble endocrine form. PMID:9687493

  4. Genetic diversity of HA1 domain of heammaglutinin gene of influenza A(H1N1)pdm09 in Tunisia

    PubMed Central

    2013-01-01

    We present major results concerning isolation and determination of the nucleotide sequence of hemagglutinin (HA1) of the pandemic (H1N1)pdm09 influenza viruses found in Tunisia. Amino acid analysis revealed minor amino acid changes in the antigenic or receptor-binding domains. We found mutations that were also present in 1918 pandemic virus, which includes S183P in 4 and S185T mutation in 19 of 27 viruses analyzed from 2011, while none of the 2009 viruses carried these mutations. Also two specific amino acid differences into N-glycosylation sites (N288T and N276H) were detected. The phylogenetic analysis revealed that the majority of the Tunisian isolates clustered with clade A/St. Petersburg/27/2011 viruses characterized by D97N and S185T mutations. However it also reveals a trend of 2010 strains to accumulate amino acid variation and form new phylogenetic clade with three specific amino acid substitutions: V47I, E172K and K308E. PMID:23679923

  5. Molecular aspects of zygotic embryogenesis in sunflower (Helianthus annuus L.): correlation of positive histone marks with HaWUS expression and putative link HaWUS/HaL1L.

    PubMed

    Salvini, Mariangela; Fambrini, Marco; Giorgetti, Lucia; Pugliesi, Claudio

    2016-01-01

    The link HaWUS/ HaL1L , the opposite transcriptional behavior, and the decrease/increase in positive histone marks bond to both genes suggest an inhibitory effect of WUS on HaL1L in sunflower zygotic embryos. In Arabidopsis, a group of transcription factors implicated in the earliest events of embryogenesis is the WUSCHEL-RELATED HOMEOBOX (WOX) protein family including WUSCHEL (WUS) and other 14 WOX protein, some of which contain a conserved WUS-box domain in addition to the homeodomain. WUS transcripts appear very early in embryogenesis, at the 16-cell embryo stage, but gradually become restricted to the center of the developing shoot apical meristem (SAM) primordium and continues to be expressed in cells of the niche/organizing center of SAM and floral meristems to maintain stem cell population. Moreover, WUS has decisive roles in the embryonic program presumably promoting the vegetative-to-embryonic transition and/or maintaining the identity of the embryonic stem cells. However, data on the direct interaction between WUS and key genes for seed development (as LEC1 and L1L) are not collected. The novelty of this report consists in the characterization of Helianthus annuus WUS (HaWUS) gene and in its analysis regarding the pattern of the methylated lysine 4 (K4) of the Histone H3 and of the acetylated histone H3 during the zygotic embryo development. Also, a parallel investigation was performed for HaL1L gene since two copies of the WUS-binding site (WUSATA), previously identified on HaL1L nucleotide sequence, were able to be bound by the HaWUS recombinant protein suggesting a not described effect of HaWUS on HaL1L transcription.

  6. Discovery of a new X-ray transient in the globular cluster Liller 1

    NASA Astrophysics Data System (ADS)

    Homan, Jeroen; van den Berg, Maureen; Heinke, Craig; Pooley, David; Degenaar, Nathalie; van den Eijnden, Jakob; Bahramian, Arash; Gendreau, Keith; Arzoumanian, Zaven

    2018-05-01

    We report on the discovery of a new X-ray transient in the globular cluster Liller 1 with Chandra. Swift/XRT monitoring observations of the globular cluster Liller 1 in early April 2018 revealed low-level activity (around 0.1 ct/s) in the core of the cluster.

  7. HA117 endows HL60 cells with a stem-like signature by inhibiting the degradation of DNMT1 via its ability to down-regulate expression of the GGL domain of RGS6

    PubMed Central

    Li, Shuangshuang; Wu, Huan; Wang, Yi; Li, Xiaoqing; Guo, Yuxia; Liang, Shaoyan

    2017-01-01

    All-trans retinoic acid (ATRA) induces complete remission in almost all patients with acute promyelocytic leukemia (APL) via its ability to induce the in vivo differentiation of APL blasts. However, prolonged ATRA treatment can result in drug resistance. In previous studies, we generated a multi-drug-resistant HL60/ATRA cell line and found it to contain a new drug resistance-related gene segment, HA117. In this study, we demonstrate that ATRA induces multi-drug-resistant subpopulations of HL60 cells with a putative stem-like signature by up-regulating the expression of the new gene segment HA117. Western blot analysis and quantitative real-time PCR demonstrated that HA117 causes alternative splicing of regulator of G-protein signaling 6 (RGS6) and down-regulation of the expression of the GGL domain of RGS6, which plays an important role in DNA methyltransferase 1 (DNMT1) degradation. Moreover, DNMT1 expression was increased in multi-drug resistance HL60/ATRA cells. Knockdown of HA117 restored expression of the GGL domain and blocked DNMT1 expression. Moreover, resistant cells displayed a putative stem-like signature with increased expression of cancer steam cell markers CD133 and CD123. The stem cell marker, Nanog, was significantly up-regulated. In conclusion, our study shows that HA117 potentially promotes the stem-like signature of the HL60/ATRA cell line by inhibiting by the ubiquitination and degradation of DNMT1 and by down-regulating the expression of the GGL domain of RGS6. These results throw light on the cellular events associated with the ATRA-induced multi-drug resistance phenotype in acute leukemia. PMID:28665981

  8. X-Ray Structure of the Human Calreticulin Globular Domain Reveals a Peptide-Binding Area and Suggests a Multi-Molecular Mechanism

    PubMed Central

    Chouquet, Anne; Païdassi, Helena; Ling, Wai Li; Frachet, Philippe; Houen, Gunnar; Arlaud, Gérard J.; Gaboriaud, Christine

    2011-01-01

    In the endoplasmic reticulum, calreticulin acts as a chaperone and a Ca2+-signalling protein. At the cell surface, it mediates numerous important biological effects. The crystal structure of the human calreticulin globular domain was solved at 1.55 Å resolution. Interactions of the flexible N-terminal extension with the edge of the lectin site are consistently observed, revealing a hitherto unidentified peptide-binding site. A calreticulin molecular zipper, observed in all crystal lattices, could further extend this site by creating a binding cavity lined by hydrophobic residues. These data thus provide a first structural insight into the lectin-independent binding properties of calreticulin and suggest new working hypotheses, including that of a multi-molecular mechanism. PMID:21423620

  9. Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth

    PubMed Central

    Agostinis, Chiara; Vidergar, Romana; Belmonte, Beatrice; Mangogna, Alessandro; Amadio, Leonardo; Geri, Pietro; Borelli, Violetta; Zanconati, Fabrizio; Tedesco, Francesco; Confalonieri, Marco; Tripodo, Claudio; Kishore, Uday; Bulla, Roberta

    2017-01-01

    C1q is the first recognition subcomponent of the complement classical pathway, which acts toward the clearance of pathogens and apoptotic cells. C1q is also known to modulate a range of functions of immune and non-immune cells, and has been shown to be involved in placental development and sensorial synaptic pruning. We have recently shown that C1q can promote tumor by encouraging their adhesion, migration, and proliferation in addition to angiogenesis and metastasis. In this study, we have examined the role of human C1q in the microenvironment of malignant pleural mesothelioma (MPM), a rare form of cancer commonly associated with exposure to asbestos. We found that C1q was highly expressed in all MPM histotypes, particularly in epithelioid rather than in sarcomatoid histotype. C1q avidly bound high and low molecular weight hyaluronic acid (HA) via its globular domain. C1q bound to HA was able to induce adhesion and proliferation of mesothelioma cells (MES) via enhancement of ERK1/2, SAPK/JNK, and p38 phosphorylation; however, it did not activate the complement cascade. Consistent with the modular organization of the globular domain, we demonstrated that C1q may bind to HA through ghA module, whereas it may interact with human MES through the ghC. In conclusion, C1q highly expressed in MPM binds to HA and enhances the tumor growth promoting cell adhesion and proliferation. These data can help develop novel diagnostic markers and molecular targets for MPM. PMID:29209316

  10. Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth.

    PubMed

    Agostinis, Chiara; Vidergar, Romana; Belmonte, Beatrice; Mangogna, Alessandro; Amadio, Leonardo; Geri, Pietro; Borelli, Violetta; Zanconati, Fabrizio; Tedesco, Francesco; Confalonieri, Marco; Tripodo, Claudio; Kishore, Uday; Bulla, Roberta

    2017-01-01

    C1q is the first recognition subcomponent of the complement classical pathway, which acts toward the clearance of pathogens and apoptotic cells. C1q is also known to modulate a range of functions of immune and non-immune cells, and has been shown to be involved in placental development and sensorial synaptic pruning. We have recently shown that C1q can promote tumor by encouraging their adhesion, migration, and proliferation in addition to angiogenesis and metastasis. In this study, we have examined the role of human C1q in the microenvironment of malignant pleural mesothelioma (MPM), a rare form of cancer commonly associated with exposure to asbestos. We found that C1q was highly expressed in all MPM histotypes, particularly in epithelioid rather than in sarcomatoid histotype. C1q avidly bound high and low molecular weight hyaluronic acid (HA) via its globular domain. C1q bound to HA was able to induce adhesion and proliferation of mesothelioma cells (MES) via enhancement of ERK1/2, SAPK/JNK, and p38 phosphorylation; however, it did not activate the complement cascade. Consistent with the modular organization of the globular domain, we demonstrated that C1q may bind to HA through ghA module, whereas it may interact with human MES through the ghC. In conclusion, C1q highly expressed in MPM binds to HA and enhances the tumor growth promoting cell adhesion and proliferation. These data can help develop novel diagnostic markers and molecular targets for MPM.

  11. A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Boonsathorn, Naphatsawan; Panthong, Sumolrat; Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development

    Highlights: • A human monoclonal antibody against influenza virus was produced from a volunteer. • The antibody was generated from the PBMCs of the volunteer using the fusion method. • The antibody neutralized heterosubtypically group 1 influenza A viruses (H1 and H9). • The antibody targeted a novel epitope in globular head region of the hemagglutinin. • Sequences of the identified epitope are highly conserved among H1 and H9 subtypes. - Abstract: Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutininmore » (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.« less

  12. The RING domain of the scaffold protein Ste5 adopts a molten globular character with high thermal and chemical stability.

    PubMed

    Walczak, Michal J; Samatanga, Brighton; van Drogen, Frank; Peter, Matthias; Jelesarov, Ilian; Wider, Gerhard

    2014-01-27

    Ste5 is a scaffold protein that controls the pheromone response of the MAP-kinase cascade in yeast cells. Upon pheromone stimulation, Ste5 (through its RING-H2 domain) interacts with the β and γ subunits of an activated heterodimeric G protein and promotes activation of the MAP-kinase cascade. With structural and biophysical studies, we show that the Ste5 RING-H2 domain exists as a molten globule under native buffer conditions, in yeast extracts, and even in denaturing conditions containing urea (7 M). Furthermore, it exhibits high thermal stability in native conditions. Binding of the Ste5 RING-H2 domain to the physiological Gβ/γ (Ste4/Ste18) ligand is accompanied by a conformational transition into a better folded, more globular structure. This study reveals novel insights into the folding mechanism and recruitment of binding partners by the Ste5 RING-H2 domain. We speculate that many RING domains may share a similar mechanism of substrate recognition and molten-globule-like character. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Characterization of Three Novel Fatty Acid- and Retinoid-Binding Protein Genes (Ha-far-1, Ha-far-2 and Hf-far-1) from the Cereal Cyst Nematodes Heterodera avenae and H. filipjevi

    PubMed Central

    Peng, Huan; Luo, Shujie; Huang, Wenkun; Cui, Jiangkuan; Li, Xin; Kong, Lingan; Jiang, Daohong; Chitwood, David J.; Peng, Deliang

    2016-01-01

    Heterodera avenae and H. filipjevi are major parasites of wheat, reducing production worldwide. Both are sedentary endoparasitic nematodes, and their development and parasitism depend strongly on nutrients obtained from hosts. Secreted fatty acid- and retinol-binding (FAR) proteins are nematode-specific lipid carrier proteins used for nutrient acquisition as well as suppression of plant defenses. In this study, we obtained three novel FAR genes Ha-far-1 (KU877266), Ha-far-2 (KU877267), Hf-far-1 (KU877268). Ha-far-1 and Ha-far-2 were cloned from H. avenae, encoding proteins of 191 and 280 amino acids with molecular masses about 17 and 30 kDa, respectively and sequence identity of 28%. Protein Blast in NCBI revealed that Ha-FAR-1 sequence is 78% similar to the Gp-FAR-1 protein from Globodera pallida, while Ha-FAR-2 is 30% similar to Rs-FAR-1 from Radopholus similis. Only one FAR protein Hf-FAR-1was identified in H. filipjevi; it had 96% sequence identity to Ha-FAR-1. The three proteins are alpha-helix-rich and contain the conserved domain of Gp-FAR-1, but Ha-FAR-2 had a remarkable peptide at the C-terminus which was random-coil-rich. Both Ha-FAR-1 and Hf-FAR-1 had casein kinase II phosphorylation sites, while Ha-FAR-2 had predicted N-glycosylation sites. Phylogenetic analysis showed that the three proteins clustered together, though Ha-FAR-1 and Hf-FAR-1 adjoined each other in a plant-parasitic nematode branch, but Ha-FAR-2 was distinct from the other proteins in the group. Fluorescence-based ligand binding analysis showed the three FAR proteins bound to a fluorescent fatty acid derivative and retinol and with dissociation constants similar to FARs from other species, though Ha-FAR-2 binding ability was weaker than that of the two others. In situ hybridization detected mRNAs of Ha-far-1 and Ha-far-2 in the hypodermis. The qRT-PCR results showed that the Ha-far-1and Ha-far-2 were expressed in all developmental stages; Ha-far-1 expressed 70 times more than Ha-far-2 in

  14. Characterization of Three Novel Fatty Acid- and Retinoid-Binding Protein Genes (Ha-far-1, Ha-far-2 and Hf-far-1) from the Cereal Cyst Nematodes Heterodera avenae and H. filipjevi.

    PubMed

    Qiao, Fen; Luo, Lilian; Peng, Huan; Luo, Shujie; Huang, Wenkun; Cui, Jiangkuan; Li, Xin; Kong, Lingan; Jiang, Daohong; Chitwood, David J; Peng, Deliang

    2016-01-01

    Heterodera avenae and H. filipjevi are major parasites of wheat, reducing production worldwide. Both are sedentary endoparasitic nematodes, and their development and parasitism depend strongly on nutrients obtained from hosts. Secreted fatty acid- and retinol-binding (FAR) proteins are nematode-specific lipid carrier proteins used for nutrient acquisition as well as suppression of plant defenses. In this study, we obtained three novel FAR genes Ha-far-1 (KU877266), Ha-far-2 (KU877267), Hf-far-1 (KU877268). Ha-far-1 and Ha-far-2 were cloned from H. avenae, encoding proteins of 191 and 280 amino acids with molecular masses about 17 and 30 kDa, respectively and sequence identity of 28%. Protein Blast in NCBI revealed that Ha-FAR-1 sequence is 78% similar to the Gp-FAR-1 protein from Globodera pallida, while Ha-FAR-2 is 30% similar to Rs-FAR-1 from Radopholus similis. Only one FAR protein Hf-FAR-1was identified in H. filipjevi; it had 96% sequence identity to Ha-FAR-1. The three proteins are alpha-helix-rich and contain the conserved domain of Gp-FAR-1, but Ha-FAR-2 had a remarkable peptide at the C-terminus which was random-coil-rich. Both Ha-FAR-1 and Hf-FAR-1 had casein kinase II phosphorylation sites, while Ha-FAR-2 had predicted N-glycosylation sites. Phylogenetic analysis showed that the three proteins clustered together, though Ha-FAR-1 and Hf-FAR-1 adjoined each other in a plant-parasitic nematode branch, but Ha-FAR-2 was distinct from the other proteins in the group. Fluorescence-based ligand binding analysis showed the three FAR proteins bound to a fluorescent fatty acid derivative and retinol and with dissociation constants similar to FARs from other species, though Ha-FAR-2 binding ability was weaker than that of the two others. In situ hybridization detected mRNAs of Ha-far-1 and Ha-far-2 in the hypodermis. The qRT-PCR results showed that the Ha-far-1and Ha-far-2 were expressed in all developmental stages; Ha-far-1 expressed 70 times more than Ha-far-2 in

  15. Crystal structure of the receptor-binding domain of botulinum neurotoxin type HA, also known as type FA or H

    DOE PAGES

    Yao, Guorui; Lam, Kwok-ho; Perry, Kay; ...

    2017-03-08

    Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A–G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently. Sequence analyses indicate that the receptor-binding domain (HC) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently tomore » some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the HC. Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-HC at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Altogether, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures.« less

  16. Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H.

    PubMed

    Yao, Guorui; Lam, Kwok-Ho; Perry, Kay; Weisemann, Jasmin; Rummel, Andreas; Jin, Rongsheng

    2017-03-08

    Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A-G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently. Sequence analyses indicate that the receptor-binding domain (H C ) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently to some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the H C . Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-H C at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Taken together, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures.

  17. Crystal structure of the receptor-binding domain of botulinum neurotoxin type HA, also known as type FA or H

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yao, Guorui; Lam, Kwok-ho; Perry, Kay

    Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A–G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently. Sequence analyses indicate that the receptor-binding domain (HC) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently tomore » some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the HC. Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-HC at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Altogether, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures.« less

  18. Crystal structure of the HA3 subcomponent of Clostridium botulinum type C progenitor toxin.

    PubMed

    Nakamura, Toshio; Kotani, Mao; Tonozuka, Takashi; Ide, Azusa; Oguma, Keiji; Nishikawa, Atsushi

    2009-01-30

    The Clostridium botulinum type C 16S progenitor toxin contains a neurotoxin and several nontoxic components, designated nontoxic nonhemagglutinin (HA), HA1 (HA-33), HA2 (HA-17), HA3a (HA-22-23), and HA3b (HA-53). The HA3b subcomponent seems to play an important role cooperatively with HA1 in the internalization of the toxin by gastrointestinal epithelial cells via binding of these subcomponents to specific oligosaccharides. In this study, we investigated the sugar-binding specificity of the HA3b subcomponent using recombinant protein fused to glutathione S-transferase and determined the three-dimensional structure of the HA3a-HA3b complex based on X-ray crystallography. The crystal structure was determined at a resolution of 2.6 A. HA3b contains three domains, domains I to III, and the structure of domain I resembles HA3a. In crystal packing, three HA3a-HA3b molecules are assembled to form a three-leaved propeller-like structure. The three HA3b domain I and three HA3a alternate, forming a trimer of dimers. In a database search, no proteins with high structural homology to any of the domains (Z score >10) were found. Especially, HA3a and HA3b domain I, mainly composed of beta-sheets, reveal a unique fold. In binding assays, HA3b bound sialic acid with high affinity, but did not bind galactose, N-acetylgalactosamine, or N-acetylglucosamine. The electron density of liganded N-acetylneuraminic acid was determined by crystal soaking. In the sugar-complex structure, the N-acetylneuraminic acid-binding site was located in the cleft formed between domains II and III of HA3b. This report provides the first determination of the three-dimensional structure of the HA3a-HA3b complex and its sialic acid binding site. Our results will provide useful information for elucidating the mechanism of assembly of the C16S toxin and for understanding the interactions with oligosaccharides on epithelial cells and internalization of the botulinum toxin complex.

  19. Identification of globular mechanochemical heads of kinesin.

    PubMed

    Scholey, J M; Heuser, J; Yang, J T; Goldstein, L S

    1989-03-23

    Kinesin is a mechanoenzyme which uses energy liberated from ATP hydrolysis to transport particles towards the 'plus ends' of microtubules. The enzyme consists of two polypeptide heavy chains of relative molecular mass (Mr) approximately 110,000-140,000 (110K-140K) plus copurifying light chains; these polypeptides are arranged in a structure consisting of two globular heads attached to a fibrous stalk which terminates in a 'feathered' tail. Here we report that a function-disrupting monoclonal antikinesin, which binds to the 45K fragment of the kinesin heavy chain, recognizes an epitope located towards the N-terminal end of the heavy chain, and decorates the two globular heads lying at one end of the intact molecules (one antibody per head). The results show that the two heavy chains of native kinesin are arranged in parallel, and that the 45K fragments, which display nucleotide-sensitive interactions with microtubules, represent mechanochemical 'heads' located at the N-terminal regions of the heavy chains. Thus, it is likely that the kinesin heads are analogous to the subfragment-1 domains of myosin.

  20. Glycosylations in the globular head of the hemagglutinin protein modulate the virulence and antigenic properties of the H1N1 influenza viruses

    PubMed Central

    Medina, Rafael A.; Stertz, Silke; Manicassamy, Balaji; Zimmermann, Petra; Sun, Xiangjie; Albrecht, Randy A.; Uusi-Kerttula, Hanni; Zagordi, Osvaldo; Belshe, Robert B.; Frey, Sharon E.; Eggink, Dirk; Tumpey, Terrence M.; García-Sastre, Adolfo

    2014-01-01

    The global spread of the 2009 pandemic H1N1 (pH1N1) virus in humans increases the likelihood that this influenza virus strain could undergo antigenic drift in the coming years. Previous seasonal H1N1 and H3N2 influenza strains acquired additional glycosylations in the globular head of their hemagglutinin (HA) proteins as they evolved over time; these are believed to shield antigenically relevant regions. We used influenza A/Netherlands/602/2009 recombinant (rpH1N1) viruses to which we added additional HA glycosylation sites reflecting their temporal appearance in previous seasonal H1N1 viruses. Additional glycosylations resulted in substantial attenuation in mice and ferrets, while deleting HA glycosylation sites from a pre-pandemic 1991 seasonal H1N1 influenza virus resulted in increased pathogenicity in mice. Sera from mice infected with wild type (WT) rpH1N1 virus showed a considerable loss of HA inhibitory (HI) activity against rpH1N1 viruses glycosylated at sites 144 or 144-172, indicating that the polyclonal antibody response elicited by WT rpH1N1 HA seems to be directed against an immunodominant region, likely site Sa, shielded by glycosylation at 144. Sera from humans vaccinated with the pH1N1 inactivated vaccine also showed reduced activity against the 144 and 144-172 mutant viruses. Remarkably, the HI activity of sera from virus-infected mice demonstrated that glycosylation at position 144 resulted in the induction of a broader polyclonal response able to cross-neutralize all WT and glycosylation mutant pH1N1 viruses. Mice infected with a recent seasonal virus in which glycosylation sites 71, 142 and 177 were removed, elicited antibodies that protected against challenge with the antigenically distant pH1N1 virus. Thus, acquisition of glycosylation sites in the HA of H1N1 human influenza viruses not only affects their pathogenicity and ability to escape from polyclonal antibodies elicited by previous influenza virus strains, but also their ability to

  1. Putative suppressing effect of IgG Fc-conjugated haemagglutinin (HA) stalk of influenza virus H7N9 on the neutralizing immunogenicity of Fc-conjugated HA head: implication for rational design of HA-based influenza vaccines.

    PubMed

    He, B; Xia, S; Yu, F; Fu, Y; Li, W; Wang, Q; Lu, L; Jiang, S

    2016-02-01

    The emergence of influenza A H7N9 in infection has posed a great threat to public health globally. Poor immunogenicity of H7N9 haemagglutinin (HA) is a major obstacle to the development of an effective H7N9 vaccine. Here, we found that the vaccine containing the H7HA head conjugated with IgG Fc (Hd-Fc) induced strong neutralizing antibody responses and protection against H7N9 infection, whilst the Fc-conjugated H7HA stalk (St-Fc)-based vaccine could not induce neutralizing antibodies, although the St-Fc-immunized mice were partially protected. The vaccines containing the full-length extracellular domain of HA conjugated with Fc and the mixture of Hd-Fc plus St-Fc induced significantly lower neutralizing antibody and haemagglutination inhibition titres than the Hd-Fc-based vaccine. These results suggest that the St-Fc may have inhibitory effects on the neutralizing immunogenicity of Hd-Fc. Therefore, the neutralizing domain(s), such as the receptor-binding domain, in the HA head should be kept and the non-neutralizing domain(s) in the HA stalk with the ability to potentially suppress the neutralizing immunogenicity of HA head should be removed from Fc-conjugated HA-based influenza vaccines to increase the neutralizing antibody response.

  2. Engineering Globular Protein Vesicles through Tunable Self-Assembly of Recombinant Fusion Proteins

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jang, Yeongseon; Choi, Won Tae; Heller, William T.

    Vesicles assembled from folded, globular proteins have potential for functions different from traditional lipid or polymeric vesicles. However, they also present challenges in understanding the assembly process and controlling vesicle properties. From detailed investigation of the assembly behavior of recombinant fusion proteins, this work reports a simple strategy to engineer protein vesicles containing functional, globular domains. This is achieved through tunable self-assembly of recombinant globular fusion proteins containing leucine zippers and elastin-like polypeptides. The fusion proteins form complexes in solution via high affinity binding of the zippers, and transition through dynamic coacervates to stable hollow vesicles upon warming. The thermalmore » driving force, which can be tuned by protein concentration or temperature, controls both vesicle size and whether vesicles are single or bi-layered. Lastly, these results provide critical information to engineer globular protein vesicles via self-assembly with desired size and membrane structure.« less

  3. Engineering Globular Protein Vesicles through Tunable Self-Assembly of Recombinant Fusion Proteins

    DOE PAGES

    Jang, Yeongseon; Choi, Won Tae; Heller, William T.; ...

    2017-07-27

    Vesicles assembled from folded, globular proteins have potential for functions different from traditional lipid or polymeric vesicles. However, they also present challenges in understanding the assembly process and controlling vesicle properties. From detailed investigation of the assembly behavior of recombinant fusion proteins, this work reports a simple strategy to engineer protein vesicles containing functional, globular domains. This is achieved through tunable self-assembly of recombinant globular fusion proteins containing leucine zippers and elastin-like polypeptides. The fusion proteins form complexes in solution via high affinity binding of the zippers, and transition through dynamic coacervates to stable hollow vesicles upon warming. The thermalmore » driving force, which can be tuned by protein concentration or temperature, controls both vesicle size and whether vesicles are single or bi-layered. Lastly, these results provide critical information to engineer globular protein vesicles via self-assembly with desired size and membrane structure.« less

  4. Minor histocompatibility antigen HA-1 and HA-2 polymorphisms in Taiwan: frequency and application in hematopoietic stem cell transplantation.

    PubMed

    Lio, Hoi-Yan; Tang, Jih-Luh; Wu, Jui; Wu, Shang-Ju; Lin, Chun-Ying; Yang, Ya-Chien

    2010-09-01

    Minor histocompatibility antigens influence the occurrence of graft-vs.-host disease and graft-vs.-leukemia effects after hematopoietic stem cell transplantation (HSCT). We determined the population frequencies of HA-1 and HA-2 alleles in Taiwan and exploited their potential applications in allogeneic HSCT. HA-1 and HA-2 were genotyped using polymerase chain reaction and restriction fragment length polymorphism in healthy controls (221 for HA-1 and 306 for HA-2) and HLA-matched donor-recipient sibling pairs with HSCT (92 for HA-1 and 38 for HA-2). The association of genetic polymorphisms with HSCT outcome was evaluated by univariate and multivariate analyses. The allele frequencies in controls were 35.3% and 64.7% for HA-1(H) and HA-1(R), and 89.0% and 11.0% for HA-2(V) and HA-2(M), respectively. HA-1 disparity was denoted in 16.3% of HLA-matched donor-recipient sibling pairs, while it was not associated with HSCT outcome. HA-2 disparity was not observed in the donor-recipient pairs studied. The possibilities of using HA-1 and HA-2 variabilities as molecular markers for hematopoietic chimerism after HSCT were 39.2% and 18.4%, respectively. Our data provide the information on allele and genotype frequencies of HA-1 and HA-2 in a Taiwanese population, and suggest that prospective genomic typing for HA-1 and HA-2 alleles of the donor and recipient could be a useful approach for molecular identification of hematopoietic chimerism after HSCT, rather than prognosis of clinical outcome.

  5. Trypanosoma cruzi H+-ATPase 1 (TcHA1) and 2 (TcHA2) genes complement yeast mutants defective in H+ pumps and encode plasma membrane P-type H+-ATPases with different enzymatic properties.

    PubMed

    Luo, Shuhong; Scott, David A; Docampo, Roberto

    2002-11-15

    Previous studies in Trypanosoma cruzi have shown that intracellular pH homeostasis requires ATP and is affected by H(+)-ATPase inhibitors, indicating a major role for ATP-driven proton pumps in intracellular pH control. In the present study, we report the cloning and sequencing of a pair of genes linked in tandem (TcHA1 and TcHA2) in T. cruzi which encode proteins with homology to fungal and plant P-type proton-pumping ATPases. The genes are expressed at the mRNA level in different developmental stages of T. cruzi: TcHA1 is expressed maximally in epimastigotes, whereas TcHA2 is expressed predominantly in trypomastigotes. The proteins predicted from the nucleotide sequence of the genes have 875 and 917 amino acids and molecular masses of 96.3 and 101.2 kDa, respectively. Full-length TcHA1 and an N-terminal truncated version of TcHA2 complemented a Saccharomyces cerevisiae strain deficient in P-type H(+)-ATPase activity, the proteins localized to the yeast plasma membrane, and ATP-driven proton pumping could be detected in proteoliposomes reconstituted from plasma membrane purified from transfected yeast. The reconstituted proton transport activity was reduced by inhibitors of P-type H(+)-ATPases. C-terminal truncation did not affect complementation of mutant yeast, suggesting the lack of C-terminal autoinhibitory domains in these proteins. ATPase activity in plasma membrane from TcHA1- and (N-terminal truncated) TcHA2-transfected yeast was inhibited to different extents by vanadate, whereas the latter yeast strain was more resistant to extremes of pH, suggesting that the native proteins may serve different functions at different stages in the T. cruzi life cycle.

  6. Globular Clusters for Faint Galaxies

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2017-07-01

    The origin of ultra-diffuse galaxies (UDGs) has posed a long-standing mystery for astronomers. New observations of several of these faint giants with the Hubble Space Telescope are now lending support to one theory.Faint-Galaxy MysteryHubble images of Dragonfly 44 (top) and DFX1 (bottom). The right panels show the data with greater contrast and extended objects masked. [van Dokkum et al. 2017]UDGs large, extremely faint spheroidal objects were first discovered in the Virgo galaxy cluster roughly three decades ago. Modern telescope capabilities have resulted in many more discoveries of similar faint galaxies in recent years, suggesting that they are a much more common phenomenon than we originally thought.Despite the many observations, UDGs still pose a number of unanswered questions. Chief among them: what are UDGs? Why are these objects the size of normal galaxies, yet so dim? There are two primary models that explain UDGs:UDGs were originally small galaxies, hence their low luminosity. Tidal interactions then puffed them up to the large size we observe today.UDGs are effectively failed galaxies. They formed the same way as normal galaxies of their large size, but something truncated their star formation early, preventing them from gaining the brightness that we would expect for galaxies of their size.Now a team of scientists led by Pieter van Dokkum (Yale University) has made some intriguing observations with Hubble that lend weight to one of these models.Globulars observed in 16 Coma-cluster UDGs by Hubble. The top right panel shows the galaxy identifications. The top left panel shows the derived number of globular clusters in each galaxy. [van Dokkum et al. 2017]Globulars GaloreVan Dokkum and collaborators imaged two UDGs with Hubble: Dragonfly 44 and DFX1, both located in the Coma galaxy cluster. These faint galaxies are both smooth and elongated, with no obvious irregular features, spiral arms, star-forming regions, or other indications of tidal interactions

  7. Sugar-binding sites of the HA1 subcomponent of Clostridium botulinum type C progenitor toxin.

    PubMed

    Nakamura, Toshio; Tonozuka, Takashi; Ide, Azusa; Yuzawa, Takayuki; Oguma, Keiji; Nishikawa, Atsushi

    2008-02-22

    Clostridium botulinum type C 16S progenitor toxin contains a hemagglutinin (HA) subcomponent, designated HA1, which appears to play an important role in the effective internalization of the toxin in gastrointestinal epithelial cells and in creating a broad specificity for the oligosaccharide structure that corresponds to various targets. In this study, using the recombinant protein fused to glutathione S-transferase, we investigated the binding specificity of the HA1 subcomponent to sugars and estimated the binding sites of HA1 based on X-ray crystallography and soaking experiments using various sugars. N-Acetylneuraminic acid, N-acetylgalactosamine, and galactose effectively inhibited the binding that occurs between glutathione S-transferase-HA1 and mucins, whereas N-acetylglucosamine and glucose did not inhibit it. The crystal structures of HA1 complex with N-acetylneuraminic acid, N-acetylgalactosamine, and galactose were also determined. There are two sugar-binding sites, sites I and II. Site I corresponds to the electron densities noted for all sugars and is located at the C-terminal beta-trefoil domain, while site II corresponds to the electron densities noted only for galactose. An aromatic amino acid residue, Trp176, at site I has a stacking interaction with the hexose ring of the sugars. On the other hand, there is no aromatic residue at site II; thus, the interaction with galactose seems to be poor. The double mutant W176A at site I and D271F at site II has no avidity for N-acetylneuraminic acid but has avidity for galactose. In this report, the binding specificity of botulinum C16S toxin HA1 to various sugars is demonstrated based on its structural features.

  8. Precerebellin is a cerebellum-specific protein with similarity to the globular domain of complement C1q B chain.

    PubMed Central

    Urade, Y; Oberdick, J; Molinar-Rode, R; Morgan, J I

    1991-01-01

    The cerebellum contains a hexadecapeptide, termed cerebellin, that is conserved in sequence from human to chicken. Three independent, overlapping cDNA clones have been isolated from a human cerebellum cDNA library that encode the cerebellin sequence. The longest clone codes for a protein of 193 amino acids that we term precerebellin. This protein has a significant similarity (31.3% identity, 52.2% similarity) to the globular (non-collagen-like) region of the B chain of human complement component C1q. The region of relatedness extends over approximately 145 amino acids located in the carboxyl terminus of both proteins. Unlike C1q B chain, no collagen-like motifs are present in the amino-terminal regions of precerebellin. The amino terminus of precerebellin contains three possible N-linked glycosylation sites. Although hydrophobic amino acids are clustered at the amino terminus, they do not conform to the classical signal-peptide motif, and no other obvious membrane-spanning domains are predicted from the cDNA sequence. The cDNA predicts that the cerebellin peptide is flanked by Val-Arg and Glu-Pro residues. Therefore, cerebellin is not liberated from precerebellin by the classical dibasic amino acid proteolytic-cleavage mechanism seen in many neuropeptide precursors. In Northern (RNA) blots, precerebellin transcripts, with four distinct sizes (1.8, 2.3, 2.7, and 3.0 kilobases), are abundant in cerebellum. These transcripts are present at either very low or undetectable levels in other brain areas and extraneural structures. A similar pattern of cerebellin precursor transcripts are seen in rat, mouse, and human cerebellum. Furthermore, a partial genomic fragment from mouse shows the same bands in Northern blots as the human cDNA clone. During rat development, precerebellin transcripts mirror the level of cerebellin peptide. Low levels of precerebellin mRNA are seen at birth. Levels increase modestly from postpartum day 1 to 8, then increase more dramatically between

  9. Modification of structure and pattern of lipid monolayer on water and solid surfaces in presence of globular protein

    NASA Astrophysics Data System (ADS)

    Sah, Bijay Kumar; Kundu, Sarathi

    2017-05-01

    Langmuir monolayers of phospholipids at the air-water interface are well-established model systems for mimicking biological membranes and hence are useful for studying lipid-protein interactions. In the present work, phases and phase transformations occurring in the lipid (DMPA) monolayer in the presence of globular protein (BSA) at neutral subphase pH (≈7.0) are highlighted and the corresponding in-plane pattern and morphology are explored from the surface pressure (π) - specific molecular area (A) isotherm, Brewster angle microscopy (BAM) and atomic force microscopy (AFM) both at air-water and air-solid interfaces. Films of pure lipid and lipid-protein complexes are deposited on solid surfaces by Langmuir-Blodgett method. Due to the presence of BSA molecules, phases and domain pattern changes in comparison with that of the pure DMPA. Moreover, accumulations of globular proteins in between lipid domains are also visible through BAM. AFM shows that the mixed film has relatively bigger globular-like morphology in comparison with that of pure DMPA domains. Combination of electrostatic and hydrophobic interactions between protein and lipid are responsible for such modifications.

  10. Globular cluster x-ray sources

    PubMed Central

    Pooley, David

    2010-01-01

    Globular clusters and x-ray astronomy have a long and fruitful history. Uhuru and OSO-7 revealed highly luminous (> 1036 ergs-1) x-ray sources in globular clusters, and Einstein and ROSAT revealed a larger population of low-luminosity (< 1033 ergs-1) x-ray sources. It was realized early on that the high-luminosity sources were low-mass x-ray binaries in outburst and that they were orders of magnitude more abundant per unit mass in globular clusters than in the rest of the galaxy. However, the low-luminosity sources proved difficult to classify. Many ideas were put forth—low-mass x-ray binaries in quiescence (qLMXBs), cataclysmic variables (CVs), active main-sequence binaries (ABs), and millisecond pulsars (MSPs)—but secure identifications were scarce. In ROSAT observations of 55 clusters, about 25 low-luminosity sources were found. Chandra has now observed over 80 Galactic globular clusters, and these observations have revealed over 1,500 x-ray sources. The superb angular resolution has allowed for many counterpart identifications, providing clues to the nature of this population. It is a heterogeneous mix of qLMXBs, CVs, ABs, and MSPs, and it has been shown that the qLMXBs and CVs are both, in part, overabundant like the luminous LMXBs. The number of x-ray sources in a cluster correlates very well with its encounter frequency. This points to dynamical formation scenarios for the x-ray sources and shows them to be excellent tracers of the complicated internal dynamics. The relation between the encounter frequency and the number of x-ray sources has been used to suggest that we have misunderstood the dynamical states of globular clusters. PMID:20404204

  11. Generation of recombinant pandemic H1N1 influenza virus with the HA cleavable by bromelain and identification of the residues influencing HA bromelain cleavage.

    PubMed

    Wang, Weijia; Suguitan, Amorsolo L; Zengel, James; Chen, Zhongying; Jin, Hong

    2012-01-20

    The proteolytic enzyme bromelain has been traditionally used to cleave the hemagglutinin (HA) protein at the C-terminus of the HA2 region to release the HA proteins from influenza virions. The bromelain cleaved HA (BHA) has been routinely used as an antigen to generate antiserum that is essential for influenza vaccine product release. The HA of the 2009 pandemic H1N1 influenza A/California/7/2009 (CA09) virus could not be cleaved efficiently by bromelain. To ensure timely delivery of BHA for antiserum production, we generated a chimeric virus that contained the HA1 region from CA09 and the HA2 region from the seasonal H1N1 A/South Dakota/6/2007 (SD07) virus that is cleavable by bromelain. The BHA from this chimeric virus was antigenically identical to CA09 and induced high levels of HA-specific antibodies and protected ferrets from wild-type H1N1 CA09 virus challenge. To determine the molecular basis of inefficient cleavage of CA09 HA by bromelain, the amino acids that differed between the HA2 of CA09 and SD07 were introduced into recombinant CA09 virus to assess their effect on bromelain cleavage. The D373N or E374G substitution in the HA2 stalk region of CA09 HA enabled efficient cleavage of CA09 HA by bromelain. Sequence analysis of the pandemic H1N1-like viruses isolated from 2010 revealed emergence of the E374K change. We found that K374 enabled the HA to be cleaved by bromelain and confirmed that the 374 residue is critical for HA bromelain cleavage. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Preparative two-step purification of recombinant H1.0 linker histone and its domains.

    PubMed

    Ivic, Nives; Bilokapic, Silvija; Halic, Mario

    2017-01-01

    H1 linker histones are small basic proteins that have a key role in the formation and maintenance of higher-order chromatin structures. Additionally, many examples have shown that linker histones play an important role in gene regulation, modulated by their various subtypes and posttranslational modifications. Obtaining high amounts of very pure linker histones, especially for efficient antibody production, remains a demanding and challenging procedure. Here we present an easy and fast method to purify human linker histone H1.0 overexpressed in Escherichia coli, as well as its domains: N-terminal/globular domain and C-terminal intrinsically disordered domain. This purification protocol relies on a simple affinity chromatography step followed by cation exchange due to the highly basic properties of histone proteins. Therefore, this protocol can also be applied to other linker histones. Highly pure proteins in amounts sufficient for most biochemical experiments can be obtained. The functional quality of purified H1.0 histone and its domains has been confirmed by pull-down, gel-mobility shift assays and the nuclear import assay.

  13. Folding energy landscape and network dynamics of small globular proteins

    PubMed Central

    Hori, Naoto; Chikenji, George; Berry, R. Stephen; Takada, Shoji

    2009-01-01

    The folding energy landscape of proteins has been suggested to be funnel-like with some degree of ruggedness on the slope. How complex the landscape, however, is still rather unclear. Many experiments for globular proteins suggested relative simplicity, whereas molecular simulations of shorter peptides implied more complexity. Here, by using complete conformational sampling of 2 globular proteins, protein G and src SH3 domain and 2 related random peptides, we investigated their energy landscapes, topological properties of folding networks, and folding dynamics. The projected energy surfaces of globular proteins were funneled in the vicinity of the native but also have other quite deep, accessible minima, whereas the randomized peptides have many local basins, including some leading to seriously misfolded forms. Dynamics in the denatured part of the network exhibited basin-hopping itinerancy among many conformations, whereas the protein reached relatively well-defined final stages that led to their native states. We also found that the folding network has the hierarchic nature characterized by the scale-free and the small-world properties. PMID:19114654

  14. Folding energy landscape and network dynamics of small globular proteins.

    PubMed

    Hori, Naoto; Chikenji, George; Berry, R Stephen; Takada, Shoji

    2009-01-06

    The folding energy landscape of proteins has been suggested to be funnel-like with some degree of ruggedness on the slope. How complex the landscape, however, is still rather unclear. Many experiments for globular proteins suggested relative simplicity, whereas molecular simulations of shorter peptides implied more complexity. Here, by using complete conformational sampling of 2 globular proteins, protein G and src SH3 domain and 2 related random peptides, we investigated their energy landscapes, topological properties of folding networks, and folding dynamics. The projected energy surfaces of globular proteins were funneled in the vicinity of the native but also have other quite deep, accessible minima, whereas the randomized peptides have many local basins, including some leading to seriously misfolded forms. Dynamics in the denatured part of the network exhibited basin-hopping itinerancy among many conformations, whereas the protein reached relatively well-defined final stages that led to their native states. We also found that the folding network has the hierarchic nature characterized by the scale-free and the small-world properties.

  15. Generation of a consensus protein domain dictionary

    PubMed Central

    Schaeffer, R. Dustin; Jonsson, Amanda L.; Simms, Andrew M.; Daggett, Valerie

    2011-01-01

    Motivation: The discovery of new protein folds is a relatively rare occurrence even as the rate of protein structure determination increases. This rarity reinforces the concept of folds as reusable units of structure and function shared by diverse proteins. If the folding mechanism of proteins is largely determined by their topology, then the folding pathways of members of existing folds could encompass the full set used by globular protein domains. Results: We have used recent versions of three common protein domain dictionaries (SCOP, CATH and Dali) to generate a consensus domain dictionary (CDD). Surprisingly, 40% of the metafolds in the CDD are not composed of autonomous structural domains, i.e. they are not plausible independent folding units. This finding has serious ramifications for bioinformatics studies mining these domain dictionaries for globular protein properties. However, our main purpose in deriving this CDD was to generate an updated CDD to choose targets for MD simulation as part of our dynameomics effort, which aims to simulate the native and unfolding pathways of representatives of all globular protein consensus folds (metafolds). Consequently, we also compiled a list of representative protein targets of each metafold in the CDD. Availability and implementation: This domain dictionary is available at www.dynameomics.org. Contact: daggett@u.washington.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21068000

  16. Intra-cluster Globular Clusters in a Simulated Galaxy Cluster

    NASA Astrophysics Data System (ADS)

    Ramos-Almendares, Felipe; Abadi, Mario; Muriel, Hernán; Coenda, Valeria

    2018-01-01

    Using a cosmological dark matter simulation of a galaxy-cluster halo, we follow the temporal evolution of its globular cluster population. To mimic the red and blue globular cluster populations, we select at high redshift (z∼ 1) two sets of particles from individual galactic halos constrained by the fact that, at redshift z = 0, they have density profiles similar to observed ones. At redshift z = 0, approximately 60% of our selected globular clusters were removed from their original halos building up the intra-cluster globular cluster population, while the remaining 40% are still gravitationally bound to their original galactic halos. As the blue population is more extended than the red one, the intra-cluster globular cluster population is dominated by blue globular clusters, with a relative fraction that grows from 60% at redshift z = 0 up to 83% for redshift z∼ 2. In agreement with observational results for the Virgo galaxy cluster, the blue intra-cluster globular cluster population is more spatially extended than the red one, pointing to a tidally disrupted origin.

  17. Interactions between globular proteins and F-actin in isotonic saline solution.

    PubMed

    Lakatos, S; Minton, A P

    1991-10-05

    Solutions of each of three different globular proteins (cytochrome c, chromophorically labeled serum albumin, and chromophorically labeled aldolase), mixed with another unlabeled globular protein or with fibrous actin, were prepared in pH 8.0 Tris-HCl buffer containing 0.15 M NaCl. Each solution was centrifuged at low speed, at 5 degrees C, until unassociated globular protein in solution achieved sedimentation equilibrium. Individual absorbance gradients of both macrosolutes in the mixtures subsequent to centrifugation were obtained via optical scans of the centrifuge tubes at two wavelengths. The gradients of each macrosolute in mixtures of two globular proteins revealed no association of globular proteins under the conditions of these experiments, but perturbation of the gradients of serum albumin, aldolase, and cytochrome c in the presence of F-actin indicated association of all three globular proteins with F-actin. Perturbation of actin gradients in the presence of serum albumin and aldolase suggested partial depolymerization of the F-actin by the globular protein. Analysis of the data with a simple phenomenological model relating free globular protein, bound globular protein, and total actin concentration provided estimates of the respective equilibrium constants for association of serum albumin and aldolase with F-actin, under the conditions of these experiments, of the order of 0.1 microM-1.

  18. Human Nek6 is a monomeric mostly globular kinase with an unfolded short N-terminal domain

    PubMed Central

    2011-01-01

    Background The NIMA-related kinases (Neks) are widespread among eukaryotes. In mammalians they represent an evolutionarily conserved family of 11 serine/threonine kinases, with 40-45% amino acid sequence identity to the Aspergillus nidulans mitotic regulator NIMA within their catalytic domains. Neks have cell cycle-related functions and were recently described as related to pathologies, particularly cancer, consisting in potential chemotherapeutic targets. Human Nek6, -7 and -9 are involved in the control of mitotic spindle formation, acting together in a mitotic kinase cascade, but their mechanism of regulation remain elusive. Results In this study we performed a biophysical and structural characterization of human Nek6 with the aim of obtaining its low resolution and homology models. SAXS experiments showed that hNek6 is a monomer of a mostly globular, though slightly elongated shape. Comparative molecular modeling together with disorder prediction analysis also revealed a flexible disordered N-terminal domain for hNek6, which we found to be important to mediate interactions with diverse partners. SEC-MALS experiments showed that hNek6 conformation is dependent on its activation/phosphorylation status, a higher phosphorylation degree corresponding to a bigger Stokes radius. Circular dichroism spectroscopy confirmed our in silico predictions of secondary structure content and thermal stability shift assays revealed a slightly higher stability of wild-type hNek6 compared to the activation loop mutant hNek6(S206A). Conclusions Our data present the first low resolution 3D structure of hNek6 protein in solution. SAXS, comparative modeling and SEC-MALS analysis revealed that hNek6 is a monomeric kinase of slightly elongated shape and a short unfolded N-terminal domain. PMID:21320329

  19. An Influenza HA and M2e Based Vaccine Delivered by a Novel Attenuated Salmonella Mutant Protects Mice against Homologous H1N1 Infection.

    PubMed

    Hajam, Irshad A; Lee, John H

    2017-01-01

    Attenuated Salmonella strains constitute a promising technology for the development of a more efficient multivalent protein based vaccines. In this study, we constructed a novel attenuated strain of Salmonella for the delivery and expression of the H1N1 hemagglutinin (HA) and the conserved extracellular domain of the matrix protein 2 (M2e). We demonstrated that the constructed Salmonella strain exhibited efficient HA and M2e protein expressions and little cytotoxicity and pathogenicity in mice. Using BALB/c mice as the model, we showed that the mice vaccinated with a Salmonella strain expressing HA and M2e protein antigens, respectively, induced significant production of HA and M2e-specific serum IgG1 and IgG2a responses, and of anti-HA interferon-γ producing T cells. Furthermore, immunization with Salmonella-HA-M2e-based vaccine via different routes provided protection in 66.66% orally, 100% intramuscularly, and 100% intraperitoneally immunized mice against the homologous H1N1 virus while none of the animals survived treated with either the PBS or the Salmonella carrying empty expression vector. Ex vivo stimulated dendritic cells (DCs) with heat killed Salmonella expressing HA demonstrated that DCs play an important role in the elicitation of HA-specific humoral immune responses in mice. In summary, Salmonella -HA-M2e-based vaccine elicits efficient antigen-specific humoral and cellular immune responses, and provides significant immune protection against a highly pathogenic H1N1 influenza virus.

  20. Akt1 binds focal adhesion kinase via the Akt1 kinase domain independently of the pleckstrin homology domain.

    PubMed

    Basson, M D; Zeng, B; Wang, S

    2015-10-01

    Akt1 and focal adhesion kinase (FAK) are protein kinases that play key roles in normal cell signaling. Individually, aberrant expression of these kinases has been linked to a variety of cancers. Together, Akt1/FAK interactions facilitate cancer metastasis by increasing cell adhesion under conditions of increased extracellular pressure. Pathological and iatrogenic sources of pressure arise from tumor growth against constraining stroma or direct perioperative manipulation. We previously reported that 15 mmHg increased extracellular pressure causes Akt1 to both directly interact with FAK and to phosphorylate and activate it. We investigated the nature of the Akt1/FAK binding by creating truncations of recombinant FAK, conjugated to glutathione S-transferase (GST), to pull down full-length Akt1. Western blots probing for Akt1 showed that FAK/Akt1 binding persisted in FAK truncations consisting of only amino acids 1-126, FAK(NT1), which contains the F1 subdomain of its band 4.1, ezrin, radixin, and moesin (FERM) domain. Using FAK(NT1) as bait, we then pulled down truncated versions of recombinant Akt1 conjugated to HA (human influenza hemagglutinin). Probes for GST-FAK(NT1) showed Akt1-FAK binding to occur in the absence of the both the Akt1 (N)-terminal pleckstrin homology (PH) domain and its adjacent hinge region. The Akt1 (C)-terminal regulatory domain was equally unnecessary for Akt1/FAK co-immunoprecipitation. Truncations involving the Akt1 catalytic domain showed that the domain by itself was enough to pull down FAK. Additionally, a fragment spanning from the PH domain to half way through the catalytic domain demonstrated increased FAK binding compared to full length Akt1. These results begin to delineate the Akt1/FAK interaction and can be used to manipulate their force-activated signal interactions. Furthermore, the finding that the N-terminal half of the Akt1 catalytic domain binds so strongly to FAK when cleaved from the rest of the protein may suggest a means

  1. REVIEW: Optics of globular photonic crystals

    NASA Astrophysics Data System (ADS)

    Gorelik, V. S.

    2007-05-01

    The results of experimental and theoretical studies of the optical properties of globular photonic crystals - new physical objects having a crystal structure with the lattice period exceeding considerably the atomic size, are presented. As globular photonic crystals, artificial opal matrices consisting of close-packed silica globules of diameter ~200 nm were used. The reflection spectra of these objects characterising the parameters of photonic bands existing in these crystals in the visible spectral region are presented. The idealised models of the energy band structure of photonic crystals investigated in the review give analytic dispersion dependences for the group velocity and the effective photon mass in a globular photonic crystal. The characteristics of secondary emission excited in globular photonic crystals by monochromatic and broadband radiation are presented. The results of investigations of single-photon-excited delayed scattering of light observed in globular photonic crystals exposed to cw UV radiation and radiation from a repetitively pulsed copper vapour laser are presented. The possibilities of using globular photonic crystals as active media for lasing in different spectral regions are considered. It is proposed to use globular photonic crystals as sensitive sensors in optoelectronic devices for molecular analysis of organic and inorganic materials by the modern methods of laser spectroscopy. The results of experimental studies of spontaneous and stimulated globular scattering of light are discussed. The conditions for observing resonance and two-photon-excited delayed scattering of light are found. The possibility of accumulation and localisation of the laser radiation energy inside a globular photonic crystal is reported.

  2. Globular Clusters Shine in a Galaxy Lacking Dark Matter

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2018-04-01

    You may have seen recent news about NGC 1052DF2, a galaxy that was discovered to have little or no dark matter. Now, a new study explores what NGC 1052DF2 does have: an enigmatic population of unusually large and luminous globular clusters.Keck/LRIS spectra (left and right) and HST images (center) of the 11 clusters associated with NGC 1052DF2. The color images each span 1 1. [van Dokkum et al. 2018]An Unusual DwarfThe ultra-diffuse galaxy NGC 1052DF2, originally identified with the Dragonfly Telescope Array, has puzzled astronomers since the discovery that its dynamical mass determined by the motions of globular-cluster-like objects spotted within it is essentially the same as its stellar mass. This equivalence implies that the galaxy is strangely lacking dark matter; the upper limit set on its dark matter halo is 400 times smaller than what we would expect for such a dwarf galaxy.Led by Pieter van Dokkum (Yale University), the team that made this discovery has now followed up with detailed Hubble Space Telescope imaging and Keck spectroscopy. Their goal? To explore the objects that allowed them to make the dynamical-mass measurement: the oddly bright globular clusters of NGC 1052DF2.Sizes (circularized half-light radii) vs. absolute magnitudes for globular clusters in NGC1052DF2 (black) and the Milky Way (red). [Adapted from van Dokkum et al. 2018]Whats Up with the Globular Clusters?Van Dokkum and collaborators spectroscopically confirmed 11 compact objects associated with the faint galaxy. These objects are globular-cluster-like in their appearance, but the peak of their luminosity distribution is offset by a factor of four from globular clusters of other galaxies; these globular clusters are significantly brighter than is typical.Using the Hubble imaging, the authors determined that NGC 1052DF2s globular clusters are more than twice the size of the Milky Ways globular clusters in the same luminosity range. As is typical for globular clusters, they are an old

  3. Promotion of PDT efficacy by HA14-1

    NASA Astrophysics Data System (ADS)

    Kessel, David; Price, Michael; Haagenson, Kelly

    2008-02-01

    Photodynamic therapy (PDT) can target the members of the Bcl-2 family that protect cells from the initiation of apoptosis, a well-known death pathway. We examined the ability of HA14-1, a non-peptidic Bcl-2/Bcl-xL antagonist, to promote the efficacy of PDT. The photosensitizer was the porphycene CPO that causes photodamage to Bcl-2 located in the endoplasmic reticulum. Using low PDT doses together with LD5-20 concentrations of HA14-1, we found a marked synergistic effect. These results indicate that such an effect occurs when PDT is coupled with pharmacologic suppression of Bcl-2 function. HA14-1 is an unstable compound that decomposes in aqueous solution. This resulted in a rapid (~60 sec) burst of fluorescence that closely mimicked the properties of many fluorescent probes, but was traced to an effect produced when HA14-1 contacts serum proteins. Other Bcl-2 antagonists that do not produce any intrinsic fluorescence also promoted PDT efficacy. Moreover, briefly storing HA14-1 in aqueous medium until the fluorescent burst is over does not inhibit a subsequent synergistic promotion of PDT efficacy. We conclude that Bcl-2 antagonists can promote the efficacy of low-dose PDT in a manner unrelated to ROS production. The most likely explanation is an enhanced loss of anti-apoptotic Bcl-2 family function such that a threshold for initiation of apoptosis is crossed.

  4. A black hole in a globular cluster.

    PubMed

    Maccarone, Thomas J; Kundu, Arunav; Zepf, Stephen E; Rhode, Katherine L

    2007-01-11

    Globular star clusters contain thousands to millions of old stars packed within a region only tens of light years across. Their high stellar densities make it very probable that their member stars will interact or collide. There has accordingly been considerable debate about whether black holes should exist in these star clusters. Some theoretical work suggests that dynamical processes in the densest inner regions of globular clusters may lead to the formation of black holes of approximately 1,000 solar masses. Other numerical simulations instead predict that stellar interactions will eject most or all of the black holes that form in globular clusters. Here we report the X-ray signature of an accreting black hole in a globular cluster associated with the giant elliptical galaxy NGC 4472 (in the Virgo cluster). This object has an X-ray luminosity of about 4 x 10(39) erg s(-1), which rules out any object other than a black hole in such an old stellar population. The X-ray luminosity varies by a factor of seven in a few hours, which excludes the possibility that the object is several neutron stars superposed.

  5. Crystal structures of ryanodine receptor SPRY1 and tandem-repeat domains reveal a critical FKBP12 binding determinant

    NASA Astrophysics Data System (ADS)

    Yuchi, Zhiguang; Yuen, Siobhan M. Wong King; Lau, Kelvin; Underhill, Ainsley Q.; Cornea, Razvan L.; Fessenden, James D.; van Petegem, Filip

    2015-08-01

    Ryanodine receptors (RyRs) form calcium release channels located in the membranes of the sarcoplasmic and endoplasmic reticulum. RyRs play a major role in excitation-contraction coupling and other Ca2+-dependent signalling events, and consist of several globular domains that together form a large assembly. Here we describe the crystal structures of the SPRY1 and tandem-repeat domains at 1.2-1.5 Å resolution, which reveal several structural elements not detected in recent cryo-EM reconstructions of RyRs. The cryo-EM studies disagree on the position of SPRY domains, which had been proposed based on homology modelling. Computational docking of the crystal structures, combined with FRET studies, show that the SPRY1 domain is located next to FK506-binding protein (FKBP). Molecular dynamics flexible fitting and mutagenesis experiments suggest a hydrophobic cluster within SPRY1 that is crucial for FKBP binding. A RyR1 disease mutation, N760D, appears to directly impact FKBP binding through interfering with SPRY1 folding.

  6. In vivo functional mapping of the conserved protein domains within murine Themis1.

    PubMed

    Zvezdova, Ekaterina; Lee, Jan; El-Khoury, Dalal; Barr, Valarie; Akpan, Itoro; Samelson, Lawrence; Love, Paul E

    2014-09-01

    Thymocyte development requires the coordinated input of signals that originate from numerous cell surface molecules. Although the majority of thymocyte signal-initiating receptors are lineage-specific, most trigger 'ubiquitous' downstream signaling pathways. T-lineage-specific receptors are coupled to these signaling pathways by lymphocyte-restricted adapter molecules. We and others recently identified a new putative adapter protein, Themis1, whose expression is largely restricted to the T lineage. Mice lacking Themis1 exhibit a severe block in thymocyte development and a striking paucity of mature T cells revealing a critical role for Themis1 in T-cell maturation. Themis1 orthologs contain three conserved domains: a proline-rich region (PRR) that binds to the ubiquitous cytosolic adapter Grb2, a nuclear localization sequence (NLS), and two copies of a novel cysteine-containing globular (CABIT) domain. In the present study, we evaluated the functional importance of each of these motifs by retroviral reconstitution of Themis1(-/-) progenitor cells. The results demonstrate an essential requirement for the PRR and NLS motifs but not the conserved CABIT cysteines for Themis1 function.

  7. HST observations of globular clusters in M 31. 1: Surface photometry of 13 objects

    NASA Technical Reports Server (NTRS)

    Pecci, F. Fusi; Battistini, P.; Bendinelli, O.; Bonoli, F.; Cacciari, C.; Djorgovski, S.; Federici, L.; Ferraro, F. R.; Parmeggiani, G.; Weir, N.

    1994-01-01

    We present the initial results of a study of globular clusters in M 31, using the Faint Object Camera (FOC) on the Hubble Space Telescope (HST). The sample of objects consists of 13 clusters spanning a range of properties. Three independent image deconvolution techniques were used in order to compensate for the optical problems of the HST, leading to mutually fully consistent results. We present detailed tests and comparisons to determine the reliability and limits of these deconvolution methods, and conclude that high-quality surface photometry of M 31 globulars is possible with the HST data. Surface brightness profiles have been extracted, and core radii, half-light radii, and central surface brightness values have been measured for all of the clusters in the sample. Their comparison with the values from ground-based observations indicates the later to be systematically and strongly biased by the seeing effects, as it may be expected. A comparison of the structural parameters with those of the Galactic globulars shows that the structural properties of the M 31 globulars are very similar to those of their Galactic counterparts. A candidate for a post-core-collapse cluster, Bo 343 = G 105, has been already identified from these data; this is the first such detection in the M 31 globular cluster system.

  8. Globular Cluster Systems in Interacting Galaxies

    NASA Astrophysics Data System (ADS)

    Zepf, S.; Murdin, P.

    2000-11-01

    GLOBULAR CLUSTERS are dynamically bound and dense collections of large numbers of coeval stars. Typical globular clusters have roughly one million stars within a radius of a few parsecs. They are also usually close to spherical, hence the name globular. By virtue of their rich, isolated population of stars they provide an important laboratory for studies of STELLAR EVOLUTION. Moreover, because of...

  9. Sequential Infection in Ferrets with Antigenically Distinct Seasonal H1N1 Influenza Viruses Boosts Hemagglutinin Stalk-Specific Antibodies

    PubMed Central

    Kirchenbaum, Greg A.; Carter, Donald M.

    2015-01-01

    ABSTRACT Broadly reactive antibodies targeting the conserved hemagglutinin (HA) stalk region are elicited following sequential infection or vaccination with influenza viruses belonging to divergent subtypes and/or expressing antigenically distinct HA globular head domains. Here, we demonstrate, through the use of novel chimeric HA proteins and competitive binding assays, that sequential infection of ferrets with antigenically distinct seasonal H1N1 (sH1N1) influenza virus isolates induced an HA stalk-specific antibody response. Additionally, stalk-specific antibody titers were boosted following sequential infection with antigenically distinct sH1N1 isolates in spite of preexisting, cross-reactive, HA-specific antibody titers. Despite a decline in stalk-specific serum antibody titers, sequential sH1N1 influenza virus-infected ferrets were protected from challenge with a novel H1N1 influenza virus (A/California/07/2009), and these ferrets poorly transmitted the virus to naive contacts. Collectively, these findings indicate that HA stalk-specific antibodies are commonly elicited in ferrets following sequential infection with antigenically distinct sH1N1 influenza virus isolates lacking HA receptor-binding site cross-reactivity and can protect ferrets against a pathogenic novel H1N1 virus. IMPORTANCE The influenza virus hemagglutinin (HA) is a major target of the humoral immune response following infection and/or seasonal vaccination. While antibodies targeting the receptor-binding pocket of HA possess strong neutralization capacities, these antibodies are largely strain specific and do not confer protection against antigenic drift variant or novel HA subtype-expressing viruses. In contrast, antibodies targeting the conserved stalk region of HA exhibit broader reactivity among viruses within and among influenza virus subtypes. Here, we show that sequential infection of ferrets with antigenically distinct seasonal H1N1 influenza viruses boosts the antibody responses

  10. Biomedical potential of chitosan/HA and chitosan/β-1,3-glucan/HA biomaterials as scaffolds for bone regeneration--A comparative study.

    PubMed

    Przekora, Agata; Palka, Krzysztof; Ginalska, Grazyna

    2016-01-01

    The aim of this work was to compare biomedical potential of chitosan/hydroxyapatite (chit/HA) and novel chitosan/β-1,3-glucan/hydroxyapatite (chit/glu/HA) materials as scaffolds for bone regeneration via characterization of their biocompatibility, porosity, mechanical properties, and water uptake behaviour. Biocompatibility of the scaffolds was assessed in direct-contact with the materials using normal human foetal osteoblast cell line. Cytotoxicity and osteoblast proliferation rate were evaluated. Porosity was assessed using computed microtomography analysis and mechanical properties were determined by compression testing. Obtained results demonstrated that chit/HA scaffold possessed significantly better mechanical properties (compressive strength: 1.23 MPa, Young's modulus: 0.46 MPa) than chit/glu/HA material (compressive strength: 0.26 MPa, Young's modulus: 0.25 MPa). However, addition of bacterial β-1,3-glucan to the chit/HA scaffold improved its flexibility and porosity. Moreover, chit/glu/HA scaffold revealed significantly higher water uptake capability (52.6% after 24h of soaking) compared to the chit/HA (30.7%) and thus can serve as a very good drug delivery carrier. Chit/glu/HA scaffold was also more favourable to osteoblast survival (near 100% viability after 24-h culture), proliferation, and spreading compared to the chit/HA (63% viability). The chit/glu/HA possesses better biomedical potential than chit/HA scaffold. Nevertheless, poor mechanical properties of the chit/glu/HA limit its application to non-load bearing implantation area. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. DDO 216-A1: A Central Globular Cluster in a Low-luminosity Transition-type Galaxy

    NASA Astrophysics Data System (ADS)

    Cole, Andrew A.; Weisz, Daniel R.; Skillman, Evan D.; Leaman, Ryan; Williams, Benjamin F.; Dolphin, Andrew E.; Johnson, L. Clifton; McConnachie, Alan W.; Boylan-Kolchin, Michael; Dalcanton, Julianne; Governato, Fabio; Madau, Piero; Shen, Sijing; Vogelsberger, Mark

    2017-03-01

    We confirm that the object DDO 216-A1 is a substantial globular cluster at the center of Local Group galaxy DDO 216 (the Pegasus dwarf irregular), using Hubble Space Telescope ACS imaging. By fitting isochrones, we find the cluster metallicity [M/H] = -1.6 ± 0.2, for reddening E(B-V) = 0.16 ± 0.02 the best-fit age is 12.3 ± 0.8 Gyr. There are ≈ 30 RR Lyrae variables in the cluster; the magnitude of the fundamental mode pulsators gives a distance modulus of 24.77 ± 0.08—identical to the host galaxy. The ratio of overtone to fundamental mode variables and their mean periods make DDO 216-A1 an Oosterhoff Type I cluster. We find a central surface brightness of 20.85 ± 0.17 F814W mag arcsec-2, a half-light radius of 3\\buildrel{\\prime\\prime}\\over{.} 1 (13.4 pc), and an absolute magnitude M814 = -7.90 ± 0.16 (M/{M}⊙ ≈ 105). King models fit to the cluster give the core radius and concentration index, r c = 2\\buildrel{\\prime\\prime}\\over{.} 1 ± 0\\buildrel{\\prime\\prime}\\over{.} 9 and c = 1.24 ± 0.39. The cluster is an “extended” cluster somewhat typical of some dwarf galaxies and the outer halo of the Milky Way. The cluster is projected ≲30 pc south of the center of DDO 216, unusually central compared to most dwarf galaxy globular clusters. Analytical models of dynamical friction and tidal destruction suggest that it probably formed at a larger distance, up to ˜1 kpc, and migrated inward. DDO 216 has an unexceptional specific cluster frequency, S N = 10. DDO 216 is the lowest-luminosity Local Group galaxy to host a 105 {M}⊙ globular cluster and the only transition-type (dSph/dIrr) galaxy in the Local Group with a globular cluster. Based on observations made with the NASA/ESA Hubble Space Telesope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5-26555. These observations were obtained under program GO-13768.

  12. Globular cluster content and evolutionary history of NGC 147

    NASA Astrophysics Data System (ADS)

    Sharina, M.; Davoust, E.

    2009-04-01

    Context: Globular clusters are representative of the oldest stellar populations. It is thus essential to have a complete census of these systems in dwarf galaxies, from which more massive galaxies are progressively formed in the hierarchical scenario. Aims: We present the results of spectroscopic observations of eight globular cluster candidates in NGC 147, a satellite dwarf elliptical galaxy of M 31. Our goal is to make a complete inventory of the globular cluster system of this galaxy, determine the properties of their stellar populations, and compare these properties with those of systems of globular clusters in other dwarf galaxies. Methods: The candidates were identified on Canada-France-Hawaii telescope photographic plates. Medium resolution spectra were obtained with the SCORPIO spectrograph at the prime focus of the 6 m telescope of the Russian Academy of Sciences. They were analyzed using predictions of stellar population synthesis models. Results: We were able to confirm the nature of all eight candidates, three of which (GC5, GC7, and GC10) are indeed globular clusters, and to estimate evolutionary parameters for the two brightest ones and for Hodge II. The bright clusters GC5 and GC7 appear to have metallicities ([Z/H] -1.5 div -1.8) that are lower than the oldest stars in the galaxy. The fainter GC Hodge II has a metallicity [Z/H] = -1.1, similar to that of the oldest stars in the galaxy. The clusters GC5 and GC7 have low alpha-element abundance ratios. The mean age of the globular clusters in NGC 147 is 9 ± 1 Gyr. We also measured the radial velocities of Hodge II and IV, and derived a mass of NGC 147 in good agreement with the value from the literature. The frequency, Sn = 6.4, and mass fraction, T = 14 of globular clusters in NGC 147 appear to be higher than those for NGC 185 and 205. Conclusions: Our results indicate that the bright clusters GC5, GC7, and Hodge III formed in the main star-forming period 8-10 Gyr ago, while the fainter clusters

  13. Structural mapping of the coiled-coil domain of a bacterial condensin and comparative analyses across all domains of life suggest conserved features of SMC proteins.

    PubMed

    Waldman, Vincent M; Stanage, Tyler H; Mims, Alexandra; Norden, Ian S; Oakley, Martha G

    2015-06-01

    The structural maintenance of chromosomes (SMC) proteins form the cores of multisubunit complexes that are required for the segregation and global organization of chromosomes in all domains of life. These proteins share a common domain structure in which N- and C- terminal regions pack against one another to form a globular ATPase domain. This "head" domain is connected to a central, globular, "hinge" or dimerization domain by a long, antiparallel coiled coil. To date, most efforts for structural characterization of SMC proteins have focused on the globular domains. Recently, however, we developed a method to map interstrand interactions in the 50-nm coiled-coil domain of MukB, the divergent SMC protein found in γ-proteobacteria. Here, we apply that technique to map the structure of the Bacillus subtilis SMC (BsSMC) coiled-coil domain. We find that, in contrast to the relatively complicated coiled-coil domain of MukB, the BsSMC domain is nearly continuous, with only two detectable coiled-coil interruptions. Near the middle of the domain is a break in coiled-coil structure in which there are three more residues on the C-terminal strand than on the N-terminal strand. Close to the head domain, there is a second break with a significantly longer insertion on the same strand. These results provide an experience base that allows an informed interpretation of the output of coiled-coil prediction algorithms for this family of proteins. A comparison of such predictions suggests that these coiled-coil deviations are highly conserved across SMC types in a wide variety of organisms, including humans. © 2015 Wiley Periodicals, Inc.

  14. HA Antibody-Mediated FcγRIIIa Activity Is Both Dependent on FcR Engagement and Interactions between HA and Sialic Acids.

    PubMed

    Cox, Freek; Kwaks, Ted; Brandenburg, Boerries; Koldijk, Martin H; Klaren, Vincent; Smal, Bastiaan; Korse, Hans J W M; Geelen, Eric; Tettero, Lisanne; Zuijdgeest, David; Stoop, Esther J M; Saeland, Eirikur; Vogels, Ronald; Friesen, Robert H E; Koudstaal, Wouter; Goudsmit, Jaap

    2016-01-01

    Interactions with receptors for the Fc region of IgG (FcγRs) have been shown to contribute to the in vivo protection against influenza A viruses provided by broadly neutralizing antibodies (bnAbs) that bind to the viral hemagglutinin (HA) stem. In particular, Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) has been shown to contribute to protection by stem-binding bnAbs. Fc-mediated effector functions appear not to contribute to protection provided by strain-specific HA head-binding antibodies. We used a panel of anti-stem and anti-head influenza A and B monoclonal antibodies with identical human IgG1 Fc domains and investigated their ability to mediate ADCC-associated FcγRIIIa activation. Antibodies which do not interfere with sialic acid binding of HA can mediate FcγRIIIa activation. However, the FcγRIIIa activation was inhibited when a mutant HA, unable to bind sialic acids, was used. Antibodies which block sialic acid receptor interactions of HA interfered with FcγRIIIa activation. The inhibition of FcγRIIIa activation by HA head-binding and sialic acid receptor-blocking antibodies was confirmed in plasma samples of H5N1 vaccinated human subjects. Together, these results suggest that in addition to Fc-FcγR binding, interactions between HA and sialic acids on immune cells are required for optimal Fc-mediated effector functions by anti-HA antibodies.

  15. Globular, Sponge-like to Layer-like Morphological Transition in 1-n-Alkyl-3-methylimidazolium Octylsulfate Ionic Liquid Homologous Series.

    PubMed

    Kapoor, Utkarsh; Shah, Jindal K

    2018-01-11

    Segregation of polar and nonpolar domains in ionic liquids for which either the cation or anion is responsible for inducing nonpolar domains is well understood. On the other hand, information regarding the nanoscale heterogeneities originating due to the presence of nonpolar content on both the ions is rudimentary at this point. The present contribution is aimed at addressing this question and focuses on a molecular dynamics simulation study to probe nanoscale structural and aggregation features of the 1-n-alkyl-3-methylimidazolium [C n mim] octylsulfate [C 8 SO 4 ] ionic liquid homologous series (n = 2, 4, 6, 8, 10, and 12). The objective of this work is to determine the effect of increasing alkyl chain length in the cation on nonpolar domain formation, especially when the alkyl chain lengths from both the ions participate in defining such domains. The results indicate that all the ionic liquids form nonpolar domains, morphology of which gradually changes from globular, sponge-like to layer-like structure with increase in the cationic alkyl chain length. The length of the nonpolar domains calculated from the total structure factor for [C 10 mim][C 8 SO 4 ] is considerably higher than that reported for other imidazolium-based ionic liquid containing smaller anions. The structure factor for [C 12 mim][C 8 SO 4 ] ionic liquid contains multiple intermediate peaks separating the charge alternation peak and pre-peak, which points to nonpolar domains of varying lengths, an observation that remains to be validated. Analysis of the heterogeneous order parameters and orientational correlation functions of the alkyl chains further suggests an increase in the spatial heterogeneity and long-range order along the homologous series. The origin of rich diversity of structures obtained by introducing nonpolar content on both the ions is discussed.

  16. Surface characterization of colloidal-sol gel derived biphasic HA/FA coatings.

    PubMed

    Cheng, Kui; Zhang, Sam; Weng, Wenjian

    2007-10-01

    Hydroxyapatite (HA) powders are ultrasonically dispersed in the precursor of fluoridated hydroxyapatite (FHA) or fluorapatite (FA) to form a "colloidal sol". HA/FA biphasic coatings are prepared on Ti6Al4V substrate via dip coating, 150 degrees C drying and 600 degrees C firing. The coatings show homogenous distribution of HA particles in the FA matrix. The relative phase proportion can be tailored by the amount of HA in the colloidal sol. The surfaces of the coatings consist of two kinds of distinct domains: HA and FA, resulting in a compositionally heterogeneous surface. The biphasic coating surface becomes increasingly rougher with HA powders, from around 200 nm of pure FA to 400-600 nm in Ra of biphasic coatings. The rougher biphasic HA/FA surfaces with chemically controllable domains will favor cell attachment, apatite layer deposition and necessary dissolution in clinical applications.

  17. Influence of carbonate ion in the crystallization medium on the formation and chemical composition of CaHA-SrHA solid solutions

    NASA Astrophysics Data System (ADS)

    Nikolaev, Anton; Kuz'mina, Maria; Frank-Kamenetskaya, Olga; Zorina, Maina

    2015-06-01

    The study of the influence of carbonate ions in a solution to Sr-distribution in system «solution-crystal» and to ion substitutions and the non-stoichiometry of formed CaHA-SrHA solid solutions was carried out. The CaHA-SrHA solid solutions were synthesized by precipitation from aqueous solutions with the atomic C/P ratio equal to 0, 0.05 and 0.1 at T = 90 °C. Resulting precipitates were studied using various methods including X-ray powder diffraction, infrared spectroscopy and different chemical analyses. The results of the study have shown that in the range of values of (Ca + Sr)/P in the water solution from 40% to 85%, the presence of carbonate ions (C/P = 0.05-0.1) promotes the incorporation of strontium in the apatite. Crystalline apatite solid solutions formed from water solutions of such composition are more defective compared to apatites that are mainly calcium or strontium. They are characterized by a smaller size coherence scattering domain length along [0 0 1] direction and a greater number of carbonate ions, water molecules and vacancies at the Ca-sites.

  18. A New Globular Cluster in the Area of VVVX

    NASA Astrophysics Data System (ADS)

    Bica, E.; Minniti, D.; Bonatto, C.; Hempel, M.

    2018-06-01

    We communicate the discovery of a new globular cluster in the Galaxy that was first detected on WISE/2MASS images and is now confirmed with VVVX photometry. It is a Palomar-like cluster projected at ℓ = 359.15°, b = 5.73°, and may be related to the bulge. We derive an absolute magnitude of MV ≈ -3.3, thus being an underluminous globular cluster. Our analyses provide a reddening of E(B - V) = 1.08 ± 0.18 and a distance to the Sun d⊙ = 6.3 ± 1 kpc, which implies a current position in the bulge volume. The estimated metallicity is [Fe/H] = -1.5 ± 0.25. It adds to the recently discovered faint globular cluster (Minniti 22) and candidates found with VVV, building up expectations of ≈50 globular clusters yet to be discovered in the bulge. We also communicate the discovery of an old open cluster in the same VVVX tile as the globular cluster. The VVVX photometry provided E(B - V) = 0.62 ± 0.1, d⊙ = 7.6 ± 1 kpc, and an age of 1.5 ± 0.3 Gyr. With a height from the plane of ≈0.8 kpc, it adds to nine Gyr-class clusters recently discovered within 0.8 ⩽ Z ⩽ 2.2 kpc, as recently probed in the single VVV tile b201. We suggest that these findings may be disclosing the thick disk at the bulge, which so far has no open cluster counterpart, and hardly any individual star. Thus, the VVV and VVVX surveys are opening new windows for follow-up studies, to employ present and future generations of large aperture telescopes.

  19. Globular Cluster Contributions to the Galactic Halo

    NASA Astrophysics Data System (ADS)

    Martell, Sarah; Grebel, Eva; Lai, David

    2010-08-01

    The goal of this project is to confirm chemically that globular clusters are the source of as much as half the population of the Galactic halo. Using moderate-resolution spectroscopy from the SEGUE survey, we have identified a previously unknown population of halo field giants with distinctly strong CN features. CN variations are typically only observed in globular clusters, so these stars are interpreted as immigrants to the halo that originally formed in globular clusters. In one night of Keck/HIRES time, we will obtain high-quality, high- resolution spectra for five such stars, and determine abundances of O, Na, Mg, Al, alpha, iron-peak and neutron-capture elements. With this information we can state clearly whether these unusual CN-strong halo stars carry the full abundance pattern seen in CN-strong globular cluster stars, with depleted C, O, and Mg and enhanced N, Na, and Al. This type of coarse ``chemical tagging'' will allow a clearer division of the Galactic halo into contributions from globular clusters and from dwarf galaxies, and will place constraints on theoretical models of globular cluster formation and evolution.

  20. Millisecond radio pulsars in globular clusters

    NASA Technical Reports Server (NTRS)

    Verbunt, Frank; Lewin, Walter H. G.; Vanparadijs, Jan

    1989-01-01

    It is shown that the number of millisecond radio pulsars, in globular clusters, should be larger than 100, applying the standard scenario that all the pulsars descend from low-mass X-ray binaries. Moreover, most of the pulsars are located in a small number of clusters. The prediction that Teran 5 and Liller 1 contain at least about a dozen millisecond radio pulsars each is made. The observations of millisecond radio pulsars in globular clusters to date, in particular the discovery of two millisecond radio pulsars in 47 Tuc, are in agreement with the standard scenario, in which the neutron star is spun up during the mass transfer phase.

  1. Gamma-ray Emission from Globular Clusters

    NASA Astrophysics Data System (ADS)

    Tam, Pak-Hin T.; Hui, Chung Y.; Kong, Albert K. H.

    2016-03-01

    Over the last few years, the data obtained using the Large Area Telescope (LAT) aboard the Fermi Gamma-ray Space Telescope has provided new insights on high-energy processes in globular clusters, particularly those involving compact objects such as MilliSecond Pulsars (MSPs). Gamma-ray emission in the 100 MeV to 10 GeV range has been detected from more than a dozen globular clusters in our galaxy, including 47 Tucanae and Terzan 5. Based on a sample of known gammaray globular clusters, the empirical relations between gamma-ray luminosity and properties of globular clusters such as their stellar encounter rate, metallicity, and possible optical and infrared photon energy densities, have been derived. The measured gamma-ray spectra are generally described by a power law with a cut-off at a few gigaelectronvolts. Together with the detection of pulsed γ-rays from two MSPs in two different globular clusters, such spectral signature lends support to the hypothesis that γ-rays from globular clusters represent collective curvature emission from magnetospheres of MSPs in the clusters. Alternative models, involving Inverse-Compton (IC) emission of relativistic electrons that are accelerated close to MSPs or pulsar wind nebula shocks, have also been suggested. Observations at >100 GeV by using Fermi/LAT and atmospheric Cherenkov telescopes such as H.E.S.S.-II, MAGIC-II, VERITAS, and CTA will help to settle some questions unanswered by current data.

