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Sample records for repeats fg domains

  1. Crystal structures of the human G3BP1 NTF2-like domain visualize FxFG Nup Repeat Specificity

    DEFF Research Database (Denmark)

    Vognsen, Tina Reinholdt; Möller, Ingvar Rúnar; Kristensen, Ole

    2013-01-01

    Ras GTPase Activating Protein SH3 Domain Binding Protein (G3BP) is a potential anti-cancer drug target implicated in several cellular functions. We have used protein crystallography to solve crystal structures of the human G3BP1 NTF2-like domain both alone and in complex with an FxFG Nup repeat...... crystal form might indicate a novel ligand binding site that, however, remains to be validated. The crystal structures give insight into the nuclear transportation mechanisms of G3BP and provide a basis for future structure based drug design....

  2. Crystal structure of the Xpo1p nuclear export complex bound to the SxFG/PxFG repeats of the nucleoporin Nup42p.

    Science.gov (United States)

    Koyama, Masako; Hirano, Hidemi; Shirai, Natsuki; Matsuura, Yoshiyuki

    2017-08-08

    Xpo1p (yeast CRM1) is the major nuclear export receptor that carries a plethora of proteins and ribonucleoproteins from the nucleus to cytoplasm. The passage of the Xpo1p nuclear export complex through nuclear pore complexes (NPCs) is facilitated by interactions with nucleoporins (Nups) containing extensive repeats of phenylalanine-glycine (so-called FG repeats), although the precise role of each Nup in the nuclear export reaction remains incompletely understood. Here we report structural and biochemical characterization of the interactions between the Xpo1p nuclear export complex and the FG repeats of Nup42p, a nucleoporin localized at the cytoplasmic face of yeast NPCs and has characteristic SxFG/PxFG sequence repeat motif. The crystal structure of Xpo1p-PKI-Nup42p-Gsp1p-GTP complex identified three binding sites for the SxFG/PxFG repeats on HEAT repeats 14-20 of Xpo1p. Mutational analyses of Nup42p showed that the conserved serines and prolines in the SxFG/PxFG repeats contribute to Xpo1p-Nup42p binding. Our structural and biochemical data suggest that SxFG/PxFG-Nups such as Nup42p and Nup159p at the cytoplasmic face of NPCs provide high-affinity docking sites for the Xpo1p nuclear export complex in the terminal stage of NPC passage and that subsequent disassembly of the nuclear export complex facilitates recycling of free Xpo1p back to the nucleus. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  3. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  4. The evolution of filamin – A protein domain repeat perspective

    OpenAIRE

    Light, Sara; Sagit, Rauan; Ithychanda, Sujay S.; Qin, Jun; Elofsson, Arne

    2012-01-01

    Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of rep...

  5. The evolution of filamin – A protein domain repeat perspective

    Science.gov (United States)

    Light, Sara; Sagit, Rauan; Ithychanda, Sujay S.; Qin, Jun; Elofsson, Arne

    2013-01-01

    Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates. PMID:22414427

  6. The evolution of filamin-a protein domain repeat perspective.

    Science.gov (United States)

    Light, Sara; Sagit, Rauan; Ithychanda, Sujay S; Qin, Jun; Elofsson, Arne

    2012-09-01

    Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Final Report, DE-FG01-06ER25718 Domain Decomposition and Parallel Computing

    Energy Technology Data Exchange (ETDEWEB)

    Widlund, Olof B. [New York Univ. (NYU), NY (United States). Courant Inst.

    2015-06-09

    The goal of this project is to develop and improve domain decomposition algorithms for a variety of partial differential equations such as those of linear elasticity and electro-magnetics.These iterative methods are designed for massively parallel computing systems and allow the fast solution of the very large systems of algebraic equations that arise in large scale and complicated simulations. A special emphasis is placed on problems arising from Maxwell's equation. The approximate solvers, the preconditioners, are combined with the conjugate gradient method and must always include a solver of a coarse model in order to have a performance which is independent of the number of processors used in the computer simulation. A recent development allows for an adaptive construction of this coarse component of the preconditioner.

  8. The diversity and evolution of Wolbachia ankyrin repeat domain genes.

    Directory of Open Access Journals (Sweden)

    Stefanos Siozios

    Full Text Available Ankyrin repeat domain-encoding genes are common in the eukaryotic and viral domains of life, but they are rare in bacteria, the exception being a few obligate or facultative intracellular Proteobacteria species. Despite having a reduced genome, the arthropod strains of the alphaproteobacterium Wolbachia contain an unusually high number of ankyrin repeat domain-encoding genes ranging from 23 in wMel to 60 in wPip strain. This group of genes has attracted considerable attention for their astonishing large number as well as for the fact that ankyrin proteins are known to participate in protein-protein interactions, suggesting that they play a critical role in the molecular mechanism that determines host-Wolbachia symbiotic interactions. We present a comparative evolutionary analysis of the wMel-related ankyrin repeat domain-encoding genes present in different Drosophila-Wolbachia associations. Our results show that the ankyrin repeat domain-encoding genes change in size by expansion and contraction mediated by short directly repeated sequences. We provide examples of intra-genic recombination events and show that these genes are likely to be horizontally transferred between strains with the aid of bacteriophages. These results confirm previous findings that the Wolbachia genomes are evolutionary mosaics and illustrate the potential that these bacteria have to generate diversity in proteins potentially involved in the symbiotic interactions.

  9. Nuclear import of cutaneous beta genus HPV8 E7 oncoprotein is mediated by hydrophobic interactions between its zinc-binding domain and FG nucleoporins

    Energy Technology Data Exchange (ETDEWEB)

    Onder, Zeynep; Moroianu, Junona, E-mail: moroianu@bc.edu

    2014-01-20

    We have previously discovered and characterized the nuclear import pathways for the E7 oncoproteins of mucosal alpha genus HPVs, type 16 and 11. Here we investigated the nuclear import of cutaneous beta genus HPV8 E7 protein using confocal microscopy after transfections of HeLa cells with EGFP-8E7 and mutant plasmids and nuclear import assays in digitonin-permeabilized HeLa cells. We determined that HPV8 E7 contains a nuclear localization signal (NLS) within its zinc-binding domain that mediates its nuclear import. Furthermore, we discovered that a mostly hydrophobic patch {sub 65}LRLFV{sub 69} within the zinc-binding domain is essential for the nuclear import and localization of HPV8 E7 via hydrophobic interactions with the FG nucleoporins Nup62 and Nup153. Substitution of the hydrophobic residues within the {sub 65}LRLFV{sub 69} patch to alanines, and not R66A mutation, disrupt the interactions between the 8E7 zinc-binding domain and Nup62 and Nup153 and consequently inhibit nuclear import of HPV8 E7. - Highlights: • HPV8 E7 has a cNLS within its zinc-binding domain that mediates its nuclear import. • Discovery of a hydrophobic patch that is critical for the nuclear import of HPV8 E7. • HPV8 E7 nuclear import is mediated by hydrophobic interactions with FG-Nups, Nup62 and Nup153.

  10. A subset of FG-nucleoporins is necessary for efficient Msn5-mediated nuclear protein export

    Science.gov (United States)

    Finn, Erin M.; DeRoo, Elise P.; Clement, George W.; Rao, Sheila; Kruse, Sarah E.; Kokanovich, Kate M.; Belanger, Kenneth D.

    2013-01-01

    The transport of proteins between the cytoplasm and nucleus requires interactions between soluble transport receptors (karyopherins) and phenylalanine-glycine (FG) repeat domains on nuclear pore complex proteins (nucleoporins). However, the role of specific FG repeat-containing nucleoporins in nuclear protein export has not been carefully investigated. We have developed a novel kinetic assay to investigate the relative export kinetics mediated by the karyopherin Msn5/Kap142 in yeast containing specific FG-Nup mutations. Using the Msn5 substrate Crz1 as a marker for Msn5-mediated protein export, we observe that deletions of NUP100 or NUP2 result in decreased rates of Crz1 export, while nup60Δ and nup42Δ mutants do not vary significantly from wild type. The decreased Msn5 export rate in nup100Δ was confirmed using Mig1-GFP as a transport substrate. A nup100ΔGLFG mutant shows defects in nuclear export kinetics similar to a nup100Δ deletion. Removal of FG-repeats from Nsp1 also decreases export kinetics, while a loss of Nup1 FXFGs does not. To confirm that our export data reflected functional differences in protein localization, we performed Crz1 transcription activation assays using a CDRE::LacZ reporter gene that is upregulated upon increased transcription activation by Crz1 in vivo. We observe that expression from this reporter increases in nup100ΔGLFG and nsp1ΔFGΔFXFG strains that exhibit decreased Crz1 export kinetics but resembles wild-type levels in nup1ΔFXFG strains that do not exhibit export defects. These data provide evidence that the export of Msn5 is likely mediated by a specific subset of FG-Nups and that the GLFG repeat domain of Nup100 is important for Msn5-mediated nuclear protein export. PMID:23295456

  11. A subset of FG-nucleoporins is necessary for efficient Msn5-mediated nuclear protein export.

    Science.gov (United States)

    Finn, Erin M; DeRoo, Elise P; Clement, George W; Rao, Sheila; Kruse, Sarah E; Kokanovich, Kate M; Belanger, Kenneth D

    2013-05-01

    The transport of proteins between the cytoplasm and nucleus requires interactions between soluble transport receptors (karyopherins) and phenylalanine-glycine (FG) repeat domains on nuclear pore complex proteins (nucleoporins). However, the role of specific FG repeat-containing nucleoporins in nuclear protein export has not been carefully investigated. We have developed a novel kinetic assay to investigate the relative export kinetics mediated by the karyopherin Msn5/Kap142 in yeast containing specific FG-Nup mutations. Using the Msn5 substrate Crz1 as a marker for Msn5-mediated protein export, we observe that deletions of NUP100 or NUP2 result in decreased rates of Crz1 export, while nup60Δ and nup42Δ mutants do not vary significantly from wild type. The decreased Msn5 export rate in nup100Δ was confirmed using Mig1-GFP as a transport substrate. A nup100ΔGLFG mutant shows defects in nuclear export kinetics similar to a nup100Δ deletion. Removal of FG-repeats from Nsp1 also decreases export kinetics, while a loss of Nup1 FXFGs does not. To confirm that our export data reflected functional differences in protein localization, we performed Crz1 transcription activation assays using a CDRE::LacZ reporter gene that is upregulated upon increased transcription activation by Crz1 in vivo. We observe that expression from this reporter increases in nup100ΔGLFG and nsp1ΔFGΔFXFG strains that exhibit decreased Crz1 export kinetics but resembles wild-type levels in nup1ΔFXFG strains that do not exhibit export defects. These data provide evidence that the export of Msn5 is likely mediated by a specific subset of FG-Nups and that the GLFG repeat domain of Nup100 is important for Msn5-mediated nuclear protein export.

  12. Repeatability of Perimacular Ganglion Cell Complex Analysis with Spectral-Domain Optical Coherence Tomography

    OpenAIRE

    Ng, Dorothy S. K.; Preeti Gupta; Yih Chung Tham; Chye Fong Peck; Tien Yin Wong; Mohammad Kamran Ikram; Cheung, Carol Y.

    2015-01-01

    Purpose. To assess the repeatability of spectral-domain optical coherence tomography to measure macular and perimacular ganglion cell complex thicknesses and compare retinal ganglion cell parameters between algorithms. Methods. Ninety-two nonglaucomatous eyes from 92 participants underwent macular and perimacular ganglion cell complex thickness measurement using OCT-HS100 Glaucoma 3D algorithm and these measurements were repeated for 34 subjects. All subjects also had macular ganglion cell-in...

  13. NMR studies on domain diffusion and alignment in modular GB1 repeats.

    Science.gov (United States)

    Walsh, Joseph D; Meier, Katlyn; Ishima, Rieko; Gronenborn, Angela M

    2010-10-20

    Modular proteins contain individual domains that are often connected by flexible, unstructured linkers. Using a model system based on the GB1 domain, we constructed tandem repeat proteins and investigated the rotational diffusion and long-range angular ordering behavior of individual domains by measuring NMR relaxation parameters and residual dipolar couplings. Although they display almost identical protein-solvent interfaces, each domain exhibits distinct rotational diffusion and alignment properties. The diffusion tensor anisotropy of the N-terminal domain (NTD) is D(‖)/D(⊥) = 1.5-1.6, similar to that of single-GB1 domains (D(‖)/D(⊥) = 1.6-1.7), whereas the value for the C-terminal domain (CTD) is D(‖)/D(⊥) = 2.0-2.2. In addition, the two domains have different rotational correlation times. These effects are observed for linkers of three to 24 residues, irrespective of linker length. The NTD and CTD also differ in their degree of magnetic alignment, even with a flexible linker of 18 residues, exhibiting D(a) values of 7.7 Hz and 9.7 Hz, respectively. Our results suggest that diffusion differences and long-range influences may persist in modular protein systems, even for systems that have highly flexible linkers and exhibit no domain-domain or domain-linker interactions.

  14. Alternative conformations of the Tau repeat domain in complex with an engineered binding protein.

    Science.gov (United States)

    Grüning, Clara S R; Mirecka, Ewa A; Klein, Antonia N; Mandelkow, Eckhard; Willbold, Dieter; Marino, Stephen F; Stoldt, Matthias; Hoyer, Wolfgang

    2014-08-15

    The aggregation of Tau into paired helical filaments is involved in the pathogenesis of several neurodegenerative diseases, including Alzheimer disease. The aggregation reaction is characterized by conformational conversion of the repeat domain, which partially adopts a cross-β-structure in the resulting amyloid-like fibrils. Here, we report the selection and characterization of an engineered binding protein, β-wrapin TP4, targeting the Tau repeat domain. TP4 was obtained by phage display using the four-repeat Tau construct K18ΔK280 as a target. TP4 binds K18ΔK280 as well as the longest isoform of human Tau, hTau40, with nanomolar affinity. NMR spectroscopy identified two alternative TP4-binding sites in the four-repeat domain, with each including two hexapeptide motifs with high β-sheet propensity. Both binding sites contain the aggregation-determining PHF6 hexapeptide within repeat 3. In addition, one binding site includes the PHF6* hexapeptide within repeat 2, whereas the other includes the corresponding hexapeptide Tau(337-342) within repeat 4, denoted PHF6**. Comparison of TP4-binding with Tau aggregation reveals that the same regions of Tau are involved in both processes. TP4 inhibits Tau aggregation at substoichiometric concentration, demonstrating that it interferes with aggregation nucleation. This study provides residue-level insight into the interaction of Tau with an aggregation inhibitor and highlights the structural flexibility of Tau. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Nucleoporin domain topology is linked to the transport status of the nuclear pore complex.

    Science.gov (United States)

    Paulillo, Sara M; Phillips, Erica M; Köser, Joachim; Sauder, Ursula; Ullman, Katharine S; Powers, Maureen A; Fahrenkrog, Birthe

    2005-08-26

    Nuclear pore complexes (NPCs) facilitate macromolecular exchange between the nucleus and cytoplasm of eukaryotic cells. The vertebrate NPC is composed of approximately 30 different proteins (nucleoporins), of which around one third contain phenylalanine-glycine (FG)-repeat domains that are thought to mediate the main interaction between the NPC and soluble transport receptors. We have recently shown that the FG-repeat domain of Nup153 is flexible within the NPC, although this nucleoporin is anchored to the nuclear side of the NPC. By using domain-specific antibodies, we have now mapped the domain topology of Nup214 in Xenopus oocytes and in human somatic cells by immuno-EM. We have found that whereas Nup214 is anchored to the cytoplasmic side of the NPC via its N-terminal and central domain, its FG-repeat domain appears flexible, residing on both sides of the NPC. Moreover, the spatial distribution of the FG-repeat domains of both Nup153 and Nup214 shifts in a transport-dependent manner, suggesting that the location of FG-repeat domains within the NPC correlates with cargo/receptor interactions and that they concomitantly move with cargo through the central pore of the NPC.

  16. Mechanism of intermediate filament recognition by plakin repeat domains revealed by envoplakin targeting of vimentin

    Science.gov (United States)

    Fogl, Claudia; Mohammed, Fiyaz; Al-Jassar, Caezar; Jeeves, Mark; Knowles, Timothy J.; Rodriguez-Zamora, Penelope; White, Scott A.; Odintsova, Elena; Overduin, Michael; Chidgey, Martyn

    2016-03-01

    Plakin proteins form critical connections between cell junctions and the cytoskeleton; their disruption within epithelial and cardiac muscle cells cause skin-blistering diseases and cardiomyopathies. Envoplakin has a single plakin repeat domain (PRD) which recognizes intermediate filaments through an unresolved mechanism. Herein we report the crystal structure of envoplakin's complete PRD fold, revealing binding determinants within its electropositive binding groove. Four of its five internal repeats recognize negatively charged patches within vimentin via five basic determinants that are identified by nuclear magnetic resonance spectroscopy. Mutations of the Lys1901 or Arg1914 binding determinants delocalize heterodimeric envoplakin from intracellular vimentin and keratin filaments in cultured cells. Recognition of vimentin is abolished when its residues Asp112 or Asp119 are mutated. The latter slot intermediate filament rods into basic PRD domain grooves through electrosteric complementarity in a widely applicable mechanism. Together this reveals how plakin family members form dynamic linkages with cytoskeletal frameworks.

  17. Structural Analyses of the Ankyrin Repeat Domain of TRPV6 and Related TRPV Ion Channels

    Energy Technology Data Exchange (ETDEWEB)

    Phelps, C.B.; Huang, R.J.; Lishko, P.V.; Wang, R.R.; Gaudet, R. (Harvard)

    2008-06-03

    Transient receptor potential (TRP) proteins are cation channels composed of a transmembrane domain flanked by large N- and C-terminal cytoplasmic domains. All members of the vanilloid family of TRP channels (TRPV) possess an N-terminal ankyrin repeat domain (ARD). The ARD of mammalian TRPV6, an important regulator of calcium uptake and homeostasis, is essential for channel assembly and regulation. The 1.7 A crystal structure of the TRPV6-ARD reveals conserved structural elements unique to the ARDs of TRPV proteins. First, a large twist between the fourth and fifth repeats is induced by residues conserved in all TRPV ARDs. Second, the third finger loop is the most variable region in sequence, length and conformation. In TRPV6, a number of putative regulatory phosphorylation sites map to the base of this third finger. Size exclusion chromatography and crystal packing indicate that the TRPV6-ARD does not assemble as a tetramer and is monomeric in solution. Adenosine triphosphate-agarose and calmodulin-agarose pull-down assays show that the TRPV6-ARD does not interact with either ligand, indicating a different functional role for the TRPV6-ARD than in the paralogous thermosensitive TRPV1 channel. Similar biochemical findings are also presented for the highly homologous mammalian TRPV5-ARD. The implications of the structural and biochemical data on the role of the ankyrin repeats in different TRPV channels are discussed.

  18. Genetics Home Reference: FG syndrome

    Science.gov (United States)

    ... Rogers RC, Schwartz CE, Battaglia A, Lyons MJ, Stevenson RE. FG syndrome, an X-linked multiple congenital ... Simensen R, Rogers RC, Schwartz CE, Friez MJ, Stevenson RE. Behavior of 10 patients with FG syndrome ( ...

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

    Science.gov (United States)

    Wang, Xianzhe; Maynard, Jennifer A.

    2015-01-01

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

  20. MSH2 ATPase domain mutation affects CTG*CAG repeat instability in transgenic mice.

    Directory of Open Access Journals (Sweden)

    Stéphanie Tomé

    2009-05-01

    Full Text Available Myotonic dystrophy type 1 (DM1 is associated with one of the most highly unstable CTG*CAG repeat expansions. The formation of further repeat expansions in transgenic mice carrying expanded CTG*CAG tracts requires the mismatch repair (MMR proteins MSH2 and MSH3, forming the MutSbeta complex. It has been proposed that binding of MutSbeta to CAG hairpins blocks its ATPase activity compromising hairpin repair, thereby causing expansions. This would suggest that binding, but not ATP hydrolysis, by MutSbeta is critical for trinucleotide expansions. However, it is unknown if the MSH2 ATPase activity is dispensible for instability. To get insight into the mechanism by which MSH2 generates trinucleotide expansions, we crossed DM1 transgenic mice carrying a highly unstable >(CTG(300 repeat tract with mice carrying the G674A mutation in the MSH2 ATPase domain. This mutation impairs MSH2 ATPase activity and ablates base-base MMR, but does not affect the ability of MSH2 (associated with MSH6 to bind DNA mismatches. We found that the ATPase domain mutation of MSH2 strongly affects the formation of CTG expansions and leads instead to transmitted contractions, similar to a Msh2-null or Msh3-null deficiency. While a decrease in MSH2 protein level was observed in tissues from Msh2(G674 mice, the dramatic reduction of expansions suggests that the expansion-biased trinucleotide repeat instability requires a functional MSH2 ATPase domain and probably a functional MMR system.

  1. Stages and conformations of the Tau repeat domain during aggregation and its effect on neuronal toxicity.

    Science.gov (United States)

    Kumar, Satish; Tepper, Katharina; Kaniyappan, Senthilvelrajan; Biernat, Jacek; Wegmann, Susanne; Mandelkow, Eva-Maria; Müller, Daniel J; Mandelkow, Eckhard

    2014-07-18

    Several neurodegenerative diseases are characterized by the aggregation and posttranslational modifications of Tau protein. Its "repeat domain" (TauRD) is mainly responsible for the aggregation properties, and oligomeric forms are thought to dominate the toxic effects of Tau. Here we investigated the conformational transitions of this domain during oligomerization and aggregation in different states of β-propensity and pseudo-phosphorylation, using several complementary imaging and spectroscopic methods. Although the repeat domain generally aggregates more readily than full-length Tau, its aggregation was greatly slowed down by phosphorylation or pseudo-phosphorylation at the KXGS motifs, concomitant with an extended phase of oligomerization. Analogous effects were observed with pro-aggregant variants of TauRD. Oligomers became most evident in the case of the pro-aggregant mutant TauRDΔK280, as monitored by atomic force microscopy, and the fluorescence lifetime of Alexa-labeled Tau (time-correlated single photon counting (TCSPC)), consistent with its pronounced toxicity in mouse models. In cell models or primary neurons, neither oligomers nor fibrils of TauRD or TauRDΔK280 had a toxic effect, as seen by assays with lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, respectively. However, oligomers of pro-aggregant TauRDΔK280 specifically caused a loss of spine density in differentiated neurons, indicating a locally restricted impairment of function. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. LRR conservation mapping to predict functional sites within protein leucine-rich repeat domains.

    Directory of Open Access Journals (Sweden)

    Laura Helft

    Full Text Available Computational prediction of protein functional sites can be a critical first step for analysis of large or complex proteins. Contemporary methods often require several homologous sequences and/or a known protein structure, but these resources are not available for many proteins. Leucine-rich repeats (LRRs are ligand interaction domains found in numerous proteins across all taxonomic kingdoms, including immune system receptors in plants and animals. We devised Repeat Conservation Mapping (RCM, a computational method that predicts functional sites of LRR domains. RCM utilizes two or more homologous sequences and a generic representation of the LRR structure to identify conserved or diversified patches of amino acids on the predicted surface of the LRR. RCM was validated using solved LRR+ligand structures from multiple taxa, identifying ligand interaction sites. RCM was then used for de novo dissection of two plant microbe-associated molecular pattern (MAMP receptors, EF-TU RECEPTOR (EFR and FLAGELLIN-SENSING 2 (FLS2. In vivo testing of Arabidopsis thaliana EFR and FLS2 receptors mutagenized at sites identified by RCM demonstrated previously unknown functional sites. The RCM predictions for EFR, FLS2 and a third plant LRR protein, PGIP, compared favorably to predictions from ODA (optimal docking area, Consurf, and PAML (positive selection analyses, but RCM also made valid functional site predictions not available from these other bioinformatic approaches. RCM analyses can be conducted with any LRR-containing proteins at www.plantpath.wisc.edu/RCM, and the approach should be modifiable for use with other types of repeat protein domains.

  3. Tetratricopeptide repeat domain 9A is an interacting protein for tropomyosin Tm5NM-1

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    Ho Gay

    2008-08-01

    Full Text Available Abstract Background Tetratricopeptide repeat domain 9A (TTC9A protein is a recently identified protein which contains three tetratricopeptide repeats (TPRs on its C-terminus. In our previous studies, we have shown that TTC9A was a hormonally-regulated gene in breast cancer cells. In this study, we found that TTC9A was over-expressed in breast cancer tissues compared with the adjacent controls (P Methods Breast samples from 25 patients including the malignant breast tissues and the adjacent normal tissues were processed for Southern blot analysis. Yeast-two-hybrid assay, GST pull-down assay and co-immunoprecipitation were used to identify and verify the interaction between TTC9A and other proteins. Results Tropomyosin Tm5NM-1 was identified as one of the TTC9A partner proteins. The interaction between TTC9A and Tm5NM-1 was further confirmed by GST pull-down assay and co-immunoprecipitation in mammalian cells. TTC9A domains required for the interaction were also characterized in this study. The results suggested that the first TPR domain and the linker fragment between the first two TPR domains of TTC9A were important for the interaction with Tm5NM-1 and the second and the third TPR might play an inhibitory role. Conclusion Since the primary function of tropomyosin is to stabilize actin filament, its interaction with TTC9A may play a role in cell shape and motility. In our previous results, we have found that progesterone-induced TTC9A expression was associated with increased cell motility and cell spreading. We speculate that TTC9A acts as a chaperone protein to facilitate the function of tropomyosins in stabilizing microfilament and it may play a role in cancer cell invasion and metastasis.

  4. Stages and Conformations of the Tau Repeat Domain during Aggregation and Its Effect on Neuronal Toxicity*

    Science.gov (United States)

    Kumar, Satish; Tepper, Katharina; Kaniyappan, Senthilvelrajan; Biernat, Jacek; Wegmann, Susanne; Mandelkow, Eva-Maria; Müller, Daniel J.; Mandelkow, Eckhard

    2014-01-01

    Several neurodegenerative diseases are characterized by the aggregation and posttranslational modifications of Tau protein. Its “repeat domain” (TauRD) is mainly responsible for the aggregation properties, and oligomeric forms are thought to dominate the toxic effects of Tau. Here we investigated the conformational transitions of this domain during oligomerization and aggregation in different states of β-propensity and pseudo-phosphorylation, using several complementary imaging and spectroscopic methods. Although the repeat domain generally aggregates more readily than full-length Tau, its aggregation was greatly slowed down by phosphorylation or pseudo-phosphorylation at the KXGS motifs, concomitant with an extended phase of oligomerization. Analogous effects were observed with pro-aggregant variants of TauRD. Oligomers became most evident in the case of the pro-aggregant mutant TauRDΔK280, as monitored by atomic force microscopy, and the fluorescence lifetime of Alexa-labeled Tau (time-correlated single photon counting (TCSPC)), consistent with its pronounced toxicity in mouse models. In cell models or primary neurons, neither oligomers nor fibrils of TauRD or TauRDΔK280 had a toxic effect, as seen by assays with lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, respectively. However, oligomers of pro-aggregant TauRDΔK280 specifically caused a loss of spine density in differentiated neurons, indicating a locally restricted impairment of function. PMID:24825901

  5. Repeatability of Perimacular Ganglion Cell Complex Analysis with Spectral-Domain Optical Coherence Tomography.

    Science.gov (United States)

    Ng, Dorothy S K; Gupta, Preeti; Tham, Yih Chung; Peck, Chye Fong; Wong, Tien Yin; Ikram, Mohammad Kamran; Cheung, Carol Y

    2015-01-01

    Purpose. To assess the repeatability of spectral-domain optical coherence tomography to measure macular and perimacular ganglion cell complex thicknesses and compare retinal ganglion cell parameters between algorithms. Methods. Ninety-two nonglaucomatous eyes from 92 participants underwent macular and perimacular ganglion cell complex thickness measurement using OCT-HS100 Glaucoma 3D algorithm and these measurements were repeated for 34 subjects. All subjects also had macular ganglion cell-inner plexiform layer thickness measured by Cirrus HD-OCT Ganglion Cell Analysis algorithm. Intraclass correlation coefficient and Pearson's correlation analyses were performed. Results. Subfields of both macular and perimacular ganglion cell complex thicknesses had high intraclass correlation coefficient values between 0.979 (95% confidence interval [CI]: 0.958-0.989) and 0.981 (95% CI: 0.963, 0.991) and between 0.70 (95% CI: 0.481-0.838) and 0.987 (95% CI: 0.956-0.989), respectively. The overall average ganglion cell complex and macular average ganglion cell-inner plexiform layer thicknesses were strongly correlated (r = 0.83,  P HS100 Glaucoma 3D algorithm is highly repeatable, and strongly correlates to retinal ganglion cell parameters assessed by Ganglion Cell Analysis algorithm. A comprehensive evaluation of retinal ganglion cells may be possible with OCT-HS100.

  6. Repeatability of Perimacular Ganglion Cell Complex Analysis with Spectral-Domain Optical Coherence Tomography

    Directory of Open Access Journals (Sweden)

    Dorothy S. K. Ng

    2015-01-01

    Full Text Available Purpose. To assess the repeatability of spectral-domain optical coherence tomography to measure macular and perimacular ganglion cell complex thicknesses and compare retinal ganglion cell parameters between algorithms. Methods. Ninety-two nonglaucomatous eyes from 92 participants underwent macular and perimacular ganglion cell complex thickness measurement using OCT-HS100 Glaucoma 3D algorithm and these measurements were repeated for 34 subjects. All subjects also had macular ganglion cell-inner plexiform layer thickness measured by Cirrus HD-OCT Ganglion Cell Analysis algorithm. Intraclass correlation coefficient and Pearson’s correlation analyses were performed. Results. Subfields of both macular and perimacular ganglion cell complex thicknesses had high intraclass correlation coefficient values between 0.979 (95% confidence interval [CI]: 0.958–0.989 and 0.981 (95% CI: 0.963, 0.991 and between 0.70 (95% CI: 0.481–0.838 and 0.987 (95% CI: 0.956–0.989, respectively. The overall average ganglion cell complex and macular average ganglion cell-inner plexiform layer thicknesses were strongly correlated (r=0.83, P<0.001.  Conclusions. The assessment of macular and perimacular retinal ganglion cell parameters by OCT-HS100 Glaucoma 3D algorithm is highly repeatable, and strongly correlates to retinal ganglion cell parameters assessed by Ganglion Cell Analysis algorithm. A comprehensive evaluation of retinal ganglion cells may be possible with OCT-HS100.

  7. Positive selection in the leucine-rich repeat domain of Gro1 genes in Solanum species

    Indian Academy of Sciences (India)

    Valentino Ruggieri; Angelina Nunziata; Amalia Barone

    2014-12-01

    In pathogen resistant plants, solvent-exposed residues in the leucine-rich repeat (LRR) proteins are thought to mediate resistance by recognizing plant pathogen elicitors. In potato, the gene Gro1-4 confers resistance to Globodera rostochiensis. The investigation of variablity in different copies of this gene represents a good model for the verification of positive selection mechanisms. Two datasets of Gro1 LRR sequences were constructed, one derived from the Gro1-4 gene, belonging to different cultivated and wild Solanum species, and the other belonging to paralogues of a resistant genotype. Analysis of non-synonymous to synonymous substitution rates $(K_{a}/K_{s})$ highlighted 14 and six amino acids with $K_{a}/K_{s} \\gt 1$ in orthologue and paralogue datasets, respectively. Selection analysis revealed that the leucine-rich regions accumulate variability in a very specific way, and we found that some combinations of amino acids in these sites might be involved in pathogen recognition. The results confirm previous studies on positive selection in the LRR domain of R protein in Arabidopsis and other model plants and extend these to wild Solanum species. Moreover, positively selected sites in the Gro1 LRR domain show that coevolution mainly occurred in two regions on the internal surface of the three-dimensional horseshoe structure of the domain, albeit with different evolutionary forces between paralogues and orthologues.

  8. The crystal structure of a partial mouse Notch-1 ankyrin domain: Repeats 4 through 7 preserve an ankyrin fold

    Energy Technology Data Exchange (ETDEWEB)

    Lubman, Olga Y.; Kopan, Raphael; Waksman, Gabriel; Korolev, Sergey (Birbeck); (St. Louis-MED); (WU-MED)

    2010-07-20

    Folding and stability of proteins containing ankyrin repeats (ARs) is of great interest because they mediate numerous protein-protein interactions involved in a wide range of regulatory cellular processes. Notch, an ankyrin domain containing protein, signals by converting a transcriptional repression complex into an activation complex. The Notch ANK domain is essential for Notch function and contains seven ARs. Here, we present the 2.2 {angstrom} crystal structure of ARs 4-7 from mouse Notch 1 (m1ANK). These C-terminal repeats were resistant to degradation during crystallization, and their secondary and tertiary structures are maintained in the absence of repeats 1-3. The crystallized fragment adopts a typical ankyrin fold including the poorly conserved seventh AR, as seen in the Drosophila Notch ANK domain (dANK). The structural preservation and stability of the C-terminal repeats shed a new light onto the mechanism of hetero-oligomeric assembly during Notch-mediated transcriptional activation.

  9. Changes in nucleoporin domain topology in response to chemical effectors.

    Science.gov (United States)

    Paulillo, Sara M; Powers, Maureen A; Ullman, Katharine S; Fahrenkrog, Birthe

    2006-10-13

    Nucleoporins represent the molecular building blocks of nuclear pore complexes (NPCs), which mediate facilitated macromolecular trafficking between the cytoplasm and nucleus of eukaryotic cells. Phenylalanine-glycine (FG) repeat motifs are found in about one-third of the nucleoporins, and they provide major binding or docking sites for soluble transport receptors. We have shown recently that localization of the FG-repeat domains of vertebrate nucleoporins Nup153 and Nup214 within the NPC is influenced by its transport state. To test whether chemical effectors, such as calcium and ATP, influence the localization of the FG-repeat domains of Nup153 and Nup214 within the NPC, we performed immuno-electron microscopy of Xenopus oocyte nuclei using domain-specific antibodies against Nup153 and Nup214, respectively. Ca2+ and ATP are known to induce conformational changes in the NPC architecture, especially at the cytoplasmic face, but also at the nuclear basket of the NPC. We have found concentrations of calcium in the micromolar range or 1 mM ATP in the surrounding buffer leaves the spatial distribution of the FG-repeat of Nup153 and Nup214 largely unchanged. In contrast, ATP depletion, calcium store depletion by EGTA or thapsigargin, and high concentrations of divalent cation (i.e. 2 mM Ca2+ and 2 mM Mg2+) constrain the distribution of the FG-repeats of Nup153 and Nup214. Our data suggest that the location of the FG-repeat domains of Nup153 and Nup214 is sensitive to chemical changes within the near-field environment of the NPC.

  10. Quantification of interaction strengths between chaperones and tetratricopeptide repeat domain-containing membrane proteins.

    Science.gov (United States)

    Schweiger, Regina; Soll, Jürgen; Jung, Kirsten; Heermann, Ralf; Schwenkert, Serena

    2013-10-18

    The three tetratricopeptide repeat domain-containing docking proteins Toc64, OM64, and AtTPR7 reside in the chloroplast, mitochondrion, and endoplasmic reticulum of Arabidopsis thaliana, respectively. They are suggested to act during post-translational protein import by association with chaperone-bound preprotein complexes. Here, we performed a detailed biochemical, biophysical, and computational analysis of the interaction between Toc64, OM64, and AtTPR7 and the five cytosolic chaperones HSP70.1, HSP90.1, HSP90.2, HSP90.3, and HSP90.4. We used surface plasmon resonance spectroscopy in combination with Interaction Map® analysis to distinguish between chaperone oligomerization and docking protein-chaperone interactions and to calculate binding affinities for all tested interactions. Complementary to this, we applied pulldown assays as well as microscale thermophoresis as surface immobilization independent techniques. The data revealed that OM64 prefers HSP70 over HSP90, whereas Toc64 binds all chaperones with comparable affinities. We could further show that AtTPR7 is able to bind HSP90 in addition to HSP70. Moreover, differences between the HSP90 isoforms were detected and revealed a weaker binding for HSP90.1 to AtTPR7 and OM64, showing that slight differences in the amino acid composition or structure of the chaperones influence binding to the tetratricopeptide repeat domain. The combinatory approach of several methods provided a powerful toolkit to determine binding affinities of similar interaction partners in a highly quantitative manner.

  11. MO-FG-204-03: Using Edge-Preserving Algorithm for Significantly Improved Image-Domain Material Decomposition in Dual Energy CT

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, W [Huazhong University of Science & Technology, Wuhan, Hubei (China); Niu, T [Zhejiang University, Hangzhou, Zhejiang (China); Xing, L [Stanford Univ School of Medicine, Stanford, CA (United States); Xiong, G; Elmore, K; Min, J [Dalio Institute of Cardiovascular Imaging NewYork-Presbyterian Hospital and, New York, NY (United States); Zhu, J; Wang, L [Huazhong University of Science and Technology, Wuhan, Hubei (China)

    2015-06-15

    Purpose: To significantly improve dual energy CT (DECT) imaging by establishing a new theoretical framework of image-domain material decomposition with incorporation of edge-preserving techniques. Methods: The proposed algorithm, HYPR-NLM, combines the edge-preserving non-local mean filter (NLM) with the HYPR-LR (Local HighlY constrained backPRojection Reconstruction) framework. Image denoising using HYPR-LR framework depends on the noise level of the composite image which is the average of the different energy images. For DECT, the composite image is the average of high- and low-energy images. To further reduce noise, one may want to increase the window size of the filter of the HYPR-LR, leading resolution degradation. By incorporating the NLM filtering and the HYPR-LR framework, HYPR-NLM reduces the boost material decomposition noise using energy information redundancies as well as the non-local mean. We demonstrate the noise reduction and resolution preservation of the algorithm with both iodine concentration numerical phantom and clinical patient data by comparing the HYPR-NLM algorithm to the direct matrix inversion, HYPR-LR and iterative image-domain material decomposition (Iter-DECT). Results: The results show iterative material decomposition method reduces noise to the lowest level and provides improved DECT images. HYPR-NLM significantly reduces noise while preserving the accuracy of quantitative measurement and resolution. For the iodine concentration numerical phantom, the averaged noise levels are about 2.0, 0.7, 0.2 and 0.4 for direct inversion, HYPR-LR, Iter- DECT and HYPR-NLM, respectively. For the patient data, the noise levels of the water images are about 0.36, 0.16, 0.12 and 0.13 for direct inversion, HYPR-LR, Iter-DECT and HYPR-NLM, respectively. Difference images of both HYPR-LR and Iter-DECT show edge effect, while no significant edge effect is shown for HYPR-NLM, suggesting spatial resolution is well preserved for HYPR-NLM. Conclusion: HYPR

  12. Differential antibiosis against Helicoverpa armigera exerted by distinct inhibitory repeat domains of Capsicum annuum proteinase inhibitors.

    Science.gov (United States)

    Joshi, Rakesh S; Gupta, Vidya S; Giri, Ashok P

    2014-05-01

    Plant defensive serine proteinase inhibitors (PIs) are known to have negative impact on digestive physiology of herbivore insects and thus have a crucial role in plant protection. Here, we have assessed the efficacy and specificity of three previously characterized inhibitory repeat domain (IRD) variants from Capsicum annuum PIs viz., IRD-7, -9 and -12 against gut proteinases from Helicoverpa armigera. Comparative study of in silico binding energy revealed that IRD-9 possesses higher affinity towards H. armigera serine proteinases as compared to IRD-7 and -12. H. armigera fed on artificial diet containing 5 TIU/g of recombinant IRD proteins exhibited differential effects on larval growth, survival rate and other nutritional parameters. Major digestive gut trypsin and chymotrypsin genes were down regulated in the IRD fed larvae, while few of them were up-regulated, this indicate alterations in insect digestive physiology. The results corroborated with proteinase activity assays and zymography. These findings suggest that the sequence variations among PIs reflect in their efficacy against proteinases in vitro and in vivo, which also could be used for developing tailor-made multi-domain inhibitor gene(s).

  13. Novel Mutations of the Tetratricopeptide Repeat Domain 7A Gene and Phenotype/Genotype Comparison

    Directory of Open Access Journals (Sweden)

    Reyin Lien

    2017-09-01

    Full Text Available The gastrointestinal tract contains the largest lymphoid organ to react with pathogenic microorganisms and suppress excess inflammation. Patients with primary immunodeficiency diseases (PIDs can suffer from refractory diarrhea. In this study, we present two siblings who began to suffer from refractory diarrhea with a poor response to aggressive antibiotic and immunosuppressive treatment after surgical release of neonatal intestinal obstruction. Their lymphocyte proliferation was low, but superoxide production and IL-10 signaling were normal. Candidate genetic approach targeted to genes involved in PIDs with inflammatory bowel disease (IBD-like manifestation was unrevealing. Whole-genome sequencing revealed novel heterozygous mutations Glu75Lys and nucleotide 520–521 CT deletion in the tetratricopeptide repeat domain 7A (TTC7A gene. A Medline search identified 49 patients with TTC7A mutations, of whom 20 survived. Their phenotypes included both multiple intestinal atresia (MIA and combined T and/or B immunodeficiency (CID in 16, both IBD and CID in 14, isolated MIA in 8, MIA, IBD, and CID complex in 8, and isolated IBD in 3. Of these 98 mutant alleles over-through the coding region clustering on exon 2 (40 alleles, exon 7 (12 alleles, and exon 20 (10 alleles, 2 common hotspot mutations were c.211 G>A (p.E71K in exon 2 in 26 alleles and AAGT deletion in exon 7 (+3 in 10 alleles. Kaplan–Meier analysis showed that those with biallelic missense mutations (p = 0.0168, unaffected tetratricopeptide repeat domains (p = 0.0311, and developing autoimmune disorders (p = 0.001 had a relatively better prognosis. Hematopoietic stem cell transplantation (HSCT restored immunity and seemed to decrease the frequency of infections; however, refractory diarrhea persisted. Clinical improvement was reported upon intestinal and liver transplantation in a child with CID and MIA of unknown genetic etiology. In conclusion, patients with TTC7A mutations

  14. Structural analysis of the KRIT1 ankyrin repeat and FERM domains reveals a conformationally stable ARD-FERM interface

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Rong [Yale Univ., New Haven, CT (United States); Li, Xiaofeng [Yale Univ., New Haven, CT (United States); Boggon, Titus J. [Yale Univ., New Haven, CT (United States)

    2015-10-14

    Cerebral cavernous malformations (CCM) are vascular dysplasias that usually occur in the brain and are associated with mutations in the KRIT1/CCM1, CCM2/MGC4607/OSM/Malcavernin, and PDCD10/CCM3/ TFAR15 genes. Here we report the 2.9 Å crystal structure of the ankyrin repeat domain (ARD) and FERM domain of the protein product of KRIT1 (KRIT1; Krev interaction trapped 1). The crystal structure reveals that the KRIT1 ARD contains 4 ankyrin repeats. There is also an unusual conformation in the ANK4 repeat that is stabilized by Trp-404, and the structure reveals a solvent exposed ankyrin groove. Domain orientations of the three copies within the asymmetric unit suggest a stable interaction between KRIT1 ARD and FERM domains, indicating a globular ARD–FERM module. It resembles the additional F0 domain found N-terminal to the FERM domain of talin. Structural analysis of KRIT1 ARD–FERM highlights surface regions of high evolutionary conservation, and suggests potential sites that could mediate interaction with binding partners. The structure therefore provides a better understanding of KRIT1 at the molecular level.

  15. Structural analysis of the KRIT1 ankyrin repeat and FERM domains reveals a conformationally stable ARD-FERM interface.

    Science.gov (United States)

    Zhang, Rong; Li, Xiaofeng; Boggon, Titus J

    2015-12-01

    Cerebral cavernous malformations (CCM) are vascular dysplasias that usually occur in the brain and are associated with mutations in the KRIT1/CCM1, CCM2/MGC4607/OSM/Malcavernin, and PDCD10/CCM3/TFAR15 genes. Here we report the 2.9 Å crystal structure of the ankyrin repeat domain (ARD) and FERM domain of the protein product of KRIT1 (KRIT1; Krev interaction trapped 1). The crystal structure reveals that the KRIT1 ARD contains 4 ankyrin repeats. There is an unusual conformation in the ANK4 repeat that is stabilized by Trp-404, and the structure reveals a solvent exposed ankyrin groove. Domain orientations of the three copies within the asymmetric unit suggest a stable interaction between KRIT1 ARD and FERM domains, indicating a globular ARD-FERM module. This resembles the additional F0 domain found N-terminal to the FERM domain of talin. Structural analysis of KRIT1 ARD-FERM highlights surface regions of high evolutionary conservation, and suggests potential sites that could mediate interaction with binding partners. The structure therefore provides a better understanding of KRIT1 at the molecular level.

  16. Plasmodium alveolins possess distinct but structurally and functionally related multi-repeat domains.

    Science.gov (United States)

    Al-Khattaf, Fatimah S; Tremp, Annie Z; Dessens, Johannes T

    2015-02-01

    The invasive and motile life stages of malaria parasites (merozoite, ookinete and sporozoite) possess a distinctive cortical structure termed the pellicle. The pellicle is characterised by a double-layered 'inner membrane complex' (IMC) located underneath the plasma membrane, which is supported by a cytoskeletal structure termed the subpellicular network (SPN). The SPN consists of intermediate filaments, whose major constituents include a family of proteins called alveolins. Here, we re-appraise the alveolins in the genus Plasmodium with respect to their repertoire, structure and interrelatedness. Amongst 13 family members identified, we distinguish two domain types that, albeit distinct at the primary structure level, are structurally related and contain tandem repeats with a consensus 12-amino acid periodicity. Analysis in Plasmodium berghei of the most divergent alveolin, PbIMC1d, reveals a zoite-specific expression in ookinetes and a subcellular localisation in the pellicle, consistent with its predicted role as a SPN component. Knockout of PbIMC1d gives rise to a wild-type phenotype with respect to ookinete morphogenesis, tensile strength, gliding motility and infectivity, presenting the first example of apparent functional redundancy amongst alveolin family members.

  17. Increased leucine-rich repeats and immunoglobulin- like domains 1 expression enhances chemosensitivity in glioma

    Institute of Scientific and Technical Information of China (English)

    Baohui Liu; Shenqi Zhang; Dong Ruan; Xiaonan Zhu; Zhentao Guo; Huimin Dong; Mingmin Yan; Qianxue Chen; Daofeng Tian; Liquan Wu; Junmin Wang; Qiang Cai; Heng Shen; Baowei Ji; Long Wang

    2011-01-01

    Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is an anti-oncogene.LRIG1 is correlated with Bcl-2 in ependymomas.Decreased Bcl-2 and manganese superoxide dismutase expression can improve the chemosensitivity of glioma.In the present study, a tissue microarray of human brain astrocytomas was constructed.To investigate the relationship of LRIG1 with Bcl-2 and manganese superoxide dismutase, LRIG1, Bcl-2 and manganese superoxide dismutase expression in our tissue microarray was determined using immunohistochemistry.In addition, we constructed the LRIG1-U251 cell line, and its responses to doxorubicin and temozolomide were detected using the MTT assay.Results showed that LRIG1 expression was significantly negatively correlated with Bcl-2 and manganese superoxide dismutase expression in glioma.Also, proliferation of LRIG1-U251 cells exposed to doxorubicin or temozolomide was significantly inhibited, i.e.in the LRIG1-U251 cell line, the chemosensitivity to doxorubicin and temozolomide was increased.This indicates that increased LRIG1 expression produces a chemosensitivity in glioma.

  18. Hybrid Sterility in Rice (Oryza sativa L.) Involves the Tetratricopeptide Repeat Domain Containing Protein.

    Science.gov (United States)

    Yu, Yang; Zhao, Zhigang; Shi, Yanrong; Tian, Hua; Liu, Linglong; Bian, Xiaofeng; Xu, Yang; Zheng, Xiaoming; Gan, Lu; Shen, Yumin; Wang, Chaolong; Yu, Xiaowen; Wang, Chunming; Zhang, Xin; Guo, Xiuping; Wang, Jiulin; Ikehashi, Hiroshi; Jiang, Ling; Wan, Jianmin

    2016-07-01

    Intersubspecific hybrid sterility is a common form of reproductive isolation in rice (Oryza sativa L.), which significantly hampers the utilization of heterosis between indica and japonica varieties. Here, we elucidated the mechanism of S7, which specially causes Aus-japonica/indica hybrid female sterility, through cytological and genetic analysis, map-based cloning, and transformation experiments. Abnormal positioning of polar nuclei and smaller embryo sac were observed in F1 compared with male and female parents. Female gametes carrying S7(cp) and S7(i) were aborted in S7(ai)/S7(cp) and S7(ai)/S7(i), respectively, whereas they were normal in both N22 and Dular possessing a neutral allele, S7(n) S7 was fine mapped to a 139-kb region in the centromere region on chromosome 7, where the recombination was remarkably suppressed due to aggregation of retrotransposons. Among 16 putative open reading frames (ORFs) localized in the mapping region, ORF3 encoding a tetratricopeptide repeat domain containing protein was highly expressed in the pistil. Transformation experiments demonstrated that ORF3 is the candidate gene: downregulated expression of ORF3 restored spikelet fertility and eliminated absolutely preferential transmission of S7(ai) in heterozygote S7(ai)/S7(cp); sterility occurred in the transformants Cpslo17-S7(ai) Our results may provide implications for overcoming hybrid embryo sac sterility in intersubspecific hybrid rice and utilization of hybrid heterosis for cultivated rice improvement.

  19. Programmable DNA-binding proteins from Burkholderia provide a fresh perspective on the TALE-like repeat domain.

    Science.gov (United States)

    de Lange, Orlando; Wolf, Christina; Dietze, Jörn; Elsaesser, Janett; Morbitzer, Robert; Lahaye, Thomas

    2014-06-01

    The tandem repeats of transcription activator like effectors (TALEs) mediate sequence-specific DNA binding using a simple code. Naturally, TALEs are injected by Xanthomonas bacteria into plant cells to manipulate the host transcriptome. In the laboratory TALE DNA binding domains are reprogrammed and used to target a fused functional domain to a genomic locus of choice. Research into the natural diversity of TALE-like proteins may provide resources for the further improvement of current TALE technology. Here we describe TALE-like proteins from the endosymbiotic bacterium Burkholderia rhizoxinica, termed Bat proteins. Bat repeat domains mediate sequence-specific DNA binding with the same code as TALEs, despite less than 40% sequence identity. We show that Bat proteins can be adapted for use as transcription factors and nucleases and that sequence preferences can be reprogrammed. Unlike TALEs, the core repeats of each Bat protein are highly polymorphic. This feature allowed us to explore alternative strategies for the design of custom Bat repeat arrays, providing novel insights into the functional relevance of non-RVD residues. The Bat proteins offer fertile grounds for research into the creation of improved programmable DNA-binding proteins and comparative insights into TALE-like evolution.