  2. Black hole binaries dynamically formed in globular clusters

    NASA Astrophysics Data System (ADS)

    Park, Dawoo; Kim, Chunglee; Lee, Hyung Mok; Bae, Yeong-Bok; Belczynski, Krzysztof

    2017-08-01

    We investigate properties of black hole (BH) binaries formed in globular clusters via dynamical processes, using directN-body simulations. We pay attention to effects of BH mass function on the total mass and mass ratio distributions of BH binaries ejected from clusters. First, we consider BH populations with two different masses in order to learn basic differences from models with single-mass BHs only. Secondly, we consider continuous BH mass functions adapted from recent studies on massive star evolution in a low metallicity environment, where globular clusters are formed. In this work, we consider only binaries that are formed by three-body processes and ignore stellar evolution and primordial binaries for simplicity. Our results imply that most BH binary mergers take place after they get ejected from the cluster. Also, mass ratios of dynamically formed binaries should be close to 1 or likely to be less than 2:1. Since the binary formation efficiency is larger for higher-mass BHs, it is likely that a BH mass function sampled by gravitational-wave observations would be weighed towards higher masses than the mass function of single BHs for a dynamically formed population. Applying conservative assumptions regarding globular cluster populations such as small BH mass fraction and no primordial binaries, the merger rate of BH binaries originated from globular clusters is estimated to be at least 6.5 yr-1 Gpc-3. Actual rate can be up to more than several times of our conservative estimate.

  3. Conformational and functional analysis of the C-terminal globular head of the reovirus cell attachment protein.

    PubMed

    Duncan, R; Horne, D; Strong, J E; Leone, G; Pon, R T; Yeung, M C; Lee, P W

    1991-06-01

    We have been investigating structure-function relationships in the reovirus cell attachment protein sigma 1 using various deletion mutants and protease analysis. In the present study, a series of deletion mutants were constructed which lacked 90, 44, 30, 12, or 4 amino acids from the C-terminus of the 455-amino acid-long reovirus type 3 (T3) sigma 1 protein. The full-length and truncated sigma 1 proteins were expressed in an in vitro transcription/translation system and assayed for L cell binding activity. It was found that the removal of as few as four amino acids from the C-terminus drastically affected the cell binding function of the sigma 1 protein. The C-terminal-truncated proteins were further characterized using trypsin, chymotrypsin, and monoclonal and polyclonal antibodies. Our results indicated that the C-terminal portions of the mutant proteins were misfolded, leading to a loss in cell binding function. The N-terminal fibrous tail of the proteins was unaffected by the deletions as was sigma 1 oligomerization, further illustrating the discrete structural and functional roles of the N- and C-terminal domains of sigma 1. In an attempt to identify smaller, functional peptides, full-length sigma 1 expressed in vitro was digested with trypsin and subsequently with chymotrypsin under various conditions. The results clearly demonstrated the highly stable nature of the C-terminal globular head of sigma 1, even when separated from the N-terminal fibrous tail. We concluded that: (1) the C-terminal globular head of sigma 1 exists as a compact, protease-resistant oligomeric structure; (2) an intact C-terminus is required for proper head folding and generation of the conformationally dependent cell binding domain.

  4. CVs and millisecond pulsar progenitors in globular clusters

    NASA Technical Reports Server (NTRS)

    Grindlay, J. E.; Cool, A. M.; Bailyn, C. D.

    1991-01-01

    The recent discovery of a large population of millisecond pulsars in globular clusters, together with earlier studies of both low luminosity X-ray sources and LMXBs in globulars, suggest there should be significant numbers of CVs in globulars. Although they have been searched for without success in selected cluster X-ray source fields, systematic surveys are lacking and would constrain binary production and both stellar and dynamical evolution in globular clusters. We describe the beginnings of such a search, using narrow band H-alpha imaging, and the sensitivities it might achieve.

  5. Ghosts of Milky Way's past: the globular cluster ESO 37-1 (E 3)

    NASA Astrophysics Data System (ADS)

    de la Fuente Marcos, R.; de la Fuente Marcos, C.; Moni Bidin, C.; Ortolani, S.; Carraro, G.

    2015-09-01

    Context. In the Milky Way, most globular clusters are highly conspicuous objects that were found centuries ago. However, a few dozen of them are faint, sparsely populated systems that were identified largely during the second half of the past century. One of the faintest is ESO 37-1 (E 3) and as such it remains poorly studied, with no spectroscopic observations published so far although it was discovered in 1976. Aims: We investigate the globular cluster E 3 in an attempt to better constrain its fundamental parameters. Spectroscopy of stars in the field of E 3 is shown here for the first time. Methods: Deep, precise VI CCD photometry of E 3 down to V ~ 26 mag is presented and analysed. Low-resolution, medium signal-to-noise ratio spectra of nine candidate members are studied to derive radial velocity and metallicity. Proper motions from the UCAC4 catalogue are used to explore the kinematics of the bright members of E 3. Results: Isochrone fitting indicates that E 3 is probably very old, with an age of about 13 Gyr; its distance from the Sun is nearly 10 kpc. It is also somewhat metal rich with [Fe/H] = -0.7. Regarding its kinematics, our tentative estimate for the proper motions is (μα cosδ,μδ) = (-7.0 ± 0.8, 3.5 ± 0.3) mas yr-1 (or a tangential velocity of 382 ± 79 km s-1) and for the radial velocity 45 ± 5 km s-1 in the solar rest frame. Conclusions: E 3 is one of the most intriguing globular clusters in the Galaxy. Having an old age and being metal rich is clearly a peculiar combination, only seen in a handful of objects like the far more conspicuous NGC 104 (47 Tucanae). In addition, its low luminosity and sparse population make it a unique template for the study of the final evolutionary phases in the life of a star cluster. Unfortunately, E 3 is among the most elusive and challenging known globular clusters because field contamination severely hampers spectroscopic studies. This research note is based on observations made with the ESO VLT at the

  6. A self-contamination model for the formation of globular star clusters

    NASA Astrophysics Data System (ADS)

    Brown, James Howard

    Described here is a model of globular cluster formation which allows the self contamination of the cluster by an earlier generation of massive stars. It is first shown that such self-contamination naturally produces an Fe/H in the range from -2.5 to -1.0, precisely the same range observed in the metal poor (halo) globular clusters; this also seems to require that the disk clusters started with a substantial initial metallicity. To minimize the problem of creating homogeneous globular clusters, the second (currently observed) generation of stars is assumed to form in the expanding supershell around the first generation stars. Both numerical and analytic models are used to address this problem. The most important result of this investigation was that the late evolution of the supershell is the most important, and that this phase of the evolution is dominated by the external medium in which the cloud is embedded. This result and the requirement that only the most tightly bound systems may become globular clusters lead to the conclusion that a globular cluster with the mass and binding energy typically observed can be formed at star formation efficiences as low as 10-20 percent. Furthermore, self contamination requires that the typical Fe/H of a bound system be about -1.6, independent of the free parameters of the model, allowing the clusters and field stars to form with different metallicity distributions in spite of their forming at the same time. Since the formation of globular clusters in this model is tied to the external pressure, the halo globular cluster masses and distribution can be used as probes of the early galactic structure. In particular, this model requires an increase in the typical globular cluster mass as one moves out from the galactic center; the masses of the halo clusters are examined, and they show considerable evidence for such a gradient. Based on a pressure distribution derived from this data, the effect of the galactic tidal field on the

  7. A Framework for Globular Proteins

    NASA Astrophysics Data System (ADS)

    Lezon, Timothy

    2006-03-01

    Due to their remarkable chemical specificity and diversity, globular proteins play a crucial role in the network of molecular interactions of life. Over the past several decades, much experimental data has been accumulated on proteins, but the overarching principles that govern the general features of proteins remain largely unknown. Here, a novel framework for understanding many key attributes of globular proteins is presented. This framework suggests that the characteristics of globular proteins that make them well-suited for biological function are the emergent properties of a unique phase of matter. Implications of this picture include the provision of a fixed backdrop for molecular evolution and natural selection and design restrictions on molecular machinery. The work described here was carried out in collaboration with Jayanth Banavar and Amos Maritan.

  8. The Globular Tail Domain of Myosin-5a Functions as a Dimer in Regulating the Motor Activity.

    PubMed

    Zhang, Wen-Bo; Yao, Lin-Lin; Li, Xiang-Dong

    2016-06-24

    Myosin-5a contains two heavy chains, which are dimerized via the coiled-coil regions. Thus, myosin-5a comprises two heads and two globular tail domains (GTDs). The GTD is the inhibitory domain that binds to the head and inhibits its motor function. Although the two-headed structure is essential for the processive movement of myosin-5a along actin filaments, little is known about the role of GTD dimerization. Here, we investigated the effect of GTD dimerization on its inhibitory activity. We found that the potent inhibitory activity of the GTD is dependent on its dimerization by the preceding coiled-coil regions, indicating synergistic interactions between the two GTDs and the two heads of myosin-5a. Moreover, we found that alanine mutations of the two conserved basic residues at N-terminal extension of the GTD not only weaken the inhibitory activity of the GTD but also enhance the activation of myosin-5a by its cargo-binding protein melanophilin (Mlph). These results are consistent with the GTD forming a head to head dimer, in which the N-terminal extension of the GTD interacts with the Mlph-binding site in the counterpart GTD. The Mlph-binding site at the GTD-GTD interface must be exposed prior to the binding of Mlph. We therefore propose that the inhibited Myo5a is equilibrated between the folded state, in which the Mlph-binding site is buried, and the preactivated state, in which the Mlph-binding site is exposed, and that Mlph is able to bind to the Myo5a in preactivated state and activates its motor function. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. High Altitude Affects Nocturnal Non-linear Heart Rate Variability: PATCH-HA Study

    PubMed Central

    Boos, Christopher J.; Bye, Kyo; Sevier, Luke; Bakker-Dyos, Josh; Woods, David R.; Sullivan, Mark; Quinlan, Tom; Mellor, Adrian

    2018-01-01

    Background: High altitude (HA) exposure can lead to changes in resting heart rate variability (HRV), which may be linked to acute mountain sickness (AMS) development. Compared with traditional HRV measures, non-linear HRV appears to offer incremental and prognostic data, yet its utility and relationship to AMS have been barely examined at HA. This study sought to examine this relationship at terrestrial HA. Methods: Sixteen healthy British military servicemen were studied at baseline (800 m, first night) and over eight consecutive nights, at a sleeping altitude of up to 3600 m. A disposable cardiac patch monitor was used, to record the nocturnal cardiac inter-beat interval data, over 1 h (0200–0300 h), for offline HRV assessment. Non-linear HRV measures included Sample entropy (SampEn), the short (α1, 4–12 beats) and long-term (α2, 13–64 beats) detrend fluctuation analysis slope and the correlation dimension (D2). The maximal rating of perceived exertion (RPE), during daily exercise, was assessed using the Borg 6–20 RPE scale. Results: All subjects completed the HA exposure. The average age of included subjects was 31.4 ± 8.1 years. HA led to a significant fall in SpO2 and increase in heart rate, LLS and RPE. There were no significant changes in the ECG-derived respiratory rate or in any of the time domain measures of HRV during sleep. The only notable changes in frequency domain measures of HRV were an increase in LF and fall in HFnu power at the highest altitude. Conversely, SampEn, SD1/SD2 and D2 all fell, whereas α1 and α2 increased (p < 0.05). RPE inversely correlated with SD1/SD2 (r = -0.31; p = 0.002), SampEn (r = -0.22; p = 0.03), HFnu (r = -0.27; p = 0.007) and positively correlated with LF (r = 0.24; p = 0.02), LF/HF (r = 0.24; p = 0.02), α1 (r = 0.32; p = 0.002) and α2 (r = 0.21; p = 0.04). AMS occurred in 7/16 subjects (43.8%) and was very mild in 85.7% of cases. HRV failed to predict AMS. Conclusion: Non-linear HRV is more sensitive to

  10. High Altitude Affects Nocturnal Non-linear Heart Rate Variability: PATCH-HA Study.

    PubMed

    Boos, Christopher J; Bye, Kyo; Sevier, Luke; Bakker-Dyos, Josh; Woods, David R; Sullivan, Mark; Quinlan, Tom; Mellor, Adrian

    2018-01-01

    Background: High altitude (HA) exposure can lead to changes in resting heart rate variability (HRV), which may be linked to acute mountain sickness (AMS) development. Compared with traditional HRV measures, non-linear HRV appears to offer incremental and prognostic data, yet its utility and relationship to AMS have been barely examined at HA. This study sought to examine this relationship at terrestrial HA. Methods: Sixteen healthy British military servicemen were studied at baseline (800 m, first night) and over eight consecutive nights, at a sleeping altitude of up to 3600 m. A disposable cardiac patch monitor was used, to record the nocturnal cardiac inter-beat interval data, over 1 h (0200-0300 h), for offline HRV assessment. Non-linear HRV measures included Sample entropy (SampEn), the short (α1, 4-12 beats) and long-term (α2, 13-64 beats) detrend fluctuation analysis slope and the correlation dimension (D2). The maximal rating of perceived exertion (RPE), during daily exercise, was assessed using the Borg 6-20 RPE scale. Results: All subjects completed the HA exposure. The average age of included subjects was 31.4 ± 8.1 years. HA led to a significant fall in SpO 2 and increase in heart rate, LLS and RPE. There were no significant changes in the ECG-derived respiratory rate or in any of the time domain measures of HRV during sleep. The only notable changes in frequency domain measures of HRV were an increase in LF and fall in HFnu power at the highest altitude. Conversely, SampEn, SD1/SD2 and D2 all fell, whereas α1 and α2 increased ( p < 0.05). RPE inversely correlated with SD1/SD2 ( r = -0.31; p = 0.002), SampEn ( r = -0.22; p = 0.03), HFnu ( r = -0.27; p = 0.007) and positively correlated with LF ( r = 0.24; p = 0.02), LF/HF ( r = 0.24; p = 0.02), α1 ( r = 0.32; p = 0.002) and α2 ( r = 0.21; p = 0.04). AMS occurred in 7/16 subjects (43.8%) and was very mild in 85.7% of cases. HRV failed to predict AMS. Conclusion: Non-linear HRV is more sensitive to

  11. Hubble Revisits a Globular Cluster’s Age

    NASA Image and Video Library

    2014-08-13

    This new NASA/ESA Hubble Space Telescope image shows the globular cluster IC 4499. Globular clusters are big balls of old stars that orbit around their host galaxy. It has long been believed that all the stars within a globular cluster form at the about same time, a property which can be used to determine the cluster's age. For more massive globulars however, detailed observations have shown that this is not entirely true — there is evidence that they instead consist of multiple populations of stars born at different times. One of the driving forces behind this behavior is thought to be gravity: more massive globulars manage to grab more gas and dust, which can then be transformed into new stars. IC 4499 is a somewhat special case. Its mass lies somewhere between low-mass globulars, which show a single generation build-up, and the more complex and massive globulars which can contain more than one generation of stars. By studying objects like IC 4499 astronomers can therefore explore how mass affects a cluster's contents. Astronomers found no sign of multiple generations of stars in IC 4499 — supporting the idea that less massive clusters in general only consist of a single stellar generation. Hubble observations of IC 4499 have also helped to pinpoint the cluster's age: observations of this cluster from the 1990s suggested a puzzlingly young age when compared to other globular clusters within the Milky Way. However, since those first estimates new Hubble data have been obtained and it has been found to be much more likely that IC 4499 is actually roughly the same age as other Milky Way clusters at approximately 12 billion years old. Credit: ESA and NASA NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the

  12. Building the Galactic halo from globular clusters: evidence from chemically unusual red giants

    NASA Astrophysics Data System (ADS)

    Martell, S. L.; Smolinski, J. P.; Beers, T. C.; Grebel, E. K.

    2011-10-01

    We present a spectroscopic search for halo field stars that originally formed in globular clusters. Using moderate-resolution SDSS-III/SEGUE-2 spectra of 561 red giants with typical halo metallicities (-1.8 ≤ [Fe/H] ≤ -1.0), we identify 16 stars, 3% of the sample, with CN and CH bandstrength behavior indicating depleted carbon and enhanced nitrogen abundances relative to the rest of the data set. Since globular clusters are the only environment known in which stars form with this pattern of atypical light-element abundances, we claim that these stars are second-generation globular cluster stars that have been lost to the halo field via normal cluster mass-loss processes. Extrapolating from theoretical models of two-generation globular cluster formation, this result suggests that globular clusters contributed significant numbers of stars to the construction of the Galactic halo: we calculate that a minimum of 17% of the present-day mass of the stellar halo was originally formed in globular clusters. The ratio of CN-strong to CN-normal stars drops with Galactocentric distance, suggesting that the inner-halo population may be the primary repository of these stars. Full Tables 1 and 3 are available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/534/A136

  13. Understanding the Current Dynamical States of Globular Clusters

    NASA Astrophysics Data System (ADS)

    Pooley, David

    2008-09-01

    We appear to be on the verge of a major paradigm shift in our understanding of the current dynamical states of Galactic globular clusters. Fregeau (2008) brought together two recent theoretical breakthroughs as well as an observational breakthrough made possible by Chandra -- that a globular cluster's X-ray source population scales with its dynamical encounter frequency -- to persuasively argue that we have misunderstood the dynamical states of Galactic globular clusters. The observational evidence hinges on Chandra results from clusters which are classified as "core collapsed," of which there are only a handful of observations. I propose a nearly complete census with Chandra of the rest of the "core collapsed" globular clusters.

  14. Supra-galactic colour patterns in globular cluster systems

    NASA Astrophysics Data System (ADS)

    Forte, Juan C.

    2017-07-01

    An analysis of globular cluster systems associated with galaxies included in the Virgo and Fornax Hubble Space Telescope-Advanced Camera Surveys reveals distinct (g - z) colour modulation patterns. These features appear on composite samples of globular clusters and, most evidently, in galaxies with absolute magnitudes Mg in the range from -20.2 to -19.2. These colour modulations are also detectable on some samples of globular clusters in the central galaxies NGC 1399 and NGC 4486 (and confirmed on data sets obtained with different instruments and photometric systems), as well as in other bright galaxies in these clusters. After discarding field contamination, photometric errors and statistical effects, we conclude that these supra-galactic colour patterns are real and reflect some previously unknown characteristic. These features suggest that the globular cluster formation process was not entirely stochastic but included a fraction of clusters that formed in a rather synchronized fashion over large spatial scales, and in a tentative time lapse of about 1.5 Gy at redshifts z between 2 and 4. We speculate that the putative mechanism leading to that synchronism may be associated with large scale feedback effects connected with violent star-forming events and/or with supermassive black holes.

  15. The CCD photometry of the globular cluster Palomar 1.

    NASA Astrophysics Data System (ADS)

    Borissova, J.; Spassova, N.

    1995-04-01

    A CCD photometry of the halo cluster Palomar 1 is presented in the Thuan-Gunn photometric system. The principal sequences of the color-magnitude diagrams are delineated in different spectral bands. The color-magnitude diagrams of the cluster show a well defined red horizontal branch, a subgiant branch and a main-sequence down to about two magnitudes below the main sequence turnoff. The giant branch is absent and the brightest stars are the horizontal branch stars. The age of the cluster determined by comparison with the isochrones of Bell & Vanden Berg (1987) is consistent with an age in the interval 12-14Gyr. A distance modulus of (m-M)_g0_=15.38+/-0.15 magnitude and E(g-r)=0.16 has been derived. An estimate of the cluster structural parameters such as core radius and concentration parameter gives r_c_=1.5pc and c=1.46. A mass estimate of 1.1 10^3^Msun_ and a mass-to-light ratio of 1.79 have been obtained using King's (1966) method. The morphology of color-magnitude diagrams allows Pal 1 to be interpreted as probably a globular cluster rather than an old open one.

  16. Crystal Structure of the Passenger Domain of the Escherichia coli Autotransporter EspP

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Khan, Shekeb; Mian, Hira S.; Sandercock, Linda E.

    2013-03-07

    Autotransporters represent a large superfamily of known and putative virulence factors produced by Gram-negative bacteria. They consist of an N-terminal 'passenger domain' responsible for the specific effector functions of the molecule and a C-terminal '{beta}-domain' responsible for translocation of the passenger across the bacterial outer membrane. Here, we present the 2.5-{angstrom} crystal structure of the passenger domain of the extracellular serine protease EspP, produced by the pathogen Escherichia coli O157:H7 and a member of the serine protease autotransporters of Enterobacteriaceae (SPATEs). Like the previously structurally characterized SPATE passenger domains, the EspP passenger domain contains an extended right-handed parallel {beta}-helix precededmore » by an N-terminal globular domain housing the catalytic function of the protease. Of note, however, is the absence of a second globular domain protruding from this {beta}-helix. We describe the structure of the EspP passenger domain in the context of previous results and provide an alternative hypothesis for the function of the {beta}-helix within SPATEs.« less

  17. In-Depth Analysis of HA and NS1 Genes in A(H1N1)pdm09 Infected Patients.

    PubMed

    Caglioti, Claudia; Selleri, Marina; Rozera, Gabriella; Giombini, Emanuela; Zaccaro, Paola; Valli, Maria Beatrice; Capobianchi, Maria Rosaria

    2016-01-01

    In March/April 2009, a new pandemic influenza A virus (A(H1N1)pdm09) emerged and spread rapidly via human-to-human transmission, giving rise to the first pandemic of the 21th century. Influenza virus may be present in the infected host as a mixture of variants, referred to as quasi-species, on which natural and immune-driven selection operates. Since hemagglutinin (HA) and non-structural 1 (NS1) proteins are relevant in respect of adaptive and innate immune responses, the present study was aimed at establishing the intra-host genetic heterogeneity of HA and NS1 genes, applying ultra-deep pyrosequencing (UDPS) to nasopharyngeal swabs (NPS) from patients with confirmed influenza A(H1N1)pdm09 infection. The intra-patient nucleotide diversity of HA was significantly higher than that of NS1 (median (IQR): 37.9 (32.8-42.3) X 10-4 vs 30.6 (27.4-33.6) X 10-4 substitutions/site, p = 0.024); no significant correlation for nucleotide diversity of NS1 and HA was observed (r = 0.319, p = 0.29). Furthermore, a strong inverse correlation between nucleotide diversity of NS1 and viral load was observed (r = - 0.74, p = 0.004). For both HA and NS1, the variants appeared scattered along the genes, thus indicating no privileged mutation site. Known polymorphisms, S203T (HA) and I123V (NS1), were observed as dominant variants (>98%) in almost all patients; three HA and two NS1 further variants were observed at frequency >40%; a number of additional variants were detected at frequency <6% (minority variants), of which three HA and four NS1 variants were novel. In few patients multiple variants were observed at HA residues 203 and 222. According to the FLUSURVER tool, some of these variants may affect immune recognition and host range; however, these inferences are based on H5N1, and their extension to A(H1N1)pdm09 requires caution. More studies are necessary to address the significance of the composite nature of influenza virus quasi-species within infected patients.

  18. X-ray illumination of globular cluster puzzles. [globular cluster X ray sources as clues to Milky Way Galaxy age and evolution

    NASA Technical Reports Server (NTRS)

    Lightman, A. P.; Grindlay, J. E.

    1982-01-01

    Globular clusters are thought to be among the oldest objects in the Galaxy, and provide, in this connection, important clues for determining the age and process of formation of the Galaxy. The present investigation is concerned with puzzles relating to the X-ray emission of globular clusters, taking into account questions regarding the location of X-ray emitting clusters (XEGC) unusually near the galactic plane and/or galactic center. An adopted model is discussed for the nature, formation, and lifetime of X-ray sources in globular clusters. An analysis of the available data is conducted in connection with a search for correlations between binary formation time scales, central relaxation times, galactic locations, and X-ray emission. The positive correlation found between distance from galactic center and two-body binary formation time for globular clusters, explanations for this correlation, and the hypothesis that X-ray sources in globular clusters require binary star systems provide a possible explanation of the considered puzzles.

  19. Photometric binary stars in Praesepe and the search for globular cluster binaries

    NASA Technical Reports Server (NTRS)

    Bolte, Michael

    1991-01-01

    A radial velocity study of the stars which are located on a second sequence above the single-star zero-age main sequence at a given color in the color-magnitude diagram of the open cluster Praesepe, (NGC 2632) shows that 10, and possibly 11, of 17 are binary systems. Of the binary systems, five have full amplitudes for their velocity variations that are greater than 50 km/s. To the extent that they can be applied to globular clusters, these results suggests that (1) observations of 'second-sequence' stars in globular clusters would be an efficient way of finding main-sequence binary systems in globulars, and (2) current instrumentation on large telescopes is sufficient for establishing unambiguously the existence of main-sequence binary systems in nearby globular clusters.

  20. Nova-driven winds in globular clusters

    NASA Technical Reports Server (NTRS)

    Scott, E. H.; Durisen, R. H.

    1978-01-01

    Recent sensitive searches for H-alpha emission from ionized intracluster gas in globular clusters have set upper limits that conflict with theoretical predictions. It is suggested that nova outbursts heat the gas, producing winds that resolve this discrepancy. The incidence of novae in globular clusters, the conversion of kinetic energy of the nova shell to thermal energy of the intracluster gas, and the characteristics of the resultant winds are discussed. Calculated emission from the nova-driven models does not conflict with any observations to date. Some suggestions are made concerning the most promising approaches for future detection of intracluster gas on the basis of these models. The possible relationship of nova-driven winds to globular cluster X-ray sources is also considered.

  1. Reconstructing galaxy histories from globular clusters.

    PubMed

    West, Michael J; Côté, Patrick; Marzke, Ronald O; Jordán, Andrés

    2004-01-01

    Nearly a century after the true nature of galaxies as distant 'island universes' was established, their origin and evolution remain great unsolved problems of modern astrophysics. One of the most promising ways to investigate galaxy formation is to study the ubiquitous globular star clusters that surround most galaxies. Globular clusters are compact groups of up to a few million stars. They generally formed early in the history of the Universe, but have survived the interactions and mergers that alter substantially their parent galaxies. Recent advances in our understanding of the globular cluster systems of the Milky Way and other galaxies point to a complex picture of galaxy genesis driven by cannibalism, collisions, bursts of star formation and other tumultuous events.

  2. Shaping Globular Clusters with Black Holes

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2018-03-01

    How many black holes lurk within the dense environments of globular clusters, and how do these powerful objects shape the properties of the cluster around them? One such cluster, NGC 3201, is now helping us to answer these questions.Hunting Stellar-Mass Black HolesSince the detection of merging black-hole binaries by the Laser Interferometer Gravitational-Wave Observatory (LIGO), the dense environments of globular clusters have received increasing attention as potential birthplaces of these compact binary systems.The central region of the globular star cluster NGC 3201, as viewed by Hubble. The black hole is in orbit with the star marked by the blue circle. [NASA/ESA]In addition, more and more stellar-mass black-hole candidates have been observed within globular clusters, lurking in binary pairs with luminous, non-compact companions. The most recent of these detections, found in the globular cluster NGC 3201, stands alone as the first stellar-mass black hole candidate discovered via radial velocity observations: the black holes main-sequence companion gave away its presence via a telltale wobble.Now a team of scientists led by Kyle Kremer (CIERA and Northwestern University) is using models of this system to better understand the impact that black holes might have on their host clusters.A Model ClusterThe relationship between black holes and their host clusters is complicated. Though the cluster environment can determine the dynamical evolution of the black holes, the retention rate of black holes in a globular cluster (i.e., how many remain in the cluster when they are born as supernovae, rather than being kicked out during the explosion) influences how the host cluster evolves.Kremer and collaborators track this complex relationship by modeling the evolution of a cluster similar to NGC 3201 with a Monte Carlo code. The code incorporates physics relevant to the evolution of black holes and black-hole binaries in globular clusters, such as two-body relaxation

  3. Dinamical properties of globular clusters: Primordial or evolutional?

    NASA Astrophysics Data System (ADS)

    Surdin, V. G.

    1995-04-01

    Some observable relations between globular cluster parameters appear as a result of dynamical evolution of the cluster system. These relations are inapplicable to the studies of the globular cluster origin

  4. GLOBULAR CLUSTERS AS CRADLES OF LIFE AND ADVANCED CIVILIZATIONS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stefano, R. Di; Ray, A., E-mail: rdistefano@cfa.harvard.edu, E-mail: akr@tifr.res.in

    2016-08-10

    Globular clusters are ancient stellar populations in compact dense ellipsoids. There is no star formation and there are no core-collapse supernovae, but several lines of evidence suggest that globular clusters are rich in planets. If so, and if advanced civilizations can develop there, then the distances between these civilizations and other stars would be far smaller than typical distances between stars in the Galactic disk, facilitating interstellar communication and travel. The potent combination of long-term stability and high stellar densities provides a globular cluster opportunity. Yet the very proximity that promotes interstellar travel also brings danger, as stellar interactions canmore » destroy planetary systems. We find, however, that large portions of many globular clusters are “sweet spots,” where habitable-zone planetary orbits are stable for long times. Globular clusters in our own and other galaxies are, therefore, among the best targets for searches for extraterrestrial intelligence (SETI). We use the Drake equation to compare the likelihood of advanced civilizations in globular clusters to that in the Galactic disk. We also consider free-floating planets, since wide-orbit planets can be ejected to travel through the cluster. Civilizations spawned in globular clusters may be able to establish self-sustaining outposts, reducing the probability that a single catastrophic event will destroy the civilization. Although individual civilizations may follow different evolutionary paths, or even be destroyed, the cluster may continue to host advanced civilizations once a small number have jumped across interstellar space. Civilizations residing in globular clusters could therefore, in a sense, be immortal.« less

  5. Globular Clusters as Cradles of Life and Advanced Civilizations

    NASA Astrophysics Data System (ADS)

    Di Stefano, R.; Ray, A.

    2016-08-01

    Globular clusters are ancient stellar populations in compact dense ellipsoids. There is no star formation and there are no core-collapse supernovae, but several lines of evidence suggest that globular clusters are rich in planets. If so, and if advanced civilizations can develop there, then the distances between these civilizations and other stars would be far smaller than typical distances between stars in the Galactic disk, facilitating interstellar communication and travel. The potent combination of long-term stability and high stellar densities provides a globular cluster opportunity. Yet the very proximity that promotes interstellar travel also brings danger, as stellar interactions can destroy planetary systems. We find, however, that large portions of many globular clusters are “sweet spots,” where habitable-zone planetary orbits are stable for long times. Globular clusters in our own and other galaxies are, therefore, among the best targets for searches for extraterrestrial intelligence (SETI). We use the Drake equation to compare the likelihood of advanced civilizations in globular clusters to that in the Galactic disk. We also consider free-floating planets, since wide-orbit planets can be ejected to travel through the cluster. Civilizations spawned in globular clusters may be able to establish self-sustaining outposts, reducing the probability that a single catastrophic event will destroy the civilization. Although individual civilizations may follow different evolutionary paths, or even be destroyed, the cluster may continue to host advanced civilizations once a small number have jumped across interstellar space. Civilizations residing in globular clusters could therefore, in a sense, be immortal.

  6. A search for novae in M 31 globular clusters

    NASA Astrophysics Data System (ADS)

    Ciardullo, Robin; Tamblyn, Peter; Phillips, A. C.

    1990-10-01

    By combining a local sky-fitting algorithm with a Fourier point-spread-function matching technique, nova outbursts have been searched for inside 54 of the globular clusters contained on the Ciardullo et al. (1987 and 1990) H-alpha survey frames of M 31. Over a mean effective survey time of about 2.0 years, no cluster exhibited a magnitude increase indicative of a nova explosion. If the cataclysmic variables (CVs) contained within globular clusters are similar to those found in the field, then these data imply that the overdensity of CVs within globulars is at least several times less than that of the high-luminosity X-ray sources. If tidal capture is responsible for the high density of hard binaries within globulars, then the probability of capturing condensed objects inside globular clusters may depend strongly on the mass of the remnant.

  7. Hubble Sees an Ancient Globular Cluster

    NASA Image and Video Library

    2017-12-08

    This image captures the stunning NGC 6535, a globular cluster 22,000 light-years away in the constellation of Serpens (The Serpent) that measures one light-year across. Globular clusters are tightly bound groups of stars which orbit galaxies. The large mass in the rich stellar centre of the globular cluster pulls the stars inward to form a ball of stars. The word globulus, from which these clusters take their name, is Latin for small sphere. Globular clusters are generally very ancient objects formed around the same time as their host galaxy. To date, no new star formation has been observed within a globular cluster, which explains the abundance of aging yellow stars in this image, most of them containing very few heavy elements. NGC 6535 was first discovered in 1852 by English astronomer John Russell Hind. The cluster would have appeared to Hind as a small, faint smudge through his telescope. Now, over 160 years later, instruments like the Advanced Camera for Surveys (ACS) and Wide Field Camera 3 (WFC3) on the NASA/ European Space Agency (ESA) Hubble Space Telescope allow us to marvel at the cluster and its contents in greater detail. Credit: ESA/Hubble & NASA, Acknowledgement: Gilles Chapdelaine NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  8. Some remarks on extragalactic globular clusters

    NASA Astrophysics Data System (ADS)

    Richtler, Tom

    2006-03-01

    I comment (in a review fashion) on a few selected topics in the field of extragalactic globular clusters with strong emphasis on recent work. The topics are: bimodality in the colour distribution of cluster systems, young massive clusters, and the brightest old clusters. Globular cluster research, per- haps more than ever, has lead to important (at least to astronomers) progress and problems in galaxy structure and formation.

  9. The Nature of LSB galaxies revealed by their Globular Clusters

    NASA Astrophysics Data System (ADS)

    Kissler-Patig, Markus

    2005-07-01

    Low Surface Brightness {LSB} galaxies encompass many of the extremes in galaxy properties. Their understanding is essential to complete our picture of galaxy formation and evolution. Due to their historical under-representation on galaxy surveys, their importance to many areas of astronomy has only recently began to be realized. Globular clusters are superb tracers of the formation histories of galaxies and have been extensively used as such in high surface brightness galaxies. We propose to investigate the nature of massive LSB galaxies by studying their globular cluster systems. No globular cluster study has been reported for LSB galaxies to date. Yet, both the presence or absence of globular clusters set very strong constraints on the conditions prevailing during LSB galaxy formation and evolution. Both in dwarf and giant high surface brightness {HSB} galaxies, globular clusters are known to form as a constant fraction of baryonic mass. Their presence/absence immediately indicates similarities or discrepancies in the formation and evolution conditions of LSB and HSB galaxies. In particular, the presence/absence of metal-poor halo globular clusters infers similarities/differences in the halo formation and assembly processes of LSB vs. HSB galaxies, while the presence/absence of metal-rich globular clusters can be used to derive the occurrence and frequency of violent events {such as mergers} in the LSB galaxy assembly history. Two band imaging with ACS will allow us to identify the globular clusters {just resolved at the selected distance} and to determine their metallicity {potentially their rough age}. The composition of the systems will be compared to the extensive census built up on HSB galaxies. Our representative sample of six LSB galaxies {cz < 2700 km/s} are selected such, that a large system of globular clusters is expected. Globular clusters will constrain phases of LSB galaxy formation and evolution that can currently not be probed by other means. HST

  10. Globular Cluster Messier 2 in Aquarius

    NASA Image and Video Library

    2003-12-11

    This image of the Globular cluster Messier 2 (M2) was taken by Galaxy Evolution Explorer on August 20, 2003. This image is a small section of a single All Sky Imaging Survey exposure of only 129 seconds in the constellation Aquarius. This picture is a combination of Galaxy Evolution Explorer images taken with the far ultraviolet (colored blue) and near ultraviolet detectors (colored red). Globular clusters are gravitationally bound systems of hundreds of thousands of stars that orbit in the halos of galaxies. The globular clusters in out Milky Way galaxy contain some of the oldest stars known. M2 lies 33,000 light years from our Sun with stars distributed in a spherical system with a radius of approximately 100 light years. http://photojournal.jpl.nasa.gov/catalog/PIA04926

  11. HIV-1 matrix domain removal ameliorates virus assembly and processing defects incurred by positive nucleocapsid charge elimination.

    PubMed

    Ko, Li-Jung; Yu, Fu-Hsien; Huang, Kuo-Jung; Wang, Chin-Tien

    2015-01-01

    Human immunodeficiency virus type 1 nucleocapsid (NC) basic residues presumably contribute to virus assembly via RNA, which serves as a scaffold for Gag-Gag interaction during particle assembly. To determine whether NC basic residues play a role in Gag cleavage (thereby impacting virus assembly), Gag processing efficiency and virus particle production were analyzed for an HIV-1 mutant NC15A, with alanine serving as a substitute for all NC basic residues. Results indicate that NC15A significantly impaired virus maturation in addition to significantly affecting Gag membrane binding and assembly. Interestingly, removal of the matrix (MA) central globular domain ameliorated the NC15A assembly and processing defects, likely through enhancement of Gag multimerization and membrane binding capacities.

  12. Supergiants and their shells in young globular clusters

    NASA Astrophysics Data System (ADS)

    Szécsi, Dorottya; Mackey, Jonathan; Langer, Norbert

    2018-04-01

    Context. Anomalous surface abundances are observed in a fraction of the low-mass stars of Galactic globular clusters, that may originate from hot-hydrogen-burning products ejected by a previous generation of massive stars. Aims: We aim to present and investigate a scenario in which the second generation of polluted low-mass stars can form in shells around cool supergiant stars within a young globular cluster. Methods: Simulations of low-metallicity massive stars (Mi 150-600 M⊙) show that both core-hydrogen-burning cool supergiants and hot ionizing stellar sources are expected to be present simulaneously in young globular clusters. Under these conditions, photoionization-confined shells form around the supergiants. We have simulated such a shell, investigated its stability and analysed its composition. Results: We find that the shell is gravitationally unstable on a timescale that is shorter than the lifetime of the supergiant, and the Bonnor-Ebert mass of the overdense regions is low enough to allow star formation. Since the low-mass stellar generation formed in this shell is made up of the material lost from the supergiant, its composition necessarily reflects the composition of the supergiant wind. We show that the wind contains hot-hydrogen-burning products, and that the shell-stars therefore have very similar abundance anomalies that are observed in the second generation stars of globular clusters. Considering the mass-budget required for the second generation star-formation, we offer two solutions. Either a top-heavy initial mass function is needed with an index of -1.71 to -2.07. Alternatively, we suggest the shell-stars to have a truncated mass distribution, and solve the mass budget problem by justifiably accounting for only a fraction of the first generation. Conclusions: Star-forming shells around cool supergiants could form the second generation of low-mass stars in Galactic globular clusters. Even without forming a photoionizaton-confined shell, the

  13. New VVV Survey Globular Cluster Candidates in the Milky Way Bulge

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Minniti, Dante; Gómez, Matías; Geisler, Douglas

    It is likely that a number of Galactic globular clusters remain to be discovered, especially toward the Galactic bulge. High stellar density combined with high and differential interstellar reddening are the two major problems for finding globular clusters located toward the bulge. We use the deep near-IR photometry of the VISTA Variables in the Vía Láctea (VVV) Survey to search for globular clusters projected toward the Galactic bulge, and hereby report the discovery of 22 new candidate globular clusters. These objects, detected as high density regions in our maps of bulge red giants, are confirmed as globular cluster candidates bymore » their color–magnitude diagrams. We provide their coordinates as well as their near-IR color–magnitude diagrams, from which some basic parameters are derived, such as reddenings and heliocentric distances. The color–magnitude diagrams reveal well defined red giant branches in all cases, often including a prominent red clump. The new globular cluster candidates exhibit a variety of extinctions (0.06 < A {sub Ks} < 2.77) and distances (5.3 < D < 9.5 kpc). We also classify the globular cluster candidates into 10 metal-poor and 12 metal-rich clusters, based on the comparison of their color–magnitude diagrams with those of known globular clusters also observed by the VVV Survey. Finally, we argue that the census for Galactic globular clusters still remains incomplete, and that many more candidate globular clusters (particularly the low luminosity ones) await to be found and studied in detail in the central regions of the Milky Way.« less

  14. Antigenicity of the 2015-2016 seasonal H1N1 human influenza virus HA and NA proteins.

    PubMed

    Clark, Amelia M; DeDiego, Marta L; Anderson, Christopher S; Wang, Jiong; Yang, Hongmei; Nogales, Aitor; Martinez-Sobrido, Luis; Zand, Martin S; Sangster, Mark Y; Topham, David J

    2017-01-01

    Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) influenza virus proteins contributes to reduced vaccine efficacy. To analyze antigenic drift in human seasonal H1N1 viruses derived from the 2009 pandemic H1N1 virus (pH1N1-like viruses) accounts for the limited effectiveness (around 40%) of vaccination against pH1N1-like viruses during the 2015-2016 season, nasal washes/swabs collected from adult subjects in the Rochester, NY area, were used to sequence and isolate the circulating viruses. The HA and NA proteins from viruses circulating during the 2015-2016 season encoded eighteen and fourteen amino acid differences, respectively, when compared to A/California/04/2009, a strain circulating at the origin of the 2009 pandemic. The circulating strains belonged to subclade 6B.1, defined by HA amino acid substitutions S101N, S179N, and I233T. Hemagglutination-inhibiting (HAI) and HA-specific neutralizing serum antibody (Ab) titers from around 50% of pH1N1-like virus-infected subjects and immune ferrets were 2-4 fold lower for the 2015-2016 circulating strains compared to the vaccine strain. In addition, using a luminex-based mPlex HA assay, the binding of human sera from subjects infected with pH1N1-like viruses to the HA proteins from circulating and vaccine strains was not identical, strongly suggesting antigenic differences in the HA protein. Additionally, NA inhibition (NAI) Ab titers in human sera from pH1N1-like virus-infected subjects increased after the infection and there were measurable antigenic differences between the NA protein of circulating strains and the vaccine strain using both ferret and human antisera. Despite having been vaccinated, infected subjects exhibited low HAI Ab titers against the vaccine and circulating strains. This suggests that poor responses to the H1N1 component of the vaccine as well as antigenic differences in the HA and NA proteins of currently circulating pH1N1-like viruses could be contributing to risk of

  15. Reversible Association of the Hemagglutinin Subcomplex, HA-33/HA-17 Trimer, with the Botulinum Toxin Complex.

    PubMed

    Sagane, Yoshimasa; Mutoh, Shingo; Koizumi, Ryosuke; Suzuki, Tomonori; Miyashita, Shin-Ichiro; Miyata, Keita; Ohyama, Tohru; Niwa, Koichi; Watanabe, Toshihiro

    2017-10-01

    Botulinum neurotoxin (BoNT) associates with nontoxic proteins, either a nontoxic nonhemagglutinin (NTNHA) or the complex of NTNHA and hemagglutinin (HA), to form M- or L-toxin complexes (TCs). Single BoNT and NTNHA molecules are associated and form M-TC. A trimer of the 70-kDa HA protein (HA-70) attaches to the M-TC to form M-TC/HA-70. Further, 1-3 arm-like 33- and 17-kDa HA molecules (HA-33/HA-17 trimer), consisting of 1 HA-17 protein and 2 HA-33 proteins, can attach to the M-TC/HA-70 complex, yielding 1-, 2-, and 3-arm L-TC. In this study, the purified 1- and 2-arm L-TCs spontaneously converted into another L-TC species after acquiring the HA-33/HA-17 trimer from other TCs during long-term storage and freezing/thawing. Transmission electron microscopy analysis provided evidence of the formation of detached HA-33/HA-17 trimers in the purified TC preparation. These findings provide evidence of reversible association/dissociation of the M-TC/HA-70 complex with the HA-33/HA-17 trimers, as well as dynamic conversion of the quaternary structure of botulinum TC in culture.

  16. RR Lyrae in Sagittarius Dwarf Globular Clusters (Poster abstract)

    NASA Astrophysics Data System (ADS)

    Pritzl, B. J.; Gehrman, T. J.; Bell, E.; Salinas, R.; Smith, H. A.; Catelan, M.

    2016-12-01

    (Abstract only) The Milky Way Galaxy was built up in part by the cannibalization of smaller dwarf galaxies. Some of them likely contained globular clusters. The Sagittarius dwarf galaxy provides a unique opportunity to study a system of globular clusters that originated outside the Milky Way. We have investigated the RR Lyrae populations in two Sagittarius globular clusters, Arp 2 and Terzan 8. The RR Lyrae are used to study the properties of the clusters and to compare this system to Milky Way globular clusters. We will discuss whether or not dwarf galaxies similar to the Sagittarius dwarf galaxy could have played a role in the formation of the Milky Way Galaxy.

  17. A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

    DOE PAGES

    Abdo, A. A.

    2010-11-24

    Context. Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. The observation of this emission provides a powerful tool to assess the millisecond pulsar population of a cluster, is essential for understanding the importance of binary systems for the evolution of globular clusters, and provides complementary insights into magnetospheric emission processes. Aims. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. Methods. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Spacemore » Telescope to study the gamma-ray emission towards 13 globular clusters. Results. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices (0.7 < Γ < 1.4) and clear evidence for an exponential cut-off in the range 1.0 - 2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices (1.0 < Γ < 1.7), however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600 - 4700 MSPs in Galactic globular clusters, commensurate with previous estimates. Conclusions. The observation of high-energy gamma-ray emission from globular clusters thus provides a reliable independent method to assess their millisecond pulsar populations.« less

  18. M31 Globular Clusters and Galaxy Formation

    NASA Astrophysics Data System (ADS)

    Gregg, M. D.; Karick, A. M.

    2005-12-01

    The brightest globular cluster in the halo of M31, cluster G1, has properties which suggest that it is not an ordinary globular but an ultra-compact dwarf galaxy: its velocity dispersion, M/L, and ellipticity are all atypically large, and its color-magnitude diagram suggests an abundance spread. Using the Keck Laser Guide Star Adaptive Optics system with NIRC2, we have begun an imaging campaign of globular clusters in M31 to measure their core sizes. Combining these data with high dispersion spectroscopy will produce masses and M/L ratios to determine if there are additional UCDs masquerading as M31 globulars. UCDs are thought to be the remnant nuclei from tidally stripped dwarf ellipticals or small spirals; finding additional examples in the cluster system of M31 has implications for galaxy formation processes. The K-band image quality during our first LGS run was very stable over many hours, with Strehl ratios of 0.35 or better, producing point sources with FWHM of 0\\farcs05. The core sizes of the clusters, which range from 0\\farcs2 to 0\\farcs8 can be easily measured from these data. The observing conditions were nearly as good in the J-band, and we obtained both colors for a number of clusters. We discuss our efforts to produce photometrically-calibrated color-magnitude diagrams of the clusters. This work is supported by National Science Foundation Grant No. 0407445 and was done at the Institute of Geophysics and Planetary Physics, under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract No. W-7405-Eng-48.

  19. Globular structure of human ovulatory cervical mucus.

    PubMed

    Brunelli, Roberto; Papi, Massimiliano; Arcovito, Giuseppe; Bompiani, Adriano; Castagnola, Massimo; Parasassi, Tiziana; Sampaolese, Beatrice; Vincenzoni, Federica; De Spirito, Marco

    2007-12-01

    Human cervical mucus is a heterogeneous mixture of mucin glycoproteins whose relative concentration changes during the ovulatory phases, thereby producing different mucus aggregation structures that can periodically permit the transit of spermatozoa for fertilization. In preovulatory phase, mucus is arranged in compact fiber-like structures where sperm transit is hindered. Previously, through observations made of fixed and dehydrated samples, a permissive structure in the ovulatory phase was attributed to the larger diameters of pores in the mucus network. Instead, by means of atomic force microscopy, we can show, for the first time, that unfixed ovulatory mucus is composed by floating globules of mucin aggregates. This finding sheds new light on the mechanism that governs spermatozoa transit toward the uterine cavity. In addition, we demonstrate that the switch from globular ovulatory to fibrous preovulatory mucus largely depends on a pH-driven mechanism. Analysis of mucin 5B primary sequence, the main mucin in ovulatory mucus, highlights pH-sensitive domains that are associated to flexible regions prone to drive aggregation. We suggest an involvement of these domains in the fiber-to-globule switch in cervical mucus.

  20. New VVV Survey Globular Cluster Candidates in the Milky Way Bulge

    NASA Astrophysics Data System (ADS)

    Minniti, Dante; Geisler, Douglas; Alonso-García, Javier; Palma, Tali; Beamín, Juan Carlos; Borissova, Jura; Catelan, Marcio; Clariá, Juan J.; Cohen, Roger E.; Contreras Ramos, Rodrigo; Dias, Bruno; Fernández-Trincado, Jose G.; Gómez, Matías; Hempel, Maren; Ivanov, Valentin D.; Kurtev, Radostin; Lucas, Phillip W.; Moni-Bidin, Christian; Pullen, Joyce; Ramírez Alegría, Sebastian; Saito, Roberto K.; Valenti, Elena

    2017-11-01

    It is likely that a number of Galactic globular clusters remain to be discovered, especially toward the Galactic bulge. High stellar density combined with high and differential interstellar reddening are the two major problems for finding globular clusters located toward the bulge. We use the deep near-IR photometry of the VISTA Variables in the Vía Láctea (VVV) Survey to search for globular clusters projected toward the Galactic bulge, and hereby report the discovery of 22 new candidate globular clusters. These objects, detected as high density regions in our maps of bulge red giants, are confirmed as globular cluster candidates by their color-magnitude diagrams. We provide their coordinates as well as their near-IR color-magnitude diagrams, from which some basic parameters are derived, such as reddenings and heliocentric distances. The color-magnitude diagrams reveal well defined red giant branches in all cases, often including a prominent red clump. The new globular cluster candidates exhibit a variety of extinctions (0.06 < A Ks < 2.77) and distances (5.3 < D < 9.5 kpc). We also classify the globular cluster candidates into 10 metal-poor and 12 metal-rich clusters, based on the comparison of their color-magnitude diagrams with those of known globular clusters also observed by the VVV Survey. Finally, we argue that the census for Galactic globular clusters still remains incomplete, and that many more candidate globular clusters (particularly the low luminosity ones) await to be found and studied in detail in the central regions of the Milky Way. Based on observations taken within the ESO programs 179.B-2002 and 298.D-5048.

  1. Monitoring bound HA1(H1N1) and HA1(H5N1) on freely suspended graphene over plasmonic platforms with infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Banerjee, Amrita; Chakraborty, Sumit; Altan-Bonnet, Nihal; Grebel, Haim

    2013-09-01

    Infrared (IR) spectroscopy provides fingerprinting of the energy and orientation of molecular bonds. The IR signals are generally weak and require amplification. Here we present a new plasmonic platform, made of freely suspended graphene, which was coating periodic metal structures. Only monolayer thick films were needed for a fast signal recording. We demonstrated unique IR absorption signals of bound proteins: these were the hemagglutinin area (HA1) of swine influenza (H1N1) and the avian influenza (H5N1) viruses bound to their respective tri-saccharides ligand receptors. The simplicity and sensitivity of such approach may find applications in fast monitoring of binding events.

  2. HUBBLE SPIES GLOBULAR CLUSTER IN NEIGHBORING GALAXY

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Hubble Space Telescope has captured a view of a globular cluster called G1, a large, bright ball of light in the center of the photograph consisting of at least 300,000 old stars. G1, also known as Mayall II, orbits the Andromeda galaxy (M31), the nearest major spiral galaxy to our Milky Way. Located 130,000 light-years from Andromeda's nucleus, G1 is the brightest globular cluster in the Local Group of galaxies. The Local Group consists of about 20 nearby galaxies, including the Milky Way. The crisp image is comparable to ground-based telescope views of similar clusters orbiting the Milky Way. The Andromeda cluster, however, is nearly 100 times farther away. A glimpse into the cluster's finer details allow astronomers to see its fainter helium-burning stars whose temperatures and brightnesses show that this cluster in Andromeda and the oldest Milky Way clusters have approximately the same age. These clusters probably were formed shortly after the beginning of the universe, providing astronomers with a record of the earliest era of galaxy formation. During the next two years, astronomers will use Hubble to study about 20 more globular clusters in Andromeda. The color picture was assembled from separate images taken in visible and near-infrared wavelengths taken in July of 1994. CREDIT: Michael Rich, Kenneth Mighell, and James D. Neill (Columbia University), and Wendy Freedman (Carnegie Observatories), and NASA Image files in GIF and JPEG format and captions may be accessed on Internet via anonymous ftp from oposite.stsci.edu in /pubinfo.

  3. Effects of cosmic string velocities and the origin of globular clusters

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lin, Ling; Yamanouchi, Shoma; Brandenberger, Robert, E-mail: ling.lin2@mail.mcgill.ca, E-mail: shoma.yamanouchi@mail.mcgill.ca, E-mail: rhb@physics.mcgill.ca

    2015-12-01

    With the hypothesis that cosmic string loops act as seeds for globular clusters in mind, we study the role that velocities of these strings will play in determining the mass distribution of globular clusters. Loops with high enough velocities will not form compact and roughly spherical objects and can hence not be the seeds for globular clusters. We compute the expected number density and mass function of globular clusters as a function of both the string tension and the peak loop velocity, and compare the results with the observational data on the mass distribution of globular clusters in our Milkymore » Way. We determine the critical peak string loop velocity above which the agreement between the string loop model for the origin of globular clusters (neglecting loop velocities) and observational data is lost.« less

  4. Binaries in globular clusters

    NASA Technical Reports Server (NTRS)

    Hut, Piet; Mcmillan, Steve; Goodman, Jeremy; Mateo, Mario; Phinney, E. S.; Pryor, Carlton; Richer, Harvey B.; Verbunt, Frank; Weinberg, Martin

    1992-01-01

    Recent observations have shown that globular clusters contain a substantial number of binaries most of which are believed to be primordial. We discuss different successful optical search techniques, based on radial-velocity variables, photometric variables, and the positions of stars in the color-magnitude diagram. In addition, we review searches in other wavelengths, which have turned up low-mass X-ray binaries and more recently a variety of radio pulsars. On the theoretical side, we give an overview of the different physical mechanisms through which individual binaries evolve. We discuss the various simulation techniques which recently have been employed to study the effects of a primordial binary population, and the fascinating interplay between stellar evolution and stellar dynamics which drives globular-cluster evolution.

  5. Ha-ras(val12) induces HSP70b transcription via the HSE/HSF1 system, but HSP70b expression is suppressed in Ha-ras(val12)-transformed cells.

    PubMed

    Stanhill, A; Levin, V; Hendel, A; Shachar, I; Kazanov, D; Arber, N; Kaminski, N; Engelberg, D

    2006-03-09

    Heat shock proteins (Hsps) are overexpressed in many tumors, but are downregulated in some tumors. To check for a direct effect of Ha-Ras(val12) on HSP70 transcription, we transiently expressed the oncoprotein in Rat1 fibroblasts and monitored its effect on HSP70b promoter-driven reporter gene. We show that expression of Ha-Ras(val12) induced this promoter. Promoter analysis via systematic deletions and point mutations revealed that Ha-Ras(val12) induces HSP70b transcription via heat shock elements (HSEs). Also, Ha-Ras(val12) induction of HSE-mediated transcription was dramatically reduced in HSF1-/- cells. Yet, residual effect of Ha-Ras(val12) that was still measured in HSF1-/- cells suggests that some of the Ha-Ras(val12) effect is Hsf1-independent. When HSF1-/- cells, stably expressing Ha-Ras(val12), were grown on soft agar only small colonies were formed suggesting a role for heat shock factor 1 (Hsf1) in Ha-Ras(val12)-mediated transformation. Although Ha-ras(Val12) seems to be an inducer of HSP70's expression, we found that in Ha-ras(Val12-)transformed fibroblasts expression of this gene is suppressed. This suppression is correlated with higher sensitivity of Ha-ras(val12)-transformed cells to heat shock. We suggest that Ha-ras(Val12) is involved in Hsf1 activation, thereby inducing the cellular protective response. Cells that repress this response are perhaps those that acquire the capability to further proliferate and become transformed clones.

  6. The Evolution of the Globular Cluster System in a Triaxial Galaxy: Can a Galactic Nucleus Form by Globular Cluster Capture?

    NASA Astrophysics Data System (ADS)

    Capuzzo-Dolcetta, Roberto

    1993-10-01

    Among the possible phenomena inducing evolution of the globular cluster system in an elliptical galaxy, dynamical friction due to field stars and tidal disruption caused by a central nucleus is of crucial importance. The aim of this paper is the study of the evolution of the globular cluster system in a triaxial galaxy in the presence of these phenomena. In particular, the possibility is examined that some galactic nuclei have been formed by frictionally decayed globular clusters moving in a triaxial potential. We find that the initial rapid growth of the nucleus, due mainly to massive clusters on box orbits falling in a short time scale into the galactic center, is later slowed by tidal disruption induced by the nucleus itself on less massive clusters in the way described by Ostriker, Binney, and Saha. The efficiency of dynamical friction is such to carry to the center of the galaxy enough globular cluster mass available to form a compact nucleus, but the actual modes and results of cluster-cluster encounters in the central potential well are complicated phenomena which remains to be investigated. The mass of the resulting nucleus is determined by the mutual feedback of the described processes, together with the initial spatial, velocity, and mass distributions of the globular cluster family. The effect on the system mass function is studied, showing the development of a low- and high-mass turnover even with an initially flat mass function. Moreover, in this paper is discussed the possibility that the globular cluster fall to the galactic center has been a cause of primordial violent galactic activity. An application of the model to M31 is presented.

  7. Evolution of the hemagglutinin expressed by human influenza A(H1N1)pdm09 and A(H3N2) viruses circulating between 2008-2009 and 2013-2014 in Germany.

    PubMed

    Wedde, Marianne; Biere, Barbara; Wolff, Thorsten; Schweiger, Brunhilde

    2015-10-01

    This report describes the evolution of the influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in Germany between 2008-2009 and 2013-2014. The phylogenetic analysis of the hemagglutinin (HA) genes of both subtypes revealed similar evolution of the HA variants that were also seen worldwide with minor exceptions. The analysis showed seven distinct HA clades for A(H1N1)pdm09 and six HA clades for A(H3N2) viruses. Herald strains of both subtypes appeared sporadically since 2008-2009. Regarding A(H1N1)pdm09, herald strains of HA clade 3 and 4 were detected late in the 2009-2010 season. With respect to A(H3N2), we found herald strains of HA clade 3, 4 and 7 between 2009 and 2012. Those herald strains were predominantly seen for minor and not for major HA clades. Generally, amino acid substitutions were most frequently found in the globular domain, including substitutions near the antigenic sites or the receptor binding site. Differences between both influenza A subtypes were seen with respect to the position of the indicated substitutions in the HA. For A(H1N1)pdm09 viruses, we found more substitutions in the stem region than in the antigenic sites. In contrast, in A(H3N2) viruses most changes were identified in the major antigenic sites and five changes of potential glycosylation sites were identified in the head of the HA monomer. Interestingly, we found in seasons with less influenza activity a relatively high increase of substitutions in the head of the HA in both subtypes. This might be explained by the fact that mutations under negative selection are subsequently compensated by secondary mutations to restore important functions e.g. receptor binding properties. A better knowledge of basic evolution strategies of influenza viruses will contribute to the refinement of predictive mathematical models for identifying novel antigenic drift variants. Copyright © 2015 Elsevier GmbH. All rights reserved.

  8. Dynamical evolution of globular-cluster systems in clusters of galaxies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Muzzio, J.C.

    1987-04-01

    The dynamical processes that affect globular-cluster systems in clusters of galaxies are analyzed. Two-body and impulsive approximations are utilized to study dynamical friction, drag force, tidal stripping, tidal radii, globular-cluster swapping, tidal accretion, and galactic cannibalism. The evolution of galaxies and the collision of galaxies are simulated numerically; the steps involved in the simulation are described. The simulated data are compared with observations. Consideration is given to the number of galaxies, halo extension, location of the galaxies, distribution of the missing mass, nonequilibrium initial conditions, mass dependence, massive central galaxies, globular-cluster distribution, and lost globular clusters. 116 references.

  9. Rates of collapse and evaporation of globular clusters

    NASA Technical Reports Server (NTRS)

    Hut, Piet; Djorgovski, S.

    1992-01-01

    Observational estimates of the dynamical relaxation times of Galactic globular clusters are used here to estimate the present rate at which core collapse and evaporation are occurring in them. A core collapse rate of 2 +/- 1 per Gyr is found, which for a Galactic age of about 12 Gyr agrees well with the fact that 27 clusters have surface brightness profiles with the morphology expected for the postcollapse phase. A destruction and evaporation rate of 5 +/- 3 per Gyr is found, suggesting that a significant fraction of the Galaxy's original complement of globular clusters have perished through the combined effects of mechanisms such as relaxation-driven evaporation and shocking due to interaction with the Galactic disk and bulge.

  10. EVIDENCE FOR AN ACCRETION ORIGIN FOR THE OUTER HALO GLOBULAR CLUSTER SYSTEM OF M31

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mackey, A. D.; Huxor, A. P.; Ferguson, A. M. N.

    2010-07-01

    We use a sample of newly discovered globular clusters from the Pan-Andromeda Archaeological Survey (PAndAS) in combination with previously cataloged objects to map the spatial distribution of globular clusters in the M31 halo. At projected radii beyond {approx}30 kpc, where large coherent stellar streams are readily distinguished in the field, there is a striking correlation between these features and the positions of the globular clusters. Adopting a simple Monte Carlo approach, we test the significance of this association by computing the probability that it could be due to the chance alignment of globular clusters smoothly distributed in the M31 halo.more » We find that the likelihood of this possibility is low, below 1%, and conclude that the observed spatial coincidence between globular clusters and multiple tidal debris streams in the outer halo of M31 reflects a genuine physical association. Our results imply that the majority of the remote globular cluster system of M31 has been assembled as a consequence of the accretion of cluster-bearing satellite galaxies. This constitutes the most direct evidence to date that the outer halo globular cluster populations in some galaxies are largely accreted.« less

  11. Globular cluster formation - The fossil record

    NASA Technical Reports Server (NTRS)

    Murray, Stephen D.; Lin, Douglas N. C.

    1992-01-01

    Properties of globular clusters which have remained unchanged since their formation are used to infer the internal pressures, cooling times, and dynamical times of the protocluster clouds immediately prior to the onset of star formation. For all globular clusters examined, it is found that the cooling times are much less than the dynamical times, implying that the protoclusters must have been maintained in thermal equilibrium by external heat sources, with fluxes consistent with those found in previous work, and giving the observed rho-T relation. Self-gravitating clouds cannot be stably heated, so that the Jeans mass forms an upper limit to the cluster masses. The observed dependence of protocluster pressure upon galactocentric position implies that the protocluster clouds were in hydrostatic equilibrium after their formation. The pressure dependence is well fitted by that expected for a quasi-statically evolving background hot gas, shock heated to its virial temperature. The observations and inferences are combined with previous theoretical work to construct a picture of globular cluster formation.

  12. Featured Image: Globular Cluster Orbits

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2017-04-01

    This figure (click for the full view) shows the meridional galactic orbits of 12 globular clusters that orbit the Milky Way. The recent release of stellar parallax data from Gaia allowed a team of scientists at Dartmouth College to improve measurements of a number of galactic globular clusters very old clusters of stars that can either orbit within the galactic disk and bulge or more distantly in the galactic halo. In a recent publication led by Erin OMalley, the team presents their findings and combines their new measurements for the clusters with proper motions from past studies to calculate the orbits that these globulars take. These calculations show us whether the clusters reside in the galactic disk and bulge (as only NGC 104 does in the sample shown here, since its orbit is confined to 8 kpc radially and 4 kpc vertically of the galactic center), or if they are halo clusters. To learn more about the authors work, you can check out the paper below!CitationErin M. OMalley et al 2017 ApJ 838 162. doi:10.3847/1538-4357/aa6574

  13. Postcollapse Evolution of Globular Clusters

    NASA Astrophysics Data System (ADS)

    Makino, Junichiro

    1996-11-01

    A number of globular clusters appear to have undergone core collapse, in the sense that their predicted collapse times are much shorter than their current ages. Simulations with gas models and the Fokker-Planck approximation have shown that the central density of a globular cluster after the collapse undergoes nonlinear oscillation with a large amplitude (gravothermal oscillation). However, the question whether such an oscillation actually takes place in real N-body systems has remained unsolved because an N-body simulation with a sufficiently high resolution would have required computing resources of the order of several GFLOPS-yr. In the present paper, we report the results of such a simulation performed on a dedicated special-purpose computer, GRAPE-4. We have simulated the evolution of isolated point-mass systems with up to 32,768 particles. The largest number of particles reported previously is 10,000. We confirm that gravothermal oscillation takes place in an N-body system. The expansion phase shows all the signatures that are considered to be evidence of the gravothermal nature of the oscillation. At the maximum expansion, the core radius is ˜1% of the half-mass radius for the run with 32,768 particles. The maximum core size, rc, depends on N as ∝ N-1/3.

  14. Identification of Carbohydrate-Binding Domains in the Attachment Proteins of Type 1 and Type 3 Reoviruses

    PubMed Central

    Chappell, James D.; Duong, Joy L.; Wright, Benjamin W.; Dermody, Terence S.

    2000-01-01

    The reovirus attachment protein, ς1, is responsible for strain-specific patterns of viral tropism in the murine central nervous system and receptor binding on cultured cells. The ς1 protein consists of a fibrous tail domain proximal to the virion surface and a virion-distal globular head domain. To better understand mechanisms of reovirus attachment to cells, we conducted studies to identify the region of ς1 that binds cell surface carbohydrate. Chimeric and truncated ς1 proteins derived from prototype reovirus strains type 1 Lang (T1L) and type 3 Dearing (T3D) were expressed in insect cells by using a baculovirus vector. Assessment of expressed protein susceptibility to proteolytic cleavage, binding to anti-ς1 antibodies, and oligomerization indicates that the chimeric and truncated ς1 proteins are properly folded. To assess carbohydrate binding, recombinant ς1 proteins were tested for the capacity to agglutinate mammalian erythrocytes and to bind sialic acid presented on glycophorin, the cell surface molecule bound by type 3 reovirus on human erythrocytes. Using a panel of two wild-type and ten chimeric and truncated ς1 proteins, the sialic acid-binding domain of type 3 ς1 was mapped to a region of sequence proposed to form the more amino terminal of two predicted β-sheet structures in the tail. This unit corresponds to morphologic region T(iii) observed in computer-processed electron micrographs of ς1 protein purified from virions. In contrast, the homologous region of T1L ς1 sequence was not implicated in carbohydrate binding; rather, sequences in the distal portion of the tail known as the neck were required. Results of these studies demonstrate that a functional receptor-binding domain, which uses sialic acid as its ligand, is contained within morphologic region T(iii) of the type 3 ς1 tail. Furthermore, our findings indicate that T1L and T3D ς1 proteins contain different arrangements of receptor-binding domains. PMID:10954547

  15. Identification of carbohydrate-binding domains in the attachment proteins of type 1 and type 3 reoviruses.

    PubMed

    Chappell, J D; Duong, J L; Wright, B W; Dermody, T S

    2000-09-01

    The reovirus attachment protein, sigma1, is responsible for strain-specific patterns of viral tropism in the murine central nervous system and receptor binding on cultured cells. The sigma1 protein consists of a fibrous tail domain proximal to the virion surface and a virion-distal globular head domain. To better understand mechanisms of reovirus attachment to cells, we conducted studies to identify the region of sigma1 that binds cell surface carbohydrate. Chimeric and truncated sigma1 proteins derived from prototype reovirus strains type 1 Lang (T1L) and type 3 Dearing (T3D) were expressed in insect cells by using a baculovirus vector. Assessment of expressed protein susceptibility to proteolytic cleavage, binding to anti-sigma1 antibodies, and oligomerization indicates that the chimeric and truncated sigma1 proteins are properly folded. To assess carbohydrate binding, recombinant sigma1 proteins were tested for the capacity to agglutinate mammalian erythrocytes and to bind sialic acid presented on glycophorin, the cell surface molecule bound by type 3 reovirus on human erythrocytes. Using a panel of two wild-type and ten chimeric and truncated sigma1 proteins, the sialic acid-binding domain of type 3 sigma1 was mapped to a region of sequence proposed to form the more amino terminal of two predicted beta-sheet structures in the tail. This unit corresponds to morphologic region T(iii) observed in computer-processed electron micrographs of sigma1 protein purified from virions. In contrast, the homologous region of T1L sigma1 sequence was not implicated in carbohydrate binding; rather, sequences in the distal portion of the tail known as the neck were required. Results of these studies demonstrate that a functional receptor-binding domain, which uses sialic acid as its ligand, is contained within morphologic region T(iii) of the type 3 sigma1 tail. Furthermore, our findings indicate that T1L and T3D sigma1 proteins contain different arrangements of receptor

  16. Antigenicity of the 2015–2016 seasonal H1N1 human influenza virus HA and NA proteins

    PubMed Central

    Anderson, Christopher S.; Wang, Jiong; Yang, Hongmei; Nogales, Aitor; Martinez-Sobrido, Luis; Zand, Martin S.; Sangster, Mark Y.; Topham, David J.

    2017-01-01

    Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) influenza virus proteins contributes to reduced vaccine efficacy. To analyze antigenic drift in human seasonal H1N1 viruses derived from the 2009 pandemic H1N1 virus (pH1N1-like viruses) accounts for the limited effectiveness (around 40%) of vaccination against pH1N1-like viruses during the 2015–2016 season, nasal washes/swabs collected from adult subjects in the Rochester, NY area, were used to sequence and isolate the circulating viruses. The HA and NA proteins from viruses circulating during the 2015–2016 season encoded eighteen and fourteen amino acid differences, respectively, when compared to A/California/04/2009, a strain circulating at the origin of the 2009 pandemic. The circulating strains belonged to subclade 6B.1, defined by HA amino acid substitutions S101N, S179N, and I233T. Hemagglutination-inhibiting (HAI) and HA-specific neutralizing serum antibody (Ab) titers from around 50% of pH1N1-like virus-infected subjects and immune ferrets were 2–4 fold lower for the 2015–2016 circulating strains compared to the vaccine strain. In addition, using a luminex-based mPlex HA assay, the binding of human sera from subjects infected with pH1N1-like viruses to the HA proteins from circulating and vaccine strains was not identical, strongly suggesting antigenic differences in the HA protein. Additionally, NA inhibition (NAI) Ab titers in human sera from pH1N1-like virus-infected subjects increased after the infection and there were measurable antigenic differences between the NA protein of circulating strains and the vaccine strain using both ferret and human antisera. Despite having been vaccinated, infected subjects exhibited low HAI Ab titers against the vaccine and circulating strains. This suggests that poor responses to the H1N1 component of the vaccine as well as antigenic differences in the HA and NA proteins of currently circulating pH1N1-like viruses could be contributing to risk of

  17. Secondary anchor polymorphism in the HA-1 minor histocompatibility antigen critically affects MHC stability and TCR recognition

    PubMed Central

    Nicholls, Sarah; Piper, Karen P.; Mohammed, Fiyaz; Dafforn, Timothy R.; Tenzer, Stefan; Salim, Mahboob; Mahendra, Premini; Craddock, Charles; van Endert, Peter; Schild, Hansjörg; Cobbold, Mark; Engelhard, Victor H.; Moss, Paul A. H.; Willcox, Benjamin E.

    2009-01-01

    T cell recognition of minor histocompatibility antigens (mHags) underlies allogeneic immune responses that mediate graft-versus-host disease and the graft-versus-leukemia effect following stem cell transplantation. Many mHags derive from single amino acid polymorphisms in MHC-restricted epitopes, but our understanding of the molecular mechanisms governing mHag immunogenicity and recognition is incomplete. Here we examined antigenic presentation and T-cell recognition of HA-1, a prototypic autosomal mHag derived from single nucleotide dimorphism (HA-1H versus HA-1R) in the HMHA1 gene. The HA-1H peptide is restricted by HLA-A2 and is immunogenic in HA-1R/R into HA-1H transplants, while HA-1R has been suggested to be a “null allele” in terms of T cell reactivity. We found that proteasomal cleavage and TAP transport of the 2 peptides is similar and that both variants can bind to MHC. However, the His>Arg change substantially decreases the stability and affinity of HLA-A2 association, consistent with the reduced immunogenicity of the HA-1R variant. To understand these findings, we determined the structure of an HLA-A2-HA-1H complex to 1.3Å resolution. Whereas His-3 is accommodated comfortably in the D pocket, incorporation of the lengthy Arg-3 is predicted to require local conformational changes. Moreover, a soluble TCR generated from HA-1H-specific T-cells bound HA-1H peptide with moderate affinity but failed to bind HA-1R, indicating complete discrimination of HA-1 variants at the level of TCR/MHC interaction. Our results define the molecular mechanisms governing immunogenicity of HA-1, and highlight how single amino acid polymorphisms in mHags can critically affect both MHC association and TCR recognition. PMID:19234124

  18. NGC 6273: Towards Defining A New Class of Galactic Globular Clusters?

    NASA Astrophysics Data System (ADS)

    Johnson, Christian I.; Rich, Robert Michael; Pilachowski, Catherine A.; Caldwell, Nelson; Mateo, Mario L.; Ira Bailey, John; Crane, Jeffrey D.

    2016-01-01

    A growing number of observations have found that several Galactic globular clusters exhibit abundance dispersions beyond the well-known light element (anti-)correlations. These clusters tend to be very massive, have >0.1 dex intrinsic metallicity dispersions, have complex sub-giant branch morphologies, and have correlated [Fe/H] and s-process element enhancements. Interestingly, nearly all of these clusters discovered so far have [Fe/H]~-1.7. In this context, we have examined the chemical composition of 18 red giant branch (RGB) stars in the massive, metal-poor Galactic bulge globular cluster NGC 6273 using high signal-to-noise, high resolution (R~27,000) spectra obtained with the Michigan/Magellan Fiber System (M2FS) and MSpec spectrograph mounted on the Magellan-Clay 6.5m telescope at Las Campanas Observatory. We find that the cluster exhibits a metallicity range from [Fe/H]=-1.80 to -1.30 and is composed of two dominant populations separated in [Fe/H] and [La/Fe] abundance. The increase in [La/Eu] as a function of [La/H] suggests that the increase in [La/Fe] with [Fe/H] is due to almost pure s-process enrichment. The most metal-rich star in our sample is not strongly La-enhanced, but is α-poor and may belong to a third "anomalous" stellar population. The two dominant populations exhibit the same [Na/Fe]-[Al/Fe] correlation found in other "normal" globular clusters. Therefore, NGC 6273 joins ω Centauri, M 22, M 2, and NGC 5286 as a possible new class of Galactic globular clusters.

  19. Novel antigenic shift in HA sequences of H1N1 viruses detected by big data analysis.

    PubMed

    Zhang, Ruiying; Xu, Chongfeng; Duan, Ziyuan

    2017-07-01

    The influenza virus H1N1 has been prevalent all over the world for nearly a century. Many studies on its evolutionary history, substitution rate and antigenicity-associated sites have been done with small datasets. To have a complete view, we analysed 3171 full-length HA sequences from human H1N1 viruses sampled from 1918 to 2016, and discovered a new clade has formed with sequences isolated in Iran. Based on genetic distance calculations, we revealed an uneven evolutionary rate among sequences isolated in different years. We also found that the HA1 fragment of the new clade is like that of viruses that existed in the 1930s, while the HA2 fragment is closely associated with strains isolated after the 2009 pandemic. This new, "mixed" HA sequence indicates a cryptic antigenic shift event occurred, and it should draw more attention to the new clade identified from sequences from Iran. Copyright © 2017. Published by Elsevier B.V.

  20. Cleavage site and Ectodomain of HA2 sub-unit sequence of three equine influenza virus isolated in Morocco

    PubMed Central

    2014-01-01

    Background The equine influenza (EI) is an infectious and contagious disease of the upper respiratory tract of horses. Two outbreaks were notified in Morocco during 1997 and 2004 respectively in Nador and Essaouira. The aims of the present study concern the amino acids sequences comparison with reference strain A/equine/Miami/1963(H3N8) of the HA2 subunit including the cleavage site of three equine influenza viruses (H3N8) isolated in Morocco: A/equine/Nador/1/1997(H3N8), A/equine/Essaouira/2/2004 (H3N8) and A/equine/Essaouira/3/2004 (H3N8). Results The obtained results demonstrated that the substitutions were located at Ectodomain (ED) and transmembrane domain (TD), and they have only one arginine in cleavage site (HA1-PEKQI-R329-GI-HA2). In the Ectodomain, the mutation N/154 2 /T deleted the NGT glycosylation site at position 154 for both strains A/equine/Essaouira/2/2004(H3N8) and A/equine/Essaouira/3/2004(H3N8). Except for mutation D/1602/Y of the A/equine/Nador/1/1997(H3N8) strain, the other mutations were involved in non conserved sites. While the transmembrane domain (TM) of the strain A/equine/Essaouira/3/2004(H3N8) exhibits a substitution at residue C/199 2 /F. For the A/equine/Nador/1/1997(H3N8) strain the HA2 shows a mutation at residue M/207 2 /L. Three Moroccan strains reveals a common substitution at the residue E/211 2 /Q located between transmembrane domain TM and the cytoplasmic domain (CD). Conclusion The given nature virulence of three Moroccan strains, the identified and reported mutations certainly played a permissive role of infection viral process. PMID:25016480

  1. Conserved neutralizing epitope at globular head of hemagglutinin in H3N2 influenza viruses.

    PubMed

    Iba, Yoshitaka; Fujii, Yoshifumi; Ohshima, Nobuko; Sumida, Tomomi; Kubota-Koketsu, Ritsuko; Ikeda, Mariko; Wakiyama, Motoaki; Shirouzu, Mikako; Okada, Jun; Okuno, Yoshinobu; Kurosawa, Yoshikazu; Yokoyama, Shigeyuki

    2014-07-01

    Neutralizing antibodies that target the hemagglutinin of influenza virus either inhibit binding of hemagglutinin to cellular receptors or prevent the low-pH-induced conformational change in hemagglutinin required for membrane fusion. In general, the former type of antibody binds to the globular head formed by HA1 and has narrow strain specificity, while the latter type binds to the stem mainly formed by HA2 and has broad strain specificity. In the present study, we analyzed the epitope and function of a broadly neutralizing human antibody against H3N2 viruses, F005-126. The crystal structure of F005-126 Fab in complex with hemagglutinin revealed that the antibody binds to the globular head, spans a cleft formed by two hemagglutinin monomers in a hemagglutinin trimer, and cross-links them. It recognizes two peptide portions (sites L and R) and a glycan linked to asparagine at residue 285 using three complementarity-determining regions and framework 3 in the heavy chain. Binding of the antibody to sites L (residues 171 to 173, 239, and 240) and R (residues 91, 92, 270 to 273, 284, and 285) is mediated mainly by van der Waals contacts with the main chains of the peptides in these sites and secondarily by hydrogen bonds with a few side chains of conserved sequences in HA1. Furthermore, the glycan recognized by F005-126 is conserved among H3N2 viruses. F005-126 has the ability to prevent low-pH-induced conformational changes in hemagglutinin. The newly identified conserved epitope, including the glycan, should be immunogenic in humans and may induce production of broadly neutralizing antibodies against H3 viruses. Antibodies play an important role in protection against influenza virus, and hemagglutinin is the major target for virus neutralizing antibodies. It has long been believed that all effective neutralizing antibodies bind to the surrounding regions of the sialic acid-binding pocket and inhibit the binding of hemagglutinin to the cellular receptor. Since

  2. Conserved Neutralizing Epitope at Globular Head of Hemagglutinin in H3N2 Influenza Viruses

    PubMed Central

    Iba, Yoshitaka; Fujii, Yoshifumi; Ohshima, Nobuko; Sumida, Tomomi; Kubota-Koketsu, Ritsuko; Ikeda, Mariko; Wakiyama, Motoaki; Shirouzu, Mikako; Okada, Jun; Okuno, Yoshinobu; Yokoyama, Shigeyuki

    2014-01-01

    ABSTRACT Neutralizing antibodies that target the hemagglutinin of influenza virus either inhibit binding of hemagglutinin to cellular receptors or prevent the low-pH-induced conformational change in hemagglutinin required for membrane fusion. In general, the former type of antibody binds to the globular head formed by HA1 and has narrow strain specificity, while the latter type binds to the stem mainly formed by HA2 and has broad strain specificity. In the present study, we analyzed the epitope and function of a broadly neutralizing human antibody against H3N2 viruses, F005-126. The crystal structure of F005-126 Fab in complex with hemagglutinin revealed that the antibody binds to the globular head, spans a cleft formed by two hemagglutinin monomers in a hemagglutinin trimer, and cross-links them. It recognizes two peptide portions (sites L and R) and a glycan linked to asparagine at residue 285 using three complementarity-determining regions and framework 3 in the heavy chain. Binding of the antibody to sites L (residues 171 to 173, 239, and 240) and R (residues 91, 92, 270 to 273, 284, and 285) is mediated mainly by van der Waals contacts with the main chains of the peptides in these sites and secondarily by hydrogen bonds with a few side chains of conserved sequences in HA1. Furthermore, the glycan recognized by F005-126 is conserved among H3N2 viruses. F005-126 has the ability to prevent low-pH-induced conformational changes in hemagglutinin. The newly identified conserved epitope, including the glycan, should be immunogenic in humans and may induce production of broadly neutralizing antibodies against H3 viruses. IMPORTANCE Antibodies play an important role in protection against influenza virus, and hemagglutinin is the major target for virus neutralizing antibodies. It has long been believed that all effective neutralizing antibodies bind to the surrounding regions of the sialic acid-binding pocket and inhibit the binding of hemagglutinin to the cellular

  3. Regulation of Hyaluronan (HA) Metabolism Mediated by HYBID (Hyaluronan-binding Protein Involved in HA Depolymerization, KIAA1199) and HA Synthases in Growth Factor-stimulated Fibroblasts.