  20. Terminal-repeat retrotransposons with GAG domain in plant genomes: a new testimony on the complex world of transposable elements.

    Science.gov (United States)

    Chaparro, Cristian; Gayraud, Thomas; de Souza, Rogerio Fernandes; Domingues, Douglas Silva; Akaffou, Sélastique; Laforga Vanzela, Andre Luis; Kochko, Alexandre de; Rigoreau, Michel; Crouzillat, Dominique; Hamon, Serge; Hamon, Perla; Guyot, Romain

    2015-01-07

    A novel structure of nonautonomous long terminal repeat (LTR) retrotransposons called terminal repeat with GAG domain (TR-GAG) has been described in plants, both in monocotyledonous, dicotyledonous and basal angiosperm genomes. TR-GAGs are relatively short elements in length (element into the virus-like particle. GAG precursors show similarities with both Copia and Gypsy GAG proteins, suggesting evolutionary relationships of TR-GAG elements with both families. Despite the lack of the enzymatic machinery required for their mobility, strong evidences suggest that TR-GAGs are still active. TR-GAGs represent ubiquitous nonautonomous structures that could be involved in the molecular diversities of plant genomes.

  1. A conserved gene family encodes transmembrane proteins with fibronectin, immunoglobulin and leucine-rich repeat domains (FIGLER

    Directory of Open Access Journals (Sweden)

    Haga Christopher L

    2007-09-01

    Full Text Available Abstract Background In mouse the cytokine interleukin-7 (IL-7 is required for generation of B lymphocytes, but human IL-7 does not appear to have this function. A bioinformatics approach was therefore used to identify IL-7 receptor related genes in the hope of identifying the elusive human cytokine. Results Our database search identified a family of nine gene candidates, which we have provisionally named fibronectin immunoglobulin leucine-rich repeat (FIGLER. The FIGLER 1–9 genes are predicted to encode type I transmembrane glycoproteins with 6–12 leucine-rich repeats (LRR, a C2 type Ig domain, a fibronectin type III domain, a hydrophobic transmembrane domain, and a cytoplasmic domain containing one to four tyrosine residues. Members of this multichromosomal gene family possess 20–47% overall amino acid identity and are differentially expressed in cell lines and primary hematopoietic lineage cells. Genes for FIGLER homologs were identified in macaque, orangutan, chimpanzee, mouse, rat, dog, chicken, toad, and puffer fish databases. The non-human FIGLER homologs share 38–99% overall amino acid identity with their human counterpart. Conclusion The extracellular domain structure and absence of recognizable cytoplasmic signaling motifs in members of the highly conserved FIGLER gene family suggest a trophic or cell adhesion function for these molecules.

  2. Repeat organization and epigenetic regulation of the DH-Cmu domain of the immunoglobulin heavy-chain gene locus.

    Science.gov (United States)

    Chakraborty, Tirtha; Chowdhury, Dipanjan; Keyes, Amanda; Jani, Anant; Subrahmanyam, Ramesh; Ivanova, Irina; Sen, Ranjan

    2007-09-07

    The first steps of murine immunoglobulin heavy-chain (IgH) gene recombination take place within a chromosomal domain that contains diversity (D(H)) and joining (J(H)) gene segments, but not variable (V(H)) gene segments. Here we show that the chromatin state of this domain is markedly heterogeneous. Specifically, only 5'- and 3'-most D(H) gene segments carry active chromatin modifications, whereas intervening D(H)s are associated with heterochromatic marks that are maintained by ongoing histone deacetylation. The intervening D(H)s form part of a tandemly repeated sequence that expresses tissue-specific, antisense oriented transcripts. We propose that the intervening D(H) genes are actively suppressed by repeat-induced epigenetic silencing, which is reflected in their infrequent representation in DJ(H) junctions compared to the flanking D(H) genes.

  3. PRR repeats in the intracellular domain of KISS1R are important for its export to cell membrane.

    Science.gov (United States)

    Chevrier, Lucie; de Brevern, Alexandre; Hernandez, Eva; Leprince, Jérome; Vaudry, Hubert; Guedj, Anne Marie; de Roux, Nicolas

    2013-06-01

    Inactivating mutations of KISS-1 receptor (KISS1R) have been recently described as a rare cause of isolated hypogonadotropic hypogonadism transmitted as a recessive trait. Few mutations have been described, and the structure-function relationship of KISS1R remains poorly understood. Here, we have taken advantage of the discovery of a novel mutation of KISS1R to characterize the structure and function of an uncommon protein motif composed of 3 proline-arginine-arginine (PRR) repeats located within the intracellular domain. A heterozygous insertion of 1 PRR repeat in-frame with 3 PRR repeats leading to synthesis of a receptor bearing 4 PRR repeats (PRR-KISS1R) was found in the index case. Functional analysis of PRR-KISS1R showed a decrease of the maximal response to kisspeptin stimulation, associated to a lower cell surface expression without modification of total expression. PRR-KISS1R exerts a dominant negative effect on the synthesis of the wild-type (WT)-KISS1R. This effect was due to the nature of inserted residues but also to the difference of the length of the intracellular domain between PRR-KISS1R and WT-KISS1R. A molecular dynamic analysis showed that the additional PRR constrained this arginine-rich region into a polyproline type II helix. Altogether, this study shows that a heterozygous insertion in KISS1R may lead to hypogonadotropic hypogonadism by a dominant negative effect on the WT receptor. An additional PRR repeat into a proline-arginine-rich motif can dramatically changed the conformation of the intracellular domain of KISS1R and its probable interaction with partner proteins.

  4. Comparative genome analysis of cortactin and HS1: the significance of the F-actin binding repeat domain

    Directory of Open Access Journals (Sweden)

    Seggelen Vera

    2005-02-01

    Full Text Available Abstract Background In human carcinomas, overexpression of cortactin correlates with poor prognosis. Cortactin is an F-actin-binding protein involved in cytoskeletal rearrangements and cell migration by promoting actin-related protein (Arp2/3 mediated actin polymerization. It shares a high amino acid sequence and structural similarity to hematopoietic lineage cell-specific protein 1 (HS1 although their functions differ considerable. In this manuscript we describe the genomic organization of these two genes in a variety of species by a combination of cloning and database searches. Based on our analysis, we predict the genesis of the actin-binding repeat domain during evolution. Results Cortactin homologues exist in sponges, worms, shrimps, insects, urochordates, fishes, amphibians, birds and mammalians, whereas HS1 exists in vertebrates only, suggesting that both genes have been derived from an ancestor cortactin gene by duplication. In agreement with this, comparative genome analysis revealed very similar exon-intron structures and sequence homologies, especially over the regions that encode the characteristic highly conserved F-actin-binding repeat domain. Cortactin splice variants affecting this F-actin-binding domain were identified not only in mammalians, but also in amphibians, fishes and birds. In mammalians, cortactin is ubiquitously expressed except in hematopoietic cells, whereas HS1 is mainly expressed in hematopoietic cells. In accordance with their distinct tissue specificity, the putative promoter region of cortactin is different from HS1. Conclusions Comparative analysis of the genomic organization and amino acid sequences of cortactin and HS1 provides inside into their origin and evolution. Our analysis shows that both genes originated from a gene duplication event and subsequently HS1 lost two repeats, whereas cortactin gained one repeat. Our analysis genetically underscores the significance of the F-actin binding domain in

  5. A nested leucine rich repeat (LRR domain: The precursor of LRRs is a ten or eleven residue motif

    Directory of Open Access Journals (Sweden)

    Matsushima Norio

    2010-09-01

    Full Text Available Abstract Background Leucine rich repeats (LRRs are present in over 60,000 proteins that have been identified in viruses, bacteria, archae, and eukaryotes. All known structures of repeated LRRs adopt an arc shape. Most LRRs are 20-30 residues long. All LRRs contain LxxLxLxxNxL, in which "L" is Leu, Ile, Val, or Phe and "N" is Asn, Thr, Ser, or Cys and "x" is any amino acid. Seven classes of LRRs have been identified. However, other LRR classes remains to be characterized. The evolution of LRRs is not well understood. Results Here we describe a novel LRR domain, or nested repeat observed in 134 proteins from 54 bacterial species. This novel LRR domain has 21 residues with the consensus sequence of LxxLxLxxNxLxxLDLxx(N/L/Q/xxx or LxxLxCxxNxLxxLDLxx(N/L/xxx. This LRR domain is characterized by a nested periodicity; it consists of alternating 10- and 11- residues units of LxxLxLxxNx(x/-. We call it "IRREKO" LRR, since the Japanese word for "nested" is "IRREKO". The first unit of the "IRREKO" LRR domain is frequently occupied by an "SDS22-like" LRR with the consensus of LxxLxLxxNxLxxLxxLxxLxx or a "Bacterial" LRR with the consensus of LxxLxLxxNxLxxLPxLPxx. In some proteins an "SDS22-like" LRR intervenes between "IRREKO" LRRs. Conclusion Proteins having "IRREKO" LRR domain are almost exclusively found in bacteria. It is suggested that IRREKO@LRR evolved from a common ancestor with "SDS22-like" and "Bacterial" classes and that the ancestor of IRREKO@LRR is 10 or 11 residues of LxxLxLxxNx(x/-. The "IRREKO" LRR is predicted to adopt an arc shape with smaller curvature in which β-strands are formed on both concave and convex surfaces.

  6. Long-range effects and functional consequences of stabilizing mutations in the ankyrin repeat domain of IκBα.

    Science.gov (United States)

    Cervantes, Carla F; Handley, Lindsey D; Sue, Shih-Che; Dyson, H Jane; Komives, Elizabeth A

    2013-03-11

    Protein domains containing three or more ankyrin repeats (ARs) are ubiquitous in all phyla. Sequence alignments previously identified certain conserved positions, which have been shown to stabilize AR domains and promote their folding. Consensus mutations [Y254L/T257A (YLTA) and C186P/A220P (CPAP)] stabilize the naturally occuring AR domain of human IκBα to denaturation; however, only the YLTA mutations stabilize the protein to proteasomal degradation. We present results from NMR experiments designed to probe the roles of these consensus mutations in IκBα. According to residual dipolar coupling analysis, the gross structures of the AR domains of both mutants appear to be similar to the wild type (WT). Comparison of chemical shifts of mutant and WT proteins reveals that the YLTA and CPAP consensus mutations cause unexpected long-range effects throughout the AR domains. Backbone dynamics experiments reveal that the YLTA mutations in the sixth AR order the C-terminal PEST sequence on the picosecond-to-nanosecond timescale, compared to either the WT or the CPAP mutant IκBαs. This property is likely the mechanism by which the half-life of YLTA IκBα is extended in vivo.

  7. Short consensus repeat domains extend the E-selectin structure in order to grab cells out of flow

    KAUST Repository

    Aleisa, Fajr

    2017-01-08

    Selectins are key adhesion molecules responsible for initiating a multistep process that leads a cell out of the blood circulation and into a tissue or organ. They are composed of an N-terminal extracellular C-type lectin like domain, followed by an Endothelial Growth Factor like domain (EGF), a defined number of short consensus repeats SCR (also called “sushi” domains), a transmembrane domain and a C-terminal cytoplasmic tail. The adhesion of cells (expressing ligands) to the endothelium (expressing the selection i.e., E-selectin) occurs through the interaction between the lectin domain of selectins and sLeX presenting ligands. Structural/function studies to date have mainly focused on investigating the influence of the lectin domain of E-selectin on its ability to bind its ligands while other domains received less atention. We prepared a number of different recombinant E-selectin proteins with changes in the SCR units. Specifically we generated wild-type E-selectin proteins as monomeric or dimeric structures, mutant proteins with varied numbers of SCRs as well as proteins where strategic residues were mutated to change the conformation of the selectin. Using a novel real time immunoprecipitation surface plasmon resonance (SPR)-based in vitro binding study developed in our lab, the interaction of recombinant E-selectin proteins with immunoprecipitated endogenous ligands (i.e. CD44) captured on a CM-5 chip was assessed. These studies provided quantitative binding kinetics with on and off rates of selectin-ligand interactions and suggested that robust binding is dependent on the presence of the SCRs and oligomerization. These results provide significant implications on the functional mechanism of E-selectin binding to its ligands.

  8. Terminal-Repeat Retrotransposons with GAG Domain in Plant Genomes: A New Testimony on the Complex World of Transposable Elements

    Science.gov (United States)

    Chaparro, Cristian; Gayraud, Thomas; de Souza, Rogerio Fernandes; Domingues, Douglas Silva; Akaffou, Sélastique; Laforga Vanzela, Andre Luis; de Kochko, Alexandre; Rigoreau, Michel; Crouzillat, Dominique; Hamon, Serge; Hamon, Perla; Guyot, Romain

    2015-01-01

    A novel structure of nonautonomous long terminal repeat (LTR) retrotransposons called terminal repeat with GAG domain (TR-GAG) has been described in plants, both in monocotyledonous, dicotyledonous and basal angiosperm genomes. TR-GAGs are relatively short elements in length (<4 kb) showing the typical features of LTR-retrotransposons. However, they carry only one open reading frame coding for the GAG precursor protein involved for instance in transposition, the assembly, and the packaging of the element into the virus-like particle. GAG precursors show similarities with both Copia and Gypsy GAG proteins, suggesting evolutionary relationships of TR-GAG elements with both families. Despite the lack of the enzymatic machinery required for their mobility, strong evidences suggest that TR-GAGs are still active. TR-GAGs represent ubiquitous nonautonomous structures that could be involved in the molecular diversities of plant genomes. PMID:25573958

  9. Intra-molecular cohesion of coils mediated by phenylalanine-glycine motifs in the natively unfolded domain of a nucleoporin

    Energy Technology Data Exchange (ETDEWEB)

    Krishnan, V V; Lau, E Y; Yamada, J; Denning, D P; Patel, S S; Colvin, M E; Rexach, M F

    2007-04-19

    The nuclear pore complex (NPC) provides the sole aqueous conduit for macromolecular exchange between the nucleus and cytoplasm of cells. Its conduit contains a size-selective gate and is populated by a family of NPC proteins that feature long natively-unfolded domains with phenylalanine-glycine repeats. These FG nucleoporins play key roles in establishing the NPC permeability barrier, but little is known about their dynamic structure. Here we used molecular modeling and biophysical techniques to characterize the dynamic ensemble of structures of a representative FG domain from the yeast nucleoporin Nup116. The results show that its FG motifs function as intra-molecular cohesion elements that impart order to the FG domain. The cohesion of coils mediated by FG motifs in the natively unfolded domain of Nup116 supports a type of tertiary structure, a native pre-molten globule, that could become quaternary at the NPC through recruitment of neighboring FG nucleoporins, forming one cohesive meshwork of intertwined filaments capable of gating protein diffusion across the NPC by size exclusion.

  10. Single-molecule FRET reveals the native-state dynamics of the IκBα ankyrin repeat domain.

    Science.gov (United States)

    Lamboy, Jorge A; Kim, Hajin; Dembinski, Holly; Ha, Taekjip; Komives, Elizabeth A

    2013-07-24

    Previous single-molecule fluorescence resonance energy transfer (smFRET) studies in which the second and sixth ankyrin repeats (ARs) of IκBα were labeled with FRET pairs showed slow fluctuations as if the IκBα AR domain was unfolding in its native state. To systematically probe where these slow dynamic fluctuations occur, we now present data from smFRET studies wherein FRET labels were placed at ARs 1 and 4 (mutant named AR 1-4), at ARs 2 and 5 (AR 2-5), and at ARs 3 and 6 (AR 3-6). The results presented here reveal that AR 6 most readily detaches/unfolds from the AR domain, undergoing substantial fluctuations at room temperature. AR 6 has fewer stabilizing consensus residues than the other IκBα ARs, probably contributing to the ease with which AR 6 "loses grip". AR 5 shows almost no fluctuations at room temperature, but a significant fraction of molecules shows fluctuations at 37 °C. Introduction of stabilizing mutations that are known to fold AR 6 dampen the fluctuations of AR 5, indicating that the AR 5 fluctuations are likely due to weakened inter-repeat stabilization from AR 6. AR 1 also fluctuates somewhat at room temperature, suggesting that fluctuations are a general behavior of ARs at ends of AR domains. Remarkably, AR 1 still fluctuates in the bound state, but mainly between 0.6 and 0.9 FRET efficiency, whereas in the free IκBα, the fluctuations extend to <0.5 FRET efficiency. Overall, our results provide a more complete picture of the energy landscape of the native state dynamics of an AR domain.

  11. The Non-canonical Tetratricopeptide Repeat (TPR) Domain of Fluorescent (FLU) Mediates Complex Formation with Glutamyl-tRNA Reductase.

    Science.gov (United States)

    Zhang, Min; Zhang, Feilong; Fang, Ying; Chen, Xuemin; Chen, Yuhong; Zhang, Wenxia; Dai, Huai-En; Lin, Rongcheng; Liu, Lin

    2015-07-10

    The tetratricopeptide repeat (TPR)-containing protein FLU is a negative regulator of chlorophyll biosynthesis in plants. It directly interacts through its TPR domain with glutamyl-tRNA reductase (GluTR), the rate-limiting enzyme in the formation of δ-aminolevulinic acid (ALA). Delineation of how FLU binds to GluTR is important for understanding the molecular basis for FLU-mediated repression of synthesis of ALA, the universal tetrapyrrole precursor. Here, we characterize the FLU-GluTR interaction by solving the crystal structures of the uncomplexed TPR domain of FLU (FLU(TPR)) at 1.45-Å resolution and the complex of the dimeric domain of GluTR bound to FLU(TPR) at 2.4-Å resolution. Three non-canonical TPR motifs of each FLU(TPR) form a concave surface and clamp the helix bundle in the C-terminal dimeric domain of GluTR. We demonstrate that a 2:2 FLU(TPR)-GluTR complex is the functional unit for FLU-mediated GluTR regulation and suggest that the formation of the FLU-GluTR complex prevents glutamyl-tRNA, the GluTR substrate, from binding with this enzyme. These results also provide insights into the spatial regulation of ALA synthesis by the membrane-located FLU protein.

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

    Science.gov (United States)

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

    2015-08-06

    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 Ca(2+)-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.

  13. Identification of multiple binding sites for the THAP domain of the Galileo transposase in the long terminal inverted-repeats.

    Science.gov (United States)

    Marzo, Mar; Liu, Danxu; Ruiz, Alfredo; Chalmers, Ronald

    2013-08-01

    Galileo is a DNA transposon responsible for the generation of several chromosomal inversions in Drosophila. In contrast to other members of the P-element superfamily, it has unusually long terminal inverted-repeats (TIRs) that resemble those of Foldback elements. To investigate the function of the long TIRs we derived consensus and ancestral sequences for the Galileo transposase in three species of Drosophilids. Following gene synthesis, we expressed and purified their constituent THAP domains and tested their binding activity towards the respective Galileo TIRs. DNase I footprinting located the most proximal DNA binding site about 70 bp from the transposon end. Using this sequence we identified further binding sites in the tandem repeats that are found within the long TIRs. This suggests that the synaptic complex between Galileo ends may be a complicated structure containing higher-order multimers of the transposase. We also attempted to reconstitute Galileo transposition in Drosophila embryos but no events were detected. Thus, although the limited numbers of Galileo copies in each genome were sufficient to provide functional consensus sequences for the THAP domains, they do not specify a fully active transposase. Since the THAP recognition sequence is short, and will occur many times in a large genome, it seems likely that the multiple binding sites within the long, internally repetitive, TIRs of Galileo and other Foldback-like elements may provide the transposase with its binding specificity.

  14. Taxonomic distribution, repeats, and functions of the S1 domain-containing proteins as members of the OB-fold family.

    Science.gov (United States)

    Deryusheva, Evgeniia I; Machulin, Andrey V; Selivanova, Olga M; Galzitskaya, Oxana V

    2017-04-01

    Proteins of the nucleic acid-binding proteins superfamily perform such functions as processing, transport, storage, stretching, translation, and degradation of RNA. It is one of the 16 superfamilies containing the OB-fold in protein structures. Here, we have analyzed the superfamily of nucleic acid-binding proteins (the number of sequences exceeds 200,000) and obtained that this superfamily prevalently consists of proteins containing the cold shock DNA-binding domain (ca. 131,000 protein sequences). Proteins containing the S1 domain compose 57% from the cold shock DNA-binding domain family. Furthermore, we have found that the S1 domain was identified mainly in the bacterial proteins (ca. 83%) compared to the eukaryotic and archaeal proteins, which are available in the UniProt database. We have found that the number of multiple repeats of S1 domain in the S1 domain-containing proteins depends on the taxonomic affiliation. All archaeal proteins contain one copy of the S1 domain, while the number of repeats in the eukaryotic proteins varies between 1 and 15 and correlates with the protein size. In the bacterial proteins, the number of repeats is no more than 6, regardless of the protein size. The large variation of the repeat number of S1 domain as one of the structural variants of the OB-fold is a distinctive feature of S1 domain-containing proteins. Proteins from the other families and superfamilies have either one OB-fold or change slightly the repeat numbers. On the whole, it can be supposed that the repeat number is a vital for multifunctional activity of the S1 domain-containing proteins. Proteins 2017; 85:602-613. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. The repeat domain of the type III effector protein PthA shows a TPR-like structure and undergoes conformational changes upon DNA interaction.

    Science.gov (United States)

    Murakami, Mário Tyago; Sforça, Mauricio Luis; Neves, Jorge Luiz; Paiva, Joice Helena; Domingues, Mariane Noronha; Pereira, André Luiz Araujo; Zeri, Ana Carolina de Mattos; Benedetti, Celso Eduardo

    2010-12-01

    Many plant pathogenic bacteria rely on effector proteins to suppress defense and manipulate host cell mechanisms to cause disease. The effector protein PthA modulates the host transcriptome to promote citrus canker. PthA possesses unusual protein architecture with an internal region encompassing variable numbers of near-identical tandem repeats of 34 amino acids termed the repeat domain. This domain mediates protein-protein and protein-DNA interactions, and two polymorphic residues in each repeat unit determine DNA specificity. To gain insights into how the repeat domain promotes protein-protein and protein-DNA contacts, we have solved the structure of a peptide corresponding to 1.5 units of the PthA repeat domain by nuclear magnetic resonance (NMR) and carried out small-angle X-ray scattering (SAXS) and spectroscopic studies on the entire 15.5-repeat domain of PthA2 (RD2). Consistent with secondary structure predictions and circular dichroism data, the NMR structure of the 1.5-repeat peptide reveals three α-helices connected by two turns that fold into a tetratricopeptide repeat (TPR)-like domain. The NMR structure corroborates the theoretical TPR superhelix predicted for RD2, which is also in agreement with the elongated shape of RD2 determined by SAXS. Furthermore, RD2 undergoes conformational changes in a pH-dependent manner and upon DNA interaction, and shows sequence similarities to pentatricopeptide repeat (PPR), a nucleic acid-binding motif structurally related to TPR. The results point to a model in which the RD2 structure changes its compactness as it embraces the DNA with the polymorphic diresidues facing the interior of the superhelix oriented toward the nucleotide bases.

  16. Nuclear Magnetic Resonance Structure of a Novel Globular Domain in RBM10 Containing OCRE, the Octamer Repeat Sequence Motif.

    Science.gov (United States)

    Martin, Bryan T; Serrano, Pedro; Geralt, Michael; Wüthrich, Kurt

    2016-01-01

    The OCtamer REpeat (OCRE) has been annotated as a 42-residue sequence motif with 12 tyrosine residues in the spliceosome trans-regulatory elements RBM5 and RBM10 (RBM [RNA-binding motif]), which are known to regulate alternative splicing of Fas and Bcl-x pre-mRNA transcripts. Nuclear magnetic resonance structure determination showed that the RBM10 OCRE sequence motif is part of a 55-residue globular domain containing 16 aromatic amino acids, which consists of an anti-parallel arrangement of six β strands, with the first five strands containing complete or incomplete Tyr triplets. This OCRE globular domain is a distinctive component of RBM10 and is more widely conserved in RBM10s across the animal kingdom than the ubiquitous RNA recognition components. It is also found in the functionally related RBM5. Thus, it appears that the three-dimensional structure of the globular OCRE domain, rather than the 42-residue OCRE sequence motif alone, confers specificity on RBM10 intermolecular interactions in the spliceosome.

  17. The relationship between the L1 and L2 domains of the insulin and epidermal growth factor receptors and leucine-rich repeat modules

    Directory of Open Access Journals (Sweden)

    Ward Colin W

    2001-07-01

    Full Text Available Abstract Background Leucine-rich repeats are one of the more common modules found in proteins. The leucine-rich repeat consensus motif is LxxLxLxxNxLxxLxxLxxLxx- where the first 11–12 residues are highly conserved and the remainder of the repeat can vary in size Leucine-rich repeat proteins have been subdivided into seven subfamilies, none of which include members of the epidermal growth factor receptor or insulin receptor families despite the similarity between the 3D structure of the L domains of the type I insulin-like growth factor receptor and some leucine-rich repeat proteins. Results Here we have used profile searches and multiple sequence alignments to identify the repeat motif Ixx-LxIxx-Nx-Lxx-Lxx-Lxx-Lxx- in the L1 and L2 domains of the insulin receptor and epidermal growth factor receptors. These analyses were aided by reference to the known three dimensional structures of the insulin-like growth factor type I receptor L domains and two members of the leucine rich repeat family, porcine ribonuclease inhibitor and internalin 1B. Pectate lyase, another beta helix protein, can also be seen to contain the sequence motif and much of the structural features characteristic of leucine-rich repeat proteins, despite the existence of major insertions in some of its repeats. Conclusion Multiple sequence alignments and comparisons of the 3D structures has shown that right-handed beta helix proteins such as pectate lyase and the L domains of members of the insulin receptor and epidermal growth factor receptor families, are members of the leucine-rich repeat superfamily.