    PubMed

    Nagaoka, Aya; Yoshida, Hiroyuki; Nakamura, Sachiko; Morikawa, Tomohiko; Kawabata, Keigo; Kobayashi, Masaki; Sakai, Shingo; Takahashi, Yoshito; Okada, Yasunori; Inoue, Shintaro

    2015-12-25

    Regulation of hyaluronan (HA) synthesis and degradation is essential to maintenance of extracellular matrix homeostasis. We recently reported that HYBID (HYaluronan-Binding protein Involved in hyaluronan Depolymerization), also called KIAA1199, plays a key role in HA depolymerization in skin and arthritic synovial fibroblasts. However, regulation of HA metabolism mediated by HYBID and HA synthases (HASs) under stimulation with growth factors remains obscure. Here we report that TGF-β1, basic FGF, EGF, and PDGF-BB commonly enhance total amount of HA in skin fibroblasts through up-regulation of HAS expression, but molecular size of newly produced HA is dependent on HYBID expression levels. Stimulation of HAS1/2 expression and suppression of HYBID expression by TGF-β1 were abrogated by blockade of the MAPK and/or Smad signaling and the PI3K-Akt signaling, respectively. In normal human skin, expression of the TGF-β1 receptors correlated positively with HAS2 expression and inversely with HYBID expression. On the other hand, TGF-β1 up-regulated HAS1/2 expression but exerted only a slight suppressive effect on HYBID expression in synovial fibroblasts from the patients with osteoarthritis or rheumatoid arthritis, resulting in the production of lower molecular weight HA compared with normal skin and synovial fibroblasts. These data demonstrate that although TGF-β1, basic FGF, EGF, and PDGF-BB enhance HA production in skin fibroblasts, TGF-β1 most efficiently contributes to production of high molecular weight HA by HAS up-regulation and HYBID down-regulation and suggests that inefficient down-regulation of HYBID by TGF-β1 in arthritic synovial fibroblasts may be linked to accumulation of depolymerized HA in synovial fluids in arthritis patients. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. The nature of the globular- to fibrous-actin transition.

    PubMed

    Oda, Toshiro; Iwasa, Mitsusada; Aihara, Tomoki; Maéda, Yuichiro; Narita, Akihiro

    2009-01-22

    Actin plays crucial parts in cell motility through a dynamic process driven by polymerization and depolymerization, that is, the globular (G) to fibrous (F) actin transition. Although our knowledge about the actin-based cellular functions and the molecules that regulate the G- to F-actin transition is growing, the structural aspects of the transition remain enigmatic. We created a model of F-actin using X-ray fibre diffraction intensities obtained from well oriented sols of rabbit skeletal muscle F-actin to 3.3 A in the radial direction and 5.6 A along the equator. Here we show that the G- to F-actin conformational transition is a simple relative rotation of the two major domains by about 20 degrees. As a result of the domain rotation, the actin molecule in the filament is flat. The flat form is essential for the formation of stable, helical F-actin. Our F-actin structure model provides the basis for understanding actin polymerization as well as its molecular interactions with actin-binding proteins.

  5. Determination of the mass of globular cluster X-ray sources

    NASA Technical Reports Server (NTRS)

    Grindlay, J. E.; Hertz, P.; Steiner, J. E.; Murray, S. S.; Lightman, A. P.

    1984-01-01

    The precise positions of the luminous X-ray sources in eight globular clusters have been measured with the Einstein X-Ray Observatory. When combined with similarly precise measurements of the dynamical centers and core radii of the globular clusters, the distribution of the X-ray source mass is determined to be in the range 0.9-1.9 solar mass. The X-ray source positions and the detailed optical studies indicate that (1) the sources are probably all of similar mass, (2) the gravitational potentials in these high-central density clusters are relatively smooth and isothermal, and (3) the X-ray sources are compact binaries and are probably formed by tidal capture.

  6. Gene fusions AHRR-NCOA2, NCOA2-ETV4, ETV4-AHRR, P4HA2-TBCK, and TBCK-P4HA2 resulting from the translocations t(5;8;17)(p15;q13;q21) and t(4;5)(q24;q31) in a soft tissue angiofibroma

    PubMed Central

    Panagopoulos, Ioannis; Gorunova, Ludmila; Viset, Trond; Heim, Sverre

    2016-01-01

    We present an angiofibroma of soft tissue with the karyotype 46,XY,t(4;5)(q24;q31),t(5;8;17)(p15;q13;q21) [8]/46,XY,t(1;14)(p31;q32)[2]/46,XY[3]. RNA-sequencing showed that the t(4;5)(q24;q31) resulted in recombination of the genes TBCK on 4q24 and P4HA2 on 5q31.1 with generation of an in-frame TBCK-P4HA2 and the reciprocal but out-of-frame P4HA2-TBCK fusion transcripts. The putative TBCK-P4HA2 protein would contain the kinase, the rhodanese-like domain, and the Tre-2/Bub2/Cdc16 (TBC) domains of TBCK together with the P4HA2 protein which is a component of the prolyl 4-hydroxylase. The t(5;8;17)(p15;q13;q21) three-way chromosomal translocation targeted AHRR (on 5p15), NCOA2 (on 8q13), and ETV4 (on 17q21) generating the in-frame fusions AHRR-NCOA2 and NCOA2-ETV4 as well as an out-of-frame ETV4-AHRR transcript. In the AHRR-NCOA2 protein, the C-terminal part of AHRR is replaced by the C-terminal part of NCOA2 which contains two activation domains. The NCOA2-ETV4 protein would contain the helix-loop-helix, PAS_9 and PAS_11, CITED domains, the SRC-1 domain of NCOA2 and the ETS DNA-binding domain of ETV4. No fusion gene corresponding to t(1;14)(p31;q32) was found. Our findings indicate that, in spite of the recurrence of AHRR-NCOA2 in angiofibroma of soft tissue, additional genetic events (or fusion genes) might be required for the development of this tumor. PMID:27633981

  7. Gene fusions AHRR-NCOA2, NCOA2-ETV4, ETV4-AHRR, P4HA2-TBCK, and TBCK-P4HA2 resulting from the translocations t(5;8;17)(p15;q13;q21) and t(4;5)(q24;q31) in a soft tissue angiofibroma.

    PubMed

    Panagopoulos, Ioannis; Gorunova, Ludmila; Viset, Trond; Heim, Sverre

    2016-11-01

    We present an angiofibroma of soft tissue with the karyotype 46,XY,t(4;5)(q24;q31),t(5;8;17)(p15;q13;q21)[8]/46,XY,t(1;14)(p31;q32)[2]/46,XY[3]. RNA‑sequencing showed that the t(4;5)(q24;q31) resulted in recombination of the genes TBCK on 4q24 and P4HA2 on 5q31.1 with generation of an in‑frame TBCK‑P4HA2 and the reciprocal but out‑of‑frame P4HA2‑TBCK fusion transcripts. The putative TBCK‑P4HA2 protein would contain the kinase, the rhodanese‑like domain, and the Tre‑2/Bub2/Cdc16 (TBC) domains of TBCK together with the P4HA2 protein which is a component of the prolyl 4‑hydroxylase. The t(5;8;17)(p15;q13;q21) three‑way chromosomal translocation targeted AHRR (on 5p15), NCOA2 (on 8q13), and ETV4 (on 17q21) generating the in‑frame fusions AHRR‑NCOA2 and NCOA2‑ETV4 as well as an out‑of‑frame ETV4‑AHRR transcript. In the AHRR‑NCOA2 protein, the C‑terminal part of AHRR is replaced by the C‑terminal part of NCOA2 which contains two activation domains. The NCOA2‑ETV4 protein would contain the helix‑loop‑helix, PAS_9 and PAS_11, CITED domains, the SRC‑1 domain of NCOA2 and the ETS DNA‑binding domain of ETV4. No fusion gene corresponding to t(1;14)(p31;q32) was found. Our findings indicate that, in spite of the recurrence of AHRR‑NCOA2 in angiofibroma of soft tissue, additional genetic events (or fusion genes) might be required for the development of this tumor.

  8. A generalized analysis of hydrophobic and loop clusters within globular protein sequences

    PubMed Central

    Eudes, Richard; Le Tuan, Khanh; Delettré, Jean; Mornon, Jean-Paul; Callebaut, Isabelle

    2007-01-01

    Background Hydrophobic Cluster Analysis (HCA) is an efficient way to compare highly divergent sequences through the implicit secondary structure information directly derived from hydrophobic clusters. However, its efficiency and application are currently limited by the need of user expertise. In order to help the analysis of HCA plots, we report here the structural preferences of hydrophobic cluster species, which are frequently encountered in globular domains of proteins. These species are characterized only by their hydrophobic/non-hydrophobic dichotomy. This analysis has been extended to loop-forming clusters, using an appropriate loop alphabet. Results The structural behavior of hydrophobic cluster species, which are typical of protein globular domains, was investigated within banks of experimental structures, considered at different levels of sequence redundancy. The 294 more frequent hydrophobic cluster species were analyzed with regard to their association with the different secondary structures (frequencies of association with secondary structures and secondary structure propensities). Hydrophobic cluster species are predominantly associated with regular secondary structures, and a large part (60 %) reveals preferences for α-helices or β-strands. Moreover, the analysis of the hydrophobic cluster amino acid composition generally allows for finer prediction of the regular secondary structure associated with the considered cluster within a cluster species. We also investigated the behavior of loop forming clusters, using a "PGDNS" alphabet. These loop clusters do not overlap with hydrophobic clusters and are highly associated with coils. Finally, the structural information contained in the hydrophobic structural words, as deduced from experimental structures, was compared to the PSI-PRED predictions, revealing that β-strands and especially α-helices are generally over-predicted within the limits of typical β and α hydrophobic clusters. Conclusion The

  9. Abundances in the Young Globulars Ruprecht 106 and PAL 12

    NASA Astrophysics Data System (ADS)

    Brown, J. A.; Wallerstein, G.; Zucker, D.

    1995-12-01

    We have observed two red giants in each of the young globular clusters Ruprecht 106 and Pal 12 with the CTIO 4m echelle and analyzed the spectra for chemical composition. We find for Rup 106 [Fe/H] =~ -1.5, [O/Fe] =~ 0.0, and [alpha /Fe] =~ -0.2. For Pal 12 we find [Fe/H] =~ -1.0 and [alpha /Fe] =~ -0.05; we have no information on oxygen in Pal 12. The light odd-Z metals Na and Al are both overdeficient in both clusters' stars. The stars are all CN-weak compared to similar giants in nearby globulars of comparable [Fe/H]. The abundance results for Rup 106 rule out the possibility that the apparent youth of the cluster as derived from its color-magnitude diagram is caused by an anomalous composition; the lack of results for oxygen prevent us from making a similar statement for Pal 12. These abundances imply a very different star formation history for the material from which these clusters formed, compared to the well-studied old nearby globulars, and are consistent with the suggestion that these clusters are accreted objects, and were not formed in the same environment as the old clusters.

  10. FORS2/VLT survey of Milky Way globular clusters. II. Fe and Mg abundances of 51 Milky Way globular clusters on a homogeneous scale

    NASA Astrophysics Data System (ADS)

    Dias, B.; Barbuy, B.; Saviane, I.; Held, E. V.; Da Costa, G. S.; Ortolani, S.; Gullieuszik, M.; Vásquez, S.

    2016-05-01

    clusters, and the available metallicity for NGC 6426 was based on integrated spectroscopy and photometry. Two other clusters, HP 1 and NGC 6558, are confirmed as candidates for the oldest globular clusters in the Milky Way. Conclusions: Stellar spectroscopy in the visible at R ~ 2000 for a large sample of globular clusters is a robust and efficient way to trace the chemical evolution of the host galaxy and to detect interesting objects for follow-up at higher resolution and with forthcoming giant telescopes. The technique used here can also be applied to globular cluster systems in nearby galaxies with current instruments and to distant galaxies with the advent of ELTs. Based on observations collected at the European Southern Observatory/Paranal, Chile, under programmes 68.B-0482(A), 69.D-0455(A), 71.D-0219(A), 077.D-0775(A), and 089.D-0493(B).Full Tables 1 and A.2 with the derived average parameters for the 758 red giant stars are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/590/A9

  11. The Newly-Discovered Outer Halo Globular Cluster System of M31

    NASA Astrophysics Data System (ADS)

    Mackey, D.; Huxor, A.; Ferguson, A.

    2012-08-01

    In this contribution we describe the discovery of a large number of globular clusters in the outer halo of M31 from the Pan-Andromeda Archaeological Survey (PAndAS). New globular clusters have also been found in the outskirts of M33, and NGC 147 and 185. Many of the remote M31 clusters are observed to preferentially project onto tidal debris streams in the stellar halo, suggesting that much of the outer M31 globular cluster system has been assembled via the accretion of satellite galaxies. We briefly discuss the global properties of the M31 halo globular cluster system.

  12. The blue globular pattern in dermoscopy.

    PubMed

    Roberti, V; Devirgiliis, V; Curzio, M; Gobbi, S; Coppola, R; Calvieri, S; Panasiti, V

    2013-01-01

    Seborrheic keratosis (SK) is a frequent benign epithelial skin tumor. Generally its diagnosis is clinical, however SK can sometimes clinically simulate a melanocytic lesion; therefore we need dermoscopy to reach a correct diagnosis. Milia-like cysts and comedo-like openings are the common dermoscopic features of SK, but it is not a rare finding that SK can display one or more dermoscopic patterns suggestive of a melanocytic origin. We describe a case series of SKs with a blue globular pattern simulating a melanocytic lesion. We retrospectively evaluated 224 SKs seen during 2011 at the Dermatoscopy Unit of the Department of Dermatology, University of Rome 'Sapienza'. Five SKs showed a blue globular pattern, without the SK main features generally seen in dermoscopy; globules were multiple, round or oval, well-demarcated, small and medium-sized, blue-colored and equally distributed within the lesion. Histopathologic examination was consistent with acanthotic SK. Identification of the blue globular pattern can be helpful for the dermoscopic diagnosis of SK, especially when its common dermoscopic features are absent. Copyright © 2013 S. Karger AG, Basel.

  13. Evaluation of the immunogenicity and protective effects of a trivalent chimeric norovirus P particle immunogen displaying influenza HA2 from subtypes H1, H3 and B

    PubMed Central

    Gong, Xin; Yin, He; Shi, Yuhua; He, Xiaoqiu; Yu, Yongjiao; Guan, Shanshan; Kuai, Ziyu; Haji, Nasteha M; Haji, Nafisa M; Kong, Wei; Shan, Yaming

    2016-01-01

    The ectodomain of the influenza A virus (IAV) hemagglutinin (HA) stem is highly conserved across strains and has shown promise as a universal influenza vaccine in a mouse model. In this study, potential B-cell epitopes were found through sequence alignment and epitope prediction in a stem fragment, HA2:90-105, which is highly conserved among virus subtypes H1, H3 and B. A norovirus (NoV) P particle platform was used to express the HA2:90-105 sequences from subtypes H1, H3 and B in loops 1, 2 and 3 of the protrusion (P) domain, respectively. Through mouse immunization and microneutralization assays, the immunogenicity and protective efficacy of the chimeric NoV P particle (trivalent HA2-PP) were tested against infection with three subtypes (H1N1, H3N2 and B) of IAV in Madin–Darby canine kidney cells. The protective efficacy of the trivalent HA2-PP was also evaluated preliminarily in vivo by virus challenge in the mouse model. The trivalent HA2-PP immunogen induced significant IgG antibody responses, which could be enhanced by a virus booster vaccination. Moreover, the trivalent HA2-PP immunogen also demonstrated in vitro neutralization of the H3 and B viruses, and in vivo protection against the H3 virus. Our results support the notion that a broadly protective vaccine approach using an HA2-based NoV P particle platform can provide cross-protection against challenge viruses of different IAV subtypes. The efficacy of the immunogen should be further enhanced for practicality, and a better understanding of the protective immune mechanism will be critical for the development of HA2-based multivalent vaccines. PMID:27222326

  14. Evaluation of the immunogenicity and protective effects of a trivalent chimeric norovirus P particle immunogen displaying influenza HA2 from subtypes H1, H3 and B.

    PubMed

    Gong, Xin; Yin, He; Shi, Yuhua; He, Xiaoqiu; Yu, Yongjiao; Guan, Shanshan; Kuai, Ziyu; Haji, Nasteha M; Haji, Nafisa M; Kong, Wei; Shan, Yaming

    2016-05-25

    The ectodomain of the influenza A virus (IAV) hemagglutinin (HA) stem is highly conserved across strains and has shown promise as a universal influenza vaccine in a mouse model. In this study, potential B-cell epitopes were found through sequence alignment and epitope prediction in a stem fragment, HA2:90-105, which is highly conserved among virus subtypes H1, H3 and B. A norovirus (NoV) P particle platform was used to express the HA2:90-105 sequences from subtypes H1, H3 and B in loops 1, 2 and 3 of the protrusion (P) domain, respectively. Through mouse immunization and microneutralization assays, the immunogenicity and protective efficacy of the chimeric NoV P particle (trivalent HA2-PP) were tested against infection with three subtypes (H1N1, H3N2 and B) of IAV in Madin-Darby canine kidney cells. The protective efficacy of the trivalent HA2-PP was also evaluated preliminarily in vivo by virus challenge in the mouse model. The trivalent HA2-PP immunogen induced significant IgG antibody responses, which could be enhanced by a virus booster vaccination. Moreover, the trivalent HA2-PP immunogen also demonstrated in vitro neutralization of the H3 and B viruses, and in vivo protection against the H3 virus. Our results support the notion that a broadly protective vaccine approach using an HA2-based NoV P particle platform can provide cross-protection against challenge viruses of different IAV subtypes. The efficacy of the immunogen should be further enhanced for practicality, and a better understanding of the protective immune mechanism will be critical for the development of HA2-based multivalent vaccines.

  15. Sequence diversity within the HA-1 gene as detected by melting temperature assay without oligonucleotide probes

    PubMed Central

    Graziano, Claudio; Giorgi, Massimo; Malentacchi, Cecilia; Mattiuz, Pier Luigi; Porfirio, Berardino

    2005-01-01

    Background The minor histocompatibility antigens (mHags) are self-peptides derived from common cellular proteins and presented by MHC class I and II molecules. Disparities in mHags are a potential risk for the development of graft-versus-host disease (GvHD) in the recipients of bone marrow from HLA-identical donors. Two alleles have been identified in the mHag HA-1. The correlation between mismatches of the mHag HA-1 and GvHD has been suggested and methods to facilitate large-scale testing were afterwards developed. Methods We used sequence specific primer (SSP) PCR and direct sequencing to detect HA-1 gene polymorphisms in a sample of 131 unrelated Italian subjects. We then set up a novel melting temperature (Tm) assay that may help identification of HA-1 alleles without oligonucleotide probes. Results We report the frequencies of HA-1 alleles in the Italian population and the presence of an intronic 5 base-pair deletion associated with the immunogeneic allele HA-1H. We also detected novel variable sites with respect to the consensus sequence of HA-1 locus. Even though recombination/gene conversion events are documented, there is considerable linkage disequilibrium in the data. The gametic associations between HA-1R/H alleles and the intronic 5-bp ins/del polymorphism prompted us to try the Tm analysis with SYBR® Green I. We show that the addition of dimethylsulfoxide (DMSO) during the assay yields distinct patterns when amplicons from HA-1H homozygotes, HA-1R homozygotes, and heterozygotes are analysed. Conclusion The possibility to use SYBR® Green I to detect Tm differences between allelic variants is attractive but requires great caution. We succeeded in allele discrimination of the HA-1 locus using a relatively short (101 bp) amplicon, only in the presence of DMSO. We believe that, at least in certain assets, Tm assays may benefit by the addition of DMSO or other agents affecting DNA strand conformation and stability. PMID:16202172

  16. Broadly protective anti-hemagglutinin stalk antibodies induced by live attenuated influenza vaccine expressing chimeric hemagglutinin.

    PubMed

    Isakova-Sivak, Irina; Korenkov, Daniil; Smolonogina, Tatiana; Kotomina, Tatiana; Donina, Svetlana; Matyushenko, Victoria; Mezhenskaya, Daria; Krammer, Florian; Rudenko, Larisa

    2018-05-01

    The development of influenza vaccines that can provide broad protection against all drifted seasonal virus variants, zoonotic infections and emerging pandemic strains, has been a priority for two decades. Here we propose a strategy of inducing broadly-reactive anti-stalk antibody by sequential immunizations with live attenuated influenza vaccines (LAIVs) expressing chimeric HAs (cHAs). These vaccines are designed to contain identical hemagglutinin stalk domains from H1N1 virus but antigenically unrelated globular head domains from avian influenza virus subtypes H5, H8 and H9. Mouse experiments demonstrated enhanced cross-protection of cHA-containing LAIVs compared to the relevant vaccine viruses expressing natural HAs, and this enhanced protection was driven by stalk-HA-reactive IgG antibodies. The establishment of fully functional cross-protective immunity after two doses of cHA LAIV vaccination in naïve animals suggests that a similar effect might be expected after a single cHA LAIV dose in primed individuals, or after two to three doses in naïve children. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Spatial location of neutralizing and non-neutralizing B cell epitopes on domain 1 of ricin toxin's binding subunit.

    PubMed

    Rong, Yinghui; Van Slyke, Greta; Vance, David J; Westfall, Jennifer; Ehrbar, Dylan; Mantis, Nicholas J

    2017-01-01

    Ricin toxin's binding subunit (RTB) is a galactose-/N-acetylgalactosamine (Gal/GalNac)-specific lectin that mediates uptake and intracellular trafficking of ricin within mammalian cells. Structurally, RTB consists of two globular domains, each divided into three homologous sub-domains (α, β, γ). In this report, we describe five new murine IgG monoclonal antibodies (mAbs) against RTB: MH3, 8A1, 8B3, LF1, and LC5. The mAbs have similar binding affinities (KD) for ricin holotoxin, but displayed a wide range of in vitro toxin-neutralizing activities. Competition ELISAs indicate that the two most potent toxin-neutralizing mAbs (MH3, 8A1), as well as one of the moderate toxin-neutralizing mAbs (LF1), recognize distinct epitopes near the low affinity Gal recognition domain in RTB subdomain 1α. Evaluated in a mouse model of systemic ricin challenge, all five mAbs afforded some benefit against intoxication, but only MH3 was protective. However, neither MH3 nor 24B11, another well-characterized mAb against RTB subdomain 1α, could passively protect mice against a mucosal (intranasal) ricin challenge. This is in contrast to SylH3, a previously characterized mAb directed against an epitope near RTB's high affinity Gal/GalNac recognition element in sub-domain 2γ, which protected animals against systemic and mucosal ricin exposure. SylH3 was significantly more effective than MH3 and 24B11 at blocking ricin attachment to host cell receptors, suggesting that mucosal immunity to ricin is best imparted by antibodies that target RTB's high affinity Gal/GalNac recognition element in subdomain 2γ, not the low affinity Gal recognition domain in subdomain 1α.

  18. Pulsar-irradiated stars in dense globular clusters

    NASA Technical Reports Server (NTRS)

    Tavani, Marco

    1992-01-01

    We discuss the properties of stars irradiated by millisecond pulsars in 'hard' binaries of dense globular clusters. Irradiation by a relativistic pulsar wind as in the case of the eclipsing millisecond pulsar PSR 1957+20 alter both the magnitude and color of the companion star. Some of the blue stragglers (BSs) recently discovered in dense globular clusters can be irradiated stars in binaries containing powerful millisecond pulsars. The discovery of pulsar-driven orbital modulations of BS brightness and color with periods of a few hours together with evidence for radio and/or gamma-ray emission from BS binaries would valuably contribute to the understanding of the evolution of collapsed stars in globular clusters. Pulsar-driven optical modulation of cluster stars might be the only observable effect of a new class of binary pulsars, i.e., hidden millisecond pulsars enshrouded in the evaporated material lifted off from the irradiated companion star.

  19. Stellar black holes in globular clusters

    NASA Technical Reports Server (NTRS)

    Kulkarni, S. R.; Hut, Piet; Mcmillan, Steve

    1993-01-01

    The recent discovery of large populations of millisec pulsars associated with neutron stars in globular clusters indicates that several hundred stellar black holes of about 10 solar masses each can form within a typical cluster. While, in clusters of high central density, the rapid dynamical evolution of the black-hole population leads to an ejection of nearly all holes on a short timescale, systems of intermediate density may involve a normal star's capture by one of the surviving holes to form a low-mass X-ray binary. One or more such binaries may be found in the globular clusters surrounding our galaxy.

  20. Chemodynamical Clustering Applied to APOGEE Data: Rediscovering Globular Clusters

    NASA Astrophysics Data System (ADS)

    Chen, Boquan; D’Onghia, Elena; Pardy, Stephen A.; Pasquali, Anna; Bertelli Motta, Clio; Hanlon, Bret; Grebel, Eva K.

    2018-06-01

    We have developed a novel technique based on a clustering algorithm that searches for kinematically and chemically clustered stars in the APOGEE DR12 Cannon data. As compared to classical chemical tagging, the kinematic information included in our methodology allows us to identify stars that are members of known globular clusters with greater confidence. We apply our algorithm to the entire APOGEE catalog of 150,615 stars whose chemical abundances are derived by the Cannon. Our methodology found anticorrelations between the elements Al and Mg, Na and O, and C and N previously identified in the optical spectra in globular clusters, even though we omit these elements in our algorithm. Our algorithm identifies globular clusters without a priori knowledge of their locations in the sky. Thus, not only does this technique promise to discover new globular clusters, but it also allows us to identify candidate streams of kinematically and chemically clustered stars in the Milky Way.

  1. Structural-based designed modular capsomere comprising HA1 for low-cost poultry influenza vaccination.

    PubMed

    Waneesorn, Jarurin; Wibowo, Nani; Bingham, John; Middelberg, Anton P J; Lua, Linda H L

    2018-05-24

    Highly pathogenic avian influenza (HPAI) viruses cause a severe and lethal infection in domestic birds. The increasing number of HPAI outbreaks has demonstrated the lack of capabilities to control the rapid spread of avian influenza. Poultry vaccination has been shown to not only reduce the virus spread in animals but also reduce the virus transmission to humans, preventing potential pandemic development. However, existing vaccine technologies cannot respond to a new virus outbreak rapidly and at a cost and scale that is commercially viable for poultry vaccination. Here, we developed modular capsomere, subunits of virus-like particle, as a low-cost poultry influenza vaccine. Modified murine polyomavirus (MuPyV) VP1 capsomere was used to present structural-based influenza Hemagglutinin (HA1) antigen. Six constructs of modular capsomeres presenting three truncated versions of HA1 and two constructs of modular capsomeres presenting non-modified HA1 have been generated. These modular capsomeres were successfully produced in stable forms using Escherichia coli, without the need for protein refolding. Based on ELISA, this adjuvanted modular capsomere (CaptHA1-3C) induced strong antibody response (almost 10 5 endpoint titre) when administered into chickens, similar to titres obtained in the group administered with insect cell-based HA1 proteins. Chickens that received adjuvanted CaptHA1-3C followed by challenge with HPAI virus were fully protected. The results presented here indicate that this platform for bacterially-produced modular capsomere could potentially translate into a rapid-response and low-cost vaccine manufacturing technology suitable for poultry vaccination. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Structure and Dynamics of the Globular Cluster Palomar 13

    NASA Astrophysics Data System (ADS)

    Bradford, J. D.; Geha, M.; Muñoz, R. R.; Santana, F. A.; Simon, J. D.; Côté, P.; Stetson, P. B.; Kirby, E.; Djorgovski, S. G.

    2011-12-01

    We present Keck/DEIMOS spectroscopy and Canada-France-Hawaii Telescope/MegaCam photometry for the Milky Way globular cluster Palomar 13. We triple the number of spectroscopically confirmed members, including many repeat velocity measurements. Palomar 13 is the only known globular cluster with possible evidence for dark matter, based on a Keck/High Resolution Echelle Spectrometer 21 star velocity dispersion of σ = 2.2 ± 0.4 km s-1. We reproduce this measurement, but demonstrate that it is inflated by unresolved binary stars. For our sample of 61 stars, the velocity dispersion is σ = 0.7+0.6 -0.5 km s-1. Combining our DEIMOS data with literature values, our final velocity dispersion is σ = 0.4+0.4 -0.3 km s-1. We determine a spectroscopic metallicity of [Fe/H] = -1.6 ± 0.1 dex, placing a 1σ upper limit of σ[Fe/H] ~ 0.2 dex on any internal metallicity spread. We determine Palomar 13's total luminosity to be MV = -2.8 ± 0.4, making it among the least luminous known globular clusters. The photometric isophotes are regular out to the half-light radius and mildly irregular outside this radius. The outer surface brightness profile slope is shallower than typical globular clusters (Σvpropr η, η = -2.8 ± 0.3). Thus at large radius, tidal debris is likely affecting the appearance of Palomar 13. Combining our luminosity with the intrinsic velocity dispersion, we find a dynamical mass of M 1/2 = 1.3+2: 7 -1.3 × 103 M ⊙ and a mass-to-light ratio of M/LV = 2.4+5.0 -2.4 M ⊙/L ⊙. Within our measurement errors, the mass-to-light ratio agrees with the theoretical predictions for a single stellar population. We conclude that, while there is some evidence for tidal stripping at large radius, the dynamical mass of Palomar 13 is consistent with its stellar mass and neither significant dark matter, nor extreme tidal heating, is required to explain the cluster dynamics. The data presented herein were obtained at the W. M. Keck Observatory, which is operated as a

  3. Globular domain of adiponectin: promising target molecule for detection of atherosclerotic lesions

    PubMed Central

    Almer, Gunter; Saba-Lepek, Matthias; Haj-Yahya, Samih; Rohde, Eva; Strunk, Dirk; Fröhlich, Eleonore; Prassl, Ruth; Mangge, Harald

    2011-01-01

    Background: Adiponectin, an adipocyte-specific plasma protein, has been shown to accumulate in injured endothelial cells during development of atherosclerotic lesions. In this study, we investigated the potential of different adiponectin subfractions with special emphasis on globular adiponectin (gAd) to recognize and visualize atherosclerotic lesions. Methods: Recombinant mouse gAd and subfractions of full-length adiponectin (ie, trimeric, hexameric, and oligomeric forms) were fluorescence-labeled. Aortas of wild-type and apoprotein E-deficient mice fed a high cholesterol diet were dissected and incubated with the labeled biomarkers. Imaging was performed using confocal laser scanning microscopy. Results: Confocal laser scanning microscopic images showed that gAd binds more strongly to atherosclerotic plaques than full-length adiponectin subfractions. Further, we showed that gAd accumulates preferentially in endothelial cells and the fibrous cap area of plaques. Here we demonstrate for the first time that gAd recognizes atherosclerotic plaques on aortic sections of apoprotein E-deficient mice. Conclusion: These results suggest that gAd, in addition to its physiological properties, is also suitable as a target molecule for prospective diagnostic strategies in imaging atherosclerotic lesions. PMID:22022204

  4. The WAGGS project - I. The WiFeS Atlas of Galactic Globular cluster Spectra

    NASA Astrophysics Data System (ADS)

    Usher, Christopher; Pastorello, Nicola; Bellstedt, Sabine; Alabi, Adebusola; Cerulo, Pierluigi; Chevalier, Leonie; Fraser-McKelvie, Amelia; Penny, Samantha; Foster, Caroline; McDermid, Richard M.; Schiavon, Ricardo P.; Villaume, Alexa

    2017-07-01

    We present the WiFeS Atlas of Galactic Globular cluster Spectra, a library of integrated spectra of Milky Way and Local Group globular clusters. We used the WiFeS integral field spectrograph on the Australian National University 2.3 m telescope to observe the central regions of 64 Milky Way globular clusters and 22 globular clusters hosted by the Milky Way's low-mass satellite galaxies. The spectra have wider wavelength coverage (3300-9050 Å) and higher spectral resolution (R = 6800) than existing spectral libraries of Milky Way globular clusters. By including Large and Small Magellanic Cloud star clusters, we extend the coverage of parameter space of existing libraries towards young and intermediate ages. While testing stellar population synthesis models and analysis techniques is the main aim of this library, the observations may also further our understanding of the stellar populations of Local Group globular clusters and make possible the direct comparison of extragalactic globular cluster integrated light observations with well-understood globular clusters in the Milky Way. The integrated spectra are publicly available via the project website.

  5. Structure of novel rat major histocompatibility complex class II genes RT1.Ha and Hb

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Arimura, Yutaka; Tang, Wei Ran; Koda, Toshiaki

    1995-03-01

    We have cloned the novel rat MHC class II genes, RT1.Ha and Hb, which are homologous to human HLA-DPA and DPB. RT1.Hb is a pseudogene, whereas RT1.Ha is apparently intact and may have transcriptional potential. In addition, with an RT1.Ha probe, we detecteda single Southern hybridization band in the genome of the mouse. This finding may aford an opportunity to analyze the HLA-DPA homologue in the mouse genome. 18 refs., 4 figs., 1 tab.

  6. The Evolution of Globular Cluster Systems In Early-Type Galaxies

    NASA Astrophysics Data System (ADS)

    Grillmair, Carl

    1999-07-01

    We will measure structural parameters {core radii and concentrations} of globular clusters in three early-type galaxies using deep, four-point dithered observations. We have chosen globular cluster systems which have young, medium-age and old cluster populations, as indicated by cluster colors and luminosities. Our primary goal is to test the hypothesis that globular cluster luminosity functions evolve towards a ``universal'' form. Previous observations have shown that young cluster systems have exponential luminosity functions rather than the characteristic log-normal luminosity function of old cluster systems. We will test to see whether such young system exhibits a wider range of structural parameters than an old systems, and whether and at what rate plausible disruption mechanisms will cause the luminosity function to evolve towards a log-normal form. A simple observational comparison of structural parameters between different age cluster populations and between diff er ent sub-populations within the same galaxy will also provide clues concerning both the formation and destruction mechanisms of star clusters, the distinction between open and globular clusters, and the advisability of using globular cluster luminosity functions as distance indicators.

  7. Common Evolutionary Origin for the Rotor Domain of Rotary Atpases and Flagellar Protein Export Apparatus

    PubMed Central

    Kishikawa, Jun-ichi; Ibuki, Tatsuya; Nakamura, Shuichi; Nakanishi, Astuko; Minamino, Tohru; Miyata, Tomoko; Namba, Keiichi; Konno, Hiroki; Ueno, Hiroshi; Imada, Katsumi; Yokoyama, Ken

    2013-01-01

    The V1- and F1- rotary ATPases contain a rotor that rotates against a catalytic A3B3 or α3β3 stator. The rotor F1-γ or V1-DF is composed of both anti-parallel coiled coil and globular-loop parts. The bacterial flagellar type III export apparatus contains a V1/F1-like ATPase ring structure composed of FliI6 homo-hexamer and FliJ which adopts an anti-parallel coiled coil structure without the globular-loop part. Here we report that FliJ of Salmonella enterica serovar Typhimurium shows a rotor like function in Thermus thermophilus A3B3 based on both biochemical and structural analysis. Single molecular analysis indicates that an anti-parallel coiled-coil structure protein (FliJ structure protein) functions as a rotor in A3B3. A rotary ATPase possessing an F1-γ-like protein generated by fusion of the D and F subunits of V1 rotates, suggesting F1-γ could be the result of a fusion of the genes encoding two separate rotor subunits. Together with sequence comparison among the globular part proteins, the data strongly suggest that the rotor domains of the rotary ATPases and the flagellar export apparatus share a common evolutionary origin. PMID:23724081

  8. No sign (yet) of intergalactic globular clusters in the Local Group

    NASA Astrophysics Data System (ADS)

    Mackey, A. D.; Beasley, M. A.; Leaman, R.

    2016-07-01

    We present Gemini Multi-Object Spectrograph (GMOS) imaging of 12 candidate intergalactic globular clusters (IGCs) in the Local Group, identified in a recent survey of the Sloan Digital Sky Survey (SDSS) footprint by di Tullio Zinn & Zinn. Our image quality is sufficiently high, at ˜0.4-0.7 arcsec, that we are able to unambiguously classify all 12 targets as distant galaxies. To reinforce this conclusion we use GMOS images of globular clusters in the M31 halo, taken under very similar conditions, to show that any genuine clusters in the putative IGC sample would be straightforward to distinguish. Based on the stated sensitivity of the di Tullio Zinn & Zinn search algorithm, we conclude that there cannot be a significant number of IGCs with MV ≤ -6 lying unseen in the SDSS area if their properties mirror those of globular clusters in the outskirts of M31 - even a population of 4 would have only a ≈1 per cent chance of non-detection.

  9. Primordial black holes in globular clusters

    NASA Technical Reports Server (NTRS)

    Sigurdsson, Steinn; Hernquist, Lars

    1993-01-01

    It has recently been recognized that significant numbers of medium-mass back holes (of order 10 solar masses) should form in globular clusters during the early stages of their evolution. Here we explore the dynamical and observational consequences of the presence of such a primordial black-hole population in a globular cluster. The holes initially segregate to the cluster cores, where they form binary and multiple black-hole systems. The subsequent dynamical evolution of the black-hole population ejects most of the holes on a relatively short timescale: a typical cluster will retain between zero and four black holes in its core, and possibly a few black holes in its halo. The presence of binary, triple, and quadruple black-hole systems in cluster cores will disrupt main-sequence and giant stellar binaries; this may account for the observed anomalies in the distribution of binaries in globular clusters. Furthermore, tidal interactions between a multiple black-hole system and a red giant star can remove much of the red giant's stellar envelope, which may explain the puzzling absence of larger red giants in the cores of some very dense clusters.

  10. Assessing the Potential of Folded Globular Polyproteins As Hydrogel Building Blocks

    PubMed Central

    2016-01-01

    The native states of proteins generally have stable well-defined folded structures endowing these biomolecules with specific functionality and molecular recognition abilities. Here we explore the potential of using folded globular polyproteins as building blocks for hydrogels. Photochemically cross-linked hydrogels were produced from polyproteins containing either five domains of I27 ((I27)5), protein L ((pL)5), or a 1:1 blend of these proteins. SAXS analysis showed that (I27)5 exists as a single rod-like structure, while (pL)5 shows signatures of self-aggregation in solution. SANS measurements showed that both polyprotein hydrogels have a similar nanoscopic structure, with protein L hydrogels being formed from smaller and more compact clusters. The polyprotein hydrogels showed small energy dissipation in a load/unload cycle, which significantly increased when the hydrogels were formed in the unfolded state. This study demonstrates the use of folded proteins as building blocks in hydrogels, and highlights the potential versatility that can be offered in tuning the mechanical, structural, and functional properties of polyproteins. PMID:28006103

  11. Evidence for an Accretion Origin for the Outer Halo Globular Cluster System of M31

    NASA Astrophysics Data System (ADS)

    Mackey, A. D.; Huxor, A. P.; Ferguson, A. M. N.; Irwin, M. J.; Tanvir, N. R.; McConnachie, A. W.; Ibata, R. A.; Chapman, S. C.; Lewis, G. F.

    2010-07-01

    We use a sample of newly discovered globular clusters from the Pan-Andromeda Archaeological Survey (PAndAS) in combination with previously cataloged objects to map the spatial distribution of globular clusters in the M31 halo. At projected radii beyond ≈30 kpc, where large coherent stellar streams are readily distinguished in the field, there is a striking correlation between these features and the positions of the globular clusters. Adopting a simple Monte Carlo approach, we test the significance of this association by computing the probability that it could be due to the chance alignment of globular clusters smoothly distributed in the M31 halo. We find that the likelihood of this possibility is low, below 1%, and conclude that the observed spatial coincidence between globular clusters and multiple tidal debris streams in the outer halo of M31 reflects a genuine physical association. Our results imply that the majority of the remote globular cluster system of M31 has been assembled as a consequence of the accretion of cluster-bearing satellite galaxies. This constitutes the most direct evidence to date that the outer halo globular cluster populations in some galaxies are largely accreted. Based on observations obtained with MegaPrime/MegaCam, a joint project of CFHT and CEA/DAPNIA, at the Canada-France-Hawaii Telescope (CFHT) which is operated by the National Research Council (NRC) of Canada, the Institut National des Science de l'Univers of the Centre National de la Recherche Scientifique (CNRS) of France, and the University of Hawaii.

  12. When a domain isn’t a domain, and why it’s important to properly filter proteins in databases

    PubMed Central

    Towse, Clare-Louise; Daggett, Valerie

    2013-01-01

    Summary Membership in a protein domain database does not a domain make; a feature we realized when generating a consensus view of protein fold space with our Consensus Domain Dictionary (CDD). This dictionary was used to select representative structures for characterization of the protein dynameome: the Dynameomics initiative. Through this endeavor we rejected a surprising 40% of the 1695 folds in the CDD as being non-autonomous folding units. Although some of this was due to the challenges of grouping similar fold topologies, the dissonance between the cataloguing and structural qualification of protein domains remains surprising. Another potential factor is previously overlooked intrinsic disorder; predicted estimates suggest 40% of proteins to have either local or global disorder. One thing is clear, filtering a structural database and ensuring a consistent definition for protein domains is crucial, and caution is prescribed when generalizations of globular domains are drawn from unfiltered protein domain datasets. PMID:23108912

  13. Spatial location of neutralizing and non-neutralizing B cell epitopes on domain 1 of ricin toxin’s binding subunit

    PubMed Central

    Rong, Yinghui; Van Slyke, Greta; Vance, David J.; Westfall, Jennifer; Ehrbar, Dylan

    2017-01-01

    Ricin toxin’s binding subunit (RTB) is a galactose-/N-acetylgalactosamine (Gal/GalNac)-specific lectin that mediates uptake and intracellular trafficking of ricin within mammalian cells. Structurally, RTB consists of two globular domains, each divided into three homologous sub-domains (α, β, γ). In this report, we describe five new murine IgG monoclonal antibodies (mAbs) against RTB: MH3, 8A1, 8B3, LF1, and LC5. The mAbs have similar binding affinities (KD) for ricin holotoxin, but displayed a wide range of in vitro toxin-neutralizing activities. Competition ELISAs indicate that the two most potent toxin-neutralizing mAbs (MH3, 8A1), as well as one of the moderate toxin-neutralizing mAbs (LF1), recognize distinct epitopes near the low affinity Gal recognition domain in RTB subdomain 1α. Evaluated in a mouse model of systemic ricin challenge, all five mAbs afforded some benefit against intoxication, but only MH3 was protective. However, neither MH3 nor 24B11, another well-characterized mAb against RTB subdomain 1α, could passively protect mice against a mucosal (intranasal) ricin challenge. This is in contrast to SylH3, a previously characterized mAb directed against an epitope near RTB’s high affinity Gal/GalNac recognition element in sub-domain 2γ, which protected animals against systemic and mucosal ricin exposure. SylH3 was significantly more effective than MH3 and 24B11 at blocking ricin attachment to host cell receptors, suggesting that mucosal immunity to ricin is best imparted by antibodies that target RTB’s high affinity Gal/GalNac recognition element in subdomain 2γ, not the low affinity Gal recognition domain in subdomain 1α. PMID:28700745

  14. Low resolution solution structure of HAMLET and the importance of its alpha-domains in tumoricidal activity.

    PubMed

    Ho, C S James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard

    2012-01-01

    HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells.

  15. Low Resolution Solution Structure of HAMLET and the Importance of Its Alpha-Domains in Tumoricidal Activity

    PubMed Central

    Ho CS, James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard

    2012-01-01

    HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells. PMID:23300861

  16. Performance evaluation of the Arkray Adams HA-8160 HbA1c analyser.

    PubMed

    Thevarajah, T Malathi; Nani, Nordin; Chew, Y Y

    2008-12-01

    HbA1c measurement is currently routinely used to predict long term outcome of diabetes, thus playing a fundamental role in the management of diabetes. The relationship between HbA1c value and long term diabetic complications has been established by a randomised control Diabetes Control and Complications Trial (DCCT) which used high performance liquid chromatography (HPLC) as a reference method for HbA1c assay. To ensure that HbA1c results from a variety HbA1c assay methods are similar to the DCCT values, the American Diabetes Association (ADA) recommended that all laboratories should use methods certified by the National Glycohemoglobin Standardization Programme (NGSP) with interassay coefficient variation (CV) of < 5% (ideally < 3%). The International Federation of Clinical Chemistry (IFCC) working group on HbA1c standardisation has set a CV < 2.5% as a criteria for its reference laboratories. To evaluate the performance of Arkray Adams HA-8160 HbA1c analyser which uses a cation exchange HPLC method and its correlation to HbA1c assay on Cobas Integra 800 which is an immunoturbidimetric method. For the imprecision study, patient samples and control material of two levels were analysed on HA-8160 analyser 20 times in a single run (within-run imprecision) and twice a day on five consecutive days (between-run imprecision). For the recovery study, two samples each with high and low values were selected and mixed in ratios of 1:3, 1:1 and 3:1, and were analysed by HA-8160. Sixty samples were analysed by both Cobas Integra 800 and HA-8160 for method comparison study. Ten uraemic samples and ten thalassaemic samples were assayed on Cobas Integra 800 and HA 8160 for interference study. Within-run CVs were 0.6% and 0.7% for medium and high value samples respectively, 0.6% and 0.7% for low and high level controls respectively. Between-run CVs were 0.5% and 0.4% for medium and high value samples respectively, 0.5% and 0.6% for low and high level controls respectively. The

  17. Young accreted globular clusters in the outer halo of M31

    NASA Astrophysics Data System (ADS)

    Mackey, A. D.; Huxor, A. P.; Ferguson, A. M. N.; Irwin, M. J.; Veljanoski, J.; McConnachie, A. W.; Ibata, R. A.; Lewis, G. F.; Tanvir, N. R.

    2013-02-01

    We report on observations of two newly discovered globular clusters in the outskirts of M31 made using the Gemini Multi-Object Spectrograph (GMOS) instrument on Gemini North. These objects, PAndAS-7 (PA-7) and PAndAS-8 (PA-8), lie at a galactocentric radius of ≈87 kpc and are projected, with separation ≈19 kpc, on to a field halo substructure known as the South-West Cloud. We measure radial velocities for the two clusters which confirm that they are almost certainly physically associated with this feature. Colour-magnitude diagrams reveal strikingly short, exclusively red horizontal branches in both PA-7 and PA-8; both also have photometric [Fe/H] = -1.35 ± 0.15. At this metallicity, the morphology of the horizontal branch is maximally sensitive to age, and we use the distinctive configurations seen in PA-7 and PA-8 to demonstrate that both objects are very likely to be at least 2 Gyr younger than the oldest Milky Way globular clusters. Our observations provide strong evidence for young globular clusters being accreted into the remote outer regions of M31 in a manner entirely consistent with the established picture for the Milky Way, and add credence to the idea that similar processes play a central role in determining the composition of globular cluster systems in large spiral galaxies in general.

  18. Structural and functional characterization of the NHR1 domain of the Drosophila neuralized E3 ligase in the notch signaling pathway.

    PubMed

    He, Fahu; Saito, Kohei; Kobayashi, Naohiro; Harada, Takushi; Watanabe, Satoru; Kigawa, Takanori; Güntert, Peter; Ohara, Osamu; Tanaka, Akiko; Unzai, Satoru; Muto, Yutaka; Yokoyama, Shigeyuki

    2009-10-23

    The Notch signaling pathway is critical for many developmental processes and requires complex trafficking of both Notch receptor and its ligands, Delta and Serrate. In Drosophila melanogaster, the endocytosis of Delta in the signal-sending cell is essential for Notch receptor activation. The Neuralized protein from D. melanogaster (Neur) is a ubiquitin E3 ligase, which binds to Delta through its first neuralized homology repeat 1 (NHR1) domain and mediates the ubiquitination of Delta for endocytosis. Tom, a Bearded protein family member, inhibits the Neur-mediated endocytosis through interactions with the NHR1 domain. We have identified the domain boundaries of the novel NHR1 domain, using a screening system based on our cell-free protein synthesis method, and demonstrated that the identified Neur NHR1 domain had binding activity to the 20-residue peptide corresponding to motif 2 of Tom by isothermal titration calorimetry experiments. We also determined the solution structure of the Neur NHR1 domain by heteronuclear NMR methods, using a (15)N/(13)C-labeled sample. The Neur NHR1 domain adopts a characteristic beta-sandwich fold, consisting of a concave five-stranded antiparallel beta-sheet and a convex seven-stranded antiparallel beta-sheet. The long loop (L6) between the beta6 and beta7 strands covers the hydrophobic patch on the concave beta-sheet surface, and the Neur NHR1 domain forms a compact globular fold. Intriguingly, in spite of the slight, but distinct, differences in the topology of the secondary structure elements, the structure of the Neur NHR1 domain is quite similar to those of the B30.2/SPRY domains, which are known to mediate specific protein-protein interactions. Further NMR titration experiments of the Neur NHR1 domain with the 20-residue Tom peptide revealed that the resonances originating from the bottom area of the beta-sandwich (the L3, L5, and L11 loops, as well as the tip of the L6 loop) were affected. In addition, a structural comparison

  19. Modeling AFM-induced PEVK extension and the reversible unfolding of Ig/FNIII domains in single and multiple titin molecules.

    PubMed Central

    Zhang, B; Evans, J S

    2001-01-01

    Molecular elasticity is associated with a select number of polypeptides and proteins, such as titin, Lustrin A, silk fibroin, and spider silk dragline protein. In the case of titin, the globular (Ig) and non-globular (PEVK) regions act as extensible springs under stretch; however, their unfolding behavior and force extension characteristics are different. Using our time-dependent macroscopic method for simulating AFM-induced titin Ig domain unfolding and refolding, we simulate the extension and relaxation of hypothetical titin chains containing Ig domains and a PEVK region. Two different models are explored: 1) a series-linked WLC expression that treats the PEVK region as a distinct entropic spring, and 2) a summation of N single WLC expressions that simulates the extension and release of a discrete number of parallel titin chains containing constant or variable amounts of PEVK. In addition to these simulations, we also modeled the extension of a hypothetical PEVK domain using a linear Hooke's spring model to account for "enthalpic" contributions to PEVK elasticity. We find that the modified WLC simulations feature chain length compensation, Ig domain unfolding/refolding, and force-extension behavior that more closely approximate AFM, laser tweezer, and immunolocalization experimental data. In addition, our simulations reveal the following: 1) PEVK extension overlaps with the onset of Ig domain unfolding, and 2) variations in PEVK content within a titin chain ensemble lead to elastic diversity within that ensemble. PMID:11159428

  20. LUMINOSITY FUNCTIONS OF LMXBs IN CENTAURUS A: GLOBULAR CLUSTERS VERSUS THE FIELD

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Voss, Rasmus; Gilfanov, Marat; Sivakoff, Gregory R.

    2009-08-10

    We study the X-ray luminosity function (XLF) of low-mass X-ray binaries (LMXB) in the nearby early-type galaxy Centaurus A, concentrating primarily on two aspects of binary populations: the XLF behavior at the low-luminosity limit and the comparison between globular cluster and field sources. The 800 ksec exposure of the deep Chandra VLP program allows us to reach a limiting luminosity of {approx}8 x 10{sup 35} erg s{sup -1}, about {approx}2-3 times deeper than previous investigations. We confirm the presence of the low-luminosity break of the overall LMXB XLF at log(L{sub X} ) {approx} 37.2-37.6, below which the luminosity distribution followsmore » a dN/d(ln L) {approx} const law. Separating globular cluster and field sources, we find a statistically significant difference between the two luminosity distributions with a relative underabundance of faint sources in the globular cluster population. This demonstrates that the samples are drawn from distinct parent populations and may disprove the hypothesis that the entire LMXB population in early-type galaxies is created dynamically in globular clusters. As a plausible explanation for this difference in the XLFs, we suggest an enhanced fraction of helium-accreting systems in globular clusters, which are created in collisions between red giants and neutron stars. Due to the four times higher ionization temperature of He, such systems are subject to accretion disk instabilities at {approx}20 times higher mass accretion rate and, therefore, are not observed as persistent sources at low luminosities.« less

  1. Registration of an oilseed sunflower germplasm HA-DM1 resistant to sunflower downy mildew

    USDA-ARS?s Scientific Manuscript database

    HA-DM1 (Reg. No.xxx, PI 674793) sunflower (Helianthus annuus L.) germplasm was developed and released cooperatively by the USDA-ARS, Sunflower and Plant Biology Research Unit and the North Dakota Agricultural Experiment Station in 2015. HA-DM1 is a BC2F4 derived oilseed maintainer line from the cros...

  2. Pal 12 - A metal-rich globular cluster in the outer halo

    NASA Technical Reports Server (NTRS)

    Cohen, J. G.; Frogel, J. A.; Persson, S. E.; Zinn, R.

    1980-01-01

    New optical and infrared observations of several stars in the distant globular cluster Pal 12 show that they have CO strengths and heavy element abundances only slightly less than in M 71, one of the more metal-rich globular clusters. Pal 12 thus has a metal abundance near the high end of the range over which globular clusters exist and lies in the outer galactic halo. Its red horizontal branch is not anomalous in view of the abundance that has been found.

  3. Exploring the Internal Dynamics of Globular Clusters

    NASA Astrophysics Data System (ADS)

    Watkins, Laura L.; van der Marel, Roeland; Bellini, Andrea; Luetzgendorf, Nora; HSTPROMO Collaboration

    2018-01-01

    Exploring the Internal Dynamics of Globular ClustersThe formation histories and structural properties of globular clusters are imprinted on their internal dynamics. Energy equipartition results in velocity differences for stars of different mass, and leads to mass segregation, which results in different spatial distributions for stars of different mass. Intermediate-mass black holes significantly increase the velocity dispersions at the centres of clusters. By combining accurate measurements of their internal kinematics with state-of-the-art dynamical models, we can characterise both the velocity dispersion and mass profiles of clusters, tease apart the different effects, and understand how clusters may have formed and evolved.Using proper motions from the Hubble Space Telescope Proper Motion (HSTPROMO) Collaboration for a set of 22 Milky Way globular clusters, and our discrete dynamical modelling techniques designed to work with large, high-quality datasets, we are studying a variety of internal cluster properties. We will present the results of theoretical work on simulated clusters that demonstrates the efficacy of our approach, and preliminary results from application to real clusters.

  4. Antibody Pressure by a Human Monoclonal Antibody Targeting the 2009 Pandemic H1N1 Virus Hemagglutinin Drives the Emergence of a Virus with Increased Virulence in Mice

    PubMed Central

    O’Donnell, Christopher D.; Vogel, Leatrice; Wright, Amber; Das, Suman R.; Wrammert, Jens; Li, Gui-Mei; McCausland, Megan; Zheng, Nai-Ying; Yewdell, Jonathan W.; Ahmed, Rafi; Wilson, Patrick C.; Subbarao, Kanta

    2012-01-01

    ABSTRACT In 2009, a novel H1N1 influenza A virus (2009 pH1N1) emerged and caused a pandemic. A human monoclonal antibody (hMAb; EM4C04), highly specific for the 2009 pH1N1 virus hemagglutinin (HA), was isolated from a severely ill 2009 pH1N1 virus-infected patient. We postulated that under immune pressure with EM4C04, the 2009 pH1N1 virus would undergo antigenic drift and mutate at sites that would identify the antibody binding site. To do so, we infected MDCK cells in the presence of EM4C04 and generated 11 escape mutants, displaying 7 distinct amino acid substitutions in the HA. Six substitutions greatly reduced MAb binding (K123N, D131E, K133T, G134S, K157N, and G158E). Residues 131, 133, and 134 are contiguous with residues 157 and 158 in the globular domain structure and contribute to a novel pH1N1 antibody epitope. One mutation near the receptor binding site, S186P, increased the binding affinity of the HA to the receptor. 186P and 131E are present in the highly virulent 1918 virus HA and were recently identified as virulence determinants in a mouse-passaged pH1N1 virus. We found that pH1N1 escape variants expressing these substitutions enhanced replication and lethality in mice compared to wild-type 2009 pH1N1 virus. The increased virulence of these viruses was associated with an increased affinity for α2,3 sialic acid receptors. Our study demonstrates that antibody pressure by an hMAb targeting a novel epitope in the Sa region of 2009 pH1N1 HA is able to inadvertently drive the development of a more virulent virus with altered receptor binding properties. This broadens our understanding of antigenic drift. PMID:22647789

  5. An Enigmatic Population of Luminous Globular Clusters in a Galaxy Lacking Dark Matter

    NASA Astrophysics Data System (ADS)

    van Dokkum, Pieter; Cohen, Yotam; Danieli, Shany; Kruijssen, J. M. Diederik; Romanowsky, Aaron J.; Merritt, Allison; Abraham, Roberto; Brodie, Jean; Conroy, Charlie; Lokhorst, Deborah; Mowla, Lamiya; O’Sullivan, Ewan; Zhang, Jielai

    2018-04-01

    We recently found an ultra diffuse galaxy (UDG) with a half-light radius of R e = 2.2 kpc and little or no dark matter. The total mass of NGC1052–DF2 was measured from the radial velocities of bright compact objects that are associated with the galaxy. Here, we analyze these objects using a combination of Hubble Space Telescope (HST) imaging and Keck spectroscopy. Their average size is < {r}h> =6.2+/- 0.5 pc and their average ellipticity is < ε > =0.18+/- 0.02. From a stacked Keck spectrum we derive an age of ≳9 Gyr and a metallicity of [Fe/H] = ‑1.35 ± 0.12. Their properties are similar to ω Centauri, the brightest and largest globular cluster in the Milky Way, and our results demonstrate that the luminosity function of metal-poor globular clusters is not universal. The fraction of the total stellar mass that is in the globular cluster system is similar to that in other UDGs, and consistent with “failed galaxy” scenarios, where star formation terminated shortly after the clusters were formed. However, the galaxy is a factor of ∼1000 removed from the relation between globular cluster mass and total galaxy mass that has been found for other galaxies, including other UDGs. We infer that a dark matter halo is not a prerequisite for the formation of metal-poor globular cluster-like objects in high-redshift galaxies.

  6. Exploring the early stages of the pH-induced conformational change of influenza hemagglutinin.

    PubMed

    Zhou, Yu; Wu, Chao; Zhao, Lifeng; Huang, Niu

    2014-10-01

    Hemagglutinin (HA) mediates the membrane fusion process of influenza virus through its pH-induced conformational change. However, it remains challenging to study its structure reorganization pathways in atomic details. Here, we first applied continuous constant pH molecular dynamics approach to predict the pK(a) values of titratable residues in H2 subtype HA. The calculated net-charges in HA1 globular heads increase from 0e (pH 7.5) to +14e (pH 4.5), indicating that the charge repulsion drives the detrimerization of HA globular domains. In HA2 stem regions, critical pH sensors, such as Glu103(2), His18(1), and Glu89(1), are identified to facilitate the essential structural reorganizations in the fusing pathways, including fusion peptide release and interhelical loop transition. To probe the contribution of identified pH sensors and unveil the early steps of pH-induced conformational change, we carried out conventional molecular dynamics simulations in explicit water with determined protonation state for each titratable residue in different environmental pH conditions. Particularly, energy barriers involving previously uncharacterized hydrogen bonds and hydrophobic interactions are identified in the fusion peptide release pathway. Nevertheless, comprehensive comparisons across HA family members indicate that different HA subtypes might employ diverse pH sensor groups along with different fusion pathways. Finally, we explored the fusion inhibition mechanism of antibody CR6261 and small molecular inhibitor TBHQ, and discovered a novel druggable pocket in H2 and H5 subtypes. Our results provide the underlying mechanism for the pH-driven conformational changes and also novel insight for anti-flu drug development. © 2014 Wiley Periodicals, Inc.

  7. VizieR Online Data Catalog: RR Lyrae in 15 Galactic globular clusters (Dambis+, 2014)

    NASA Astrophysics Data System (ADS)

    Dambis, A. K.; Rastorguev, A. S.; Zabolotskikh, M. V.

    2014-11-01

    Last year, the WISE All-Sky Data Release (Cutri et al., 2012, Cat. II/328) was made public, mapping the entire sky in four mid-infrared bands W1, W2, W3 and W4 with the effective wavelengths of 3.368, 4.618, 12.082 and 22.194um, respectively. We cross-correlated the WISE single-exposure data base with the Catalogue of Galactic globular-cluster variables by Clement et al. (2001AJ....122.2587C), the Catalogue of Accurate Equatorial Coordinates for Variable Stars in Globular Clusters by Samus et al. (2009PASP..121.1378S, Cat. J/PASP/121/1378) and the catalogue of Sawyer Hogg (1973PDDO....3....6S, Cat. V/97) (for ω Cen, NGC 6723 and NGC 6934) to compute (via Fourier fits) the intensity-mean average W1- and W2-band magnitudes, 1> and , for a total of 357 and 272 RR Lyrae type variables in 15 and 9 Galactic globular clusters, respectively. (1 data file).

  8. A survey for dwarf galaxy remnants around 14 globular clusters in the outer halo

    NASA Astrophysics Data System (ADS)

    Sollima, A.; Martínez Delgado, D.; Muñoz, R. R.; Carballo-Bello, J. A.; Valls-Gabaud, D.; Grebel, E. K.; Santana, F. A.; Côté, P.; Djorgovski, S. G.

    2018-06-01

    We report the results of a systematic photometric survey of the peripheral regions of a sample of 14 globular clusters in the outer halo of the Milky Way at distances dGC > 25 kpc from the Galactic Centre. The survey is aimed at searching for the remnants of the host satellite galaxies where these clusters could originally have been formed before being accreted on to the Galactic halo. The limiting surface brightness varies within our sample, but reaches μV, lim = 30-32 mag arcsec-2. For only two globular clusters (NGC 7492 and Whiting 1; already suggested to be associated with the Sagittarius galaxy), we detect extended stellar populations that cannot be associated with either the clusters themselves or with the surrounding Galactic field population. We show that the lack of substructures around globular clusters at these Galactocentric distances is still compatible with the predictions of cosmological simulations whereby in the outer halo the Galactic globular cluster system is built up through hierarchical accretion at early epochs.

  9. HUBBLE PINPOINTS WHITE DWARFS IN GLOBULAR CLUSTER

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Peering deep inside a cluster of several hundred thousand stars, NASA's Hubble Space Telescope uncovered the oldest burned-out stars in our Milky Way Galaxy. Located in the globular cluster M4, these small, dying stars - called white dwarfs - are giving astronomers a fresh reading on one of the biggest questions in astronomy: How old is the universe? The ancient white dwarfs in M4 are about 12 to 13 billion years old. After accounting for the time it took the cluster to form after the big bang, astronomers found that the age of the white dwarfs agrees with previous estimates for the universe's age. In the top panel, a ground-based observatory snapped a panoramic view of the entire cluster, which contains several hundred thousand stars within a volume of 10 to 30 light-years across. The Kitt Peak National Observatory's 0.9-meter telescope took this picture in March 1995. The box at left indicates the region observed by the Hubble telescope. The Hubble telescope studied a small region of the cluster. A section of that region is seen in the picture at bottom left. A sampling of an even smaller region is shown at bottom right. This region is only about one light-year across. In this smaller region, Hubble pinpointed a number of faint white dwarfs. The blue circles pinpoint the dwarfs. It took nearly eight days of exposure time over a 67-day period to find these extremely faint stars. Globular clusters are among the oldest clusters of stars in the universe. The faintest and coolest white dwarfs within globular clusters can yield a globular cluster's age. Earlier Hubble observations showed that the first stars formed less than 1 billion years after the universe's birth in the big bang. So, finding the oldest stars puts astronomers within arm's reach of the universe's age. M4 is 7,000 light-years away in the constellation Scorpius. Hubble's Wide Field and Planetary Camera 2 made the observations from January through April 2001. These optical observations were combined to

  10. LITHIUM-RICH GIANTS IN GLOBULAR CLUSTERS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kirby, Evan N.; Cohen, Judith G.; Guhathakurta, Puragra

    Although red giants deplete lithium on their surfaces, some giants are Li-rich. Intermediate-mass asymptotic giant branch (AGB) stars can generate Li through the Cameron–Fowler conveyor, but the existence of Li-rich, low-mass red giant branch (RGB) stars is puzzling. Globular clusters are the best sites to examine this phenomenon because it is straightforward to determine membership in the cluster and to identify the evolutionary state of each star. In 72 hours of Keck/DEIMOS exposures in 25 clusters, we found four Li-rich RGB and two Li-rich AGB stars. There were 1696 RGB and 125 AGB stars with measurements or upper limits consistentmore » with normal abundances of Li. Hence, the frequency of Li-richness in globular clusters is (0.2 ± 0.1)% for the RGB, (1.6 ± 1.1)% for the AGB, and (0.3 ± 0.1)% for all giants. Because the Li-rich RGB stars are on the lower RGB, Li self-generation mechanisms proposed to occur at the luminosity function bump or He core flash cannot explain these four lower RGB stars. We propose the following origin for Li enrichment: (1) All luminous giants experience a brief phase of Li enrichment at the He core flash. (2) All post-RGB stars with binary companions on the lower RGB will engage in mass transfer. This scenario predicts that 0.1% of lower RGB stars will appear Li-rich due to mass transfer from a recently Li-enhanced companion. This frequency is at the lower end of our confidence interval.« less

  11. Expression and Purification of a Matrix Metalloprotease Transmembrane Domain in Escherichia coli.

    PubMed

    Galea, Charles A

    2017-01-01

    Membrane tethered matrix metalloproteases are bound to the plasma membrane by a glycosylphosphatidylinositol-anchor or a transmembrane domain. To date, most studies of membrane-bound matrix metalloprotease have focused on the globular catalytic and protein-protein interaction domains of these enzymes. However, the transmembrane domains have been poorly studied even though they are known to mediate intracellular signaling via interaction with various cellular proteins. The expression and purification of the transmembrane domain of these proteins can be challenging due to their hydrophobic nature. In this chapter we describe the purification of a transmembrane domain for a membrane-bound matrix metalloprotease expressed in E. coli and its initial characterization by NMR spectroscopy.

  12. Nanofibers made of globular proteins.

    PubMed

    Dror, Yael; Ziv, Tamar; Makarov, Vadim; Wolf, Hila; Admon, Arie; Zussman, Eyal

    2008-10-01

    Strong nanofibers composed entirely of a model globular protein, namely, bovine serum albumin (BSA), were produced by electrospinning directly from a BSA solution without the use of chemical cross-linkers. Control of the spinnability and the mechanical properties of the produced nanofibers was achieved by manipulating the protein conformation, protein aggregation, and intra/intermolecular disulfide bonds exchange. In this manner, a low-viscosity globular protein solution could be modified into a polymer-like spinnable solution and easily spun into fibers whose mechanical properties were as good as those of natural fibers made of fibrous protein. We demonstrate here that newly formed disulfide bonds (intra/intermolecular) have a dominant role in both the formation of the nanofibers and in providing them with superior mechanical properties. Our approach to engineer proteins into biocompatible fibrous structures may be used in a wide range of biomedical applications such as suturing, wound dressing, and wound closure.

  13. Search for Carbon-Rich Asymptotic Giant Branch Stars in Milky Way Globular Clusters

    NASA Astrophysics Data System (ADS)

    Indahl, Briana; Pessev, P.

    2014-01-01

    From our current understanding of stellar evolution, it would not be expected to find carbon rich asymptotic giant branch (AGB) stars in Milky Way globular clusters. Due to the low metallicity of the population II stars making up the globular clusters and their age, stars large enough to fuse carbon should have already evolved off of the asymptotic giant branch. Recently, however, there have been serendipitous discoveries of these types of stars. Matsunaga et al. (2006) discovered a Mira variable in the globular cluster Lynga 7. It was later confirmed by Feast et al. (2012) that the star is a member of the cluster and must be a product of a stellar merger. In the same year, Sharina et al. (2012) discovered a carbon star in the low metallicity globular cluster NGC6426 and reports it to be a CH star. Five more of these types of stars have been made as serendipitous discoveries and have been reported by Harding (1962), Dickens (1972), Cote et al. (1997), and Van Loon (2007). The abundance of these types of carbon stars in Milky Way globular clusters has been unknown because the discovery of these types of objects has only ever been a serendipitous discovery. These stars could have been easily overlooked in the past as they are outside the typical parameter space of galactic globular clusters. Also advances in near-infrared instruments and observing techniques have made it possible to detect the fainter carbon stars in binary systems. Having an understanding of the abundances of carbon stars in galactic globular clusters will aid in the modeling of globular cluster and galaxy formation leading to a better understanding of these processes. To get an understanding of the abundances of these stars we conducted the first comprehensive search for AGB carbon stars into all Milky Way globular clusters listed in the Harris Catalog (expect for Pyxis). I have found 128 carbon star candidates using methods of comparing color magnitude diagrams of the clusters with the carbon

  14. STELLAR ENCOUNTER RATE IN GALACTIC GLOBULAR CLUSTERS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bahramian, Arash; Heinke, Craig O.; Sivakoff, Gregory R.

    2013-04-01

    The high stellar densities in the cores of globular clusters cause significant stellar interactions. These stellar interactions can produce close binary mass-transferring systems involving compact objects and their progeny, such as X-ray binaries and radio millisecond pulsars. Comparing the numbers of these systems and interaction rates in different clusters drives our understanding of how cluster parameters affect the production of close binaries. In this paper we estimate stellar encounter rates ({Gamma}) for 124 Galactic globular clusters based on observational data as opposed to the methods previously employed, which assumed 'King-model' profiles for all clusters. By deprojecting cluster surface brightness profilesmore » to estimate luminosity density profiles, we treat 'King-model' and 'core-collapsed' clusters in the same way. In addition, we use Monte Carlo simulations to investigate the effects of uncertainties in various observational parameters (distance, reddening, surface brightness) on {Gamma}, producing the first catalog of globular cluster stellar encounter rates with estimated errors. Comparing our results with published observations of likely products of stellar interactions (numbers of X-ray binaries, numbers of radio millisecond pulsars, and {gamma}-ray luminosity) we find both clear correlations and some differences with published results.« less

  15. C1QTNF1 attenuates angiotensin II-induced cardiac hypertrophy via activation of the AMPKa pathway.

    PubMed

    Wu, Leiming; Gao, Lu; Zhang, Dianhong; Yao, Rui; Huang, Zhen; Du, Binbin; Wang, Zheng; Xiao, Lili; Li, Pengcheng; Li, Yapeng; Liang, Cui; Zhang, Yanzhou

    2018-06-01

    Complement C1q tumor necrosis factor related proteins (C1QTNFs) have been reported to have diverse biological influence on the cardiovascular system. C1QTNF1 is a member of the CTRP superfamily. C1QTNF1 is expressed in the myocardium; however, its function in myocytes has not yet been investigated. To systematically investigate the roles of C1QTNF1 in angiotensin II (Ang II)-induced cardiac hypertrophy. C1QTNF1 knock-out mice were used with the aim of determining the role of C1QTNF1 in cardiac hypertrophy in the adult heart. Data from experiments showed that C1QTNF1 was up-regulated during cardiac hypertrophic processes, which were triggered by increased reactive oxygen species. C1QTNF1 deficiency accelerated cardiac hypertrophy, fibrosis, inflammation responses, and oxidative stress with deteriorating cardiac dysfunction in the Ang II-induced cardiac hypertrophy mouse model. We identified C1QTNF1 as a negative regulator of cardiomyocyte hypertrophy in Ang II-stimulated neonatal rat cardiomyocytes using the recombinant human globular domain of C1QTNF1 and C1QTNF1 siRNA. Injection of the recombinant human globular domain of C1QTNF1 also suppressed the Ang II-induced cardiac hypertrophic response in vivo. The anti-hypertrophic effects of C1QTNF1 rely on AMPKa activation, which inhibits mTOR P70S6K phosphorylation. An AMPKa inhibitor abrogated the anti-hypertrophic effects of the recombinant human globular domain of C1QTNF1 both in vivo and vitro. Moreover, C1QTNF1-mediated AMPKa activation was triggered by the inhibition of PDE1-4, which subsequently activated the cAMP/PKA/LKB1 pathway. Our results demonstrated that C1QTNF1 improves cardiac function and inhibits cardiac hypertrophy and fibrosis by increasing and activating AMPKa, suggesting that C1QTNF1 could be a therapeutic target for cardiac hypertrophy and heart failure. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Oral vaccine of Lactococcus lactis harbouring pandemic H1N1 2009 haemagglutinin1 and nisP anchor fusion protein elevates anti-HA1 sIgA levels in mice.

    PubMed

    Joan, Stella Siaw Xiu; Pui-Fong, Jee; Song, Adelene Ai-Lian; Chang, Li-Yen; Yusoff, Khatijah; AbuBakar, Sazaly; Rahim, Raha Abdul

    2016-05-01

    An oral lactococcal-based vaccine which haboured the haemagglutinin1 (HA1) antigen fused to nisP anchor protein for the purpose of surface displaying the HA1 antigen was developed against H1N1 virus. Recombinant L. lactis strains expressed HA1-nisP fusion proteins when induced with nisin, as confirmed through western blotting. However, immunofluorescense did not detect any surface-displayed proteins, suggesting that the protein was either unsuccessfully translocated or improperly displayed. Despite this, oral administration of recombinant L. lactis strains to BALB/c mice revealed that significant levels of anti-HA1 sIgA antibodies were detected in mice fecal suspension samples of mice group NZ9000 (pNZ:HN) when compared to the negative control NZ9000 (pNZ8048) group. Specific anti-HA1 sIgA antibodies were locally produced and live recombinant lactococcal vaccine was able to elicit humoral response of BALB/c mice despite unsuccessful surface display of the HA1 epitope.

  17. AmeriFlux US-Ha1 Harvard Forest EMS Tower (HFR1)

    DOE Data Explorer

    Munger, J. William [Harvard University

    2016-01-01

    This is the AmeriFlux version of the carbon flux data for the site US-Ha1 Harvard Forest EMS Tower (HFR1). Site Description - The Harvard Forest tower is on land owned by Harvard University. The site is designated as an LTER site. Most of the surrounding area was cleared for agrigulture during European settlement in 1600-1700. The site has been regrowing since before 1900 (based on tree ring chronologies) and is now predominantly red oak and red maple, with patches of mature hemlock stand and individual white pine. Overstory trees were uprooted by hurricane in 1938. Climate measurements have been made at Harvard Forest since 1964.

  18. Globular Head-Displayed Conserved Influenza H1 Hemagglutinin Stalk Epitopes Confer Protection against Heterologous H1N1 Virus.

    PubMed

    Klausberger, Miriam; Tscheliessnig, Rupert; Neff, Silke; Nachbagauer, Raffael; Wohlbold, Teddy John; Wilde, Monika; Palmberger, Dieter; Krammer, Florian; Jungbauer, Alois; Grabherr, Reingard

    2016-01-01

    Significant genetic variability in the head region of the influenza A hemagglutinin, the main target of current vaccines, makes it challenging to develop a long-lived seasonal influenza prophylaxis. Vaccines based on the conserved hemagglutinin stalk domain might provide broader cross-reactive immunity. However, this region of the hemagglutinin is immunosubdominant to the head region. Peptide-based vaccines have gained much interest as they allow the immune system to focus on relevant but less immunogenic epitopes. We developed a novel influenza A hemagglutinin-based display platform for H1 hemagglutinin stalk peptides that we identified in an epitope mapping assay using human immune sera and synthetic HA peptides. Flow cytometry and competition assays suggest that the identified stalk sequences do not recapitulate the epitopes of already described broadly neutralizing stalk antibodies. Vaccine constructs displaying 25-mer stalk sequences provided up to 75% protection from lethal heterologous virus challenge in BALB/c mice and induced antibody responses against the H1 hemagglutinin. The developed platform based on a vaccine antigen has the potential to be either used as stand-alone or as prime-vaccine in combination with conventional seasonal or pandemic vaccines for the amplification of stalk-based cross-reactive immunity in humans or as platform to evaluate the relevance of viral peptides/epitopes for protection against influenza virus infection.

  19. The ACS Survey of Galactic Globular Clusters. VIII. Effects of Environment on Globular Cluster Global Mass Functions

    NASA Astrophysics Data System (ADS)

    Paust, Nathaniel E. Q.; Reid, I. Neill; Piotto, Giampaolo; Aparicio, Antonio; Anderson, Jay; Sarajedini, Ata; Bedin, Luigi R.; Chaboyer, Brian; Dotter, Aaron; Hempel, Maren; Majewski, Steven; Marín-Franch, A.; Milone, Antonino; Rosenberg, Alfred; Siegel, Michael

    2010-02-01

    We have used observations obtained as part of the Hubble Space Telescope/ACS Survey of Galactic Globular Clusters to construct global present-day mass functions for 17 globular clusters utilizing multi-mass King models to extrapolate from our observations to the global cluster behavior. The global present-day mass functions for these clusters are well matched by power laws from the turnoff, ≈0.8 M sun, to 0.2-0.3 M sun on the lower main sequence. The slopes of those power-law fits, α, have been correlated with an extensive set of intrinsic and extrinsic cluster properties to investigate which parameters may influence the form of the present-day mass function. We do not confirm previous suggestions of correlations between α and either metallicity or Galactic location. However, we do find a strong statistical correlation with the related parameters central surface brightness, μ V , and inferred central density, ρ0. The correlation is such that clusters with denser cores (stronger binding energy) tend to have steeper mass functions (a higher proportion of low-mass stars), suggesting that dynamical evolution due to external interactions may have played a key role in determining α. Thus, the present-day mass function may owe more to nurture than to nature. Detailed modeling of external dynamical effects is therefore a requisite for determining the initial mass function for Galactic globular clusters.

  20. Sistemas de cúmulos globulares extragalácticos

    NASA Astrophysics Data System (ADS)

    Forte, J. C.

    Se describen las características de los sistemas de cúmulos globulares asociados a galaxias elípticas en una variedad de medios y, en particular, aquellas vinculadas con la distribución espacial, frecuencia específica y composición química. Esta discusión se hace dentro de un conjunto de esquemas orientados a explicar las primeras fases de la formación de las galaxias dominantes en cúmulos y del rol de los sistemas de cúmulos globulares en esos procesos.

  1. Edades relativas de cúmulos globulares

    NASA Astrophysics Data System (ADS)

    Miller Bertolami, M.; Forte, J. C.

    El trabajo de Rossemberg et al (1999), estudia las edades relativas de cúmulos globulares galácticos mediante el análisis de ciertos parámetros morfológicos de los diagramas color-magnitud de dichos cúmulos. Este trabajo se centra en tres puntos: analizar la consistencia de los resultados obtenidos por Rossemberg et al (1999) al emplear observaciones en el sistema fotométrico de Washington, más precisamente, las magnitudes C y T1 en lugar de las magnitudes V e I utilizadas por dichos autores. De la existencia de colores integrados, metalicidad y edad (relativa) para 21 de los cúmulos utilizados en dicho trabajo, se analiza la consistencia de estos resultados con las dependencias de color integrado como función de la edad y la metalicidad que se desprenden de los modelos teóricos de luz integrada por Worthey (1994), Schulz (2002) y Lee et al (2002). Por último se lleva a cabo una breve comparación de la morfología de los diagramas color-magnitud de los cúmulos globulares y de las isocronas utilizadas, a fin de intentar identificar algunas de las posibles causas de las diferencias observadas en los incisos anteriores.

  2. Hypothesized kinetic models for describing the growth of globular and encrusting demosponges.

    PubMed

    Sipkema, Detmer; Yosef, Nejla A M; Adamczewski, Marcin; Osinga, Ronald; Mendola, Dominick; Tramper, Johannes; Wijffels, René H

    2006-01-01

    The marine sponges Dysidea avara and Chondrosia reniformis (globular forms) were cultured in the laboratory on a diet of viable Phaeodactylum tricornutum cells and dissolved nutrients (algae and fish powders). Our growth data were combined with literature data for Pseudosuberites andrewsi (a globular sponge) and for the encrusting sponges Oscarella lobularis, Hemimycale columella, and Crambe crambe. The suitability of three growth models-linear, exponential, and radial accretive-for describing the growth of globular and encrusting sponges was assessed. Radial accretive growth was determined to be the best model to describe growth of both encrusting and globular sponges. Average growth rates of 0.051+/-0.016 and 0.019+/-0.003 mm/day (calculated as the increase of the radius of the sponge per day) were obtained experimentally for D. avara and C. reniformis, respectively.

  3. Predictions of a population of cataclysmic variables in globular clusters

    NASA Technical Reports Server (NTRS)

    Di Stefano, R.; Rappaport, S.

    1994-01-01

    We have studied the number of cataclysmic variables (CVs) that should be active in globular clusters during the present epoch as a result of binary formation via two-body tidal capture. We predict the orbital period and luminosity distributions of CVs in globular clusters. The results arebased on Monte Carlo simulations combined with evolution calculations appropriate to each system formed during the lifetime of two specific globular clusters, omega Cen and 47 Tuc. From our study of these two clusters, which represent the range of core densities and states of mass segregation that are likely to be interesting, we extrapolate our results to the Galactic globlular cluster system. Although there is at present little direct observational evidence of CVs in globular clusters, we find that there should be a large number of active systems. We predict that there should be more than approximately 100 CVs in both 47 Tuc and omega Cen and several thousand in the Galactic globular cluster system. These numbers are based on two-body processes alone and represent a lower bound on the number of systems that may have been formed as a result of stellar interaction within globular clusters. The relation between these calculations and the paucity of optically detected CVs in globular clusters is discussed. Should future observations fail to find convincing evidence of a substantial population of cluster CVs, then the two-body tidal capture scenario is likely to be seriously constrained. Of the CVs we espect in 47 Tuc and omega Cen, approximately 45 and 20, respectively, should have accretion luminosities above 10(exp 33) ergs/s. If one utilizes a relation for converting accretion luminosity to hard X-ray luminosity that is based on observations of Galactic plane CVs, even these sources will not exhibit X-ray luminosities above 10(exp 33) ergs/s. While we cannot account directly for the most luminous subset of the low-luminosity globular cluster X-ray sources without assuming an

  4. Lithium-rich Giants in Globular Clusters

    NASA Astrophysics Data System (ADS)

    Kirby, Evan N.; Guhathakurta, Puragra; Zhang, Andrew J.; Hong, Jerry; Guo, Michelle; Guo, Rachel; Cohen, Judith G.; Cunha, Katia

    2016-03-01

    Although red giants deplete lithium on their surfaces, some giants are Li-rich. Intermediate-mass asymptotic giant branch (AGB) stars can generate Li through the Cameron-Fowler conveyor, but the existence of Li-rich, low-mass red giant branch (RGB) stars is puzzling. Globular clusters are the best sites to examine this phenomenon because it is straightforward to determine membership in the cluster and to identify the evolutionary state of each star. In 72 hours of Keck/DEIMOS exposures in 25 clusters, we found four Li-rich RGB and two Li-rich AGB stars. There were 1696 RGB and 125 AGB stars with measurements or upper limits consistent with normal abundances of Li. Hence, the frequency of Li-richness in globular clusters is (0.2 ± 0.1)% for the RGB, (1.6 ± 1.1)% for the AGB, and (0.3 ± 0.1)% for all giants. Because the Li-rich RGB stars are on the lower RGB, Li self-generation mechanisms proposed to occur at the luminosity function bump or He core flash cannot explain these four lower RGB stars. We propose the following origin for Li enrichment: (1) All luminous giants experience a brief phase of Li enrichment at the He core flash. (2) All post-RGB stars with binary companions on the lower RGB will engage in mass transfer. This scenario predicts that 0.1% of lower RGB stars will appear Li-rich due to mass transfer from a recently Li-enhanced companion. This frequency is at the lower end of our confidence interval. The data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

  5. Predictions of Gamma-ray Emission from Globular Cluster Millisecond Pulsars Above 100 MeV

    NASA Technical Reports Server (NTRS)

    Venter, C.; de Jaker, O.C.; Clapson, A.C.

    2009-01-01

    The recent Fermi detection of the globular cluster (GC) 47 Tucanae highlighted the importance of modeling collective gamma-ray emission of millisecond pulsars (MSPs) in GCs. Steady flux from such populations is also expected in the very high energy (VHE) domain covered by ground-based Cherenkov telescopes. We present pulsed curvature radiation (CR) as well as unpulsed inverse Compton (IC) calculations for an ensemble of MSPs in the GCs 47 Tucanae and Terzan 5. We demonstrate that the CR from these GCs should be easily detectable for Fermi, while constraints on the total number of MSps and the nebular B-field may be derived using the IC flux components.

  6. High resolution infrared spectra of Bulge Globular Clusters: Liller 1, NGC 6553, and Ter 5

    NASA Astrophysics Data System (ADS)

    Origlia, L.; Rich, R. M.; Castro, S. M.

    2001-12-01

    Using the NIRSPEC spectrograph at Keck II, we have obtained echelle spectra covering the range 1.5-1.8μ m for 2 of the brightest giants in Liller 1 and NGC 6553, old metal rich globular clusters in the Galactic bulge. We also report a preliminary analysis for two giants in the obscured bulge globular cluster Ter 5. We use spectrum synthesis for the abundance analysis, and find [Fe/H]=-0.3+/-0.2 and [O/H]=+0.3+/- 0.1 (from the OH lines) for the giants in Liller 1 and NGC 6553. We measure strong lines for the alpha elements Mg, Ca, and Si, but the lower sensitivity of these lines to abundance permits us to only state a general [α /Fe]=+0.3+/-0.2 dex. The composition of the clusters is similar to that of field stars in the bulge and is consistent with a scenario in which the clusters formed early, with rapid enrichment. Our iron abundance for NGC 6553 is poorly consistent with either the low or the high values recently reported in the literature, unless unusally large, or no α -element enhancements are adopted, respectively. We will also present an abundance analsyis for 2 giants in the highly reddened bulge cluster Ter 5, which appears to be near the Solar metallicity. R. Michael Rich acknowledges finacial support from grant AST-0098739, from the National Science Foundation. Data presented herein were obtained at the W.M.Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation. The authors gratefully acknowledge those of Hawaiian ancestry on whose sacred mountain we are privileged to be guests. Without their generous hospitality, none of the observations presented would have been possible.

  7. The missing bulge globular clusters in M31 - New optical candidates

    NASA Technical Reports Server (NTRS)

    Wirth, A.; Smarr, L. L.; Bruno, T. L.

    1985-01-01

    A new method to attack the question of the 'missing' globular clusters in the bulge of M31 is used. Image-processing techniques were used on 13 videocamera fields to obtain an accurate photometric census of stellar objects in M31's bulge down to a limiting B magnitude of 21. This luminosity distribution is compared with the Bahcall-Soneira model of galactic foreground stars. A statistically significant excess of bright images in the luminosity range of globular clusters at M31's distance is found. If the optical candidates considered prove to be globular clusters, they would double the number of known globular clusters in the surveyed region. The colors of a subsample of the candidates are the same as those of the known globular clusters. It is concluded that the previously observed flattening away from a de Vaucouleurs law in the radial distribution of M31 may be an observational selection effect. As an offshoot of this analysis, no evidence is found for very luminous stars in the inner bulge of M31. The lack of such stars indicates that there has not been active star formation (with a normal IMF) in the recent past. Coupled with the existence of many planetary nebulae in the bulge, this may strengthen the case for a galactic wind in M31's bulge.

  8. MiR-30e suppresses proliferation of hepatoma cells via targeting prolyl 4-hydroxylase subunit alpha-1 (P4HA1) mRNA

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Feng, Guoxing; Shi, Hui; Li, Jiong

    Aberrant microRNA expression has been shown to be characteristic of many cancers. It has been reported that the expression levels of miR-30e are decreased in liver cancer tissues. However, the role of miR-30e in hepatocellular carcinoma remains poorly understood. In the present study, we investigated the significance of miR-30e in hepatocarcinogenesis. Bioinformatics analysis reveals a putative target site of miR-30e in the 3′-untranslated region (3′UTR) of prolyl 4-hydroxylase subunit alpha-1 (P4HA1) mRNA. Moreover, luciferase reporter gene assays verified that miR-30e directly targeted 3′UTR of P4HA1 mRNA. Then, we demonstrated that miR-30e was able to reduce the expression of P4HA1 atmore » the levels of mRNA and protein using reverse transcription-polymerase chain reaction and Western blot analysis. Enforced expression of miR-30e suppressed proliferation of HepG2 cells by 5-ethynyl-2-deoxyuridine (EdU) assay and reduced colony formation of these cells by colony formation analysis. Conversely, anti-miR-30e enhanced the proliferation of hepatoma cells in vitro. Interestingly, the ectopic expression of P4HA1 could efficiently rescue the inhibition of cell proliferation mediated by miR-30e in HepG2 cells. Meanwhile, silencing of P4HA1 abolished the anti-miR-30e-induced proliferation of cells. Clinically, quantitative real-time PCR showed that miR-30e was down-regulated in liver tumor tissues relative to their peritumor tissues. The expression levels of miR-30e were negatively correlated to those of P4HA1 mRNA in clinical liver tumor tissues. Thus, we conclude that miR-30e suppresses proliferation of hepatoma cells through targeting P4HA1 mRNA. Our finding provides new insights into the mechanism of hepatocarcinogenesis. - Highlights: • P4HA1 is a novel target gene of miR-30e. • P4HA1 is increased in clinical HCC tissues. • MiR-30e is negatively correlated with P4HA1 in clinical HCC tissues. • MiR-30e suppresses the proliferation of HCC cells

  9. In vitro testing of calcium phosphate (HA, TCP, and biphasic HA-TCP) whiskers.

    PubMed

    Jalota, Sahil; Bhaduri, Sarit B; Tas, A Cuneyt

    2006-09-01

    Calcium phosphate [single-phase hydroxyapatite (HA, Ca(10)(PO(4))(6)(OH)(2)), single-phase tricalcium phosphate (beta-TCP, Ca(3)(PO(4))(2)), and biphasic HA-TCP] whiskers were formed by using a novel microwave-assisted molten salt mediated process. Aqueous solutions containing NaNO(3), HNO(3), Ca(NO(3))(2) x 4H(2)O, and KH(2)PO(4) (with or without urea) were used as starting reagents. These solutions were irradiated in a household microwave oven for 5 min. As-recovered precursors were then simply stirred in water at room temperature for 1 h to obtain the whiskers of the desired calcium phosphate (CaP) bioceramics. These whiskers were evaluated, respectively, in vitro by (1) soaking those in synthetic body fluid (SBF) solutions at 37 degrees C for one week, and (2) performing cell attachment and total protein assay tests on the neat whiskers by using a mouse osteoblast cell line (7F2). beta-TCP, HA, and HA-TCP biphasic whiskers were all found to possess apatite-inducing ability when soaked in SBF. SBF-soaked whiskers were found to have BET surface areas ranging from 45 to 112 m(2)/g. Although the osteoblast viability and protein concentrations were found to be the highest on the neat HA whiskers, cells were attached and proliferated on all the whiskers.

  10. A CN Band Survey of Red Giants in the Globular Cluster M53

    NASA Astrophysics Data System (ADS)

    Martell, S. L.; Smith, G. H.

    2004-12-01

    We investigate the star-to-star variations in λ 3883 CN bandstrength among red giant stars in the low-metallicity globular cluster M53 ([Fe/H] = --2.0). Our data were taken with the Kast spectrograph on the 3-meter Shane telescope at Lick Observatory in April 2001. Star-to-star variations in CN bandstrength are common in intermediate- and high-metallicity globular clusters ([Fe/H] ≥ --1.6). Our data were obtained to test whether that variation will also be present in a low-metallicity globular cluster, or whether it will be suppressed by the overall lack of metals in the stars. Our preliminary result is that the λ 3883 CN band is weak in our program stars, which span the brightest magnitude of the red giant branch. On visual inspection, the M53 giants appear to be similar in their CN bandstrength to the four CN-weak giants in NGC 6752 whose average spectrum is plotted in Fig. 4 of Norris et al. (1981, ApJ, 244, 205). This work is planned to form part of a larger study of the metallicity dependence of CN bandstrength and carbon abundance behavior on the upper giant branch of globular clusters. This work is supported by NSF grant AST 00-98453 and by an award from the ARCS foundation, Northern California Chapter.

  11. Low-luminosity stellar mass functions in globular clusters

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Richer, H.B.; Fahlman, G.G.; Buonanno, R.

    New data are presented on cluster luminosity functions and mass functions for selected fields in the globular clusters M13 and M71, extending down the main sequence to at least 0.2 solar mass. In this experiment, CCD photometry data were obtained at the prime focus of the CFHT on the cluster fields that were far from the cluster center. Luminosity functions were constructed, using the ADDSTAR routine to correct for the background, and mass functions were derived using the available models. The mass functions obtained for M13 and M71 were compared to existing data for NGC 6397. Results show that (1)more » all three globular clusters display a marked change in slope at about 0.4 solar mass, with the slopes becoming considerably steeper toward lower masses; (2) there is no correlation between the slope of the mass function and metallicity; and (3) the low-mass slope of the mass function for M13 is much steeper than for NGC 6397 and M71. 22 refs.« less

  12. Bayesian Analysis and Characterization of Multiple Populations in Galactic Globular Clusters

    NASA Astrophysics Data System (ADS)

    Wagner-Kaiser, Rachel A.; Stenning, David; Sarajedini, Ata; von Hippel, Ted; van Dyk, David A.; Robinson, Elliot; Stein, Nathan; Jefferys, William H.; BASE-9, HST UVIS Globular Cluster Treasury Program

    2017-01-01

    Globular clusters have long been important tools to unlock the early history of galaxies. Thus, it is crucial we understand the formation and characteristics of the globular clusters (GCs) themselves. Historically, GCs were thought to be simple and largely homogeneous populations, formed via collapse of a single molecular cloud. However, this classical view has been overwhelmingly invalidated by recent work. It is now clear that the vast majority of globular clusters in our Galaxy host two or more chemically distinct populations of stars, with variations in helium and light elements at discrete abundance levels. No coherent story has arisen that is able to fully explain the formation of multiple populations in globular clusters nor the mechanisms that drive stochastic variations from cluster to cluster.We use Cycle 21 Hubble Space Telescope (HST) observations and HST archival ACS Treasury observations of 30 Galactic Globular Clusters to characterize two distinct stellar populations. A sophisticated Bayesian technique is employed to simultaneously sample the joint posterior distribution of age, distance, and extinction for each cluster, as well as unique helium values for two populations within each cluster and the relative proportion of those populations. We find the helium differences among the two populations in the clusters fall in the range of 0.04 to 0.11. Because adequate models varying in CNO are not presently available, we view these spreads as upper limits and present them with statistical rather than observational uncertainties. Evidence supports previous studies suggesting an increase in helium content concurrent with increasing mass of the cluster. We also find that the proportion of the first population of stars increases with mass. Our results are examined in the context of proposed globular cluster formation scenarios.

  13. Structural insights into the histone H1-nucleosome complex

    PubMed Central

    Zhou, Bing-Rui; Feng, Hanqiao; Kato, Hidenori; Dai, Liang; Yang, Yuedong; Zhou, Yaoqi; Bai, Yawen

    2013-01-01

    Linker H1 histones facilitate formation of higher-order chromatin structures and play important roles in various cell functions. Despite several decades of effort, the structural basis of how H1 interacts with the nucleosome remains elusive. Here, we investigated Drosophila H1 in complex with the nucleosome, using solution nuclear magnetic resonance spectroscopy and other biophysical methods. We found that the globular domain of H1 bridges the nucleosome core and one 10-base pair linker DNA asymmetrically, with its α3 helix facing the nucleosomal DNA near the dyad axis. Two short regions in the C-terminal tail of H1 and the C-terminal tail of one of the two H2A histones are also involved in the formation of the H1–nucleosome complex. Our results lead to a residue-specific structural model for the globular domain of the Drosophila H1 in complex with the nucleosome, which is different from all previous experiment-based models and has implications for chromatin dynamics in vivo. PMID:24218562

  14. The gamma-ray pulsar population of globular clusters: implications for the GeV excess

    NASA Astrophysics Data System (ADS)

    Hooper, Dan; Linden, Tim

    2016-08-01

    It has been suggested that the GeV excess, observed from the region surrounding the Galactic Center, might originate from a population of millisecond pulsars that formed in globular clusters. With this in mind, we employ the publicly available Fermi data to study the gamma-ray emission from 157 globular clusters, identifying a statistically significant signal from 25 of these sources (ten of which are not found in existing gamma-ray catalogs). We combine these observations with the predicted pulsar formation rate based on the stellar encounter rate of each globular cluster to constrain the gamma-ray luminosity function of millisecond pulsars in the Milky Way's globular cluster system. We find that this pulsar population exhibits a luminosity function that is quite similar to those millisecond pulsars observed in the field of the Milky Way (i.e. the thick disk). After pulsars are expelled from a globular cluster, however, they continue to lose rotational kinetic energy and become less luminous, causing their luminosity function to depart from the steady-state distribution. Using this luminosity function and a model for the globular cluster disruption rate, we show that millisecond pulsars born in globular clusters can account for only a few percent or less of the observed GeV excess. Among other challenges, scenarios in which the entire GeV excess is generated from such pulsars are in conflict with the observed mass of the Milky Way's Central Stellar Cluster.

  15. The gamma-ray pulsar population of globular clusters: implications for the GeV excess

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hooper, Dan; Linden, Tim, E-mail: dhooper@fnal.gov, E-mail: linden.70@osu.edu

    It has been suggested that the GeV excess, observed from the region surrounding the Galactic Center, might originate from a population of millisecond pulsars that formed in globular clusters. With this in mind, we employ the publicly available Fermi data to study the gamma-ray emission from 157 globular clusters, identifying a statistically significant signal from 25 of these sources (ten of which are not found in existing gamma-ray catalogs). We combine these observations with the predicted pulsar formation rate based on the stellar encounter rate of each globular cluster to constrain the gamma-ray luminosity function of millisecond pulsars in themore » Milky Way's globular cluster system. We find that this pulsar population exhibits a luminosity function that is quite similar to those millisecond pulsars observed in the field of the Milky Way (i.e. the thick disk). After pulsars are expelled from a globular cluster, however, they continue to lose rotational kinetic energy and become less luminous, causing their luminosity function to depart from the steady-state distribution. Using this luminosity function and a model for the globular cluster disruption rate, we show that millisecond pulsars born in globular clusters can account for only a few percent or less of the observed GeV excess. Among other challenges, scenarios in which the entire GeV excess is generated from such pulsars are in conflict with the observed mass of the Milky Way's Central Stellar Cluster.« less

  16. The gamma-ray pulsar population of globular clusters: Implications for the GeV excess

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hooper, Dan; Linden, Tim

    In this study, it has been suggested that the GeV excess, observed from the region surrounding the Galactic Center, might originate from a population of millisecond pulsars that formed in globular clusters. With this in mind, we employ the publicly available Fermi data to study the gamma-ray emission from 157 globular clusters, identifying a statistically significant signal from 25 of these sources (ten of which are not found in existing gamma-ray catalogs). We combine these observations with the predicted pulsar formation rate based on the stellar encounter rate of each globular cluster to constrain the gamma-ray luminosity function of millisecondmore » pulsars in the Milky Way's globular cluster system. We find that this pulsar population exhibits a luminosity function that is quite similar to those millisecond pulsars observed in the field of the Milky Way (i.e. the thick disk). After pulsars are expelled from a globular cluster, however, they continue to lose rotational kinetic energy and become less luminous, causing their luminosity function to depart from the steady-state distribution. Using this luminosity function and a model for the globular cluster disruption rate, we show that millisecond pulsars born in globular clusters can account for only a few percent or less of the observed GeV excess. Among other challenges, scenarios in which the entire GeV excess is generated from such pulsars are in conflict with the observed mass of the Milky Way's Central Stellar Cluster.« less

  17. The gamma-ray pulsar population of globular clusters: Implications for the GeV excess

    DOE PAGES

    Hooper, Dan; Linden, Tim

    2016-08-09

    In this study, it has been suggested that the GeV excess, observed from the region surrounding the Galactic Center, might originate from a population of millisecond pulsars that formed in globular clusters. With this in mind, we employ the publicly available Fermi data to study the gamma-ray emission from 157 globular clusters, identifying a statistically significant signal from 25 of these sources (ten of which are not found in existing gamma-ray catalogs). We combine these observations with the predicted pulsar formation rate based on the stellar encounter rate of each globular cluster to constrain the gamma-ray luminosity function of millisecondmore » pulsars in the Milky Way's globular cluster system. We find that this pulsar population exhibits a luminosity function that is quite similar to those millisecond pulsars observed in the field of the Milky Way (i.e. the thick disk). After pulsars are expelled from a globular cluster, however, they continue to lose rotational kinetic energy and become less luminous, causing their luminosity function to depart from the steady-state distribution. Using this luminosity function and a model for the globular cluster disruption rate, we show that millisecond pulsars born in globular clusters can account for only a few percent or less of the observed GeV excess. Among other challenges, scenarios in which the entire GeV excess is generated from such pulsars are in conflict with the observed mass of the Milky Way's Central Stellar Cluster.« less

  18. A Science Portal and Archive for Extragalactic Globular Cluster Systems Data

    NASA Astrophysics Data System (ADS)

    Young, Michael; Rhode, Katherine L.; Gopu, Arvind

    2015-01-01

    For several years we have been carrying out a wide-field imaging survey of the globular cluster populations of a sample of giant spiral, S0, and elliptical galaxies with distances of ~10-30 Mpc. We use mosaic CCD cameras on the WIYN 3.5-m and Kitt Peak 4-m telescopes to acquire deep BVR imaging of each galaxy and then analyze the data to derive global properties of the globular cluster system. In addition to measuring the total numbers, specific frequencies, spatial distributions, and color distributions for the globular cluster populations, we have produced deep, high-quality images and lists of tens to thousands of globular cluster candidates for the ~40 galaxies included in the survey.With the survey nearing completion, we have been exploring how to efficiently disseminate not only the overall results, but also all of the relevant data products, to the astronomical community. Here we present our solution: a scientific portal and archive for extragalactic globular cluster systems data. With a modern and intuitive web interface built on the same framework as the WIYN One Degree Imager Portal, Pipeline, and Archive (ODI-PPA), our system will provide public access to the survey results and the final stacked mosaic images of the target galaxies. In addition, the astrometric and photometric data for thousands of identified globular cluster candidates, as well as for all point sources detected in each field, will be indexed and searchable. Where available, spectroscopic follow-up data will be paired with the candidates. Advanced imaging tools will enable users to overlay the cluster candidates and other sources on the mosaic images within the web interface, while metadata charting tools will allow users to rapidly and seamlessly plot the survey results for each galaxy and the data for hundreds of thousands of individual sources. Finally, we will appeal to other researchers with similar data products and work toward making our portal a central repository for data

  19. Blue Straggler Stars in the Globular Cluster M53

    NASA Astrophysics Data System (ADS)

    Rey, S. C.; Lee, Young-Wook; Chun, Mun-Suk; Byun, Yong-Ik

    The first large-format CCD color-magnitude diagram (CMD) in the B and V passbands is presented for the Galactic globular cluster M53 (NGC 5024). We have discovered more than 100 new blue straggler (BS) candidates in the field of M53. The analysis of bright BS stars (V < 19.0) clearly shows a bimodal radial distribution, with a high frequency in the inner and outer regions. The distribution is similar to that found in M3, a globular cluster with similar central density and concentration.

  20. Green synthesis of nanosilver particles by Aspergillus terreus HA1N and Penicillium expansum HA2N and its antifungal activity against mycotoxigenic fungi.

    PubMed

    Ammar, H A M; El-Desouky, T A

    2016-07-01

    The aim of this study was to synthesize silver nanoparticles (AgNPs) by an eco-friendly and low-cost method using the fungi Aspergillus terreus HA1N and Penicillium expansum HA2N as an alternative to chemical procedures mostly requiring drastic experimental conditions emitting toxic chemical byproducts. Also, this study has been extended to evaluate the effect of AgNPs on the growth of some mycotoxigenic fungi and ochratoxin A (OTA) produced by Aspergillus ochraceus. The AgNPs have been characterized by UV-Visible Spectrophotometer, Dynamic Light Scattering (DLS), Fourier Transform Infrared Spectroscopy (FTIR) and Transmission Electron Microscope (TEM). The TEM analysis has revealed that the size of AgNPs ranged between 14 and 25 nm in the case of P. expansum and 10-18 nm in the case of A. terreus. The antifungal activity of AgNP colloids has indicated that the highest inhibition zone was detected with AgNPs synthesized by A. terreus HA1N against all tested fungi. The highest inhibition zone was detected with Aspergillus niger at concentrations 3 and 6 μg of AgNP solution (7·56 ± 0·38 and 11·3 ± 1·8 mm, respectively) while, A. ochraceus showed the maximum inhibition zone (16·33 ± 0·96 mm) at the concentration 9 μg of AgNPs synthesized by A. terreus. The results have also indicated that the AgNPs synthesized by A. terreus and P. expansum at the concentration 220 μg/100 ml media gave the highest reduction of OTA, where the percentages of reduction were 58·87 and 52·18% respectively. The smallest size AgNPs synthesized by A. terreus HA1N are better in their antifungal activity against all tested mycotoxigenic fungi than the largest one synthesized by P. expansum HA2N. This is the first study focused on using AgNPs in control of OTA production. © 2016 The Society for Applied Microbiology.

  1. Silencing of HaAce1 gene by host-delivered artificial microRNA disrupts growth and development of Helicoverpa armigera.

    PubMed

    Saini, Ravi Prakash; Raman, Venkat; Dhandapani, Gurusamy; Malhotra, Era Vaidya; Sreevathsa, Rohini; Kumar, Polumetla Ananda; Sharma, Tilak R; Pattanayak, Debasis

    2018-01-01

    The polyphagous insect-pest, Helicoverpa armigera, is a serious threat to a number of economically important crops. Chemical application and/or cultivation of Bt transgenic crops are the two strategies available now for insect-pest management. However, environmental pollution and long-term sustainability are major concerns against these two options. RNAi is now considered as a promising technology to complement Bt to tackle insect-pests menace. In this study, we report host-delivered silencing of HaAce1 gene, encoding the predominant isoform of H. armigera acetylcholinesterase, by an artificial microRNA, HaAce1-amiR1. Arabidopsis pre-miRNA164b was modified by replacing miR164b/miR164b* sequences with HaAce1-amiR1/HaAce1-amiR1* sequences. The recombinant HaAce1-preamiRNA1 was put under the control of CaMV 35S promoter and NOS terminator of plant binary vector pBI121, and the resultant vector cassette was used for tobacco transformation. Two transgenic tobacco lines expressing HaAce1-amiR1 was used for detached leaf insect feeding bioassays. Larval mortality of 25% and adult deformity of 20% were observed in transgenic treated insect group over that control tobacco treated insect group. The reduction in the steady-state level of HaAce1 mRNA was 70-80% in the defective adults compared to control. Our results demonstrate promise for host-delivered amiRNA-mediated silencing of HaAce1 gene for H. armigera management.

  2. Variable Stars in Large Magellanic Cloud Globular Clusters. II. NGC 1786

    NASA Astrophysics Data System (ADS)

    Kuehn, Charles A.; Smith, Horace A.; Catelan, Márcio; Pritzl, Barton J.; De Lee, Nathan; Borissova, Jura

    2012-12-01

    This is the second in a series of papers studying the variable stars in Large Magellanic Cloud globular clusters. The primary goal of this series is to study how RR Lyrae stars in Oosterhoff-intermediate systems compare to their counterparts in Oosterhoff I/II systems. In this paper, we present the results of our new time-series B-V photometric study of the globular cluster NGC 1786. A total of 65 variable stars were identified in our field of view. These variables include 53 RR Lyraes (27 RRab, 18 RRc, and 8 RRd), 3 classical Cepheids, 1 Type II Cepheid, 1 Anomalous Cepheid, 2 eclipsing binaries, 3 Delta Scuti/SX Phoenicis variables, and 2 variables of undetermined type. Photometric parameters for these variables are presented. We present physical properties for some of the RR Lyrae stars, derived from Fourier analysis of their light curves. We discuss several different indicators of Oosterhoff type which indicate that the Oosterhoff classification of NGC 1786 is not as clear cut as what is seen in most globular clusters. Based on observations taken with the SMARTS 1.3 m telescope operated by the SMARTS Consortium and observations taken at the Southern Astrophysical Research (SOAR) telescope, which is a joint project of the Ministério da Ciência, Tecnologia, e Inovação (MCTI) da República Federativa do Brasil, the U.S. National Optical Astronomy Observatory (NOAO), the University of North Carolina at Chapel Hill (UNC), and Michigan State University (MSU).

  3. Internet Protocol Handbook. Volume 4. The Domain Name System (DNS) handbook

    DTIC Science & Technology

    1989-08-01

    Mockapetris [Page 1] 4-11 INTERNET PROTOCOL HA TDBOOK - Voue Four 1989 RFC 1034 Domain Concepts and Facilities November 1987 bandwidth consumed in distributing...Domain Names- Concepts and Facilities KFC 1034 RFC 1034 Domain Concepts and Facilities November 1’)87 - Queries contain a bit called recursion desired...during periodic sweeps to reclaim the memory consumed by old RRS. Mockapetris [Page 33] 4-43 INTERNET PROTOCOL HANDBOOK - Volume Four 1989 RFC 1034

  4. Predicting the helix packing of globular proteins by self-correcting distance geometry.

    PubMed

    Mumenthaler, C; Braun, W

    1995-05-01

    A new self-correcting distance geometry method for predicting the three-dimensional structure of small globular proteins was assessed with a test set of 8 helical proteins. With the knowledge of the amino acid sequence and the helical segments, our completely automated method calculated the correct backbone topology of six proteins. The accuracy of the predicted structures ranged from 2.3 A to 3.1 A for the helical segments compared to the experimentally determined structures. For two proteins, the predicted constraints were not restrictive enough to yield a conclusive prediction. The method can be applied to all small globular proteins, provided the secondary structure is known from NMR analysis or can be predicted with high reliability.

  5. The colour-magnitude relation of globular clusters in Centaurus and Hydra. Constraints on star cluster self-enrichment with a link to massive Milky Way globular clusters

    NASA Astrophysics Data System (ADS)

    Fensch, J.; Mieske, S.; Müller-Seidlitz, J.; Hilker, M.

    2014-07-01

    Aims: We investigate the colour-magnitude relation of metal-poor globular clusters, the so-called blue tilt, in the Hydra and Centaurus galaxy clusters and constrain the primordial conditions for star cluster self-enrichment. Methods: We analyse U,I photometry for about 2500 globular clusters in the central regions of Hydra and Centaurus, based on VLT/FORS1 data. We measure the relation between mean colour and luminosity for the blue and red subpopulation of the globular cluster samples. We convert these relations into mass-metallicity space and compare the obtained GC mass-metallicity relation with predictions from the star cluster self-enrichment model by Bailin & Harris (2009, ApJ, 695, 1082). For this we include effects of dynamical and stellar evolution and a physically well motivated primordial mass-radius scaling. Results: We obtain a mass-metallicity scaling of Z ∝ M0.27 ± 0.05 for Centaurus GCs and Z ∝ M0.40 ± 0.06 for Hydra GCs, consistent with the range of observed relations in other environments. We find that the GC mass-metallicity relation already sets in at present-day masses of a few and is well established in the luminosity range of massive MW clusters like ω Centauri. The inclusion of a primordial mass-radius scaling of star clusters significantly improves the fit of the self-enrichment model to the data. The self-enrichment model accurately reproduces the observed relations for average primordial half-light radii rh ~ 1-1.5 pc, star formation efficiencies f⋆ ~ 0.3-0.4, and pre-enrichment levels of [Fe/H] - 1.7 dex. The slightly steeper blue tilt for Hydra can be explained either by a ~30% smaller average rh at fixed f⋆ ~ 0.3, or analogously by a ~20% smaller f⋆ at fixed rh ~ 1.5 pc. Within the self-enrichment scenario, the observed blue tilt implies a correlation between GC mass and width of the stellar metallicity distribution. We find that this implied correlation matches the trend of width with GC mass measured in Galactic GCs

  6. Two stellar-mass black holes in the globular cluster M22.

    PubMed

    Strader, Jay; Chomiuk, Laura; Maccarone, Thomas J; Miller-Jones, James C A; Seth, Anil C

    2012-10-04

    Hundreds of stellar-mass black holes probably form in a typical globular star cluster, with all but one predicted to be ejected through dynamical interactions. Some observational support for this idea is provided by the lack of X-ray-emitting binary stars comprising one black hole and one other star ('black-hole/X-ray binaries') in Milky Way globular clusters, even though many neutron-star/X-ray binaries are known. Although a few black holes have been seen in globular clusters around other galaxies, the masses of these cannot be determined, and some may be intermediate-mass black holes that form through exotic mechanisms. Here we report the presence of two flat-spectrum radio sources in the Milky Way globular cluster M22, and we argue that these objects are black holes of stellar mass (each ∼10-20 times more massive than the Sun) that are accreting matter. We find a high ratio of radio-to-X-ray flux for these black holes, consistent with the larger predicted masses of black holes in globular clusters compared to those outside. The identification of two black holes in one cluster shows that ejection of black holes is not as efficient as predicted by most models, and we argue that M22 may contain a total population of ∼5-100 black holes. The large core radius of M22 could arise from heating produced by the black holes.

  7. Evolution of redback radio pulsars in globular clusters

    NASA Astrophysics Data System (ADS)

    Benvenuto, O. G.; De Vito, M. A.; Horvath, J. E.

    2017-02-01

    Context. We study the evolution of close binary systems composed of a normal, intermediate mass star and a neutron star considering a chemical composition typical of that present in globular clusters (Z = 0.001). Aims: We look for similarities and differences with respect to solar composition donor stars, which we have extensively studied in the past. As a definite example, we perform an application on one of the redbacks located in a globular cluster. Methods: We performed a detailed grid of models in order to find systems that represent the so-called redback binary radio pulsar systems with donor star masses between 0.6 and 2.0 solar masses and orbital periods in the range 0.2-0.9 d. Results: We find that the evolution of these binary systems is rather similar to those corresponding to solar composition objects, allowing us to account for the occurrence of redbacks in globular clusters, as the main physical ingredient is the irradiation feedback. Redback systems are in the quasi-RLOF state, that is, almost filling their corresponding Roche lobe. During the irradiation cycle the system alternates between semi-detached and detached states. While detached the system appears as a binary millisecond pulsar, called a redback. Circumstellar material, as seen in redbacks, is left behind after the previous semi-detached phase. Conclusions: The evolution of binary radio pulsar systems considering irradiation successfully accounts for, and provides a way for, the occurrence of redback pulsars in low-metallicity environments such as globular clusters. This is the case despite possible effects of the low metal content of the donor star that could drive systems away from redback configuration.

  8. Isolation of avian influenza H5N1 virus from vaccinated commercial layer flock in Egypt

    PubMed Central

    2012-01-01

    Background Uninterrupted transmission of highly pathogenic avian influenza virus (HPAIV) H5N1 of clade 2.2.1 in Egypt since 2006 resulted in establishment of two main genetic clusters. The 2.2.1/C group where all recent human and majority of backyard origin viruses clustered together, meanwhile the majority of viruses derived from vaccinated poultry in commercial farms grouped in 2.2.1.1 clade. Findings In the present investigation, an HPAIV H5N1 was isolated from twenty weeks old layers chickens that were vaccinated with a homologous H5N1 vaccine at 1, 7 and 16 weeks old. At twenty weeks of age, birds showed cyanosis of comb and wattle, decrease in egg production and up to 27% mortality. Examined serum samples showed low antibody titer in HI test (Log2 3.2± 4.2). The hemagglutinin (HA) and neuraminidase (NA) genes of the isolated virus were closely related to viruses in 2.2.1/C group isolated from poultry in live bird market (LBM) and backyards or from infected people. Conspicuous mutations in the HA and NA genes including a deletion within the receptor binding domain in the HA globular head region were observed. Conclusions Despite repeated vaccination of layer chickens using a homologous H5N1 vaccine, infection with HPAIV H5N1 resulted in significant morbidity and mortality. In endemic countries like Egypt, rigorous control measures including enforcement of biosecurity, culling of infected birds and constant update of vaccine virus strains are highly required to prevent circulation of HPAIV H5N1 between backyard birds, commercial poultry, LBM and humans. PMID:23185975

  9. LBT/MODS spectroscopy of globular clusters in the irregular galaxy NGC 4449

    NASA Astrophysics Data System (ADS)

    Annibali, F.; Morandi, E.; Watkins, L. L.; Tosi, M.; Aloisi, A.; Buzzoni, A.; Cusano, F.; Fumana, M.; Marchetti, A.; Mignoli, M.; Mucciarelli, A.; Romano, D.; van der Marel, R. P.

    2018-05-01

    We present intermediate-resolution (R ˜ 1000) spectra in the ˜3500-10 000 Å range of 14 globular clusters in the Magellanic irregular galaxy NGC 4449 acquired with the Multi-Object Double Spectrograph on the Large Binocular Telescope. We derived Lick indices in the optical and the Ca II triplet index in the near-infrared in order to infer the clusters' stellar population properties. The inferred cluster ages are typically older than ˜9 Gyr, although ages are derived with large uncertainties. The clusters exhibit intermediate metallicities, in the range -1.2 ≲ [Fe/H] ≲ -0.7, and typically sub-solar [α/Fe] ratios, with a peak at ˜-0.4. These properties suggest that (i) during the first few Gyr NGC 4449 formed stars slowly and inefficiently, with galactic winds having possibly contributed to the expulsion of the α-elements, and (ii) globular clusters in NGC 4449 formed relatively `late', from a medium already enriched in the products of Type Ia supernovae. The majority of clusters appear also underabundant in CN compared to Milky Way halo globular clusters, perhaps because of the lack of a conspicuous N-enriched, second generation of stars like that observed in Galactic globular clusters. Using the cluster velocities, we infer the dynamical mass of NGC 4449 inside 2.88 kpc to be M(<2.88 kpc) = 3.15^{+3.16}_{-0.75} × 10^9 M_{\\odot }. We also report the serendipitous discovery of a planetary nebula within one of the targeted clusters, a rather rare event.

  10. An AO-assisted Variability Study of Four Globular Clusters

    NASA Astrophysics Data System (ADS)

    Salinas, R.; Contreras Ramos, R.; Strader, J.; Hakala, P.; Catelan, M.; Peacock, M. B.; Simunovic, M.

    2016-09-01

    The image-subtraction technique applied to study variable stars in globular clusters represented a leap in the number of new detections, with the drawback that many of these new light curves could not be transformed to magnitudes due to severe crowding. In this paper, we present observations of four Galactic globular clusters, M 2 (NGC 7089), M 10 (NGC 6254), M 80 (NGC 6093), and NGC 1261, taken with the ground-layer adaptive optics module at the SOAR Telescope, SAM. We show that the higher image quality provided by SAM allows for the calibration of the light curves of the great majority of the variables near the cores of these clusters as well as the detection of new variables, even in clusters where image-subtraction searches were already conducted. We report the discovery of 15 new variables in M 2 (12 RR Lyrae stars and 3 SX Phe stars), 12 new variables in M 10 (11 SX Phe and 1 long-period variable), and 1 new W UMa-type variable in NGC 1261. No new detections are found in M 80, but previous uncertain detections are confirmed and the corresponding light curves are calibrated into magnitudes. Additionally, based on the number of detected variables and new Hubble Space Telescope/UVIS photometry, we revisit a previous suggestion that M 80 may be the globular cluster with the richest population of blue stragglers in our Galaxy. Based on observations obtained at the Southern Astrophysical Research (SOAR) telescope, which is a joint project of the Ministério da Ciência, Tecnologia, e Inovação (MCTI) da República Federativa do Brasil, the U.S. National Optical Astronomy Observatory (NOAO), the University of North Carolina at Chapel Hill (UNC), and Michigan State University (MSU).

  11. Selective observation of the disordered import signal of a globular protein by in-cell NMR: The example of frataxins

    PubMed Central

    Popovic, Matija; Sanfelice, Domenico; Pastore, Chiara; Prischi, Filippo; Temussi, Piero Andrea; Pastore, Annalisa

    2015-01-01

    We have exploited the capability of in-cell NMR to selectively observe flexible regions within folded proteins to carry out a comparative study of two members of the highly conserved frataxin family which are found both in prokaryotes and in eukaryotes. They all contain a globular domain which shares more than 50% identity, which in eukaryotes is preceded by an N-terminal tail containing the mitochondrial import signal. We demonstrate that the NMR spectrum of the bacterial ortholog CyaY cannot be observed in the homologous E. coli system, although it becomes fully observable as soon as the cells are lysed. This behavior has been observed for several other compact globular proteins as seems to be the rule rather than the exception. The NMR spectrum of the yeast ortholog Yfh1 contains instead visible signals from the protein. We demonstrate that they correspond to the flexible N-terminal tail indicating that this is flexible and unfolded. This flexibility of the N-terminus agrees with previous studies of human frataxin, despite the extensive sequence diversity of this region in the two proteins. Interestingly, the residues that we observe in in-cell experiments are not visible in the crystal structure of a Yfh1 mutant designed to destabilize the first helix. More importantly, our results show that, in cell, the protein is predominantly present not as an aggregate but as a monomeric species. PMID:25772583

  12. Effects of Dynamical Evolution on Globular Clusters’ Internal Kinematics

    NASA Astrophysics Data System (ADS)

    Tiongco, Maria; Vesperini, Enrico; Varri, Anna Lisa

    2018-01-01

    The synergy between recent photometric, spectroscopic, and astrometric studies is revealing that globular clusters deviate from the traditional picture of dynamically simple and single stellar population systems. Complex kinematical features such as velocity anisotropy and rotation, and the existence of multiple stellar populations are some of the key observational findings. My thesis work has aimed to build a theoretical framework to interpret these new observational results and to understand their link with a globular cluster’s dynamical history.I have focused on the study of the evolution of globular clusters' internal kinematics, as driven by two-body relaxation, and the interplay between internal angular momentum and the external Galactic tidal field. With a specifically-designed, large survey of direct N-body simulations, I have explored the three-dimensional structure of the velocity space of tidally-perturbed clusters, by characterizing their degree of anisotropy and their rotational properties. These studies have proved that a cluster's kinematical properties contain a distinct imprints of the cluster’s initial structural properties, dynamical history, and tidal environment. By relaxing a number of simplifying assumptions that are traditionally imposed, I have also showed how the interplay between a cluster's internal evolution and the interaction with the host galaxy can produce complex morphological and kinematical properties, such as a counter-rotating core and a twisting of the projected isodensity contours.Building on this fundamental understanding, I have then studied the dynamics of multiple stellar populations in globular clusters, with attention to the largely unexplored role of angular momentum. I have analyzed the evolution of clusters with stellar populations characterized by different initial structural and kinematical properties to determine how long these differences are preserved, and in what cases they could still be observable in

  13. An Archival Search For Young Globular Clusters in Galaxies

    NASA Astrophysics Data System (ADS)

    Whitmore, Brad

    1995-07-01

    One of the most intriguing results from HST has been the discovery of ultraluminous star clusters in interacting and merging galaxies. These clusters have the luminosities, colors, and sizes that would be expected of young globular clusters produced by the interaction. We propose to use the data in the HST Archive to determine how prevalent this phenomena is, and to determine whether similar clusters are produced in other environments. Three samples will be extracted and studied in a systematic and consistent manner: 1} interacting and merging galaxies, 2} starburst galaxies, 3} a control sample of ``normal'' galaxies. A preliminary search of the archives shows that there are at least 20 galaxies in each of these samples, and the number will grow by about 50 observations become available. The data will be used to determine the luminosity function, color histogram , spatial distribution, and structural properties of the clusters using the same techniques employed in our study of NGC 7252 {``Atoms -for-Peace'' galaxy} and NGC 4038/4039 {``The Antennae''}. Our ultimate goals are: 1} to understand how globular clusters form, and 2} to use the clusters as evolutionary tracers to unravel the histories of interacting galaxies.

  14. Reddenings, Metallicities, and Possible Abundance Anomalies in Young Globular Clusters

    NASA Astrophysics Data System (ADS)

    Sarajedini, Ata; Layden, Andrew

    1997-01-01

    We present new photometry in the VI passbands for the ``young'' globular clusters Rup 106, Ter 7, and Arp 2. After formulating the simultaneous reddening and metallicity (SRM) method of Sarajedini (1994) in the BV passbands, we apply it, along with the SRM method in VI, to the red giant branches (RGBs) of these clusters using B-V photometry from the literature and the V-I data presented herein. We find [Fe/H] = -1.90 +/- 0.10, E(B-V) = 0.18 +/- 0.02 for Rup 106, [Fe/H] = -0.82 +/- 0.15, E(B-V) = 0.07 +/- 0.03 for Ter 7, and [Fe/H] = -1.84 +/- 0.09, E(B-V) = 0.10 +/- 0.02 for Arp 2. Furthermore, in light of this new abundance for Ter 7 and recent work on the luminosity of the red horizontal branch, we rederive the age of Ter 7 finding it to be some 6 Gyr younger than 47 Tuc. We show that the SRM method is insensitive to age for clusters with purely red HBs and ages as young as ~ 5 Gyr; for clusters with bluer HBs, the SRM method is only mildly sensitive to age differences between such clusters and the calibrating (standard) clusters. From these metallicity estimates, we conclude that the photometric abundances of the program clusters based on the properties of the RGB are systematically lower (Delta [Fe/H] = 0.1-0.4 dex) than those derived using other indicators, in particular the Ca 2 triplet method. We note that the young globular clusters Pal 12 and possibly IC 4499 also exhibit this behavior. We suggest that this discrepancy is due to systematic differences in the [alpha /Fe] ratios between the young clusters and the ``normal'' Galactic globulars used to calibrate the abundance determination methods. However, we are unable to completely reconcile all the observations of Rup 106 using this approach. Systematic differences in [alpha /Fe] between the young clusters and the rest of the Galactic globulars may indicate differences in their chemical enrichment histories, perhaps due to differing environments at the times of their formation. Interestingly, both Ter 7

  15. Mutations in type 3 reovirus that determine binding to sialic acid are contained in the fibrous tail domain of viral attachment protein sigma1.

    PubMed

    Chappell, J D; Gunn, V L; Wetzel, J D; Baer, G S; Dermody, T S

    1997-03-01

    The reovirus attachment protein, sigma1, determines numerous aspects of reovirus-induced disease, including viral virulence, pathways of spread, and tropism for certain types of cells in the central nervous system. The sigma1 protein projects from the virion surface and consists of two distinct morphologic domains, a virion-distal globular domain known as the head and an elongated fibrous domain, termed the tail, which is anchored into the virion capsid. To better understand structure-function relationships of sigma1 protein, we conducted experiments to identify sequences in sigma1 important for viral binding to sialic acid, a component of the receptor for type 3 reovirus. Three serotype 3 reovirus strains incapable of binding sialylated receptors were adapted to growth in murine erythroleukemia (MEL) cells, in which sialic acid is essential for reovirus infectivity. MEL-adapted (MA) mutant viruses isolated by serial passage in MEL cells acquired the capacity to bind sialic acid-containing receptors and demonstrated a dependence on sialic acid for infection of MEL cells. Analysis of reassortant viruses isolated from crosses of an MA mutant virus and a reovirus strain that does not bind sialic acid indicated that the sigma1 protein is solely responsible for efficient growth of MA mutant viruses in MEL cells. The deduced sigma1 amino acid sequences of the MA mutant viruses revealed that each strain contains a substitution within a short region of sequence in the sigma1 tail predicted to form beta-sheet. These studies identify specific sequences that determine the capacity of reovirus to bind sialylated receptors and suggest a location for a sialic acid-binding domain. Furthermore, the results support a model in which type 3 sigma1 protein contains discrete receptor binding domains, one in the head and another in the tail that binds sialic acid.

  16. Origins of structure in globular proteins.

    PubMed Central

    Chan, H S; Dill, K A

    1990-01-01

    The principal forces of protein folding--hydrophobicity and conformational entropy--are nonspecific. A long-standing puzzle has, therefore, been: What forces drive the formation of the specific internal architectures in globular proteins? We find that any self-avoiding flexible polymer molecule will develop large amounts of secondary structure, helices and parallel and antiparallel sheets, as it is driven to increasing compactness by any force of attraction among the chain monomers. Thus structure formation arises from the severity of steric constraints in compact polymers. This steric principle of organization can account for why short helices are stable in globular proteins, why there are parallel and anti-parallel sheets in proteins, and why weakly unfolded proteins have some secondary structure. On this basis, it should be possible to construct copolymers, not necessarily using amino acids, that can collapse to maximum compactness in incompatible solvents and that should then have structural organization resembling that of proteins. Images PMID:2385597

  17. Betaine protects urea-induced denaturation of myosin subfragment-1.

    PubMed

    Ortiz-Costa, Susana; Sorenson, Martha M; Sola-Penna, Mauro

    2008-07-01

    We have demonstrated previously that urea inhibits the activity and alters the tertiary structure of skeletal muscle myosin in a biphasic manner. This was attributed to differential effects on its globular and filamentous portion. The inhibition of catalytic activity was counteracted by methylamines. With the aim of comprehending the effects of urea on the catalytic (globular) portion of myosin, this study examines the effects of urea and the countereffects of betaine on the catalytic activity and structure of myosin subfragment-1. It is shown that urea inactivates subfragment-1 in parallel with its ability to induce exposure of the enzyme hydrophobic domains, as assessed using intrinsic and extrinsic fluorescence. Both effects are counteracted by betaine, which alone does not significantly affect subfragment-1. Urea also enhances the accessibility of thiol groups, promotes aggregation and decreases the alpha-helix content of S1, effects that are also counteracted by betaine. We conclude that urea-induced inactivation of the enzyme is caused by partial unfolding of the myosin catalytic domain.

  18. The Age of the Inner Halo Globular Cluster NGC 6652

    NASA Technical Reports Server (NTRS)

    Chaboyer, Brian; Sarajedini, Ata; Armandroff, Taft E.

    2000-01-01

    Hubble Space Telescope (HST) (V,I) photometry has been obtained for the inner halo globular cluster NGC 6652. The photometry reaches approximately 4 mag below the turn-off and includes a well populated horizontal branch (HB). This cluster is located close to the Galactic center at RGC approximately equal to 2.0 kpc with a reddening of E(V-I) = 0.15 +/- 0.02 and has a metallicity of [Fe/H] approximately equal to -0.85. Based upon DELTA V (sup SGB) (sub HB), NGC 6652 is 11.7 plus or minus 1.6 Gyr old. Using A HB precise differential ages for 47 Tuc (a thick disk globular), M107 and NGC 1851 (both halo clusters) were obtained. NGC 6652 appears to be the same age as 47 Tuc and NGC 1851 (within +/- 1.2 Gyr), while there is a slight suggestion that M107 is older than NGC 6652 by 2.3 +/- 1.5 Gyr. As this is a less than 2 sigma result, this issue needs to be investigated further before a definitive statement regarding the relative age of M107 and NGC 6652 may be made.

  19. VizieR Online Data Catalog: Globular cluster candidates in NGC253 (Cantiello+, 2018)

    NASA Astrophysics Data System (ADS)

    Cantiello, M.; Grado, A.; Rejkuba, M.; Arnaboldi, M.; Capaccioli, M.; Greggio, L.; Iodice, E.; Limatola, L.

    2017-11-01

    Photometric catalogs for globular cluster (GC) candidates over the 1 sq. degree area around NGC253. The catalogues are based on ugri-band photometry from the VST data, and JKs photometry from VISTA. Aperture magnitudes, corrected for aperture correction are reported. (1 data file).

  20. Trophoblast expression of the minor histocompatibility antigen HA-1 is regulated by oxygen and is increased in placentas from preeclamptic women.

    PubMed

    Linscheid, C; Heitmann, E; Singh, P; Wickstrom, E; Qiu, L; Hodes, H; Nauser, T; Petroff, M G

    2015-08-01

    Maternal T-cells reactive towards paternally inherited fetal minor histocompatibility antigens are expanded during pregnancy. Placental trophoblast cells express at least four fetal antigens, including human minor histocompatibility antigen 1 (HA-1). We investigated oxygen as a potential regulator of HA-1 and whether HA-1 expression is altered in preeclamptic placentas. Expression and regulation of HA-1 mRNA and protein were examined by qRT-PCR and immunohistochemistry, using first, second, and third trimester placentas, first trimester placental explant cultures, and term purified cytotrophoblast cells. Low oxygen conditions were achieved by varying ambient oxygen, and were mimicked using cobalt chloride. HA-1 mRNA and protein expression levels were evaluated in preeclamptic and control placentas. HA-1 protein expression was higher in the syncytiotrophoblast of first trimester as compared to second trimester and term placentas (P<0.01). HA-1 mRNA was increased in cobalt chloride-treated placental explants and purified cytotrophoblast cells (P = 0.04 and P<0.01, respectively) and in purified cytotrophoblast cells cultured under 2% as compared to 8% and 21% oxygen (P<0.01). HA-1 mRNA expression in preeclamptic vs. control placentas was increased 3.3-fold (P = 0.015). HA-1 protein expression was increased in syncytial nuclear aggregates and the syncytiotrophoblast of preeclamptic vs. control placentas (P = 0.02 and 0.03, respectively). Placental HA-1 expression is regulated by oxygen and is increased in the syncytial nuclear aggregates and syncytiotrophoblast of preeclamptic as compared to control placentas. Increased HA-1 expression, combined with increased preeclamptic syncytiotrophoblast deportation, provides a novel potential mechanism for exposure of the maternal immune system to increased fetal antigenic load during preeclampsia. Published by Elsevier Ltd.

  1. Rosat Observations of Nine Globular Clusters

    NASA Technical Reports Server (NTRS)

    Rappaport, S.; Dewey, D.; Levine, A.; Macri, L.

    1994-01-01

    The ROSAT HRI was used to image fields around nine Galactic globular clusters that have central densities in the range of 10(exp 4) - 10(exp 5) solar mass pc(exp -3) and that had not previously been observed with the Einstein Observatory. We detected X-ray sources associated with Pal 2 and NGC 6304 with luminosities of 1.1 x 10(exp 34) ergs/s and 1.2 x 10(exp 33) ergs/s, respectively. No X-ray emission was detected from the source in Ter 6, thus confirming its transient nature. In all, there were 23 serendipitous sources found in the nine fields; none was apparently associated with any of the other seven clusters. The results are discussed in the context of low-luminosity cluster X-ray sources, in general.

  2. Shapiro effect as a possible cause of the low-frequency pulsar timing noise in globular clusters

    NASA Astrophysics Data System (ADS)

    Larchenkova, T. I.; Kopeikin, S. M.

    2006-01-01

    A prolonged timing of millisecond pulsars has revealed low-frequency uncorrelated (infrared) noise, presumably of astrophysical origin, in the pulse arrival time (PAT) residuals for some of them. Currently available pulsar timing methods allow the statistical parameters of this noise to be reliably measured by decomposing the PAT residual function into orthogonal Fourier harmonics. In most cases, pulsars in globular clusters show a low-frequency modulation of their rotational phase and spin rate. The relativistic time delay of the pulsar signal in the curved spacetime of randomly distributed and moving globular cluster stars (the Shapiro effect) is suggested as a possible cause of this modulation. Extremely important (from an astrophysical point of view) information about the structure of the globular cluster core, which is inaccessible to study by other observational methods, could be obtained by analyzing the spectral parameters of the low-frequency noise caused by the Shapiro effect and attributable to the random passages of stars near the line of sight to the pulsar. Given the smallness of the aberration corrections that arise from the nonstationarity of the gravitational field of the randomly distributed ensemble of stars under consideration, a formula is derived for the Shapiro effect for a pulsar in a globular cluster. The derived formula is used to calculate the autocorrelation function of the low-frequency pulsar noise, the slope of its power spectrum, and the behavior of the σz statistic that characterizes the spectral properties of this noise in the form of a time function. The Shapiro effect under discussion is shown to manifest itself for large impact parameters as a low-frequency noise of the pulsar spin rate with a spectral index of n = -1.8 that depends weakly on the specific model distribution of stars in the globular cluster. For small impact parameters, the spectral index of the noise is n = -1.5.

  3. Chemical Abundances of Giants in Globular Clusters

    NASA Astrophysics Data System (ADS)

    Gratton, Raffaele G.; Bragaglia, Angela; Carretta, Eugenio; D'Orazi, Valentina; Lucatello, Sara

    A large fraction of stars form in clusters. According to a widespread paradigma, stellar clusters are prototypes of single stellar populations. According to this concept, they formed on a very short time scale, and all their stars share the same chemical composition. Recently it has been understood that massive stellar clusters (the globular clusters) rather host various stellar populations, characterized by different chemical composition: these stellar populations have also slightly different ages, stars of the second generations being formed from the ejecta of part of those of an earlier one. Furthermore, it is becoming clear that the efficiency of the process is quite low: many more stars formed within this process than currently present in the clusters. This implies that a significant, perhaps even dominant fraction of the ancient population of galaxies formed within the episodes that lead to formation the globular clusters.

  4. Optimal integrated abundances for chemical tagging of extragalactic globular clusters

    NASA Astrophysics Data System (ADS)

    Sakari, Charli M.; Venn, Kim; Shetrone, Matthew; Dotter, Aaron; Mackey, Dougal

    2014-09-01

    High-resolution integrated light (IL) spectroscopy provides detailed abundances of distant globular clusters whose stars cannot be resolved. Abundance comparisons with other systems (e.g. for chemical tagging) require understanding the systematic offsets that can occur between clusters, such as those due to uncertainties in the underlying stellar population. This paper analyses high-resolution IL spectra of the Galactic globular clusters 47 Tuc, M3, M13, NGC 7006, and M15 to (1) quantify potential systematic uncertainties in Fe, Ca, Ti, Ni, Ba, and Eu and (2) identify the most stable abundance ratios that will be useful in future analyses of unresolved targets. When stellar populations are well modelled, uncertainties are ˜0.1-0.2 dex based on sensitivities to the atmospheric parameters alone; in the worst-case scenarios, uncertainties can rise to 0.2-0.4 dex. The [Ca I/Fe I] ratio is identified as the optimal integrated [α/Fe] indicator (with offsets ≲ 0.1 dex), while [Ni I/Fe I] is also extremely stable to within ≲ 0.1 dex. The [Ba II/Eu II] ratios are also stable when the underlying populations are well modelled and may also be useful for chemical tagging.

  5. A catalogue of masses, structural parameters and velocity dispersion profiles of 112 Milky Way globular clusters

    NASA Astrophysics Data System (ADS)

    Baumgardt, H.; Hilker, M.

    2018-05-01

    We have determined masses, stellar mass functions and structural parameters of 112 Milky Way globular clusters by fitting a large set of N-body simulations to their velocity dispersion and surface density profiles. The velocity dispersion profiles were calculated based on a combination of more than 15,000 high-precision radial velocities which we derived from archival ESO/VLT and Keck spectra together with ˜20, 000 published radial velocities from the literature. Our fits also include the stellar mass functions of the globular clusters, which are available for 47 clusters in our sample, allowing us to self-consistently take the effects of mass segregation and ongoing cluster dissolution into account. We confirm the strong correlation between the global mass functions of globular clusters and their relaxation times recently found by Sollima & Baumgardt (2017). We also find a correlation of the escape velocity from the centre of a globular cluster and the fraction of first generation stars (FG) in the cluster recently derived for 57 globular clusters by Milone et al. (2017), but no correlation between the FG star fraction and the global mass function of a globular cluster. This could indicate that the ability of a globular cluster to keep the wind ejecta from the polluting star(s) is the crucial parameter determining the presence and fraction of second generation stars and not its later dynamical mass loss.

  6. Binary Black Hole Mergers from Globular Clusters: Implications for Advanced LIGO.

    PubMed

    Rodriguez, Carl L; Morscher, Meagan; Pattabiraman, Bharath; Chatterjee, Sourav; Haster, Carl-Johan; Rasio, Frederic A

    2015-07-31

    The predicted rate of binary black hole mergers from galactic fields can vary over several orders of magnitude and is extremely sensitive to the assumptions of stellar evolution. But in dense stellar environments such as globular clusters, binary black holes form by well-understood gravitational interactions. In this Letter, we study the formation of black hole binaries in an extensive collection of realistic globular cluster models. By comparing these models to observed Milky Way and extragalactic globular clusters, we find that the mergers of dynamically formed binaries could be detected at a rate of ∼100 per year, potentially dominating the binary black hole merger rate. We also find that a majority of cluster-formed binaries are more massive than their field-formed counterparts, suggesting that Advanced LIGO could identify certain binaries as originating from dense stellar environments.

  7. Globular Cluster Star Classification: Application to M13

    NASA Astrophysics Data System (ADS)

    Caimmi, R.

    2013-06-01

    Starting from recent determination of Fe, O, Na abundances on a restricted sample (N=67) of halo and thick disk stars, a natural and well motivated selection criterion is defined for the classification globular cluster stars. An application is performed to M13 using a sample (N=113) for which Fe, O, Na abundances have been recently inferred from observations. A comparison is made between the current and earlier M13 star classifications. Both O and Na empirical differential abundance distributions are determined for each class and for the whole sample (with the addition of Fe in the last case) and compared with their theoretical counterparts due to cosmic scatter obeying a Gaussian distribution whose parameters are inferred from related subsamples. The occurrence of an agreement between the empirical and theoretical distributions is interpreted as absence of significant chemical evolution and vice versa. The procedure is repeated with regard to four additional classes depending on whether oxygen and sodium abundance is above (stage CE) or below (stage AF) a selected threshold. Both O and Na empirical differential abundance distributions, related to the whole sample, exhibit a linear fit for the AF and CE stage. Within the errors, the oxygen slope for the CE stage is equal and of opposite sign with respect to the sodium slope for AF stage, while the contrary holds when dealing with the oxygen slope for the AF stage with respect to the sodium slope for the CE stage. In the light of simple models of chemical evolution applied to M13, oxygen depletion appears to be mainly turned into sodium enrichment for [O/H]≥-1.35 and [Na/H]≤-1.45, while one or more largely preferred channels occur for [O/H]<-1.35 and [Na/H]>-1.45. In addition, the primordial to the current M13 mass ratio can be inferred from the true sodium yield in units of the sodium solar abundance. Though the above results are mainly qualitative due to large (∓.5 dex) uncertainties in abundance

  8. Modelling the crystallization of the globular proteins

    NASA Astrophysics Data System (ADS)

    Shiryayev, Andrey S.

    Crystallization of globular proteins has become a very important subject in recent yearn. However there is still no understanding of the particular conditions that lead to the crystallization. Since nucleation of a crystalline droplet is the critical step toward the formation of the solid phase from the supersaturated solution, this is the focus of current studies. In this work we use different approaches to investigate the collective behavior of a system of globular proteins. Especially we focused on the models which have a metastable critical point, because this reflects the properties of solutions of globular proteins. The first approach is a continuum model of globular proteins. This model was first presented by Talanquer and Oxtoby and is based on the van der Waals theory. The model can have either a stable or a metastable critical point. For the system with the metastable critical point we studied the behavior of the free energy barrier to nucleation; we found that along particular pathways the barrier to nucleation has a minimim around the critical point. As well, the number of molecules in the critical cluster was found to diverge as one approaches the critical point, though most of the molecules are in the fluid tail of the droplet. Our results are an extension of earlier work [17, 7]. The properties of the solvent affect the behavior of the solution. In our second approach, we proposed a model that takes into account the contribution of the solvent free energy to the free energy of the globular proteins. We show that one can map the phase diagram of a repulsive hard core plus attractive square well interacting system to the same system particles in the solvent environment. In particular we show that this leads to phase diagrams with upper critical points, lower critical points and even closed loops with both upper and lower critical points, similar to the one found before [10]. For systems with interaction different from the square well, in the presence

  9. Phylogenetic and nucleotide sequence analysis of influenza A (H1N1) HA and NA genes of strains isolated from Saudi Arabia.

    PubMed

    Al-Qahtani, Ahmed Ali; Mubin, Muhammad; Dela Cruz, Damian M; Althawadi, Sahar Isa; Ul Rehman, Muhammad Shah Nawaz; Bohol, Marie Fe F; Al-Ahdal, Mohammed N

    2017-01-30

    In early 2009, a novel influenza A (H1N1) virus appeared in Mexico and rapidly disseminated worldwide. Little is known about the phylogeny and evolutionary dynamics of the H1N1 strain found in Saudi Arabia. Nucleotide sequencing and bioinformatics analyses were used to study molecular variation between the virus isolates. In this report, 72 hemagglutinin (HA) and 45 neuraminidase (NA) H1N1 virus gene sequences, isolated in 2009 from various regions of Saudi Arabia, were analyzed. Genetic characterization indicated that viruses from two different clades, 6 and 7, were circulating in the region, with clade 7, the most widely circulating H1N1 clade globally in 2009, being predominant. Sequence analysis of the HA and NA genes revealed a high degree of sequence identity with the corresponding genes from viruses circulating in the South East Asia region and with the A/California/7/2009 strain. New mutations in the HA gene of pandemic H1N1 (pH1N1) viruses, that could alter viral fitness, were identified. Relaxed-clock and Bayesian Skyline Plot analyses, based on the isolates used in this study and closely related globally representative strains, indicated marginally higher substitution rates than the type strain (5.14×10-3 and 4.18×10-3 substitutions/nucleotide/year in the HA and NA genes, respectively). The Saudi isolates were antigenically homogeneous and closely related to the prototype vaccine strain A/California/7/2009. The antigenic site of the HA gene had acquired novel mutations in some isolates, making continued monitoring of these viruses vital for the identification of potentially highly virulent and drug resistant variants.

  10. Globular clusters as tracers of stellar bimodality in elliptical galaxies: the case of NGC 1399

    NASA Astrophysics Data System (ADS)

    Forte, Juan C.; Faifer, Favio; Geisler, Doug

    2005-02-01

    Globular cluster systems (GCSs) frequently show a bimodal distribution of cluster integrated colours. This work explores the arguments to support the idea that the same feature is shared by the diffuse stellar population of the galaxy they are associated with. The particular case of NGC 1399, one of the dominant central galaxies in the Fornax cluster, for which a new B surface brightness profile and (B-RKC) colours are presented, is discussed taking advantage of a recently published wide-field study of its GCS. The results show that the galaxy brightness profile and colour gradient, as well as the behaviour of the cumulative globular cluster specific frequency, are compatible with the presence of two dominant stellar populations, associated with the so-called `blue' and `red' globular cluster families. These globular families are characterized by different intrinsic specific frequencies (defined in terms of each stellar population): Sn= 3.3 +/- 0.3 in the case of the red globulars and Sn= 14.3 +/- 2.5 for the blue ones. We stress that this result does not necessarily conflict with recent works that point out a clear difference between the metallicity distribution of (resolved) halo stars and globulars when comparing their number statistics. The region within 0.5arcmin of the centre shows a deviation from the model profile (in both surface brightness and colour) that may be explained in terms of the presence of a bulge-like high-metallicity component. Otherwise, the model gives an excellent fit up to 12arcmin (or 66.5Kpc) from the centre, the galactocentric limit of our blue brightness profile. The inferred specific frequencies imply that, in terms of their associated stellar populations, the formation of the blue globulars took place with an efficiency about six times higher than that corresponding to their red counterparts. The similarity of the spatial distribution of the blue globulars with that inferred for dark matter, as well as with that of the X

  11. Effect of a low-frequency magnetic field on the structure of globular blood proteins

    NASA Astrophysics Data System (ADS)

    Zalesskaya, G. A.; Ulashchik, V. S.; Mit'kovskaya, N. P.; Laskina, O. V.; Kuchinskii, A. V.

    2007-09-01

    We used IR Fourier absorption spectra of blood to study changes in the structure of globular blood proteins with extracorporeal autohemomagnetotherapy, used to treat ischemic heart disease. We compare the spectra of blood before and after magnetotherapy in the regions: amide I (1655 cm-1), amide II (1545 cm-1), amide III (1230-1350 cm-1), amide IV and amide V (400-700 cm-1). We have shown that pronounced changes in the spectra in the indicated regions on direct exposure of blood in vivo to a low-frequency pulsed magnetic field are connected with conformational changes in the secondary structure of globular blood proteins, which are apparent in the increase in the contribution of the α-helix conformation. We discuss the magnetotherapy-initiated appearance of new IR absorption bands at 1018 and 1038 cm-1 and an increase in the intensity of a number of other bands located in the 1000-1200 cm-1 region, which suggests a change in the concentration of some blood components.

  12. Horizontal branch stars, and galactic and magellanic cloud globular clusters

    NASA Technical Reports Server (NTRS)

    Deboer, K. S.

    1981-01-01

    Seven blue horizontal branch stars in the field were observed and a few HB stars were isolated in globular clusters. Energy distributions are compared to assess possible differences and also used in comparison with model atmospheres. Observed energy distributions of HB stars in NGC 6397 are used to estimate the total number of HB stars which produced the integrated fluxes as observed by ANS. Preliminary results are given for colors of globular clusters observed in the Magellanic Clouds and for their extent, based on the Washburn IUE extraction.

  13. Identification of Hard X-ray Sources in Galactic Globular Clusters: Simbol-X Simulations

    NASA Astrophysics Data System (ADS)

    Servillat, M.

    2009-05-01

    Globular clusters harbour an excess of X-ray sources compared to the number of X-ray sources in the Galactic plane. It has been proposed that many of these X-ray sources are cataclysmic variables that have an intermediate magnetic field, i.e. intermediate polars, which remains to be confirmed and understood. We present here several methods to identify intermediate polars in globular clusters from multiwavelength analysis. First, we report on XMM-Newton, Chandra and HST observations of the very dense Galactic globular cluster NGC 2808. By comparing UV and X-ray properties of the cataclysmic variable candidates, the fraction of intermediate polars in this cluster can be estimated. We also present the optical spectra of two cataclysmic variables in the globular cluster M 22. The HeII (4868 Å) emission line in these spectra could be related to the presence of a magnetic field in these objects. Simulations of Simbol-X observations indicate that the angular resolution is sufficient to study X-ray sources in the core of close, less dense globular clusters, such as M 22. The sensitivity of Simbol-X in an extended energy band up to 80 keV will allow us to discriminate between hard X-ray sources (such as magnetic cataclysmic variables) and soft X-ray sources (such as chromospherically active binaries).

  14. Disrupted globular clusters and the gamma-ray excess in the Galactic Centre

    NASA Astrophysics Data System (ADS)

    Fragione, Giacomo; Antonini, Fabio; Gnedin, Oleg Y.

    2018-04-01

    The Fermi Large Area Telescope has provided the most detailed view towards the Galactic Centre (GC) in high-energy gamma-rays. Besides the interstellar emission and point source contributions, the data suggest a residual diffuse gamma-ray excess. The similarity of its spatial distribution with the expected profile of dark matter has led to claims that this may be evidence for dark matter particle annihilation. Here, we investigate an alternative explanation that the signal originates from millisecond pulsars (MSPs) formed in dense globular clusters and deposited at the GC as a consequence of cluster inspiral and tidal disruption. We use a semi-analytical model to calculate the formation, migration, and disruption of globular clusters in the Galaxy. Our model reproduces the mass of the nuclear star cluster and the present-day radial and mass distribution of globular clusters. For the first time, we calculate the evolution of MSPs from disrupted globular clusters throughout the age of the Galaxy and consistently include the effect of the MSP spin-down due to magnetic-dipole braking. The final gamma-ray amplitude and spatial distribution are in good agreement with the Fermi observations and provide a natural astrophysical explanation for the GC excess.

  15. Integrated-light spectroscopy of globular clusters at the infrared Ca II lines

    NASA Technical Reports Server (NTRS)

    Armandroff, Taft E.; Zinn, Robert

    1988-01-01

    Integrated-light spectroscopy has been obtained for 27 globular clusters at the Ca II IR triplet. Line strengths and radial velocities have been measured from the spectra. For the well-studied clusters in the sample, the strength of the Ca II lines is very well correlated with previous metallicity estimates. Thus, the triplet is useful as a metallicity indicator in globular cluster integrated-light spectra. The greatly reduced effect of interstellar extinction at these wavelengths (compared to the blue region of the spectrum) has permitted observations of some of the most heavily reddened clusters in the Galaxy. For several such clusters, the Ca II triplet metallicities are in poor agreement with metallicity estimates from IR photometry by Malkan (1981). The strength of an interstellar band at 8621A has been used to estimate the amount of extinction towards these clusters. Using the new metallicity and radial-velocity data, the metallicity distribution, kinematics, and spatial distribution of the disk globular cluster system have been analyzed. Results very similar to those of Zinn (1985) have been found. The relation of the disk globulars to the stellar thick disk is discussed.

  16. Construction and cellular immune response induction of HA-based alphavirus replicon vaccines against human-avian influenza (H5N1).

    PubMed

    Yang, Shi-gui; Wo, Jian-er; Li, Min-wei; Mi, Fen-fang; Yu, Cheng-bo; Lv, Guo-liang; Cao, Hong-Cui; Lu, Hai-feng; Wang, Bao-hong; Zhu, Hanping; Li, Lan-Juan

    2009-12-09

    Several approaches are being taken worldwide to develop vaccines against H5N1 viruses; most of them, however, pose both practical and immunological challenges. One potential strategy for improving the immunogenicity of vaccines involves the use of alphavirus replicons and VP22, a herpes simplex type 1 (HSV-1) protein. In this study, we analysed the antigenic peptides and homogeneity of the HA sequences (human isolates of the H5N1 subtype, from 1997 to 2003) and explored a novel alphavirus replicon system of VP22 fused with HA, to assess whether the immunogenicity of an HA-based replicon vaccine could be induced and augmented via fusion with VP22. Further, replicon particles expressing VP22, and enhanced green fluorescent protein (EGFP) were individually used as controls. Cellular immune responses in mice immunised with replicons were evaluated by identifying specific intracellular cytokine production with flow cytometry (FCM). Animal-based experimentation indicated that both the IL-4 expression of CD4(+) T cells and the IFN-gamma expression of CD8(+) T cells were significantly increased in mice immunised with VPR-HA and VPR-VP22/HA. A dose titration effect vis-à-vis both IL-4 expression and IFN-gamma expression were observed in VPR-HA- and VPR-VP22/HA-vaccinated mice. Our results revealed that both VPR-VP22/HA and VPR-HA replicon particles presented a promising approach for developing vaccines against human-avian influenza, and VP22 could enhance the immunogenicity of the HA antigens to which it is fused.

  17. The Impact of HA Oligomer Content on Physical, Mechanical, and Biologic Properties of Divinyl Sulfone-Crosslinked HA Hydrogels

    PubMed Central

    Ibrahim, Samir; Kang, Qian K; Ramamurthi, Anand

    2009-01-01

    In recent studies, we showed that exogenous hyaluronic acid oligomers (HA-o) stimulate functional endothelialization, though native long-chain HA is more bioinert and possibly more biocompatible. Thus, in this study, hydrogels containing high molecular weight (HMW) HA (1×106 Da) and HA oligomer mixtures (HA-o: 0.75–10 kDa) were created by crosslinking with divinyl sulfone (DVS). The incorporation of HA oligomers was found to compromise the physical and mechanical properties of the gels (rheology, apparent crosslinking density, swelling ratio, degradation) and to very mildly enhance inflammatory cell recruitment in vivo; increasing the DVS crosslinker content within the gels in general, had the opposite effect, though the relatively high concentration of DVS within these gels (necessary to create a solid gel) also stimulated a mild sub-cutaneous inflammatory response in vivo and VCAM-1 expression by ECs cultured atop; ICAM-expression levels remained very low irrespective extent of DVS crosslinking or HA-o content. The greatest EC attachment and proliferation (MTT assay) was observed on gels that contained the highest amount of HA-o. The study shows that the beneficial EC response to HA oligomers and biocompatibility of HA is mostly unaltered by their chemical derivatization and crosslinking into a hydrogel. However, the study also demonstrates that the relatively high concentrations of DVS, necessary to create solid gels, compromises their biocompatibility. Moreover, the poor mechanics of even these heavily crosslinked gels, in the context of vascular implantation, necessitates the investigation of other, more appropriate crosslinking agents. Alternately, the outcomes of this study may be used to guide an approach based on chemical immobilization and controlled surface-presentation of both bioactive HA oligomers and more biocompatible HMW HAon synthetic or tissue engineered grafts already in use, without the use of a crosslinker, so that improved, predictable

  18. A dihydropyridine receptor alpha1s loop region critical for skeletal muscle contraction is intrinsically unstructured and binds to a SPRY domain of the type 1 ryanodine receptor.

    PubMed

    Cui, Yanfang; Tae, Han-Shen; Norris, Nicole C; Karunasekara, Yamuna; Pouliquin, Pierre; Board, Philip G; Dulhunty, Angela F; Casarotto, Marco G

    2009-03-01

    The II-III loop of the dihydropyridine receptor (DHPR) alpha(1s) subunit is a modulator of the ryanodine receptor (RyR1) Ca(2+) release channel in vitro and is essential for skeletal muscle contraction in vivo. Despite its importance, the structure of this loop has not been reported. We have investigated its structure using a suite of NMR techniques which revealed that the DHPR II-III loop is an intrinsically unstructured protein (IUP) and as such belongs to a burgeoning structural class of functionally important proteins. The loop does not possess a stable tertiary fold: it is highly flexible, with a strong N-terminal helix followed by nascent helical/turn elements and unstructured segments. Its residual structure is loosely globular with the N and C termini in close proximity. The unstructured nature of the II-III loop may allow it to easily modify its interaction with RyR1 following a surface action potential and thus initiate rapid Ca(2+) release and contraction. The in vitro binding partner for the II-III was investigated. The II-III loop interacts with the second of three structurally distinct SPRY domains in RyR1, whose function is unknown. This interaction occurs through two preformed N-terminal alpha-helical regions and a C-terminal hydrophobic element. The A peptide corresponding to the helical N-terminal region is a common probe of RyR function and binds to the same SPRY domain as the full II-III loop. Thus the second SPRY domain is an in vitro binding site for the II-III loop. The possible in vivo role of this region is discussed.

  19. A Detailed Survey of Pulsating Variables in Five Globular Clusters (Abstract)

    NASA Astrophysics Data System (ADS)

    Murphy, B. W.

    2016-12-01

    (Abstract only) Globular clusters are ideal laboratories for conducting a stellar census. Of particular interest are pulsating variables, which provide astronomers with a tool to probe the properties of the stars and the cluster. We observed each of five globular clusters hundreds to thousands of times over a time span ranging from 2 to 4 years in B, V, and I filters using the SARA 0.6-meter telescope located at Cerro Tololo Interamerican Observatory and the 0.9-meter telescope located at Kitt Peak, Arizona. The images were analyzed using difference image analysis to identify and produce light curves of all variables found in each cluster. In total we identified 377 variables with 140 of these being newly discovered increasing the number of known variables stars in these clusters by 60%. Of the total we have identified 319 RR Lyrae variables (193 RR0, 18 RR01, 101 RR1, 7 RR2), 9 SX Phe stars, 5 Cepheid variables, 11 eclipsing variables, and 33 long period variables. For IC4499 we identified 64 RR0, 18 RR01, 14 RR1, 4 RR2, 1 SX Phe, 1 eclipsing binary, and 2 long period variables. For NGC4833 we identified 10 RR0, 7 RR1, 3 RR2, 6 SX Phe, 5 eclipsing binaries, and 9 long period variables. For NGC6171 (M107) we identified 14 RR0, 7 RR1, and 1 SX Phe. For NGC6402 (M14) we identified 55 RR0, 57 RR1, 1 RR2, 1 SX Phe, 6 Cepheids, 1 eclipsing binary, and 15 long period variables. For NGC6584 we identified 50 RR0, 16 RR1, 4 eclipsing binaries, and 7 long period variables. From our extensive data set we were able to obtain sufficient temporal and complete phase coverage of the RR Lyrae variables. This has allowed us not only to properly classify each of the RR Lyrae variables but also to use Fourier decomposition of the B, V, and I light curves to further analyze the properties of the variable stars and hence the physical properties of each globular cluster.

  20. Quantifying domain-ligand affinities and specificities by high-throughput holdup assay

    PubMed Central

    Vincentelli, Renaud; Luck, Katja; Poirson, Juline; Polanowska, Jolanta; Abdat, Julie; Blémont, Marilyne; Turchetto, Jeremy; Iv, François; Ricquier, Kevin; Straub, Marie-Laure; Forster, Anne; Cassonnet, Patricia; Borg, Jean-Paul; Jacob, Yves; Masson, Murielle; Nominé, Yves; Reboul, Jérôme; Wolff, Nicolas; Charbonnier, Sebastian; Travé, Gilles

    2015-01-01

    Many protein interactions are mediated by small linear motifs interacting specifically with defined families of globular domains. Quantifying the specificity of a motif requires measuring and comparing its binding affinities to all its putative target domains. To this aim, we developed the high-throughput holdup assay, a chromatographic approach that can measure up to a thousand domain-motif equilibrium binding affinities per day. Extracts of overexpressed domains are incubated with peptide-coated resins and subjected to filtration. Binding affinities are deduced from microfluidic capillary electrophoresis of flow-throughs. After benchmarking the approach on 210 PDZ-peptide pairs with known affinities, we determined the affinities of two viral PDZ-binding motifs derived from Human Papillomavirus E6 oncoproteins for 209 PDZ domains covering 79% of the human PDZome. We obtained exquisite sequence-dependent binding profiles, describing quantitatively the PDZome recognition specificity of each motif. This approach, applicable to many categories of domain-ligand interactions, has a wide potential for quantifying the specificities of interactomes. PMID:26053890

  1. Characterization of Monoclonal Antibodies against HA Protein of H1N1 Swine Influenza Virus and Protective Efficacy against H1 Viruses in Mice.

    PubMed

    Liu, Yun; Li, Hongtao; Xue, Yujia; Zhao, Shuang; Li, Chenxi; Qu, Liandong; Zhang, Yun; Liu, Ming

    2017-08-08

    H1N1 swine influenza viruses (SIV) are prevalent in pigs globally, and occasionally emerge in humans, which raises concern about their pandemic threats. To stimulate hemagglutination (HA) of A/Swine/Guangdong/LM/2004 (H1N1) (SW/GD/04) antibody response, eukaryotic expression plasmid pCI-neo-HA was constructed and used as an immunogen to prepare monoclonal antibodies (mAbs). Five mAbs (designed 8C4, 8C6, 9D6, 8A4, and 8B1) against HA protein were obtained and characterized. Western blot showed that the 70 kDa HA protein could be detected by all mAbs in MDCK cells infected with SW/GD/04. Three mAbs-8C4, 8C6, and 9D6-have hemagglutination inhibition (HI) and neutralization test (NT) activities, and 8C6 induces the highest HI and NT titers. The protection efficacy of 8C6 was investigated in BALB/c mice challenged with homologous or heterologous strains of the H1 subtype SIV. The results indicate that mAb 8C6 protected the mice from viral infections, especially the homologous strain, which was clearly demonstrated by the body weight changes and reduction of viral load. Thus, our findings document for the first time that mAb 8C6 might be of potential therapeutic value for H1 subtype SIV infection.

  2. Competition of supermassive black holes and galactic spheroids in the destruction of globular clusters

    NASA Technical Reports Server (NTRS)

    Charlton, Jane C.; Laguna, Pablo

    1995-01-01

    The globular clusters that we observe in galaxies may be only a fraction of the initial population. Among the evolutionary influences on the population is the destruction of globular clusters by tidal forces as the cluster moves through the field of influence of a disk, a bulge, and/or a putative nuclear component (black hole). We have conducted a series of N-body simulations of globular clusters on bound and marginally bound orbits through poetentials that include black hole and speroidal components. The degree of concentration of the spheroidal component can have a considerable impact on the extent to which a globular cluster is disrupted. If half the mass of a 10(exp 10) solar mass spheroid is concentrated within 800 pc, then only black holes with masses greater than 10(exp 9) solar mass can have a significant tidal influence over that already exerted by the bulge. However, if the matter in the spheroidal component is not so strongly concentrated toward the center of the galaxy, a more modest central black hole (down to 10(exp 8) solar mass) could have a dominant influence on the globular cluster distribution, particularly if many of the clusters were initially on highly radial orbits. Our simulations show that the stars that are stripped from a globular cluster follow orbits with roughly the same eccentricity as the initial cluster orbit, spreading out along the orbit like a 'string of pearls.' Since only clusters on close to radial orbits will suffer substantial disruption, the population of stripped stars will be on orbits of high eccentricity.