  18. The nebulette repeat domain is necessary for proper maintenance of tropomyosin with the cardiac sarcomere.

    Science.gov (United States)

    Bonzo, Jeremy R; Norris, Andrea A; Esham, Michael; Moncman, Carole L

    2008-11-15

    Nebulette is a cardiac-specific isoform of the giant actin-binding protein nebulin. Nebulette, having a mass of approximately 100 kDa, is only predicted to extend 150 nm from the edge of the Z-lines. Overexpression of the nebulette C-terminal linker and/or SH3 domains in chicken cardiomyocytes results in a loss of endogenous nebulette with a concomitant loss of tropomyosin (TPM) and troponin, as well as a shortening of the thin filaments. These data suggest that nebulette's position in the sarcomere is important for the maintenance of TPM, troponin and thin filament length. To evaluate this hypothesis, N-terminal nested truncations tagged with GFP were expressed in chicken cardiomyocytes and the cells were analyzed for the distribution of myofilament proteins. Minimal effects on the myofilaments were observed with N-terminal deletions of up to 10 modules; however, deletion of 15 modules replicated the phenotype observed with expression of the C-terminal fragments. Expression of internal deletions of nebulette verifies that a site between module 10 and 15 is important for TPM maintenance within the sarcomeric lattice. We have additionally isolated TPM cDNAs from a yeast two hybrid (Y2H) analysis. These data indicate the importance of the nebulette-TPM interactions in the maintenance and stability of the thin filaments.

  19. The repeat domain of the melanosome fibril protein Pmel17 forms the amyloid core promoting melanin synthesis.

    Science.gov (United States)

    McGlinchey, Ryan P; Shewmaker, Frank; McPhie, Peter; Monterroso, Begoña; Thurber, Kent; Wickner, Reed B

    2009-08-18

    Pmel17 is a melanocyte protein necessary for eumelanin deposition 1 in mammals and found in melanosomes in a filamentous form. The luminal part of human Pmel17 includes a region (RPT) with 10 copies of a partial repeat sequence, pt.e.gttp.qv., known to be essential in vivo for filament formation. We show that this RPT region readily forms amyloid in vitro, but only under the mildly acidic conditions typical of the lysosome-like melanosome lumen, and the filaments quickly become soluble at neutral pH. Under the same mildly acidic conditions, the Pmel filaments promote eumelanin formation. Electron diffraction, circular dichroism, and solid-state NMR studies of Pmel17 filaments show that the structure is rich in beta sheet. We suggest that RPT is the amyloid core domain of the Pmel17 filaments so critical for melanin formation.

  20. Toxic PR poly-dipeptides encoded by the C9orf72 repeat expansion target LC domain polymers

    Science.gov (United States)

    Lin, Yi; Mori, Eiichiro; Kato, Masato; Xiang, Siheng; Wu, Leeju; Kwon, Ilmin; McKnight, Steven L.

    2016-01-01

    Summary Two complementary approaches were used in search of the intracellular targets of the toxic PR poly-dipeptide encoded by the repeat sequences expanded in the C9orf72 form of amyotrophic lateral sclerosis. The top categories of PRn-bound proteins include constituents of non-membrane invested cellular organelles and intermediate filaments. PRn targets are enriched for the inclusion of low complexity (LC) sequences. Evidence is presented indicating that LC sequences represent the direct target of PRn binding, and that interaction between the PRn poly-dipeptide and LC domains is polymer-dependent. These studies indicate that PRn-mediated toxicity may result from broad impediments to the dynamics of cell structure and information flow from gene to message to protein. PMID:27768897

  1. Toxic PR Poly-Dipeptides Encoded by the C9orf72 Repeat Expansion Target LC Domain Polymers.

    Science.gov (United States)

    Lin, Yi; Mori, Eiichiro; Kato, Masato; Xiang, Siheng; Wu, Leeju; Kwon, Ilmin; McKnight, Steven L

    2016-10-20

    Two complementary approaches were used in search of the intracellular targets of the toxic PR poly-dipeptide encoded by the repeat sequences expanded in the C9orf72 form of amyotrophic lateral sclerosis. The top categories of PRn-bound proteins include constituents of non-membrane invested cellular organelles and intermediate filaments. PRn targets are enriched for the inclusion of low complexity (LC) sequences. Evidence is presented indicating that LC sequences represent the direct target of PRn binding and that interaction between the PRn poly-dipeptide and LC domains is polymer-dependent. These studies indicate that PRn-mediated toxicity may result from broad impediments to the dynamics of cell structure and information flow from gene to message to protein.

  2. Structural and Biochemical Consequences of Disease-Causing Mutations in the Ankyrin Repeat Domain of the Human TRPV4 Channel

    Energy Technology Data Exchange (ETDEWEB)

    Inada, Hitoshi; Procko, Erik; Sotomayor, Marcos; Gaudet, Rachelle (Harvard-Med); (Harvard)

    2012-10-23

    The TRPV4 calcium-permeable cation channel plays important physiological roles in osmosensation, mechanosensation, cell barrier formation, and bone homeostasis. Recent studies reported that mutations in TRPV4, including some in its ankyrin repeat domain (ARD), are associated with human inherited diseases, including neuropathies and skeletal dysplasias, probably because of the increased constitutive activity of the channel. TRPV4 activity is regulated by the binding of calmodulin and small molecules such as ATP to the ARD at its cytoplasmic N-terminus. We determined structures of ATP-free and -bound forms of human TRPV4-ARD and compared them with available TRPV-ARD structures. The third inter-repeat loop region (Finger 3 loop) is flexible and may act as a switch to regulate channel activity. Comparisons of TRPV-ARD structures also suggest an evolutionary link between ARD structure and ATP binding ability. Thermal stability analyses and molecular dynamics simulations suggest that ATP increases stability in TRPV-ARDs that can bind ATP. Biochemical analyses of a large panel of TRPV4-ARD mutations associated with human inherited diseases showed that some impaired thermal stability while others weakened ATP binding ability, suggesting molecular mechanisms for the diseases.

  3. The molecular chaperone Hsp70 activates protein phosphatase 5 (PP5) by binding the tetratricopeptide repeat (TPR) domain.

    Science.gov (United States)

    Connarn, Jamie N; Assimon, Victoria A; Reed, Rebecca A; Tse, Eric; Southworth, Daniel R; Zuiderweg, Erik R P; Gestwicki, Jason E; Sun, Duxin

    2014-01-31

    Protein phosphatase 5 (PP5) is auto-inhibited by intramolecular interactions with its tetratricopeptide repeat (TPR) domain. Hsp90 has been shown to bind PP5 to activate its phosphatase activity. However, the functional implications of binding Hsp70 to PP5 are not yet clear. In this study, we find that both Hsp90 and Hsp70 bind to PP5 using a luciferase fragment complementation assay. A fluorescence polarization assay shows that Hsp90 (MEEVD motif) binds to the TPR domain of PP5 almost 3-fold higher affinity than Hsp70 (IEEVD motif). However, Hsp70 binding to PP5 stimulates higher phosphatase activity of PP5 than the binding of Hsp90. We find that PP5 forms a stable 1:1 complex with Hsp70, but the interaction appears asymmetric with Hsp90, with one PP5 binding the dimer. Solution NMR studies reveal that Hsc70 and PP5 proteins are dynamically independent in complex, tethered by a disordered region that connects the Hsc70 core and the IEEVD-TPR contact area. This tethered binding is expected to allow PP5 to carry out multi-site dephosphorylation of Hsp70-bound clients with a range of sizes and shapes. Together, these results demonstrate that Hsp70 recruits PP5 and activates its phosphatase activity which suggests dual roles for PP5 that might link chaperone systems with signaling pathways in cancer and development.

  4. Clinical and behavioral characteristics in FG syndrome.

    Science.gov (United States)

    Graham, J M; Superneau, D; Rogers, R C; Corning, K; Schwartz, C E; Dykens, E M

    1999-08-27

    FG syndrome is a rare X-linked recessive form of mental retardation, first described by Opitz and Kaveggia in 1974. Based on over 50 reported cases, FG syndrome is associated with agenesis of the corpus callosum, minor facial anomalies (high, broad forehead with frontal cowlick, ocular hypertelorism, down-slanted palpebral fissures, and small cupped auricles), relative macrocephaly, broad thumbs and halluces, and prominent fetal fingertip pads. Affected individuals manifest neonatal hypotonia and severe constipation, which usually resolves during mid-childhood. The hypotonia with joint hyperlaxity evolves into spasticity with joint contractures in later life. Affability, hyperactivity, and excessive talkativeness are noted frequently in patients with FG syndrome. Recently, we described three additional families (six additional patients) with FG syndrome who support the localization of a gene for the FG syndrome in chromosome region Xq12-q21 [Graham JM Jr, Tackels D, Dibbern K, Superneau D, Rodgers C, Corning K, Schwartz CE. 1998. Am J Med Genet 80:145-156.]. Using these same families and one additional sporadic case of FG syndrome, we compared behavioral and personality characteristics of 6 FG boys with other boys with syndromic and nonsyndromic mental retardation: eight with Down syndrome, seven with Prader-Willi syndrome, eight with nonspecific mental retardation, and 13 with Williams syndrome. Using the Vineland Adaptive Behavior Scales, the Reiss Personality Profiles, and the Achenbach Child Behavior Checklist, parents were asked to characterize the behavior and personality of their boys from ages 4 to 10 years. When compared with Williams syndrome, the FG boys had fewer internalizing behaviors and were significantly less anxious and withdrawn but had similar socially oriented, attention-seeking behaviors. On the Reiss Profile, FG boys were also quite similar to Williams syndrome boys. On the Vineland Scales, FG boys demonstrated significant relative strengths

  5. Cosmography in F(G) modified gravity

    CERN Document Server

    Setare, M R

    2012-01-01

    Investigating the accelerated expansion of the universe with cosmography is a best method to constraint cosmological models. In this work, in the $F(G)$ modified gravity framework, we obtain equations of motion in a flat FRW metric. Then we reconstruct the present day values of $F(G)$ and its derivatives with the cosmographic parameters on the only assumption that the universe is homogenous and isotropic on large scale. Also we investigate the conditions of cosmologically viable $F(G)$ gravity models with the fiducial data set values.

  6. Effects of pH on aggregation kinetics of the repeat domain of a functional amyloid, Pmel17

    Science.gov (United States)

    Pfefferkorn, Candace M.; McGlinchey, Ryan P.; Lee, Jennifer C.

    2010-01-01

    Pmel17 is a functional amyloidogenic protein whose fibrils act as scaffolds for pigment deposition in human skin and eyes. We have used the repeat domain (RPT, residues 315–444), an essential luminal polypeptide region of Pmel17, as a model system to study conformational changes from soluble unstructured monomers to β-sheet-containing fibrils. Specifically, we report on the effects of solution pH (4 → 7) mimicking pH conditions of melanosomes, acidic organelles where Pmel17 fibrils are formed. Local, secondary, and fibril structure were monitored via intrinsic Trp fluorescence, circular dichroism spectroscopy, and transmission electron microscopy, respectively. We find that W423 is a highly sensitive probe of amyloid assembly with spectral features reflecting local conformational and fibril morphological changes. A critical pH regime (5 ± 0.5) was identified for fibril formation suggesting the involvement of at least three carboxylic acids in the structural rearrangement necessary for aggregation. Moreover, we demonstrate that RPT fibril morphology can be transformed directly by changing solution pH. Based on these results, we propose that intramelanosomal pH regulates Pmel17 amyloid formation and its subsequent dissolution in vivo. PMID:21106765

  7. Ankyrin repeat domain-encoding genes in the wPip strain of Wolbachia from the Culex pipiens group

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    Parkhill Julian

    2007-09-01

    Full Text Available Abstract Background Wolbachia are obligate endosymbiotic bacteria maternally transmitted through the egg cytoplasm that are responsible for several reproductive disorders in their insect hosts, such as cytoplasmic incompatibility (CI in infected mosquitoes. Species in the Culex pipiens complex display an unusually high number of Wolbachia-induced crossing types, and based on present data, only the wPip strain is present. Results The sequencing of the wPip strain of Wolbachia revealed the presence of 60 ankyrin repeat domain (ANK encoding genes and expression studies of these genes were carried out in adult mosquitoes. One of these ANK genes, pk2, is shown to be part of an operon of three prophage-associated genes with sex-specific expression, and is present in two identical copies in the genome. Another homolog of pk2 is also present that is differentially expressed in different Cx. pipiens group strains. A further two ANK genes showed sex-specific regulation in wPip-infected Cx. pipiens group adults. Conclusion The high number, variability and differential expression of ANK genes in wPip suggest an important role in Wolbachia biology, and the gene family provides both markers and promising candidates for the study of reproductive manipulation.

  8. F&G Street Marsh Contaminants Investigation

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — F&G Street Marsh, located in San Diego Bay National Wildlife Refuge, Chula Vista, San Diego, California, is a tidally influenced wetland providing habitat for...

  9. Structure and Membrane Binding Properties of the Endosomal Tetratricopeptide Repeat (TPR) Domain-containing Sorting Nexins SNX20 and SNX21.

    Science.gov (United States)

    Clairfeuille, Thomas; Norwood, Suzanne J; Qi, Xiaying; Teasdale, Rohan D; Collins, Brett M

    2015-06-01

    Sorting nexins (SNX) orchestrate membrane trafficking and signaling events required for the proper distribution of proteins within the endosomal network. Their phox homology (PX) domain acts as a phosphoinositide (PI) recognition module that targets them to specific endocytic membrane domains. The modularity of SNX proteins confers a wide variety of functions from signaling to membrane deformation and cargo binding, and many SNXs are crucial modulators of endosome dynamics and are involved in a myriad of physiological and pathological processes such as neurodegenerative diseases, cancer, and inflammation. Here, we have studied the poorly characterized SNX20 and its paralogue SNX21, which contain an N-terminal PX domain and a C-terminal PX-associated B (PXB) domain of unknown function. The two proteins share similar PI-binding properties and are recruited to early endosomal compartments by their PX domain. The crystal structure of the SNX21 PXB domain reveals a tetratricopeptide repeat (TPR)-fold, a module that typically binds short peptide motifs, with three TPR α-helical repeats. However, the C-terminal capping helix adopts a highly unusual and potentially self-inhibitory topology. SAXS solution structures of SNX20 and SNX21 show that these proteins adopt a compact globular architecture, and membrane interaction analyses indicate the presence of overlapping PI-binding sites that may regulate their intracellular localization. This study provides the first structural analysis of this poorly characterized subfamily of SNX proteins, highlighting a likely role as endosome-associated scaffolds.

  10. A 170kDa multi-domain cystatin of Fasciola gigantica is active in the male reproductive system.

    Science.gov (United States)

    Geadkaew, Amornrat; Kosa, Nanthawat; Siricoon, Sinee; Grams, Suksiri Vichasri; Grams, Rudi

    2014-09-01

    Cystatins are functional as intra- and extracellular inhibitors of cysteine proteases and are expressed as single or multi-domain proteins. We have previously described two single domain type 1 cystatins in the trematode Fasciola gigantica that are released into the parasite's intestinal tract and exhibit inhibitory activity against endogenous and host cathepsin L and B proteases. In contrast, the here presented 170kDa multi-domain cystatin (FgMDC) comprises signal peptide and 12 tandem repeated cystatin-like domains with similarity to type 2 single domain cystatins. The domains show high sequence divergence with identity values often cystatins. Domain-specific antisera detected multiple forms of FgMDC ranging from 120kDa molecular mass in immunoblots of parasite crude extracts and ES product with different banding patterns for each antiserum demonstrating complex processing of the proprotein. The four domains with the highest conserved QVVAG motifs were expressed in Escherichia coli and the refolded recombinant proteins blocked cysteine protease activity in the parasite's ES product. Strikingly, immunohistochemical analysis using seven domain-specific antisera localized FgMDC in testis lobes and sperm. It is speculated that the processed cystatin-like domains have function analogous to the mammalian group of male reproductive tissue-specific type 2 cystatins and are functional in spermiogenesis and fertilization.

  11. Probing the mechanism of amyloidogenesis through a tandem repeat of the PI3-SH3 domain suggests a generic model for protein aggregation and fibril formation.

    Science.gov (United States)

    Bader, Reto; Bamford, Richard; Zurdo, Jesús; Luisi, Ben F; Dobson, Christopher M

    2006-02-10

    Aggregation of the SH3 domain of the PI3 kinase, both as a single domain and as a tandem repeat in which the C terminus of one domain is linked to the N terminus of another by a flexible linker of ten glycine/serine residues, has been studied under a range of conditions in order to investigate the mechanism of protein aggregation and amyloid formation. The tandem repeat was found to form amyloid fibrils much more readily than the single domain under the acidic conditions used here, and the fibrils themselves have higher morphological homogeneity. The folding-unfolding transition of the PI3-SH3 domain shows two-state behaviour and is pH dependent; at pH 3.6, which is near the pH mid-point for folding and only slightly below the isoelectric point of the protein, both the single domain and the tandem repeat spontaneously form broad distributions of soluble oligomers without requirement for nucleation. Under prolonged incubation under these conditions, the oligomers convert into thin, curly fibrils that interact with thioflavin-T, suggesting that they contain an organised beta-sheet structure. Under more acidic conditions (pH 2.0) where the proteins are fully denatured and carry a positive net charge, long, straight fibrils are formed in a process having a pronounced lag phase. The latter was found to be reduced dramatically by the addition of oligomers exceeding a critical size of approximately 20 molecules. The results suggest that the process of aggregation of these SH3 domains can take place by a variety of mechanisms, ranging from downhill formation of relatively amorphous species to nucleated formation of highly organised structures, the relative importance of which varies greatly with solution conditions. Comparison with the behaviour of other amyloidogenic systems suggests that the general mechanistic features outlined here are likely to be common to at least a wide variety of peptides and proteins.

  12. The ankyrin repeats and DHHC S-acyl transferase domain of AKR1 act independently to regulate switching from vegetative to mating states in yeast.

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    Piers A Hemsley

    Full Text Available Signal transduction from G-protein coupled receptors to MAPK cascades through heterotrimeric G-proteins has been described for many eukaryotic systems. One of the best-characterised examples is the yeast pheromone response pathway, which is negatively regulated by AKR1. AKR1-like proteins are present in all eukaryotes and contain a DHHC domain and six ankyrin repeats. Whilst the DHHC domain dependant S-acyl transferase (palmitoyl transferase function of AKR1 is well documented it is not known whether the ankyrin repeats are also required for this activity. Here we show that the ankyrin repeats of AKR1 are required for full suppression of the yeast pheromone response pathway, by sequestration of the Gβγ dimer, and act independently of AKR1 S-acylation function. Importantly, the functions provided by the AKR1 ankyrin repeats and DHHC domain are not required on the same molecule to fully restore WT phenotypes and function. We also show that AKR1 molecules are S-acylated at locations other than the DHHC cysteine, increasing the abundance of AKR1 in the cell. Our results have important consequences for studies of AKR1 function, including recent attempts to characterise S-acylation enzymology and kinetics. Proteins similar to AKR1 are found in all eukaryotes and our results have broad implications for future work on these proteins and the control of switching between Gβγ regulated pathways.

  13. Cross-talk between the epidermal growth factor-like repeats/fibronectin 6-8 repeats domains of Tenascin-R and microglia modulates neural stem/progenitor cell proliferation and differentiation.

    Science.gov (United States)

    Liao, Hong; Huang, Wenhui; Niu, Rui; Sun, Lixin; Zhang, Luyong

    2008-01-01

    Mounting evidence has demonstrated that the microenvironment of stem/progenitor cells plays an important role in their proliferation and commitment to their fate. However, it remains unclear how all elements, such as astrocytes, microglia, extracellular matrix molecules, soluble factors, and their cross-talk interactions in the microenvironments, affect neural stem/progenitor cell fate. This work explored the influences of cross-talk between Tenascin-R (TN-R) and microglia on neural stem/progenitor cell proliferation and differentiation. Our results show that microglia triggered by TN-R distinct domains EGF-like repeats (EGFL) and fibronectin 6-8 repeats (FN6-8) significantly enhanced the proliferation of neural stem/progenitor cells and also obviously induced the differentiation into neurons but not oligodendrocytes. Neurite processes of neurons generated from neural progenitor cells were promoted by both EGFL and FN6-8 domains-activated microglia. Microglia triggered by EGFL and FN6-8 secreted brain-derived neurotrophic factor (BDNF) and transforming growth factor-beta (TGF-beta); interestingly, FN6-8 could activate microglia to secrete nerve growth factor in addition to BDNF and TGF-beta, but EGFL domain could not. All these data implied that the cross-talk between TN-R distinct domains EGFL/FN6-8 and microglia promoted neural stem/progenitor cell proliferation and induced their differentiation into neurons.

  14. Anchoring skeletal muscle development and disease: The role of ankyrin repeat domain containing proteins in muscle physiology

    NARCIS (Netherlands)

    J-M. Tee (Jin-Ming); M.P. Peppelenbosch (Maikel)

    2010-01-01

    textabstractThe ankyrin repeat is a protein module with high affinity for other ankyrin repeats based on strong Van der Waals forces. The resulting dimerization is unusually resistant to both mechanical forces and alkanization, making this module exceedingly useful for meeting the extraordinary dema

  15. One repeat of the cell wall binding domain is sufficient for anchoring the Lactobacillus acidophilus surface layer protein

    NARCIS (Netherlands)

    Smit, E.; Pouwels, P.H.

    2002-01-01

    The N-terminal repeat (SAC1) of the S-protein of Lactobacillus acidophilus bound efficiently and specifically to cell wall fragments (CWFs) when fused to green fluorescent protein, whereas the C-terminal repeat (SAC2) did not. Treatment of CWFs with hydrofluoric acid, but not phenol, prevented bindi

  16. A Two-amino Acid Mutation Encountered in Duchenne Muscular Dystrophy Decreases Stability of the Rod Domain 23 (R23) Spectrin-like Repeat of Dystrophin.

    Science.gov (United States)

    Legardinier, Sébastien; Legrand, Baptiste; Raguénès-Nicol, Céline; Bondon, Arnaud; Hardy, Serge; Tascon, Christophe; Le Rumeur, Elisabeth; Hubert, Jean-François

    2009-03-27

    Lack of functional dystrophin causes severe Duchenne muscular dystrophy. The subsarcolemmal location of dystrophin, as well as its association with both cytoskeleton and membrane, suggests a role in the mechanical regulation of muscular membrane stress. In particular, phenotype rescue in a Duchenne muscular dystrophy mice model has shown that some parts of the central rod domain of dystrophin, constituted by 24 spectrin-like repeats, are essential. In this study, we made use of rare missense pathogenic mutations in the dystrophin gene and analyzed the biochemical properties of the isolated repeat 23 bearing single or double mutations E2910V and N2912D found in muscle dystrophy with severity grading. No dramatic effect on secondary and tertiary structure of the repeat was found in mutants compared with wild type as revealed by circular dichroism and NMR. Thermal and chemical unfolding data from circular dichroism and tryptophan fluorescence show significant decrease of stability for the mutants, and stopped-flow spectroscopy shows decreased refolding rates. The most deleterious single mutation is the N2912D replacement, although we observe additive effects of the two mutations on repeat stability. Based on three-dimensional structures built by homology molecular modeling, we discuss the modifications of the mutation-induced repeat stability. We conclude that the main forces involved in repeat stability are electrostatic inter-helix interactions that are disrupted following mutations. This study represents the first analysis at the protein level of the consequences of missense mutations in the human dystrophin rod domain. Our results suggest that it may participate in mechanical weakening of dystrophin-deficient muscle.

  17. Inducible polymerization and two-dimensional assembly of the repeats-in-toxin (RTX) domain from the Pseudomonas aeruginosa alkaline protease.

    Science.gov (United States)

    Zhang, Liang; Franks, Jonathon; Stolz, Donna B; Conway, James F; Thibodeau, Patrick H

    2014-10-21

    Self-assembling proteins represent potential scaffolds for the organization of enzymatic activities. The alkaline protease repeats-in-toxin (RTX) domain from Pseudomonas aeruginosa undergoes multiple structural transitions in the presence and absence of calcium, a native structural cofactor. In the absence of calcium, this domain is capable of spontaneous, ordered polymerization, producing amyloid-like fibrils and large two-dimensional protein sheets. This polymerization occurs under near-physiological conditions, is rapid, and can be controlled by regulating calcium in solution. Fusion of the RTX domain to a soluble protein results in the incorporation of engineered protein function into these macromolecular assemblies. Applications of this protein sequence in bacterial adherence and colonization and the generation of biomaterials are discussed.