  3. Unraveling the Planar-Globular Transition in Gold Nanoclusters through Evolutionary Search

    DOE PAGES

    Kinaci, Alper; Narayanan, Badri; Sen, Fatih G.; ...

    2016-11-28

    Au nanoclusters are of technological relevance for catalysis, photonics, sensors, and of fundamental scientific interest owing to planar to globular structural transformation at an anomalously high number of atoms i.e. in the range 12-14. The nature and causes of this transition remain a mystery. In order to unravel this conundrum, high throughput density functional theory (DFT) calculations, coupled with a global structural optimization scheme based on a modified genetic algorithm (GA) are conducted. Furthermore, more than 20,000 Au 12, Au 13, and Au 14 nanoclusters are evaluated. With any DFT functional, globular and planar structures coexist across the size rangemore » of interest. Contrary to what was previously believed, the planar-globular transition is gradual at room temperature rather than a sharp transition. The effects of anionicity, s-d band hybridization and long range interactions on the dimensional transition are quantified by using the structures adjacent to minima. Anionicity marginally changes the relative stability of the clusters. The degree of s-d hybridization is varied via changing the Hubbard U value which corroborate that s-d hybridization alone does not stabilize planar structures. van der Waals interactions, on the other hand, stabilize globular structures. Our results elucidate the balance between the different reasons of the dimensional transition in gold nanoclusters.« less

  4. Highly stretchable HA/SA hydrogels for tissue engineering.

    PubMed

    Zhu, Chengcheng; Yang, Rui; Hua, Xiaobin; Chen, Hong; Xu, Jumei; Wu, Rile; Cen, Lian

    2018-04-01

    A highly stretchable hyaluronic acid (HA)/sodium alginate (SA) hydrogel was developed in this study based on an interpenetrating polymer network. HA/SA hydrogels were prepared by mixing two polysaccharides followed by covalent crosslinking via epoxy groups on HA molecules and ionic crosslinking via divalent ions on SA chains sequentially. The effect of HA/SA ratio on the pore size and distribution, swelling ratio, elongation and rheological properties as well as protein loading and release properties of HA/SA hydrogels was explored. Moreover, a surface modification method, layer-by-layer (LBL) assembly technique, was applied to modify the hydrogel to evaluate the hydrogel's tenability in varying biological performance. It was then shown that the hydrogels had the pore sizes ranging from 100 to 50 μm. With the increase in SA content of the resulting hydrogels, the pore size, swelling ratio, and storage modulus (G') and loss modulus (G″) of the hydrogel all decreased, whereas the in vitro bulk weight loss was fastened. Moreover, elongation at break (EB) value increased first, reached a peak value and then decreased, that is HA8/SA1 (HA:SA = 8:1) had the highest EB value of 417%. This hydrogel could retain 33.2% of the pre-loaded protein even after 72 h, which could be further attenuated when LBL was used to shell the hydrogel. The growth of fibroblasts on HA8/SA1 hydrogel gave preliminary assessment on its suitability as a cellular carrier, while the LBL modified HA8/SA1 hydrogel also favored the anchoring of keratinocytes, further enhancing its cell carrier role for tissue regeneration, especially skin engineering.

  5. Synergistic interaction of platelet derived growth factor (PDGF) with the surface of PLLA/Col/HA and PLLA/HA scaffolds produces rapid osteogenic differentiation.

    PubMed

    Raghavendran, Hanumantha Rao Balaji; Mohan, Saktiswaren; Genasan, Krishnamurithy; Murali, Malliga Raman; Naveen, Sangeetha Vasudevaraj; Talebian, Sepehr; McKean, Robert; Kamarul, Tunku

    2016-03-01

    Scaffolds with structural features similar to the extracellular matrix stimulate rapid osteogenic differentiation in favorable microenvironment and with growth factor supplementation. In this study, the osteogenic potential of electrospun poly-l-lactide/hydroxyapatite/collagen (PLLA/Col/HA, PLLA/HA and PLLA/Col) scaffolds were tested in vitro with the supplementation of platelet derived growth factor-BB (PDGF-BB). Cell attachment and topography, mineralization, extracellular matrix protein localization, and gene expression of the human mesenchymal stromal cells were compared between the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA. The levels of osteocalcin, calcium, and mineralization were significantly greater in the PLLA/Col/HA and PLLA/HA compared with PLLA/Col. High expression of fibronectin, intracellular adhesion molecule, cadherin, and collagen 1 (Col1) suggests that PLLA/Col/HA and PLLA/HA scaffolds had superior osteoinductivity than PLLA/Col. Additionally, osteopontin, osteocalcin, osterix, Runt-related transcription factor 2 (Runx2), and bone morphogenic protein (BMP2) expression were higher in PLLA/Col/HA and PLLA/HA compared with PLLA/Col. In comparison with PLLA/Col, the PLLA/Col/HA and PLLA/HA scaffolds presented a significant upregulation of the genes Runx2, Col 1, Integrin, osteonectin (ON), bone gamma-carboxyglutamic acid-containing protein (BGALP), osteopontin (OPN), and BMP2. The upregulation of these genes was further increased with PDGF-BB supplementation. These results show that PDGF-BB acts synergistically with PLLA/Col/HA and PLLA/HA to enhance the osteogenic differentiation potential. Therefore, this combination can be used for the rapid expansion of bone marrow stromal cells into bone-forming cells for tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Globular and fibrous structure in barley chromosomes revealed by high-resolution scanning electron microscopy.

    PubMed

    Iwano, M; Fukui, K; Takaichi, S; Isogai, A

    1997-08-01

    Barley chromosomes were prepared for high-resolution scanning electron microscopy using a combination of enzyme maceration, treatment in acetic acid and osmium impregnation using thiocarbohydrazide. Using this technique, the three-dimensional ultrastructure of interphase nuclei and mitotic chromosomes was examined. In Interphase, different levels of chromatin condensation were observed, consisting of fibrils 10 nm in diameter, 20- to 40-nm fibres and a higher order complex. In prophase, globular and strand-like structures composed of 20- to 40-nm fibres were dominant. As the cells progressed through the cell cycle and the chromatin condensed, globular and strand-like structures (chromomeres) were coiled and packed to form chromosomes. Chromomeres were observed as globular protuberances on the surface of metaphase chromosomes. These findings indicate that the chromomere is a fundamental substructure of the higher order architecture of the chromosome. In the centromeric region, there were no globular protuberances, but 20- to 40-nm fibres were folded compactly to form a higher level organization surrounding the chromosomal axia.

  7. Formation of highly stable chimeric trimers by fusion of an adenovirus fiber shaft fragment with the foldon domain of bacteriophage t4 fibritin.

    PubMed

    Papanikolopoulou, Katerina; Forge, Vincent; Goeltz, Pierrette; Mitraki, Anna

    2004-03-05

    The folding of beta-structured, fibrous proteins is a largely unexplored area. A class of such proteins is used by viruses as adhesins, and recent studies revealed novel beta-structured motifs for them. We have been studying the folding and assembly of adenovirus fibers that consist of a globular C-terminal domain, a central fibrous shaft, and an N-terminal part that attaches to the viral capsid. The globular C-terminal, or "head" domain, has been postulated to be necessary for the trimerization of the fiber and might act as a registration signal that directs its correct folding and assembly. In this work, we replaced the head of the fiber by the trimerization domain of the bacteriophage T4 fibritin, termed "foldon." Two chimeric proteins, comprising the foldon domain connected at the C-terminal end of four fiber shaft repeats with or without the use of a natural linker sequence, fold into highly stable, SDS-resistant trimers. The structural signatures of the chimeric proteins as seen by CD and infrared spectroscopy are reported. The results suggest that the foldon domain can successfully replace the fiber head domain in ensuring correct trimerization of the shaft sequences. Biological implications and implications for engineering highly stable, beta-structured nanorods are discussed.

  8. Ancient Planet in a Globular Cluster Core

    NASA Image and Video Library

    2010-03-31

    Release Date: July 10, 2003 A rich starry sky fills the view from an ancient gas-giant planet in the core of the globular star cluster M4, as imagined in this artist's concept. The 13-billion-year-old planet orbits a helium white-dwarf star and the millisecond pulsar B1620-26, seen at lower left. The globular cluster is deficient in heavier elements for making planets, so the existence of such a world implies that planet formation may have been quite efficient and common in the early universe. Object Names: B1620-26, M4 Image Type: Artwork Illustration Credit: NASA and G. Bacon (STScI) To learn more about this image go to: www.nasa.gov/centers/goddard/news/topstory/2003/0709hstss... NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

  9. Options and obstacles for designing a universal influenza vaccine.

    PubMed

    Jang, Yo Han; Seong, Baik Lin

    2014-08-18

    Since the discovery of antibodies specific to a highly conserved stalk region of the influenza virus hemagglutinin (HA), eliciting such antibodies has been considered the key to developing a universal influenza vaccine that confers broad-spectrum protection against various influenza subtypes. To achieve this goal, a prime/boost immunization strategy has been heralded to redirect host immune responses from the variable globular head domain to the conserved stalk domain of HA. While this approach has been successful in eliciting cross-reactive antibodies against the HA stalk domain, protective efficacy remains relatively poor due to the low immunogenicity of the domain, and the cross-reactivity was only within the same group, rather than among different groups. Additionally, concerns are raised on the possibility of vaccine-associated enhancement of viral infection and whether multiple boost immunization protocols would be considered practical from a clinical standpoint. Live attenuated vaccine hitherto remains unexplored, but is expected to serve as an alternative approach, considering its superior cross-reactivity. This review summarizes recent advancements in the HA stalk-based universal influenza vaccines, discusses the pros and cons of these approaches with respect to the potentially beneficial and harmful effects of neutralizing and non-neutralizing antibodies, and suggests future guidelines towards the design of a truly protective universal influenza vaccine.

  10. Options and Obstacles for Designing a Universal Influenza Vaccine

    PubMed Central

    Jang, Yo Han; Seong, Baik Lin

    2014-01-01

    Since the discovery of antibodies specific to a highly conserved stalk region of the influenza virus hemagglutinin (HA), eliciting such antibodies has been considered the key to developing a universal influenza vaccine that confers broad-spectrum protection against various influenza subtypes. To achieve this goal, a prime/boost immunization strategy has been heralded to redirect host immune responses from the variable globular head domain to the conserved stalk domain of HA. While this approach has been successful in eliciting cross-reactive antibodies against the HA stalk domain, protective efficacy remains relatively poor due to the low immunogenicity of the domain, and the cross-reactivity was only within the same group, rather than among different groups. Additionally, concerns are raised on the possibility of vaccine-associated enhancement of viral infection and whether multiple boost immunization protocols would be considered practical from a clinical standpoint. Live attenuated vaccine hitherto remains unexplored, but is expected to serve as an alternative approach, considering its superior cross-reactivity. This review summarizes recent advancements in the HA stalk-based universal influenza vaccines, discusses the pros and cons of these approaches with respect to the potentially beneficial and harmful effects of neutralizing and non-neutralizing antibodies, and suggests future guidelines towards the design of a truly protective universal influenza vaccine. PMID:25196381

  11. Hubble Space Telescope discovery of candidate young globular clusters in the merger remnant NGC 7252

    NASA Technical Reports Server (NTRS)

    Whitmore, Bradley C.; Schweizer, Francois; Leitherer, Claus; Borne, Kirk; Robert, Carmelle

    1993-01-01

    New, high-resolution images of the central region of NGC 7252 obtained with the Planetary Camera of the HST are presented. NGC 7252 is a prototypical example of a remnant of two merged disk galaxies. Our most striking result is the discovery of a population of about 40 blue pointlike objects in this galaxy. The mean absolute magnitude of these objects is Mv = -13 mag; the mean color is V-I = 0.7 mag; and the mean effective radius is 10 pc. The luminosities, colors, projected spatial distribution, and sizes are all compatible with the hypothesis that these objects formed within the last 1 Gyr following the collision of two spiral galaxies, and that they are young globular clusters. It therefore appears that the number of globular clusters may increase during the merger of gas-rich galaxies. This weakens van den Bergh's objection against ellipticals being formed through disk mergers, based mainly on the fact that disk galaxies have fewer globular clusters per unit luminosity than ellipticals do. NGC 7252 shows a single, semistellar nucleus; relatively bright spiral structure is seen within 1.6 kpc of the center, presumably formed through the continued infall of gas into a disk around the center of the galaxy.

  12. Binding Rate Constants Reveal Distinct Features of Disordered Protein Domains.

    PubMed

    Dogan, Jakob; Jonasson, Josefin; Andersson, Eva; Jemth, Per

    2015-08-04

    Intrinsically disordered proteins (IDPs) are abundant in the proteome and involved in key cellular functions. However, experimental data about the binding kinetics of IDPs as a function of different environmental conditions are scarce. We have performed an extensive characterization of the ionic strength dependence of the interaction between the molten globular nuclear co-activator binding domain (NCBD) of CREB binding protein and five different protein ligands, including the intrinsically disordered activation domain of p160 transcriptional co-activators (SRC1, TIF2, ACTR), the p53 transactivation domain, and the folded pointed domain (PNT) of transcription factor ETS-2. Direct comparisons of the binding rate constants under identical conditions show that the association rate constant, kon, for interactions between NCBD and disordered protein domains is high at low salt concentrations (90-350 × 10(6) M(-1) s(-1) at 4 °C) but is reduced significantly (10-30-fold) with an increasing ionic strength and reaches a plateau around physiological ionic strength. In contrast, the kon for the interaction between NCBD and the folded PNT domain is only 7 × 10(6) M(-1) s(-1) (4 °C and low salt) and displays weak ionic strength dependence, which could reflect a distinctly different association that relies less on electrostatic interactions. Furthermore, the basal rate constant (in the absence of electrostatic interactions) is high for the NCBD interactions, exceeding those typically observed for folded proteins. One likely interpretation is that disordered proteins have a large number of possible collisions leading to a productive on-pathway encounter complex, while folded proteins are more restricted in terms of orientation. Our results highlight the importance of electrostatic interactions in binding involving IDPs and emphasize the significance of including ionic strength as a factor in studies that compare the binding properties of IDPs to those of ordered proteins.

  13. Janus-faced Sestrin2 controls ROS and mTOR signalling through two separate functional domains

    NASA Astrophysics Data System (ADS)

    Kim, Hanseong; An, Sojin; Ro, Seung-Hyun; Teixeira, Filipa; Jin Park, Gyeong; Kim, Cheal; Cho, Chun-Seok; Kim, Jeong-Sig; Jakob, Ursula; Hee Lee, Jun; Cho, Uhn-Soo

    2015-11-01

    Sestrins are stress-inducible metabolic regulators with two seemingly unrelated but physiologically important functions: reduction of reactive oxygen species (ROS) and inhibition of the mechanistic target of rapamycin complex 1 (mTORC1). How Sestrins fulfil this dual role has remained elusive so far. Here we report the crystal structure of human Sestrin2 (hSesn2), and show that hSesn2 is twofold pseudo-symmetric with two globular subdomains, which are structurally similar but functionally distinct from each other. While the N-terminal domain (Sesn-A) reduces alkylhydroperoxide radicals through its helix-turn-helix oxidoreductase motif, the C-terminal domain (Sesn-C) modified this motif to accommodate physical interaction with GATOR2 and subsequent inhibition of mTORC1. These findings clarify the molecular mechanism of how Sestrins can attenuate degenerative processes such as aging and diabetes by acting as a simultaneous inhibitor of ROS accumulation and mTORC1 activation.

  14. A thermodynamic definition of protein domains.

    PubMed

    Porter, Lauren L; Rose, George D

    2012-06-12

    Protein domains are conspicuous structural units in globular proteins, and their identification has been a topic of intense biochemical interest dating back to the earliest crystal structures. Numerous disparate domain identification algorithms have been proposed, all involving some combination of visual intuition and/or structure-based decomposition. Instead, we present a rigorous, thermodynamically-based approach that redefines domains as cooperative chain segments. In greater detail, most small proteins fold with high cooperativity, meaning that the equilibrium population is dominated by completely folded and completely unfolded molecules, with a negligible subpopulation of partially folded intermediates. Here, we redefine structural domains in thermodynamic terms as cooperative folding units, based on m-values, which measure the cooperativity of a protein or its substructures. In our analysis, a domain is equated to a contiguous segment of the folded protein whose m-value is largely unaffected when that segment is excised from its parent structure. Defined in this way, a domain is a self-contained cooperative unit; i.e., its cooperativity depends primarily upon intrasegment interactions, not intersegment interactions. Implementing this concept computationally, the domains in a large representative set of proteins were identified; all exhibit consistency with experimental findings. Specifically, our domain divisions correspond to the experimentally determined equilibrium folding intermediates in a set of nine proteins. The approach was also proofed against a representative set of 71 additional proteins, again with confirmatory results. Our reframed interpretation of a protein domain transforms an indeterminate structural phenomenon into a quantifiable molecular property grounded in solution thermodynamics.

  15. Integrated K-band spectra of old and intermediate-age globular clusters in the Large Magellanic Cloud

    NASA Astrophysics Data System (ADS)

    Lyubenova, M.; Kuntschner, H.; Rejkuba, M.; Silva, D. R.; Kissler-Patig, M.; Tacconi-Garman, L. E.; Larsen, S. S.

    2010-02-01

    Current stellar population models have arguably the largest uncertainties in the near-IR wavelength range, partly due to a lack of large and well calibrated empirical spectral libraries. In this paper we present a project whose aim it is to provide the first library of luminosity weighted integrated near-IR spectra of globular clusters to be used to test the current stellar population models and serve as calibrators for future ones. Our pilot study presents spatially integrated K-band spectra of three old (≥10 Gyr) and metal poor ([Fe/H] ~ -1.4), and three intermediate age (1-2 Gyr) and more metal rich ([Fe/H] ~ - 0.4) globular clusters in the LMC. We measured the line strengths of the Na I, Ca I and 12CO (2-0) absorption features. The Na I index decreases with increasing age and decreasing metallicity of the clusters. The DCO index, used to measure the 12CO (2-0) line strength, is significantly reduced by the presence of carbon-rich TP-AGB stars in the globular clusters with age ~1 Gyr. This is in contradiction to the predictions of the stellar population models of Maraston (2005, MNRAS, 362, 799). We find that this disagreement is due to the different CO absorption strength of carbon-rich Milky Way TP-AGB stars used in the models and the LMC carbon stars in our sample. For globular clusters with age ≥ 2 Gyr we find DCO index measurements consistent with the model predictions. Based on observation collected at the ESO Paranal La Silla Observatory, Chile, Prog. ID 078.B-0205.Spectra in FITS format are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/510/A19

  16. Characterization of monomeric DNA-binding protein Histone H1 in Leishmania braziliensis.

    PubMed

    Carmelo, Emma; González, Gloria; Cruz, Teresa; Osuna, Antonio; Hernández, Mariano; Valladares, Basilio

    2011-08-01

    Histone H1 in Leishmania presents relevant differences compared to higher eukaryote counterparts, such as the lack of a DNA-binding central globular domain. Despite that, it is apparently fully functional since its differential expression levels have been related to changes in chromatin condensation and infectivity, among other features. The localization and the aggregation state of L. braziliensis H1 has been determined by immunolocalization, mass spectrometry, cross-linking and electrophoretic mobility shift assays. Analysis of H1 sequences from the Leishmania Genome Database revealed that our protein is included in a very divergent group of histones H1 that is present only in L. braziliensis. An antibody raised against recombinant L. braziliensis H1 recognized specifically that protein by immunoblot in L. braziliensis extracts, but not in other Leishmania species, a consequence of the sequence divergences observed among Leishmania species. Mass spectrometry analysis and in vitro DNA-binding experiments have also proven that L. braziliensis H1 is monomeric in solution, but oligomerizes upon binding to DNA. Finally, despite the lack of a globular domain, L. braziliensis H1 is able to form complexes with DNA in vitro, with higher affinity for supercoiled compared to linear DNA.

  17. Integrated Light Chemical Abundance Analyses of 7 M31 Outer Halo Globular Clusters from the Pan-Andromeda Archaeological Survey

    NASA Astrophysics Data System (ADS)

    Sakari, Charli; Venn, Kim; Mackey, Dougal; Shetrone, Matthew D.; Dotter, Aaron L.; Wallerstein, George

    2015-01-01

    Detailed chemical abundances of globular clusters provide insight into the formation and evolution of galaxies and their globular cluster systems. This talk presents detailed chemical abundances for seven M31 outer halo globular clusters (with projected radii greater than 30 kpc), as derived from high resolution integrated light spectra. Five of these clusters were recently discovered in the Pan-Andromeda Archaeological Survey (PAndAS). The integrated abundances show that 4 of these clusters are metal-poor ([Fe/H] < -1.5) while the other 3 are more metal-rich. The most metal-poor globular clusters are α-enhanced, though 3 of the 4 are possibly less α-enhanced than MW stars (at the 1σ level). Other chemical abundance ratios ([Ba/Eu], [Eu/Ca], and [Ni/Fe]) are consistent with origins in low mass dwarf galaxies (similar to Fornax). The most metal-rich cluster ([Fe/H] ~ -1) stands out as being chemically distinct from Milky Way field stars of the same metallicity---its chemical abundance ratios agree best with the stars and clusters in the Large Magellanic Cloud (LMC) and the Sagittarius dwarf spheroidal (Sgr) than with the Milky Way field stars. The other metal-rich clusters, H10 and H23, look similar to the LMC and Milky Way field stars in all abundance ratios. These results indicate that M31's outer halo is being at least partially built up by the accretion of dwarf satellites, in agreement with previous observations.

  18. New bound on neutrino dipole moments from globular-cluster stars

    NASA Technical Reports Server (NTRS)

    Raffelt, Georg G.

    1990-01-01

    Neutrino dipole moments mu(nu) would increase the core mass of red giants at the helium flash by delta(Mc) = 0.015 solar mass x mu(nu)/10 to the -12th muB (where muB is the Bohr magneton) because of enhanced neutrino losses. Existing measurements of the bolometric magnitudes of the brightest red giants in 26 globular clusters, number counts of horizontal-branch stars and red giants in 15 globular clusters, and statistical parallax determinations of field RR Lyr luminosities yield delta(Mc) = 0.009 + or - 0.012 solar mass, so that conservatively mu(nu) is less than 3 x 10 to the -12th muB.

  19. No energy equipartition in globular clusters

    NASA Astrophysics Data System (ADS)

    Trenti, Michele; van der Marel, Roeland

    2013-11-01

    It is widely believed that globular clusters evolve over many two-body relaxation times towards a state of energy equipartition, so that velocity dispersion scales with stellar mass as σ ∝ m-η with η = 0.5. We show here that this is incorrect, using a suite of direct N-body simulations with a variety of realistic initial mass functions and initial conditions. No simulated system ever reaches a state close to equipartition. Near the centre, the luminous main-sequence stars reach a maximum ηmax ≈ 0.15 ± 0.03. At large times, all radial bins convergence on an asymptotic value η∞ ≈ 0.08 ± 0.02. The development of this `partial equipartition' is strikingly similar across our simulations, despite the range of different initial conditions employed. Compact remnants tend to have higher η than main-sequence stars (but still η < 0.5), due to their steeper (evolved) mass function. The presence of an intermediate-mass black hole (IMBH) decreases η, consistent with our previous findings of a quenching of mass segregation under these conditions. All these results can be understood as a consequence of the Spitzer instability for two-component systems, extended by Vishniac to a continuous mass spectrum. Mass segregation (the tendency of heavier stars to sink towards the core) has often been studied observationally, but energy equipartition has not. Due to the advent of high-quality proper motion data sets from the Hubble Space Telescope, it is now possible to measure η for real clusters. Detailed data-model comparisons open up a new observational window on globular cluster dynamics and evolution. A first comparison of our simulations to observations of Omega Cen yields good agreement, supporting the view that globular clusters are not generally in energy equipartition. Modelling techniques that assume equipartition by construction (e.g. multi-mass Michie-King models) are approximate at best.

  20. A class of spherical, truncated, anisotropic models for application to globular clusters

    NASA Astrophysics Data System (ADS)

    de Vita, Ruggero; Bertin, Giuseppe; Zocchi, Alice

    2016-05-01

    Recently, a class of non-truncated, radially anisotropic models (the so-called f(ν)-models), originally constructed in the context of violent relaxation and modelling of elliptical galaxies, has been found to possess interesting qualities in relation to observed and simulated globular clusters. In view of new applications to globular clusters, we improve this class of models along two directions. To make them more suitable for the description of small stellar systems hosted by galaxies, we introduce a "tidal" truncation by means of a procedure that guarantees full continuity of the distribution function. The new fT(ν)-models are shown to provide a better fit to the observed photometric and spectroscopic profiles for a sample of 13 globular clusters studied earlier by means of non-truncated models; interestingly, the best-fit models also perform better with respect to the radial-orbit instability. Then, we design a flexible but simple two-component family of truncated models to study the separate issues of mass segregation and multiple populations. We do not aim at a fully realistic description of globular clusters to compete with the description currently obtained by means of dedicated simulations. The goal here is to try to identify the simplest models, that is, those with the smallest number of free parameters, but still have the capacity to provide a reasonable description for clusters that are evidently beyond the reach of one-component models. With this tool, we aim at identifying the key factors that characterize mass segregation or the presence of multiple populations. To reduce the relevant parameter space, we formulate a few physical arguments based on recent observations and simulations. A first application to two well-studied globular clusters is briefly described and discussed.

  1. Structural and Functional Characterization of the Recombinant Death Domain from Death-Associated Protein Kinase

    PubMed Central

    Dioletis, Evangelos; Dingley, Andrew J.; Driscoll, Paul C.

    2013-01-01

    Death-associated protein kinase (DAPk) is a calcium/calmodulin-regulated Ser/Thr-protein kinase that functions at an important point of integration for cell death signaling pathways. DAPk has a structurally unique multi-domain architecture, including a C-terminally positioned death domain (DD) that is a positive regulator of DAPk activity. In this study, recombinant DAPk-DD was observed to aggregate readily and could not be prepared in sufficient yield for structural analysis. However, DAPk-DD could be obtained as a soluble protein in the form of a translational fusion protein with the B1 domain of streptococcal protein G. In contrast to other DDs that adopt the canonical six amphipathic α-helices arranged in a compact fold, the DAPk-DD was found to possess surprisingly low regular secondary structure content and an absence of a stable globular fold, as determined by circular dichroism (CD), NMR spectroscopy and a temperature-dependent fluorescence assay. Furthermore, we measured the in vitro interaction between extracellular-regulated kinase-2 (ERK2) and various recombinant DAPk-DD constructs. Despite the low level of structural order, the recombinant DAPk-DD retained the ability to interact with ERK2 in a 11 ratio with a K d in the low micromolar range. Only the full-length DAPk-DD could bind ERK2, indicating that the apparent ‘D-motif’ located in the putative sixth helix of DAPk-DD is not sufficient for ERK2 recognition. CD analysis revealed that binding of DAPk-DD to ERK2 is not accompanied by a significant change in secondary structure. Taken together our data argue that the DAPk-DD, when expressed in isolation, does not adopt a classical DD fold, yet in this state retains the capacity to interact with at least one of its binding partners. The lack of a stable globular structure for the DAPk-DD may reflect either that its folding would be supported by interactions absent in our experimental set-up, or a limitation in the structural bioinformatics

  2. Structural and functional characterization of the recombinant death domain from death-associated protein kinase.

    PubMed

    Dioletis, Evangelos; Dingley, Andrew J; Driscoll, Paul C

    2013-01-01

    Death-associated protein kinase (DAPk) is a calcium/calmodulin-regulated Ser/Thr-protein kinase that functions at an important point of integration for cell death signaling pathways. DAPk has a structurally unique multi-domain architecture, including a C-terminally positioned death domain (DD) that is a positive regulator of DAPk activity. In this study, recombinant DAPk-DD was observed to aggregate readily and could not be prepared in sufficient yield for structural analysis. However, DAPk-DD could be obtained as a soluble protein in the form of a translational fusion protein with the B1 domain of streptococcal protein G. In contrast to other DDs that adopt the canonical six amphipathic α-helices arranged in a compact fold, the DAPk-DD was found to possess surprisingly low regular secondary structure content and an absence of a stable globular fold, as determined by circular dichroism (CD), NMR spectroscopy and a temperature-dependent fluorescence assay. Furthermore, we measured the in vitro interaction between extracellular-regulated kinase-2 (ERK2) and various recombinant DAPk-DD constructs. Despite the low level of structural order, the recombinant DAPk-DD retained the ability to interact with ERK2 in a 11 ratio with a K d in the low micromolar range. Only the full-length DAPk-DD could bind ERK2, indicating that the apparent 'D-motif' located in the putative sixth helix of DAPk-DD is not sufficient for ERK2 recognition. CD analysis revealed that binding of DAPk-DD to ERK2 is not accompanied by a significant change in secondary structure. Taken together our data argue that the DAPk-DD, when expressed in isolation, does not adopt a classical DD fold, yet in this state retains the capacity to interact with at least one of its binding partners. The lack of a stable globular structure for the DAPk-DD may reflect either that its folding would be supported by interactions absent in our experimental set-up, or a limitation in the structural bioinformatics

  3. Abundances of Local Group Globular Clusters Using High Resolution Integrated Light Spectroscopy

    NASA Astrophysics Data System (ADS)

    Sakari, Charli; McWilliam, A.; Venn, K.; Shetrone, M. D.; Dotter, A. L.; Mackey, D.

    2014-01-01

    Abundances and kinematics of extragalactic globular clusters provide valuable clues about galaxy and globular cluster formation in a wide variety of environments. In order to obtain such information about distant, unresolved systems, specific observational techniques are required. An Integrated Light Spectrum (ILS) provides a single spectrum from an entire stellar population, and can therefore be used to determine integrated cluster abundances. This dissertation investigates the accuracy of high resolution ILS analysis methods, using ILS (taken with the Hobby-Eberly Telescope) of globular clusters associated with the Milky Way (47 Tuc, M3, M13, NGC 7006, and M15) and then applies the method to globular clusters in the outer halo of M31 (from the Pan-Andromeda Archaeological Survey, or PAndAS). Results show that: a) as expected, the high resolution method reproduces individual stellar abundances for elements that do not vary within a cluster; b) the presence of multiple populations does affect the abundances of elements that vary within the cluster; c) certain abundance ratios are very sensitive to systematic effects, while others are not; and d) certain abundance ratios (e.g. [Ca/Fe]) can be accurately obtained from unresolved systems. Applications of ILABUNDS to the PAndAS clusters reveal that accretion may have played an important role in the formation of M31's outer halo.

  4. 7 CFR Appendix A to Subpart E of... - Form FmHA 49-1, Application for Loan and Guarantee

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true Form FmHA 49-1, Application for Loan and Guarantee A Appendix A to Subpart E of Part 1980 Agriculture Regulations of the Department of Agriculture (Continued... Industrial Loan Program Pt. 1980, Subpt. E, App. A Appendix A to Subpart E of Part 1980—Form FmHA 49-1...

  5. 7 CFR Appendix A to Subpart E of... - Form FmHA 49-1, Application for Loan and Guarantee

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 14 2011-01-01 2011-01-01 false Form FmHA 49-1, Application for Loan and Guarantee A Appendix A to Subpart E of Part 1980 Agriculture Regulations of the Department of Agriculture (Continued... Industrial Loan Program Pt. 1980, Subpt. E, App. A Appendix A to Subpart E of Part 1980—Form FmHA 49-1...

  6. Globular cluster seeding by primordial black hole population

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dolgov, A.; Postnov, K., E-mail: dolgov@fe.infn.it, E-mail: kpostnov@gmail.com

    Primordial black holes (PBHs) that form in the early Universe in the modified Affleck-Dine (AD) mechanism of baryogenesis should have intrinsic log-normal mass distribution of PBHs. We show that the parameters of this distribution adjusted to provide the required spatial density of massive seeds (≥ 10{sup 4} M {sub ⊙}) for early galaxy formation and not violating the dark matter density constraints, predict the existence of the population of intermediate-mass PBHs with a number density of 0∼ 100 Mpc{sup −3}. We argue that the population of intermediate-mass AD PBHs can also seed the formation of globular clusters in galaxies. Inmore » this scenario, each globular cluster should host an intermediate-mass black hole with a mass of a few thousand solar masses, and should not obligatorily be immersed in a massive dark matter halo.« less

  7. THE SIZE DIFFERENCE BETWEEN RED AND BLUE GLOBULAR CLUSTERS IS NOT DUE TO PROJECTION EFFECTS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Webb, Jeremy J.; Harris, William E.; Sills, Alison, E-mail: webbjj@mcmaster.ca

    Metal-rich (red) globular clusters in massive galaxies are, on average, smaller than metal-poor (blue) globular clusters. One of the possible explanations for this phenomenon is that the two populations of clusters have different spatial distributions. We test this idea by comparing clusters observed in unusually deep, high signal-to-noise images of M87 with a simulated globular cluster population in which the red and blue clusters have different spatial distributions, matching the observations. We compare the overall distribution of cluster effective radii as well as the relationship between effective radius and galactocentric distance for both the observed and simulated red and bluemore » sub-populations. We find that the different spatial distributions does not produce a significant size difference between the red and blue sub-populations as a whole or at a given galactocentric distance. These results suggest that the size difference between red and blue globular clusters is likely due to differences during formation or later evolution.« less

  8. Spontaneous Unfolding-Refolding of Fibronectin Type III Domains Assayed by Thiol Exchange

    PubMed Central

    Shah, Riddhi; Ohashi, Tomoo; Erickson, Harold P.; Oas, Terrence G.

    2017-01-01

    Globular proteins are not permanently folded but spontaneously unfold and refold on time scales that can span orders of magnitude for different proteins. A longstanding debate in the protein-folding field is whether unfolding rates or folding rates correlate to the stability of a protein. In the present study, we have determined the unfolding and folding kinetics of 10 FNIII domains. FNIII domains are one of the most common protein folds and are present in 2% of animal proteins. FNIII domains are ideal for this study because they have an identical seven-strand β-sandwich structure, but they vary widely in sequence and thermodynamic stability. We assayed thermodynamic stability of each domain by equilibrium denaturation in urea. We then assayed the kinetics of domain opening and closing by a technique known as thiol exchange. For this we introduced a buried Cys at the identical location in each FNIII domain and measured the kinetics of labeling with DTNB over a range of urea concentrations. A global fit of the kinetics data gave the kinetics of spontaneous unfolding and refolding in zero urea. We found that the folding rates were relatively similar, ∼0.11 s−1, for the different domains. The unfolding rates varied widely and correlated with thermodynamic stability. Our study is the first to address this question using a set of domains that are structurally homologous but evolved with widely varying sequence identity and thermodynamic stability. These data add new evidence that thermodynamic stability correlates primarily with unfolding rate rather than folding rate. The study also has implications for the question of whether opening of FNIII domains contributes to the stretching of fibronectin matrix fibrils. PMID:27909052

  9. Globular adiponectin inhibits ethanol-induced reactive oxygen species production through modulation of NADPH oxidase in macrophages: involvement of liver kinase B1/AMP-activated protein kinase pathway.

    PubMed

    Kim, Mi Jin; Nagy, Laura E; Park, Pil-Hoon

    2014-09-01

    Adiponectin, an adipokine predominantly secreted from adipocytes, has been shown to play protective roles against chronic alcohol consumption. Although excessive reactive oxygen species (ROS) production in macrophages is considered one of the critical events for ethanol-induced damage in various target tissues, the effect of adiponectin on ethanol-induced ROS production is not clearly understood. In the present study, we investigated the effect of globular adiponectin (gAcrp) on ethanol-induced ROS production and the potential mechanisms underlying these effects of gAcrp in macrophages. Here we demonstrated that gAcrp prevented ethanol-induced ROS production in both RAW 264.7 macrophages and primary murine peritoneal macrophages. Globular adiponectin also inhibited ethanol-induced activation of NADPH oxidase. In addition, gAcrp suppressed ethanol-induced increase in the expression of NADPH oxidase subunits, including Nox2 and p22(phox), via modulation of nuclear factor-κB pathway. Furthermore, pretreatment with compound C, a selective inhibitor of AMPK, or knockdown of AMPK by small interfering RNA restored suppression of ethanol-induced ROS production and Nox2 expression by gAcrp. Finally, we found that gAcrp treatment induced phosphorylation of liver kinase B1 (LKB1), an upstream signaling molecule mediating AMPK activation. Knockdown of LKB1 restored gAcrp-suppressed Nox2 expression, suggesting that LKB1/AMPK pathway plays a critical role in the suppression of ethanol-induced ROS production and activation of NADPH oxidase by gAcrp. Taken together, these results demonstrate that globular adiponectin prevents ethanol-induced ROS production, at least in part, via modulation of NADPH oxidase in macrophages. Further, LKB1/AMPK axis plays an important role in the suppression of ethanol-induced NADPH oxidase activation by gAcrp in macrophages. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  10. A detached stellar-mass black hole candidate in the globular cluster NGC 3201

    NASA Astrophysics Data System (ADS)

    Giesers, Benjamin; Dreizler, Stefan; Husser, Tim-Oliver; Kamann, Sebastian; Anglada Escudé, Guillem; Brinchmann, Jarle; Carollo, C. Marcella; Roth, Martin M.; Weilbacher, Peter M.; Wisotzki, Lutz

    2018-03-01

    As part of our massive spectroscopic survey of 25 Galactic globular clusters with MUSE, we performed multiple epoch observations of NGC 3201 with the aim of constraining the binary fraction. In this cluster, we found one curious star at the main-sequence turn-off with radial velocity variations of the order of 100 km s- 1, indicating the membership to a binary system with an unseen component since no other variations appear in the spectra. Using an adapted variant of the generalized Lomb-Scargle periodogram, we could calculate the orbital parameters and found the companion to be a detached stellar-mass black hole with a minimum mass of 4.36 ± 0.41 M⊙. The result is an important constraint for binary and black hole evolution models in globular clusters as well as in the context of gravitational wave sources.

  11. MUSE crowded field 3D spectroscopy of over 12 000 stars in the globular cluster NGC 6397. I. The first comprehensive HRD of a globular cluster

    NASA Astrophysics Data System (ADS)

    Husser, Tim-Oliver; Kamann, Sebastian; Dreizler, Stefan; Wendt, Martin; Wulff, Nina; Bacon, Roland; Wisotzki, Lutz; Brinchmann, Jarle; Weilbacher, Peter M.; Roth, Martin M.; Monreal-Ibero, Ana

    2016-04-01

    Aims: We demonstrate the high multiplex advantage of crowded field 3D spectroscopy with the new integral field spectrograph MUSE by means of a spectroscopic analysis of more than 12 000 individual stars in the globular cluster NGC 6397. Methods: The stars are deblended with a point spread function fitting technique, using a photometric reference catalogue from HST as prior, including relative positions and brightnesses. This catalogue is also used for a first analysis of the extracted spectra, followed by an automatic in-depth analysis via a full-spectrum fitting method based on a large grid of PHOENIX spectra. Results: We analysed the largest sample so far available for a single globular cluster of 18 932 spectra from 12 307 stars in NGC 6397. We derived a mean radial velocity of vrad = 17.84 ± 0.07 km s-1 and a mean metallicity of [Fe/H] = -2.120 ± 0.002, with the latter seemingly varying with temperature for stars on the red giant branch (RGB). We determine Teff and [Fe/H] from the spectra, and log g from HST photometry. This is the first very comprehensive Hertzsprung-Russell diagram (HRD) for a globular cluster based on the analysis of several thousands of stellar spectra, ranging from the main sequence to the tip of the RGB. Furthermore, two interesting objects were identified; one is a post-AGB star and the other is a possible millisecond-pulsar companion. Data products are available at http://muse-vlt.eu/scienceBased on observations obtained at the Very Large Telescope (VLT) of the European Southern Observatory, Paranal, Chile (ESO Programme ID 60.A-9100(C)).

  12. Sugar-induced conformational change found in the HA-33/HA-17 trimer of the botulinum toxin complex.

    PubMed

    Sagane, Yoshimasa; Hayashi, Shintaro; Matsumoto, Takashi; Miyashita, Shin-Ichiro; Inui, Ken; Miyata, Keita; Yajima, Shunsuke; Suzuki, Tomonori; Hasegawa, Kimiko; Yamano, Akihito; Nishikawa, Atsushi; Ohyama, Tohru; Watanabe, Toshihiro; Niwa, Koichi

    2013-08-30

    Large-sized botulinum toxin complex (L-TC) is formed by conjugation of neurotoxin, nontoxic nonhemagglutinin and hemagglutinin (HA) complex. The HA complex is formed by association of three HA-70 molecules and three HA-33/HA-17 trimers, comprised of a single HA-17 and two HA-33 proteins. The HA-33/HA-17 trimer isolated from serotype D L-TC has the ability to bind to and penetrate through the intestinal epithelial cell monolayer in a sialic acid-dependent manner, and thus it plays an important role in toxin delivery through the intestinal cell wall. In this study, we determined the solution structure of the HA-33/HA-17 trimer by using small-angle X-ray scattering (SAXS). The SAXS image of HA-33/HA-17 exhibited broadly similar appearance to the crystal image of the complex. On the other hand, in the presence of N-acetylneuraminic acid, glucose and galactose, the solution structure of the HA-33/HA-17 trimer was drastically altered compared to the structure in the absence of the sugars. Sugar-induced structural change of the HA-33/HA-17 trimer may contribute to cell binding and subsequent transport across the intestinal cell layer. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Identification of a Region in the Stalk Domain of the Nipah Virus Receptor Binding Protein That Is Critical for Fusion Activation

    PubMed Central

    Talekar, Aparna; DeVito, Ilaria; Salah, Zuhair; Palmer, Samantha G.; Chattopadhyay, Anasuya; Rose, John K.; Xu, Rui; Wilson, Ian A.; Moscona, Anne

    2013-01-01

    Paramyxoviruses, including the emerging lethal human Nipah virus (NiV) and the avian Newcastle disease virus (NDV), enter host cells through fusion of the viral and target cell membranes. For paramyxoviruses, membrane fusion is the result of the concerted action of two viral envelope glycoproteins: a receptor binding protein and a fusion protein (F). The NiV receptor binding protein (G) attaches to ephrin B2 or B3 on host cells, whereas the corresponding hemagglutinin-neuraminidase (HN) attachment protein of NDV interacts with sialic acid moieties on target cells through two regions of its globular domain. Receptor-bound G or HN via its stalk domain triggers F to undergo the conformational changes that render it competent to mediate fusion of the viral and cellular membranes. We show that chimeric proteins containing the NDV HN receptor binding regions and the NiV G stalk domain require a specific sequence at the connection between the head and the stalk to activate NiV F for fusion. Our findings are consistent with a general mechanism of paramyxovirus fusion activation in which the stalk domain of the receptor binding protein is responsible for F activation and a specific connecting region between the receptor binding globular head and the fusion-activating stalk domain is required for transmitting the fusion signal. PMID:23903846

  14. The globular cluster NGC 7492 and the Sagittarius tidal stream: together but unmixed

    NASA Astrophysics Data System (ADS)

    Carballo-Bello, J. A.; Corral-Santana, J. M.; Catelan, M.; Martínez-Delgado, D.; Muñoz, R. R.; Sollima, A.; Navarrete, C.; Duffau, S.; Côté, P.; Mora, M. D.

    2018-03-01

    We have derived from VIMOS spectroscopy the radial velocities for a sample of 71 stars selected from CFHT/Megacam photometry around the Galactic globular cluster NGC 7492. In the resulting velocity distribution, it is possible to distinguish two relevant non-Galactic kinematic components along the same line of sight: a group of stars at 〈vr〉 ˜ 125 km s-1 which is compatible with the velocity of the old leading arm of the Sagittarius tidal stream, and a larger number of objects at 〈vr〉 ˜ -110 km s-1 that might be identified as members of the trailing wrap of the same stream. The systemic velocity of NGC 7492 set at vr ˜ -177 km s-1 differs significantly from that of both components, thus our results confirm that this cluster is not one of the globular clusters deposited by the Sagittarius dwarf spheroidal in the Galactic halo, even if it is immersed in the stream. A group of stars with 〈vr〉 ˜ - 180 km s-1 might be comprised of cluster members along one of the tidal tails of NGC 7492.

  15. The most metal-poor Galactic globular cluster: the first spectroscopic observations of ESO280-SC06

    NASA Astrophysics Data System (ADS)

    Simpson, Jeffrey D.

    2018-07-01

    We present the first spectroscopic observations of the very metal-poor Milky Way globular cluster ESO280-SC06. Using spectra acquired with the 2dF/AAOmega spectrograph on the Anglo-Australian Telescope, we have identified 13 members of the cluster, and estimate from their infrared calcium triplet lines that the cluster has a metallicity of [Fe/H]=-2.48^{+0.06 }_{ -0.11}. This would make it the most metal-poor globular cluster known in the Milky Way. This result was verified with comparisons to three other metal-poor globular clusters that had been observed and analysed in the same manner. We also present new photometry of the cluster from EFOSC2 and SkyMapper and confirm that the cluster is located 22.9 ± 2.1 kpc from the Sun and 15.2 ± 2.1 kpc from the Galactic Centre, and has a radial velocity of 92.5^{+2.4 }_{ -1.6} km s-1. These new data finds the cluster to have a radius about half that previously estimated, and we find that the cluster has a dynamical mass of the cluster of (12 ± 2) × 103 M⊙. Unfortunately, we lack reliable proper motions to fully characterize its orbit about the Galaxy. Intriguingly, the photometry suggests that the cluster lacks a well-populated horizontal branch, something that has not been observed in a cluster so ancient or metal poor.

  16. The most metal-poor Galactic globular cluster: the first spectroscopic observations of ESO280-SC06

    NASA Astrophysics Data System (ADS)

    Simpson, Jeffrey D.

    2018-04-01

    We present the first spectroscopic observations of the very metal-poor Milky Way globular cluster ESO280-SC06. Using spectra acquired with the 2dF/AAOmega spectrograph on the Anglo-Australian Telescope, we have identified 13 members of the cluster, and estimate from their infrared calcium triplet lines that the cluster has a metallicity of [Fe/H]={-2.48}^{+0.06}_{-0.11}. This would make it the most metal-poor globular cluster known in the Milky Way. This result was verified with comparisons to three other metal-poor globular clusters that had been observed and analyzed in the same manner. We also present new photometry of the cluster from EFOSC2 and SkyMapper and confirm that the cluster is located 22.9 ± 2.1 kpc from the Sun and 15.2 ± 2.1 kpc from the Galactic centre, and has a radial velocity of 92.5 + 2.4-1.6 km s-1. These new data finds the cluster to have a radius about half that previously estimated, and we find that the cluster has a dynamical mass of the cluster of (12 ± 2) × 103 M⊙. Unfortunately, we lack reliable proper motions to fully characterize its orbit about the Galaxy. Intriguingly, the photometry suggests that the cluster lacks a well-populated horizontal branch, something that has not been observed in a cluster so ancient or metal-poor.

  17. BLUE STRAGGLERS IN GLOBULAR CLUSTER 47 TUCANAE

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The core of globular cluster 47 Tucanae is home to many blue stragglers, rejuvenated stars that glow with the blue light of young stars. A ground-based telescope image (on the left) shows the entire crowded core of 47 Tucanae, located 15,000 light-years away in the constellation Tucana. Peering into the heart of the globular cluster's bright core, the Hubble Space Telescope's Wide Field and Planetary Camera 2 separated the dense clump of stars into many individual stars (image on right). Some of these stars shine with the light of old stars; others with the blue light of blue stragglers. The yellow circles in the Hubble telescope image highlight several of the cluster's blue stragglers. Analysis for this observation centered on one massive blue straggler. Astronomers theorize that blue stragglers are formed either by the slow merger of stars in a double-star system or by the collision of two unrelated stars. For the blue straggler in 47 Tucanae, astronomers favor the slow merger scenario. This image is a 3-color composite of archival Hubble Wide Field and Planetary Camera 2 images in the ultraviolet (blue), blue (green), and violet (red) filters. Color tables were assigned and scaled so that the red giant stars appear orange, main-sequence stars are white/green, and blue stragglers are appropriately blue. The ultraviolet images were taken on Oct. 25, 1995, and the blue and violet images were taken on Sept. 1, 1995. Credit: Rex Saffer (Villanova University) and Dave Zurek (STScI), and NASA

  18. Medium resolution spectroscopy and chemical composition of Galactic globular clusters

    NASA Astrophysics Data System (ADS)

    Khamidullina, D. A.; Sharina, M. E.; Shimansky, V. V.; Davoust, E.

    We used integrated-light medium-resolution spectra of six Galactic globular clusters and model stellar atmospheres to carry out population synthesis and to derive chemical composition and age of the clusters. We used medium-resolution spectra of globular clusters published by Schiavon et al. (2005), as well as our long-slit observations with the 1.93 m telescope of the Haute Provence Observatory. The observed spectra were fitted to the theoretical ones interactively. As an initial approach, we used masses, radii and log g of stars in the clusters corresponding to the best fitting isochrones in the observed color-magnitude diagrams. The computed synthetic blanketed spectra of stars were summed according to the Chabrier mass function. To improve the determination of age and helium content, the shape and depth of the Balmer absorption lines was analysed. The abundances of Mg, Ca, C and several other elements were derived. A reasonable agreement with the literature data both in chemical composition and in age of the clusters is found. Our method might be useful for the development of stellar population models and for a better understanding of extragalactic star clusters.

  19. Globular Adiponectin Inhibits Lipopolysaccharide-Primed Inflammasomes Activation in Macrophages via Autophagy Induction: The Critical Role of AMPK Signaling

    PubMed Central

    Kim, Mi Jin; Kim, Eun Hye; TiliJa Pun, Nirmala; Chang, Jae-Hoon; Kim, Jung-Ae; Jeong, Jee-Heon; Choi, Dong Young; Kim, Sang-Hyun; Park, Pil-Hoon

    2017-01-01

    The inflammasome acts as a key platform for the activation of pro-inflammatory cytokines. Adiponectin exhibits potent anti-inflammatory properties. However, the effect of adiponectin on the modulation of the inflammasome has not been explored. Herein, we show that globular adiponectin (gAcrp) suppressed lipopolysaccharide (LPS)-primed inflammasomes activation in murine peritoneal macrophages judged by prevention of interleukin-1β (IL-1β) maturation, caspase-1 activation, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) speck formation, and pyroptotic cell death. Interestingly, pretreatment with 3-methyl adenine, a pharmacological inhibitor of autophagy, abrogated the suppressive effects of gAcrp on IL-1β secretion and caspase-1 activation, indicating the crucial role of autophagy induction in gAcrp-modulation of the inflammasome activation. In addition, inhibition of 5′Adenosine monophaspahate (AMP)-activated protein kinase (AMPK) signaling abolished suppressive effect of gAcrp on inflammasomes activation. Furthermore, autophagy induction or inhibition of the inflammasome activation by gAcrp was not observed in macrophages deficient in AMPK. Taken together, these results indicate that adiponectin inhibits LPS-primed inflammasomes activation in macrophages via autophagy induction and AMPK signaling-dependent mechanisms. PMID:28617316

  20. Features of globular cluster's dynamics with an intermediate-mass black hole

    NASA Astrophysics Data System (ADS)

    Ryabova, Marina V.; Gorban, Alena S.; Shchekinov, Yuri A.; Vasiliev, Evgenii O.

    2018-02-01

    In this paper, we address the question of how a central intermediate-mass black hole (IMBH) in a globular cluster (GC) affects dynamics, core collapse, and formation of the binary population. It is shown that the central IMBH forms a binary system that affects dynamics of stars in the cluster significantly. The presence of an intermediate-mass black hole with mass ≥ 1.0-1.7%of the total stellar mass in the cluster inhibits the formation of binary stars population.

  1. Mutiple Stellar Populations in Blanco DECam Bulge Survey Globular Clusters

    NASA Astrophysics Data System (ADS)

    Miller, Doryan; Pilachowski, C. A.; Johnson, C. I.; Rich, R. Michael; Clarkson, William I.; Young, M.; Michael, S.

    2018-01-01

    Preliminary SDSS ugrizY photometric observations of globular cluster stars included in the Blanco DECam Bulge Survey (BDBS) were examined to determine the suitability of these data to characterize stellar populations within clusters. The BDBS fields include around two dozen globular clusters, including the iron-complex cluster M22 and the pulsar-rich cluster Terzan 5. Many globular clusters show evidence for multiple stellar populations as a spread in the u-g color of stars in a given phase of stellar evolution, and in some clusters, the populations have different radial distributions. BDBS clusters with low and/or non-variable reddening and long dynamical mixing time scales were selected for study, and photometry for RGB and main sequence stars within two half-light radii from the center of each cluster was extracted from the BDBS preliminary catalog. Field contamination was reduced in each candidate cluster by removing all stars more than a tenth of a magnitude from the best-fit fiducial curves following the g-r vs r color-magnitude diagram. The remaining stars were split into separate populations based on u-g color, and effective cumulative distribution functions vs. half-light radius were compared to identify differences in the populations’ radial distributions.

  2. Multiple Populations in Globular Clusters - The Spectroscopic View

    NASA Astrophysics Data System (ADS)

    Cohen, Judith G.

    2015-03-01

    I review the evidence supporting and characterizing multiple populations within globular clusters (GCs) based on spectroscopy, i.e. on abundance variations within the stellar population of an individual GC, which dates back to almost 40 years ago. I discuss some of my recent work in this area.

  3. Caveolin-1 down-regulation is required for Wnt5a-Frizzled 2 signalling in Ha-RasV12 -induced cell transformation.

    PubMed

    Lin, Hsiu-Kuan; Lin, Hsi-Hui; Chiou, Yu-Wei; Wu, Ching-Lung; Chiu, Wen-Tai; Tang, Ming-Jer

    2018-05-01

    Caveolin-1 (Cav1) is down-regulated during MK4 (MDCK cells harbouring inducible Ha-Ras V12 gene) transformation by Ha-Ras V12 . Cav1 overexpression abrogates the Ha-Ras V12 -driven transformation of MK4 cells; however, the targeted down-regulation of Cav1 is not sufficient to mimic this transformation. Cav1-silenced cells, including MK4/shCav1 cells and MDCK/shCav1 cells, showed an increased cell area and discontinuous junction-related proteins staining. Cellular and mechanical transformations were completed when MDCK/shCav1 cells were treated with medium conditioned by MK4 cells treated with IPTG (MK4+I-CM) but not with medium conditioned by MK4 cells. Nanoparticle tracking analysis showed that Ha-Ras V12 -inducing MK4 cells increased exosome-like microvesicles release compared with their normal counterparts. The cellular and mechanical transformation activities of MK4+I-CM were abolished after heat treatment and exosome depletion and were copied by exosomes derived from MK4+I-CM (MK4+I-EXs). Wnt5a, a downstream product of Ha-Ras V12 , was markedly secreted by MK4+I-CM and MK4+I-EXs. Suppression of Wnt5a expression and secretion using the porcupine inhibitor C59 or Wnt5a siRNA inhibited the Ha-Ras V12 - and MK4+I-CM-induced transformation of MK4 cells and MDCK/shCav1 cells, respectively. Cav1 down-regulation, either by Ha-Ras V12 or targeted shRNA, increased frizzled-2 (Fzd2) protein levels without affecting its mRNA levels, suggesting a novel role of Cav1 in negatively regulating Fzd2 expression. Additionally, silencing Cav1 facilitated the internalization of MK4+I-EXs in MDCK cells. These data suggest that Cav1-dependent repression of Fzd2 and exosome uptake is potentially relevant to its antitransformation activity, which hinders the activation of Ha-Ras V12 -Wnt5a-Stat3 pathway. Altogether, these results suggest that both decreasing Cav1 and increasing exosomal Wnt5a must be implemented during Ha-Ras V12 -driven cell transformation. © 2018 The Authors

  4. The Observational and Theoretical Tidal Radii of Globular Clusters in M87

    NASA Astrophysics Data System (ADS)

    Webb, Jeremy J.; Sills, Alison; Harris, William E.

    2012-02-01

    Globular clusters have linear sizes (tidal radii) which theory tells us are determined by their masses and by the gravitational potential of their host galaxy. To explore the relationship between observed and expected radii, we utilize the globular cluster population of the Virgo giant M87. Unusually deep, high signal-to-noise images of M87 are used to measure the effective and limiting radii of approximately 2000 globular clusters. To compare with these observations, we simulate a globular cluster population that has the same characteristics as the observed M87 cluster population. Placing these simulated clusters in the well-studied tidal field of M87, the orbit of each cluster is solved and the theoretical tidal radius of each cluster is determined. We compare the predicted relationship between cluster size and projected galactocentric distance to observations. We find that for an isotropic distribution of cluster velocities, theoretical tidal radii are approximately equal to observed limiting radii for R gc < 10 kpc. However, the isotropic simulation predicts a steep increase in cluster size at larger radii, which is not observed in large galaxies beyond the Milky Way. To minimize the discrepancy between theory and observations, we explore the effects of orbital anisotropy on cluster sizes, and suggest a possible orbital anisotropy profile for M87 which yields a better match between theory and observations. Finally, we suggest future studies which will establish a stronger link between theoretical tidal radii and observed radii.

  5. Spectrum syntheses of high-resolution integrated light spectra of Galactic globular clusters

    NASA Astrophysics Data System (ADS)

    Sakari, Charli M.; Shetrone, Matthew; Venn, Kim; McWilliam, Andrew; Dotter, Aaron

    2013-09-01

    Spectrum syntheses for three elements (Mg, Na and Eu) in high-resolution integrated light spectra of the Galactic globular clusters 47 Tuc, M3, M13, NGC 7006 and M15 are presented, along with calibration syntheses of the solar and Arcturus spectra. Iron abundances in the target clusters are also derived from integrated light equivalent width analyses. Line profiles in the spectra of these five globular clusters are well fitted after careful consideration of the atomic and molecular spectral features, providing levels of precision that are better than equivalent width analyses of the same integrated light spectra, and that are comparable to the precision in individual stellar analyses. The integrated light abundances from the 5528 and 5711 Å Mg I lines, the 6154 and 6160 Å Na I lines, and the 6645 Å Eu II line fall within the observed ranges from individual stars; however, these integrated light abundances do not always agree with the average literature abundances. Tests with the second parameter clusters M3, M13 and NGC 7006 show that assuming an incorrect horizontal branch morphology is likely to have only a small ( ≲ 0.06 dex) effect on these Mg, Na and Eu abundances. These tests therefore show that integrated light spectrum syntheses can be applied to unresolved globular clusters over a wide range of metallicities and horizontal branch morphologies. Such high precision in integrated light spectrum syntheses is valuable for interpreting the chemical abundances of globular cluster systems around other galaxies.

  6. Pyroelectricity in globular protein lysozyme films

    NASA Astrophysics Data System (ADS)

    Stapleton, A.; Noor, M. R.; Haq, E. U.; Silien, C.; Soulimane, T.; Tofail, S. A. M.

    2018-03-01

    Pyroelectricity is the ability of certain non-centrosymmetric materials to generate an electric charge in response to a change in temperature and finds use in a range of applications from burglar alarms to thermal imaging. Some biological materials also exhibit pyroelectricity but the examples of the effect are limited to fibrous proteins, polypeptides, and tissues and organs of animals and plants. Here, we report pyroelectricity in polycrystalline aggregate films of lysozyme, a globular protein.

  7. Effect of Water-Glass Coating on HA and HA-TCP Samples for MSCs Adhesion, Proliferation, and Differentiation.

    PubMed

    Bajpai, Indu; Kim, Duk Yeon; Kyong-Jin, Jung; Song, In-Hwan; Kim, Sukyoung

    2016-01-01

    Ca-P and silicon based materials have become very popular as bone tissue engineering materials. In this study, water-glass (also known as sodium silicate glass) was coated on sintered hydroxyapatite (HA) and HA-TCP (TCP stands for tricalcium phosphate) samples and subsequently heat-treated at 600°C for 2 hrs. X-rays diffraction showed the presence of β- and α-TCP phases along with HA in the HA-TCP samples. Samples without coating, with water-glass coating, and heat-treated after water-glass coating were used to observe the adhesion and proliferation response of bone marrow derived-mesenchymal stem cells (MSCs). Cell culture was carried out for 4 hrs, 1 day, and 7 days. Interestingly, all samples showed similar response for cell adhesion and proliferation up to 7-day culture but fibronectin, E-cadherin, and osteogenic differentiation related genes (osteocalcin and osteopontin) were significantly induced in heat-treated water-glass coated HA-TCP samples. A water-glass coating on Ca-P samples was not found to influence the cell proliferation response significantly but activated some extracellular matrix genes and induced osteogenic differentiation in the MSCs.

  8. Conformational divergence in the HA-33/HA-17 trimer of serotype C and D botulinum toxin complex.

    PubMed

    Sagane, Yoshimasa; Hayashi, Shintaro; Akiyama, Tomonori; Matsumoto, Takashi; Hasegawa, Kimiko; Yamano, Akihito; Suzuki, Tomonori; Niwa, Koichi; Watanabe, Toshihiro; Yajima, Shunsuke

    2016-08-05

    Clostridium botulinum produces a large toxin complex (L-TC) comprising botulinum neurotoxin associated with auxiliary nontoxic proteins. A complex of 33- and 17-kDa hemagglutinins (an HA-33/HA-17 trimer) enhances L-TC transport across the intestinal epithelial cell layer via binding HA-33 to a sugar on the cell surface. At least two subtypes of serotype C/D HA-33 exhibit differing preferences for the sugars sialic acid and galactose. Here, we compared the three-dimensional structures of the galactose-binding HA-33 and HA-33/HA-17 trimers produced by the C-Yoichi strain. Comparisons of serotype C/D HA-33 sequences reveal a variable region with relatively low sequence similarity across the C. botulinum strains; the variability of this region may influence the manner of sugar-recognition by HA-33. Crystal structures of sialic acid- and galactose-binding HA-33 are broadly similar in appearance. However, small-angle X-ray scattering revealed distinct solution structures for HA-33/HA-17 trimers. A structural change in the C-terminal variable region of HA-33 might cause a dramatic shift in the conformation and sugar-recognition mode of HA-33/HA-17 trimer. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. SEARCH FOR RED DWARF STARS IN GLOBULAR CLUSTER NGC 6397

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Left A NASA Hubble Space Telescope image of a small region (1.4 light-years across) in the globular star cluster NGC 6397. Simulated stars (diamonds) have been added to this view of the same region of the cluster to illustrate what astronomers would have expected to see if faint red dwarf stars were abundant in the Milky Way Galaxy. The field would then contain 500 stars, according to theoretical calculations. Right The unmodified HST image shows far fewer stars than would be expected, according to popular theories of star formation. HST resolves about 200 stars. The stellar density is so low that HST can literally see right through the cluster and resolve far more distant background galaxies. From this observation, scientists have identified the surprising cutoff point below which nature apparently doesn't make many stars smaller that 1/5 the mass of our Sun. These HST findings provide new insights into star formation in our Galaxy. Technical detail:The globular cluster NGC 6397, one of the nearest and densest agglomerations of stars, is located 7,200 light-years away in the southern constellation Ara. This visible-light picture was taken on March 3, 1994 with the Wide Field Planetary Camera 2, as part the HST parallel observing program. Credit: F. Paresce, ST ScI and ESA and NASA

  10. Tidal stripping stellar substructures around four metal-poor globular clusters in the galactic bulge

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chun, Sang-Hyun; Kang, Minhee; Jung, DooSeok

    2015-01-01

    We investigate the spatial density configuration of stars around four metal-poor globular clusters (NGC 6266, NGC 6626, NGC 6642, and NGC 6723) in the Galactic bulge region using wide-field deep J, H, and K imaging data obtained with the Wide Field Camera near-infrared array on the United Kingdom Infrared Telescope. A statistical weighted filtering algorithm for the stars on the color–magnitude diagram is applied in order to sort cluster member candidates from the field star contamination. In two-dimensional isodensity contour maps of the clusters, we find that all four of the globular clusters exhibit strong evidence of tidally stripped stellarmore » features beyond the tidal radius in the form of tidal tails or small density lobes/chunks. The orientations of the extended stellar substructures are likely to be associated with the effect of dynamic interaction with the Galaxy and the cluster's space motion. The observed radial density profiles of the four globular clusters also describe the extended substructures; they depart from theoretical King and Wilson models and have an overdensity feature with a break in the slope of the profile at the outer region of clusters. The observed results could imply that four globular clusters in the Galactic bulge region have experienced strong environmental effects such as tidal forces or bulge/disk shocks of the Galaxy during the dynamical evolution of globular clusters. These observational results provide further details which add to our understanding of the evolution of clusters in the Galactic bulge region as well as the formation of the Galaxy.« less

  11. Possible role of PAPR-1 in protecting human HaCaT cells against cytotoxicity of SiO2 nanoparticles.

    PubMed

    Gong, Chunmei; Yang, Linqing; Zhou, Jichang; Guo, Xiang; Zhuang, Zhixiong

    2017-10-05

    Nano-SiO 2 materials play a significant role in the engineered nanomaterials (ENMs) field. The ease of their production as well as their relatively low cost has promoted the wide use of these products in many fields. Nano-SiO 2 exposure is known to cause severe DNA damage; however, the underlying mechanisms remain poorly understood. In a previous study, we found that nano-SiO 2 exposure regulate the expression of the poly(ADP-ribose) polymerases-1 (PARP-1), a pivotal DNA repair gene, in human HaCaT cells. Here, we employed lentivirus-mediated RNA interference (RNAi) to knock down PAPR-1 expression in HaCaT cells and explored the potential role of PARP-1 in nano-SiO 2 induced cytotoxicity. We found that nano-SiO 2 treatment of HaCaT cells causes decreased cell viability, increased apoptosis and DNA damage. Nano-SiO 2 -treated HaCaT cells were also found to have slightly changed cell cycle distribution. Lentivirus-mediated PAPR-1 knockdown partially aggravated cytotoxicity and increased apoptosis induced by nano-SiO 2 treatment. Nano-SiO 2 had significant toxicity to human HaCaT cells and causes DNA damage. PAPR-1 knock-down cell line appears more sensitive to nano-SiO 2 than the control cells in DNA damage. The results suggest that PAPR-1 is involved in protecting cells from damage caused by nano-SiO 2 . Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Simultaneous detection of assembly and disassembly of multivalent HA tag and anti-HA antibody in single in-capillary assay.

    PubMed

    Wang, Jianhao; Qin, Yuqin; Qin, Haifang; Liu, Li; Ding, Shumin; Teng, Yiwan; Ji, Junling; Qiu, Lin; Jiang, Pengju

    2016-08-01

    Herein, we have developed an in-capillary assay for simultaneous detection of the assembly and disassembly of the multivalent HA tag peptide and antibody. HA tag with hexahistidine at C terminus (YPYDVPDYAG4 H6 , termed YPYDH6 ) was conjugated with quantum dots (QDs) by metal-affinity force to form a multivalent HA tag (QD-YPYDH6 ). QD-YPYDH6 and monoclonal anti-HA antibody (anti-HA) were sequentially injected into the capillary. They were mixed and assembled inside the capillary. The reaction products were online discriminated and detected by fluorescence coupled capillary electrophoresis (CE-FL). For the in-capillary assay, the binding efficiency of the multivalent HA tag and antibody on was influenced by the molar ratio and injection time. Such novel assay could even give out the self-assembly kinetic constant of QDs and YPYDH6 as KD of 34.1 μM with n (binding cooperativeness) of 2.2 by Hill equation. More importantly, the simultaneous detection of the assembly and imidazole (Im) induced disassembly of the QD-YPYDH6 -anti-HA complex was achieved in a single in-capillary assay. Our study demonstrated a new method for the online detection of antigen-antibody interactions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Testing modified gravity with globular clusters: the case of NGC 2419

    NASA Astrophysics Data System (ADS)

    Llinares, Claudio

    2018-05-01

    The dynamics of globular clusters has been studied in great detail in the context of general relativity as well as with modifications of gravity that strongly depart from the standard paradigm such as Modified Newtonian Dynamics. However, at present there are no studies that aim to test the impact that less extreme modifications of gravity (e.g. models constructed as alternatives to dark energy) have on the behaviour of globular clusters. This Letter presents fits to the velocity dispersion profile of the cluster NGC 2419 under the symmetron-modified gravity model. The data show an increase in the velocity dispersion towards the centre of the cluster which could be difficult to explain within general relativity. By finding the best-fitting solution associated with the symmetron model, we show that this tension does not exist in modified gravity. However, the best-fitting parameters give a model that is inconsistent with the dynamics of the Solar system. Exploration of different screening mechanisms should give us the chance to understand if it is possible to maintain the appealing properties of the symmetron model when it comes to globular clusters and at the same time recover the Solar system dynamics properly.

  14. Formation of black hole x-ray binaries in globular clusters

    NASA Astrophysics Data System (ADS)

    Kremer, Kyle; Chatterjee, Sourav; Rodriguez, Carl; Rasio, Frederic

    2018-01-01

    We explore the formation of mass-transferring binary systems containing black holes within globular clusters. We show that it is possible to form mass-transferring binaries with main sequence, giant, and white dwarf companions with a variety of orbital parameters in globular clusters spanning a large range in present-day properties. We show that the presence of mass-transferring black hole systems has little correlation with the total number of black holes within the cluster at any time. In addition to mass-transferring binaries retained within their host clusters at late times, we also examine the black hole and neutron star binaries that are ejected from their host clusters. These ejected systems may contribute to the low-mass x-ray binary population in the galactic field.

  15. Gravitational microlensing by low-mass objects in the globular cluster M22.

    PubMed

    Sahu, K C; Casertano, S; Livio, M; Gilliland, R L; Panagia, N; Albrow, M D; Potter, M

    2001-06-28

    Gravitational microlensing offers a means of determining directly the masses of objects ranging from planets to stars, provided that the distances and motions of the lenses and sources can be determined. A globular cluster observed against the dense stellar field of the Galactic bulge presents ideal conditions for such observations because the probability of lensing is high and the distances and kinematics of the lenses and sources are well constrained. The abundance of low-mass objects in a globular cluster is of particular interest, because it may be representative of the very early stages of star formation in the Universe, and therefore indicative of the amount of dark baryonic matter in such clusters. Here we report a microlensing event associated with the globular cluster M22. We determine the mass of the lens to be 0.13(+0.03)(-0.02) solar masses. We have also detected six events that are unresolved in time. If these are also microlensing events, they imply that a non-negligible fraction of the cluster mass resides in the form of free-floating planetary-mass objects.

  16. Image-Subtraction Photometry of Variable Stars in the Globular Clusters NGC 6388 and NGC 6441

    NASA Technical Reports Server (NTRS)

    Corwin, Michael T.; Sumerel, Andrew N.; Pritzl, Barton J.; Smith, Horace A.; Catelan, M.; Sweigart, Allen V.; Stetson, Peter B.

    2006-01-01

    We have applied Alard's image subtraction method (ISIS v2.1) to the observations of the globular clusters NGC 6388 and NGC 6441 previously analyzed using standard photometric techniques (DAOPHOT, ALLFRAME). In this reanalysis of observations obtained at CTIO, besides recovering the variables previously detected on the basis of our ground-based images, we have also been able to recover most of the RR Lyrae variables previously detected only in the analysis of Hubble Space Telescope WFPC2 observations of the inner region of NGC 6441. In addition, we report five possible new variables not found in the analysis of the EST observations of NGC 6441. This dramatically illustrates the capabilities of image subtraction techniques applied to ground-based data to recover variables in extremely crowded fields. We have also detected twelve new variables and six possible variables in NGC 6388 not found in our previous groundbased studies. Revised mean periods for RRab stars in NGC 6388 and NGC 6441 are 0.676 day and 0.756 day, respectively. These values are among the largest known for any galactic globular cluster. Additional probable type II Cepheids were identified in NGC 6388, confirming its status as a metal-rich globular cluster rich in Cepheids.

  17. The Structure of the Neurotoxin- Associated Protein HA33/A from Clostridium botulinum Suggests a Reoccurring Beta-Trefoil Fold in the Progenitor Toxin Complex

    DTIC Science & Technology

    2004-12-16

    mistletoe lectin I. The ricin and mistle- toe lectin I structures revealed a domain architec- ture that are similar to HA33/A with two b-trefoil...domains. The complex crystal structures of ricin bound to lactose and mistletoe lectin I bound to galactose revealed that only the 1a and 2g repeats of...H., Tonevitsky, A. G., Agapov, I. I., Saward, S., Pfuller, U. & Palmer, R. A. (2003). Crystal structure at 3 Å of mistletoe lectin I, a dimeric

  18. Influence of insertion site of the avian influenza virus haemagglutinin (HA) gene within the Newcastle disease virus genome on HA expression.

    PubMed

    Ramp, Kristina; Skiba, Martin; Karger, Axel; Mettenleiter, Thomas C; Römer-Oberdörfer, Angela

    2011-02-01

    Members of the order Mononegavirales express their genes in a transcription gradient from 3' to 5'. To assess how this impacts on expression of a foreign transgene, the haemagglutinin (HA) of highly pathogenic avian influenza virus (HPAIV) A/chicken/Vietnam/P41/05 (subtype H5N1) was inserted between the phosphoprotein (P) and matrix protein (M), M and fusion protein (F), or F and haemagglutinin-neuraminidase protein (HN) genes of attenuated Newcastle disease virus (NDV) Clone 30. In addition, the gene encoding the neuraminidase of HPAIV A/duck/Vietnam/TG24-01/05 (subtype H5N1) was inserted into the NDV genome either alone or in combination with the HA gene. All recombinants replicated well in embryonated chicken eggs. The expression levels of HA-specific mRNA and protein were quantified by Northern blot analysis and mass spectrometry, with good correlation. HA expression levels differed only moderately and were highest in the recombinant carrying the HA insertion between the F and HN genes of NDV.

  19. A novel pathogenic mechanism of highly pathogenic avian influenza H5N1 viruses involves hemagglutinin mediated resistance to serum innate inhibitors.

    PubMed

    Panaampon, Jutatip; Ngaosuwankul, Nathamon; Suptawiwat, Ornpreya; Noisumdaeng, Pirom; Sangsiriwut, Kantima; Siridechadilok, Bunpote; Lerdsamran, Hatairat; Auewarakul, Prasert; Pooruk, Phisanu; Puthavathana, Pilaipan

    2012-01-01

    In this study, the effect of innate serum inhibitors on influenza virus infection was addressed. Seasonal influenza A(H1N1) and A(H3N2), 2009 pandemic A(H1N1) (H1N1pdm) and highly pathogenic avian influenza (HPAI) A(H5N1) viruses were tested with guinea pig sera negative for antibodies against all of these viruses as evaluated by hemagglutination-inhibition and microneutralization assays. In the presence of serum inhibitors, the infection by each virus was inhibited differently as measured by the amount of viral nucleoprotein produced in Madin-Darby canine kidney cells. The serum inhibitors inhibited seasonal influenza A(H3N2) virus the most, while the effect was less in seasonal influenza A(H1N1) and H1N1pdm viruses. The suppression by serum inhibitors could be reduced by heat inactivation or treatment with receptor destroying enzyme. In contrast, all H5N1 strains tested were resistant to serum inhibitors. To determine which structure (hemagglutinin (HA) and/or neuraminidase (NA)) on the virus particles that provided the resistance, reverse genetics (rg) was applied to construct chimeric recombinant viruses from A/Puerto Rico/8/1934(H1N1) (PR8) plasmid vectors. rgPR8-H5 HA and rgPR8-H5 HANA were resistant to serum inhibitors while rgPR8-H5 NA and PR8 A(H1N1) parental viruses were sensitive, suggesting that HA of HPAI H5N1 viruses bestowed viral resistance to serum inhibition. These results suggested that the ability to resist serum inhibition might enable the viremic H5N1 viruses to disseminate to distal end organs. The present study also analyzed for correlation between susceptibility to serum inhibitors and number of glycosylation sites present on the globular heads of HA and NA. H3N2 viruses, the subtype with highest susceptibility to serum inhibitors, harbored the highest number of glycosylation sites on the HA globular head. However, this positive correlation cannot be drawn for the other influenza subtypes.

  20. Transient intermediates are populated in the folding pathways of single-domain two-state folding protein L

    NASA Astrophysics Data System (ADS)

    Maity, Hiranmay; Reddy, Govardhan

    2018-04-01

    Small single-domain globular proteins, which are believed to be dominantly two-state folders, played an important role in elucidating various aspects of the protein folding mechanism. However, recent single molecule fluorescence resonance energy transfer experiments [H. Y. Aviram et al. J. Chem. Phys. 148, 123303 (2018)] on a single-domain two-state folding protein L showed evidence for the population of an intermediate state and it was suggested that in this state, a β-hairpin present near the C-terminal of the native protein state is unfolded. We performed molecular dynamics simulations using a coarse-grained self-organized-polymer model with side chains to study the folding pathways of protein L. In agreement with the experiments, an intermediate is populated in the simulation folding pathways where the C-terminal β-hairpin detaches from the rest of the protein structure. The lifetime of this intermediate structure increased with the decrease in temperature. In low temperature conditions, we also observed a second intermediate state, which is globular with a significant fraction of the native-like tertiary contacts satisfying the features of a dry molten globule.

  1. Cross reactivity of serum antibody responses elicited by DNA vaccines expressing HA antigens from H1N1 subtype influenza vaccines in the past 30 years.

    PubMed

    Almansour, Iman; Chen, Huaiqing; Wang, Shixia; Lu, Shan

    2013-10-01

    In the past three decades, ten H1 subtype influenza vaccines have been recommended for global seasonal flu vaccination. Some of them were used only for one year before being replaced by another H1 flu vaccine while others may be used for up to seven years. While the selection of a new seasonal flu vaccine was based on the escape of a new emerging virus that was not effectively protected by the existing flu formulation, there is limited information on the magnitude and breadth of cross reactivity among H1 subtype virus circulation over a long period. In the current study, HA-expressing DNA vaccines were constructed to express individual HA antigens from H1 subtype vaccines used in the past 30 y. Rabbits naïve to HA antibody responses were immunized with these HA DNA vaccines and the cross reactivity of these sera against HA antigen and related H1 viruses in the same period was studied. Our data indicate that the level of cross reactivity was different for different viral isolates and the key mutations responsible for the cross reactivity may involve only a limited number of residues. Our results provide useful information for the development of improved seasonal vaccines than can achieve broad protection against viruses within the same H1 subtype.

  2. Stalking influenza by vaccination with pre-fusion headless HA mini-stem.

    PubMed

    Valkenburg, Sophie A; Mallajosyula, V Vamsee Aditya; Li, Olive T W; Chin, Alex W H; Carnell, George; Temperton, Nigel; Varadarajan, Raghavan; Poon, Leo L M

    2016-03-07

    Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies induced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity.

  3. Trazando la materia oscura con cúmulos globulares

    NASA Astrophysics Data System (ADS)

    Forte, J. C.

    Se describe la estrategia adoptada para mapear la distribución de materia oscura y bariónica en galaxias elípticas cuyos cúmulos globulares están siendo observados con los telescopios VLT y Gemini. Se ejemplifican los resultados con los datos obtenidos en el cúmulo de Fornax.

  4. The Structural Parameters of the Globular Clusters in M31 with PAndAS

    NASA Astrophysics Data System (ADS)

    Woodley, Kristin; Pan-Andromeda Archaeological Survey (PAndAS)

    2012-05-01

    The Pan-Andromeda Archaeological Survey (PAndAS) has obtained images with the Canada France Hawaii Telescope using the instrument MegaCam, covering over 400 square degrees in the sky and extending beyond 150 kpc in radius from the center of M31. With this extensive data set, we have measured the structural parameters of all confirmed globular clusters in M31 as well as for a large fraction of the candidate globular clusters in the Revised Bologna Catalog V.4 (Galleti et al. 2004, A&A, 416, 917). In this paper, we present their parameters, including their core-, effective (half-light)-, and tidal radii, as well as their ellipticities measured in a homogeneous manner with ISHAPE (Larsen 1999, A&AS, 139, 393). We examine these parameters as functions of radial position, luminosity, color, metallicity, and age. We also use our measurements as an additional parameter to help constrain the candidacy of the unconfirmed globular clusters.

  5. Dating the Tidal Disruption of Globular Clusters with GAIA Data on Their Stellar Streams

    NASA Astrophysics Data System (ADS)

    Bose, Sownak; Ginsburg, Idan; Loeb, Abraham

    2018-05-01

    The Gaia mission promises to deliver precision astrometry at an unprecedented level, heralding a new era for discerning the kinematic and spatial coordinates of stars in our Galaxy. Here, we present a new technique for estimating the age of tidally disrupted globular cluster streams using the proper motions and parallaxes of tracer stars. We evolve the collisional dynamics of globular clusters within the evolving potential of a Milky Way-like halo extracted from a cosmological ΛCDM simulation and analyze the resultant streams as they would be observed by Gaia. The simulations sample a variety of globular cluster orbits, and account for stellar evolution and the gravitational influence of the disk of the Milky Way. We show that a characteristic timescale, obtained from the dispersion of the proper motions and parallaxes of stars within the stream, is a good indicator for the time elapsed since the stream has been freely expanding away due to the tidal disruption of the globular cluster. This timescale, in turn, places a lower limit on the age of the cluster. The age can be deduced from astrometry using a modest number of stars, with the error on this estimate depending on the proximity of the stream and the number of tracer stars used.