  18. The ACR11 encodes a novel type of chloroplastic ACT domain repeat protein that is coordinately expressed with GLN2 in Arabidopsis

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    Hsu Chih-Ping

    2011-08-01

    Full Text Available Abstract Background The ACT domain, named after bacterial aspartate kinase, chorismate mutase and TyrA (prephenate dehydrogenase, is a regulatory domain that serves as an amino acid-binding site in feedback-regulated amino acid metabolic enzymes. We have previously identified a novel type of ACT domain-containing protein family, the ACT domain repeat (ACR protein family, in Arabidopsis. Members of the ACR family, ACR1 to ACR8, contain four copies of the ACT domain that extend throughout the entire polypeptide. Here, we describe the identification of four novel ACT domain-containing proteins, namely ACR9 to ACR12, in Arabidopsis. The ACR9 and ACR10 proteins contain three copies of the ACT domain, whereas the ACR11 and ACR12 proteins have a putative transit peptide followed by two copies of the ACT domain. The functions of these plant ACR proteins are largely unknown. Results The ACR11 and ACR12 proteins are predicted to target to chloroplasts. We used protoplast transient expression assay to demonstrate that the Arabidopsis ACR11- and ACR12-green fluorescent fusion proteins are localized to the chloroplast. Analysis of an ACR11 promoter-β-glucuronidase (GUS fusion in transgenic Arabidopsis revealed that the GUS activity was mainly detected in mature leaves and sepals. Interestingly, coexpression analysis revealed that the GLN2, which encodes a chloroplastic glutamine synthetase, has the highest mutual rank in the coexpressed gene network connected to ACR11. We used RNA gel blot analysis to confirm that the expression pattern of ACR11 is similar to that of GLN2 in various organs from 6-week-old Arabidopsis. Moreover, the expression of ACR11 and GLN2 is highly co-regulated by sucrose and light/dark treatments in 2-week-old Arabidopsis seedlings. Conclusions This study reports the identification of four novel ACT domain repeat proteins, ACR9 to ACR12, in Arabidopsis. The ACR11 and ACR12 proteins are localized to the chloroplast, and the expression

  19. Leucine-rich repeat, immunoglobulin-like and transmembrane domain 3 (LRIT3) is a modulator of FGFR1

    NARCIS (Netherlands)

    Kim, S.D.; Liu, J.L.; Roscioli, T.; Buckley, M.F.; Yagnik, G.; Boyadjiev, S.A.; Kim, J.

    2012-01-01

    Fibroblast growth factor receptors (FGFRs) play critical roles in craniofacial and skeletal development via multiple signaling pathways including MAPK, PI3K/AKT, and PLC-?. FGFR-mediated signaling is modulated by several regulators. Proteins with leucine-rich repeat (LRR) and/or immunoglobulin (IG)

  20. Alternative splicing of the angiogenesis associated extra-domain B of fibronectin regulates the accessibility of the B-C loop of the type III repeat 8.

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    Elisa Ventura

    Full Text Available BACKGROUND: Fibronectin (FN is a multi-domain molecule involved in many cellular processes, including tissue repair, embryogenesis, blood clotting, and cell migration/adhesion. The biological activities of FN are mediated by exposed loops located mainly at the interdomain interfaces that interact with various molecules such as, but not only, integrins. Different FN isoforms arise from the alternative splicing of the pre-mRNA. In malignancies, the splicing pattern of FN pre-mRNA is altered; in particular, the FN isoform containing the extra-domain B (ED-B, a complete FN type III repeat constituted by 91 residues, is undetectable in normal adult tissues, but exhibits a much greater expression in fetal and tumor tissues, and is accumulated around neovasculature during angiogenic processes, thus making ED-B one of the best markers and targets of angiogenesis. The functions of ED-B are still unclear; however, it has been postulated that the insertion of an extra-domain such as ED-B modifies the domain-domain interface and may unmask loops that are otherwise cryptic, thus giving FN new potential activities. METHODOLOGY: We used the mAb C6, which reacts with ED-B containing FN, but not with ED-B-free FN and various recombinant FN fragments containing mutations, to precisely localize the epitopes recognized by the mAb C6. CONCLUSION: We formally demonstrated that the inclusion of the alternatively spliced angiogenesis-associated ED-B leads to the unmasking of the FNIII 8 B-C loop that is cryptic in FN molecules lacking ED-B. Thus, the mAb C6, in addition to providing a new reagent for angiogenesis targeting, represents a new tool for the study of the potential biological functions of the B-C loop of the repeat FNIII 8 that is unmasked during angiogenic processes.

  1. Regulation of Nucleocytoplasmic Shuttling of Bruton's Tyrosine Kinase (Btk) through a Novel SH3-Dependent Interaction with Ankyrin Repeat Domain 54 (ANKRD54)

    Science.gov (United States)

    Hussain, Alamdar; Mohammad, Dara K.; Mohamed, Abdalla J.; Nguyen, Vivian; Metalnikov, Pavel; Colwill, Karen; Pawson, Tony; Nore, Beston F.

    2012-01-01

    Bruton's tyrosine kinase (Btk), belonging to the Tec family of tyrosine kinases (TFKs), is essential for B-lymphocyte development. Abrogation of Btk signaling causes human X-linked agammaglobulinemia (XLA) and murine X-linked immunodeficiency (Xid). We employed affinity purification of Flag-tagged Btk, combined with tandem mass spectrometry, to capture and identify novel interacting proteins. We here characterize the interaction with ankryin repeat domain 54 protein (ANKRD54), also known as Lyn-interacting ankyrin repeat protein (Liar). While Btk is a nucleocytoplasmic protein, the Liar pool was found to shuttle at a higher rate than Btk. Importantly, our results suggest that Liar mediates nuclear export of both Btk and another TFK, Txk/Rlk. Liar-mediated Btk shuttling was enriched for activation loop, nonphosphorylated Btk and entirely dependent on Btk's SH3 domain. Liar also showed reduced binding to an aspartic acid phosphomimetic SH3 mutant. Three other investigated nucleus-located proteins, Abl, estrogen receptor β (ERβ), and transcription factor T-bet, were all unaffected by Liar. We mapped the interaction site to the C terminus of the Btk SH3 domain. A biotinylated, synthetic Btk peptide, ARDKNGQEGYIPSNYVTEAEDS, was sufficient for this interaction. Liar is the first protein identified that specifically influences the nucleocytoplasmic shuttling of Btk and Txk and belongs to a rare group of known proteins carrying out this activity in a Crm1-dependent manner. PMID:22527282

  2. Interplay between I308 and Y310 residues in the third repeat of microtubule-binding domain is essential for tau filament formation.

    Science.gov (United States)

    Naruto, Keiko; Minoura, Katsuhiko; Okuda, Ryouhei; Taniguchi, Taizo; In, Yasuko; Ishida, Toshimasa; Tomoo, Koji

    2010-10-08

    Investigation of the mechanism of tau polymerization is indispensable for finding inhibitory conditions or identifying compounds preventing the formation of paired helical filament or oligomers. Tau contains a microtubule-binding domain consisting of three or four repeats in its C-terminal half. It has been considered that the key event in tau polymerization is the formation of a β-sheet structure arising from a short hexapeptide (306)VQIVYK(311) in the third repeat of tau. In this paper, we report for the first time that the C-H⋯π interaction between Ile308 and Tyr310 is the elemental structural scaffold essential for forming a dry "steric zipper" structure in tau amyloid fibrils.

  3. Effects of the deletion and over-expression of Fusarium graminearum gene FgHal2 on host response to mycovirus Fusarium graminearum virus 1.

    Science.gov (United States)

    Yu, Jisuk; Lee, Kyung-Mi; Son, Moonil; Kim, Kook-Hyung

    2015-09-01

    The mycovirus Fusarium graminearum virus 1 (FgV1) is associated with reduced virulence (hypovirulence) of Fusarium graminearum. Transcriptomic and proteomic expression profiling have shown that many F. graminearum genes are differentially expressed as a consequence of FgV1 infection. Several of these genes may be related to the maintenance of the virus life cycle. The host gene, FgHal2, which has a highly conserved 3'-phosphoadenosine 5'-phosphatase (PAP phosphatase-like) domain or inositol monophosphatase (IMPase) superfamily domain, shows reduced expression in response to FgV1 infection. We generated targeted gene deletion and over-expression mutants to clarify the possible function(s) of FgHal2 and its relationship to FgV1. The gene deletion mutant showed retarded growth, reduced aerial mycelia formation and reduced pigmentation, whereas over-expression mutants were morphologically similar to the wild-type (WT). Furthermore, compared with the WT, the gene deletion mutant produced fewer conidia and these showed abnormal morphology. The FgHal2 expression level was decreased by FgV1 infection at 120 h post-inoculation (hpi), whereas the levels were nine-fold greater for both the virus-free and virus-infected over-expression mutant than for the WT. FgV1 RNA accumulation was decreased in the deletion mutant at 48, 72 and 120 hpi. FgV1 RNA accumulation in the over-expression mutant was reduced relative to that of the WT at 48 and 120 hpi, but was similar to that of the WT at 72 hpi. The vertical transmission rate of FgV1 in the gene deletion mutant was low, suggesting that FgHal2 may be required for the maintenance of FgV1 in the host cell. Together, these results indicate that the putative 3'(2'),5'-bisphosphate nucleotidase gene, FgHal2, has diverse biological functions in the host fungus and may affect the viral RNA accumulation and transmission of FgV1.

  4. Bipartite Topology of Treponema pallidum Repeat Proteins C/D and I: OUTER MEMBRANE INSERTION, TRIMERIZATION, AND PORIN FUNCTION REQUIRE A C-TERMINAL β-BARREL DOMAIN.

    Science.gov (United States)

    Anand, Arvind; LeDoyt, Morgan; Karanian, Carson; Luthra, Amit; Koszelak-Rosenblum, Mary; Malkowski, Michael G; Puthenveetil, Robbins; Vinogradova, Olga; Radolf, Justin D

    2015-05-08

    We previously identified Treponema pallidum repeat proteins TprC/D, TprF, and TprI as candidate outer membrane proteins (OMPs) and subsequently demonstrated that TprC is not only a rare OMP but also forms trimers and has porin activity. We also reported that TprC contains N- and C-terminal domains (TprC(N) and TprC(C)) orthologous to regions in the major outer sheath protein (MOSP(N) and MOSP(C)) of Treponema denticola and that TprC(C) is solely responsible for β-barrel formation, trimerization, and porin function by the full-length protein. Herein, we show that TprI also possesses bipartite architecture, trimeric structure, and porin function and that the MOSP(C)-like domains of native TprC and TprI are surface-exposed in T. pallidum, whereas their MOSP(N)-like domains are tethered within the periplasm. TprF, which does not contain a MOSP(C)-like domain, lacks amphiphilicity and porin activity, adopts an extended inflexible structure, and, in T. pallidum, is tightly bound to the protoplasmic cylinder. By thermal denaturation, the MOSP(N) and MOSP(C)-like domains of TprC and TprI are highly thermostable, endowing the full-length proteins with impressive conformational stability. When expressed in Escherichia coli with PelB signal sequences, TprC and TprI localize to the outer membrane, adopting bipartite topologies, whereas TprF is periplasmic. We propose that the MOSP(N)-like domains enhance the structural integrity of the cell envelope by anchoring the β-barrels within the periplasm. In addition to being bona fide T. pallidum rare outer membrane proteins, TprC/D and TprI represent a new class of dual function, bipartite bacterial OMP.

  5. A repeat sequence domain of the ring-exported protein-1 of Plasmodium falciparum controls export machinery architecture and virulence protein trafficking.

    Science.gov (United States)

    McHugh, Emma; Batinovic, Steven; Hanssen, Eric; McMillan, Paul J; Kenny, Shannon; Griffin, Michael D W; Crawford, Simon; Trenholme, Katharine R; Gardiner, Donald L; Dixon, Matthew W A; Tilley, Leann

    2015-12-01

    The malaria parasite Plasmodium falciparum dramatically remodels its host red blood cell to enhance its own survival, using a secretory membrane system that it establishes outside its own cell. Cisternal organelles, called Maurer's clefts, act as a staging point for the forward trafficking of virulence proteins to the red blood cell (RBC) membrane. The Ring-EXported Protein-1 (REX1) is a Maurer's cleft resident protein. We show that inducible knockdown of REX1 causes stacking of Maurer's cleft cisternae without disrupting the organization of the knob-associated histidine-rich protein at the RBC membrane. Genetic dissection of the REX1 sequence shows that loss of a repeat sequence domain results in the formation of giant Maurer's cleft stacks. The stacked Maurer's clefts are decorated with tether-like structures and retain the ability to dock onto the RBC membrane skeleton. The REX1 mutant parasites show deficient export of the major virulence protein, PfEMP1, to the red blood cell surface and markedly reduced binding to the endothelial cell receptor, CD36. REX1 is predicted to form a largely α-helical structure, with a repetitive charge pattern in the repeat sequence domain, providing potential insights into the role of REX1 in Maurer's cleft sculpting.

  6. SNARE protein FgVam7 controls growth, asexual and sexual development, and plant infection in Fusarium graminearum.

    Science.gov (United States)

    Zhang, Haifeng; Li, Bing; Fang, Qin; Li, Ying; Zheng, Xiaobo; Zhang, Zhengguang

    2016-01-01

    Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins play critical and conserved roles in membrane fusion and vesicle transport of eukaryotic cells. Previous studies have shown that various homologues of SNARE proteins are also important in the infection of host plants by pathogenic fungi. Here, we report the characterization of a SNARE homologue, FgVam7, from Fusarium graminearum that causes head blight in wheat and barley worldwide. Phylogenetic analysis and domain comparison reveal that FgVam7 is homologous to Vam7 proteins of Saccharomyces cerevisiae (ScVam7), Magnaporthe oryzae (MoVam7) and several additional fungi by containing a PhoX homology (PX) domain and a SNARE domain. We show that FgVam7 plays a regulatory role in cellular differentiation and virulence in F. graminearum. Deletion of FgVAM7 significantly reduces vegetative growth, conidiation and conidial germination, sexual reproduction and virulence. The ΔFgvam7 mutant also exhibits a defect in vacuolar maintenance and delayed endocytosis. Moreover, the ΔFgvam7 mutant is insensitive to salt and osmotic stresses, and hypersensitive to cell wall stressors. Further characterization of FgVam7 domains indicate that the PX and SNARE domains are conserved in controlling Vam7 protein localization and function, respectively. Finally, FgVam7 has been shown to positively regulate the expression of several deoxynivalenol (DON) biosynthesis genes TRI5, TRI6 and TRI101, and DON production. Our studies provide evidence for SNARE proteins as an additional means of regulatory mechanisms that govern growth, differentiation and virulence of pathogenic fungi.

  7. Inhibitor of apoptosis (IAP)-like protein lacks a baculovirus IAP repeat (BIR) domain and attenuates cell death in plant and animal systems.

    Science.gov (United States)

    Kim, Woe Yeon; Lee, Sun Yong; Jung, Young Jun; Chae, Ho Byoung; Nawkar, Ganesh M; Shin, Mi Rim; Kim, Sun Young; Park, Jin Ho; Kang, Chang Ho; Chi, Yong Hun; Ahn, Il Pyung; Yun, Dae Jin; Lee, Kyun Oh; Kim, Young-Myeong; Kim, Min Gab; Lee, Sang Yeol

    2011-12-09

    A novel Arabidopsis thaliana inhibitor of apoptosis was identified by sequence homology to other known inhibitor of apoptosis (IAP) proteins. Arabidopsis IAP-like protein (AtILP) contained a C-terminal RING finger domain but lacked a baculovirus IAP repeat (BIR) domain, which is essential for anti-apoptotic activity in other IAP family members. The expression of AtILP in HeLa cells conferred resistance against tumor necrosis factor (TNF)-α/ActD-induced apoptosis through the inactivation of caspase activity. In contrast to the C-terminal RING domain of AtILP, which did not inhibit the activity of caspase-3, the N-terminal region, despite displaying no homology to known BIR domains, potently inhibited the activity of caspase-3 in vitro and blocked TNF-α/ActD-induced apoptosis. The anti-apoptotic activity of the AtILP N-terminal domain observed in plants was reproduced in an animal system. Transgenic Arabidopsis lines overexpressing AtILP exhibited anti-apoptotic activity when challenged with the fungal toxin fumonisin B1, an agent that induces apoptosis-like cell death in plants. In AtIPL transgenic plants, suppression of cell death was accompanied by inhibition of caspase activation and DNA fragmentation. Overexpression of AtILP also attenuated effector protein-induced cell death and increased the growth of an avirulent bacterial pathogen. The current results demonstrated the existence of a novel plant IAP-like protein that prevents caspase activation in Arabidopsis and showed that a plant anti-apoptosis gene functions similarly in plant and animal systems.

  8. Structural and biochemical analysis of nuclease domain of clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 3 (Cas3).

    Science.gov (United States)

    Mulepati, Sabin; Bailey, Scott

    2011-09-09

    RNA transcribed from clustered regularly interspaced short palindromic repeats (CRISPRs) protects many prokaryotes from invasion by foreign DNA such as viruses, conjugative plasmids, and transposable elements. Cas3 (CRISPR-associated protein 3) is essential for this CRISPR protection and is thought to mediate cleavage of the foreign DNA through its N-terminal histidine-aspartate (HD) domain. We report here the 1.8 Å crystal structure of the HD domain of Cas3 from Thermus thermophilus HB8. Structural and biochemical studies predict that this enzyme binds two metal ions at its active site. We also demonstrate that the single-stranded DNA endonuclease activity of this T. thermophilus domain is activated not by magnesium but by transition metal ions such as manganese and nickel. Structure-guided mutagenesis confirms the importance of the metal-binding residues for the nuclease activity and identifies other active site residues. Overall, these results provide a framework for understanding the role of Cas3 in the CRISPR system.

  9. Global analysis of ankyrin repeat domain C3HC4-type RING finger gene family in plants.

    Directory of Open Access Journals (Sweden)

    Xiaowei Yuan

    Full Text Available Ankyrin repeat (ANK C3HC4-type RING finger (RF genes comprise a large family in plants and play important roles in various physiological processes of plant life. In this study, we identified 187 ANK C3HC4-type RF proteins from 29 species with complete genomes and named the ANK C3HC4-type RF proteins the XB3-like proteins because they are structurally related to the rice (Oryza sativa XB3. A phylogenetic relationship analysis suggested that the XB3-like genes originated from ferns, and the encoded proteins fell into 3 major groups. Among these groups, we found that the spacing between the metal ligand position 6 and 7, and the conserved residues, which was in addition to the metal ligand amino acids, in the C3HC4-type RF were different. Using a wide range of protein structural analyses, protein models were established, and all XB3-like proteins were found to contain two to seven ANKs and a C3HC4-type RF. The microarray data for the XB3-like genes of Arabidopsis, Oryza sative, Zea mays and Glycine max revealed that the expression of XB3-like genes was in different tissues and during different life stages. The preferential expression of XB3-like genes in specified tissues and the response to phytohormone and abiotic stress treatments of Arabidopsis and Zea mays not only confirmed the microarray analysis data but also demonstrated that the XB3-like proteins play roles in plant growth and development as well as in stress responses. Our data provide a very useful reference for the identification and functional analysis of members of this gene family and also provide a new method for the genome-wide analysis of gene families.

  10. Intronic mutations outside of Alu-repeat-rich domains of the LDL receptor gene are a cause of familial hypercholesterolemia.

    Science.gov (United States)

    Amsellem, Sabine; Briffaut, Dorothée; Carrié, Alain; Rabès, Jean Pierre; Girardet, Jean Philippe; Fredenrich, Alexandre; Moulin, Philippe; Krempf, Michel; Reznik, Yves; Vialettes, Bernard; de Gennes, Jean Luc; Brukert, Eric; Benlian, Pascale

    2002-12-01

    Familial hypercholesterolemia (FH), a frequent monogenic condition complicated by premature cardiovascular disease, is characterized by high allelic heterogeneity at the low-density lipoprotein receptor ( LDLR) locus. Despite more than a decade of genetic testing, knowledge about intronic disease-causing mutations has remained limited because of lack of available genomic sequences. Based on the finding from bioinformatic analysis that Alu repeats represent 85% of LDLR intronic sequences outside exon-intron junctions, we designed a strategy to improve the exploration of genomic regions in the vicinity of exons in 110 FH subjects from an admixed population. In the first group of 42 patients of negative mutation carriers, as previously established by former screening strategies (denaturing gradient gel electrophoresis, DNA sequencing with former primers overlapping splice-sites, Southern Blotting), about half ( n=22) were found to be carriers of at least one heterozygous mutation. Among a second group of 68 newly recruited patients, 27% of mutation carriers ( n=37) had a splicing regulatory mutation. Overall, out of the 54 mutations identified, 13 were intronic, and 18 were novel, out of which nearly half were intronic. Two novel intronic mutations (IVS8-10G-->A within the polypyrimidine tract and IVS7+10G-->A downstream of donor site) might create potential aberrant splice sites according to neural-network computed estimation, contrary to 31 common single nucleotide variations also identified at exon-intron junctions. This new strategy of detecting the most likely disease-causing LDLR mutations outside of Alu-rich genomic regions reveals that intronic mutations may have a greater impact than previously reported on the molecular basis of FH.

  11. Expression and sub-cellular localization of leucine-rich repeats and immunoglobulin-like domains are related to antioxidant enzymes in human ependymoma and oligodendroglioma

    Institute of Scientific and Technical Information of China (English)

    Wei Yi; Lin Liu; Okechi Humphrey; Qianxue Chen; Shulan Huang

    2011-01-01

    The current study investigated correlations between the expression of leucine-rich repeats and immunoglobulin-like domain 1 (LRIG1) and antioxidant enzymes and related proteins, including manganese superoxide dismutase, glutamate cysteine ligase catalytic or regulatory subunit, thioredoxin and thioredoxin reductase, in both human ependymoma and oligodendroglioma. Results revealed that the cytoplasmic expression of LRIG1 was associated with expression of glutamate cysteine ligase catalytic subunit in the human ependymoma, while the nuclear expression of LRIG1 was associated with expression of thioredoxin reductase. In human oligodendroglioma, the cytoplasmic expression of LRIG1 was associated with expression of the glutamate cysteine ligase catalytic subunit. Both the nuclear and perinuclear expressions of LRIG1 were associated with expression of glutamate cysteine ligase regulatory subunit. These results indicated that several antioxidant enzymes and related proteins contributed to LRIG1 expression, and that these may participate in the antioxidation of the cells.

  12. A novel bispecific peptide HIV-1 fusion inhibitor targeting the N-terminal heptad repeat and fusion peptide domains in gp41.

    Science.gov (United States)

    Jiang, Xifeng; Jia, Qiyan; Lu, Lu; Yu, Fei; Zheng, Jishen; Shi, Weiguo; Cai, Lifeng; Jiang, Shibo; Liu, Keliang

    2016-12-01

    HIV-1 fusion with the target cell is initiated by the insertion of the gp41 fusion peptide (FP) into the target cell membrane and the interaction between the gp41 N- and C-terminal heptad repeats (NHR and CHR), followed by the formation of the six-helix bundle (6-HB) fusion core. Therefore, both FP and NHR are important targets for HIV-1 fusion inhibitors. Here, we designed and synthesized a dual-target peptidic HIV-1 fusion inhibitor, 4HR-LBD-VIRIP, in which 4HR-LBD is able to bind to the gp41 NHR domain, while VIRIP is able to interact with gp41 FP. We found that 4HR-LBD-VIRIP is about tenfold more potent than 4HR-LBD and VIRIP in inhibiting HIV-1IIIB infection and HIV-1 envelope glycoprotein (Env)-mediated cell-cell fusion, suggesting that this dual-target HIV-1 fusion inhibitor possesses a strong synergistic antiviral effect. A biophysical analysis indicates that 4HR-LBD-VIRIP can interact with N70 peptide that contains the gp41 NHR and FP domains and binds with lipid membrane. This study provides a new approach for designing novel viral fusion inhibitors against HIV and other enveloped viruses with class I membrane fusion proteins.

  13. A small peptide modeled after the NRAGE repeat domain inhibits XIAP-TAB1-TAK1 signaling for NF-κB activation and apoptosis in P19 cells.