  6. The Hubble Space Telescope UV Legacy Survey of Galactic globular clusters - XIII. ACS/WFC parallel-field catalogues

    NASA Astrophysics Data System (ADS)

    Simioni, M.; Bedin, L. R.; Aparicio, A.; Piotto, G.; Milone, A. P.; Nardiello, D.; Anderson, J.; Bellini, A.; Brown, T. M.; Cassisi, S.; Cunial, A.; Granata, V.; Ortolani, S.; van der Marel, R. P.; Vesperini, E.

    2018-05-01

    As part of the Hubble Space Telescope UV Legacy Survey of Galactic globular clusters, 110 parallel fields were observed with the Wide Field Channel of the Advanced Camera for Surveys, in the outskirts of 48 globular clusters, plus the open cluster NGC 6791. Totalling about 0.3 deg2 of observed sky, this is the largest homogeneous Hubble Space Telescope photometric survey of Galalctic globular clusters outskirts to date. In particular, two distinct pointings have been obtained for each target on average, all centred at about 6.5 arcmin from the cluster centre, thus covering a mean area of about 23 arcmin2 for each globular cluster. For each field, at least one exposure in both F475W and F814W filters was collected. In this work, we publicly release the astrometric and photometric catalogues and the astrometrized atlases for each of these fields.

  7. Spectroscopic confirmation of the low-latitude object FSR 1716 as an old globular cluster

    NASA Astrophysics Data System (ADS)

    Koch, Andreas; Kunder, Andrea; Wojno, Jennifer

    2017-09-01

    Star clusters are invaluable tracers of the Galactic components and the discovery and characterization of low-mass stellar systems can be used to appraise their prevailing disruption mechanisms and time scales. However, owing to significant foreground contamination, high extinction, and still uncharted interfaces of the underlying Milky Way components, objects at low Galactic latitudes are notoriously difficult to characterize. Here, we present the first spectroscopic campaign to identify the chemodynamical properties of the low-latitude star cluster FSR 1716. While its photometric age and distance are far from settled, the presence of RR Lyrae variables indicates a rather old cluster variety. Using medium-resolution (R 10 600) calcium triplet (CaT) spectroscopy obtained with the wide-field, multi-fiber AAOmega instrument, we identified six member candidates with a mean velocity of -30 km s-1 and a velocity dispersion of 2.5 ± 0.9 km s-1. The latter value implies a dynamic mass of 1.3 × 104M⊙, typical of a low-mass globular cluster. Combined with our derived CaT metallicity of -1.38 ± 0.20 dex, this object is finally confirmed as an old, metal-poor globular cluster.

  8. A dynamical study of Galactic globular clusters under different relaxation conditions

    NASA Astrophysics Data System (ADS)

    Zocchi, A.; Bertin, G.; Varri, A. L.

    2012-03-01

    Aims: We perform a systematic combined photometric and kinematic analysis of a sample of globular clusters under different relaxation conditions, based on their core relaxation time (as listed in available catalogs), by means of two well-known families of spherical stellar dynamical models. Systems characterized by shorter relaxation time scales are expected to be better described by isotropic King models, while less relaxed systems might be interpreted by means of non-truncated, radially-biased anisotropic f(ν) models, originally designed to represent stellar systems produced by a violent relaxation formation process and applied here for the first time to the study of globular clusters. Methods: The comparison between dynamical models and observations is performed by fitting simultaneously surface brightness and velocity dispersion profiles. For each globular cluster, the best-fit model in each family is identified, along with a full error analysis on the relevant parameters. Detailed structural properties and mass-to-light ratios are also explicitly derived. Results: We find that King models usually offer a good representation of the observed photometric profiles, but often lead to less satisfactory fits to the kinematic profiles, independently of the relaxation condition of the systems. For some less relaxed clusters, f(ν) models provide a good description of both observed profiles. Some derived structural characteristics, such as the total mass or the half-mass radius, turn out to be significantly model-dependent. The analysis confirms that, to answer some important dynamical questions that bear on the formation and evolution of globular clusters, it would be highly desirable to acquire larger numbers of accurate kinematic data-points, well distributed over the cluster field. Appendices are available in electronic form at http://www.aanda.org

  9. Infrared and laser-Raman spectroscopic studies of thermally-induced globular protein gels.

    PubMed

    Clark, A H; Saunderson, D H; Suggett, A

    1981-03-01

    Infrared and laser-Raman spectroscopy have been used to follow secondary structure changes during the heat-set gelation of a number of aqueous (D2O) globular protein solutions. Measurements of the infrared Amide I' absorption band around 1650 cm-1, for BSA gels of varying clarity and texture, have shown that the very considerable variations in network structure underlying these materials are not reflected in obvious differences in secondary structure. In all cases aggregation is accompanied by development of beta-sheet of a kind common in fibrous protein systems, but for BSA at least this does not appear to vary significantly in amount from one gel type to another. Infrared studies of gels formed from other protein systems have confirmed this tendency for beta-sheet to develop during aggregation, and the tendency is further substantiated by laser-Raman evidence which provides the extra information that in most of the examples studied alpha-helix content simultaneously falls. From these, and other observations, some generalisations are made about the thermally-induced sol-to-gel transformations of globular proteins.

  10. The Gaia-ESO Survey. Mg-Al anti-correlation in iDR4 globular clusters

    NASA Astrophysics Data System (ADS)

    Pancino, E.; Romano, D.; Tang, B.; Tautvaišienė, G.; Casey, A. R.; Gruyters, P.; Geisler, D.; San Roman, I.; Randich, S.; Alfaro, E. J.; Bragaglia, A.; Flaccomio, E.; Korn, A. J.; Recio-Blanco, A.; Smiljanic, R.; Carraro, G.; Bayo, A.; Costado, M. T.; Damiani, F.; Jofré, P.; Lardo, C.; de Laverny, P.; Monaco, L.; Morbidelli, L.; Sbordone, L.; Sousa, S. G.; Villanova, S.

    2017-05-01

    We use Gaia-ESO (GES) Survey iDR4 data to explore the Mg-Al anti-correlation in globular clusters that were observed as calibrators, as a demonstration of the quality of Gaia-ESO Survey data and analysis. The results compare well with the available literature, within 0.1 dex or less, after a small (compared to the internal spreads) offset between the UVES and GIRAFFE data of 0.10-0.15 dex was taken into account. In particular, for the first time we present data for NGC 5927, which is one of the most metal-rich globular clusters studied in the literature so far with [ Fe / H ] = - 0.39 ± 0.04 dex; this cluster was included to connect with the open cluster regime in the Gaia-ESO Survey internal calibration. The extent and shape of the Mg-Al anti-correlation provide strong constraints on the multiple population phenomenon in globular clusters. In particular, we studied the dependency of the Mg-Al anti-correlation extension with metallicity, present-day mass,and age of the clusters, using GES data in combination with a large set of homogenized literature measurements.We find a dependency with both metallicity and mass, which is evident when fitting for the two parameters simultaneously, but we do not find significant dependency with age. We confirm that the Mg-Al anti-correlation is not seen in all clusters, but disappears for the less massive or most metal-rich clusters. We also use our data set to see whether a normal anti-correlation would explain the low [Mg/α] observed in some extragalactic globular clusters, but find that none of the clusters in our sample can reproduce it; a more extreme chemical composition, such as that of NGC 2419, would be required. We conclude that GES iDR4 data already meet the requirements set by the main survey goals and can be used to study globular clusters in detail, even if the analysis procedures were not specifically designed for them. Based on data products from observations made with ESO Telescopes at the La Silla Paranal

  11. Neuroprotection and lifespan extension in Ppt1−/− mice by NtBuHA: therapeutic implications for INCL

    PubMed Central

    Sarkar, Chinmoy; Chandra, Goutam; Peng, Shyiong; Zhang, Zhongjian; Liu, Aiyi; Mukherjee, Anil B.

    2013-01-01

    Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating childhood neurodegenerative lysosomal storage disease (LSD) that has no effective treatment. It is caused by inactivating mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1-deficiency impairs the cleavage of thioester linkage in palmitoylated proteins (constituents of ceroid), preventing degradation by lysosomal hydrolases. Consequently, accumulation of lysosomal ceroid leads to INCL. Thioester linkage is cleaved by nucleophilic attack. Hydroxylamine, a potent nucleophilic cellular metabolite, may have therapeutic potential for INCL but its toxicity precludes clinical application. Here we report that a hydroxylamine-derivative, N-(tert-Butyl) hydroxylamine (NtBuHA), is non-toxic, cleaves thioester linkage in palmitoylated proteins and mediates lysosomal ceroid depletion in cultured cells from INCL patients. Importantly, in Ppt1−/− mice, which mimic INCL, NtBuHA crossed the blood-brain-barrier, depleted lysosomal ceroid, suppressed neuronal apoptosis, slowed neurological deterioration and extended lifespan. Our findings provide the proof of concept that thioesterase-mimetic and antioxidant small molecules like NtBuHA are potential drug-targets for thioesterase deficiency diseases like INCL. PMID:24056696

  12. Influenza A virus hemagglutinin glycosylation compensates for antibody escape fitness costs.

    PubMed

    Kosik, Ivan; Ince, William L; Gentles, Lauren E; Oler, Andrew J; Kosikova, Martina; Angel, Matthew; Magadán, Javier G; Xie, Hang; Brooke, Christopher B; Yewdell, Jonathan W

    2018-01-01

    Rapid antigenic evolution enables the persistence of seasonal influenza A and B viruses in human populations despite widespread herd immunity. Understanding viral mechanisms that enable antigenic evolution is critical for designing durable vaccines and therapeutics. Here, we utilize the primerID method of error-correcting viral population sequencing to reveal an unexpected role for hemagglutinin (HA) glycosylation in compensating for fitness defects resulting from escape from anti-HA neutralizing antibodies. Antibody-free propagation following antigenic escape rapidly selected viruses with mutations that modulated receptor binding avidity through the addition of N-linked glycans to the HA globular domain. These findings expand our understanding of the viral mechanisms that maintain fitness during antigenic evolution to include glycan addition, and highlight the immense power of high-definition virus population sequencing to reveal novel viral adaptive mechanisms.

  13. [An Autopsy Case of Globular Glial Tauopathy Presenting with Amyotrophic Lateral Sclerosis with Dementia].

    PubMed

    Sasaki, Ryogen; Mimuro, Maya; Kokubo, Yasumasa; Imai, Hiroshi; Yoshida, Mari; Tomimoto, Hidekazu

    2016-08-01

    We report an autopsy case of globular glial tauopathy (GGT) presenting clinically with amyotrophic lateral sclerosis (ALS) with dementia. A 79-year-old female developed weakness in the right upper limb, which progressed gradually. She developed apathy and speech disorder at 80 years of age. On neurological examination, she showed signs of upper and lower motor neuron disorder and dementia, but no extrapyramidal signs. The clinical diagnosis was ALS with dementia. The autopsy revealed left predominant marked atrophy of the frontal lobe due to severe neuronal loss and Gliosis. Immunohistochemistry using anti-4-repeat tau antibody revealed numerous globular glial inclusions. Severe neurodegeneration in the primary motor cortex and corticospinal tract was observed. There were distinctive tau-positive inclusions in both Betz and anterior horn cells. TDP-43-positive inclusions in motor neurons were not detected. Sequence analysis of the tau gene revealed no mutations in exons 1-5, 7, 9-13, or the adjacent intronic sequences. GGT can cause a clinical phenotype of ALS with dementia. (Received December 28, 2015; Accepted February 23, 2016; Published August 1, 2016).

  14. Reassortment between Influenza B Lineages and the Emergence of a Coadapted PB1–PB2–HA Gene Complex

    PubMed Central

    Dudas, Gytis; Bedford, Trevor; Lycett, Samantha; Rambaut, Andrew

    2015-01-01

    Influenza B viruses make a considerable contribution to morbidity attributed to seasonal influenza. Currently circulating influenza B isolates are known to belong to two antigenically distinct lineages referred to as B/Victoria and B/Yamagata. Frequent exchange of genomic segments of these two lineages has been noted in the past, but the observed patterns of reassortment have not been formalized in detail. We investigate interlineage reassortments by comparing phylogenetic trees across genomic segments. Our analyses indicate that of the eight segments of influenza B viruses only segments coding for polymerase basic 1 and 2 (PB1 and PB2) and hemagglutinin (HA) proteins have maintained separate Victoria and Yamagata lineages and that currently circulating strains possess PB1, PB2, and HA segments derived entirely from one or the other lineage; other segments have repeatedly reassorted between lineages thereby reducing genetic diversity. We argue that this difference between segments is due to selection against reassortant viruses with mixed-lineage PB1, PB2, and HA segments. Given sufficient time and continued recruitment to the reassortment-isolated PB1–PB2–HA gene complex, we expect influenza B viruses to eventually undergo sympatric speciation. PMID:25323575

  15. Confirmation of an Intermediate-Mass Black Hole in an Extragalactic Globular Cluster

    NASA Astrophysics Data System (ADS)

    Irwin, Jimmy

    2015-10-01

    The long and controversial search for black holes within globular clusters has reached the point where extragalactic globular clusters provide fertile hunting grounds for finding black holes of both stellar and intermediate-mass (IMBH) varieties. While a luminous X-ray point source within a cluster can indicate the presence of a black hole, little can generally be said of its mass without further observation. In the event that a black hole tidally disrupts a passing star in the cluster, optical/UV emission lines from the X-ray-illuminated debris can not only demonstrate the existence of a black hole in the cluster, but can also provide powerful constraints on the mass of the black hole, the composition of the disrupted star, and even the time since the tidal disruption event took place. We propose an HST COS G140L UV spectrum of a globular cluster within the Fornax elliptical galaxy NGC1399 that exhibits unusual optical [N II] and [O III] forbidden emission lines that are believed to result from such a tidal disruption event by a 100 solar mass black hole. Our models predict that the ratios of the expected emission lines from carbon, nitrogen, and oxygen that should be present in the UV spectrum of the source will be able to distinguish a stellar-mass black hole from an IMBH as the disruptor, as well as determine the nature of the disrupted star. If the mass of the black hole is constrained to be in excess of 100 solar masses, this would provide one of the most compelling pieces of evidence to date that IMBHs exist within globular clusters.

  16. Assembly and Architecture of Biogenesis of Lysosome-related Organelles Complex-1 (BLOC-1)*

    PubMed Central

    Lee, Hyung Ho; Nemecek, Daniel; Schindler, Christina; Smith, William J.; Ghirlando, Rodolfo; Steven, Alasdair C.; Bonifacino, Juan S.; Hurley, James H.

    2012-01-01

    BLOC-1 (biogenesis of lysosome-related organelles complex-1) is critical for melanosome biogenesis and has also been implicated in neurological function and disease. We show that BLOC-1 is an elongated complex that contains one copy each of the eight subunits pallidin, Cappuccino, dysbindin, Snapin, Muted, BLOS1, BLOS2, and BLOS3. The complex appears as a linear chain of eight globular domains, ∼300 Å long and ∼30 Å in diameter. The individual domains are flexibly connected such that the linear chain undergoes bending by as much as 45°. Two stable subcomplexes were defined, pallidin-Cappuccino-BLOS1 and dysbindin-Snapin-BLOS2. Both subcomplexes are 1:1:1 heterotrimers that form extended structures as indicated by their hydrodynamic properties. The two subcomplexes appear to constitute flexible units within the larger BLOC-1 chain, an arrangement conducive to simultaneous interactions with multiple BLOC-1 partners in the course of tubular endosome biogenesis and sorting. PMID:22203680

  17. A split motor domain in a cytoplasmic dynein

    PubMed Central

    Straube, Anne; Enard, Wolfgang; Berner, Alexandra; Wedlich-Söldner, Roland; Kahmann, Regine; Steinberg, Gero

    2001-01-01

    The heavy chain of dynein forms a globular motor domain that tightly couples the ATP-cleavage region and the microtubule-binding site to transform chemical energy into motion along the cytoskeleton. Here we show that, in the fungus Ustilago maydis, two genes, dyn1 and dyn2, encode the dynein heavy chain. The putative ATPase region is provided by dyn1, while dyn2 includes the predicted microtubule-binding site. Both genes are located on different chromosomes, are transcribed into independent mRNAs and are translated into separate polypeptides. Both Dyn1 and Dyn2 co-immunoprecipitated and co-localized within growing cells, and Dyn1–Dyn2 fusion proteins partially rescued mutant phenotypes, suggesting that both polypeptides interact to form a complex. In cell extracts the Dyn1–Dyn2 complex dissociated, and microtubule affinity purification indicated that Dyn1 or associated polypeptides bind microtubules independently of Dyn2. Both Dyn1 and Dyn2 were essential for cell survival, and conditional mutants revealed a common role in nuclear migration, cell morphogenesis and microtubule organization, indicating that the Dyn1–Dyn2 complex serves multiple cellular functions. PMID:11566874

  18. Globular Cluster Variable Stars—Atlas and Coordinate Improvement using AAVSOnet Telescopes (Abstract)

    NASA Astrophysics Data System (ADS)

    Welch, D.; Henden, A.; Bell, T.; Suen, C.; Fare, I.; Sills, A.

    2015-12-01

    (Abstract only) The variable stars of globular clusters have played and continue to play a significant role in our understanding of certain classes of variable stars. Since all stars associated with a cluster have the same age, metallicity, distance and usually very similar (if not identical reddenings), such variables can produce uniquely powerful constraints on where certain types of pulsation behaviors are excited. Advanced amateur astronomers are increasingly well-positioned to provide long-term CCD monitoring of globular cluster variable star but are hampered by a long history of poor or inaccessible finder charts and coordinates. Many of variable-rich clusters have published photographic finder charts taken in relatively poor seeing with blue-sensitive photographic plates. While useful signal-to-noise ratios are relatively straightforward to achieve for RR Lyrae, Type 2 Cepheids, and red giant variables, correct identification remains a difficult issue—particularly when images are taken at V or longer wavelengths. We describe the project and report its progress using the OC61, TMO61, and SRO telescopes of AAVSOnet after the first year of image acquisition and demonstrate several of the data products being developed for globular cluster variables.

  19. [Family of ribosomal proteins S1 contains unique conservative domain].

    PubMed

    Deriusheva, E I; Machulin, A V; Selivanova, O M; Serdiuk, I N

    2010-01-01

    Different representatives of bacteria have different number of amino acid residues in the ribosomal proteins S1. This number varies from 111 (Spiroplasma kunkelii) to 863 a.a. (Treponema pallidum). Traditionally and for lack of this protein three-dimensional structure, its architecture is represented as repeating S1 domains. Number of these domains depends on the protein's length. Domain's quantity and its boundaries data are contained in the specialized databases, such as SMART, Pfam and PROSITE. However, for the same object these data may be very different. For search of domain's quantity and its boundaries, new approach, based on the analysis of dicted secondary structure (PsiPred), was used. This approach allowed us to reveal structural domains in amino acid sequences of S1 proteins and at that number varied from one to six. Alignment of S1 proteins, containing different domain's number, with the S1 RNAbinding domain of Escherichia coli PNPase elicited a fact that in family of ribosomal proteins SI one domain has maximal homology with S1 domain from PNPase. This conservative domain migrates along polypeptide chain and locates in proteins, containing different domain's number, according to specified pattern. In this domain as well in the S1 domain from PNPase, residues Phe-19, Phe-22, His-34, Asp-64 and Arg-68 are clustered on the surface and formed RNA binding site.

  20. The globular cluster systems of 54 Coma ultra-diffuse galaxies: statistical constraints from HST data

    NASA Astrophysics Data System (ADS)

    Amorisco, N. C.; Monachesi, A.; Agnello, A.; White, S. D. M.

    2018-04-01

    We use data from the HST Coma Cluster Treasury program to assess the richness of the globular cluster systems (GCSs) of 54 Coma ultra-diffuse galaxies (UDGs), 18 of which have a half-light radius exceeding 1.5 kpc. We use a hierarchical Bayesian method tested on a large number of mock data sets to account consistently for the high and spatially varying background counts in Coma. These include both background galaxies and intra-cluster globular clusters (ICGCs), which are disentangled from the population of member globular clusters (GCs) in a probabilistic fashion. We find no candidate for a GCS as rich as that of the Milky Way, our sample has GCSs typical of dwarf galaxies. For the standard relation between GCS richness and halo mass, 33 galaxies have a virial mass Mvir ≤ 1011 M⊙ at 90 per cent probability. Only three have Mvir > 1011 M⊙ with the same confidence. The mean colour and spread in colour of the UDG GCs are indistinguishable from those of the abundant population of ICGCs. The majority of UDGs in our sample are consistent with the relation between stellar mass and GC richness of `normal' dwarf galaxies. Nine systems, however, display GCSs that are richer by a factor of 3 or more (at 90 per cent probability). Six of these have sizes ≲1.4 kpc. Our results imply that the physical mechanisms responsible for the extended size of the UDGs and for the enhanced GC richness of some cluster dwarfs are at most weakly correlated.

  1. Crystallization and preliminary X-ray crystallographic analysis of the variable domain of Scl2.3, a streptococcal collagen-like protein from invasive M3-type Streptococcus pyogenes.

    PubMed

    Squeglia, Flavia; Bachert, Beth; Romano, Maria; Lukomski, Slawomir; Berisio, Rita

    2013-09-01

    Streptococcal collagen-like proteins (Scls) are widely expressed by the well recognized human pathogen Streptococcus pyogenes. These surface proteins contain a signature central collagen-like region and an amino-terminal globular domain, termed the variable domain, which is protruded away from the cell surface by the collagen-like domain. Despite their recognized importance in bacterial pathogenicity, no structural information is presently available on proteins of the Scl class. The variable domain of Scl2 from invasive M3-type S. pyogenes has successfully been crystallized using vapour-diffusion methods. The crystals diffracted to 1.5 Å resolution and belonged to space group H32, with unit-cell parameters a = 44.23, b = 44.23, c = 227.83 Å. The crystal structure was solved by single-wavelength anomalous dispersion using anomalous signal from a europium chloride derivative.|

  2. The potassium abundance in the globular clusters NGC 104, NGC 6752 and NGC 6809

    NASA Astrophysics Data System (ADS)

    Mucciarelli, A.; Merle, T.; Bellazzini, M.

    2017-04-01

    We derived potassium abundances in red-giant-branch stars in the Galactic globular clusters NGC 104 (144 stars), NGC 6752 (134 stars), and NGC 6809 (151 stars) using high-resolution spectra collected with FLAMES at the ESO - Very Large Telescope. In the samples we consider, we do not find significant intrinsic spreads in [K/Fe], which confirms the previous findings, but which is at variance with the cases of the massive clusters NGC 2419 and NGC 2808. Additionally, marginally significant [K/Fe]-[O/Fe] anti-correlations are found in NGC 104 and NGC 6809, and [K/Fe]-[Na/Fe] correlations are found in NGC 104 and NGC 6752. No evidence of [K/Fe]-[Mg/Fe] anti-correlation are found. The results of our analysis are consistent with a scenario in which the process leading to the multi-populations in globular clusters also implies enrichment in the K abundance, the amplitude of the associated [K/Fe] enhancement becoming measurable only in stars showing the most extreme effects of O and Mg depletion. Stars enhanced in [K/Fe] have so far only been found in clusters harbouring some Mg-poor stars, while the other globulars, without a Mg-poor sub-population, show small or null [K/Fe] spreads. Full Table 1 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/600/A104

  3. Three dehalogenases and physiological restraints in the biodegradation of haloalkanes by Arthrobacter sp. strain HA1.

    PubMed Central

    Scholtz, R; Messi, F; Leisinger, T; Cook, A M

    1988-01-01

    Arthrobacter sp. strain HA1 utilizes 18 C2-to-C8 1-haloalkanes for growth and synthesizes an inducible 1-bromoalkane debrominase of unknown physiological function (R. Scholtz, T. Leisinger, F. Suter, and A.M. Cook, J. Bacteriol. 169:5016-5021, 1987) in addition to an inducible 1-chlorohexane halidohydrolase which dehalogenates some 50 substrates, including alpha, omega-dihaloalkanes. alpha, omega-Dihaloalkanes were utilized by cultures of strain HA1 under certain conditions only. C9 and C8 homologs prevented growth. At suitable concentrations, C7-to-C5 homologs could serve as sole sources of carbon and energy for growth. C4 and C3 homologs could be utilized only in the presence of a second substrate (e.g., butanol), and the C2 homolog was not degraded. Kinetics of growth and substrate utilization indicated that cells of strain HA1 growing in butanol-salts medium could be used to test whether compounds induced the 1-chlorohexane halidohydrolase. No gratuitous induction of synthesis of the enzyme was observed. Many enzyme substrates (e.g., bromobenzene) did not induce synthesis of the enzyme, though the enzyme sequence to degrade the product (phenol) was present. Some inducers (e.g., bromomethane) were enzyme substrates but not growth substrates. In an attempt to find a physiological role for the 1-bromoalkane debrominase, we observed that several long-chain haloaliphatic compounds (greater than C9; e.g., 1-bromohexadecane and 1-chlorohexadecane) were utilized for growth and that induced cells could dehalogenate several 1-haloalkanes (at least C4 to C16). The dehalogenation of the long-chain compounds could not be assayed in the cell extract, so we presume that a third haloalkane dehalogenase was present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3223767

  4. No Evidence for Multiple Stellar Populations in the Low-mass Galactic Globular Cluster E 3

    NASA Astrophysics Data System (ADS)

    Salinas, Ricardo; Strader, Jay

    2015-08-01

    Multiple stellar populations are a widespread phenomenon among Galactic globular clusters. Even though the origin of the enriched material from which new generations of stars are produced remains unclear, it is likely that self-enrichment will be feasible only in clusters massive enough to retain this enriched material. We searched for multiple populations in the low mass (M˜ 1.4× {10}4 {M}⊙ ) globular cluster E3, analyzing SOAR/Goodman multi-object spectroscopy centered on the blue cyanogen (CN) absorption features of 23 red giant branch stars. We find that the CN abundance does not present the typical bimodal behavior seen in clusters hosting multistellar populations, but rather a unimodal distribution that indicates the presence of a genuine single stellar population, or a level of enrichment much lower than in clusters that show evidence for two populations from high-resolution spectroscopy. E3 would be the first bona fide Galactic old globular cluster where no sign of self-enrichment is found. Based on observations obtained at the Southern Astrophysical Research (SOAR) Telescope, which is a joint project of the Ministério da Ciência, Tecnologia, e Inovação (MCTI) da República Federativa do Brasil, the US National Optical Astronomy Observatory (NOAO), the University of North Carolina at Chapel Hill (UNC), and Michigan State University (MSU).

  5. Ultraviolet properties of individual hot stars in globular cluster cores. 1: NGC 1904 (M 79)

    NASA Technical Reports Server (NTRS)

    Altner, Bruce; Matilsky, Terry A.

    1992-01-01

    As part of an observing program using the International Ultraviolet Explorer (IUE) satellite to investigate the ultraviolet properties of stars found within the cores of galactic globular clusters with blue horizontal branches (HBs), we obtained three spectra of the cluster NGC 1904 (M 79). All three were long integration-time, short-wavelength (SWP) spectra obtained at the so called 'center of light' and all three showed evidence of sources within the IUE large aperture (21.4 in. by 10 in.). In this paper we shall describe the analysis of these spectra and present evidence that the UV sources represent individual hot stars in the post-HB stage of evolution.

  6. Titin domains progressively unfolded by force are homogenously distributed along the molecule.

    PubMed

    Bianco, Pasquale; Mártonfalvi, Zsolt; Naftz, Katalin; Kőszegi, Dorina; Kellermayer, Miklós

    2015-07-21

    Titin is a giant filamentous protein of the muscle sarcomere in which stretch induces the unfolding of its globular domains. However, the mechanisms of how domains are progressively selected for unfolding and which domains eventually unfold have for long been elusive. Based on force-clamp optical tweezers experiments we report here that, in a paradoxical violation of mechanically driven activation kinetics, neither the global domain unfolding rate, nor the folded-state lifetime distributions of full-length titin are sensitive to force. This paradox is reconciled by a gradient of mechanical stability so that domains are gradually selected for unfolding as the magnitude of the force field increases. Atomic force microscopic screening of extended titin molecules revealed that the unfolded domains are distributed homogenously along the entire length of titin, and this homogeneity is maintained with increasing overstretch. Although the unfolding of domains with progressively increasing mechanical stability makes titin a variable viscosity damper, the spatially randomized variation of domain stability ensures that the induced structural changes are not localized but are distributed along the molecule's length. Titin may thereby provide complex safety mechanims for protecting the sarcomere against structural disintegration under excessive mechanical conditions. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  7. Differential osteogenic activity of osteoprogenitor cells on HA and TCP/HA scaffold of tissue engineered bone.

    PubMed

    Ng, Angela M H; Tan, K K; Phang, M Y; Aziyati, O; Tan, G H; Isa, M R; Aminuddin, B S; Naseem, M; Fauziah, O; Ruszymah, B H I

    2008-05-01

    Biomaterial, an essential component of tissue engineering, serves as a scaffold for cell attachment, proliferation, and differentiation; provides the three dimensional (3D) structure and, in some applications, the mechanical strength required for the engineered tissue. Both synthetic and naturally occurring calcium phosphate based biomaterial have been used as bone fillers or bone extenders in orthopedic and reconstructive surgeries. This study aims to evaluate two popular calcium phosphate based biomaterial i.e., hydroxyapatite (HA) and tricalcium phosphate/hydroxyapatite (TCP/HA) granules as scaffold materials in bone tissue engineering. In our strategy for constructing tissue engineered bone, human osteoprogenitor cells derived from periosteum were incorporated with human plasma-derived fibrin and seeded onto HA or TCP/HA forming 3D tissue constructs and further maintained in osteogenic medium for 4 weeks to induce osteogenic differentiation. Constructs were subsequently implanted intramuscularly in nude mice for 8 weeks after which mice were euthanized and constructs harvested for evaluation. The differential cell response to the biomaterial (HA or TCP/HA) adopted as scaffold was illustrated by the histology of undecalcified constructs and evaluation using SEM and TEM. Both HA and TCP/HA constructs showed evidence of cell proliferation, calcium deposition, and collagen bundle formation albeit lesser in the former. Our findings demonstrated that TCP/HA is superior between the two in early bone formation and hence is the scaffold material of choice in bone tissue engineering. Copyright 2007 Wiley Periodicals, Inc.

  8. Globular adiponectin induces a pro-inflammatory response in human astrocytic cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana

    Highlights: • Adiponectin receptors are expressed in human astrocytes. • Globular adiponectin induces secretion of IL-6 and MCP-1 from cultured astrocytes. • Adiponectin may play a pro-inflammatory role in astrocytes. - Abstract: Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observedmore » link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3 K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes.« less

  9. Fourier Decomposition and Properties of the Variable Stars in the Globular Cluster NGC 4833

    NASA Astrophysics Data System (ADS)

    Reed, Hunter M.; Pajkos, Michael A.; Murphy, Brian W.; Darragh, Andrew

    2016-01-01

    Globular clusters provide an ideal setting to study stellar evolution of stars of similar composition and age. RR Lyrae stars found in globular clusters have a variety of uses in probing the physical characteristics of the stellar population itself and its evolution. Building upon our previous study, we focus on the RR Lyrae stars in the globular cluster NGC 4833. From March through June 2014, we used the Southeastern Association for Research in Astronomy 0.6-meter telescope located at CTIO to collect nearly 1,500 images of NGC 4833 in the B, V, R, and I bands. Using difference image analysis we identified 40 variable stars. Of these, 20 were RR Lyrae stars with 10 being of type RR0, 7 of type RR1, and 3 of type RR2. Additionally, 6 SX Phe, 5 eclipsing binaries, and 9 long period variables were identified. The average period of the type RR0, RR1, and RR2 type variables were 0.69597 days, 0.39547 days, and 0.30654 days, respectively. The periods of the RR Lyrae stars and ratio of N1/(N0+N1) of 0.41 is indicative of an Oosterhoff Type II cluster. The observations of the RR Lyrae stars were of very high quality and phase coverage allowing us to perform Fourier decomposition of their light curves. From this Fourier decomposition we were able to determine the physical characteristics of the RR Lyrae stars. We found the mean iron abundance to be [Fe/H]JKZW = -1.87 ± 0.06, the mean apparent V-magnitude RR0 and RR1 type variables to be VRR = 15.51 ± 0.11, a mean absolute V-magnitude of MV = 0.636 ± 0.053; and an effective temperature for RR0's and RR1's of log10Teff = 3.797 and log10Teff = 3.855, respectively. The multi-band photometry allowed us to determine the reddening of the cluster, E(B-V) = 0.342 ± 0.021, which resulted in a distance of D(kpc) = 5.91 ± 0.31 to NGC 4833.

  10. Variable Stars in Large Magellanic Cloud Globular Clusters. III. Reticulum

    NASA Astrophysics Data System (ADS)

    Kuehn, Charles A.; Dame, Kyra; Smith, Horace A.; Catelan, Márcio; Jeon, Young-Beom; Nemec, James M.; Walker, Alistair R.; Kunder, Andrea; Pritzl, Barton J.; De Lee, Nathan; Borissova, Jura

    2013-06-01

    This is the third in a series of papers studying the variable stars in old globular clusters in the Large Magellanic Cloud. The primary goal of this series is to look at how the characteristics and behavior of RR Lyrae stars in Oosterhoff-intermediate systems compare to those of their counterparts in Oosterhoff-I/II systems. In this paper we present the results of our new time-series BVI photometric study of the globular cluster Reticulum. We found a total of 32 variables stars (22 RRab, 4 RRc, and 6 RRd stars) in our field of view. We present photometric parameters and light curves for these stars. We also present physical properties, derived from Fourier analysis of light curves, for some of the RR Lyrae stars. We discuss the Oosterhoff classification of Reticulum and use our results to re-derive the distance modulus and age of the cluster. Based on observations taken with the SMARTS 1.3 m telescope operated by the SMARTS Consortium and observations taken at the Southern Astrophysical Research (SOAR) telescope, which is a joint project of the Ministério da Ciência, Tecnologia, e Inovação (MCTI) da República Federativa do Brasil, the U.S. National Optical Astronomy Observatory (NOAO), the University of North Carolina at Chapel Hill (UNC), and Michigan State University (MSU).

  11. AGB Sodium Abundances in the Globular Cluster 47 Tucanae (NGC 104)

    NASA Astrophysics Data System (ADS)

    Johnson, Christian I.; McDonald, Iain; Pilachowski, Catherine A.; Mateo, Mario; Bailey, John I., III; Cordero, Maria J.; Zijlstra, Albert A.; Crane, Jeffrey D.; Olszewski, Edward; Shectman, Stephen A.; Thompson, Ian

    2015-02-01

    A recent analysis comparing the [Na/Fe] distributions of red giant branch (RGB) and asymptotic giant branch (AGB) stars in the Galactic globular cluster NGC 6752 found that the ratio of Na-poor to Na-rich stars changes from 30:70 on the RGB to 100:0 on the AGB. The surprising paucity of Na-rich stars on the AGB in NGC 6752 warrants additional investigations to determine if the failure of a significant fraction of stars to ascend the AGB is an attribute common to all globular clusters. Therefore, we present radial velocities, [Fe/H], and [Na/Fe] abundances for 35 AGB stars in the Galactic globular cluster 47 Tucanae (47 Tuc; NGC 104), and compare the AGB [Na/Fe] distribution with a similar RGB sample published previously. The abundances and velocities were derived from high-resolution spectra obtained with the Michigan/Magellan Fiber System and MSpec spectrograph on the Magellan-Clay 6.5 m telescope. We find the average heliocentric radial velocity and [Fe/H] values to be < R{{V}helio.}> = -18.56 km s-1 (σ = 10.21 km s-1) and < [Fe/H]> = -0.68 (σ = 0.08), respectively, in agreement with previous literature estimates. The average [Na/Fe] abundance is 0.12 dex lower in the 47 Tuc AGB sample compared to the RGB sample, and the ratio of Na-poor to Na-rich stars is 63:37 on the AGB and 45:55 on the RGB. However, in contrast to NGC 6752, the two 47 Tuc populations have nearly identical [Na/Fe] dispersion and interquartile range values. The data presented here suggest that only a small fraction (≲20%) of Na-rich stars in 47 Tuc may fail to ascend the AGB, which is a similar result to that observed in M13. Regardless of the cause for the lower average [Na/Fe] abundance in AGB stars, we find that Na-poor stars and at least some Na-rich stars in 47 Tuc evolve through the early AGB phase. The contrasting behavior of Na-rich stars in 47 Tuc and NGC 6752 suggests that the RGB [Na/Fe] abundance alone is insufficient for predicting if a star will ascend the AGB.

  12. VizieR Online Data Catalog: Tidal radii of 7 globular clusters (Lehmann+ 1997)

    NASA Astrophysics Data System (ADS)

    Lehmann, I.; Scholz, R.-D.

    1998-02-01

    We present new tidal radii for seven Galactic globular clusters using the method of automated star counts on Schmidt plates of the Tautenburg, Palomar and UK telescopes. The plates were fully scanned with the APM system in Cambridge (UK). Special account was given to a reliable background subtraction and the correction of crowding effects in the central cluster region. For the latter we used a new kind of crowding correction based on a statistical approach to the distribution of stellar images and the luminosity function of the cluster stars in the uncrowded area. The star counts were correlated with surface brightness profiles of different authors to obtain complete projected density profiles of the globular clusters. Fitting an empirical density law (King 1962AJ.....67..471K) we derived the following structural parameters: tidal radius rt, core radius rc and concentration parameter c. In the cases of NGC 5466, M 5, M 12, M 13 and M 15 we found an indication for a tidal tail around these objects (cf. Grillmair et al., 1995AJ....109.2553G). (1 data file).

  13. HA222 polymorphism in Influenza A(H1N1) 2009 isolates from Intensive Care Units and ambulatory patients during three influenza seasons.

    PubMed

    Corcioli, F; Arvia, R; Pierucci, F; Clausi, V; Bonizzoli, M; Peris, A; Azzi, A

    2014-02-13

    Amino acid substitutions which can affect the receptor binding specificity of the influenza virus, like the substitution of aspartic acid with glycine in position 222 of the haemagglutinin (HA) of influenza virus A(H1N1) 2009, have been associated with increased viral pathogenicity and increased tropism for the lower respiratory tract. In this paper, the polymorphic site 222 and the site 223 of the HA1 polypeptide of H1N1 2009 viruses were analyzed in order to better clarify the role of these substitutions in H1N1 2009 virus virulence. Viral strains included in this study were collected in Tuscany during 3 different influenza seasons from patients with severe as well as with mild forms of influenza caused by A(H1N1) 2009 virus. In addition, the oseltamivir resistance of the H1N1 2009 strains circulating during the same seasons was monitored with the aim to evaluate whether these changes in the HA and in neuraminidase (NA) tend to be linked and to influence each other. Altogether, the results indicate that in severe forms of influenza viral population is more variable than in mild influenza, as regards the site 222. The frequency of such substitutions varied among the three seasons, it was highest in the season 2010-2011 and very low in the season 2012-2013. However these differences were not significant. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. A Wide-Field Photometric Survey for Extratidal Tails Around Five Metal-Poor Globular Clusters in the Galactic Halo

    NASA Astrophysics Data System (ADS)

    Chun, Sang-Hyun; Kim, Jae-Woo; Sohn, Sangmo T.; Park, Jang-Hyun; Han, Wonyong; Kim, Ho-Il; Lee, Young-Wook; Lee, Myung Gyoon; Lee, Sang-Gak; Sohn, Young-Jong

    2010-02-01

    Wide-field deep g'r'i' images obtained with the Megacam of the Canada-France-Hawaii Telescope are used to investigate the spatial configuration of stars around five metal-poor globular clusters M15, M30, M53, NGC 5053, and NGC 5466, in a field-of-view ~3°. Applying a mask filtering algorithm to the color-magnitude diagrams of the observed stars, we sorted cluster's member star candidates that are used to examine the characteristics of the spatial stellar distribution surrounding the target clusters. The smoothed surface density maps and the overlaid isodensity contours indicate that all of the five metal-poor globular clusters exhibit strong evidence of extratidal overdensity features over their tidal radii, in the form of extended tidal tails around the clusters. The orientations of the observed extratidal features show signatures of tidal tails tracing the clusters' orbits, inferred from their proper motions, and effects of dynamical interactions with the Galaxy. Our findings include detections of a tidal bridge-like feature and an envelope structure around the pair of globular clusters M53 and NGC 5053. The observed radial surface density profiles of target clusters have a deviation from theoretical King models, for which the profiles show a break at 0.5-0.7rt , extending the overdensity features out to 1.5-2rt . Both radial surface density profiles for different angular sections and azimuthal number density profiles confirm the overdensity features of tidal tails around the five metal-poor globular clusters. Our results add further observational evidence that the observed metal-poor halo globular clusters originate from an accreted satellite system, indicative of the merging scenario of the formation of the Galactic halo. Based on observations carried out at the Canada-France-Hawaii Telescope, operated by the National Research Council of Canada, the Centre National de la Recherche Scientifique de France, and the University of Hawaii. This is part of the

  15. [Study of beta-turns in globular proteins].

    PubMed

    Amirova, S R; Milchevskiĭ, Iu V; Filatov, I V; Esipova, N G; Tumanian, V G

    2005-01-01

    The formation of beta-turns in globular proteins has been studied by the method of molecular mechanics. Statistical method of discriminant analysis was applied to calculate energy components and sequences of oligopeptide segments, and after this prediction of I type beta-turns has been drawn. The accuracy of true positive prediction is 65%. Components of conformational energy considerably affecting beta-turn formation were delineated. There are torsional energy, energy of hydrogen bonds, and van der Waals energy.

  16. HA-1077 inhibits cell migration/invasion of oral squamous cell carcinoma.

    PubMed

    Moreira Carboni, Simone de Sales Costa; Rodrigues Lima, Nathália Alves; Pinheiro, Nanci Mendes; Tavares-Murta, Beatriz Martins; Crema, Virgínia Oliveira

    2015-10-01

    Oral squamous cell carcinoma (OSCC) is the most malignant lesion occurring in the head and neck. The Rho-kinases (ROCKs), effectors of Rho proteins, are involved in actin cytoskeletal organization, cell migration, and maintenance cortex. The HA-1077 inhibits the ROCKs. This study aimed to evaluate the effect of treatment with HA-1077 on cell motility in SCC-4 cells, a cell line originating from human OSCC. F-actin of SCC-4 cells treated or not with HA-1077 (1, 50 and 100 μmol/l), and also HA-1077 50 μmol/l and/or inhibitors Y-27632 30 μmol/l was stained with rhodamine-conjugated phalloidin and analyzed by confocal microscopy. Approximately 1×10 cells/well, control and treated with HA-1077 (25, 50, and 100 μmol/l) were added to the migration plate assay. In addition, 1×10 cells/well, control and treated with HA-1077 50 μmol/l, were tested by invasion assays (plate coated with Matrigel). The inhibition of ROCKs with HA-1077 and/or Y-27632 leads to morphological changes, affecting the organization of the actin. The inhibitory effect of HA-1077 (P<0.0001) was dose dependent as the number of cells migrated at 100 μmol/l was statistically different: 25 μmol/l (P<0.0001) and 50 μmol/l (P<0.01). The number of cells treated with HA-1077 50 μmol/l decreased compared with control cells that invaded through Matrigel (P<0.0001). This study shows an inhibitory effect of HA-1077 on cell migration and invasion, suggesting that the use of HA-1077 can be a potential therapy for OSCC.

  17. Molecular Characterization and Phylogenetic Analysis of the Hemagglutinin 1 Protein of Human Influenza A Virus Subtype H1N1 Circulating in Kenya During 2007-2008

    DTIC Science & Technology

    2012-01-01

    10.1093/infdis/jis586 S46 • JID 2012:206 (Suppl 1) • Bulimo et al by guest on N ovem ber 20, 2012 http://jid.oxfordjournals.org/ D ow nloaded from Report...immunogenic sites at which immune -driven natural selection happens, the N-terminal (HA1) domain of the HA protein contains the maximum concentration of...antibodies to neutralize the virus. Because the human immune response to viral infection is incompletely cross-protective, amino acid variants of the HA1

  18. New cataclysmic variables and other exotic binaries in the globular cluster 47 Tucanae*

    NASA Astrophysics Data System (ADS)

    Rivera Sandoval, L. E.; van den Berg, M.; Heinke, C. O.; Cohn, H. N.; Lugger, P. M.; Anderson, J.; Cool, A. M.; Edmonds, P. D.; Wijnands, R.; Ivanova, N.; Grindlay, J. E.

    2018-04-01

    We present 22 new (+3 confirmed) cataclysmic variables (CVs) in the non-core-collapsed globular cluster 47 Tucanae (47 Tuc). The total number of CVs in the cluster is now 43, the largest sample in any globular cluster so far. For the identifications we used near-ultraviolet (NUV) and optical images from the Hubble Space Telescope, in combination with X-ray results from the Chandra X-ray Observatory. This allowed us to build the deepest NUV CV luminosity function of the cluster to date. We found that the CVs in 47 Tuc are more concentrated towards the cluster centre than the main-sequence turn-off stars. We compared our results to the CV populations of the core-collapsed globular clusters NGC 6397 and NGC 6752. We found that 47 Tuc has fewer bright CVs per unit mass than those two other clusters. That suggests that dynamical interactions in core-collapsed clusters play a major role creating new CVs. In 47 Tuc, the CV population is probably dominated by primordial and old dynamically formed systems. We estimated that the CVs in 47 Tuc have total masses of ˜1.4 M⊙. We also found that the X-ray luminosity function of the CVs in the three clusters is bimodal. Additionally, we discuss a possible double degenerate system and an intriguing/unclassified object. Finally, we present four systems that could be millisecond pulsar companions given their X-ray and NUV/optical colours. For one of them we present very strong evidence for being an ablated companion. The other three could be CO or He white dwarfs.

  19. Binary black hole mergers from globular clusters: Masses, merger rates, and the impact of stellar evolution

    NASA Astrophysics Data System (ADS)

    Rodriguez, Carl L.; Chatterjee, Sourav; Rasio, Frederic A.

    2016-04-01

    The recent discovery of GW150914, the binary black hole merger detected by Advanced LIGO, has the potential to revolutionize observational astrophysics. But to fully utilize this new window into the Universe, we must compare these new observations to detailed models of binary black hole formation throughout cosmic time. Expanding upon our previous work [C. L. Rodriguez, M. Morscher, B. Pattabiraman, S. Chatterjee, C.-J. Haster, and F. A. Rasio, Phys. Rev. Lett. 115, 051101 (2015).], we study merging binary black holes formed in globular clusters using our Monte Carlo approach to stellar dynamics. We have created a new set of 52 cluster models with different masses, metallicities, and radii to fully characterize the binary black hole merger rate. These models include all the relevant dynamical processes (such as two-body relaxation, strong encounters, and three-body binary formation) and agree well with detailed direct N -body simulations. In addition, we have enhanced our stellar evolution algorithms with updated metallicity-dependent stellar wind and supernova prescriptions, allowing us to compare our results directly to the most recent population synthesis predictions for merger rates from isolated binary evolution. We explore the relationship between a cluster's global properties and the population of binary black holes that it produces. In particular, we derive a numerically calibrated relationship between the merger times of ejected black hole binaries and a cluster's mass and radius. With our improved treatment of stellar evolution, we find that globular clusters can produce a significant population of massive black hole binaries that merge in the local Universe. We explore the masses and mass ratios of these binaries as a function of redshift, and find a merger rate of ˜5 Gpc-3yr-1 in the local Universe, with 80% of sources having total masses from 32 M⊙ to 64 M⊙. Under standard assumptions, approximately one out of every seven binary black hole mergers

  20. Osteogenic properties of PBLG-g-HA/PLLA nanocomposites.

    PubMed

    Liao, Lan; Yang, Shuang; Miron, Richard J; Wei, Junchao; Zhang, Yufeng; Zhang, Meng

    2014-01-01

    New development of biomaterial scaffolds remains a prominent issue for the regeneration of lost or fractured bone. Of these scaffolds, a number of bioactive polymers have been synthesized and fabricated for diverse biological roles. Although recent evidence has demonstrated that composite scaffolds such as HA/PLLA have improved properties when compared to either HA or PLLA alone, recent investigations have demonstrated that the phase compatibility between HA and PLLA layers is weak preventing optimal enhancement of the mechanical properties and making the composites prone to breakdown. In the present study, poly (γ-benzyl-L-glutamate) modified hydroxyapatite/(poly (L-lactic acid)) (PBLG-g-HA/PLLA) composite scaffolds were fabricated with improved phase compatibility and tested for their osteogenic properties in 18 Wistar female rats by analyzing new bone formation in 3 mm bilateral femur defects in vivo. At time points, 2, 4 and 8 weeks post surgery, bone formation was evaluated by µ-CT and histological analysis by comparing 4 treatment groups; 1) blank defect, 2) PLLA, 3) HA/PLLA and 4) PBLG-g-HA/PLLA scaffolds. The in vivo analysis demonstrated that new bone formation was much more prominent in HA/PLLA and PBLG-g-HA/PLLA groups as depicted by µ-CT, H&E staining and immunohistochemistry for collagen I. TRAP staining was also utilized to determine the influence of osteoclast cell number and staining intensity to the various scaffolds. No significant differences in either staining intensity or osteoclast numbers between all treatment modalities was observed, however blank defects did contain a higher number of osteoclast-like cells. The results from the present study illustrate the potential of PBLG-g-HA/PLLA scaffolds for bone tissue engineering applications by demonstrating favorable osteogenic properties.

  1. High pressure effects on the structural functionality of condensed globular-protein matrices.

    PubMed

    Savadkoohi, Sobhan; Kasapis, Stefan

    2016-07-01

    High pressure technology is the outcome of consumer demand for better quality control of processed foods. There is great potential to apply HPP to condensed systems of globular proteins for the generation of industry-relevant biomaterials with advanced techno- and biofunctionality. To this end, research demonstrates that application of high hydrostatic pressure generates a coherent structure and preserves the native conformation in condensed globular proteins, which is an entirely unexpected but interesting outcome on both scientific and technological grounds. In microbiological challenge tests, high pressure at conventional commercial conditions, demonstrated to effectively reduce the concentration of typical Gram negative or Gram positive foodborne pathogens, and proteolytic enzymes in high-solid protein samples. This may have industrial significance in relation to the formulation and stabilisation of "functional food" products as well as in protein ingredients and concentrates by replacing spray dried powders with condensed HPP-treated pastes that maintain structure and bioactivity. Fundamental concepts and structural functionality of condensed matrices of globular proteins are the primary interest in this mini-review, which may lead to opportunities for industrial exploitation, but earlier work on low-solid systems is also summarised presently to put recent developments in context of this rapidly growing field. Copyright © 2016. Published by Elsevier B.V.

  2. Domain architecture and oligomerization properties of the paramyxovirus PIV 5 hemagglutinin-neuraminidase (HN) protein

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yuan Ping; Leser, George P.; Demeler, Borries

    2008-09-01

    The mechanism by which the paramyxovirus hemagglutinin-neuraminidase (HN) protein couples receptor binding to activation of virus entry remains to be fully understood, but the HN stalk is thought to play an important role in the process. We have characterized ectodomain constructs of the parainfluenza virus 5 HN to understand better the underlying architecture and oligomerization properties that may influence HN functions. The PIV 5 neuraminidase (NA) domain is monomeric whereas the ectodomain forms a well-defined tetramer. The HN stalk also forms tetramers and higher order oligomers with high {alpha}-helical content. Together, the data indicate that the globular NA domains formmore » weak intersubunit interactions at the end of the HN stalk tetramer, while stabilizing the stalk and overall oligomeric state of the ectodomain. Electron microscopy of the HN ectodomain reveals flexible arrangements of the NA and stalk domains, which may be important for understanding how these two HN domains impact virus entry.« less

  3. A DYING STAR IN GLOBULAR CLUSTER

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A DYING STAR IN GLOBULAR CLUSTER M15 The globular cluster Messier 15 is shown in this color image obtained with the NASA Hubble Space Telescope's Wide Field Planetary Camera 2 (WFPC2). Lying some 40,000 light-years from Earth in the direction of the constellation Pegasus, M15 is one of nearly 150 known globular clusters that form a vast halo surrounding our Milky Way galaxy. Each of these clusters is a spherical association of hundreds of thousands of ancient stars. The image, prepared by the Hubble Heritage team, attempts to show the stars in M15 in their true colors. The brightest cluster stars are red giants, with an orange color due to surface temperatures lower than our Sun's. Most of the fainter stars are hotter, giving them a bluish-white color. If we lived in the core of M15, our sky would blaze with tens of thousands of brilliant stars both day and night! Nestled among the myriads of stars visible in the Hubble image is an astronomical oddity. The pinkish object to the upper left of the cluster's core is a gas cloud surrounding a dying star. Known as Kuestner 648, this was the first planetary nebula to be identified in a globular cluster. In 1928, F. G. Pease, working at the 100-inch telescope of California's Mount Wilson Observatory, photographed the spectrum of K 648 and discovered the telltale bright emission of a nebular gas cloud rather than a normal star. In the ensuing 70 years, only three more planetary nebulae have been discovered in globular clusters. The stars in M15 and other globular clusters are estimated to be about 12 billion years old. They were among the first generations of stars to form in the Milky Way. Our Sun, by comparison, is a youthful 4.6 billion years old. As a star like the Sun ages, it exhausts the hydrogen that fuels its nuclear fusion, and increases in size to become a red giant. Then it ejects its outer layers into space, producing a planetary nebula. The remnant star at the center of the nebula gradually dies away as a

  4. Amyloidogenic Regions and Interaction Surfaces Overlap in Globular Proteins Related to Conformational Diseases

    PubMed Central

    Castillo, Virginia; Ventura, Salvador

    2009-01-01

    Protein aggregation underlies a wide range of human disorders. The polypeptides involved in these pathologies might be intrinsically unstructured or display a defined 3D-structure. Little is known about how globular proteins aggregate into toxic assemblies under physiological conditions, where they display an initially folded conformation. Protein aggregation is, however, always initiated by the establishment of anomalous protein-protein interactions. Therefore, in the present work, we have explored the extent to which protein interaction surfaces and aggregation-prone regions overlap in globular proteins associated with conformational diseases. Computational analysis of the native complexes formed by these proteins shows that aggregation-prone regions do frequently overlap with protein interfaces. The spatial coincidence of interaction sites and aggregating regions suggests that the formation of functional complexes and the aggregation of their individual subunits might compete in the cell. Accordingly, single mutations affecting complex interface or stability usually result in the formation of toxic aggregates. It is suggested that the stabilization of existing interfaces in multimeric proteins or the formation of new complexes in monomeric polypeptides might become effective strategies to prevent disease-linked aggregation of globular proteins. PMID:19696882

  5. TOPDOM: database of conservatively located domains and motifs in proteins.

    PubMed

    Varga, Julia; Dobson, László; Tusnády, Gábor E

    2016-09-01

    The TOPDOM database-originally created as a collection of domains and motifs located consistently on the same side of the membranes in α-helical transmembrane proteins-has been updated and extended by taking into consideration consistently localized domains and motifs in globular proteins, too. By taking advantage of the recently developed CCTOP algorithm to determine the type of a protein and predict topology in case of transmembrane proteins, and by applying a thorough search for domains and motifs as well as utilizing the most up-to-date version of all source databases, we managed to reach a 6-fold increase in the size of the whole database and a 2-fold increase in the number of transmembrane proteins. TOPDOM database is available at http://topdom.enzim.hu The webpage utilizes the common Apache, PHP5 and MySQL software to provide the user interface for accessing and searching the database. The database itself is generated on a high performance computer. tusnady.gabor@ttk.mta.hu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  6. The Muon Collider as a $H/A$ factory

    DOE PAGES

    Eichten, Estia; Martin, Adam; Univ. of Notre Dame, IN

    2013-11-22

    We show that a muon collider is ideally suited for the study of heavy H/A scalars, cousins of the Higgs boson found in two-Higgs doublet models and required in supersymmetric models. The key aspects of H/A are: (1) they are narrow, yet have a width-to-mass ratio far larger than the expected muon collider beam-energy resolution, and (2) the larger muon Yukawa allows efficient s-channel production. We study in detail a representative Natural Supersymmetry model which has a 1.5 Tev H/A withmore » $$m_H$$- $$m_A$$ = 10 Gev. The large event rates at resonant peak allow the determination of the individual H and A resonance parameters (including CP) and the decays into electroweakinos provides a wealth of information unavailable to any other present or planned collider.« less

  7. Crystal Structure of a Complex of the Intracellular Domain of Interferon λ Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1.

    PubMed

    Zhang, Di; Wlodawer, Alexander; Lubkowski, Jacek

    2016-11-20

    The crystal structure of a construct consisting of the FERM and SH2-like domains of the human Janus kinase 1 (JAK1) bound to a fragment of the intracellular domain of the interferon-λ receptor 1 (IFNLR1) has been determined at the nominal resolution of 2.1Å. In this structure, the receptor peptide forms an 85-Å-long extended chain, in which both the previously identified box1 and box2 regions bind simultaneously to the FERM and SH2-like domains of JAK1. Both domains of JAK1 are generally well ordered, with regions not seen in the crystal structure limited to loops located away from the receptor-binding regions. The structure provides a much more complete and accurate picture of the interactions between JAK1 and IFNLR1 than those given in earlier reports, illuminating the molecular basis of the JAK-cytokine receptor association. A glutamate residue adjacent to the box2 region in IFNLR1 mimics the mode of binding of a phosphotyrosine in classical SH2 domains. It was shown here that a deletion of residues within the box1 region of the receptor abolishes stable interactions with JAK1, although it was previously shown that box2 alone is sufficient to stabilize a similar complex of the interferon-α receptor and TYK2. Published by Elsevier Ltd.

  8. Crystal Structure of a Two-domain Fragment of Hepatocyte Growth Factor Activator Inhibitor-1: FUNCTIONAL INTERACTIONS BETWEEN THE KUNITZ-TYPE INHIBITOR DOMAIN-1 AND THE NEIGHBORING POLYCYSTIC KIDNEY DISEASE-LIKE DOMAIN.

    PubMed

    Hong, Zebin; De Meulemeester, Laura; Jacobi, Annemarie; Pedersen, Jan Skov; Morth, J Preben; Andreasen, Peter A; Jensen, Jan K

    2016-07-01

    Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a type I transmembrane protein and inhibitor of several serine proteases, including hepatocyte growth factor activator and matriptase. The protein is essential for development as knock-out mice die in utero due to placental defects caused by misregulated extracellular proteolysis. HAI-1 contains two Kunitz-type inhibitor domains (Kunitz), which are generally thought of as a functionally self-contained protease inhibitor unit. This is not the case for HAI-1, where our results reveal how interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. Here we present an x-ray crystal structure of an HAI-1 fragment covering the internal domain and Kunitz-1. The structure reveals not only that the previously uncharacterized internal domain is a member of the polycystic kidney disease domain family but also how the two domains engage in interdomain interactions. Supported by solution small angle x-ray scattering and a combination of site-directed mutagenesis and functional assays, we show that interdomain interactions not only stabilize the fold of the internal domain but also stimulate the inhibitory activity of Kunitz-1. By completing our structural characterization of the previously unknown N-terminal region of HAI-1, we provide new insight into the interplay between tertiary structure and the inhibitory activity of a multidomain protease inhibitor. We propose a previously unseen mechanism by which the association of an auxiliary domain stimulates the inhibitory activity of a Kunitz-type inhibitor (i.e. the first structure of an intramolecular interaction between a Kunitz and another domain). © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. From Globular Clusters to Tidal Dwarfs: Structure Formation in Tidal Tails

    NASA Astrophysics Data System (ADS)

    Knierman, K.; Hunsberger, S.; Gallagher, S.; Charlton, J.; Whitmore, B.; Hibbard, J.; Kundu, A.; Zaritsky, D.

    1999-12-01

    Galaxy interactions trigger star formation in tidal debris. How does this star formation depend on the local and global physical conditions? Using WFPC2/HST images, we investigate the range of structure within tidal tails of four classic ``Toomre Sequence'' mergers: NGC 4038/9 (``Antennae''), NGC 7252 (``Atoms for Peace''), NGC 3921, and NGC 3256. These tails contain a variety of stellar associations with sizes from globular clusters up to dwarf Irregulars. We explore whether there is a continuum between the two extremes. Our eight fields sample seven tidal tails at a variety of stages in the evolutionary sequence. Some of these tails are rich in HI while others are HI poor. Large tidal dwarfs are embedded in three of the tails. Using V and I WFPC2 images, we measure luminosities and colors of substructures within the tidal tails. The properties of globular cluster candidates in the tails will be contrasted with those of the hundreds of young clusters in the central regions of these mergers. We address whether globular clusters form and survive in the tidal tails and whether tidal dwarfs are composed of only young stars. By comparing the properties of structures in the tails of the four mergers with different ages, we examine systematic evolution of structure along the evolutionary sequence and as a function of HI content. We acknowledge support from NASA through STScI, and from NSF for an REU supplement for Karen Knierman.

  10. Globular cluster systems - Comparative evolution of Galactic halos

    NASA Astrophysics Data System (ADS)

    Harris, William E.

    Space distributions, metallicity/age distributions, and kinematics are considered for the Milky Way halo system. Comparisons are made with other systems, and time scales for dynamical evolution are considered. It is noted that the globular cluster subsystems of halos resemble each other more closely than their parent galaxies do; this forms a reasonable basis for supposing that they represent a kind of underlying unity in the protogalaxy formation process.

  11. Biochemical characterization of domain-specific glycoproteins of the rat hepatocyte plasma membrane.

    PubMed

    Bartles, J R; Braiterman, L T; Hubbard, A L

    1985-10-15

    Seven integral proteins (CE 9, HA 21, HA 116, HA 16, HA 4, HA 201, and HA 301) were isolated from rat hepatocyte plasma membranes by immunoaffinity chromatography on monoclonal antibody-Sepharose. Six of the proteins (all but HA 16) exhibit domain-specific localizations (either bile canalicular or sinusoidal/lateral) about the hepatocyte surface. We identified three of these protein antigens as leucine aminopeptidase (HA 201), dipeptidyl peptidase IV (HA 301), and the asialoglycoprotein receptor (HA 116). We also developed 125I-lectin blotting procedures that, when used in conjunction with chemical and glycosidase treatments, permitted a comparison of the types of oligosaccharides present on the seven proteins. All seven are sialoglycoproteins, based upon the effects of prior neuraminidase and periodate-aniline-cyanoborohydride treatments of blots on labeling by 125I-wheat germ agglutinin. 125I-labeled Ricinus communis agglutinin I and 125I-peanut agglutinin blotting of the desialylated proteins revealed few if any conventional O-linked oligosaccharides, suggesting that the sialyl residues represent termini of N-linked complex-type oligosaccharides. Depending upon the protein, we estimated the presence of 2-26 N-linked oligosaccharides/polypeptide chain from the Mr reductions accompanying chemical or enzymatic deglycosylation. Three of these mature plasma membrane proteins (HA 21, HA 116, and HA 4) have both high mannose-type and complex-type oligosaccharides on every copy of their polypeptide chains. The labeling of these three proteins by 125I-concanavalin A was sensitive to treatment with endoglycosidase H, and each exhibited a quantitative reduction in Mr after the treatment, as assessed independently by 125I-wheat germ agglutinin blotting. At this level of analysis, we were unable to discern differences in the types of oligosaccharides present on these seven glycoproteins that correlate with their patterns of expression within the plasma membrane domains of

  12. A Proper Motions Study of the Globular Cluster NGC 3201

    NASA Astrophysics Data System (ADS)

    Sariya, Devesh P.; Jiang, Ing-Guey; Yadav, R. K. S.

    2017-03-01

    With a high value of heliocentric radial velocity, a retrograde orbit, and suspected to have an extragalactic origin, NGC 3201 is an interesting globular cluster for kinematical studies. Our purpose is to calculate the relative proper motions (PMs) and membership probability for the stars in the wide region of globular cluster NGC 3201. PM based membership probabilities are used to isolate the cluster sample from the field stars. The membership catalog will help address the question of chemical inhomogeneity in the cluster. Archive CCD data taken with a wide-field imager (WFI) mounted on the ESO 2.2 m telescope are reduced using the high-precision astrometric software developed by Anderson et al. for the WFI images. The epoch gap between the two observational runs is ˜14.3 years. To standardize the BVI photometry, Stetson’s secondary standard stars are used. The CCD data with an epoch gap of ˜14.3 years enables us to decontaminate the cluster stars from field stars efficiently. The median precision of PMs is better than ˜0.8 mas yr-1 for stars having V< 18 mag that increases up to ˜1.5 mas yr-1 for stars with 18< V< 20 mag. Kinematic membership probabilities are calculated using PMs for stars brighter than V˜ 20 mag. An electronic catalog of positions, relative PMs, BVI magnitudes, and membership probabilities in the ˜19.7 × 17 arcmin2 region of NGC 3201 is presented. We use our membership catalog to identify probable cluster members among the known variables and X-ray sources in the direction of NGC 3201. Based on observations with the MPG/ESO 2.2 m and ESO/VLT telescopes, located at La Silla and Paranal Observatory, Chile, under DDT programs 164.O-0561(F), 093.A-9028(A), and the archive material.

  13. Globular cluster chemistry in fast-rotating dwarf stars belonging to intermediate-age open clusters

    NASA Astrophysics Data System (ADS)

    Pancino, Elena

    2018-06-01

    The peculiar chemistry observed in multiple populations of Galactic globular clusters is not generally found in other systems such as dwarf galaxies and open clusters, and no model can currently fully explain it. Exploring the boundaries of the multiple-population phenomenon and the variation of its extent in the space of cluster mass, age, metallicity, and compactness has proven to be a fruitful line of investigation. In the framework of a larger project to search for multiple populations in open clusters that is based on literature and survey data, I found peculiar chemical abundance patterns in a sample of intermediate-age open clusters with publicly available data. More specifically, fast-rotating dwarf stars (v sin i ≥ 50 km s-1) that belong to four clusters (Pleiades, Ursa Major, Come Berenices, and Hyades) display a bimodality in either [Na/Fe] or [O/Fe], or both, with the low-Na and high-O peak more populated than the high-Na and low-O peak. Additionally, two clusters show a Na-O anti-correlation in the fast-rotating stars, and one cluster shows a large [Mg/Fe] variation in stars with high [Na/Fe], reaching the extreme Mg depletion observed in NGC 2808. Even considering that the sample sizes are small, these patterns call for attention in the light of a possible connection with the multiple population phenomenon of globular clusters. The specific chemistry observed in these fast-rotating dwarf stars is thought to be produced by a complex interplay of different diffusion and mixing mechanisms, such as rotational mixing and mass loss, which in turn are influenced by metallicity, binarity, mass, age, variability, and so on. However, with the sample in hand, it was not possible to identify which stellar parameters cause the observed Na and O bimodality and Na-O anti-correlation. This suggests that other stellar properties might be important in addition to stellar rotation. Stellar binarity might influence the rotational properties and enhance rotational

  14. A Deep X-ray Survey of the Globular Cluster Omega Centauri

    NASA Astrophysics Data System (ADS)

    Henleywillis, Simon; Cool, Adrienne M.; Haggard, Daryl; Heinke, Craig; Callanan, Paul; Zhao, Yue

    2018-03-01

    We identify 233 X-ray sources, of which 95 are new, in a 222 ks exposure of Omega Centauri with the Chandra X-ray Observatory's ACIS-I detector. The limiting unabsorbed flux in the core is fX(0.5-6.0 keV) ≃ 3×10-16 erg s-1 cm-2 (Lx ≃ 1×1030 erg s-1 at 5.2 kpc). We estimate that ˜60 ± 20 of these are cluster members, of which ˜30 lie within the core (rc = 155 arcsec), and another ˜30 between 1-2 core radii. We identify four new optical counterparts, for a total of 45 likely identifications. Probable cluster members include 18 cataclysmic variables (CVs) and CV candidates, one quiescent low-mass X-ray binary, four variable stars, and five stars that are either associated with ω Cen's anomalous red giant branch, or are sub-subgiants. We estimate that the cluster contains 40 ± 10 CVs with Lx > 1031 erg s-1, confirming that CVs are underabundant in ω Cen relative to the field. Intrinsic absorption is required to fit X-ray spectra of six of the nine brightest CVs, suggesting magnetic CVs, or high-inclination systems. Though no radio millisecond pulsars (MSPs) are currently known in ω Cen, more than 30 unidentified sources have luminosities and X-ray colours like those of MSPs found in other globular clusters; these could be responsible for the Fermi-detected gamma-ray emission from the cluster. Finally, we identify a CH star as the counterpart to the second-brightest X-ray source in the cluster and argue that it is a symbiotic star. This is the first such giant/white dwarf binary to be identified in a globular cluster.

  15. Involvement of suppressor of cytokine signaling-1 in globular adiponectin-induced granulocyte colony-stimulating factor in RAW 264 cell.

    PubMed

    Fujimoto, Akie; Akifusa, Sumio; Hirofuji, Takao; Yamashita, Yoshihisa

    2011-09-01

    We previously demonstrated that treatment with a globular type of adiponectin (gAd) induced expression of granulocyte colony-stimulating factor (G-CSF) via the MEK/ERK signaling pathway in a murine macrophage cell line, RAW 264. In the present study, we investigated whether suppressor of cytokine signaling-1 (SOCS1) has roles in the regulation of gAd-induced G-CSF generation. Intracellular G-CSF generation induced by gAd treatment peaked after 10h and then attenuated. SOCS1 mRNA and protein were expressed at 1h and 4h after gAd treatment, respectively. Overexpression of SOCS1 reduced G-CSF generation and phosphorylation of ERK, JNK, and p38 MAPK in gAd-treated cells. While gAd treatment induced the translocation of STAT3 to the nucleus under control conditions, STAT3 stayed in the cytosol when SOCS1 was overexpressed. Additionally, knockdown of SOCS1 by interfering RNA caused levels of G-CSF to continue to rise beyond 10h after gAd treatment. These results suggest that SOCS1 is involved in providing negative feedback for gAd-induced production of G-CSF. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Intermediate-Mass Black Holes in Globular Cluster Systems

    NASA Astrophysics Data System (ADS)

    Wrobel, J. M.; Miller-Jones, J. C. A.; Nyland, K. E.; Maccarone, T. J.

    2018-01-01

    Theory suggests that globular clusters (GCs) of stars can host intermediate-mass black holes (IMBHs) with masses of about 100 to 100,000 solar masses. We invoke a semi-empirical model to predict the mass of an IMBH that, if undergoing accretion in the long-lived hard X-ray state, is consistent with the synchrotron radio luminosity of a GC. We apply this model to extant images from the Karl G. Jansky Very Large Array (VLA) and to simulated images from the Next Generation Very Large Array (ngVLA). Guided by our VLA results for M81's system of 206 probable GCs at a distance of 3.6 Mpc, we consider using the ngVLA to study the hundreds of globular cluster systems out to a distance of 25 Mpc. With its sensitivity, spatial resolution, and field of view, we conclude that the ngVLA at 2cm will efficiently probe IMBH masses for tens of thousands of GCs. Finding IMBHs in GCs could validate a formation channel for seed BHs in the early universe, underpin gravitational wave predictions for space missions, and test scaling relations between stellar systems and the central BHs they host. The NRAO is a facility of the NSF, operated under cooperative agreement by AUI, Inc.

  17. Charge State of the Globular Histone Core Controls Stability of the Nucleosome

    PubMed Central

    Fenley, Andrew T.; Adams, David A.; Onufriev, Alexey V.

    2010-01-01

    Presented here is a quantitative model of the wrapping and unwrapping of the DNA around the histone core of the nucleosome that suggests a mechanism by which this transition can be controlled: alteration of the charge state of the globular histone core. The mechanism is relevant to several classes of posttranslational modifications such as histone acetylation and phosphorylation; several specific scenarios consistent with recent in vivo experiments are considered. The model integrates a description based on an idealized geometry with one based on the atomistic structure of the nucleosome, and the model consistently accounts for both the electrostatic and nonelectrostatic contributions to the nucleosome free energy. Under physiological conditions, isolated nucleosomes are predicted to be very stable (38 ± 7 kcal/mol). However, a decrease in the charge of the globular histone core by one unit charge, for example due to acetylation of a single lysine residue, can lead to a significant decrease in the strength of association with its DNA. In contrast to the globular histone core, comparable changes in the charge state of the histone tail regions have relatively little effect on the nucleosome's stability. The combination of high stability and sensitivity explains how the nucleosome is able to satisfy the seemingly contradictory requirements for thermodynamic stability while allowing quick access to its DNA informational content when needed by specific cellular processes such as transcription. PMID:20816070

  18. Chemical analysis of eight giant stars of the globular cluster NGC 6366

    NASA Astrophysics Data System (ADS)

    Puls, Arthur A.; Alves-Brito, Alan; Campos, Fabíola; Dias, Bruno; Barbuy, Beatriz

    2018-05-01

    The metal-rich Galactic globular cluster NGC 6366 is the fifth closest to the Sun. Despite its interest, it has received scarce attention, and little is known about its internal structure. Its kinematics suggests a link to the halo, but its metallicity indicates otherwise. We present a detailed chemical analysis of eight giant stars of NGC 6366, using high-resolution and high-quality spectra (R > 40 000, S/N > 60) obtained at the VLT (8.2 m) and CFHT (3.6 m) telescopes. We attempted to characterize its chemistry and to search for evidence of multiple stellar populations. The atmospheric parameters were derived using the method of excitation and ionization equilibrium of Fe I and Fe II lines and from those atmospheric parameters we calculated the abundances for other elements and found that none of the elements measured presents star-to-star variation greater than the uncertainties. We compared the derived abundances with those of other globular clusters and field stars available in the literature. We determined a mean [Fe/H] = -0.60 ± 0.03 for NGC 6366 and found some similarity of this object with M 71, another inner halo globular cluster. The Na-O anticorrelation extension is short and no star-to-star variation in Al is found. The presence of second generation stars is not evident in NGC 6366.

  19. Hydrophobicity diversity in globular and nonglobular proteins measured with the Gini index.

    PubMed

    Carugo, Oliviero

    2017-12-01

    Amino acids and their properties are variably distributed in proteins and different compositions determine all protein features, ranging from solubility to stability and functionality. Gini index, a tool to estimate distribution uniformity, is widely used in macroeconomics and has numerous statistical applications. Here, Gini index is used to analyze the distribution of hydrophobicity in proteins and to compare hydrophobicity distribution in globular and intrinsically disordered proteins. Based on the analysis of carefully selected high-quality data sets of proteins extracted from the Protein Data Bank (http://www.rcsb.org) and from the DisProt database (http://www.disprot.org/), it is observed that hydrophobicity is distributed in a more diverse way in intrinsically disordered proteins than in folded and soluble globular proteins. This correlates with the observation that the amino acid composition deviates from the uniformity (estimate with the Shannon and the Gini-Simpson indices) more in intrinsically disordered proteins than in globular and soluble proteins. Although statistical tools tike the Gini index have received little attention in molecular biology, these results show that they allow one to estimate sequence diversity and that they are useful to delineate trends that can hardly be described, otherwise, in simple and concise ways. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Structural and functional properties of the N transcriptional activation domain of thyroid transcription factor-1: similarities with the acidic activation domains.

    PubMed Central

    Tell, G; Perrone, L; Fabbro, D; Pellizzari, L; Pucillo, C; De Felice, M; Acquaviva, R; Formisano, S; Damante, G

    1998-01-01

    The thyroid transcription factor 1 (TTF-1) is a tissue-specific transcription factor involved in the development of thyroid and lung. TTF-1 contains two transcriptional activation domains (N and C domain). The primary amino acid sequence of the N domain does not show any typical characteristic of known transcriptional activation domains. In aqueous solution the N domain exists in a random-coil conformation. The increase of the milieu hydrophobicity, by the addition of trifluoroethanol, induces a considerable gain of alpha-helical structure. Acidic transcriptional activation domains are largely unstructured in solution, but, under hydrophobic conditions, folding into alpha-helices or beta-strands can be induced. Therefore our data indicate that the inducibility of alpha-helix by hydrophobic conditions is a property not restricted to acidic domains. Co-transfections experiments indicate that the acidic domain of herpes simplex virus protein VP16 (VP16) and the TTF-1 N domain are interchangeable and that a chimaeric protein, which combines VP16 linked to the DNA-binding domain of TTF-1, undergoes the same regulatory constraints that operate for the wild-type TTF-1. In addition, we demonstrate that the TTF-1 N domain possesses two typical properties of acidic activation domains: TBP (TATA-binding protein) binding and ability to activate transcription in yeast. Accordingly, the TTF-1 N domain is able to squelch the activity of the p65 acidic domain. Altogether, these structural and functional data suggest that a non-acidic transcriptional activation domain (TTF-1 N domain) activates transcription by using molecular mechanisms similar to those used by acidic domains. TTF-1 N domain and acidic domains define a family of proteins whose common property is to activate transcription through the use of mechanisms largely conserved during evolutionary development. PMID:9425125

  1. Constraints on the formation history of the elliptical galaxy NGC 3923 from the colors of its globular clusters

    NASA Technical Reports Server (NTRS)

    Zepf, Stephen E.; Ashman, Keith M.; Geisler, Doug

    1995-01-01

    We present a study of the colors of globular clusters associated with the elliptical galaxy NGC 3923. Our final sample consists of Wasington system C and T(sub 1) photometry for 143 globular cluster candidates with an expected contamination of no more than 10%. We find that the color distribution of the NGC 3923 globular cluster system (GCS) is broad and appears to have at least two peaks. A mixture modeling analysis of the color distribution indicates that a two-component model is favored over a single-component one at a high level of confidence (greater than 99%). This evidence for more than one population in the GCS of NGC 3923 is similar to that previously noted for the four other elliptical galaxies for which similar data have been published. Furthermore, we find that the NGC 3923 GCS is redder than the GCSs of previously studed elliptical galaxies of similar luminosity. The median metallicity inferred from our (C-(T(sub 1)))(sub 0) colors is (Fe/H)(sub med) = -0.56, with an uncertainty of 0.14 dex arising from all sources of uncertainty in the mean color. This is more metal rich than the median metallicity found for the GCS of M87 using the same method, (Fe/H)(sub med) = -0.94. Since M87 is more luminous than NGC 3923, this result points to significant scatter about any trend of higher GCS metallicity with increasing galaxy luminosity. We also show that there is a color gradient in the NGC 3923 GCS corresponding to about -0.5 dex in Delta(Fe/H)/Delta(log r). We conclude that the shape of the color distribution of individual GCSs and the variation in mean color among the GCSs of ellipticals are difficult to understand if elliptical galaxies are formed in a single protogalactic collapse. Models in which ellipticals and their globular clusters are formed in more than one event, such as a merger scenario, are more successful in accounting for these observations.

  2. Detection of high-energy gamma-ray emission from the globular cluster 47 Tucanae with Fermi.

    PubMed

    Abdo, A A; Ackermann, M; Ajello, M; Atwood, W B; Axelsson, M; Baldini, L; Ballet, J; Barbiellini, G; Bastieri, D; Baughman, B M; Bechtol, K; Bellazzini, R; Berenji, B; Blandford, R D; Bloom, E D; Bonamente, E; Borgland, A W; Bregeon, J; Brez, A; Brigida, M; Bruel, P; Burnett, T H; Caliandro, G A; Cameron, R A; Caraveo, P A; Casandjian, J M; Cecchi, C; Celik, O; Charles, E; Chaty, S; Chekhtman, A; Cheung, C C; Chiang, J; Ciprini, S; Claus, R; Cohen-Tanugi, J; Conrad, J; Cutini, S; Dermer, C D; de Palma, F; Digel, S W; Dormody, M; do Couto e Silva, E; Drell, P S; Dubois, R; Dumora, D; Farnier, C; Favuzzi, C; Fegan, S J; Focke, W B; Frailis, M; Fukazawa, Y; Fusco, P; Gargano, F; Gasparrini, D; Gehrels, N; Germani, S; Giebels, B; Giglietto, N; Giordano, F; Glanzman, T; Godfrey, G; Grenier, I A; Grove, J E; Guillemot, L; Guiriec, S; Hanabata, Y; Harding, A K; Hayashida, M; Hays, E; Horan, D; Hughes, R E; Jóhannesson, G; Johnson, A S; Johnson, R P; Johnson, T J; Johnson, W N; Kamae, T; Katagiri, H; Kawai, N; Kerr, M; Knödlseder, J; Kuehn, F; Kuss, M; Lande, J; Latronico, L; Lemoine-Goumard, M; Longo, F; Loparco, F; Lott, B; Lovellette, M N; Lubrano, P; Makeev, A; Mazziotta, M N; McConville, W; McEnery, J E; Meurer, C; Michelson, P F; Mitthumsiri, W; Mizuno, T; Moiseev, A A; Monte, C; Monzani, M E; Morselli, A; Moskalenko, I V; Murgia, S; Nolan, P L; Norris, J P; Nuss, E; Ohsugi, T; Omodei, N; Orlando, E; Ormes, J F; Paneque, D; Panetta, J H; Parent, D; Pelassa, V; Pepe, M; Pierbattista, M; Piron, F; Porter, T A; Rainò, S; Rando, R; Razzano, M; Rea, N; Reimer, A; Reimer, O; Reposeur, T; Ritz, S; Rochester, L S; Rodriguez, A Y; Romani, R W; Roth, M; Ryde, F; Sadrozinski, H F-W; Sanchez, D; Sander, A; Saz Parkinson, P M; Sgrò, C; Smith, D A; Smith, P D; Spandre, G; Spinelli, P; Starck, J-L; Strickman, M S; Suson, D J; Tajima, H; Takahashi, H; Tanaka, T; Thayer, J B; Thayer, J G; Thompson, D J; Tibaldo, L; Torres, D F; Tosti, G; Tramacere, A; Uchiyama, Y; Usher, T L; Vasileiou, V; Vilchez, N; Vitale, V; Wang, P; Webb, N; Winer, B L; Wood, K S; Ylinen, T; Ziegler, M

    2009-08-14

    We report the detection of gamma-ray emissions above 200 megaelectron volts at a significance level of 17sigma from the globular cluster 47 Tucanae, using data obtained with the Large Area Telescope onboard the Fermi Gamma-ray Space Telescope. Globular clusters are expected to emit gamma rays because of the large populations of millisecond pulsars that they contain. The spectral shape of 47 Tucanae is consistent with gamma-ray emission from a population of millisecond pulsars. The observed gamma-ray luminosity implies an upper limit of 60 millisecond pulsars present in 47 Tucanae.