    Directory of Open Access Journals (Sweden)

    Jennifer A Rochira

    Full Text Available In normal growth and development, apoptosis is necessary to shape the central nervous system and to eliminate excess neurons which are not required for innervation. In some diseases, however, apoptosis can be either overactive as in some neurodegenerative disorders or severely attenuated as in the spread of certain cancers. Bone morphogenetic proteins (BMPs transmit signals for regulating cell growth, differentiation, and apoptosis. Responding to BMP receptors stimulated from BMP ligands, neurotrophin receptor-mediated MAGE homolog (NRAGE binds and functions with the XIAP-TAK1-TAB1 complex to activate p38(MAPK and induces apoptosis in cortical neural progenitors. NRAGE contains a unique repeat domain that is only found in human, mouse, and rat homologs that we theorize is pivotal in its BMP MAPK role. Previously, we showed that deletion of the repeat domain inhibits apoptosis, p38(MAPK phosphorylation, and caspase-3 cleavage in P19 neural progenitor cells. We also showed that the XIAP-TAB1-TAK1 complex is dependent on NRAGE for IKK-α/β phosphorylation and NF-κB activation. XIAP is a major inhibitor of caspases, the main executioners of apoptosis. Although it has been shown previously that NRAGE binds to the RING domain of XIAP, it has not been determined which NRAGE domain binds to XIAP. Here, we used fluorescence resonance energy transfer (FRET to determine that there is a strong likelihood of a direct interaction between NRAGE and XIAP occurring at NRAGE's unique repeat domain which we also attribute to be the domain responsible for downstream signaling of NF-κB and activating IKK subunits. From these results, we designed a small peptide modeled after the NRAGE repeat domain which we have determined inhibits NF-κB activation and apoptosis in P19 cells. These intriguing results illustrate that the paradigm of the NRAGE repeat domain may hold promising therapeutic strategies in developing pharmaceutical solutions for combating harmful

  14. Creation of a novel telomere-cutting endonuclease based on the EN domain of telomere-specific non-long terminal repeat retrotransposon, TRAS1

    Directory of Open Access Journals (Sweden)

    Yoshitake Kazutoshi

    2010-04-01

    Full Text Available Abstract Background The ends of chromosomes, termed telomeres consist of repetitive DNA. The telomeric sequences shorten with cell division and, when telomeres are critically abbreviated, cells stop proliferating. However, in cancer cells, by the expression of telomerase which elongates telomeres, the cells can continue proliferating. Many approaches for telomere shortening have been pursued in the past, but to our knowledge, cutting telomeres in vivo has not so far been demonstrated. In addition, there is lack of information on the cellular effects of telomere shortening in human cells. Results Here, we created novel chimeric endonucleases to cut telomeres by fusing the endonuclease domain (TRAS1EN of the silkworm's telomere specific non-long terminal repeat retrotransposon TRAS1 to the human telomere-binding protein, TRF1. An in vitro assay demonstrated that the TRAS1EN-TRF1 chimeric endonucleases (T-EN and EN-T cut the human (TTAGGGn repeats specifically. The concentration of TRAS1EN-TRF1 chimeric endonucleases necessary for the cleavage of (TTAGGGn repeats was about 40-fold lower than that of TRAS1EN alone. When TRAS1EN-TRF1 endonucleases were introduced into human U2OS cancer cells using adenovirus vectors, the enzymes localized at telomeres of nuclei, cleaved and shortened the telomeric DNA by double-strand breaks. When human U2OS and HFL-1 fibroblast cells were infected with EN-T recombinant adenovirus, their cellular proliferation was suppressed for about 2 weeks after infection. In contrast, the TRAS1EN mutant (H258A chimeric endonuclease fused with TRF1 (ENmut-T did not show the suppression effect. The EN-T recombinant adenovirus induced telomere shortening in U2OS cells, activated the p53-dependent pathway and caused the senescence associated cellular responses, while the ENmut-T construct did not show such effects. Conclusions A novel TRAS1EN-TRF1 chimeric endonuclease (EN-T cuts the human telomeric repeats (TTAGGGn specifically in

  15. Repeatability and Reproducibility of Retinal Neuronal and Axonal Measures on Spectral-Domain Optical Coherence Tomography in Patients with Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Edwin Hong-Teck Loh

    2017-08-01

    Full Text Available BackgroundWith increasing interest in determining if measurement of retinal neuronal structure with spectral-domain optical coherence tomography (SD-OCT is useful in accessing neurodegenerative process in cognitive decline and development of dementia, it is important to evaluate whether the SD-OCT measurements are repeatable and reproducible in these patients.MethodsThis is a retrospective cohort study. Patients with Alzheimer’s disease (AD or mild cognitive impairment (MCI with no change in global clinical dementia rating (CDR score at 1-year follow-up were eligible to be included. Ganglion cell-inner plexiform layer (GC-IPL and retinal nerve fiber layer (RNFL parameters were measured with SD-OCT at baseline, 6-month, and 1-year follow-up visits. At baseline, SD-OCT scans were repeated to access intra-visit repeatability of the SD-OCT measurement. SD-OCT measurement over three visits was used to access inter-visit reproducibility. We calculated intraclass correlation coefficients (ICC and coefficients of variation (CoVs.ResultsWe included 32 patients with stable AD and 29 patients with stable MCI in the final analysis. For GC-IPL measures, the average intra-visit ICC was 0.969 (range: 0.948–0.985, and CoV was 1.81% (range: 1.14–2.40; while the average inter-visit ICC was 0.968 (0.941–0.985, and CoV was 1.91% (range: 1.24–2.32. The average ICC and CoV of intra-visit RNFL measured were 0.965 (range: 0.937–0.986 and 2.32% (range: 1.34–2.90%, respectively. The average ICC and CoV of inter-visit RNFL measures were 0.927 (range: 0.845–0.961 and 3.83% (range: 2.71–5.25%, respectively.ConclusionBoth GC-IPL and RNFL measurements had good intra-visit repeatability and inter-visit reproducibility over 1 year in elderly patients with no decline in cognitive function, suggesting that SD-OCT is a reliable tool to assess neurodegenerative process over time.

  16. Acetohydroxyacid synthase FgIlv2 and FgIlv6 are involved in BCAA biosynthesis, mycelial and conidial morphogenesis, and full virulence in Fusarium graminearum.

    Science.gov (United States)

    Liu, Xin; Han, Qi; Xu, Jianhong; Wang, Jian; Shi, Jianrong

    2015-11-10

    In this study, we characterized FgIlv2 and FgIlv6, the catalytic and regulatory subunits of acetohydroxyacid synthase (AHAS) from the important wheat head scab fungus Fusarium graminearum. AHAS catalyzes the first common step in the parallel pathways toward branched-chain amino acids (BCAAs: isoleucine, leucine, valine) and is the inhibitory target of several commercialized herbicides. Both FgILV2 and FgILV6 deletion mutants were BCAA-auxotrophic and showed reduced aerial hyphal growth and red pigmentation when cultured on PDA plates. Conidial formation was completely blocked in the FgILV2 deletion mutant ΔFgIlv2-4 and significantly reduced in the FgILV6 deletion mutant ΔFgIlv6-12. The auxotrophs of ΔFgIlv2-4 and ΔFgIlv6-12 could be restored by exogenous addition of BCAAs but relied on the designated nitrogen source the medium contained. Deletion of FgILV2 or FgILV6 also leads to hypersensitivity to various cellular stresses and reduced deoxynivalenol production. ΔFgIlv2-4 lost virulence completely on flowering wheat heads, whereas ΔFgIlv6-12 could cause scab symptoms in the inoculated spikelet but lost its aggressiveness. Taken together, our study implies the potential value of antifungals targeting both FgIlv2 and FgIlv6 in F. graminearum.

  17. Crystal structure of the G3BP2 NTF2-like domain in complex with a canonical FGDF motif peptide

    DEFF Research Database (Denmark)

    Kristensen, Ole

    2015-01-01

    The crystal structure of the NTF2-like domain of the human Ras GTPase SH3 Binding Protein (G3BP), isoform 2, was determined at a resolution of 2.75 Å in complex with a peptide containing a FGDF sequence motif. The overall structure of the protein is highly similar to the homodimeric N...... molecular modeling suggested that FGDF-motif containing peptides bind in an extended conformation into a hydrophobic groove on the surface of the G3BP NTF2-like domain in a manner similar to the known binding of FxFG nucleoporin repeats. The results in this paper provide evidence for a different binding...

  18. The C-terminal pentapeptide of Nanog tryptophan repeat domain interacts with Nac1 and regulates stem cell proliferation but not pluripotency.

    Science.gov (United States)

    Ma, Tianhua; Wang, Zhe; Guo, Yunqian; Pei, Duanqing

    2009-06-12

    Overexpression of Nanog in mouse embryonic stem (ES) cells has been shown to abrogate the requirement of leukemia inhibitory factor for self-renewal in culture. Little is known about the molecular mechanism of Nanog function. Here we describe the role of the tryptophan repeat (WR) domain, one of the two transactivators at its C terminus, in regulating stem cell proliferation as well as pluripotency. We first created a supertransactivator, W2W3x10, by duplicating repeats W2W3 10 times and discovered that it can functionally substitute for wild type WR at sustaining pluripotency, albeit with a significantly slower cell cycle, phenocopying Nanog(9W) with the C-terminal pentapeptide (WNAAP) of WR deleted. ES cells carrying both W2W3x10 and Nanog(9W) have a longer G1 phase, a shorter S phase in cell cycle distribution and progression analysis, and a lower level of pAkt(Ser473) compared with wild type Nanog, suggesting that both mutants impact the cell cycle machinery via the phosphatidylinositol 3-kinase/Akt pathway. Both mutants remain competent in dimerizing with Nanog but cannot form a complex with Nac1 efficiently, suggesting that WNAAP may be involved in Nac1 binding. By tagging Gal4DBD with WNAAP, we demonstrated that this pentapeptide is sufficient to confer Nac1 binding. Furthermore, we can rescue W2W3x10 by placing WNAAP at the corresponding locations. Finally, we found that Nanog and Nac1 synergistically up-regulate ERas expression and promote the proliferation of ES cells. These results suggest that Nanog interacts with Nac1 through WNAAP to regulate the cell cycle of ES cells via the ERas/phosphatidylinositol 3-kinase/Akt pathway, but not pluripotency, thus decoupling cell cycle control from pluripotency.

  19. Pleckstrin Homology (PH) Domain Leucine-rich Repeat Protein Phosphatase Controls Cell Polarity by Negatively Regulating the Activity of Atypical Protein Kinase C.

    Science.gov (United States)

    Xiong, Xiaopeng; Li, Xin; Wen, Yang-An; Gao, Tianyan

    2016-11-25

    The proper establishment of epithelial polarity allows cells to sense and respond to signals that arise from the microenvironment in a spatiotemporally controlled manner. Atypical PKCs (aPKCs) are implicated as key regulators of epithelial polarity. However, the molecular mechanism underlying the negative regulation of aPKCs remains largely unknown. In this study, we demonstrated that PH domain leucine-rich repeat protein phosphatase (PHLPP), a novel family of Ser/Thr protein phosphatases, plays an important role in regulating epithelial polarity by controlling the phosphorylation of both aPKC isoforms. Altered expression of PHLPP1 or PHLPP2 disrupted polarization of Caco2 cells grown in 3D cell cultures as indicated by the formation of aberrant multi-lumen structures. Overexpression of PHLPP resulted in a decrease in aPKC phosphorylation at both the activation loop and the turn motif sites; conversely, knockdown of PHLPP increased aPKC phosphorylation. Moreover, in vitro dephosphorylation experiments revealed that both aPKC isoforms were substrates of PHLPP. Interestingly, knockdown of PKCζ, but not PKCι, led to similar disruption of the polarized lumen structure, suggesting that PKCζ likely controls the polarization process of Caco2 cells. Furthermore, knockdown of PHLPP altered the apical membrane localization of aPKCs and reduced the formation of aPKC-Par3 complex. Taken together, our results identify a novel role of PHLPP in regulating aPKC and cell polarity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Genetic analysis of the leucine-rich repeat and lg domain containing Nogo receptor-interacting protein 1 gene in essential tremor.

    Science.gov (United States)

    Liang, Hui; Song, Zhi; Deng, Xiong; Xu, Hongbo; Zhu, Anding; Zheng, Wen; Zhao, Yongxiang; Deng, Hao

    2013-10-01

    Variants in the leucine-rich repeat and lg domain containing nogo receptor-interacting protein 1 gene (LINGO1) have been identified to be associated with the increased risk of essential tremor (ET), especially among Caucasians. To explore whether the LINGO1 gene plays a role in ET susceptibility, we performed a systematic genetic analysis of the coding region in the LINGO1 gene. Four nucleotide variants have been genotyped, including three known variants (rs2271398, rs2271397, and rs3743481), and a novel G → C transition (ss491228439). Extended analysis showed no significant difference in genotypic and allelic distributions between 151 patients and 301 control subjects for these four variants (all P > 0.05). However, further sex-stratified analysis revealed that the C allele of rs2271397 and ss491228439 contributed the risk of ET in female (P = 0.017, OR = 2.139, 95 % CI 1.135 ~ 4.030 for rs2271397 and P = 0.038, OR = 1.812, 95 % CI 1.027 ~ 3.194 for ss491228439). Haplotype analysis indicated that A465-C474-C714 haplotype was significantly associated with increased risk of ET in female (P = 0.041, OR = 1.800, 95 % CI 1.020 ~ 3.178). Our results indicate that the LINGO1 variants are associated with ET in Chinese Han female patients.

  1. A tetratricopeptide repeat domain-containing protein SSR1 located in mitochondria is involved in root development and auxin polar transport in Arabidopsis.

    Science.gov (United States)

    Zhang, Min; Wang, Cuiping; Lin, Qingfang; Liu, Aihua; Wang, Ting; Feng, Xuanjun; Liu, Jie; Han, Huiling; Ma, Yan; Bonea, Diana; Zhao, Rongmin; Hua, Xuejun

    2015-08-01

    Auxin polar transport mediated by a group of Pin-formed (PIN) transporters plays important roles in plant root development. However, the mechanism underlying the PIN expression and targeting in response to different developmental and environmental stimuli is still not fully understood. Here, we report a previously uncharacterized gene SSR1, which encodes a mitochondrial protein with tetratricopeptide repeat (TPR) domains, and show its function in root development in Arabidopsis thaliana. In ssr1-2, a SSR1 knock-out mutant, the primary root growth was dramatically inhibited due to severely impaired cell proliferation and cell elongation. Significantly lowered level of auxin was found in ssr1-2 roots by auxin measurement and was further supported by reduced expression of DR5-driven reporter gene. As a result, the maintenance of the root stem cell niche is compromised in ssr1-2. It is further revealed that the expression level of several PIN proteins, namely, PIN1, PIN2, PIN3, PIN4 and PIN7, were markedly reduced in ssr1-2 roots. In particular, we showed that the reduced protein level of PIN2 on cell membrane in ssr1-2 is due to impaired retrograde trafficking, possibly resulting from a defect in retromer sorting system, which destines PIN2 for degradation in vacuoles. In conclusion, our results indicated that SSR1 is functioning in root development in Arabidopsis, possibly by affecting PIN protein expression and subcellular targeting.

  2. Down-regulation of Leucine-rich Repeats and Immunoglobulin-like Domain Proteins (LRIG1-3) in HP75 Pituitary Adenoma Cell Line

    Institute of Scientific and Technical Information of China (English)

    GUO Dongsheng; HAN Lin; SHU Kai; CHEN Jian; LEI Ting

    2007-01-01

    Three human leucine-rich repeats and immunoglobulin-like domains (LRIG) genes and proteins, named LRIG1-3, has been previously characterized and it was proposed that they may act as suppressors of tumor growth. The LRIG1 protein can inhibit the growth of tumors of glial cells and the down-regulation of the LRIG1 gene may be involved in the development and progression of the tumor. Real-time reverse transcription-polymerase chain reaction (RT-PCR) is a recently developed technique for quantitative assessment of specific RNA levels. In the current study, it was demonstrated that LRIG1-3 and EGFR mRNA was detected in human pituitary adenoma cell lines and a normal pituitary sample, with differences in the expression levels. Compared to the normal pituitary samples, the expression of LRIG1-3 in HP75 cell line was lower, but the expression of EGFR in HP75 cell line was higher. The results are consistent with LRIG1-3 being tumour suppressor genes, and LRIG genes decreasing the expression of EGFR. The ratio of EGFR/LRIG1 was increased at least 13-fold in HP75 cells compared with the normal pituitary cells, which was also the case for the ratio of EGFR/LRIG2 (14-fold increase in HP75) and EGFR/LRIG3 (11-fold increase in HP75). Further studies were needed to elucidate the explicit role of LRIG genes as negative regulators of oncogenesis in human pituitary adenoma.

  3. New type of starch-binding domain: the direct repeat motif in the C-terminal region of Bacillus sp. no. 195 alpha-amylase contributes to starch binding and raw starch degrading.

    Science.gov (United States)

    Sumitani, J; Tottori, T; Kawaguchi, T; Arai, M

    2000-09-01

    The alpha-amylase from Bacillus sp. no. 195 (BAA) consists of two domains: one is the catalytic domain similar to alpha-amylases from animals and Streptomyces in the N-terminal region; the other is the functionally unknown domain composed of an approx. 90-residue direct repeat in the C-terminal region. The gene coding for BAA was expressed in Streptomyces lividans TK24. Three active forms of the gene products were found. The pH and thermal profiles of BAAs, and their catalytic activities for p-nitrophenyl maltopentaoside and soluble starch, showed almost the same behaviours. The largest, 69 kDa, form (BAA-alpha) was of the same molecular mass as that of the mature protein estimated from the nucleotide sequence, and had raw-starch-binding and -degrading abilities. The second largest, 60 kDa, form (BAA-beta), whose molecular mass was the same as that of the natural enzyme from Bacillus sp. no. 195, was generated by proteolytic processing between the two repeat sequences in the C-terminal region, and had lower activities for raw starch binding and degrading than those of BAA-alpha. The smallest, 50 kDa, form (BAA-gamma) contained only the N-terminal catalytic domain as a result of removal of the C-terminal repeat sequence, which led to loss of binding and degradation of insoluble starches. Thus the starch adsorption capacity and raw-starch-degrading activity of BAAs depends on the existence of the repeat sequence in the C-terminal region. BAA-alpha was specifically adsorbed on starch or dextran (alpha-1,4 or alpha-1,6 glucan), and specifically desorbed with maltose or beta-cyclodextrin. These observations indicated that the repeat sequence of the enzyme was functional in the starch-binding domain (SBD). We propose the designation of the homologues to the SBD of glucoamylase from Aspergillus niger as family I SBDs, the homologues to that of glucoamylase from Rhizopus oryzae as family II, and the homologues of this repeat sequence of BAA as family III.

  4. The N-terminal repeat and the ligand binding domain A of SdrI protein is involved in hydrophobicity of S. saprophyticus.

    Science.gov (United States)

    Kleine, Britta; Ali, Liaqat; Wobser, Dominique; Sakιnç, Türkân

    2015-03-01

    Staphylococcus saprophyticus is an important cause of urinary tract infection, and its cell surface hydrophobicity may contribute to virulence by facilitating adherence of the organism to uroepithelia. S. saprophyticus expresses the surface protein SdrI, a member of the serine-aspartate repeat (SD) protein family, which has multifunctional properties. The SdrI knock out mutant has a reduced hydrophobicity index (HPI) of 25%, and expressed in the non-hydrophobic Staphylococcus carnosus strain TM300 causes hydrophobicity. Using hydrophobic interaction chromatography (HIC), we confined the hydrophobic site of SdrI to the N-terminal repeat region. S. saprophyticus strains carrying different plasmid constructs lacking either the N-terminal repeats, both B or SD-repeats were less hydrophobic than wild type and fully complemented SdrI mutant (HPI: 51%). The surface hydrophobicity and HPI of both wild type and the complemented strain were also influenced by calcium (Ca(2+)) and were reduced from 81.3% and 82.4% to 10.9% and 12.3%, respectively. This study confirms that the SdrI protein of S. saprophyticus is a crucial factor for surface hydrophobicity and also gives a first significant functional description of the N-terminal repeats, which in conjunction with the B-repeats form an optimal hydrophobic conformation.

  5. Solar System Constraints on f(G) Dark Energy

    CERN Document Server

    Davis, Stephen C

    2007-01-01

    Corrections to solar system gravity are derived for f(G) gravity theories, in which a function of the Gauss-Bonnet curvature term is added to the gravitational action. Their effects on Newton's law, as felt by the planets, and on the frequency shift of signals from the Cassini spacecraft, are both determined. Despite the fact that the Gauss-Bonnet term is quadratic in curvature, the resulting constraints are substantial. It is shown that they practically rule out f(G) as an explanation for the late-time acceleration of the universe, except when it reduces to something very close to a cosmological constant.

  6. Language and Development in FG Syndrome with Callosal Agenesis.

    Science.gov (United States)

    McCardle, Peggy; Wilson, Bruce

    1993-01-01

    The FG syndrome is characterized by unusual facies; sudden infant death; developmental delay; and abnormalities of the cardiac, gastrointestinal, and central nervous systems. Serial evaluations of one case with isolated agenesis of the corpus callosum found consistent patterns over time in specific language impairments in syntactic and…

  7. Final Report DE-FG02-07ER64416

    Energy Technology Data Exchange (ETDEWEB)

    Seymour, Joseph D.

    2014-02-01

    The document provides the Final Report for DE-FG02-07ER64416 on the use of magnetic resonance (MR) methods to quantify transport in porous media impacted by biological and chemical processes. Products resulting from the research in the form of peer reviewed publications and conference presentations are presented. The research correlated numerical simulations and MR measurements to test simulation methodology. Biofilm and uranium detection by MR was demonstrated.

  8. The near-infrared spectroscopy-derived deoxygenated haemoglobin breaking-point is a repeatable measure that demarcates exercise intensity domains.

    Science.gov (United States)

    Iannetta, Danilo; Qahtani, Ahmad; Mattioni Maturana, Felipe; Murias, Juan Manuel

    2017-09-01

    A breaking-point in the near-infrared spectroscopy (NIRS)-derived deoxygenated haemoglobin ([HHb]) profile towards the end of a ramp incremental (RI) cycling test has been associated to the respiratory compensation point (RCP). Despite the physiological value of this measure, its repeatability remains unknown. The aim was to examine the repeatability of the [HHb] breaking-point ([HHb]BP) and its association to RCP during a RI cycling test. A repeated measures design was performed on 11 males (30.5±8.4 year; 76.5±8.4kg) and 4 females (30.5±5.9 year; 61.9±4.4 Kg). Gas exchange and NIRS [HHb] data were collected during RI tests performed on two different days separated by 48h. The [HHb]BP and the RCP were determined and compared for each trial. The [HHb]BP and the respiratory compensation point (RCP) occurred at the same VO2 in test 1 and test 2 ([HHb]BP: 3.49±0.52Lmin(-1) test 1; 3.48±0.45Lmin(-1) test 2; RCP: 3.38±0.40Lmin(-1) test 1; 3.38±0.44Lmin(-1) test 2) (P>0.05). The VO2 associated with the [HHb]BP and the VO2 at RCP were not significantly different from each other either in test 1 as well as in test 2 (P>0.05). Neither test 1 nor test 2 showed significant mean average error between the VO2 at the [HHb]BP and RCP using Bland & Altman plots. The [HHb]BP is a repeatable measure that consistently occurs towards the end of a RI test. The association between the [HHb]BP and the RCP reinforces the idea that these parameters may share similar mechanistic basis. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  9. Identification of Bacillus thuringiensis Cry3Aa toxin domain II loop 1 as the binding site of Tenebrio molitor cadherin repeat CR12.

    Science.gov (United States)

    Zúñiga-Navarrete, Fernando; Gómez, Isabel; Peña, Guadalupe; Amaro, Itzel; Ortíz, Ernesto; Becerril, Baltazar; Ibarra, Jorge E; Bravo, Alejandra; Soberón, Mario

    2015-04-01

    Bacillus thuringiensis Cry toxins exert their toxic effect by specific recognition of larval midgut proteins leading to oligomerization of the toxin, membrane insertion and pore formation. The exposed domain II loop regions of Cry toxins have been shown to be involved in receptor binding. Insect cadherins have shown to be functionally involved in toxin binding facilitating toxin oligomerization. Here, we isolated a VHH (VHHA5) antibody by phage display that binds Cry3Aa loop 1 and competed with the binding of Cry3Aa to Tenebrio molitor brush border membranes. VHHA5 also competed with the binding of Cry3Aa to a cadherin fragment (CR12) that was previously shown to be involved in binding and toxicity of Cry3Aa, indicating that Cry3Aa binds CR12 through domain II loop 1. Moreover, we show that a loop 1 mutant, previously characterized to have increased toxicity to T. molitor, displayed a correlative enhanced binding affinity to T. molitor CR12 and to VHHA5. These results show that Cry3Aa domain II loop 1 is a binding site of CR12 T. molitor cadherin.

  10. C6: A Monoclonal Antibody Specific for a Fibronectin Epitope Situated at the Interface between the Oncofoetal Extra-Domain B and the Repeat III8

    OpenAIRE

    Elisa Ventura; Cinzia Cordazzo; Rodolfo Quarto; Luciano Zardi; Camillo Rosano

    2016-01-01

    Background Fibronectin (FN) is a large multidomain molecule that is involved in many cellular processes. Different FN isoforms arise from alternative splicing of the pre-mRNA including, most notably, the FN isoform that contains the “extra-domain-B” (ED-B). The FN isoform containing ED-B (known as B-FN) is undetectable in healthy adult tissues but is present in large amounts in neoplastic and foetal tissues as well as on the blood vessels during angiogenesis. Thus, antibodies specific for B-F...

  11. The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs.

    Science.gov (United States)

    Purushotham, Sangeetha; Deivanayagam, Champion

    2014-08-01

    Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs as the first step in pathogenesis. Studying this interaction using recombinant proteins, we observed that calcium increases the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340. Our results also show that AgI/II adheres specifically with nanomolar affinity to the calcium-induced SRCR conformation in an immobilized state and not in solution. This interaction is significantly dependent on the O-linked carbohydrates present on the SRCRs. This study also establishes that a single SRCR domain of GP340 contains the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere. Compared with the single SRCR domain, the three tandem SRCR domains displayed a collective/cooperative increase in their bacterial adherence and aggregation. The previously described SRCRP2 peptide that was shown to aggregate several oral streptococci displayed limited aggregation and also nonspecific adherence compared to SRCR domains. Finally, we show distinct species-specific adherence/aggregation between Streptococcus mutans AgI/II and Streptococcus gordonii SspB in their interaction with the SRCRs. This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections.

  12. The conserved residue Arg46 in the N-terminal heptad repeat domain of HIV-1 gp41 is critical for viral fusion and entry.

    Directory of Open Access Journals (Sweden)

    Xiaoyi Wang

    Full Text Available During the process of HIV-1 fusion with the target cell, the N-terminal heptad repeat (NHR of gp41 interacts with the C-terminal heptad repeat (CHR to form fusogenic six-helix bundle (6-HB core. We previously identified a crucial residue for 6-HB formation and virus entry--Lys63 (K63 in the C-terminal region of NHR (aa 54-70, which forms a hydrophobic cavity. It can form an important salt bridge with Asp121 (D121 in gp41 CHR. Here, we found another important conserved residue for virus fusion and entry, Arg46 (R46, in the N-terminal region of NHR (aa 35-53, which forms a hydrogen bond with a polar residue, Asn43 (N43, in NHR, as a part of the hydrogen-bond network. R46 can also form a salt bridge with a negatively charged residue, Glu137 (E137, in gp41 CHR. Substitution of R46 with the hydrophobic residue Ala (R46A or the negatively charged residue Glu (R46E resulted in disruption of the hydrogen bond network, breakage of the salt bridge and reduction of 6-HB's stability, leading to impairment of viral fusion and decreased inhibition of N36, an NHR peptide. Similarly, CHR peptide C34 with substitution of E137 for Ala (E137A or Arg (E137R also exhibited reduced inhibitory activity against HIV-1 infection and HIV-1-mediated cell-to-cell fusion. These results suggest that the positively charged residue R46 and its hydrogen bond network, together with the salt bridge between R46 and E137, are important for viral fusion and entry and may therefore serve as a target for designing novel HIV fusion/entry inhibitors.

  13. Revisiting the TALE repeat.

    Science.gov (United States)

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

  14. Peptides corresponding to the predicted heptad repeat 2 domain of the feline coronavirus spike protein are potent inhibitors of viral infection.

    Directory of Open Access Journals (Sweden)

    I-Jung Liu

    Full Text Available BACKGROUND: Feline infectious peritonitis (FIP is a lethal immune-mediated disease caused by feline coronavirus (FCoV. Currently, no therapy with proven efficacy is available. In searching for agents that may prove clinically effective against FCoV infection, five analogous overlapping peptides were designed and synthesized based on the putative heptad repeat 2 (HR2 sequence of the spike protein of FCoV, and the antiviral efficacy was evaluated. METHODS: Plaque reduction assay and MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide cytotoxicity assay were performed in this study. Peptides were selected using a plaque reduction assay to inhibit Feline coronavirus infection. RESULTS: The results demonstrated that peptide (FP5 at concentrations below 20 μM inhibited viral replication by up to 97%. The peptide (FP5 exhibiting the most effective antiviral effect was further combined with a known anti-viral agent, human interferon-α (IFN-α, and a significant synergistic antiviral effect was observed. CONCLUSION: Our data suggest that the synthetic peptide FP5 could serve as a valuable addition to the current FIP prevention methods.

  15. Built-in inflation in f(G) gravity

    Science.gov (United States)

    Sharif, M.; Fatima, H. Ismat

    2016-10-01

    In this paper, we study the role of Gauss-Bonnet term for the early and late time accelerating phases of the universe with the help of two viable f(G) models in the background of flat FRW universe model. These models show inflationary behavior as well as the present accelerating expansion of the universe. The contribution of Gauss-Bonnet term in pressure and energy density is used to calculate equation of state (EoS) parameter for the modified fluid which behaves like cosmological constant with \\Hdot = 0. We discuss early inflation and late accelerating expansion of the universe through scale factor evaluated from equation of continuity numerically.

  16. The Pentapeptide Repeat Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Vetting,M.; Hegde, S.; Fajardo, J.; Fiser, A.; Roderick, S.; Takiff, H.; Blanchard, J.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S, T,A, V][D, N][L, F]-[S, T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Mycobacterium tuberculosis. The structure revealed that the pentapeptide repeats encode the folding of a novel right-handed quadrilateral {beta}-helix. MfpA binds to DNA gyrase and inhibits its activity. The rod-shaped, dimeric protein exhibits remarkable size, shape and electrostatic similarity to DNA.

  17. (1)H, (15)N and (13)C resonance assignments for free and IEEVD peptide-bound forms of the tetratricopeptide repeat domain from the human E3 ubiquitin ligase CHIP.

    Science.gov (United States)

    Zhang, Huaqun; McGlone, Cameron; Mannion, Matthew M; Page, Richard C

    2017-04-01

    The ubiquitin ligase CHIP catalyzes covalent attachment of ubiquitin to unfolded proteins chaperoned by the heat shock proteins Hsp70/Hsc70 and Hsp90. CHIP interacts with Hsp70/Hsc70 and Hsp90 by binding of a C-terminal IEEVD motif found in Hsp70/Hsc70 and Hsp90 to the tetratricopeptide repeat (TPR) domain of CHIP. Although recruitment of heat shock proteins to CHIP via interaction with the CHIP-TPR domain is well established, alterations in structure and dynamics of CHIP upon binding are not well understood. In particular, the absence of a structure for CHIP-TPR in the free form presents a significant limitation upon studies seeking to rationally design inhibitors that may disrupt interactions between CHIP and heat shock proteins. Here we report the (1)H, (13)C, and (15)N backbone and side chain chemical shift assignments for CHIP-TPR in the free form, and backbone chemical shift assignments for CHIP-TPR in the IEEVD-bound form. The NMR resonance assignments will enable further studies examining the roles of dynamics and structure in regulating interactions between CHIP and the heat shock proteins Hsp70/Hsc70 and Hsp90.

  18. NMR studies of the R2 repeat and related peptide fragments of the DNA binding domain of c-Myb. New light on the structure and folding of R2.

    Science.gov (United States)

    Ségalas, I.; Desjardins, S.; Oulyadi, H.; Prigent, Y.; Tribouillard, S.; Bernardi, E.; Schoofs, A. R.; Davoust1, D.; Toma, F.

    1999-10-01

    The solution structure of the R2 repeat of the DNA binding domain of the protooncogene c-Myb contains a N-terminal structural motif comprising two antiparallel helices. The motif is stabilized by interactions involving conserved residues. The recognition region in C-terminal position is flexible. This structure differs from that of R2 of another c-Myb protein. La structure en solution de la répétition R2 du domaine de liaison à l'ADN du protooncogène c-Myb possède un motif à deux hélices antiparallèles dans la moitié N-terminale, stabilisé par des interactions entre résidus conservés. La région de reconnaissance à l'ADN en position C-terminale est flexible. Cette structure diffère de celle montrée pour la répétition R2 d'une autre protéine c-Myb.

  19. Deployment Repeatability

    Science.gov (United States)

    2016-04-01

    controlled to great precision, but in a Cubesat , there may be no attitude determination at all. Such a Cubesat might treat sun angle and tumbling rates as...could be sensitive to small differences in motor controller timing. In these cases, the analyst might choose to model the entire deployment path, with...knowledge of the material damage model or motor controller timing precision. On the other hand, if many repeated and environmentally representative

  20. SOT1, a pentatricopeptide repeat protein with a small MutS-related domain, is required for correct processing of plastid 23S-4.5S rRNA precursors in Arabidopsis thaliana.

    Science.gov (United States)

    Wu, Wenjuan; Liu, Sheng; Ruwe, Hannes; Zhang, Delin; Melonek, Joanna; Zhu, Yajuan; Hu, Xupeng; Gusewski, Sandra; Yin, Ping; Small, Ian D; Howell, Katharine A; Huang, Jirong

    2016-03-01

    Ribosomal RNA processing is essential for plastid ribosome biogenesis, but is still poorly understood in higher plants. Here, we show that SUPPRESSOR OF THYLAKOID FORMATION1 (SOT1), a plastid-localized pentatricopeptide repeat (PPR) protein with a small MutS-related domain, is required for maturation of the 23S-4.5S rRNA dicistron. Loss of SOT1 function leads to slower chloroplast development, suppression of leaf variegation, and abnormal 23S and 4.5S processing. Predictions based on the PPR motif sequences identified the 5' end of the 23S-4.5S rRNA dicistronic precursor as a putative SOT1 binding site. This was confirmed by electrophoretic mobility shift assay, and by loss of the abundant small RNA 'footprint' associated with this site in sot1 mutants. We found that more than half of the 23S-4.5S rRNA dicistrons in sot1 mutants contain eroded and/or unprocessed 5' and 3' ends, and that the endonucleolytic cleavage product normally released from the 5' end of the precursor is absent in a sot1 null mutant. We postulate that SOT1 binding protects the 5' extremity of the 23S-4.5S rRNA dicistron from exonucleolytic attack, and favours formation of the RNA structure that allows endonucleolytic processing of its 5' and 3' ends. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  1. Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)–Mixed Lineage Leukemia (MLL) Protein–Protein Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Karatas, Hacer; Li, Yangbing; Liu, Liu; Ji, Jiao; Lee, Shirley; Chen, Yong; Yang, Jiuling; Huang, Liyue; Bernard, Denzil; Xu, Jing; Townsend, Elizabeth C.; Cao, Fang; Ran, Xu; Li, Xiaoqin; Wen, Bo; Sun, Duxin; Stuckey, Jeanne A; Lei, Ming; Dou, Yali; Wang, Shaomeng (Michigan)

    2017-06-06

    We report herein the design, synthesis, and evaluation of macrocyclic peptidomimetics that bind to WD repeat domain 5 (WDR5) and block the WDR5–mixed lineage leukemia (MLL) protein–protein interaction. Compound 18 (MM-589) binds to WDR5 with an IC50 value of 0.90 nM (Ki value <1 nM) and inhibits the MLL H3K4 methyltransferase (HMT) activity with an IC50 value of 12.7 nM. Compound 18 potently and selectively inhibits cell growth in human leukemia cell lines harboring MLL translocations and is >40 times better than the previously reported compound MM-401. Cocrystal structures of 16 and 18 complexed with WDR5 provide structural basis for their high affinity binding to WDR5. Additionally, we have developed and optimized a new AlphaLISA-based MLL HMT functional assay to facilitate the functional evaluation of these designed compounds. Compound 18 represents the most potent inhibitor of the WDR5–MLL interaction reported to date, and further optimization of 18 may yield a new therapy for acute leukemia.

  2. Transcriptome-Based Discovery of Fusarium graminearum Stress Responses to FgHV1 Infection.

    Science.gov (United States)

    Wang, Shuangchao; Zhang, Jingze; Li, Pengfei; Qiu, Dewen; Guo, Lihua

    2016-11-17

    Fusarium graminearum hypovirus 1 (FgHV1), which is phylogenetically related to Cryphonectria hypovirus 1 (CHV1), is a virus in the family Hypoviridae that infects the plant pathogenic fungus F. graminearum. Although hypovirus FgHV1 infection does not attenuate the virulence of the host (hypovirulence), it results in defects in mycelial growth and spore production. We now report that the vertical transmission rate of FgHV1 through asexual spores reached 100%. Using RNA deep sequencing, we performed genome-wide expression analysis to reveal phenotype-related genes with expression changes in response to FgHV1 infection. A total of 378 genes were differentially expressed, suggesting that hypovirus infection causes a significant alteration of fungal gene expression. Nearly two times as many genes were up-regulated as were down-regulated. A differentially expressed gene enrichment analysis identified a number of important pathways. Metabolic processes, the ubiquitination system, and especially cellular redox regulation were the most affected categories in F. graminearum challenged with FgHV1. The p20, encoded by FgHV1 could induce H₂O₂ accumulation and hypersensitive response in Nicotiana benthamiana leaves. Moreover, hypovirus FgHV1 may regulate transcription factors and trigger the RNA silencing pathway in F. graminearum.

  3. Multichannel and repeatable self-healing of mechanical enhanced graphene-thermoplastic polyurethane composites.

    Science.gov (United States)

    Huang, Lu; Yi, Ningbo; Wu, Yingpeng; Zhang, Yi; Zhang, Qian; Huang, Yi; Ma, Yanfeng; Chen, Yongsheng

    2013-04-18

    A novel self-healing material, which was fabricated using few-layered graphene (FG) and thermoplastic polyurethane (TPU) via a facile method, not only exhibits a mechanical enhanced property, but also can be repeatedly healed by various methods including infrared (IR) light, electricity and electromagnetic wave with healing efficiencies higher than 98%.

  4. Origin and fate of repeats in bacteria.

    Science.gov (United States)

    Achaz, G; Rocha, E P C; Netter, P; Coissac, E

    2002-07-01

    We investigated 53 complete bacterial chromosomes for intrachromosomal repeats. In previous studies on eukaryote chromosomes, we proposed a model for the dynamics of repeats based on the continuous genesis of tandem repeats, followed by an active process of high deletion rate, counteracted by rearrangement events that may prevent the repeats from being deleted. The present study of long repeats in the genomes of Bacteria and Archaea suggests that our model of interspersed repeats dynamics may apply to them. Thus the duplication process might be a consequence of very ancient mechanisms shared by all three domains. Moreover, we show that there is a strong negative correlation between nucleotide composition bias and the repeat density of genomes. We hypothesise that in highly biased genomes, non-duplicated small repeats arise more frequently by random effects and are used as primers for duplication mechanisms, leading to a higher density of large repeats.

  5. Seedling Lethal1, a Pentatricopeptide Repeat Protein Lacking an E/E+ or DYW Domain in Arabidopsis, Is Involved in Plastid Gene Expression and Early Chloroplast Development1[C][W

    Science.gov (United States)

    Pyo, Young Jae; Kwon, Kwang-Chul; Kim, Anna; Cho, Myeon Haeng

    2013-01-01

    Chloroplasts are the site of photosynthesis and the biosynthesis of essential metabolites, including amino acids, fatty acids, and secondary metabolites. It is known that many seedling-lethal mutants are impaired in chloroplast function or development, indicating the development of functional chloroplast is essential for plant growth and development. Here, we isolated a novel transfer DNA insertion mutant, dubbed sel1 (for seedling lethal1), that exhibited a pigment-defective and seedling-lethal phenotype with a disrupted pentatricopeptide repeat (PPR) gene. Sequence analysis revealed that SEL1 is a member of the PLS subgroup, which is lacking known E/E+ or DYW domains at the C terminus, in the PLS subfamily of the PPR protein family containing a putative N-terminal transit peptide and 14 putative PPR or PPR-like motifs. Confocal microscopic analysis showed that the SEL1-green fluorescent protein fusion protein is localized in chloroplasts. Transmission electron microscopic analysis revealed that the sel1 mutant is impaired in the etioplast, as well as in chloroplast development. In sel1 mutants, plastid-encoded proteins involved in photosynthesis were rarely detected due to the lack of the corresponding transcripts. Furthermore, transcript profiles of plastid genes revealed that, in sel1 mutants, the transcript levels of plastid-encoded RNA polymerase-dependent genes were greatly reduced, but those of nuclear-encoded RNA polymerase-dependent genes were increased or not changed. Additionally, the RNA editing of two editing sites of the acetyl-CoA carboxylase beta subunit gene transcripts in the sel1 mutant was compromised, though it is not directly connected with the sel1 mutant phenotype. Our results demonstrate that SEL1 is involved in the regulation of plastid gene expression required for normal chloroplast development. PMID:24144791

  6. FgRIC8 is involved in regulating vegetative growth, conidiation, deoxynivalenol production and virulence in Fusarium graminearum.

    Science.gov (United States)

    Wu, Jinjin; Liu, Yuting; Lv, Wuyun; Yue, Xiaofeng; Que, Yawei; Yang, Nan; Zhang, Zhengguang; Ma, Zhonghua; Talbot, Nicholas J; Wang, Zhengyi

    2015-10-01

    Proteins of the resistance to inhibitors of cholinesterase 8 (Ric8) group act as guanine nucleotide exchange factors (GEFs) and play important roles in regulating G-protein signaling in animals. In filamentous fungi, putative Ric8 orthologs have so far been identified in Magnaporthe oryzae, Neurospora crassa, Aspergillus nidulans and Aspergillus fumigatus. Here, we report the functional investigation of a potential RIC8 ortholog (FgRIC8) in the wheat head blight pathogen Fusarium graminearum. Targeted gene deletion mutants of FgRIC8 exhibited a significant reduction in vegetative growth, conidiation, pigment production as well as deoxynivalenol (DON) biosynthesis. Pathogenicity assays using a point-inoculated spikelet approach showed that the mutants were severely impaired in virulence on flowering wheat heads. Quantitative RT-PCR analysis revealed that genes encoding F. graminearum Gα (FgGpa1 and FgGpa3), Gβ (FgGpb1) and Gγ (FgGpg1) subunits were significantly down-regulated in Fgric8 mutants. Moreover, we showed that FgRic8 physically interacts with both FgGpa1 and FgGpa3, but not FgGpa2, in yeast two-hybrid assays. The intracellular cAMP levels in Fgric8 mutants were significantly decreased compared to the isogenic wild-type strain. Taken together, our results indicate that FgRic8 plays critical roles in fungal development, secondary metabolism and virulence in F. graminearum and may act as a regulator of G protein alpha subunits.

  7. Small scale effect on linear vibration of buckled size-dependent FG nanobeams

    Directory of Open Access Journals (Sweden)

    Sima Ziaee

    2015-06-01

    The present study is an attempt to present linear free vibration of buckled FG nano-beams. It is assumed that the material properties of FGMs are graded in the thickness direction. The partial differential equation of motion is derived based on Euler–Bernoulli beam theory, von-Karman geometric nonlinearity and Eringen’s nonlocal elasticity theory. The exact solution of the post-buckling configurations of FG nano-beams and polynomial-based differential quadrature method are employed to study the linear behaviour of vibrated nano-beams around their post-buckling configurations. The results show the important role of compressive axial force exerted on FG nano-beams in nonlocal behaviour of vibrating FG nano-beams.

  8. Explication of Definitional Description and Empirical Use of Fraction of Orally Administered Drugs Absorbed From the Intestine (Fa) and Intestinal Availability (Fg): Effect of P-glycoprotein and CYP3A on Fa and Fg.

    Science.gov (United States)

    Tanaka, Yuta; Kitamura, Yoshiaki; Maeda, Kazuya; Sugiyama, Yuichi

    2016-02-01

    Conventionally, it is believed that the fraction of orally administered drugs absorbed from the intestine (Fa) and intestinal availability (Fg) are independently determined by the apical membrane permeation and intestinal metabolism, respectively. However, the validity of this belief has not been well discussed, and Fa and Fg are often used without careful definition. In this review, Fa and Fg are mathematically described based on their definitions under the linear kinetics of metabolism and transport. Even considering with different models, intestinal metabolic enzymes such as cytochrome P450 3A affected both Fa and Fg, whereas apical efflux transporters including P-glycoprotein had no influence on Fg at least under the linear condition. To determine whether Fa and Fg calculated using different clinical methods are identical, empirical Fa and Fg were mathematically described based on "feces method" and "grapefruit juice method" and compared with their definitions. Fa and Fg obtained by the feces method corresponded with their definitions whereas the grapefruit juice method provided smaller Fa and larger Fg particularly for dual substrates of P-glycoprotein and cytochrome P450 3A with low membrane permeability. Our analyses suggest that the definitions and calculation methods of Fa and Fg should be considered when we intend to separately determine these values.

  9. Roc, a Ras/GTPase domain in complex proteins

    NARCIS (Netherlands)

    Bosgraaf, Leonard; Haastert, Peter J.M. van

    2003-01-01

    We identified a novel group of the Ras/GTPase superfamily, termed Roc, that is present as domain in complex proteins together with other domains, including leucine-rich repeats (LRRs), ankyrin repeats, WD40 repeats, kinase domains, RasGEF and RhoGAP domains. Roc is always succeeded by a novel 300–40

  10. QCD ghost reconstruction of f(G) gravity and its thermodynamic consequences

    Science.gov (United States)

    Chattopadhyay, Surajit

    2016-07-01

    In the present study we have presented a reconstruction scheme for f(G) gravity, where G represents Gauss-Bonnet invariant and we have chosen the scale factor in power-law form. It should be mentioned that f(G) gravity is not ``ad hoc" but comes out from the problem of non-local gravity theories. The works of Capozziello et al. (2013, 2014) need to be mentioned in this context. Capozziello et al. (2013) studied the Gauss-Bonnet gravity with Lagrange multiplier constraints in view to recover realistic dark energy behaviors and could recover the so-called Little Rip cosmology. Capozziello et al. (2014) built several solutions for F(R) + F(G) gravity with matter, but without Lagrange multipliers. In the present work, considering a flat FRW universe, we have considered a correspondence between f(G) gravity and QCD ghost dark energy. After getting a reconstructed solution for f(G) we have plotted f(G) against G, where it is apparent that f(G)→ 0 as G→ 0, which is one of the sufficient conditions for a realistic model. We have plotted the effective equation of state parameter for n>1 and observed that w_{eff}≥ -1 i.e. it behaves like quintessence. For n≈ 2, w_{eff} is reaching -1 at late stage of the universe. However, it is not crossing the phantom boundary. Subsequently, considering dynamical apparent horizon as the enveloping horizon of the universe we have derived expression for the time derivative of total entropy dot{S}_{total} and we have observed that dot{S}_{total}>0 throughout the evolution of the universe. This indicated validity of the generalized second law of thermodynamics under this reconstruction of f(G) gravity. References: Capozziello, S., Francaviglia, M., Makarenko, A. N.: Astrophys. Space Sci., 603 (2014) Capozziello, S., Makarenko, A. N., Odintsov, S. D.: Phys. Rev. D, 87 084037 (2013)

  11. Towards a possible solution for the coincidence problem: f(G) gravity as background

    CERN Document Server

    Rudra, Prabir

    2014-01-01

    In this article we address the well-known cosmic coincidence problem in the framework of the f(G) gravity. In order to achieve this, an interaction between dark energy and dark matter is considered. A set-up is designed and a constraint equation is obtained which generates the f(G) models that do not suffer from the coincidence problem. Due to the absence of a universally accepted interaction term introduced by a fundamental theory, the study is conducted over three different forms of logically chosen interaction terms. To illustrate the set-up three widely known models of f(G) gravity are taken into consideration and the problem is studied under the designed set-up. The study reveals that the popular f(G) gravity models does not approve of a satisfactory solution of the long standing coincidence problem, thus proving to be a major setback for them as successful models of universe. Finally, two non-conventional models of f(G) gravity have been proposed and studied in the framework of the designed set-up. It i...

  12. Towards a possible solution for the coincidence problem: f(G) gravity as background

    Science.gov (United States)

    Rudra, Prabir

    2016-07-01

    In this article we address the well-known cosmic coincidence problem in the framework of the f(G) gravity. In order to achieve this, an interaction between dark energy and dark matter is considered. A set-up is designed and a constraint equation is obtained which generates the f(G) models that do not suffer from the coincidence problem. Due to the absence of a universally accepted interaction term introduced by a fundamental theory, the study is conducted over three different forms of logically chosen interaction terms. To illustrate the set-up three widely known models of f(G) gravity are taken into consideration and the problem is studied under the designed set-up. The study reveals that the popular f(G) gravity models does not approve of a satisfactory solution of the long standing coincidence problem, thus proving to be a major setback for them as successful models of universe. Finally, two non-conventional models of f(G) gravity have been proposed and studied in the framework of the designed set-up. It is seen that a complete solution of the coincidence problem is achieved for these models. The study also reveals that the 'b-interaction' term is much more preferable compared to the other interactions, due to its greater compliance with the recent observational data.

  13. FgNoxR, a regulatory subunit of NADPH oxidases, is required for female fertility and pathogenicity in Fusarium graminearum.

    Science.gov (United States)

    Zhang, Chengkang; Lin, Yahong; Wang, Jianqiang; Wang, Yang; Chen, Miaoping; Norvienyeku, Justice; Li, Guangpu; Yu, Wenying; Wang, Zonghua

    2016-01-01

    Fusarium graminearum is a filamentous fungal pathogen that causes wheat Fusarium head blight. In this study, we identified FgNoxR, a regulatory subunit of NADPH oxidases (Nox) in F. graminearum, and found that it plays an important role in the pathogenicity of F. graminearum. FgNoxR is localized on punctate structures throughout the cytoplasm in aerial hyphae while these structures tend to accumulate at or near the plasma membrane, septa and hyphal tips in germinated conidia. Deletion of the FgNOXR gene results in reduced conidiation and germination. Importantly, sexual development is totally abolished in the FgNOXR deletion mutant. In addition, the disease lesion of FgNOXR deletion mutant is limited to the inoculated spikelets of wheat heads. Finally, FgNoxR interacts with FgRac1 and FgNoxA, and all three proteins are required for female fertility. Taken together, our data indicate that FgNoxR contributes to conidiation, sexual reproduction and pathogenesis in F. graminearum.

  14. Domains and domain loss

    DEFF Research Database (Denmark)

    Haberland, Hartmut

    2005-01-01

    The domain concept, originally suggested by Schmidt-Rohr in the 1930’s (as credited in Fishman’s writings in the 1970s), was an attempt to sort out different areas of language use in multilingual societies, which are relevant for language choice. In Fishman’s version, domains were considered...... not described in terms of domains, and recent research e.g. about the multilingual communities in the Danish-German border area seems to confirm this....

  15. Cosmological Evolution of Pilgrim Dark Energy in f(G Gravity

    Directory of Open Access Journals (Sweden)

    Abdul Jawad

    2015-01-01

    Full Text Available We analyze the behavior of pilgrim dark energy with Hubble horizon in f(G gravity. We reconstruct the f(G models through correspondence phenomenon by assuming two values of pilgrim dark energy parameter (u=2, -2. We evaluate the equation of state parameter which shows evolution of the universe in the quintessence, vacuum, and phantom phase for both cases of u and give favor the pilgrim dark energy phenomenon. Also, squared speed of sound exhibits the stability of f(G model for both cases of u. The wPDE-wPDE′ also provides freezing and thawing regions in this scenario. In this framework, the r-s plane also corresponds to different dark energy scenarios.