  3. Effect of molecular weight of hyaluronic acid (HA) on viscoelasticity and particle texturing feel of HA dermal biphasic fillers.

    PubMed

    Chun, Cheolbyong; Lee, Deuk Yong; Kim, Jin-Tae; Kwon, Mi-Kyung; Kim, Young-Zu; Kim, Seok-Soon

    2016-01-01

    Hyaluronic acid (HA) dermal biphasic fillers are synthesized for their efficacy in correcting aesthetic defects such as wrinkles, scars and facial contouring defects. The fillers consist of crosslinked HA microspheres suspended in a noncrosslinked HA. To extend the duration of HAs within the dermis and obtain the particle texturing feel, HAs are crosslinked to obtain the suitable mechanical properties. Hyaluronic acid (HA) dermal biphasic fillers are prepared by mixing the crosslinked HA microspheres and the noncrosslinked HAs. The elastic modulus of the fillers increased with raising the volume fraction of the microspheres. The mechanical properties and the particle texturing feel of the fillers made from crosslinked HA (1058 kDa) microspheres suspended in noncrosslinked HA (1368 kDa) are successfully achieved, which are adequate for the fillers. Dermal biphasic HA fillers made from 1058 kDa exhibit suitable elastic moduli (211 to 420 Pa) and particle texturing feel (scale 7 ~ 9).

  4. Investigation of boundary conditions for biomimetic HA deposition on titanium oxide surfaces.

    PubMed

    Lindgren, M; Astrand, M; Wiklund, U; Engqvist, H

    2009-07-01

    To improve the clinical outcome of metal implants, i.e. earlier loading and reduction of the incidence of revision surgery, better bone bonding ability is wanted. One method to achieve this is to change the surface chemistry to give a surface that facilitates bone bonding in vivo, i.e. a bioactive surface. Crystalline titanium oxide has recently been proven to be bioactive in vitro and is an interesting option to the more common hydroxylapatite (HA) coatings on implants. A materials possible in vitro bioactivity is tested through soaking in simulated body fluid and studies of possible HA formation on the surface. For bioactive materials, the formed HA layer can also be used as a coating. The aim of the current paper is to investigate some boundary conditions for HA formation on crystalline titanium oxide surfaces regarding influence from coating thickness, soaking time and soaking temperature. The influence from soaking time and temperature on the HA growth were investigated on oxidised Ti samples, (24 h at 800 degrees C) resulting in a rutile surface structure. The oxidised samples were tested at three temperatures (4, 37 and 65 degrees C) and four times (1 h, 1 day, 1 week and 4 weeks). The influence from titanium coating thickness on the HA growth was investigated via depositing thin films of crystalline titanium dioxide on Ti plates using a reactive magnetron sputtering process. Four different PVD runs with coating thicknesses between 19 and 74 nm were tested. The soaking temperature had an effect on the HA formation and growth on both rutile surfaces and native oxide on Ti substrates. Higher temperatures lead to easier formation of HA. It was even possible, at 65 degrees C, to grow HA on native titanium oxide from soaking in PBS. The coating quality was better for HA formed at 65 degrees C compared to 37 degrees C. All PVD-coatings showed HA growth after 1 week in PBS at 37 degrees C, thus even very thin coatings of crystalline titanium oxide coatings are

  5. [Construction of porous hydroxyapatite (HA) block loaded with cultured chondrocytes].

    PubMed

    Yan, M; Dang, G

    1999-07-01

    To construct a kind of bone healing enhancing implant with cultured chondrocytes bound to hydroxyapatite (HA). Chondrocytes were obtained from the costicartilage of rat and were cultured on the porous HA blocks, 3 mm x 3 mm x 4 mm size, for three and seven days. Scanning electron micrograph was taken to show whether the cells grew outside and inside the pore of HA block. The cells cultured on tiny glass sheet for 2 days were used to prove where the cells come from by in situ hybridization technique with alpha1 (II) cDNA probe. Scanning electron micrographs showed that the pores of the HA surface and inside of the blocks are filled with cultured cells, especially the longer cultured block. The cells were chondrocytes confirmed by in situ hybridization. The porous HA can be used as cell cultured substrate and chondrocyte can adhere and proliferate inside the porous HA block.

  6. Sub-Domains of Ricin’s B Subunit as Targets of Toxin Neutralizing and Non-Neutralizing Monoclonal Antibodies

    PubMed Central

    Yermakova, Anastasiya; Vance, David J.; Mantis, Nicholas J.

    2012-01-01

    The B subunit (RTB) of ricin toxin is a galactose (Gal)−/N-acetylgalactosamine (GalNac)-specific lectin that mediates attachment, entry, and intracellular trafficking of ricin in host cells. Structurally, RTB consists of two globular domains with identical folding topologies. Domains 1 and 2 are each comprised of three homologous sub-domains (α, β, γ) that likely arose by gene duplication from a primordial carbohydrate recognition domain (CRD), although only sub-domains 1α and 2γ retain functional lectin activity. As part of our ongoing effort to generate a comprehensive B cell epitope map of ricin, we report the characterization of three new RTB-specific monoclonal antibodies (mAbs). All three mAbs, JB4, B/J F9 and C/M A2, were initially identified based on their abilities to neutralize ricin in a Vero cell cytotoxicty assay and to partially (or completely) block ricin attachment to cell surfaces. However, only JB4 proved capable of neutralizing ricin in a macrophage apoptosis assay and in imparting passive immunity to mice in a model of systemic intoxication. Using a combination of techniques, including competitive ELISAs, pepscan analysis, differential reactivity by Western blot, as well as affinity enrichment of phage displayed peptides, we tentatively localized the epitopes recognized by the non-neutralizing mAbs B/J F9 and C/M A2 to sub-domains 2α and 2β, respectively. Furthermore, we propose that the epitope recognized by JB4 is within sub-domain 2γ, adjacent to RTB’s high affinity Gal/GalNAc CRD. These data suggest that recognition of RTB’s sub-domains 1α and 2γ are critical determinants of antibody neutralizing activity and protective immunity to ricin. PMID:22984492

  7. The Breadth of Cross Sub-Type Neutralisation Activity of a Single Domain Antibody to Influenza Hemagglutinin Can Be Increased by Antibody Valency

    PubMed Central

    Hufton, Simon E.; Risley, Paul; Ball, Christina R.; Major, Diane; Engelhardt, Othmar G.; Poole, Stephen

    2014-01-01

    The response to the 2009 A(H1N1) influenza pandemic has highlighted the need for additional strategies for intervention which preclude the prior availability of the influenza strain. Here, 18 single domain VHH antibodies against the 2009 A(H1N1) hemagglutinin (HA) have been isolated from a immune alpaca phage displayed library. These antibodies have been grouped as having either (i) non-neutralising, (ii) H1N1 restricted neutralising or (iii) broad cross-subtype neutralising activity. The ability to neutralise different viral subtypes, including highly pathogenic avian influenza (H5N1), correlated with the absence of hemagglutination inhibition activity, loss of binding to HA at acid pH and the absence of binding to the head domain containing the receptor binding site. This data supports their binding to epitopes in the HA stem region and a mechanism of action other than blocking viral attachment to cell surface receptors. After conversion of cross-neutralising antibodies R1a-B6 and R1a-A5 into a bivalent format, no significant enhancement in neutralisation activity was seen against A(H1N1) and A(H5N1) viruses. However, bivalent R1a-B6 showed an 18 fold enhancement in potency against A(H9N2) virus and, surprisingly, gained the ability to neutralise an A(H2N2) virus. This demonstrates that cross-neutralising antibodies, which make lower affinity interactions with the membrane proximal stem region of more divergent HA sub-types, can be optimised by bivalency so increasing their breadth of anti-viral activity. The broad neutralising activity and favourable characteristics, such as high stability, simple engineering into bivalent molecules and low cost production make these single domain antibodies attractive candidates for diagnostics and immunotherapy of pandemic influenza. PMID:25084445

  8. Transport features of nano-hydroxylapatite (n-HA) embedded silicone rubber (SR) systems: influence of SR/n-HA interaction, degree of reinforcement and morphology.

    PubMed

    M, Bindu; G, Unnikrishnan

    2017-09-27

    We report the transport characteristics of silicone rubber/nano-hydroxylapatite (SR/n-HA) systems at room temperature with reference to the effects of n-HA loading, morphology and penetrant nature, using toluene, xylene, ethyl acetate and butyl acetate in the liquid phase and methanol, ethanol, 1-propanol, 2-propanol and butanol in the vapour phase as probe molecules. The interaction between the n-HA particles and SR matrix has been confirmed by FTIR analysis. As the n-HA content in the SR matrix increased, the penetrant uptake has been found to decrease. The observations have been correlated with the density and void content of the systems. Scanning electron microscopy images have been found to be complementary to the observed transport features. The reinforcement effect of n-HA particles on the SR matrix has been verified by Kraus equation. Molecular mass between the cross links has been observed to decrease with an increase in n-HA loading. The results have been compared with affine, phantom network, parallel, series and Maxwell models. The transport data have been complemented by observations on biological fluid uptake with urea, d-glucose, KI, saline water, phosphate buffer and artificial urine as the media.

  9. A fully automatic evolutionary classification of protein folds: Dali Domain Dictionary version 3

    PubMed Central

    Dietmann, Sabine; Park, Jong; Notredame, Cedric; Heger, Andreas; Lappe, Michael; Holm, Liisa

    2001-01-01

    The Dali Domain Dictionary (http://www.ebi.ac.uk/dali/domain) is a numerical taxonomy of all known structures in the Protein Data Bank (PDB). The taxonomy is derived fully automatically from measurements of structural, functional and sequence similarities. Here, we report the extension of the classification to match the traditional four hierarchical levels corresponding to: (i) supersecondary structural motifs (attractors in fold space), (ii) the topology of globular domains (fold types), (iii) remote homologues (functional families) and (iv) homologues with sequence identity above 25% (sequence families). The computational definitions of attractors and functional families are new. In September 2000, the Dali classification contained 10 531 PDB entries comprising 17 101 chains, which were partitioned into five attractor regions, 1375 fold types, 2582 functional families and 3724 domain sequence families. Sequence families were further associated with 99 582 unique homologous sequences in the HSSP database, which increases the number of effectively known structures several-fold. The resulting database contains the description of protein domain architecture, the definition of structural neighbours around each known structure, the definition of structurally conserved cores and a comprehensive library of explicit multiple alignments of distantly related protein families. PMID:11125048

  10. Kinase Associated-1 Domains Drive MARK/PAR1 Kinases to Membrane Targets by Binding Acidic Phospholipids

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moravcevic, Katarina; Mendrola, Jeannine M.; Schmitz, Karl R.

    Phospholipid-binding modules such as PH, C1, and C2 domains play crucial roles in location-dependent regulation of many protein kinases. Here, we identify the KA1 domain (kinase associated-1 domain), found at the C terminus of yeast septin-associated kinases (Kcc4p, Gin4p, and Hsl1p) and human MARK/PAR1 kinases, as a membrane association domain that binds acidic phospholipids. Membrane localization of isolated KA1 domains depends on phosphatidylserine. Using X-ray crystallography, we identified a structurally conserved binding site for anionic phospholipids in KA1 domains from Kcc4p and MARK1. Mutating this site impairs membrane association of both KA1 domains and intact proteins and reveals the importancemore » of phosphatidylserine for bud neck localization of yeast Kcc4p. Our data suggest that KA1 domains contribute to coincidence detection, allowing kinases to bind other regulators (such as septins) only at the membrane surface. These findings have important implications for understanding MARK/PAR1 kinases, which are implicated in Alzheimer's disease, cancer, and autism.« less

  11. The "Globularization Hypothesis" of the Language-ready Brain as a Developmental Frame for Prosodic Bootstrapping Theories of Language Acquisition.

    PubMed

    Irurtzun, Aritz

    2015-01-01

    In recent research (Boeckx and Benítez-Burraco, 2014a,b) have advanced the hypothesis that our species-specific language-ready brain should be understood as the outcome of developmental changes that occurred in our species after the split from Neanderthals-Denisovans, which resulted in a more globular braincase configuration in comparison to our closest relatives, who had elongated endocasts. According to these authors, the development of a globular brain is an essential ingredient for the language faculty and in particular, it is the centrality occupied by the thalamus in a globular brain that allows its modulatory or regulatory role, essential for syntactico-semantic computations. Their hypothesis is that the syntactico-semantic capacities arise in humans as a consequence of a process of globularization, which significantly takes place postnatally (cf. Neubauer et al., 2010). In this paper, I show that Boeckx and Benítez-Burraco's hypothesis makes an interesting developmental prediction regarding the path of language acquisition: it teases apart the onset of phonological acquisition and the onset of syntactic acquisition (the latter starting significantly later, after globularization). I argue that this hypothesis provides a developmental rationale for the prosodic bootstrapping hypothesis of language acquisition (cf. i.a. Gleitman and Wanner, 1982; Mehler et al., 1988, et seq.; Gervain and Werker, 2013), which claim that prosodic cues are employed for syntactic parsing. The literature converges in the observation that a large amount of such prosodic cues (in particular, rhythmic cues) are already acquired before the completion of the globularization phase, which paves the way for the premises of the prosodic bootstrapping hypothesis, allowing babies to have a rich knowledge of the prosody of their target language before they can start parsing the primary linguistic data syntactically.

  12. Use of multiple picosecond high-mass molecular dynamics simulations to predict crystallographic B-factors of folded globular proteins.

    PubMed

    Pang, Yuan-Ping

    2016-09-01

    Predicting crystallographic B-factors of a protein from a conventional molecular dynamics simulation is challenging, in part because the B-factors calculated through sampling the atomic positional fluctuations in a picosecond molecular dynamics simulation are unreliable, and the sampling of a longer simulation yields overly large root mean square deviations between calculated and experimental B-factors. This article reports improved B-factor prediction achieved by sampling the atomic positional fluctuations in multiple picosecond molecular dynamics simulations that use uniformly increased atomic masses by 100-fold to increase time resolution. Using the third immunoglobulin-binding domain of protein G, bovine pancreatic trypsin inhibitor, ubiquitin, and lysozyme as model systems, the B-factor root mean square deviations (mean ± standard error) of these proteins were 3.1 ± 0.2-9 ± 1 Å 2 for Cα and 7.3 ± 0.9-9.6 ± 0.2 Å 2 for Cγ, when the sampling was done for each of these proteins over 20 distinct, independent, and 50-picosecond high-mass molecular dynamics simulations with AMBER forcefield FF12MC or FF14SB. These results suggest that sampling the atomic positional fluctuations in multiple picosecond high-mass molecular dynamics simulations may be conducive to a priori prediction of crystallographic B-factors of a folded globular protein.

  13. Time-Series Photometry of Variable Stars in the Globular Cluster NGC 288

    NASA Astrophysics Data System (ADS)

    Lee, Dong-Joo; Koo, Jae-Rim; Hong, Kyeongsoo; Kim, Seung-Lee; Lee, Jae Woo; Lee, Chung-Uk; Jeon, Young-Beom; Kim, Yun-Hak; Lim, Beomdu; Ryu, Yoon-Hyun; Cha, Sang-Mok; Lee, Yongseok; Kim, Dong-Jin; Park, Byeong-Gon; Kim, Chun-Hwey

    2016-12-01

    We present the results of BV time-series photometry of the globular cluster NGC 288. Observations were carried out to search for variable stars using the Korea Microlensing Telescope Network (KMTNet) 1.6-m telescopes and a 4k pre-science CCD camera during a test observation from August to December, 2014. We found a new SX Phe star and confirmed twelve previously known variable stars in NGC 288. For the semi-regular variable star V1, we newly determined a period of 37.3 days from light curves spanning 137 days. The light-curve solution of the eclipsing binary V10 indicates that the system is probably a detached system. The pulsation properties of nine SX Phe stars were examined by applying multiple frequency analysis to their light curves. We derived a new Period-Luminosity (P-L) relation, < M_{V} rangle = -2.476(±0.300) log P - 0.354(±0.385), from six SX Phe stars showing the fundamental mode. Additionally, the period ratios of three SX Phe stars that probably have a double-radial mode were investigated; P_{FO}/P_{F} = 0.779 for V5, P_{TO}/P_{FO} = 0.685 for V9, P_{SO}/P_{FO} = 0.811 for V11. This paper is the first contribution in a series assessing the detections and properties of variable stars in six southern globular clusters with the KMTNet system.

  14. Fukuyoa paulensis gen. et sp. nov., a New Genus for the Globular Species of the Dinoflagellate Gambierdiscus (Dinophyceae)

    PubMed Central

    Gómez, Fernando; Qiu, Dajun; Lopes, Rubens M.; Lin, Senjie

    2015-01-01

    The marine epiphytic dinoflagellate Gambierdiscus is a toxicologically important genus responsible for ciguatera fish poisoning, the principal cause of non-bacterial illness associated with fish consumption. The genus currently contains species exhibiting either globular or anterior-posteriorly compressed morphologies with marked differences in cell shape and plate arrangement. Here we report a third globular, epiphytic and tychoplanktonic species from the coasts of Ubatuba, Brazil. The new species can be distinguished from G. yasumotoi and G. ruetzleri by its broader first apical plate that occupies a larger portion of the epitheca. Accordingly, phylogenetic trees from small subunit (SSU) and large subunit (LSU) ribosomal DNA sequences also showed strongly supported separation of the new species from the G. yasumotoi / G. ruetzleri group albeit with short distance. The molecular phylogenies, which included new sequences of the planktonic species Goniodoma polyedricum, further indicated that the globular species of Gambierdiscus formed a tight clade, clearly separated (with strong bootstrap support) from the clade of lenticular species including the type for Gambierdiscus. The morphological and molecular data in concert support the split of Gambierdiscus sensu lato into two genera. Gambierdiscus sensu stricto should be reserved for the species with lenticular shapes, highly compressed anterioposteriorly, with short-shank fishhook apical pore plate, large 2' plate, low and ascending cingular displacement, and pouch-like sulcal morphology. The new genus name Fukuyoa gen. nov. should be applied to the globular species, slightly laterally compressed, with long-shank fishhook apical pore plate, large 1' plate, greater and descending cingular displacement, and not pouch-like vertically-oriented sulcal morphology. Fukuyoa contains the new species Fukuyoa paulensis gen. et sp. nov., and F. yasumotoi comb. nov. and F. ruetzleri comb. nov. PMID:25831082

  15. A Spectroscopic Analysis of the Galactic Globular Cluster NGC 6273 (M19)

    NASA Astrophysics Data System (ADS)

    Johnson, Christian I.; Rich, R. Michael; Pilachowski, Catherine A.; Caldwell, Nelson; Mateo, Mario; Bailey, John I., III; Crane, Jeffrey D.

    2015-08-01

    A combined effort utilizing spectroscopy and photometry has revealed the existence of a new globular cluster class. These “anomalous” clusters, which we refer to as “iron-complex” clusters, are differentiated from normal clusters by exhibiting large (≳0.10 dex) intrinsic metallicity dispersions, complex sub-giant branches, and correlated [Fe/H] and s-process enhancements. In order to further investigate this phenomenon, we have measured radial velocities and chemical abundances for red giant branch stars in the massive, but scarcely studied, globular cluster NGC 6273. The velocities and abundances were determined using high resolution (R ˜ 27,000) spectra obtained with the Michigan/Magellan Fiber System (M2FS) and MSpec spectrograph on the Magellan-Clay 6.5 m telescope at Las Campanas Observatory. We find that NGC 6273 has an average heliocentric radial velocity of +144.49 km s-1 (σ = 9.64 km s-1) and an extended metallicity distribution ([Fe/H] = -1.80 to -1.30) composed of at least two distinct stellar populations. Although the two dominant populations have similar [Na/Fe], [Al/Fe], and [α/Fe] abundance patterns, the more metal-rich stars exhibit significant [La/Fe] enhancements. The [La/Eu] data indicate that the increase in [La/Fe] is due to almost pure s-process enrichment. A third more metal-rich population with low [X/Fe] ratios may also be present. Therefore, NGC 6273 joins clusters such as ω Centauri, M2, M22, and NGC 5286 as a new class of iron-complex clusters exhibiting complicated star formation histories. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile.

  16. Antibodies induced by the HA2 glycopolypeptide of influenza virus haemagglutinin improve recovery from influenza A virus infection.

    PubMed

    Gocník, M; Fislová, T; Mucha, V; Sládková, T; Russ, G; Kostolansky, F; Varecková, E

    2008-04-01

    The haemagglutinin (HA) of influenza A virus consists of two glycopolypeptides designated HA1 and HA2. Antibodies recognizing HA1 inhibit virus haemagglutination, neutralize virus infectivity and provide good protection against infection, but do not cross-react with the HA of other subtypes. Little is known regarding the biological activities of antibodies against HA2. To study the role of antibodies directed against HA2 during influenza virus infection, two vaccinia virus recombinants (rVVs) were used expressing chimeric molecules of HA, in which HA1 and HA2 were derived from different HA subtypes. The KG-11 recombinant expressed HA1 from A/PR/8/34 (H1N1) virus and HA2 from A/NT/60 (H3N2) virus, whilst KG-12 recombinant expressed HA1 from A/NT/60 virus and HA2 from A/PR/8/34 virus. Immunization of BALB/c mice with rVV expressing HA2 of the HA subtype homologous to the challenge virus [A/PR/8/34 (H1N1) or A/Mississippi/1/85 (H3N2)] did not prevent virus infection, but nevertheless resulted in an increase in mice survival and faster elimination of virus from the lungs. Passive immunization with antibodies purified from mice immunized with rVVs confirmed that antibodies against HA2 were responsible for the described effect on virus infection. Based on the facts that HA2 is a rather conserved part of the HA and that antibodies against HA2, as shown here, may moderate virus infection, future vaccine design should deal with the problem of how to increase the HA2 antibody response.

  17. Hot Subdwarfs in Globular Clusters

    NASA Astrophysics Data System (ADS)

    Moehler, S.; Heber, U.; Saffer, R.; Thejll, P.

    1995-12-01

    We will present data on sdB stars in the globular clusters M 15, M 22, and NGC 6752. While NGC 6752 has been known to harbour sdBs for quite some time already (Heber et al., 1986), it has also been the only globular cluster known to do so. Only recently, sdB candidates in M 15 (Durrell & Harris, 1993) and in M 22 (Thejll, priv. comm) have been discovered. An analysis of one of the sdBs in M 15 was presented recently (Moehler, in press), while the data on the ones in M 22 will be shown at this meeting for the first time. The physical parameters of these stars (teff and log g ) are derived from optical and IUE spectrophotometric data, intermediate resolution spectroscopy and Stromgren photometry. Knowing the distances of the clusters we can also determine masses. We want to compare the physical parameters of these stars for the different clusters to see what their evolutionary status is and how (or whether at all) it is affected by metallicity. We will also compare our findings to sdB stars found in the field of the Milky Way. In addition we want to see whether the problems encountered with the analyses of blue HB stars (Moehler et al., 1995) apply also to the sdB stars. These analyses showed the BHB stars to have significantly lower surface gravities and masses than predicted by theory. It turned out that this effect did not extend to the sdBs in NGC 6752 studied by Heber et al. (1986) which however constituted a sample too small to draw any meaningful conclusions. Durrell P.R., Harris W.E., 1993, AJ{105}{1420} Heber U., Kudritzki R.P., Caloi V., Castellani V., Danziger J., Gilmozzi R., 1986, \\aua{162}{171--179} Moehler S., Heber U., de Boer K.S., 1995, \\aua{294}{65} Moehler S., 1995, to appear in The Formation of the Galactic Halo - Inside and Out}, Proceedings of the meeting at Tucson, Oct. 9-11, 1995, ASP Conf. Ser.

  18. Optical studies of the X-ray globular cluster NGC 6624

    NASA Technical Reports Server (NTRS)

    Canizares, C. R.; Grindlay, J. E.; Hiltner, W. A.; Liller, W.; Mcclintock, J. E.

    1978-01-01

    Photographic, photometric, and spectroscopic studies of the core of the globular cluster NGC 6624 have been undertaken with the aim of obtaining some evidence regarding the location and nature of the associated X-ray source 3U 1820-30. The studies include an extended simultaneous observation with the SAS 3 satellite, which was carried out to search (unsuccessfully) for optical emission during X-ray bursts. All the results reported are shown to be negative, but serve to set some constraints on the source properties. The photometric results are used to derive a core radius of 5.0 + or - 0.5 arcsec (0.19 + or 0.02 pc at 8 kpc) and a central density of 110,000 solar masses per cu pc for the cluster. It is found that NGC 6624 is one of the most centrally dense globular clusters but otherwise normal and that the colors and spectrum of the nucleus are the same as those of the cluster as a whole. An X-ray source similar to HZ Her at maximum light is ruled out.

  19. Activity-guided separation and characterization of new halocin HA3 from fermented broth of Haloferax larsenii HA3.

    PubMed

    Kumar, Vijay; Tiwari, Santosh Kumar

    2017-05-01

    Haloferax larsenii HA3 was able to grow optimally in HS medium containing 15% NaCl, at pH 7.2 and 42 °C in aerobic conditions. Strain HA3 was found to be round shape, Gram-negative, catalase-positive, sensitive to bile acid, and resistant to chloramphenicol, and could not utilize arginine. The lipid profile revealed the presence of glycerol diether moiety (GDEM) suggesting Haloarchaea characteristics. Phylogenetic analysis based on 16S rRNA gene sequence similarities showed that it was closely related to H. larsenii ZJ206. Interestingly, strain HA3 was found to produce halocin HA3 which was purified using ultrafiltration and chromatography. It was found to be stable up to 80 °C, pH 2.0-10.0, organic solvents, surfactants, and detergents tested. However, the activity of halocin HA3 was completely reduced in the presence of proteinase K and trypsin. It was found to be halocidal against H. larsenii HA10, rupturing cell boundary and leading to cell death. The molecular weight of halocin HA3 was found to be ~13 kDa and MALDI-TOF MS/MS analysis suggested no homology with known halocins. The N-terminal ten amino-acid residues, NH 2 MNLGIILETN-COOH, suggested a new/novel halocin. These properties of halocin HA3 may be applicable for control of Haloarchaea in environments and salted foods.

  20. Small-Angle X-Ray Scattering of the Cholesterol Incorporation into Human ApoA1-POPC Discoidal Particles

    PubMed Central

    Midtgaard, Søren Roi; Pedersen, Martin Cramer; Arleth, Lise

    2015-01-01

    Structural and functional aspects of high-density lipoproteins have been studied for over half a century. Due to the plasticity of this highly complex system, new aspects continue to be discovered. Here, we present a structural study of the human Apolipoprotein A1 (ApoA1) and investigate the role of its N-terminal domain, the so-called globular domain of ApoA1, in discoidal complexes with phospholipids and increasing amounts of cholesterol. Using a combination of solution-based small-angle x-ray scattering (SAXS) and molecular constrained data modeling, we show that the ApoA1-1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)-based particles are disk shaped with an elliptical cross section and composed by a central lipid bilayer surrounded by two stabilizing ApoA1 proteins. This structure is very similar to the particles formed in the so-called nanodisc system, which is based on N-terminal truncated ApoA1 protein. Although it is commonly agreed that the nanodisc is plain disk shaped, several more advanced structures have been proposed for the full-length ApoA1 in combination with POPC and cholesterol. This prompted us to make a detailed comparative study of the ApoA1 and nanodisc systems upon cholesterol uptake. Based on the presented SAXS analysis it is found that the N-terminal domains of ApoA1-POPC-cholesterol particles are not globular but instead an integrated part of the protein belt stabilizing the particles. Upon incorporation of increasing amounts of cholesterol, the presence of the N-terminal domain allows the bilayer thickness to increase while maintaining an overall flat bilayer structure. This is contrasted by the energetically more strained and less favorable lens shape required to fit the SAXS data from the N-terminal truncated nanodisc system upon cholesterol incorporation. This suggests that the N-terminal domain of ApoA1 actively participates in the stabilization of the ApoA1-POPC-cholesterol discoidal particle and allows for a more optimal

  1. ABCA1, ABCG1, and ABCG4 are distributed to distinct membrane meso-domains and disturb detergent-resistant domains on the plasma membrane.

    PubMed

    Sano, Osamu; Ito, Shiho; Kato, Reiko; Shimizu, Yuji; Kobayashi, Aya; Kimura, Yasuhisa; Kioka, Noriyuki; Hanada, Kentaro; Ueda, Kazumitsu; Matsuo, Michinori

    2014-01-01

    ATP-binding cassette A1 (ABCA1), ABCG1, and ABCG4 are lipid transporters that mediate the efflux of cholesterol from cells. To analyze the characteristics of these lipid transporters, we examined and compared their distributions and lipid efflux activity on the plasma membrane. The efflux of cholesterol mediated by ABCA1 and ABCG1, but not ABCG4, was affected by a reduction of cellular sphingomyelin levels. Detergent solubility and gradient density ultracentrifugation assays indicated that ABCA1, ABCG1, and ABCG4 were distributed to domains that were solubilized by Triton X-100 and Brij 96, resistant to Triton X-100 and Brij 96, and solubilized by Triton X-100 but resistant to Brij 96, respectively. Furthermore, ABCG1, but not ABCG4, was colocalized with flotillin-1 on the plasma membrane. The amounts of cholesterol extracted by methyl-β-cyclodextrin were increased by ABCA1, ABCG1, or ABCG4, suggesting that cholesterol in non-raft domains was increased. Furthermore, ABCG1 and ABCG4 disturbed the localization of caveolin-1 to the detergent-resistant domains and the binding of cholera toxin subunit B to the plasma membrane. These results suggest that ABCA1, ABCG1, and ABCG4 are localized to distinct membrane meso-domains and disturb the meso-domain structures by reorganizing lipids on the plasma membrane; collectively, these observations may explain the different substrate profiles and lipid efflux roles of these transporters.

  2. ABCA1, ABCG1, and ABCG4 Are Distributed to Distinct Membrane Meso-Domains and Disturb Detergent-Resistant Domains on the Plasma Membrane

    PubMed Central

    Sano, Osamu; Ito, Shiho; Kato, Reiko; Shimizu, Yuji; Kobayashi, Aya; Kimura, Yasuhisa; Kioka, Noriyuki; Hanada, Kentaro; Ueda, Kazumitsu; Matsuo, Michinori

    2014-01-01

    ATP-binding cassette A1 (ABCA1), ABCG1, and ABCG4 are lipid transporters that mediate the efflux of cholesterol from cells. To analyze the characteristics of these lipid transporters, we examined and compared their distributions and lipid efflux activity on the plasma membrane. The efflux of cholesterol mediated by ABCA1 and ABCG1, but not ABCG4, was affected by a reduction of cellular sphingomyelin levels. Detergent solubility and gradient density ultracentrifugation assays indicated that ABCA1, ABCG1, and ABCG4 were distributed to domains that were solubilized by Triton X-100 and Brij 96, resistant to Triton X-100 and Brij 96, and solubilized by Triton X-100 but resistant to Brij 96, respectively. Furthermore, ABCG1, but not ABCG4, was colocalized with flotillin-1 on the plasma membrane. The amounts of cholesterol extracted by methyl-β-cyclodextrin were increased by ABCA1, ABCG1, or ABCG4, suggesting that cholesterol in non-raft domains was increased. Furthermore, ABCG1 and ABCG4 disturbed the localization of caveolin-1 to the detergent-resistant domains and the binding of cholera toxin subunit B to the plasma membrane. These results suggest that ABCA1, ABCG1, and ABCG4 are localized to distinct membrane meso-domains and disturb the meso-domain structures by reorganizing lipids on the plasma membrane; collectively, these observations may explain the different substrate profiles and lipid efflux roles of these transporters. PMID:25302608

  3. Structural Basis for Endosomal Targeting by the Bro1 Domain

    PubMed Central

    Kim, Jaewon; Sitaraman, Sujatha; Hierro, Aitor; Beach, Bridgette M.; Odorizzi, Greg; Hurley, James H.

    2010-01-01

    Summary Proteins delivered to the lysosome or the yeast vacuole via late endosomes are sorted by the ESCRT complexes and by associated proteins, including Alix and its yeast homolog Bro1. Alix, Bro1, and several other late endosomal proteins share a conserved 160 residue Bro1 domain whose boundaries, structure, and function have not been characterized. The crystal structure of the Bro1 domain of Bro1 reveals a folded core of 367 residues. The extended Bro1 domain is necessary and sufficient for binding to the ESCRT-III subunit Snf7 and for the recruitment of Bro1 to late endosomes. The structure resembles a boomerang with its concave face filled in and contains a triple tetratricopeptide repeat domain as a substructure. Snf7 binds to a conserved hydrophobic patch on Bro1 that is required for protein complex formation and for the protein-sorting function of Bro1. These results define a conserved mechanism whereby Bro1 domain-containing proteins are targeted to endosomes by Snf7 and its orthologs. PMID:15935782

  4. Kinematic fingerprint of core-collapsed globular clusters

    NASA Astrophysics Data System (ADS)

    Bianchini, P.; Webb, J. J.; Sills, A.; Vesperini, E.

    2018-03-01

    Dynamical evolution drives globular clusters towards core collapse, which strongly shapes their internal properties. Diagnostics of core collapse have so far been based on photometry only, namely on the study of the concentration of the density profiles. Here, we present a new method to robustly identify core-collapsed clusters based on the study of their stellar kinematics. We introduce the kinematic concentration parameter, ck, the ratio between the global and local degree of energy equipartition reached by a cluster, and show through extensive direct N-body simulations that clusters approaching core collapse and in the post-core collapse phase are strictly characterized by ck > 1. The kinematic concentration provides a suitable diagnostic to identify core-collapsed clusters, independent from any other previous methods based on photometry. We also explore the effects of incomplete radial and stellar mass coverage on the calculation of ck and find that our method can be applied to state-of-art kinematic data sets.

  5. High-Resolution CCD Spectra of Stars in Globular Clusters. IX. The "Young" Clusters Ruprecht 106 and PAL 12

    NASA Astrophysics Data System (ADS)

    Brown, Jeffrey A.; Wallerstein, George; Zucker, Daniel

    1997-07-01

    We have performed a spectroscopic abundance analysis of two stars each in the anomalously young globular clusters Rup 106 and Pal 12. We find [Fe/H] =~ -1.45 for Rup 106 and -1.0 for Pal 12. The abundance ratios in both clusters are peculiar in comparison to other globulars: the alpha -elements are not enhanced over the solar ratio. We find that oxygen in Rup 106 is also relatively low, with [O/Fe] =~ 0.0 - +0.1. The similarity of the ratio of the alpha-elements to iron to the solar ratio shows that species contributed by supernovae of type Ia have ``caught up" with species produced by SN II's. The similar contributions of the alpha - and Fe-peak species to disk stars shows that age, not metallicity, is the determining factor in the ratio of SN II/SN Ia nucleosynthesis. Galactic enrichment models show that these abundance ratios can be understood as being the result of these two clusters coming from an environment with multiple discontinuous star formation events.

  6. The STREGA survey - II. Globular cluster Palomar 12

    NASA Astrophysics Data System (ADS)

    Musella, I.; Di Criscienzo, M.; Marconi, M.; Raimondo, G.; Ripepi, V.; Cignoni, M.; Bono, G.; Brocato, E.; Dall'Ora, M.; Ferraro, I.; Grado, A.; Iannicola, G.; Limatola, L.; Molinaro, R.; Moretti, M. I.; Stetson, P. B.; Capaccioli, M.; Cioni, M.-R. L.; Getman, F.; Schipani, P.

    2018-01-01

    In the framework of the STREGA (STRucture and Evolution of the GAlaxy) survey, two fields around the globular cluster Pal 12 were observed with the aim of detecting the possible presence of streams and/or an extended halo. The adopted stellar tracers are the main sequence, turn-off and red giant branch stars. We discuss the luminosity function and the star counts in the observed region covering about 2 tidal radii, confirming that Pal 12 appears to be embedded in the Sagittarius Stream. Adopting an original approach to separate cluster and field stars, we do not find any evidence of significant extra-tidal Pal 12 stellar populations. The presence of the Sagittarius stream seems to have mimicked a larger tidal radius in previous studies. Indeed, adopting a King model, a redetermination of this value gives rT = 0.22 ± 0.1 deg.

  7. The Globular Cluster NGC 5286. I. A New CCD BV Color-Magnitude Diagram

    NASA Astrophysics Data System (ADS)

    Zorotovic, M.; Catelan, M.; Zoccali, M.; Pritzl, B. J.; Smith, H. A.; Stephens, A. W.; Contreras, R.; Escobar, M. E.

    2009-01-01

    We present BV photometry of the Galactic globular cluster NGC 5286, based on 128 V frames and 133 B frames, and covering the entire face of the cluster. Our photometry reaches almost two magnitudes below the turn-off level, and is accordingly suitable for age analysis. Field stars were removed statistically from the cluster's color-magnitude diagram (CMD), and a differential reddening correction applied, thus allowing a precise ridgeline to be calculated. Using the latter, a metallicity of [Fe/H] = -1.70 ± 0.05 in the Zinn & West scale, and [Fe/H] = -1.47 ± 0.02 in the Carretta & Gratton scale, was derived on the basis of several parameters measured from the red giant branch, in good agreement with the value provided in the Harris catalog. Comparing the NGC 5286 CMD with the latest photometry for M3 by P. B. Stetson, and using VandenBerg isochrones for a suitable chemical composition, we find evidence that NGC 5286 is around 1.7 ± 0.9 Gyr older than M3. This goes in the right sense to help account for the blue horizontal branch of NGC 5286, for which we provide a measurement of several morphological indicators. If NGC 5286 is a bona fide member of the Canis Major dwarf spheroidal galaxy, as previously suggested, our results imply that the latter's oldest components may be at least as old as the oldest Milky Way globular clusters. Based on observations obtained with the 1.3 m Warsaw telescope at the Las Campanas Observatory, Chile.

  8. The Evolutionary Pattern of Glycosylation Sites in Influenza Virus (H5N1) Hemagglutinin and Neuraminidase

    PubMed Central

    Chen, Wentian; Zhong, Yaogang; Qin, Yannan; Sun, Shisheng; Li, Zheng

    2012-01-01

    Two glycoproteins, hemagglutinin (HA) and neuraminidase (NA), on the surface of influenza viruses play crucial roles in transfaunation, membrane fusion and the release of progeny virions. To explore the distribution of N-glycosylation sites (glycosites) in these two glycoproteins, we collected and aligned the amino acid sequences of all the HA and NA subtypes. Two glycosites were located at HA0 cleavage sites and fusion peptides and were strikingly conserved in all HA subtypes, while the remaining glycosites were unique to their subtypes. Two to four conserved glycosites were found in the stalk domain of NA, but these are affected by the deletion of specific stalk domain sequences. Another highly conserved glycosite appeared at the top center of tetrameric global domain, while the others glycosites were distributed around the global domain. Here we present a detailed investigation of the distribution and the evolutionary pattern of the glycosites in the envelope glycoproteins of IVs, and further focus on the H5N1 virus and conclude that the glycosites in H5N1 have become more complicated in HA and less influential in NA in the last five years. PMID:23133677

  9. Blue Stragglers and Other Stars of Mass Consumption in Globular Clusters

    NASA Astrophysics Data System (ADS)

    Panurach, Teresa; Leigh, Nathan

    2018-01-01

    Simulations of globular clusters suggest that collisions between main-sequence (MS) stars happen frequently. Stellar evolution models show that these collision products can be photometrically identified, appearing off the MS locus. These collision products can appear brighter and bluer than the MS turnoff, called “blue stragglers,” or even less massive and redder than the MS. We use proper motion-cleaned photometry from the Hubble Space Telescope of 38 globular clusters to identify candidate collision products. We compare the spectral energy distributions of our candidates to theoretical templates for single and multiple star systems, to constrain the possible presence of a binary companion and test consistency with theoretical stellar evolution models for collision products. For the BSs, we also compare the observed velocities from the proper motion catalog along with mass estimates derived from isochrone-fitting to theoretical predictions for both the collision and binary mass transfer models and find better agreement with the former.

  10. THE BLUE HOOK POPULATIONS OF MASSIVE GLOBULAR CLUSTERS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brown, Thomas M.; Smith, Ed; Sweigart, Allen V.

    2010-08-01

    We present new Hubble Space Telescope ultraviolet color-magnitude diagrams of five massive Galactic globular clusters: NGC 2419, NGC 6273, NGC 6715, NGC 6388, and NGC 6441. These observations were obtained to investigate the 'blue hook' (BH) phenomenon previously observed in UV images of the globular clusters {omega} Cen and NGC 2808. Blue hook stars are a class of hot (approximately 35,000 K) subluminous horizontal branch stars that occupy a region of the HR diagram that is unexplained by canonical stellar evolution theory. By coupling new stellar evolution models to appropriate non-LTE synthetic spectra, we investigate various theoretical explanations for thesemore » stars. Specifically, we compare our photometry to canonical models at standard cluster abundances, canonical models with enhanced helium (consistent with cluster self-enrichment at early times), and flash-mixed models formed via a late helium-core flash on the white dwarf cooling curve. We find that flash-mixed models are required to explain the faint luminosity of the BH stars, although neither the canonical models nor the flash-mixed models can explain the range of color observed in such stars, especially those in the most metal-rich clusters. Aside from the variation in the color range, no clear trends emerge in the morphology of the BH population with respect to metallicity.« less

  11. Neutrino and axion bounds from the globular cluster M5 (NGC 5904).

    PubMed

    Viaux, N; Catelan, M; Stetson, P B; Raffelt, G G; Redondo, J; Valcarce, A A R; Weiss, A

    2013-12-06

    The red-giant branch (RGB) in globular clusters is extended to larger brightness if the degenerate helium core loses too much energy in "dark channels." Based on a large set of archival observations, we provide high-precision photometry for the Galactic globular cluster M5 (NGC 5904), allowing for a detailed comparison between the observed tip of the RGB with predictions based on contemporary stellar evolution theory. In particular, we derive 95% confidence limits of g(ae)<4.3×10(-13) on the axion-electron coupling and μ(ν)<4.5×10(-12)μ(B) (Bohr magneton μ(B)=e/2m(e)) on a neutrino dipole moment, based on a detailed analysis of statistical and systematic uncertainties. The cluster distance is the single largest source of uncertainty and can be improved in the future.

  12. p-capture reaction cycles in rotating massive stars and their impact on elemental abundances in globular cluster stars: A case study of O, Na and Al

    NASA Astrophysics Data System (ADS)

    Mahanta, Upakul; Goswami, Aruna; Duorah, Hiralal; Duorah, Kalpana

    2017-08-01

    Elemental abundance patterns of globular cluster stars can provide important clues for understanding cluster formation and early chemical evolution. The origin of the abundance patterns, however, still remains poorly understood. We have studied the impact of p-capture reaction cycles on the abundances of oxygen, sodium and aluminium considering nuclear reaction cycles of carbon-nitrogen-oxygen-fluorine, neon-sodium and magnesium-aluminium in massive stars in stellar conditions of temperature range 2×107 to 10×107 K and typical density of 102 gm cc-1. We have estimated abundances of oxygen, sodium and aluminium with respect to Fe, which are then assumed to be ejected from those stars because of rotation reaching a critical limit. These ejected abundances of elements are then compared with their counterparts that have been observed in some metal-poor evolved stars, mainly giants and red giants, of globular clusters M3, M4, M13 and NGC 6752. We observe an excellent agreement with [O/Fe] between the estimated and observed abundance values for globular clusters M3 and M4 with a correlation coefficient above 0.9 and a strong linear correlation for the remaining two clusters with a correlation coefficient above 0.7. The estimated [Na/Fe] is found to have a correlation coefficient above 0.7, thus implying a strong correlation for all four globular clusters. As far as [Al/Fe] is concerned, it also shows a strong correlation between the estimated abundance and the observed abundance for globular clusters M13 and NGC 6752, since here also the correlation coefficient is above 0.7 whereas for globular cluster M4 there is a moderate correlation found with a correlation coefficient above 0.6. Possible sources of these discrepancies are discussed.

  13. Abundance differences among globular-cluster giants: Primordial versus evolutionary scenarios

    NASA Astrophysics Data System (ADS)

    Kraft, Robert P.

    1994-06-01

    primordial scenario. Among mildly metal-poor giants, i.e., those in the range from solar metallicity to (Fe/H) approximately -1, recent observational evidence suggesting the existence of a substructure in the (el/Fe) ratios of the heavier alpha elements, e.g., Si, Mg, Ca, and Ti, is discussed. The possible influence of this effect on the interpretation of the integrated spectra of extragalactic globular clusters and E galaxies is noted.

  14. Construction and heterologous expression of a truncated Haemagglutinin (HA) protein from the avian influenza virus H5N1 in Escherichia coli.

    PubMed

    Chee Wei, T; Nurul Wahida, A G; Shaharum, S

    2014-12-01

    Malaysia first reported H5N1 poultry case in 2004 and subsequently outbreak in poultry population in 2007. Here, a recombinant gene encoding of peptide epitopes, consisting fragments of HA1, HA2 and a polybasic cleavage site of H5N1 strain Malaysia, was amplified and cloned into pET-47b(+) bacterial expression vector. DNA sequencing and alignment analysis confirmed that the gene had no alteration and in-frame to the vector. Then, His-tagged truncated HA protein was expressed in Escherichia coli BL21 (DE3) under 1 mM IPTG induction. The protein expression was optimized under a time-course induction study and further purified using Ni-NTA agarose under reducing condition. Migration size of protein was detected at 15 kDa by Western blot using anti-His tag monoclonal antibody and demonstrated no discrepancy compared to its calculated molecular weight.

  15. Characterization of New PEEK/HA Composites with 3D HA Network Fabricated by Extrusion Freeforming.

    PubMed

    Vaezi, Mohammad; Black, Cameron; Gibbs, David M R; Oreffo, Richard O C; Brady, Mark; Moshrefi-Torbati, Mohamed; Yang, Shoufeng

    2016-05-26

    Addition of bioactive materials such as calcium phosphates or Bioglass, and incorporation of porosity into polyetheretherketone (PEEK) has been identified as an effective approach to improve bone-implant interfaces and osseointegration of PEEK-based devices. In this paper, a novel production technique based on the extrusion freeforming method is proposed that yields a bioactive PEEK/hydroxyapatite (PEEK/HA) composite with a unique configuration in which the bioactive phase (i.e., HA) distribution is computer-controlled within a PEEK matrix. The 100% interconnectivity of the HA network in the biocomposite confers an advantage over alternative forms of other microstructural configurations. Moreover, the technique can be employed to produce porous PEEK structures with controlled pore size and distribution, facilitating greater cellular infiltration and biological integration of PEEK composites within patient tissue. The results of unconfined, uniaxial compressive tests on these new PEEK/HA biocomposites with 40% HA under both static and cyclic mode were promising, showing the composites possess yield and compressive strength within the range of human cortical bone suitable for load bearing applications. In addition, preliminary evidence supporting initial biological safety of the new technique developed is demonstrated in this paper. Sufficient cell attachment, sustained viability in contact with the sample over a seven-day period, evidence of cell bridging and matrix deposition all confirmed excellent biocompatibility.

  16. Chemical composition of stars in globular clusters: M5, M13, and M3

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pilachowski, C.A.; Wallerstein, G.; Myckky Leep, E.

    The composition of giant stars in the globular clusters M3, M5, and M13 have been determined by detailed model atmosphere analysis; the average iron deficiencies relative to the Sun are -1.55, -1.33, and -1.42, respectively. Oxygen is overabundant relative to iron in M3 and M5 but not in M13. Differences in the oxygen abundance can account for variation in horizontal-branch morphology; clusters of intermediate metallicity with high oxygen have red horizontal-branch stars, and those with low oxygen have only blue horizontal-branch stars Z/sub cno/ is the second abundance parameter.

  17. Role of the HaHOG1 MAP Kinase in Response of the Conifer Root and But Rot Pathogen (Heterobasidion annosum) to Osmotic and Oxidative Stress

    PubMed Central

    Raffaello, Tommaso; Keriö, Susanna; Asiegbu, Fred O.

    2012-01-01

    The basidiomycete Heterobasidion annosum (Fr.) Bref. s.l. is a filamentous white rot fungus, considered to be the most economically important pathogen of conifer trees. Despite the severity of the tree infection, very little is known about the molecular and biochemical aspects related to adaptation to abiotic stresses. In this study, the osmotic and oxidative tolerance as well as the role of the HaHOG1 Mitogen Activated Protein Kinase (MAPK) gene were investigated. The transcript levels of the yeast orthologues GPD1, HSP78, STL1, GRE2 and the ATPase pumps ENA1, PMR1, PMC1 known to have an important role in osmotolerance were also quantified under salt osmotic conditions. The HaHOG1 gene was used for a heterologous expression and functional study in the Saccharomyces cerevisiae Δhog1 strain. Moreover, the phosphorylation level of HaHog1p was studied under salt osmotic and oxidative stress. The result showed that H. annosum displayed a decreased growth when exposed to an increased concentration of osmotic and oxidative stressors. GPD1, HSP78, STL1 and GRE2 showed an induction already at 10 min after exposure to salt stress. Among the ATPase pumps studied, PMC1 was highly induced when the fungus was exposed to 0.2 M CaCl2 for 60 min. The heterologous expression of the HaHOG1 sequence in yeast confirmed that the gene is able to restore the osmotolerance and oxidative tolerance in the S. cerevisiae hog1Δ mutant strain. The HaHog1p was strongly phosphorylated in the presence of NaCl, KCl, H2O2 but not in the presence of CaCl2 and MgCl2. The GFP-HaHog1p fusion protein accumulated in the nuclei of the S. cerevisiae hog1Δ cells when exposed to high osmotic conditions but not under oxidative stress. These results provide the first insights about the response of H. annosum to osmotic and oxidative stress and elucidate the role of the HaHOG1 gene in such conditions. PMID:22319614

  18. New Halo Stars of the Galactic Globular Clusters M3 and M13 in the LAMOST DR1 Catalog

    NASA Astrophysics Data System (ADS)

    Navin, Colin A.; Martell, Sarah L.; Zucker, Daniel B.

    2016-10-01

    M3 and M13 are Galactic globular clusters with previous reports of surrounding stellar halos. We present the results of a search for members and extratidal cluster halo stars within and outside of the tidal radius of these clusters in the LAMOST Data Release 1. We find seven candidate cluster members (inside the tidal radius) of both M3 and M13, respectively. In M3 we also identify eight candidate extratidal cluster halo stars at distances up to ˜9.8 times the tidal radius, and in M13 we identify 12 candidate extratidal cluster halo stars at distances up to ˜13.8 times the tidal radius. These results support previous indications that both M3 and M13 are surrounded by extended stellar halos, and we find that the GC destruction rates corresponding to the observed mass loss are generally significantly higher than theoretical studies predict.

  19. On the cold denaturation of globular proteins

    NASA Astrophysics Data System (ADS)

    Ascolese, Eduardo; Graziano, Giuseppe

    2008-12-01

    The recent finding that yeast frataxin shows, at pH 7.0, cold denaturation at 274 K and hot denaturation at 303 K [A. Pastore, S.R. Martin, A. Politou, K.C. Kondapalli, T. Stemmler, P.A. Temussi, J. Am. Chem. Soc. 129 (2007) 5374] calls for a deeper rationalization of the molecular mechanisms stabilizing-destabilizing the native state of globular proteins. It is shown that the statistical thermodynamic model originally developed by Ikegami can reproduce in a more-than-qualitative manner the two conformational transitions of yeast frataxin, providing important clues on their molecular origin.

  20. The structure of the bacteriophage PRD1 spike sheds light on the evolution of viral capsid architecture.

    PubMed

    Merckel, Michael C; Huiskonen, Juha T; Bamford, Dennis H; Goldman, Adrian; Tuma, Roman

    2005-04-15

    Comparisons of bacteriophage PRD1 and adenovirus protein structures and virion architectures have been instrumental in unraveling an evolutionary relationship and have led to a proposal of a phylogeny-based virus classification. The structure of the PRD1 spike protein P5 provides further insight into the evolution of viral proteins. The crystallized P5 fragment comprises two structural domains: a globular knob and a fibrous shaft. The head folds into a ten-stranded jelly roll beta barrel, which is structurally related to the tumor necrosis factor (TNF) and the PRD1 coat protein domains. The shaft domain is a structural counterpart to the adenovirus spike shaft. The structural relationships between PRD1, TNF, and adenovirus proteins suggest that the vertex proteins may have originated from an ancestral TNF-like jelly roll coat protein via a combination of gene duplication and deletion.

  1. Protection of guinea pigs by vaccination with a recombinant swinepox virus co-expressing HA1 genes of swine H1N1 and H3N2 influenza viruses.

    PubMed

    Xu, Jiarong; Yang, Deji; Huang, Dongyan; Xu, Jiaping; Liu, Shichao; Lin, Huixing; Zhu, Haodan; Liu, Bao; Lu, Chengping

    2013-03-01

    Swine influenza (SI) is an acute respiratory infectious disease of swine caused by swine influenza virus (SIV). SIV is not only an important respiratory pathogen in pigs but also a potent threat to human health. Here, we report the construction of a recombinant swinepox virus (rSPV/H3-2A-H1) co-expressing hemagglutinin (HA1) of SIV subtypes H1N1 and H3N2. Immune responses and protection efficacy of the rSPV/H3-2A-H1 were evaluated in guinea pigs. Inoculation of rSPV/H3-2A-H1 yielded neutralizing antibodies against SIV H1N1 and H3N2. The IFN-γ and IL-4 concentrations in the supernatant of lymphocytes stimulated with purified SIV HA1 antigen were significantly higher (P < 0.01) than those of the control groups. Complete protection of guinea pigs against SIV H1N1 or H3N2 challenge was observed. No SIV shedding was detected from guinea pigs vaccinated with rSPV/H3-2A-H1 after challenge. Most importantly, the guinea pigs immunized with rSPV/H3-2A-H1 did not show gross and micrographic lung lesions. However, the control guinea pigs experienced distinct gross and micrographic lung lesions at 7 days post-challenge. Our data suggest that the recombinant swinepox virus encoding HA1 of SIV H1N1 and H3N2 might serve as a promising candidate vaccine for protection against SIV H1N1 and H3N2 infections.

  2. Membrane Localization is Critical for Activation of the PICK1 BAR Domain

    PubMed Central

    Madsen, Kenneth L.; Eriksen, Jacob; Milan-Lobo, Laura; Han, Daniel S.; Niv, Masha Y.; Ammendrup-Johnsen, Ina; Henriksen, Ulla; Bhatia, Vikram K.; Stamou, Dimitrios; Sitte, Harald H.; McMahon, Harvey T.; Weinstein, Harel; Gether, Ulrik

    2013-01-01

    The PSD-95/Discs-large/ZO-1 homology (PDZ) domain protein, protein interacting with C kinase 1 (PICK1) contains a C-terminal Bin/amphiphysin/Rvs (BAR) domain mediating recognition of curved membranes; however, the molecular mechanisms controlling the activity of this domain are poorly understood. In agreement with negative regulation of the BAR domain by the N-terminal PDZ domain, PICK1 distributed evenly in the cytoplasm, whereas truncation of the PDZ domain caused BAR domain-dependent redistribution to clusters colocalizing with markers of recycling endosomal compartments. A similar clustering was observed both upon truncation of a short putative α-helical segment in the linker between the PDZ and the BAR domains and upon coexpression of PICK1 with a transmembrane PDZ ligand, including the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR2 subunit, the GluR2 C-terminus transferred to the single transmembrane protein Tac or the dopamine transporter C-terminus transferred to Tac. In contrast, transfer of the GluR2 C-terminus to cyan fluorescent protein, a cytosolic protein, did not elicit BAR domain-dependent clustering. Instead, localizing PICK1 to the membrane by introducing an N-terminal myristoylation site produced BAR domain-dependent, but ligand-independent, PICK1 clustering. The data support that in the absence of PDZ ligand, the PICK1 BAR domain is inhibited through a PDZ domain-dependent and linker-dependent mechanism. Moreover, they suggest that unmasking of the BAR domain’s membrane-binding capacity is not a consequence of ligand binding to the PDZ domain per se but results from, and coincides with, recruitment of PICK1 to a membrane compartment. PMID:18466293

  3. Statistical Mechanical Foundation for the Two-State Transition in Protein Folding of Small Globular Proteins

    NASA Astrophysics Data System (ADS)

    Iguchi, Kazumoto

    We discuss the statistical mechanical foundation for the two-state transition in the protein folding of small globular proteins. In the standard arguments of protein folding, the statistical search for the ground state is carried out from astronomically many conformations in the configuration space. This leads us to the famous Levinthal's paradox. To resolve the paradox, Gō first postulated that the two-state transition - all-or-none type transition - is very crucial for the protein folding of small globular proteins and used the Gō's lattice model to show the two-state transition nature. Recently, there have been accumulated many experimental results that support the two-state transition for small globular proteins. Stimulated by such recent experiments, Zwanzig has introduced a minimal statistical mechanical model that exhibits the two-state transition. Also, Finkelstein and coworkers have discussed the solution of the paradox by considering the sequential folding of a small globular protein. On the other hand, recently Iguchi have introduced a toy model of protein folding using the Rubik's magic snake model, in which all folded structures are exactly known and mathematically represented in terms of the four types of conformations: cis-, trans-, left and right gauche-configurations between the unit polyhedrons. In this paper, we study the relationship between the Gō's two-state transition, the Zwanzig's statistical mechanics model and the Finkelsteinapos;s sequential folding model by applying them to the Rubik's magic snake models. We show that the foundation of the Gō's two-state transition model relies on the search within the equienergy surface that is labeled by the contact order of the hydrophobic condensation. This idea reproduces the Zwanzig's statistical model as a special case, realizes the Finkelstein's sequential folding model and fits together to understand the nature of the two-state transition of a small globular protein by calculating the

  4. Starch Binding Domain-containing Protein 1 Plays a Dominant Role in Glycogen Transport to Lysosomes in Liver*

    PubMed Central

    Sun, Tao; Yi, Haiqing; Yang, Chunyu; Kishnani, Priya S.; Sun, Baodong

    2016-01-01

    A small portion of cellular glycogen is transported to and degraded in lysosomes by acid α-glucosidase (GAA) in mammals, but it is unclear why and how glycogen is transported to the lysosomes. Stbd1 has recently been proposed to participate in glycogen trafficking to lysosomes. However, our previous study demonstrated that knockdown of Stbd1 in GAA knock-out mice did not alter lysosomal glycogen storage in skeletal muscles. To further determine whether Stbd1 participates in glycogen transport to lysosomes, we generated GAA/Stbd1 double knock-out mice. In fasted double knock-out mice, glycogen accumulation in skeletal and cardiac muscles was not affected, but glycogen content in liver was reduced by nearly 73% at 3 months of age and by 60% at 13 months as compared with GAA knock-out mice, indicating that the transport of glycogen to lysosomes was suppressed in liver by the loss of Stbd1. Exogenous expression of human Stbd1 in double knock-out mice restored the liver lysosomal glycogen content to the level of GAA knock-out mice, as did a mutant lacking the Atg8 family interacting motif (AIM) and another mutant that contains only the N-terminal 24 hydrophobic segment and the C-terminal starch binding domain (CBM20) interlinked by an HA tag. Our results demonstrate that Stbd1 plays a dominant role in glycogen transport to lysosomes in liver and that the N-terminal transmembrane region and the C-terminal CBM20 domain are critical for this function. PMID:27358407

  5. Follow up of stellar migrants from globular clusters using the Hobby-Eberly Telescope

    NASA Astrophysics Data System (ADS)

    Shetrone, Matthew D.; Martell, Sarah L.

    2017-01-01

    Nearly all globular clusters contain at least two populations of stars. The first generation has abundances very similar to that of the average Milky Way halo stars at that metallicity. The second generation, presumably polluted by the massive stars of the first generation, have abundance patterns which include lower abundances of C, O, and Mg and higher abundances of N, Al and Na compared to first generation. Martell & Grebel (2010) identified a number of potential second generation stars using the CH and CN bandstrengths from SDSS-II/SEGUE spectra. We have followed up these candidates with moderate resolution spectra using HRS on the Hobby-Eberly Telescope. We present the success rate of finding globular cluster migrants and discuss the reasons why some stars exhibit a CN false positive signal in CN and CH.

  6. Long single [alpha]-helical tail domains bridge the gap between structure and function of myosin VI

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Spink, Benjamin J.; Sivaramakrishnan, Sivaraj; Lipfert, Jan

    2008-09-29

    Myosin VI has challenged the lever arm hypothesis of myosin movement because of its ability to take {approx}36-nm steps along actin with a canonical lever arm that seems to be too short to allow such large steps. Here we demonstrate that the large step of dimeric myosin VI is primarily made possible by a medial tail in each monomer that forms a rare single {alpha}-helix of {approx}10 nm, which is anchored to the calmodulin-bound IQ domain by a globular proximal tail. With the medial tail contributing to the {approx}36-nm step, rather than dimerizing as previously proposed, we show that themore » cargo binding domain is the dimerization interface. Furthermore, the cargo binding domain seems to be folded back in the presence of the catalytic head, constituting a potential regulatory mechanism that inhibits dimerization.« less

  7. HST Snapshot Study of Variable Stars in Globular Clusters: Inner Region of NGC 6441

    NASA Technical Reports Server (NTRS)

    Pritzl, Barton J.; Smith, Horace A.; Stetson, Peter B.; Catelan, Marcio; Sweigart, Allen V.; Layden, Andrew C.; Rich, R. Michael

    2003-01-01

    We present the results of a Hubble Space Telescope snapshot program to survey the inner region of the metal-rich globular cluster NGC 6441 for its variable stars. A total of 57 variable stars was found including 38 RR Lyrae stars, 6 Population II Cepheids, and 12 long period variables. Twenty-four of the RR Lyrae stars and all of the Population II Cepheids were previously undiscovered in ground-based surveys. Of the RR Lyrae stars observed in h s survey, 26 are pulsating in the fundamental mode with a mean period of 0.753 d and 12 are first-overtone mode pulsators with a mean period of 0.365 d. These values match up very well with those found in ground-based surveys. Combining all the available data for NGC 6441, we find mean periods of 0.759 d and 0.375 d for the RRab and RRc stars, respectively. We also find that the RR Lyrae in this survey are located in the same regions of a period-amplitude diagram as those found in ground-based surveys. The overall ratio of RRc to total RR Lyrae is 0.33. Although NGC 6441 is a metal-rich globular cluster and would, on that ground, be expected either to have few RR Lyrae stars, or to be an Oosterhoff type I system, its RR Lyrae more closely resemble those in Oosterhoff type II globular clusters. However, even compared to typical Oosterhoff type II systems, the mean period of its RRab stars is unusually long. We also derived I-band period-luminosity relations for the RR Lyrae stars. Of the six Population II Cepheids, five are of W Virginis type and one is a BL Herculis variable star. This makes NGC 6441, along with NGC 6388, the most metal-rich globular cluster known to contain these types of variable stars. Another variable, V118, may also be a Population II Cepheid given its long period and its separation in magnitude from the RR Lyrae stars. We examine the period-luminosity relation for these Population II Cepheids and compare it to those in other globular clusters and in the Large Magellanic Cloud. We argue that there does

  8. ADCC employing an NK cell line (haNK) expressing the high affinity CD16 allele with avelumab, an anti-PD-L1 antibody.

    PubMed

    Jochems, Caroline; Hodge, James W; Fantini, Massimo; Tsang, Kwong Y; Vandeveer, Amanda J; Gulley, James L; Schlom, Jeffrey

    2017-08-01

    NK-92 cells, and their derivative, designated aNK, were obtained from a patient with non-Hodgkin lymphoma. Prior clinical studies employing adoptively transferred irradiated aNK cells have provided evidence of clinical benefit and an acceptable safety profile. aNK cells have now been engineered to express IL-2 and the high affinity (ha) CD16 allele (designated haNK). Avelumab is a human IgG1 anti-PD-L1 monoclonal antibody, which has shown evidence of clinical activity in a range of human tumors. Prior in vitro studies have shown that avelumab has the ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) of human tumor cells when combined with NK cells. In the studies reported here, the ability of avelumab to enhance the lysis of a range of human carcinoma cells by irradiated haNK cells via the ADCC mechanism is demonstrated; this ADCC is shown to be inhibited by anti-CD16 blocking antibody and by concanamycin A, indicating the use of the granzyme/perforin pathway in tumor cell lysis. Studies also show that while NK cells have the ability to lyse aNK or haNK cells, the addition of NK cells to irradiated haNK cells does not inhibit haNK-mediated lysis of human tumor cells, with or without the addition of avelumab. Avelumab-mediated lysis of tumor cells by irradiated haNK cells is also shown to be similar to that of NK cells bearing the V/V Fc receptor high affinity allele. These studies thus provide the rationale for the clinical evaluation of the combined use of avelumab with that of irradiated adoptively transferred haNK cells. © 2017 UICC.

  9. Evolutionary versatility of eukaryotic protein domains revealed by their bigram networks

    PubMed Central

    2011-01-01

    Background Protein domains are globular structures of independently folded polypeptides that exert catalytic or binding activities. Their sequences are recognized as evolutionary units that, through genome recombination, constitute protein repertoires of linkage patterns. Via mutations, domains acquire modified functions that contribute to the fitness of cells and organisms. Recent studies have addressed the evolutionary selection that may have shaped the functions of individual domains and the emergence of particular domain combinations, which led to new cellular functions in multi-cellular animals. This study focuses on modeling domain linkage globally and investigates evolutionary implications that may be revealed by novel computational analysis. Results A survey of 77 completely sequenced eukaryotic genomes implies a potential hierarchical and modular organization of biological functions in most living organisms. Domains in a genome or multiple genomes are modeled as a network of hetero-duplex covalent linkages, termed bigrams. A novel computational technique is introduced to decompose such networks, whereby the notion of domain "networking versatility" is derived and measured. The most and least "versatile" domains (termed "core domains" and "peripheral domains" respectively) are examined both computationally via sequence conservation measures and experimentally using selected domains. Our study suggests that such a versatility measure extracted from the bigram networks correlates with the adaptivity of domains during evolution, where the network core domains are highly adaptive, significantly contrasting the network peripheral domains. Conclusions Domain recombination has played a major part in the evolution of eukaryotes attributing to genome complexity. From a system point of view, as the results of selection and constant refinement, networks of domain linkage are structured in a hierarchical modular fashion. Domains with high degree of networking

  10. Evolutionary versatility of eukaryotic protein domains revealed by their bigram networks.

    PubMed

    Xie, Xueying; Jin, Jing; Mao, Yongyi

    2011-08-18

    Protein domains are globular structures of independently folded polypeptides that exert catalytic or binding activities. Their sequences are recognized as evolutionary units that, through genome recombination, constitute protein repertoires of linkage patterns. Via mutations, domains acquire modified functions that contribute to the fitness of cells and organisms. Recent studies have addressed the evolutionary selection that may have shaped the functions of individual domains and the emergence of particular domain combinations, which led to new cellular functions in multi-cellular animals. This study focuses on modeling domain linkage globally and investigates evolutionary implications that may be revealed by novel computational analysis. A survey of 77 completely sequenced eukaryotic genomes implies a potential hierarchical and modular organization of biological functions in most living organisms. Domains in a genome or multiple genomes are modeled as a network of hetero-duplex covalent linkages, termed bigrams. A novel computational technique is introduced to decompose such networks, whereby the notion of domain "networking versatility" is derived and measured. The most and least "versatile" domains (termed "core domains" and "peripheral domains" respectively) are examined both computationally via sequence conservation measures and experimentally using selected domains. Our study suggests that such a versatility measure extracted from the bigram networks correlates with the adaptivity of domains during evolution, where the network core domains are highly adaptive, significantly contrasting the network peripheral domains. Domain recombination has played a major part in the evolution of eukaryotes attributing to genome complexity. From a system point of view, as the results of selection and constant refinement, networks of domain linkage are structured in a hierarchical modular fashion. Domains with high degree of networking versatility appear to be evolutionary

  11. Sulforaphane suppresses ultraviolet B-induced inflammation in HaCaT keratinocytes and HR-1 hairless mice.

    PubMed

    Shibata, Akira; Nakagawa, Kiyotaka; Yamanoi, Hiroko; Tsuduki, Tsuyoshi; Sookwong, Phumon; Higuchi, Ohki; Kimura, Fumiko; Miyazawa, Teruo

    2010-08-01

    Ultraviolet B (UVB) irradiation induces skin damage and inflammation. One way to reduce the inflammation is via the use of molecules termed photochemopreventive agents. Sulforaphane (4-methylsulfinylbutyl isothiocyanate, SF), which is found in cruciferous vegetables, is known for its potent physiological properties. This study was designed to evaluate the effect of SF on skin inflammation in vitro and in vivo. In in vitro study using immortalized human keratinocytes (HaCaT), UVB caused marked inflammatory responses [i.e., decrease of HaCaT viability and increase of production of an inflammatory marker interleukin-6 (IL-6)]. SF recovered the cell proliferation and suppressed the IL-6 production. These anti-inflammatory effects of SF were explained by its ability to reduce UVB-induced inflammatory gene expressions [IL-6, IL-1beta and cyclooxgenase-2 (COX-2)]. Because SF seems to have an impact on COX-2 expression, we focused on COX-2 and found that SF reduced UVB-induced COX-2 protein expression. In support of this, PGE(2) released from HaCaT was suppressed by SF. Western blot analysis revealed that SF inhibited p38, ERK and SAPK/JNK activation, indicating that the inhibition of mitogen-activated protein kinases (MAPK) by SF would attenuate the expression of inflammatory mediators (e.g., COX-2), thereby reducing inflammatory responses. Moreover, we conducted skin thickening assay using HR-1 hairless mice and found that UVB-induced skin thickness, COX-2 protein expression and hyperplasia were all suppressed by feeding SF to the mice. These results suggest that SF has a potential use as a compound for protection against UVB-induced skin inflammation. Copyright 2010 Elsevier Inc. All rights reserved.

  12. HA metabolism in skin homeostasis and inflammatory disease.

    PubMed

    Kavasi, Rafaela-Maria; Berdiaki, Aikaterini; Spyridaki, Ioanna; Corsini, Emanuela; Tsatsakis, Aristidis; Tzanakakis, George; Nikitovic, Dragana

    2017-03-01

    Hyaluronan (HA), an unsulfated glycosaminoglycan, is an important component of the complex extracellular matrix network which surrounds and supports cells in tissues. HA is detected in all vertebrate tissues, but the bulk of HA is produced and deposited in the skin. In this review we focus on the role of HA in skin-associated inflammatory disease and wound healing. Properties of HA are directly dependent on its molecular weight. Thus, high molecular weight HA (HMWHA) is deposited in normal tissues during homeostasis and promotes their stability whereas low molecular weight HA fragments (LMWHA), on the other hand, may arise from enzymatic or chemical activities. The degradation of HMWHA to LMWHA fragments, often leads to the generation of biologically active oligosaccharides with different properties and postulated functions in wound scar formation and inflammation. More detailed studies of HA involvement in skin-associated inflammatory disease may result in novel treatment modalities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Sus scrofa miR-204 and miR-4331 Negatively Regulate Swine H1N1/2009 Influenza A Virus Replication by Targeting Viral HA and NS, Respectively.

    PubMed

    Zhang, Shishuo; Wang, Ruifang; Su, Huijuan; Wang, Biaoxiong; Sizhu, Suolang; Lei, Zhixin; Jin, Meilin; Chen, Huanchun; Cao, Jiyue; Zhou, Hongbo

    2017-04-03

    The prevalence of swine pandemic H1N1/2009 influenza A virus (SIV-H1N1/2009) in pigs has the potential to generate novel reassortant viruses, posing a great threat to human health. Cellular microRNAs (miRNAs) have been proven as promising small molecules for regulating influenza A virus replication by directly targeting viral genomic RNA. In this study, we predicted potential Sus scrofa (ssc-, swine) miRNAs targeting the genomic RNA of SIV-H1N1/2009 by RegRNA 2.0, and identified ssc-miR-204 and ssc-miR-4331 to target viral HA and NS respectively through dual-luciferase reporter assays. The messenger RNA (mRNA) levels of viral HA and NS were significantly suppressed when newborn pig trachea (NPTr) cells respectively overexpressed ssc-miR-204 and ssc-miR-4331 and were infected with SIV-H1N1/2009, whereas the suppression effect could be restored when respectively decreasing endogenous ssc-miR-204 and ssc-miR-4331 with inhibitors. Because of the importance of viral HA and NS in the life cycle of influenza A virus, ssc-miR-204 and ssc-miR-4331 exhibited an inhibition effect on SIV-H1N1/2009 replication. The antiviral effect was sequence-specific of SIV-H1N1/2009, for the target sites in HA and NS of H5N1 or H9N2 influenza A virus were not conserved. Furthermore, SIV-H1N1/2009 infection reversely downregulated the expression of ssc-miR-204 and ssc-miR-4331, which might facilitate the virus replication in the host. In summary, this work will provide us some important clues for controlling the prevalence of SIV-H1N1/2009 in pig populations.

  14. Influence of non-thermal plasma on structural and electrical properties of globular and nanostructured conductive polymer polypyrrole in water suspension.

    PubMed

    Galář, Pavel; Khun, Josef; Kopecký, Dušan; Scholtz, Vladimír; Trchová, Miroslava; Fučíková, Anna; Jirešová, Jana; Fišer, Ladislav

    2017-11-08

    Non-thermal plasma has proved its benefits in medicine, plasma assisted polymerization, food industry and many other fields. Even though, the ability of non-thermal plasma to modify surface properties of various materials is generally known, only limited attention has been given to exploitations of this treatment on conductive polymers. Here, we show study of non-thermal plasma treatment on properties of globular and nanostructured polypyrrole in the distilled water. We observe that plasma presence over the suspension level doesn't change morphology of the polymer (shape), but significantly influences its elemental composition and physical properties. After 60 min of treatment, the relative concentration of chloride counter ions decreased approximately 3 and 4 times for nanostructured and globular form, respectively and concentration of oxygen increased approximately 3 times for both forms. Simultaneously, conductivity decrease (14 times for globular and 2 times for nanostructured one) and changes in zeta potential characteristics of both samples were observed. The modification evolution was dominated by multi-exponential function with time constants having values approximately 1 and 10 min for both samples. It is expected that these time constants are related to two modification processes connected to direct presence of the spark and to long-lived species generated by the plasma.

  15. Effects of incorporation of HA/ZrO(2) into glass ionomer cement (GIC).

    PubMed

    Gu, Y W; Yap, A U J; Cheang, P; Khor, K A

    2005-03-01

    Glass ionomer cements (GICs) are a class of bioactive cements that bond directly to bone. In this paper, a new bioactive hydroxyapatite (HA)/zirconia (ZrO(2))-filled GIC composite was developed to improve the biocompatibility and bioactivity of the GICs with the surrounding bone and connective tissues. Nano-sized HA/30 wt% ZrO(2) powders were heat treated at 700 degrees Celsius and 800 degrees Celsius for 3 h to elucidate the influence of the crystallinity of composite powders on the performance of HA/ZrO(2)-GICs. The effects of different volume percentages of HA/ZrO(2) powders (4, 12, 28 and 40 vol%) substituted within GICs were investigated based on their microhardness, compressive strength and diametral tensile strength. The HA/ZrO(2)-GICs composite was soaked in distilled water for 1 day and 1 week before subjecting the samples to mechanical testing. Results showed that the glass and HA/ZrO(2) particles were distributed uniformly in the GIC matrix. The substitution of highly crystalline HA/ZrO(2) improved the mechanical properties of the HA/ZrO(2)-GICs due to the slow resorption rate for highly crystalline powders in distilled water. The mechanical properties of HA/ZrO(2)-GICs increased with increasing soak time due to the continuous formation of aluminium salt bridges, which improved the final strength of the cements. The compositions 4 and 12 vol% HA/ZrO(2)-GICs exhibited superior mechanical properties than the original GICs. The mechanical properties of HA/ZrO(2)-GICs were found to be much better than those of HA-GICs because ZrO(2) has the attributes of high strength, high modulus, and is significantly harder than glass and HA particles. Furthermore, ZrO(2) does not dissolve with increasing soaking time.

  16. NMR solution structure of the activation domain of human procarboxypeptidase A2

    PubMed Central

    Jiménez, M. Angeles; Villegas, Virtudes; Santoro, Jorge; Serrano, Luis; Vendrell, Josep; Avilés, Francesc X.; Rico, Manuel

    2003-01-01

    The activation domain of human procarboxypeptidase A2, ADA2h, is an 81-residue globular domain released during the proteolytic activation of the proenzyme. The role of this and other similar domains as assistants of the correct folding of the enzyme is not fully understood. The folding pathway of ADA2h was characterized previously, and it was also observed that under certain conditions it may convert into amyloid fibrils in vitro. To gain insight into these processes, a detailed description of its three-dimensional structure in aqueous solution is required so that eventual changes could be properly monitored. A complete assignment of the 1H and 15N resonances of ADA2h was performed, and the solution structure, as derived from a set of 1688 nonredundant constraints, is very well defined (pairwise backbone RMSD = 0.67 ± 0.17 Å for residues 10–80). The structure is composed of two antiparallel α-helices comprising residues 19–32 and 58–69 packed on the same side of a three-stranded β-sheet spanning residues 10–15, 50–55, and 73–75. The global fold for the isolated human A2 activation domain is very similar to that of porcine carboxypeptidase B, as well as to the structure of the domain in the crystal of the intact human proenzyme. The observed structural differences relative to the intact human proenzyme are located at the interface between the activation domain and the enzyme and can be related with the activation mechanism. The backbone amide proton exchange behavior of ADA2h was also examined. The global free energy of unfolding obtained from exchange data of the most protected amide protons at pH 7.0 and 298K is 4.9 ± 0.3 kcal.mole−1, in good agreement with the values determined by thermal or denaturant unfolding studies. PMID:12538893

  17. Dynamical Friction in Multi-component Evolving Globular Clusters

    NASA Astrophysics Data System (ADS)

    Alessandrini, Emiliano; Lanzoni, Barbara; Miocchi, Paolo; Ciotti, Luca; Ferraro, Francesco R.

    2014-11-01

    We use the Chandrasekhar formalism and direct N-body simulations to study the effect of dynamical friction on a test object only slightly more massive than the field stars, orbiting a spherically symmetric background of particles with a mass spectrum. The main goal is to verify whether the dynamical friction time (t DF) develops a non-monotonic radial dependence that could explain the bimodality of the blue straggler radial distributions observed in globular clusters. In these systems, in fact, relaxation effects lead to a mass and velocity radial segregation of the different mass components, so that mass-spectrum effects on t DF are expected to be dependent on radius. We find that in spite of the presence of different masses, t DF is always a monotonic function of radius, at all evolutionary times and independently of the initial concentration of the simulated cluster. This is because the radial dependence of t DF is largely dominated by the total mass density profile of the background stars (which is monotonically decreasing with radius). Hence, a progressive temporal erosion of the blue straggler star (BSS) population at larger and larger distances from the cluster center remains the simplest and the most likely explanation of the shape of the observed BSS radial distributions, as suggested in previous works. We also confirm the theoretical expectation that approximating a multi-mass globular cluster as made of (averaged) equal-mass stars can lead to significant overestimations of t DF within the half-mass radius.

  18. The effect of the type of HA on the degradation of PLGA/HA composites.

    PubMed

    Naik, Ashutosh; Shepherd, David V; Shepherd, Jennifer H; Best, Serena M; Cameron, Ruth E

    2017-01-01

    The aim of this study is to explore the importance of the potentially competing effects of buffering effects of the calcium phosphate filler and particle-mediated water sorption on the degradation products of poly(d,l lactide-co-glycolide (50:50))(PLGA)/hydroxyapatite(HA) composites. Further the influence of type of HA on the mechanical properties of the composites was investigated. Phase pure HA was synthesised via a reaction between aqueous solutions of calcium hydroxide and orthophosphoric acid. The powder produced was either used as produced (uncalcined) or calcined in air or calcined in a humidified argon atmosphere. An in-vitro degradation study was carried out in phosphate buffered saline (PBS). The results obtained indicated that the degradation rate of the composite might be better understood if both the buffering effects and the rate of water sorption by the composites are considered. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Characterization, Corrosion Resistance, and Cell Response of High-Velocity Flame-Sprayed HA and HA/TiO2 Coatings on 316L SS

    NASA Astrophysics Data System (ADS)

    Singh, Tejinder Pal; Singh, Harpreet; Singh, Hazoor

    2012-09-01

    The main aim of this study is to evaluate corrosion and biocompatibility behavior of thermal spray hydroxyapatite (HA) and hydroxyapatite/titania bond (HA/TiO2)-coated 316L stainless steel (316L SS). In HA/TiO2 coatings, TiO2 was used as a bond coat between HA top coat and 316L SS substrate. The coatings were characterized by x-ray diffraction and scanning electron microscopy/energy dispersive spectroscopy, and corrosion resistance determined for the uncoated substrate and the two coatings. The biological behavior was investigated by the cell culture studies using osteosarcoma cell line KHOS-NP (R-970-5). The corrosion resistance of the steel was found to increase after the deposition of the HA and HA/TiO2 bond coatings. Both HA, as well as, HA/TiO2 coatings exhibit excellent bond strength of 49 and 47 MPa, respectively. The cell culture studies showed that HA-coated 316L SS specimens appeared more biocompatible than the uncoated and HA/TiO2-coated 316L SS specimens.

  20. Selective pre-priming of HA-specific CD4 T cells restores immunological reactivity to HA on heterosubtypic influenza infection.

    PubMed

    Alam, Shabnam; Chan, Cory; Qiu, Xing; Shannon, Ian; White, Chantelle L; Sant, Andrea J; Nayak, Jennifer L

    2017-01-01

    A hallmark of the immune response to influenza is repeated encounters with proteins containing both genetically conserved and variable components. Therefore, the B and T cell repertoire is continually being remodeled, with competition between memory and naïve lymphocytes. Our previous work using a mouse model of secondary heterosubtypic influenza infection has shown that this competition results in a focusing of CD4 T cell response specificity towards internal virion proteins with a selective decrease in CD4 T cell reactivity to the novel HA epitopes. Strikingly, this shift in CD4 T cell specificity was associated with a diminished anti-HA antibody response. Here, we sought to determine whether the loss in HA-specific reactivity that occurs as a consequence of immunological memory could be reversed by selectively priming HA-specific CD4 T cells prior to secondary infection. Using a peptide-based priming strategy, we found that selective expansion of the anti-HA CD4 T cell memory repertoire enhanced HA-specific antibody production upon heterosubtypic infection. These results suggest that the potentially deleterious consequences of repeated exposure to conserved influenza internal virion proteins could be reversed by vaccination strategies that selectively arm the HA-specific CD4 T cell compartment. This could be a potentially useful pre-pandemic vaccination strategy to promote accelerated neutralizing antibody production on challenge with a pandemic influenza strain that contains few conserved HA epitopes.

  1. The homologous HD-Zip I transcription factors HaHB1 and AtHB13 confer cold tolerance via the induction of pathogenesis-related and glucanase proteins.

    PubMed

    Cabello, Julieta V; Arce, Agustín L; Chan, Raquel L

    2012-01-01

    Plants deal with cold temperatures via different signal transduction pathways. The HD-Zip I homologous transcription factors HaHB1 from sunflower and AtHB13 from Arabidopsis were identified as playing a key role in such cold response. The expression patterns of both genes were analyzed indicating an up-regulation by low temperatures. When these genes were constitutively expressed in Arabidopsis, the transgenic plants showed similar phenotypes including cell membrane stabilization under freezing treatments and cold tolerance. An exploratory transcriptomic analysis of HaHB1 transgenic plants indicated that several transcripts encoding glucanases and chitinases were induced. Moreover, under freezing conditions some proteins accumulated in HaHB1 plants apoplasts and these extracts exerted antifreeze activity in vitro. Three genes encoding two glucanases and a chitinase were overexpressed in Arabidopsis and these plants were able to tolerate freezing temperatures. All the obtained transgenic plants exhibited cell membrane stabilization after a short freezing treatment. Finally, HaHB1 and AtHB13 were used to transiently transform sunflower and soybean leading to the up-regulation of HaHB1/AtHB13-target homologues thus indicating the conservation of cold response pathways. We propose that HaHB1 and AtHB13 are involved in plant cold tolerance via the induction of proteins able to stabilize cell membranes and inhibit ice growth. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

  2. Novel functions of CCM1 delimit the relationship of PTB/PH domains.

    PubMed

    Zhang, Jun; Dubey, Pallavi; Padarti, Akhil; Zhang, Aileen; Patel, Rinkal; Patel, Vipulkumar; Cistola, David; Badr, Ahmed

    2017-10-01

    Three NPXY motifs and one FERM domain in CCM1 makes it a versatile scaffold protein for tethering the signaling components together within the CCM signaling complex (CSC). The cellular role of CCM1 protein remains inadequately expounded. Both phosphotyrosine binding (PTB) and pleckstrin homology (PH) domains were recognized as structurally related but functionally distinct domains. By utilizing molecular cloning, protein binding assays and RT-qPCR to identify novel cellular partners of CCM1 and its cellular expression patterns; by screening candidate PTB/PH proteins and subsequently structurally simulation in combining with current X-ray crystallography and NMR data to defined the essential structure of PTB/PH domain for NPXY-binding and the relationship among PTB, PH and FERM domain(s). We identified a group of 28 novel cellular partners of CCM1, all of which contain either PTB or PH domain(s), and developed a novel classification system for these PTB/PH proteins based on their relationship with different NPXY motifs of CCM1. Our results demonstrated that CCM1 has a wide spectrum of binding to different PTB/PH proteins and perpetuates their specificity to interact with certain PTB/PH domains through selective combination of three NPXY motifs. We also demonstrated that CCM1 can be assembled into oligomers through intermolecular interaction between its F3 lobe in FERM domain and one of the three NPXY motifs. Despite being embedded in FERM domain as F3 lobe, F3 module acts as a fully functional PH domain to interact with NPXY motif. The most salient feature of the study was that both PTB and PH domains are structurally and functionally comparable, suggesting that PTB domain is likely evolved from PH domain with polymorphic structural additions at its N-terminus. A new β1A-strand of the PTB domain was discovered and new minimum structural requirement of PTB/PH domain for NPXY motif-binding was determined. Based on our data, a novel theory of structure, function and

  3. BamA POTRA Domain Interacts with a Native Lipid Membrane Surface.

    PubMed

    Fleming, Patrick J; Patel, Dhilon S; Wu, Emilia L; Qi, Yifei; Yeom, Min Sun; Sousa, Marcelo Carlos; Fleming, Karen G; Im, Wonpil

    2016-06-21

    The outer membrane of Gram-negative bacteria is an asymmetric membrane with lipopolysaccharides on the external leaflet and phospholipids on the periplasmic leaflet. This outer membrane contains mainly β-barrel transmembrane proteins and lipidated periplasmic proteins (lipoproteins). The multisubunit protein β-barrel assembly machine (BAM) catalyzes the insertion and folding of the β-barrel proteins into this membrane. In Escherichia coli, the BAM complex consists of five subunits, a core transmembrane β-barrel with a long periplasmic domain (BamA) and four lipoproteins (BamB/C/D/E). The BamA periplasmic domain is composed of five globular subdomains in tandem called POTRA motifs that are key to BAM complex formation and interaction with the substrate β-barrel proteins. The BAM complex is believed to undergo conformational cycling while facilitating insertion of client proteins into the outer membrane. Reports describing variable conformations and dynamics of the periplasmic POTRA domain have been published. Therefore, elucidation of the conformational dynamics of the POTRA domain in full-length BamA is important to understand the function of this molecular complex. Using molecular dynamics simulations, we present evidence that the conformational flexibility of the POTRA domain is modulated by binding to the periplasmic surface of a native lipid membrane. Furthermore, membrane binding of the POTRA domain is compatible with both BamB and BamD binding, suggesting that conformational selection of different POTRA domain conformations may be involved in the mechanism of BAM-facilitated insertion of outer membrane β-barrel proteins. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  4. Keap1/Cullin3 Modulates p62/SQSTM1 Activity via UBA domain Ubiquitination

    PubMed Central

    Lee, YouJin; Chou, Tsui-Fen; Pittman, Sara K.; Keith, Amy L.; Razani, Babak; Weihl, Conrad C.

    2017-01-01

    Summary p62/SQSTM1 (p62) is a scaffolding protein that facilitates the formation and degradation of ubiquitinated aggregates via its self-interaction and ubiquitin binding domains. The regulation of this process is unclear but may relate to the post-translational modification of p62. In the present study, we find that Keap1/Cullin3 ubiquitinates p62 at lysine 420 within its UBA domain. Substitution of lysine 420 with an arginine diminishes p62 sequestration and degradation activity similar to that seen when the UBA domain is deleted. Overexpression of Keap1/Cullin3 in p62-WT expressing cells increases ubiquitinated inclusion formation, p62’s association with LC3 and rescues proteotoxicity. This effect is not seen in cells expressing a mutant p62 that fails to interact with Keap1. Interestingly, p62 disease mutants have diminished or absent UBA domain ubiquitination. These data suggest that the ubiquitination of p62’s UBA domain at lysine 420 may regulate p62’s function and be disrupted in p62 associated disease. PMID:28380357

  5. VizieR Online Data Catalog: Variable stars in globular clusters (Figuera Jaimes+, 2016)

    NASA Astrophysics Data System (ADS)

    Figuera Jaimes, R.; Bramich, D. M.; Skottfelt, J.; Kains, N.; Jorgensen, U. G.; Horne, K.; Dominik, M.; Alsubai, K. A.; Bozza, V.; Calchi Novati, S.; Ciceri, S.; D'Ago, G.; Galianni, P.; Gu, S.-H.; W Harpsoe, K. B.; Haugbolle, T.; Hinse, T. C.; Hundertmark, M.; Juncher, D.; Korhonen, H.; Mancini, L.; Popovas, A.; Rabus, M.; Rahvar, S.; Scarpetta, G.; Schmidt, R. W.; Snodgrass, C.; Southworth, J.; Starkey, D.; Street, R. A.; Surdej, J.; Wang, X.-B.; Wertz, O.

    2016-02-01

    Observations were taken during 2013 and 2014 as part of an ongoing program at the 1.54m Danish telescope at the ESO observatory at La Silla in Chile that was implemented from April to September each year. table1.dat file contains the time-series I photometry for all the variables in the globular clusters studied in this work. We list standard and instrumental magnitudes and their uncertainties corresponding to the variable star identification, filter, and epoch of mid-exposure. For completeness, we also list the reference flux, difference flux, and photometric scale factor, along with the uncertainties on the reference and difference fluxes. (2 data files).

  6. Crystal Structure of the Neuropilin-1 MAM Domain: Completing the Neuropilin-1 Ectodomain Picture.

    PubMed

    Yelland, Tamas; Djordjevic, Snezana

    2016-11-01

    Neuropilins (NRPs) are single-pass transmembrane receptors involved in several signaling pathways that regulate key physiological processes such as vascular morphogenesis and axon guidance. The MAM domain of NRP, which has previously been implicated in receptor multimerization, was the only portion of the ectopic domain of the NRPs for which the structure, until now, has been elusive. Using site-directed mutagenesis in the linker region preceding the MAM domain we generated a protein construct amenable to crystallization. Here we present the crystal structure of the MAM domain of human NRP1 at 2.24 Å resolution. The protein exhibits a jellyroll topology, with Ca 2+ ions bound at the inter-strand space enhancing the thermostability of the domain. We show that the MAM domain of NRP1 is monomeric in solution and insufficient to drive receptor dimerization, which leads us to propose a different role for this domain in the context of NRP membrane assembly and signaling. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Spectroscopy of Hot Horizontal Branch Stars in Globular Clusters

    NASA Astrophysics Data System (ADS)

    Moni-Bidin, C. M.

    2006-06-01

    We will present our latest results on spectroscopy of hot horizontal branch stars in globular clusters. This class of stars still presents many puzzling features, and many aspects of their formation and evolution are still unclear. Extreme Horizontal Branch (EHB) stars, also known as Subdwarf B (sdB) stars, are post-He flash stars with a He-burning core and high effective temperature (T_{eff} ≥ 20000 K). They originate from stars of low initial mass that during their evolution have lost great part of their external envelope. Many channel for the formation of these stars have been studied in literature. The scenarios involving dynamical interactions inside close binary systems, deeply investigated by Han et al. (2003, MNRAS, 341, 669), have been recently preferred, since between field sdB stars many close binary systems have been detected. (Morales-Rueda et al. 2003, MNRAS, 338, 752). Maxted et al. (2001, MNRAS, 326, 1391) estimated that 69+/-9% of field sdB stars are close binary systems. Latest results indicates that also this scenario presents some problems (Lisker et al. 2005, A&A, 430, 223), and Napiwotzki et al. (2004) found a lower fraction of binaries among their sample (42%). Moni Bidin et al. (2005, A&A, submitted) recently showed that in globular cluster NGC6752 the binary fraction among EHB stars is sensibly lower than what observed among field sdBs, estimating an upper limit of 20%. This difference between field and cluster sdBs is quite surprising. We are performing further investigation of these stars extending our search for close binary systems to other two clusters with a rich population of EHB stars. This will allow us to tell if the results on NGC6752 indicate a pecular cluster or the lack of binaries is a common trend of EHB stars in globular clusters. Moreover, with a larger sample we will be able to better estimate the binary fraction, or an upper limit for it. With our contribution we are going to show our results on this investigation that

  8. BRCT-domain protein BRIT1 influences class switch recombination

    PubMed Central

    Yen, Wei-Feng; Chaudhry, Ashutosh; Vaidyanathan, Bharat; Yewdell, William T.; Pucella, Joseph N.; Sharma, Rahul; Li, Kaiyi; Rudensky, Alexander Y.; Chaudhuri, Jayanta

    2017-01-01

    DNA double-strand breaks (DSBs) serve as obligatory intermediates for Ig heavy chain (Igh) class switch recombination (CSR). The mechanisms by which DSBs are resolved to promote long-range DNA end-joining while suppressing genomic instability inherently associated with DSBs are yet to be fully elucidated. Here, we use a targeted short-hairpin RNA screen in a B-cell lymphoma line to identify the BRCT-domain protein BRIT1 as an effector of CSR. We show that conditional genetic deletion of BRIT1 in mice leads to a marked increase in unrepaired Igh breaks and a significant reduction in CSR in ex vivo activated splenic B cells. We find that the C-terminal tandem BRCT domains of BRIT1 facilitate its interaction with phosphorylated H2AX and that BRIT1 is recruited to the Igh locus in an activation-induced cytidine deaminase (AID) and H2AX-dependent fashion. Finally, we demonstrate that depletion of another BRCT-domain protein, MDC1, in BRIT1-deleted B cells increases the severity of CSR defect over what is observed upon loss of either protein alone. Our results identify BRIT1 as a factor in CSR and demonstrate that multiple BRCT-domain proteins contribute to optimal resolution of AID-induced DSBs. PMID:28724724

  9. Photometric study of the eclipsing blue straggler V205 in the globular cluster NGC 5139

    NASA Astrophysics Data System (ADS)

    Li, K.

    2018-02-01

    B and V light curves of an EA-type binary V205 in the globular cluster NGC 5139 are analyzed by the W-D program. We found that V205 is possibly a detached binary and the mass ratio is 0.1596. The secondary component is touching or nearly touching its inner Roche Lobe. By studying the O - C diagram of V205, we discovered that the orbital period is continuously decrease at a rate of dp / dt = - 1.89(± 0.01) ×10-7 d yr-1 and should be caused by angular momentum and mass loss. The angular momentum loss will drive it evolve into a contact binary. Since V205 is a proper motion member of NGC 5139, we estimated its absolute parameters based on the distance modulus of the cluster and determined that: a = 2.50R⊙ , M1 = 0.76M⊙ , R1 = 1.14R⊙ , L1 = 5.46L⊙ , M2 = 0.12M⊙ , R2 = 0.52R⊙ , and L2 = 0.70L⊙ . V205 occupied the blue straggler stars on the color-magnitude diagram of NGC 5139. It is an eclipsing blue straggler and is most possibly formed by mass transfer between the two components. Since original short-period systems similar to V205 should be evolved in such a long life time of the globular cluster, the short-period binary should undergo special evolutionary stages. High accuracy photometric and high resolution spectral observations are essential for this unusual system.

  10. Observing RR Lyrae Variables in the M3 Globular Cluster with the BYU West Mountain Observatory (Abstract)

    NASA Astrophysics Data System (ADS)

    Joner, M. D.

    2016-06-01

    (Abstract only) We have utilized the 0.9-meter telescope of the Brigham Young University West Mountain Observatory to secure data on the northern hemisphere globular cluster NGC 5272 (M3). We made 216 observations in the V filter spaced between March and August 2012. We present light curves of the M3 RR Lyrae stars using different techniques. We compare light curves produced using DAOPHOT and ISIS software packages for stars in both the halo and core regions of this globular cluster. The light curve fitting is done using FITLC.

  11. HaLT2- an enhanced lumber grading trainer

    Treesearch

    Powsiri Klinkhachorn; Charles Gatchell; Charles McMillin; Ravi Kothari; Dennis Yost

    1992-01-01

    This paper reports on HaLT2, an improved version of HaLT (Hardwood Lumber Traning Program)- a computer program that provides training in lumber grading. The newly added enhancements In HaLT2 will provide training for both novice and experienced hardwood lumber graders in accordance with National Hardwood Lumber Assodation (NHLA) rules. HaLT2 is more accurate, easier to...

  12. Astrometry in the globular cluster M13. II. Membership probabilities from old proper motions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cudworth, K.

    Astrometric cluster membership probabilities have been derived from proper motions measured by other authors for stars in the region of the globular cluster M13. Several stars of individual interest are discussed.

  13. Contribution of Primordial Binary Evolution to the Two Blue-straggler Sequences in Globular Cluster M30

    NASA Astrophysics Data System (ADS)

    Jiang, Dengkai; Chen, Xuefei; Li, Lifang; Han, Zhanwen

    2017-11-01

    Two blue-straggler sequences discovered in globular cluster M30 provide a strong constraint on the formation mechanisms of blue stragglers. We study the formation of blue-straggler binaries through binary evolution, and find that binary evolution can contribute to the blue stragglers in both of the sequences. Whether a blue-straggler is located in the blue sequence or red sequence depends on the contribution of the mass donor to the total luminosity of the binary, which is generally observed as a single star in globular clusters. The blue stragglers in the blue sequence have a cool white dwarf companion, while the majority (˜60%) of the objects in the red sequence are binaries that are still experiencing mass transfer. However, there are also some objects for which the donors have just finished the mass transfer (the stripped-core stars, ˜10%) or the blue stragglers (the accretors) have evolved away from the blue sequence (˜30%). Meanwhile, W UMa contact binaries found in both sequences may be explained by various mass ratios, that is, W UMa contact binaries in the red sequence have two components with comparable masses (e.g., mass ratio q ˜ 0.3-1.0), while those in the blue sequence have low mass ratios (e.g., q< 0.3). However, the fraction of the blue sequence in M30 cannot be reproduced by binary population synthesis if we assumed the initial parameters of a binary sample to be the same as those of the field. This possibly indicates that dynamical effects on binary systems are very important in globular clusters.

  14. Observing globular cluster RR Lyraes with the BYU West Mountain Observatory

    NASA Astrophysics Data System (ADS)

    Jeffery, E. J.; Joner, M. D.; Walton, R. S.

    2016-05-01

    We have utilized the 0.9-meter telescope of the Brigham Young University West Mountain Observatory to secure data on six northern hemi- sphere globular clusters. Here we present observations of RR Lyrae stars located in these clusters. We compare light curves produced using both DAOPHOT and ISIS software packages. Light curve fitting is done with FITLC.

  15. The extended stellar substructures of four metal-poor globular clusters in the galactic bulge

    NASA Astrophysics Data System (ADS)

    Chun, Sang-Hyun; Sohn, Young-Jong

    2015-08-01

    We investigated stellar spatial density distribution around four metal-poor globular clusters (NGC 6266, NGC 6626, NGC 6642 and NGC 6723) in order to find extended stellar substructures. Wide-field deep J, H, and K imaging data were taken using the WFCAM near-infrared array on United Kingdom Infrared Telescope (UKIRT). The contamination of field stars around clusters was minimised by applying a statistical weighted filtering algorithm for the stars on the color-magnitude diagram. In two-dimensional isodensity contour map, we find that all four of the globular clusters shows tidal stripping stellar features in the form of tidal tails (NGC 6266 and NGC 6723) or small density lobes/chunk (NGC 6642 and NGC 6723). The stellar substructures extend toward the Galactic centre or anticancer, and the proper motion direction of the clusters. The radial density profiles of the clusters also depart from theoretical King and Wilson models and show overdensity feature with a break in a slope of profile at the outer region of clusters. The observed results indicate that four globular clusters in the Galactic bulge have experienced strong tidal force or bulge/disk shock effect of the Galaxy. These observational results provide us further constraints to understand the evolution of clusters in the Galactic bulge region as well as the formation of the Galaxy.

  16. Identification and Structural Characterization of a Broadly Neutralizing Antibody Targeting a Novel Conserved Epitope on the Influenza Virus H5N1 Hemagglutinin

    PubMed Central

    Du, Lanying; Jin, Lei; Zhao, Guangyu; Sun, Shihui; Li, Junfeng; Yu, Hong; Li, Ye; Zheng, Bo-Jian; Liddington, Robert C.

    2013-01-01

    The unabated circulation of the highly pathogenic avian influenza A virus/H5N1 continues to be a serious threat to public health worldwide. Because of the high frequency of naturally occurring mutations, the emergence of H5N1 variants with high virulence has raised great concerns about the potential transmissibility of the virus in humans. Recent studies have shown that laboratory-mutated or reassortant H5N1 viruses could be efficiently transmitted among mammals, particularly ferrets, the best animal model for humans. Thus, it is critical to establish effective strategies to combat future H5N1 pandemics. In this study, we identified a broadly neutralizing monoclonal antibody (MAb), HA-7, that potently neutralized all tested strains of H5N1 covering clades 0, 1, 2.2, 2.3.4, and 2.3.2.1 and completely protected mice against lethal challenges of H5N1 viruses from clades 1 and 2.3.4. HA-7 specifically targeted the globular head of the H5N1 virus hemagglutinin (HA). Using electron microscopy technology with three-dimensional reconstruction (3D-EM), we discovered that HA-7 bound to a novel and highly conserved conformational epitope that was centered on residues 81 to 83 and 117 to 122 of HA1 (H5 numbering). We further demonstrated that HA-7 inhibited viral entry during postattachment events but not at the receptor-binding step, which is fully consistent with the 3D-EM result. Taken together, we propose that HA-7 could be humanized as an effective passive immunotherapeutic agent for antiviral stockpiling for future influenza pandemics caused by emerging unpredictable H5N1 strains. Our study also provides a sound foundation for the rational design of vaccines capable of inducing broad-spectrum immunity against H5N1. PMID:23221567

  17. Reliability of confidence intervals calculated by bootstrap and classical methods using the FIA 1-ha plot design

    Treesearch

    H. T. Schreuder; M. S. Williams

    2000-01-01

    In simulation sampling from forest populations using sample sizes of 20, 40, and 60 plots respectively, confidence intervals based on the bootstrap (accelerated, percentile, and t-distribution based) were calculated and compared with those based on the classical t confidence intervals for mapped populations and subdomains within those populations. A 68.1 ha mapped...

  18. Characterization of domain-peptide interaction interface: a case study on the amphiphysin-1 SH3 domain.

    PubMed

    Hou, Tingjun; Zhang, Wei; Case, David A; Wang, Wei

    2008-02-29

    Many important protein-protein interactions are mediated by peptide recognition modular domains, such as the Src homology 3 (SH3), SH2, PDZ, and WW domains. Characterizing the interaction interface of domain-peptide complexes and predicting binding specificity for modular domains are critical for deciphering protein-protein interaction networks. Here, we propose the use of an energetic decomposition analysis to characterize domain-peptide interactions and the molecular interaction energy components (MIECs), including van der Waals, electrostatic, and desolvation energy between residue pairs on the binding interface. We show a proof-of-concept study on the amphiphysin-1 SH3 domain interacting with its peptide ligands. The structures of the human amphiphysin-1 SH3 domain complexed with 884 peptides were first modeled using virtual mutagenesis and optimized by molecular mechanics (MM) minimization. Next, the MIECs between domain and peptide residues were computed using the MM/generalized Born decomposition analysis. We conducted two types of statistical analyses on the MIECs to demonstrate their usefulness for predicting binding affinities of peptides and for classifying peptides into binder and non-binder categories. First, combining partial least squares analysis and genetic algorithm, we fitted linear regression models between the MIECs and the peptide binding affinities on the training data set. These models were then used to predict binding affinities for peptides in the test data set; the predicted values have a correlation coefficient of 0.81 and an unsigned mean error of 0.39 compared with the experimentally measured ones. The partial least squares-genetic algorithm analysis on the MIECs revealed the critical interactions for the binding specificity of the amphiphysin-1 SH3 domain. Next, a support vector machine (SVM) was employed to build classification models based on the MIECs of peptides in the training set. A rigorous training-validation procedure was

  19. Disulfide bonding arrangements in active forms of the somatomedin B domain of human vitronectin.

    PubMed

    Kamikubo, Yuichi; De Guzman, Roberto; Kroon, Gerard; Curriden, Scott; Neels, Jaap G; Churchill, Michael J; Dawson, Philip; Ołdziej, Stanisław; Jagielska, Anna; Scheraga, Harold A; Loskutoff, David J; Dyson, H Jane

    2004-06-01

    The N-terminal cysteine-rich somatomedin B (SMB) domain (residues 1-44) of the human glycoprotein vitronectin contains the high-affinity binding sites for plasminogen activator inhibitor-1 (PAI-1) and the urokinase receptor (uPAR). We previously showed that the eight cysteine residues of recombinant SMB (rSMB) are organized into four disulfide bonds in a linear uncrossed pattern (Cys(5)-Cys(9), Cys(19)-Cys(21), Cys(25)-Cys(31), and Cys(32)-Cys(39)). In the present study, we use an alternative method to show that this disulfide bond arrangement remains a major preferred one in solution, and we determine the solution structure of the domain using NMR analysis. The solution structure shows that the four disulfide bonds are tightly packed in the center of the domain, replacing the traditional hydrophobic core expected for a globular protein. The few noncysteine hydrophobic side chains form a cluster on the outside of the domain, providing a distinctive binding surface for the physiological partners PAI-1 and uPAR. The hydrophobic surface consists mainly of side chains from the loop formed by the Cys(25)-Cys(31) disulfide bond, and is surrounded by conserved acidic and basic side chains, which are likely to contribute to the specificity of the intermolecular interactions of this domain. Interestingly, the overall fold of the molecule is compatible with several arrangements of the disulfide bonds. A number of different disulfide bond arrangements were able to satisfy the NMR restraints, and an extensive series of conformational energy calculations performed in explicit solvent confirmed that several disulfide bond arrangements have comparable stabilization energies. An experimental demonstration of the presence of alternative disulfide conformations in active rSMB is provided by the behavior of a mutant in which Asn(14) is replaced by Met. This mutant has the same PAI-1 binding activity as rVN1-51, but its fragmentation pattern following cyanogen bromide treatment is

  20. Exploring the nature and synchronicity of early cluster formation in the Large Magellanic Cloud - II. Relative ages and distances for six ancient globular clusters

    NASA Astrophysics Data System (ADS)

    Wagner-Kaiser, R.; Mackey, Dougal; Sarajedini, Ata; Chaboyer, Brian; Cohen, Roger E.; Yang, Soung-Chul; Cummings, Jeffrey D.; Geisler, Doug; Grocholski, Aaron J.

    2017-11-01

    We analyse Hubble Space Telescope observations of six globular clusters in the Large Magellanic Cloud (LMC) from programme GO-14164 in Cycle 23. These are the deepest available observations of the LMC globular cluster population; their uniformity facilitates a precise comparison with globular clusters in the Milky Way. Measuring the magnitude of the main-sequence turn-off point relative to template Galactic globular clusters allows the relative ages of the clusters to be determined with a mean precision of 8.4 per cent, and down to 6 per cent for individual objects. We find that the mean age of our LMC cluster ensemble is identical to the mean age of the oldest metal-poor clusters in the Milky Way halo to 0.2 ± 0.4 Gyr. This provides the most sensitive test to date of the synchronicity of the earliest epoch of globular cluster formation in two independent galaxies. Horizontal branch magnitudes and subdwarf fitting to the main sequence allow us to determine distance estimates for each cluster and examine their geometric distribution in the LMC. Using two different methods, we find an average distance to the LMC of 18.52 ± 0.05.

  1. Chemical Complexity in the Eu-enhanced Monometallic Globular NGC 5986

    NASA Astrophysics Data System (ADS)

    Johnson, Christian I.; Caldwell, Nelson; Rich, R. Michael; Mateo, Mario; Bailey, John I., III; Olszewski, Edward W.; Walker, Matthew G.

    2017-06-01

    NGC 5986 is a poorly studied but relatively massive Galactic globular cluster that shares several physical and morphological characteristics with “iron-complex” clusters known to exhibit significant metallicity and heavy-element dispersions. In order to determine whether NGC 5986 joins the iron-complex cluster class, we investigated the chemical composition of 25 red giant branch and asymptotic giant branch cluster stars using high-resolution spectra obtained with the Magellan-M2FS instrument. Cluster membership was verified using a combination of radial velocity and [Fe/H] measurements, and we found the cluster to have a mean heliocentric radial velocity of +99.76 km s-1 (σ = 7.44 km s-1). We derived a mean metallicity of [Fe/H] = -1.54 dex (σ = 0.08 dex), but the cluster’s small dispersion in [Fe/H] and low [La/Eu] abundance preclude it from being an iron-complex cluster. NGC 5986 has < [{Eu}/{Fe}]> =+0.76 {dex} (σ = 0.08 dex), which is among the highest ratios detected in a Galactic cluster, but the small [Eu/Fe] dispersion is puzzling because such high values near [Fe/H] ˜ -1.5 are typically only found in dwarf galaxies exhibiting large [Eu/Fe] variations. NGC 5986 exhibits classical globular cluster characteristics, such as uniformly enhanced [α/Fe] ratios, a small dispersion in Fe-peak abundances, and (anti)correlated light-element variations. Similar to NGC 2808, we find evidence that NGC 5986 may host at least four to five populations with distinct light-element compositions, and the presence of a clear Mg-Al anticorrelation along with an Al-Si correlation suggests that the cluster gas experienced processing at temperatures ≳65-70 MK. However, the current data do not support burning temperatures exceeding ˜100 MK. We find some evidence that the first- and second-generation stars in NGC 5986 may be fully spatially mixed, which could indicate that the cluster has lost a significant fraction of its original mass. This paper includes data gathered

  2. Probing Globular Cluster Formation in Low Metallicity Dwarf Galaxies

    NASA Astrophysics Data System (ADS)

    Johnson, Kelsey E.; Hunt, Leslie K.; Reines, Amy E.

    2008-12-01

    The ubiquitous presence of globular clusters around massive galaxies today suggests that these extreme star clusters must have been formed prolifically in the earlier universe in low-metallicity galaxies. Numerous adolescent and massive star clusters are already known to be present in a variety of galaxies in the local universe; however most of these systems have metallicities of 12 + log(O/H) > 8, and are thus not representative of the galaxies in which today's ancient globular clusters were formed. In order to better understand the formation and evolution of these massive clusters in environments with few heavy elements, we have targeted several low-metallicity dwarf galaxies with radio observations, searching for newly-formed massive star clusters still embedded in their birth material. The galaxies in this initial study are HS 0822+3542, UGC 4483, Pox 186, and SBS 0335-052, all of which have metallicities of 12 + log(O/H) < 7.75. While no thermal radio sources, indicative of natal massive star clusters, are found in three of the four galaxies, SBS 0335-052 hosts two such objects, which are incredibly luminous. The radio spectral energy distributions of these intense star-forming regions in SBS 0335-052 suggest the presence of ~12,000 equivalent O-type stars, and the implied star formation rate is nearing the maximum starburst intensity limit.

  3. Luminosity Function of Faint Globular Clusters in M87

    NASA Astrophysics Data System (ADS)

    Waters, Christopher Z.; Zepf, Stephen E.; Lauer, Tod R.; Baltz, Edward A.; Silk, Joseph

    2006-10-01

    We present the luminosity function to very faint magnitudes for the globular clusters in M87, based on a 30 orbit Hubble Space Telescope (HST) WFPC2 imaging program. The very deep images and corresponding improved false source rejection allow us to probe the mass function further beyond the turnover than has been done before. We compare our luminosity function to those that have been observed in the past, and confirm the similarity of the turnover luminosity between M87 and the Milky Way. We also find with high statistical significance that the M87 luminosity function is broader than that of the Milky Way. We discuss how determining the mass function of the cluster system to low masses can constrain theoretical models of the dynamical evolution of globular cluster systems. Our mass function is consistent with the dependence of mass loss on the initial cluster mass given by classical evaporation, and somewhat inconsistent with newer proposals that have a shallower mass dependence. In addition, the rate of mass loss is consistent with standard evaporation models, and not with the much higher rates proposed by some recent studies of very young cluster systems. We also find that the mass-size relation has very little slope, indicating that there is almost no increase in the size of a cluster with increasing mass.

  4. Study of the spray to globular transition in gas metal arc welding: a spectroscopic investigation

    NASA Astrophysics Data System (ADS)

    Valensi, F.; Pellerin, S.; Castillon, Q.; Boutaghane, A.; Dzierzega, K.; Zielinska, S.; Pellerin, N.; Briand, F.

    2013-06-01

    The gas metal arc welding (GMAW) process is strongly influenced by the composition of the shielding gas. In particular, addition of CO2 increases the threshold current for the transition from unstable globular to more stable spray transfer mode. We report on the diagnostics—using optical emission spectroscopy—of a GMAW plasma in pure argon and in mixtures of argon, CO2 and N2 while operated in spray and globular transfer modes. The spatially resolved plasma parameters are obtained by applying the Abel transformation to laterally integrated emission data. The Stark widths of some iron lines are used to determine both electron density and temperature, and line intensities yield relative contents of neutral and ionized iron to argon. Our experimental results indicate a temperature drop on the arc axis in the case of spray arc transfer. This drop reduces with addition of N2 and disappears in globular transfer mode when CO2 is added. Despite the temperature increase, the electron density decreases with CO2 concentration. The highest concentration of iron is observed in the plasma column upper part (close to the anode) and for GMAW with CO2. Our results are compared with recently published works where the effect of non-homogeneous metal vapour concentration has been taken into account.

  5. CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Statistical interior properties of globular proteins

    NASA Astrophysics Data System (ADS)

    Jiang, Zhou-Ting; Zhang, Lin-Xi; Sun, Ting-Ting; Wu, Tai-Quan

    2009-10-01

    The character of forming long-range contacts affects the three-dimensional structure of globular proteins deeply. As the different ability to form long-range contacts between 20 types of amino acids and 4 categories of globular proteins, the statistical properties are thoroughly discussed in this paper. Two parameters NC and ND are defined to confine the valid residues in detail. The relationship between hydrophobicity scales and valid residue percentage of each amino acid is given in the present work and the linear functions are shown in our statistical results. It is concluded that the hydrophobicity scale defined by chemical derivatives of the amino acids and nonpolar phase of large unilamellar vesicle membranes is the most effective technique to characterise the hydrophobic behavior of amino acid residues. Meanwhile, residue percentage Pi and sequential residue length Li of a certain protein i are calculated under different conditions. The statistical results show that the average value of Pi as well as Li of all-α proteins has a minimum among these 4 classes of globular proteins, indicating that all-α proteins are hardly capable of forming long-range contacts one by one along their linear amino acid sequences. All-β proteins have a higher tendency to construct long-range contacts along their primary sequences related to the secondary configurations, i.e. parallel and anti-parallel configurations of β sheets. The investigation of the interior properties of globular proteins give us the connection between the three-dimensional structure and its primary sequence data or secondary configurations, and help us to understand the structure of protein and its folding process well.

  6. Keap1/Cullin3 Modulates p62/SQSTM1 Activity via UBA Domain Ubiquitination.

    PubMed

    Lee, YouJin; Chou, Tsui-Fen; Pittman, Sara K; Keith, Amy L; Razani, Babak; Weihl, Conrad C

    2017-04-04

    p62/SQSTM1 (p62) is a scaffolding protein that facilitates the formation and degradation of ubiquitinated aggregates via its self-interaction and ubiquitin binding domains. The regulation of this process is unclear but may relate to the post-translational modification of p62. In the present study, we find that Keap1/Cullin3 ubiquitinates p62 at lysine 420 within its UBA domain. Substitution of lysine 420 with an arginine diminishes p62 sequestration and degradation activity similar what is seen when the UBA domain is deleted. Overexpression of Keap1/Cullin3 in p62-WT-expressing cells increases ubiquitinated inclusion formation and p62's association with LC3 and rescues proteotoxicity. This effect is not seen in cells expressing a mutant p62 that fails to interact with Keap1. Interestingly, p62 disease mutants have diminished or absent UBA domain ubiquitination. These data suggest that the ubiquitination of p62's UBA domain at lysine 420 may regulate p62's function and be disrupted in p62-associated disease. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Starch Binding Domain-containing Protein 1 Plays a Dominant Role in Glycogen Transport to Lysosomes in Liver.

    PubMed

    Sun, Tao; Yi, Haiqing; Yang, Chunyu; Kishnani, Priya S; Sun, Baodong

    2016-08-05

    A small portion of cellular glycogen is transported to and degraded in lysosomes by acid α-glucosidase (GAA) in mammals, but it is unclear why and how glycogen is transported to the lysosomes. Stbd1 has recently been proposed to participate in glycogen trafficking to lysosomes. However, our previous study demonstrated that knockdown of Stbd1 in GAA knock-out mice did not alter lysosomal glycogen storage in skeletal muscles. To further determine whether Stbd1 participates in glycogen transport to lysosomes, we generated GAA/Stbd1 double knock-out mice. In fasted double knock-out mice, glycogen accumulation in skeletal and cardiac muscles was not affected, but glycogen content in liver was reduced by nearly 73% at 3 months of age and by 60% at 13 months as compared with GAA knock-out mice, indicating that the transport of glycogen to lysosomes was suppressed in liver by the loss of Stbd1. Exogenous expression of human Stbd1 in double knock-out mice restored the liver lysosomal glycogen content to the level of GAA knock-out mice, as did a mutant lacking the Atg8 family interacting motif (AIM) and another mutant that contains only the N-terminal 24 hydrophobic segment and the C-terminal starch binding domain (CBM20) interlinked by an HA tag. Our results demonstrate that Stbd1 plays a dominant role in glycogen transport to lysosomes in liver and that the N-terminal transmembrane region and the C-terminal CBM20 domain are critical for this function. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Integrated light chemical tagging analyses of seven M31 outer halo globular clusters from the Pan-Andromeda Archaeological Survey

    NASA Astrophysics Data System (ADS)

    Sakari, Charli M.; Venn, Kim A.; Mackey, Dougal; Shetrone, Matthew D.; Dotter, Aaron; Ferguson, Annette M. N.; Huxor, Avon

    2015-04-01

    Detailed chemical abundances are presented for seven M31 outer halo globular clusters (with projected distances from M31 greater than 30 kpc), as derived from high-resolution integrated light spectra taken with the Hobby-Eberly Telescope. Five of these clusters were recently discovered in the Pan-Andromeda Archaeological Survey (PAndAS) - this paper presents the first determinations of integrated Fe, Na, Mg, Ca, Ti, Ni, Ba, and Eu abundances for these clusters. Four of the target clusters (PA06, PA53, PA54, and PA56) are metal poor ([Fe/H] < -1.5), α-enhanced (though they are possibly less α-enhanced than Milky Way stars at the 1σ level), and show signs of star-to-star Na and Mg variations. The other three globular clusters (H10, H23, and PA17) are more metal rich, with metallicities ranging from [Fe/H] = -1.4 to -0.9. While H23 is chemically similar to Milky Way field stars, Milky Way globular clusters, and other M31 clusters, H10 and PA17, have moderately low [Ca/Fe], compared to Milky Way field stars and clusters. Additionally, PA17's high [Mg/Ca] and [Ba/Eu] ratios are distinct from Milky Way stars, and are in better agreement with the stars and clusters in the Large Magellanic Cloud. None of the clusters studied here can be conclusively linked to any of the identified streams from PAndAS; however, based on their locations, kinematics, metallicities, and detailed abundances, the most metal-rich PAndAS clusters H23 and PA17 may be associated with the progenitor of the Giant Stellar Stream, H10 may be associated with the SW cloud, and PA53 and PA56 may be associated with the eastern cloud.

  9. The properties of the disk system of globular clusters

    NASA Technical Reports Server (NTRS)

    Armandroff, Taft E.

    1989-01-01

    A large refined data sample is used to study the properties and origin of the disk system of globular clusters. A scale height for the disk cluster system of 800-1500 pc is found which is consistent with scale-height determinations for samples of field stars identified with the Galactic thick disk. A rotational velocity of 193 + or - 29 km/s and a line-of-sight velocity dispersion of 59 + or - 14 km/s have been found for the metal-rich clusters.

  10. The optimal SAM surface functional group for producing a biomimetic HA coating on Ti.

    PubMed

    Liu, D P; Majewski, P; O'Neill, B K; Ngothai, Y; Colby, C B

    2006-06-15

    Commercial interest is growing in biomimetic methods that employ self assembled mono-layers (SAMs) to produce biocompatible HA coatings on Ti-based orthopedic implants. Recently, separate studies have considered HA formation for various SAM surface functional groups. However, these have often neglected to verify crystallinity of the HA coating, which is essential for optimal bioactivity. Furthermore, differing experimental and analytical methods make performance comparisons difficult. This article investigates and evaluates HA formation for four of the most promising surface functional groups: --OH, --SO(3)H, --PO(4)H(2) and --COOH. All of them successfully formed a HA coating at Ca/P ratios between 1.49 and 1.62. However, only the --SO(3)H and --COOH end groups produced a predominantly crystalline HA. Furthermore, the --COOH end group yielded the thickest layer and possessed crystalline characteristics very similar to that of the human bone. The --COOH end group appears to provide the optimal SAM surface interface for nucleation and growth of biomimetic crystalline HA. Intriguingly, this finding may lend support to explanations elsewhere of why human bone sialoprotein is such a potent nucleator of HA and is attributed to the protein's glutamic acid-rich sequences.

  11. Registration of two double rust resistant germplasms, HA-R12 and HA-R13 for confection sunflower

    USDA-ARS?s Scientific Manuscript database

    The confection sunflower (Helianthus annuus L.) germplasms HA-R12 (Reg. No. ______, PI 673104) and HA-R13 (Reg. No. ______, PI 673105) were developed by the USDA-ARS, Sunflower and Plant Biology Research Unit in collaboration with the North Dakota Agricultural Experiment Station, and released in Jul...

  12. C1q/TNF-related Protein 4 (CTRP4) Is a Unique Secreted Protein with Two Tandem C1q Domains That Functions in the Hypothalamus to Modulate Food Intake and Body Weight*

    PubMed Central

    Byerly, Mardi S.; Petersen, Pia S.; Ramamurthy, Santosh; Seldin, Marcus M.; Lei, Xia; Provost, Elayne; Wei, Zhikui; Ronnett, Gabriele V.; Wong, G. William

    2014-01-01

    CTRP4 is a unique member of the C1q family, possessing two tandem globular C1q domains. Its physiological function is poorly defined. Here, we show that CTRP4 is an evolutionarily conserved, ∼34-kDa secretory protein expressed in the brain. In human, mouse, and zebrafish brain, CTRP4 expression begins early in development and is widespread in the central nervous system. Neurons, but not astrocytes, express and secrete CTRP4, and secreted proteins form higher-order oligomeric complexes. CTRP4 is also produced by peripheral tissues and circulates in blood. Its serum levels are increased in leptin-deficient obese (ob/ob) mice. Functional studies suggest that CTRP4 acts centrally to modulate energy metabolism. Refeeding following an overnight fast induced the expression of CTRP4 in the hypothalamus. Central administration of recombinant protein suppressed food intake and altered the whole-body energy balance in both chow-fed and high-fat diet-fed mice. Suppression of food intake by CTRP4 is correlated with a decreased expression of orexigenic neuropeptide (Npy and Agrp) genes in the hypothalamus. These results establish CTRP4 as a novel nutrient-responsive central regulator of food intake and energy balance. PMID:24366864

  13. Nanocrystallized SrHA/SrHA SrTiO3/SrTiO3 TiO2 multilayer coatings formed by micro-arc oxidation for photocatalytic application

    NASA Astrophysics Data System (ADS)

    Han, Y.; Chen, D. H.; Zhang, L.

    2008-08-01

    Novel photocatalytic coatings containing strontium hydroxyapatite (SrHA), strontium titanate (SrTiO3), and TiO2 were formed by micro-arc oxidation (MAO) in an aqueous electrolyte containing strontium acetate and β-glycerophosphate disodium at 530 V for 0.1-5 min. The structure evolution of the coatings was investigated as a function of processing time, and the photocatalytic activity of the coatings was evaluated by measuring the decomposition rate of methyl orange under ultraviolet irradiation. During the MAO processing of the coatings, it was observed that some granules appeared in the electrolyte adjacent to the anode and they increased in amount as the processing time was prolonged. The obtained results show that the granules are amorphous and poorly crystallized SrHA with negative charges. The coating prepared for 5 min presents a microporous structure of SrHA/SrHA-SrTiO3/SrTiO3-TiO2 multilayers, in which the SrHA outermost layer and the SrHA-SrTiO3 intermediate layer are nanocrystallized. It is suggested that formation of the granules, electro-migration of the granules onto the pre-formed layer, and crystallization of the adhered granules are possible mechanisms for the formation of a SrHA/SrHA-SrTiO3/SrTiO3-TiO2 multilayer coating. This coating shows much higher photocatalytic decomposition efficiency relative to the MAO-formed TiO2 coating, and is expected to have an important photocatalytic application.

  14. Dynamical evolution and spatial mixing of multiple population globular clusters

    NASA Astrophysics Data System (ADS)

    Vesperini, Enrico; McMillan, Stephen L. W.; D'Antona, Francesca; D'Ercole, Annibale

    2013-03-01

    Numerous spectroscopic and photometric observational studies have provided strong evidence for the widespread presence of multiple stellar populations in globular clusters. In this paper, we study the long-term dynamical evolution of multiple population clusters, focusing on the evolution of the spatial distributions of the first- (FG) and second-generation (SG) stars. In previous studies, we have suggested that SG stars formed from the ejecta of FG AGB stars are expected initially to be concentrated in the cluster inner regions. Here, by means of N-body simulations, we explore the time-scales and the dynamics of the spatial mixing of the FG and the SG populations and their dependence on the SG initial concentration. Our simulations show that, as the evolution proceeds, the radial profile of the SG/FG number ratio, NSG/NFG, is characterized by three regions: (1) a flat inner part; (2) a declining part in which FG stars are increasingly dominant and (3) an outer region where the NSG/NFG profile flattens again (the NSG/NFG profile may rise slightly again in the outermost cluster regions). Until mixing is complete and the NSG/NFG profile is flat over the entire cluster, the radial variation of NSG/NFG implies that the fraction of SG stars determined by observations covering a limited range of radial distances is not, in general, equal to the SG global fraction, (NSG/NFG)glob. The distance at which NSG/NFG equals (NSG/NFG)glob is approximately between 1 and 2 cluster half-mass radii. The time-scale for complete mixing depends on the SG initial concentration, but in all cases complete mixing is expected only for clusters in advanced evolutionary phases, having lost at least 60-70 per cent of their mass due to two-body relaxation (in addition to the early FG loss due to the cluster expansion triggered by SNII ejecta and gas expulsion).The results of our simulations suggest that in many Galactic globular clusters the SG should still be more spatially concentrated than the

  15. Models of globular proteins in aqueous solutions

    NASA Astrophysics Data System (ADS)

    Wentzel, Nathaniel James

    Protein crystallization is a continuing area of research. Currently, there is no universal theory for the conditions required to crystallize proteins. A better understanding of protein crystallization will be helpful in determining protein structure and preventing and treating certain diseases. In this thesis, we will extend the understanding of globular proteins in aqueous solutions by analyzing various models for protein interactions. Experiments have shown that the liquid-liquid phase separation curves for lysozyme in solution with salt depend on salt type and salt concentration. We analyze a simple square well model for this system whose well depth depends on salt type and salt concentration, to determine the phase coexistence surfaces from experimental data. The surfaces, calculated from a single Monte Carlo simulation and a simple scaling argument, are shown as a function of temperature, salt concentration and protein concentration for two typical salts. Urate Oxidase from Asperigillus flavus is a protein used for studying the effects of polymers on the crystallization of large proteins. Experiments have determined some aspects of the phase diagram. We use Monte Carlo techniques and perturbation theory to predict the phase diagram for a model of urate oxidase in solution with PEG. The model used includes an electrostatic interaction, van der Waals attraction, and a polymerinduced depletion interaction. The results agree quantitatively with experiments. Anisotropy plays a role in globular protein interactions, including the formation of hemoglobin fibers in sickle cell disease. Also, the solvent conditions have been shown to play a strong role in the phase behavior of some aqueous protein solutions. Each has previously been treated separately in theoretical studies. Here we propose and analyze a simple, combined model that treats both anisotropy and solvent effects. We find that this model qualitatively explains some phase behavior, including the existence of

  16. Hubble Admires a Youthful Globular Star Cluster

    NASA Image and Video Library

    2017-12-08

    Hubble sees an unusal global cluster that is enriching the interstellar medium with metals Globular clusters offer some of the most spectacular sights in the night sky. These ornate spheres contain hundreds of thousands of stars, and reside in the outskirts of galaxies. The Milky Way contains over 150 such clusters — and the one shown in this NASA/ESA Hubble Space Telescope image, named NGC 362, is one of the more unusual ones. As stars make their way through life they fuse elements together in their cores, creating heavier and heavier elements — known in astronomy as metals — in the process. When these stars die, they flood their surroundings with the material they have formed during their lifetimes, enriching the interstellar medium with metals. Stars that form later therefore contain higher proportions of metals than their older relatives. By studying the different elements present within individual stars in NGC 362, astronomers discovered that the cluster boasts a surprisingly high metal content, indicating that it is younger than expected. Although most globular clusters are much older than the majority of stars in their host galaxy, NGC 362 bucks the trend, with an age lying between 10 and 11 billion years old. For reference, the age of the Milky Way is estimated to be above 13 billion years. This image, in which you can view NGC 362’s individual stars, was taken by Hubble’s Advanced Camera for Surveys (ACS). Credit: ESA/Hubble& NASA NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  17. Biogenesis of influenza a virus hemagglutinin cross-protective stem epitopes.

    PubMed

    Magadán, Javier G; Altman, Meghan O; Ince, William L; Hickman, Heather D; Stevens, James; Chevalier, Aaron; Baker, David; Wilson, Patrick C; Ahmed, Rafi; Bennink, Jack R; Yewdell, Jonathan W

    2014-06-01

    Antigenic variation in the globular domain of influenza A virus (IAV) hemagglutinin (HA) precludes effective immunity to this major human pathogen. Although the HA stem is highly conserved between influenza virus strains, HA stem-reactive antibodies (StRAbs) were long considered biologically inert. It is now clear, however, that StRAbs reduce viral replication in animal models and protect against pathogenicity and death, supporting the potential of HA stem-based immunogens as drift-resistant vaccines. Optimally designing StRAb-inducing immunogens and understanding StRAb effector functions require thorough comprehension of HA stem structure and antigenicity. Here, we study the biogenesis of HA stem epitopes recognized in cells infected with various drifted IAV H1N1 strains using mouse and human StRAbs. Using a novel immunofluorescence (IF)-based assay, we find that human StRAbs bind monomeric HA in the endoplasmic reticulum (ER) and trimerized HA in the Golgi complex (GC) with similar high avidity, potentially good news for producing effective monomeric HA stem immunogens. Though HA stem epitopes are nestled among several N-linked oligosaccharides, glycosylation is not required for full antigenicity. Rather, as N-linked glycans increase in size during intracellular transport of HA through the GC, StRAb binding becomes temperature-sensitive, binding poorly to HA at 4°C and well at 37°C. A de novo designed, 65-residue protein binds the mature HA stem independently of temperature, consistent with a lack of N-linked oligosaccharide steric hindrance due to its small size. Likewise, StRAbs bind recombinant HA carrying simple N-linked glycans in a temperature-independent manner. Chemical cross-linking experiments show that N-linked oligosaccharides likely influence StRAb binding by direct local effects rather than by globally modifying the conformational flexibility of HA. Our findings indicate that StRAb binding to HA is precarious, raising the possibility that

  18. La galaxia NGC 6876 y su sistema de cúmulos globulares

    NASA Astrophysics Data System (ADS)

    Ennis, A. I.; Bassino, L. P.; Caso, J. P.

    2017-10-01

    We present preliminary results of the deep photometric study of the elliptical galaxy NGC6876, located at the center of the Pavo group, and its globular cluster system. We use images obtained with the GMOS camera mounted on the Gemini South telescope, in the and bands, with the purpose of disentangling the evolutionary history of the galaxy on the basis of their characteristics.

  19. The Scale Sizes of Globular Clusters: Tidal Limits, Evolution, and the Outer Halo

    NASA Astrophysics Data System (ADS)

    Harris, William

    2011-10-01

    The physical factors that determine the linear sizes of massive star clusters are not well understood. Their scale sizes were long thought to be governed by the tidal field of the parent galaxy, but major questions are now emerging. Globular clusters, for example, have mean sizes nearly independent of location in the halo. Paradoxically, the recently discovered "anomalous extended clusters" in M31 and elsewhere have scale sizes that fit much better with tidal theory, but they are puzzlingly rare. Lastly, the persistent size difference between metal-poor and metal-rich clusters still lacks a quantitative explanation. Many aspects of these observations call for better modelling of dynamical evolution in the outskirts of clusters, and also their conditions of formation including the early rapid mass loss phase of protoclusters. A new set of accurate measurements of scale sizes and structural parameters, for a large and homogeneous set of globular clusters, would represent a major advance in this subject. We propose to carry out a {WFC3+ACS} imaging survey of the globular clusters in the supergiant Virgo elliptical M87 to cover the complete run of the halo. M87 is an optimum target system because of its huge numbers of clusters and HST's ability to resolve the cluster profiles accurately. We will derive cluster effective radii, central concentrations, luminosities, and colors for more than 4000 clusters using PSF-convolved King-model profile fitting. In parallel, we are developing theoretical tools to model the expected distribution of cluster sizes versus galactocentric distance as functions of cluster mass, concentration, and orbital anisotropy.

  20. Abundance of intrinsic structural disorder in the histone H1 subtypes.

    PubMed

    Kowalski, Andrzej

    2015-12-01

    The intrinsically disordered proteins consist of partially structured regions linked to the unstructured stretches, which consequently form the transient and dynamic conformational ensembles. They undergo disorder to order transition upon binding their partners. Intrinsic disorder is attributed to histones H1, perceived as assemblers of chromatin structure and the regulators of DNA and proteins activity. In this work, the comparison of intrinsic disorder abundance in the histone H1 subtypes was performed both by the analysis of their amino acid composition and by the prediction of disordered stretches, as well as by identifying molecular recognition features (MoRFs) and ANCHOR protein binding regions (APBR) that are responsible for recognition and binding. Both human and model organisms-animals, plants, fungi and protists-have H1 histone subtypes with the properties typical of disordered state. They possess a significantly higher content of hydrophilic and charged amino acid residues, arranged in the long regions, covering over half of the whole amino acid residues in chain. Almost complete disorder corresponds to histone H1 terminal domains, including MoRFs and ANCHOR. Those motifs were also identified in a more ordered histone H1 globular domain. Compared to the control (globular and fibrous) proteins, H1 histones demonstrate the increased folding rate and a higher proportion of low-complexity segments. The results of this work indicate that intrinsic disorder is an inherent structural property of histone H1 subtypes and it is essential for establishing a protein conformation which defines functional outcomes affecting on DNA- and/or partner protein-dependent cell processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Eisosomes Are Dynamic Plasma Membrane Domains Showing Pil1-Lsp1 Heteroligomer Binding Equilibrium

    PubMed Central

    Olivera-Couto, Agustina; Salzman, Valentina; Mailhos, Milagros; Digman, Michelle A.; Gratton, Enrico; Aguilar, Pablo S.

    2015-01-01

    Eisosomes are plasma membrane domains concentrating lipids, transporters, and signaling molecules. In the budding yeast Saccharomyces cerevisiae, these domains are structured by scaffolds composed mainly by two cytoplasmic proteins Pil1 and Lsp1. Eisosomes are immobile domains, have relatively uniform size, and encompass thousands of units of the core proteins Pil1 and Lsp1. In this work we used fluorescence fluctuation analytical methods to determine the dynamics of eisosome core proteins at different subcellular locations. Using a combination of scanning techniques with autocorrelation analysis, we show that Pil1 and Lsp1 cytoplasmic pools freely diffuse whereas an eisosome-associated fraction of these proteins exhibits slow dynamics that fit with a binding-unbinding equilibrium. Number and brightness analysis shows that the eisosome-associated fraction is oligomeric, while cytoplasmic pools have lower aggregation states. Fluorescence lifetime imaging results indicate that Pil1 and Lsp1 directly interact in the cytoplasm and within the eisosomes. These results support a model where Pil1-Lsp1 heterodimers are the minimal eisosomes building blocks. Moreover, individual-eisosome fluorescence fluctuation analysis shows that eisosomes in the same cell are not equal domains: while roughly half of them are mostly static, the other half is actively exchanging core protein subunits. PMID:25863055

  2. Integrated J- and H-band spectra of globular clusters in the LMC: implications for stellar population models and galaxy age dating

    NASA Astrophysics Data System (ADS)

    Lyubenova, M.; Kuntschner, H.; Rejkuba, M.; Silva, D. R.; Kissler-Patig, M.; Tacconi-Garman, L. E.

    2012-07-01

    Context. The rest-frame near-IR spectra of intermediate age (1-2 Gyr) stellar populations are dominated by carbon based absorption features offering a wealth of information. Yet, spectral libraries that include the near-IR wavelength range do not sample a sufficiently broad range of ages and metallicities to allow for accurate calibration of stellar population models and thus the interpretation of the observations. Aims: In this paper we investigate the integrated J- and H-band spectra of six intermediate age and old globular clusters in the Large Magellanic Cloud (LMC). Methods: The observations for six clusters were obtained with the SINFONI integral field spectrograph at the ESO VLT Yepun telescope, covering the J (1.09-1.41 μm) and H-band (1.43-1.86 μm) spectral range. The spectral resolution is 6.7 Å in J and 6.6 Å in H-band (FWHM). The observations were made in natural seeing, covering the central 24″ × 24″ of each cluster and in addition sampling the brightest eight red giant branch and asymptotic giant branch (AGB) star candidates within the clusters' tidal radii. Targeted clusters cover the ages of ~1.3 Gyr (NGC 1806, NGC 2162), 2 Gyr (NGC 2173) and ~13 Gyr (NGC 1754, NGC 2005, NGC 2019). Results.H-band C2 and K-band 12CO (2-0) feature strengths for the LMC globular clusters are compared to the models of Maraston (2005). C2 is reasonably well reproduced by the models at all ages, while 12CO (2-0) shows good agreement for older (age ≥ 2 Gyr) populations, but the younger (1.3 Gyr) globular clusters do not follow the models. We argue that this is due to the fact that the empirical calibration of the models relies on only a few Milky Way carbon star spectra, which show different 12CO (2-0) index strengths than the LMC stars. The C2 absorption feature strength correlates strongly with age. It is present essentially only in populations that have 1-2 Gyr old stars, while its value is consistent with zero for older populations. The distinct spectral

  3. The Low-Mass X-Ray Binary X1832-330 in the Globular Cluster NGC 6652: A Serendipitous ASCA Observation

    NASA Technical Reports Server (NTRS)

    Mukai, Koji; Smale, Alan P.

    1999-01-01

    The Low Mass X-ray Binary (LMXB) X1832-330 in NGC 6652 is one of about 10 bright X-ray sources to have been discovered in Globular Clusters. We report on a serendipitous ASCA observation of this Globular Cluster LMXB, during which a Type I burst was detected and the persistent, non-burst emission of the source was at its brightest level recorded to date. No orbital modulation was detected, which argues against a high inclination for the X1832-330 system. The spectrum of the persistent emission can be fit with a power law plus a partial covering absorber, although other models are not ruled out. Our time-resolved spectral analysis through the burst shows, for the first time, clear evidence for spectral cooling from kT = 2.4 +/- 0.6 keV to kT = 1.0 +/- 0.1 keV during the decay. The measured peak flux during the burst is approximately 10% of the Eddington luminosity for a 1.4 Solar Mass neutron star. These are characteristic of a Type I burst, in the context of the relatively low quiescent luminosity of X1832-330.

  4. Growth of chronic myeloid leukemia cells is inhibited by infection with Ad-SH2-HA adenovirus that disrupts Grb2-Bcr-Abl complexes.

    PubMed

    Peng, Zhi; Luo, Hong-Wei; Yuan, Ying; Shi, Jing; Huang, Shi-Feng; Li, Chun-Li; Cao, Wei-Xi; Huang, Zong-Gan; Feng, Wen-Li

    2011-05-01

    The persistence of Bcr-Abl-positive cells in patients on imatinib therapy indicates that inhibition of the Bcr-Abl kinase activity alone might not be sufficient to eradicate the leukemia cells. Many downstream effectors of Bcr-Abl have been described, including activation of both the Grb2-SoS-Ras-MAPK and Grb2-Gab2-PI3K-Akt pathways. The Bcr-Abl-Grb2 interaction, which is mediated by the direct interaction of the Grb2 SH2 domain with the phospho-Bcr-Abl Y177, is required for activation of these signaling pathways. Therefore, disrupting their interaction represents a potential therapeutic strategy for inhibiting the oncogenic downstream signals of Bcr-Abl. Adenovirus Ad-SH2-HA expressing the Grb2 SH2 domain was constructed and applied in this study. As expected, Ad-SH2-HA efficiently infected CML cells and functioned by binding to the phospho-Bcr-Abl Y177 site, competitively disrupting the Grb2 SH2-phospho-Bcr-Abl Y177 complex. They induced potent anti-proliferation and apoptosis-inducing effects in CML cell lines. Moreover, the Ras, MAPK and Akt activities were significantly reduced in the Ad-SH2-HA treated cells. These were not observed with the point-mutated control adenovirus Ad-Sm-HA with abolished phospho-Bcr-Abl Y177 binding sites. These data indicate that, in addition to the direct targeting of Bcr-Abl, selective inhibition of its downstream signaling pathways may be a therapeutic option for CML, and the Ad-SH2-HA-mediated killing strategy could be explored as a promising anti-leukemia agent in CML.

  5. HVOF-Sprayed Nano TiO2-HA Coatings Exhibiting Enhanced Biocompatibility

    NASA Astrophysics Data System (ADS)

    Lima, R. S.; Dimitrievska, S.; Bureau, M. N.; Marple, B. R.; Petit, A.; Mwale, F.; Antoniou, J.

    2010-01-01

    Biomedical thermal spray coatings produced via high-velocity oxy-fuel (HVOF) from nanostructured titania (n-TiO2) and 10 wt.% hydroxyapatite (HA) (n-TiO2-10wt.%HA) powders have been engineered as possible future alternatives to HA coatings deposited via air plasma spray (APS). This approach was chosen due to (i) the stability of TiO2 in the human body (i.e., no dissolution) and (ii) bond strength values on Ti-6Al-4V substrates more than two times higher than those of APS HA coatings. To explore the bioperformance of these novel materials and coatings, human mesenchymal stem cells (hMSCs) were cultured from 1 to 21 days on the surface of HVOF-sprayed n-TiO2 and n-TiO2-10 wt.%HA coatings. APS HA coatings and uncoated Ti-6Al-4V substrates were employed as controls. The profiles of the hMSCs were evaluated for (i) cellular proliferation, (ii) biochemical analysis of alkaline phosphatase (ALP) activity, (iii) cytoskeleton organization (fluorescent/confocal microscopy), and (iv) cell/substrate interaction via scanning electron microscopy (SEM). The biochemical analysis indicated that the hMSCs cultured on n-TiO2-10 wt.%HA coatings exhibited superior levels of bioactivity than hMSCs cultured on APS HA and pure n-TiO2 coatings. The cytoskeleton organization demonstrated a higher degree of cellular proliferation on the HVOF-sprayed n-TiO2-10wt.%HA coatings when compared to the control coatings. These results are considered promising for engineering improved performance in the next generation of thermally sprayed biomedical coatings.

  6. Imaging of Homeostatic, Neoplastic, and Injured Tissues by HA-Based Probes

    PubMed Central

    Veiseh, Mandana; Breadner, Daniel; Ma, Jenny; Akentieva, Natalia; Savani, Rashmin C; Harrison, Rene; Mikilus, David; Collis, Lisa; Gustafson, Stefan; Lee, Ting-Yim; Koropatnick, James; Luyt, Leonard G.; Bissell, Mina J.; Turley, Eva A.

    2013-01-01

    An increase in hyaluronan (HA) synthesis, cellular uptake, and metabolism occurs during the remodeling of tissue microenvironments following injury and during disease processes such as cancer. We hypothesized that multimodality HA-based probes selectively target and detectably accumulate at sites of high HA metabolism, thus providing a flexible imaging strategy for monitoring disease and repair processes. Kinetic analyses confirmed favorable available serum levels of the probe following intravenous (i.v.) or subcutaneous (s.c.) injection. Nuclear (technetium-HA, 99mTc-HA, and iodine-HA, 125I-HA), optical (fluorescent Texas Red-HA, TR-HA), and magnetic resonance (gadolinium-HA, Gd-HA) probes imaged liver (99mTc-HA), breast cancer cells/xenografts (TR-HA, Gd-HA), and vascular injury (125I-HA, TR-HA). Targeting of HA probes to these sites appeared to result from selective HA receptor-dependent localization. Our results suggest that HA-based probes, which do not require polysaccharide backbone modification to achieve favorable half-life and distribution, can detect elevated HA metabolism in homeostatic, injured, and diseased tissues. PMID:22066590

  7. VizieR Online Data Catalog: Globular and open clusters observed by SDSS/SEGUE (Morrison+, 2016)

    NASA Astrophysics Data System (ADS)

    Morrison, H. L.; Ma, Z.; Clem, J. L.; An, D.; Connor, T.; Schechtman-Rook, A.; Casagrande, L.; Rockosi, C.; Yanny, B.; Harding, P.; Beers, T. C.; Johnson, J. A.; Schneider, D. P.

    2018-03-01

    The SEGUE project observed a number of globular and open clusters for calibration purposes. For calibration of the red giants, we selected the globular clusters M92, M13 and M71 (spanning metallicities from -2.4 to -0.8) and the open clusters Be 29, NGC 7789 and NGC 6791, whose [Fe/H] values range from -0.4 to +0.4. In all but one case, the clusters are within the SDSS footprint and so ugriz photometry is available for the cluster stars. The SDSS cluster images were analyzed using DAOPHOT (Stetson 1987PASP...99..191S) by An et al. (2008ApJS..179..326A) because the SDSS photometric pipeline was not designed to handle crowded fields. (8 data files).

  8. Tadpole-like Conformations of Huntingtin Exon 1 Are Characterized by Conformational Heterogeneity that Persists regardless of Polyglutamine Length.

    PubMed

    Newcombe, Estella A; Ruff, Kiersten M; Sethi, Ashish; Ormsby, Angelique R; Ramdzan, Yasmin M; Fox, Archa; Purcell, Anthony W; Gooley, Paul R; Pappu, Rohit V; Hatters, Danny M

    2018-05-11

    Soluble huntingtin exon 1 (Httex1) with expanded polyglutamine (polyQ) engenders neurotoxicity in Huntington's disease. To uncover the physical basis of this toxicity, we performed structural studies of soluble Httex1 for wild-type and mutant polyQ lengths. Nuclear magnetic resonance experiments show evidence for conformational rigidity across the polyQ region. In contrast, hydrogen-deuterium exchange shows absence of backbone amide protection, suggesting negligible persistence of hydrogen bonds. The seemingly conflicting results are explained by all-atom simulations, which show that Httex1 adopts tadpole-like structures with a globular head encompassing the N-terminal amphipathic and polyQ regions and the tail encompassing the C-terminal proline-rich region. The surface area of the globular domain increases monotonically with polyQ length. This stimulates sharp increases in gain-of-function interactions in cells for expanded polyQ, and one of these interactions is with the stress-granule protein Fus. Our results highlight plausible connections between Httex1 structure and routes to neurotoxicity. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Spectroscopic Confirmation of the Dwarf Galaxies Hydra II and Pisces II and the Globular Cluster Laevens 1

    NASA Astrophysics Data System (ADS)

    Kirby, Evan N.; Simon, Joshua D.; Cohen, Judith G.

    2015-09-01

    We present Keck/DEIMOS spectroscopy of stars in the recently discovered Milky Way satellites Hydra II, Pisces II, and Laevens 1. We measured a velocity dispersion of {5.4}-2.4+3.6 km s-1 for Pisces II, but we did not resolve the velocity dispersions of Hydra II or Laevens 1. We marginally resolved the metallicity dispersions of Hydra II and Pisces II but not Laevens 1. Furthermore, Hydra II and Pisces II obey the luminosity-metallicity relation for Milky Way dwarf galaxies (< [{Fe}/{{H}}]> =-2.02+/- 0.08 and -2.45+/- 0.07, respectively), whereas Laevens 1 does not (< [{Fe}/{{H}}]> =-1.68+/- 0.05). The kinematic and chemical properties suggest that Hydra II and Pisces II are dwarf galaxies, and Laevens 1 is a globular cluster. We determined that two of the previously observed blue stars near the center of Laevens 1 are not members of the cluster. A third blue star has ambiguous membership. Hydra II has a radial velocity < {v}{helio}> =303.1+/- 1.4 km s-1, similar to the leading arm of the Magellanic stream. The mass-to-light ratio for Pisces II is {370}-240+310 {M}⊙ /{L}⊙ . It is not among the most dark matter-dominated dwarf galaxies, but it is still worthy of inclusion in the search for gamma-rays from dark matter self-annihilation. The data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation.

  10. Stellar abundances and ages for metal-rich Milky Way globular clusters. Stellar parameters and elemental abundances for 9 HB stars in NGC 6352

    NASA Astrophysics Data System (ADS)

    Feltzing, S.; Primas, F.; Johnson, R. A.

    2009-01-01

    Context: Metal-rich globular clusters provide important tracers of the formation of our Galaxy. Moreover, and not less important, they are very important calibrators for the derivation of properties of extra-galactic metal-rich stellar populations. Nonetheless, only a few of the metal-rich globular clusters in the Milky Way have been studied using high-resolution stellar spectra to derive elemental abundances. Additionally, Rosenberg et al. identified a small group of metal-rich globular clusters that appeared to be about 2 billion years younger than the bulk of the Milky Way globular clusters. However, it is unclear if like is compared with like in this dataset as we do not know the enhancement of α-elements in the clusters and the amount of α-elements is well known to influence the derivation of ages for globular clusters. Aims: We derive elemental abundances for the metal-rich globular cluster NGC 6352 and we present our methods to be used in up-coming studies of other metal-rich globular clusters. Methods: We present a study of elemental abundances for α- and iron-peak elements for nine HB stars in the metal-rich globular cluster NGC 6352. The elemental abundances are based on high-resolution, high signal-to-noise spectra obtained with the UVES spectrograph on VLT. The elemental abundances have been derived using standard LTE calculations and stellar parameters have been derived from the spectra themselves by requiring ionizational as well as excitational equilibrium. Results: We find that NGC 6352 has [Fe/H] = -0.55, is enhanced in the α-elements to about +0.2 dex for Ca, Si, and Ti relative to Fe. For the iron-peak elements we find solar values. Based on the spectroscopically derived stellar parameters we find that an E(B-V) = 0.24 and (m-M) ≃ 14.05 better fits the data than the nominal values. An investigation of log gf-values for suitable Fe i lines lead us to the conclusion that the commonly used correction to the May et al. (1974) data should not be

  11. Flexible DNA binding of the BTB/POZ-domain protein FBI-1.

    PubMed

    Pessler, Frank; Hernandez, Nouria

    2003-08-01

    POZ-domain transcription factors are characterized by the presence of a protein-protein interaction domain called the POZ or BTB domain at their N terminus and zinc fingers at their C terminus. Despite the large number of POZ-domain transcription factors that have been identified to date and the significant insights that have been gained into their cellular functions, relatively little is known about their DNA binding properties. FBI-1 is a BTB/POZ-domain protein that has been shown to modulate HIV-1 Tat trans-activation and to repress transcription of some cellular genes. We have used various viral and cellular FBI-1 binding sites to characterize the interaction of a POZ-domain protein with DNA in detail. We find that FBI-1 binds to inverted sequence repeats downstream of the HIV-1 transcription start site. Remarkably, it binds efficiently to probes carrying these repeats in various orientations and spacings with no particular rotational alignment, indicating that its interaction with DNA is highly flexible. Indeed, FBI-1 binding sites in the adenovirus 2 major late promoter, the c-fos gene, and the c-myc P1 and P2 promoters reveal variously spaced direct, inverted, and everted sequence repeats with the consensus sequence G(A/G)GGG(T/C)(C/T)(T/C)(C/T) for each repeat.

  12. Antibacterial Property of Cold-Sprayed HA-Ag/PEEK Coating

    NASA Astrophysics Data System (ADS)

    Sanpo, Noppakun; Tan, Meng Lu; Cheang, Philip; Khor, K. A.

    2009-03-01

    The antibacterial behavior of HA-Ag (silver-doped hydroxyapatite) nanopowder and their composite coatings were investigated against Escherichia coli (DH5α). HA-Ag nanopowder and PEEK (poly-ether-ether-ketone)-based HA-Ag composite powders were synthesized using in-house powder processing techniques. Bacteria culture assay of HA-Ag nanopowder and their composite powders displayed excellent bacteriostatic activity against E. coli. The antibacterial activity increased with increasing concentration of HA-Ag nanoparticle in these composite powders. These nanocomposite powders were subsequently used as feedstock to generate antibacterial coatings via cold spray technology. The ratios of HA-Ag to PEEK in their composite powders were 80:20, 60:40, 40:60, and 20:80 (wt.%). Microstructural characterization and phase analysis of feedstock powders and as-deposited coatings were carried out using FESEM/EDX and XRD. Antibacterial nanocomposite HA-Ag/PEEK coatings were successfully deposited using cold spraying parameters of 11-12 bars at preheated air temperature between 150 and 160 °C. These as-sprayed coatings of HA-Ag/PEEK composite powders comprising varying HA-Ag and PEEK ratios retained their inherent antibacterial property as verified from bacterial assay. The results indicated that the antibacterial activity increased with increasing HA-Ag nanopowder concentration in the composite powder feedstock and cold-sprayed coating.

  13. Influence of the concentrations of hyaluronic acid on the properties and biocompatibility of Cs-Gel-HA membranes.

    PubMed

    Liu, Haifeng; Yin, Yuji; Yao, Kangde; Ma, Dongrui; Cui, Lei; Cao, Yilin

    2004-08-01

    The object of this study was to investigate the relationship between the concentrations of HA solutions and the physicochemical properties and the biocompatibility of Cs-Gel-HA membranes. The addition of different concentrations of HA not only improved the wettability significantly and extended the degradation time of Cs-Gel-HA membranes, but also changed their mechanical properties. The concentration of HA had a significant influence on the biocompatibility of Cs-Gel-HA membranes. Results demonstrated that it was only the concentrations of HA in a certain range (0.01-0.1%), that could promote the cell adhesion, migration and proliferation, while the concentration of HA was above 0.1% it would either reduce or even inhibit these behaviors.

  14. The Phe105 loop of Alix Bro1 domain plays a key role in HIV-1 release

    PubMed Central

    Sette, Paola; Mu, Ruiling; Dussupt, Vincent; Jiang, Jiansheng; Snyder, Greg; Smith, Patrick; Xiao, Tsan. Sam; Bouamr, Fadila

    2011-01-01

    Summary Alix and cellular paralogs HD-PTP and Brox contain N-terminal Bro1 domains that bind ESCRT-III CHMP4. In contrast to HD-PTP and Brox, expression of the Bro1 domain of Alix alleviates HIV-1 release defects due to interrupted access to ESCRT. In an attempt to elucidate this functional discrepancy, we solved the crystal structures of the Bro1 domains of HD-PTP and Brox. They revealed typical “boomerang” folds they share with the Bro1 Alix domain. However, they each contain unique structural features that may be relevant to their specific function(s). In particular, phenylalanine residue in position 105 (Phe105) of Alix belongs to a long loop that is unique to its Bro1 domain. Concurrently mutation of Phe105 and surrounding residues at the tip of the loop compromises the function of Alix in HIV-1 budding without affecting its interactions with Gag or CHMP4. These studies identify a new functional determinant in the Bro1 domain of Alix. PMID:21889351

  15. Rubidium and Lead Abundances in Giant Stars of the Globular Clusters M13 and NGC 6752

    NASA Astrophysics Data System (ADS)

    Yong, David; Aoki, Wako; Lambert, David L.; Paulson, Diane B.

    2006-03-01

    We present measurements of the neutron-capture elements Rb and Pb in five giant stars of the globular cluster NGC 6752 and Pb measurements in four giants of the globular cluster M13. The abundances were derived by comparing synthetic spectra with high-resolution, high signal-to-noise ratio spectra obtained using HDS on the Subaru telescope and MIKE on the Magellan telescope. The program stars span the range of the O-Al abundance variation. In NGC 6752, the mean abundances are [Rb/Fe]=-0.17+/-0.06 (σ=0.14), [Rb/Zr]=-0.12+/-0.06 (σ=0.13), and [Pb/Fe]=-0.17+/-0.04 (σ=0.08). In M13 the mean abundance is [Pb/Fe]=-0.28+/-0.03 (σ=0.06). Within the measurement uncertainties, we find no evidence for star-to-star variation for either Rb or Pb within these clusters. None of the abundance ratios [Rb/Fe], [Rb/Zr], or [Pb/Fe] are correlated with the Al abundance. NGC 6752 may have slightly lower abundances of [Rb/Fe] and [Rb/Zr] compared to the small sample of field stars at the same metallicity. For M13 and NGC 6752 the Pb abundances are in accord with predictions from a Galactic chemical evolution model. If metal-poor intermediate-mass asymptotic giant branch stars did produce the globular cluster abundance anomalies, then such stars do not synthesize significant quantities of Rb or Pb. Alternatively, if such stars do synthesize large amounts of Rb or Pb, then they are not responsible for the abundance anomalies seen in globular clusters. Based in part on data collected at the Subaru Telescope, which is operated by the National Astronomical Observatory of Japan, and on observations made with the Magellan Clay Telescope at Las Campanas Observatory.

  16. Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome.

    PubMed

    Saturveithan, C; Premganesh, G; Fakhrizzaki, S; Mahathir, M; Karuna, K; Rauf, K; William, H; Akmal, H; Sivapathasundaram, N; Jaspreet, K

    2016-07-01

    Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option.

  17. Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome

    PubMed Central

    Premganesh, G; Fakhrizzaki, S; Mahathir, M; Karuna, K; Rauf, K; William, H; Akmal, H; Sivapathasundaram, N; Jaspreet, K

    2016-01-01

    Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option. PMID:28435559

  18. Constraints on Helium Enhancement in the Globular Cluster M3 (NGC 5272): The Horizontal Branch Test

    NASA Technical Reports Server (NTRS)

    Catelan, M.; Grundahl, F.; Sweigart, A. V.; Valcarce, A. A. R.; Cortes, C.

    2007-01-01

    It has recently been suggested that the presence of multiple populations showing various amounts of helium enhancement is a common feature among globular star clusters. In this scenario, such a helium enhancement would be particularly apparent in the enhanced luminosity of thc blue horizontal branch (HB) stars compared to the red HB stars. In this Letter, wc test this scenario in the case of the Galactic globular cluster M3 (NGC 5272), using high-precision Stromgren photometry and spectroscopic gravities for blue HB stars. We find that any helium enhancement among the cluster's blue HB stars must be significantly less than I%, thus ruling out the much higher helium enhancements that have been proposed in the literature.

  19. Neutron stars and millisecond pulsars from accretion-induced collapse in globular clusters

    NASA Technical Reports Server (NTRS)

    Bailyn, Charles D.; Grindlay, Jonathan E.

    1990-01-01

    This paper examines the limits on the number of millisecond pulsars which could be formed in globular clusters by the generally accepted scenario (in which a neutron star is created by the supernova of an initially massive star and subsequently captures a companion to form a low-mass X-ray binary which eventually becomes a millisecond pulsar). It is found that, while the number of observed low-mass X-ray binaries can be adequately explained in this way, the reasonable assumption that the pulsar luminosity function in clusters extends below the current observational limits down to the luminosity of the faintest millisecond pulsars in the field suggests a cluster population of millisecond pulsars which is substantially larger than the standard model can produce. Alleviating this problem by postulating much shorter lifetimes for the X-ray binaries requires massive star populations sufficiently large that the mass loss resulting from their evolution would be likely to unbind the cluster. It is argued that neutron star formation in globular clusters by accretion-induced collapse of white dwarfs may resolve the discrepancy in birthrates.

  20. Glycosylation of Residue 141 of Subtype H7 Influenza A Hemagglutinin (HA) Affects HA-Pseudovirus Infectivity and Sensitivity to Site A Neutralizing Antibodies.

    PubMed

    Alvarado-Facundo, Esmeralda; Vassell, Russell; Schmeisser, Falko; Weir, Jerry P; Weiss, Carol D; Wang, Wei

    2016-01-01

    Human infections with H7 subtype influenza virus have been reported, including an H7N7 outbreak in Netherlands in 2003 and H7N9 infections in China in 2013. Previously, we reported murine monoclonal antibodies (mAbs) that recognize the antigenic site A of H7 hemagglutinin (HA). To better understand protective immunity of H7 vaccines and vaccine candidate selection, we used these mAbs to assess the antigenic relatedness among two H7 HA isolated from past human infections and determine residues that affect susceptibility to neutralization. We found that these mAbs neutralize pseudoviruses bearing HA of A/Shanghai/02/2013(H7N9), but not A/Netherlands/219/2003(H7N7). Glycosylation of the asparagine residue at position 141 (N141) (N133, H3 HA numbering) in the HA of A/Netherlands/219/2003 HA is responsible for this resistance, and it affects the infectivity of HA-pseudoviruses. The presence of threonine at position 143 (T135, H3 HA numbering) in the HA of A/Netherlands/219/2003, rather than an alanine found in the HA of A/Shanghai/02/2013(H7N9), accounts for these differences. These results demonstrate a key role for glycosylation of residue N141 in affecting H7 influenza HA-mediated entry and sensitivity to neutralizing antibodies, which have implications for candidate vaccine design.