  16. ANALYSIS OF SHAKEDOWN OF FG BREE PLATE SUBJECTED TO COUPLED THERMAL-MECHANICAL LOADINGS

    Institute of Scientific and Technical Information of China (English)

    Xianghe Peng; Ning Hu; Hengwei Zheng; Cuirong Fang

    2009-01-01

    The static and kinematic shakedown of a functionally graded (FG) Bree plate is analyzed. The plate is subjected to coupled constant mechanical load and cyclically varying tem-perature. The material is assumed linearly elastic and nonlinear isotropic hardening with elastic modulus, yield strength and the thermal expansion coefficient varying exponentially through the thickness of the plate. The boundaries between the shakedown area and the areas of elasticity, incremental collapse and reversed plasticity are determined, respectively. The shakedown of the counterpart made of homogeneous material with average material properties is also analyzed. The comparison between the results obtained in the two cases exhibits distinct qualitative and quantitative difference, indicating the importance of shakedown analysis for FG structures. Since FG structures are usually used in the cases where severe coupled cyclic thermal and mechani-cal loadings are applied, the approach developed and the results obtained are significant for the analysis and design of such kind of structures.

  17. Wormhole solutions for f(G) gravity in galactic halo region

    Science.gov (United States)

    Sharif, M.; Ismat Fatima, H.

    2016-04-01

    In this paper, we study static spherically symmetric wormhole solutions in galactic halo region. Two observational results, Navarro-Frenk-White energy density profile in standard cosmological model and the observed flat rotational curves, are used to discuss traversable wormholes supported by galactic halo in modified Gauss-Bonnet gravity. We explore these solutions either by considering a viable f(G) model to construct shape function or by specifying the shape function to deduce f(G) model. We explore energy conditions and find physically acceptable wormhole solutions threaded by normal matter for all values of r. Finally, we investigate stability of the resulting wormhole solutions.

  18. Characterization of a New Pm2 Allele Conferring Powdery Mildew Resistance in the Wheat Germplasm Line FG-1.

    Science.gov (United States)

    Ma, Pengtao; Xu, Hongxng; Li, Lihui; Zhang, Hongxia; Han, Guohao; Xu, Yunfeng; Fu, Xiaoyi; Zhang, Xiaotian; An, Diaoguo

    2016-01-01

    Powdery mildew has a negative impact on wheat production. Novel host resistance increases the diversity of resistance genes and helps to control the disease. In this study, wheat line FG-1 imported from France showed a high level of powdery mildew resistance at both the seedling and adult stages. An F2 population and F2:3 families from the cross FG-1 × Mingxian 169 both fit Mendelian ratios for a single dominant resistance gene when tested against multiple avirulent Blumeria tritici f. sp. tritici (Bgt) races. This gene was temporarily designated PmFG. PmFG was mapped on the multi-allelic Pm2 locus of chromosome 5DS using seven SSR, 10 single nucleotide polymorphism (SNP)-derived and two SCAR markers with the flanking markers Xbwm21/Xcfd81/Xscar112 (distal) and Xbwm25 (proximal) at 0.3 and 0.5 cM being the closest. Marker SCAR203 co-segregated with PmFG. Allelism tests between PmFG and documented Pm2 alleles confirmed that PmFG was allelic with Pm2. Line FG-1 produced a significantly different reaction pattern compared to other lines with genes at or near Pm2 when tested against 49 Bgt isolates. The PmFG-linked marker alleles detected by the SNP-derived markers revealed significant variation between FG-1 and other lines with genes at or near Pm2. It was concluded that PmFG is a new allele at the Pm2 locus. Data from seven closely linked markers tested on 31 wheat cultivars indicated opportunities for marker-assisted pyramiding of this gene with other genes for powdery mildew resistance and additional traits.

  19. Repeat-until-success quantum repeaters

    Science.gov (United States)

    Bruschi, David Edward; Barlow, Thomas M.; Razavi, Mohsen; Beige, Almut

    2014-09-01

    We propose a repeat-until-success protocol to improve the performance of probabilistic quantum repeaters. Conventionally, these rely on passive static linear-optics elements and photodetectors to perform Bell-state measurements (BSMs) with a maximum success rate of 50%. This is a strong impediment for entanglement swapping between distant quantum memories. Every time a BSM fails, entanglement needs to be redistributed between the corresponding memories in the repeater link. The key ingredients of our scheme are repeatable BSMs. Under ideal conditions, these turn probabilistic quantum repeaters into deterministic ones. Under realistic conditions, our protocol too might fail. However, using additional threshold detectors now allows us to improve the entanglement generation rate by almost orders of magnitude, at a nominal distance of 1000 km, compared to schemes that rely on conventional BSMs. This improvement is sufficient to make the performance of our scheme comparable to the expected performance of some deterministic quantum repeaters.

  20. Final Progress Report for FG02-89ER14030

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Maureen R

    2011-10-26

    Intracellular Dynamics of Energy-Transducing Organelles. The location and interaction of intracellular organelles is important for exchange of substrate and product between compartments for optimum functioning of biochemical pathways and energy transduction. Plastids and stromules, tubular plastid extensions, are highly dynamic in many plant tissues. Stromules can connect two or more plastids and proteins and macromolecular complexes can be transferred between them. Stromules have been observed to form close contacts with other organelles, the plasma membrane, and can pass through channels in the nucleus. Chloroplasts move in response to light and mechanical stimulus. Especially in non-green cells, plastids change shape and position, and stromules extend and retract. Stromules appear to be involved in recycling of chloroplast proteins when photosynthesis is limited, through an autophagic process that results in degradation of portions of the stromal contents without complete destruction of the chloroplast. Mutations in several genes known to mediate chloroplast division result in altered stromule morphology in some cells. Plastid and stromule motility is mediated by the actin cytoskeleton. The possible role of myosins in chloroplast movement was investigated by labeling the cargo-binding tails of six Arabidopsis myosin XI proteins with yellow fluorescent protein (YFP). The fluorescent proteins were found to localize to vesicles and peroxisomes. The portion of the myosin tail domain fused to YFP affected whether specific or non-specific localization was observed. In contrast to experiments in animal cells, movement of labeled organelles was not entirely inhibited by expression of defective myosin in which the motor domain was replaced with a fluorescent protein. None of the six myosin proteins tested labeled plastids or chloroplasts. However, the Arabidopsis myosin XI gene family expresses an additional seven myosins that await further examination. These experiments

  1. Functional roles of FgLaeA in controlling secondary metabolism, sexual development, and virulence in Fusarium graminearum.

    Directory of Open Access Journals (Sweden)

    Hee-Kyoung Kim

    Full Text Available Fusarium graminearum, the causal agent of Fusarium head blight in cereal crops, produces mycotoxins such as trichothecenes and zearalenone in infected plants. Here, we focused on the function of FgLaeA in F. graminearum, a homolog of Aspergillus nidulans LaeA encoding the global regulator for both secondary metabolism and sexual development. Prior to gene analysis, we constructed a novel luciferase reporter system consisting of a transgenic F. graminearum strain expressing a firefly luciferase gene under control of the promoter for either TRI6 or ZEB2 controlling the biosynthesis of these mycotoxins. Targeted deletion of FgLaeA led to a dramatic reduction of luminescence in reporter strains, indicating that FgLaeA controls the expression of these transcription factors in F. graminearum; reduced toxin accumulation was further confirmed by GC-MS analysis. Overexpression of FgLaeA caused the increased production of trichothecenes and additional metabolites. RNA seq-analysis revealed that gene member(s belonging to ~70% of total tentative gene clusters, which were previously proposed, were differentially expressed in the ΔFgLaeA strain. In addition, ΔFgLaeA strains exhibited an earlier induction of sexual fruiting body (perithecia formation and drastically reduced disease symptoms in wheat, indicating that FgLaeA seems to negatively control perithecial induction, but positively control virulence toward the host plant. FgLaeA was constitutively expressed under both mycotoxin production and sexual development conditions. Overexpression of a GFP-FgLaeA fusion construct in the ΔFgLaeA strain restored all phenotypic changes to wild-type levels and led to constitutive expression of GFP in both nuclei and cytoplasm at different developmental stages. A split luciferase assay demonstrated that FgLaeA was able to interact with FgVeA, a homolog of A. nidulans veA. Taken together, these results demonstrate that FgLaeA, a member of putative FgVeA complex

  2. Field test results for steam oxidation of TP347H FG - growth of inner oxide

    DEFF Research Database (Denmark)

    Montgomery, Melanie; Jianmin, Jia; Larsen, OH;

    2005-01-01

    A series of field tests have been conducted with TP347H FG in test superheater loops in coal-fired and biomass fired boilers of steam pressure 256 and 91 bar respectively. The exposure times are from 3,500 to 30,000 hours and the temperature range is from 450-630¢XC. The morphology, composition...

  3. The essential YycFG two-component system controls cell wall metabolism in Bacillus subtilis

    DEFF Research Database (Denmark)

    Bisicchia, Paola; Noone, David; Lioliou, Efthimia

    2007-01-01

    Adaptation of bacteria to the prevailing environmental and nutritional conditions is often mediated by two-component signal transduction systems (TCS). The Bacillus subtilis YycFG TCS has attracted special attention as it is essential for viability and its regulon is poorly defined. Here we show...

  4. Thermo-mechanical analysis of FG nanobeam with attached tip mass: an exact solution

    Science.gov (United States)

    Ghadiri, Majid; Jafari, Ali

    2016-12-01

    Present disquisition proposes an analytical solution method for exploring the vibration characteristics of a cantilever functionally graded nanobeam with a concentrated mass exposed to thermal loading for the first time. Thermo-mechanical properties of FGM nanobeam are supposed to change through the thickness direction of beam based on the rule of power-law (P-FGM). The small-scale effect is taken into consideration based on nonlocal elasticity theory of Eringen. Linear temperature rise (LTR) through thickness direction is studied. Existence of centralized mass in the free end of nanobeam influences the mechanical and physical properties. Timoshenko beam theory is employed to derive the nonlocal governing equations and boundary conditions of FGM beam attached with a tip mass under temperature field via Hamilton's principle. An exact solution procedure is exploited to achieve the non-dimensional frequency of FG nanobeam exposed to temperature field with a tip mass. A parametric study is led to assess the efficacy of temperature changes, tip mass, small scale, beam thickness, power-law exponent, slenderness and thermal loading on the natural frequencies of FG cantilever nanobeam with a point mass at the free end. It is concluded that these parameters play remarkable roles on the dynamic behavior of FG nanobeam subjected to LTR with a tip mass. The results for simpler states are confirmed with known data in the literature. Presented numerical results can serve as benchmarks for future thermo-mechanical analyses of FG nanobeam with tip mass.

  5. Physical Characterization and Origin of Binary Near-Earth Asteroid (175706) 1996 FG3

    NARCIS (Netherlands)

    Walsh, Kevin J.; Delbo', Marco; Mueller, Michael; Binzel, Richard P.; DeMeo, Francesca E.

    2012-01-01

    The near-Earth asteroid (NEA) (175706) 1996 FG3 is a particularly interesting spacecraft target: a binary asteroid with a low-Δv heliocentric orbit. The orbit of its satellite has provided valuable information about its mass density while its albedo and colors suggest it is primitive or part of the

  6. Physical Characterization and Origin of Binary Near-Earth Asteroid (175706) 1996 FG3

    NARCIS (Netherlands)

    Walsh, Kevin J.; Delbo', Marco; Mueller, Michael; Binzel, Richard P.; DeMeo, Francesca E.

    2012-01-01

    The near-Earth asteroid (NEA) (175706) 1996 FG3 is a particularly interesting spacecraft target: a binary asteroid with a low-Δv heliocentric orbit. The orbit of its satellite has provided valuable information about its mass density while its albedo and colors suggest it is primitive or part of the

  7. On the effect of distortion and dispersion in fringe signal of the FG5 absolute gravimeters

    Science.gov (United States)

    Křen, Petr; Pálinkáš, Vojtech; Mašika, Pavel

    2016-02-01

    The knowledge of absolute gravity acceleration at the level of 1  ×  10-9 is needed in geosciences (e.g. for monitoring crustal deformations and mass transports) and in metrology for watt balance experiments related to the new SI definition of the unit of kilogram. The gravity reference, which results from the international comparisons held with the participation of numerous absolute gravimeters, is significantly affected by qualities of instruments prevailing in the comparisons (i.e. at present, FG5 gravimeters). Therefore, it is necessary to thoroughly investigate all instrumental (particularly systematic) errors. This paper deals with systematic errors of the FG5#215 coming from the distorted fringe signal and from the electronic dispersion at several electronic components including cables. In order to investigate these effects, we developed a new experimental system for acquiring and analysing the data parallel to the FG5 built-in system. The new system based on the analogue-to-digital converter with digital waveform processing using the FFT swept band pass filter is developed and tested on the FG5#215 gravimeter equipped with a new fast analogue output. The system is characterized by a low timing jitter, digital handling of the distorted swept signal with determination of zero-crossings for the fundamental frequency sweep and also for its harmonics and can be used for any gravimeter based on the laser interferometry. Comparison of the original FG5 system and the experimental systems is provided on g-values, residuals and additional measurements/models. Moreover, advanced approach for the solution of the free-fall motion is presented, which allows to take into account a non-linear gravity change with height.

  8. Automated protein structure modeling in CASP9 by I-TASSER pipeline combined with QUARK-based ab initio folding and FG-MD-based structure refinement.

    Science.gov (United States)

    Xu, Dong; Zhang, Jian; Roy, Ambrish; Zhang, Yang

    2011-01-01

    I-TASSER is an automated pipeline for protein tertiary structure prediction using multiple threading alignments and iterative structure assembly simulations. In CASP9 experiments, two new algorithms, QUARK and fragment-guided molecular dynamics (FG-MD), were added to the I-TASSER pipeline for improving the structural modeling accuracy. QUARK is a de novo structure prediction algorithm used for structure modeling of proteins that lack detectable template structures. For distantly homologous targets, QUARK models are found useful as a reference structure for selecting good threading alignments and guiding the I-TASSER structure assembly simulations. FG-MD is an atomic-level structural refinement program that uses structural fragments collected from the PDB structures to guide molecular dynamics simulation and improve the local structure of predicted model, including hydrogen-bonding networks, torsion angles, and steric clashes. Despite considerable progress in both the template-based and template-free structure modeling, significant improvements on protein target classification, domain parsing, model selection, and ab initio folding of β-proteins are still needed to further improve the I-TASSER pipeline. Copyright © 2011 Wiley-Liss, Inc.

  9. Hemoglobin Wood beta97(FG4) His replaced by Leu. A new high-oxygen-affinity hemoglobin associated with familial erythrocytosis.

    Science.gov (United States)

    Taketa, F; Huang, Y P; Libnoch, J A; Dessel, B H

    1975-08-19

    The characterization of hemoglobin Wood (beta97(FG4) His replaced by Leu), a high oxygen affinity hemoglobin with reduced Hill constant is described. The amino acid substitution occurs at the alpha1beta2 interface, in the same position as in hemoglobin Malmö (beta97(FG4) His replaced by Gln) and in an homologous position when compared with hemoglobins Chesapeake (alpha92(FG4) Arg replaced by Leu) and J. Capetown (alpha92(fg4) arg replaced by Gln).

  10. Atomic structure of the nuclear pore complex targeting domain of a Nup116 homologue from the yeast, Candida glabrata

    Energy Technology Data Exchange (ETDEWEB)

    Sampathkumar, Parthasarathy; Kim, Seung Joong; Manglicmot, Danalyn; Bain, Kevin T.; Gilmore, Jeremiah; Gheyi, Tarun; Phillips, Jeremy; Pieper, Ursula; Fernandez-Martinez, Javier; Franke, Josef D.; Matsui, Tsutomu; Tsuruta, Hiro; Atwell, Shane; Thompson, Devon A.; Emtage, J. Spencer; Wasserman, Stephen R.; Rout, Michael P.; Sali, Andrej; Sauder, J. Michael; Almo, Steven C.; Burley, Stephen K. (Einstein); (SLAC); (Rockefeller); (UCSF); (Lilly)

    2012-10-23

    The nuclear pore complex (NPC), embedded in the nuclear envelope, is a large, dynamic molecular assembly that facilitates exchange of macromolecules between the nucleus and the cytoplasm. The yeast NPC is an eightfold symmetric annular structure composed of {approx}456 polypeptide chains contributed by {approx}30 distinct proteins termed nucleoporins. Nup116, identified only in fungi, plays a central role in both protein import and mRNA export through the NPC. Nup116 is a modular protein with N-terminal 'FG' repeats containing a Gle2p-binding sequence motif and a NPC targeting domain at its C-terminus. We report the crystal structure of the NPC targeting domain of Candida glabrata Nup116, consisting of residues 882-1034 [CgNup116(882-1034)], at 1.94 {angstrom} resolution. The X-ray structure of CgNup116(882-1034) is consistent with the molecular envelope determined in solution by small-angle X-ray scattering. Structural similarities of CgNup116(882-1034) with homologous domains from Saccharomyces cerevisiae Nup116, S. cerevisiae Nup145N, and human Nup98 are discussed.

  11. Nucleotide polymorphisms and protein structure changes in the Fg16 gene of Fusarium graminearum sensu stricto

    Directory of Open Access Journals (Sweden)

    Mostafa Abedi-Tizaki

    2016-09-01

    Full Text Available Fusarium graminearum is one of the most important causes of wheat scab in different parts of the world. This fungus is able to produce widespread trichothecene mycotoxins such as nivalenol (NIV and deoxynivalenol (DON which are harmful for both human and animals. The Fg16 target is located in chromosome 1 of the F. graminearum genome coding for a hypothetical protein whose function is not yet known. The Fg16 gene is involved in lipid biosynthesis and leads to sexual development during colonization in wheat stalks. This gene is used to detect F. graminearum and determine the lineage of F. graminearum complex species. In the present study, polymerase chain reaction–single strand conformational polymorphism (PCR–SSCP and DNA sequencing methods were employed in screening for genetic variation in 172 F. graminearum s.s. isolates. The PCR reaction forced the amplification of 410-bp fragments of Fg16. Two single nucleotide polymorphisms (T82C and A352T and one amino acid exchange (C65S with three patterns (TA/TA, CT/CT and TA/CT genotypes were found in the Fg16 gene fragment. Two haplotypes, 1A and 1B, were identified within F. graminearum s.s. populations in northern and western regions of Iran. Two different secondary structures of protein were predicted for CT/CT and TA/CT genotypes of Fg16 gene. The average diversity levels detected were relatively high (He: 0.3238; Heu: 0.334; Ho: 0.2894; mean PIC: 0.514; mean Shannon's information index: 0.4132; mean number of alleles per locus: 1.473. On the basis of the obtained results, it was revealed that the Fg16 gene had a high degree of polymorphism that can be considered for future control programming strategies and thus the associations between the SSCP patterns with different traits of F. graminearum such as wheat colonization, perithecium formation on stalk tissues and lineage discrimination should be investigated.

  12. A type 2C protein phosphatase FgPtc3 is involved in cell wall integrity, lipid metabolism, and virulence in Fusarium graminearum.

    Directory of Open Access Journals (Sweden)

    Jinhua Jiang

    Full Text Available Type 2C protein phosphatases (PP2Cs play important roles in regulating many biological processes in eukaryotes. Currently, little is known about functions of PP2Cs in filamentous fungi. The causal agent of wheat head blight, Fusarium graminearum, contains seven putative PP2C genes, FgPTC1, -3, -5, -5R, -6, -7 and -7R. In order to investigate roles of these PP2Cs, we constructed deletion mutants for all seven PP2C genes in this study. The FgPTC3 deletion mutant (ΔFgPtc3-8 exhibited reduced aerial hyphae formation and deoxynivalenol (DON production, but increased production of conidia. The mutant showed increased resistance to osmotic stress and cell wall-damaging agents on potato dextrose agar plates. Pathogencity assays showed that ΔFgPtc3-8 is unable to infect flowering wheat head. All of the defects were restored when ΔFgPtc3-8 was complemented with the wild-type FgPTC3 gene. Additionally, the FgPTC3 partially rescued growth defect of a yeast PTC1 deletion mutant under various stress conditions. Ultrastructural and histochemical analyses showed that conidia of ΔFgPtc3-8 contained an unusually high number of large lipid droplets. Furthermore, the mutant accumulated a higher basal level of glycerol than the wild-type progenitor. Quantitative real-time PCR assays showed that basal expression of FgOS2, FgSLT2 and FgMKK1 in the mutant was significantly higher than that in the wild-type strain. Serial analysis of gene expression in ΔFgPtc3-8 revealed that FgPTC3 is associated with various metabolic pathways. In contrast to the FgPTC3 mutant, the deletion mutants of FgPTC1, FgPTC5, FgPTC5R, FgPTC6, FgPTC7 or FgPTC7R did not show aberrant phenotypic features when grown on PDA medium or inoculated on wheat head. These results indicate FgPtc3 is the key PP2C that plays a critical role in a variety of cellular and biological functions, including cell wall integrity, lipid and secondary metabolisms, and virulence in F. graminearum.

  13. Long term steam oxidation of TP 347H FG in power plants

    DEFF Research Database (Denmark)

    Hansson, Anette Nørgaard; Korcakova, Leona; Hald, John

    2005-01-01

    The long term oxidation behaviour of TP 347H FG at ultra supercritical steam conditions was assessed by exposing the steel in test superheater loops in a Danish coal-fired power plant. The steamside oxide layer was investigated with scanning electron microscopy and energy dispersive Xray diffract......The long term oxidation behaviour of TP 347H FG at ultra supercritical steam conditions was assessed by exposing the steel in test superheater loops in a Danish coal-fired power plant. The steamside oxide layer was investigated with scanning electron microscopy and energy dispersive Xray...... diffraction in order to reveal the effect of oxidation time and temperature on the microstructure. A double layered oxide formed during steam oxidation. The morphology of the inner Cr-containing layer was influenced by the oxidation temperature. At temperatures below 585 degrees C, it consisted of regions...

  14. Investigation of steam oxidation behaviour of TP347H FG Part 2: Exposure at 91 bar

    DEFF Research Database (Denmark)

    Jianmin, J; Montgomery, Melanie; Larsen, OH

    2005-01-01

    Tube specimens of TP347FG were exposed in a test superheater loop in a biomass plant in Denmark. The specimens were exposed to surface metal temperatures in the range of 455-568C, steam pressure of 91 bar and exposure duration of 3500 and 8700 hours. The oxide thickness and morphology was investi......Tube specimens of TP347FG were exposed in a test superheater loop in a biomass plant in Denmark. The specimens were exposed to surface metal temperatures in the range of 455-568C, steam pressure of 91 bar and exposure duration of 3500 and 8700 hours. The oxide thickness and morphology...... was investigated using light optical and scanning electron microscopy. The oxide present on the specimens is a duplex oxide with an inner chromium rich oxide and an outer iron rich oxide. The inner oxide consisted of a primary iron chromium nickel oxide in the original alloy grain and a chromium rich oxide...

  15. EXACT SOLUTION FOR TEMPERATURE-DEPENDENT BUCKLING ANALYSIS OF FG-CNT-REINFORCED MINDLIN PLATES

    Directory of Open Access Journals (Sweden)

    Seyed Mohammad Mousavi

    2016-03-01

    Full Text Available This research deals with the buckling analysis of nanocomposite polymeric temperature-dependent plates reinforced by single-walled carbon nanotubes (SWCNTs. For the carbon-nanotube reinforced composite (CNTRC plate, uniform distribution (UD and three types of functionally graded (FG distribution patterns of SWCNT reinforcements are assumed. The material properties of FG-CNTRC plate are graded in the thickness direction and estimated based on the rule of mixture. The CNTRC is located in a elastic medium which is simulated with temperature-dependent Pasternak medium. Based on orthotropic Mindlin plate theory, the governing equations are derived using Hamilton’s principle and solved by Navier method. The influences of the volume fractions of carbon nanotubes, elastic medium, temperature and distribution type of CNTs are considered on the buckling of the plate. Results indicate that CNT distribution close to top and bottom are more efficient than those distributed nearby the mid-plane for increasing the stiffness of plates.

  16. FG90 chitosan as a new polymer for metronidazole mucoadhesive tablets for vaginal administration.

    Science.gov (United States)

    Perioli, Luana; Ambrogi, Valeria; Pagano, Cinzia; Scuota, Stefania; Rossi, Carlo

    2009-07-30

    Topical administration of the antibacterial metronidazole (MET) represents the most common therapy in the treatment of bacterial vaginosis (BV). The formulations generally available for BV therapy are creams, gels, vaginal lavages and vaginal suppositories. In this study, a new dosage form, containing MET, was developed with the aim to realize vaginal mucoadhesive tablets by including bioadhesive polymers as chitosan (FG90C), polyvinylpyrrolidone (PVPK90) and polycarbophil (PCPAA1), blended in different ratios. All formulations were characterized by studies of DSC, friability, hardness, hydration, mucoadhesion, in vitro release and antibacterial activity. All polymer mixtures employed were used to prepare tablets with the compactness and hardness so as allow the application on vaginal mucosa. FG90C performances improved in particular when mixed to PVPK90 (1:1 ratio). This kind of delivery system is suitable for formulating MET for topical application representing a good alternative to traditional dosage forms for vaginal topical administration.

  17. Final Technical Report - DOE Grant No. DE-FG02-07ER46424

    Energy Technology Data Exchange (ETDEWEB)

    Stroud, David [The Ohio State Univ., Columbus, OH (United States)

    2016-08-05

    We present a final report on the activities undertaken under DOE Grant No. DE-FG02-07ER46424, titled "Interaction effects in quasi one-dimensional electronic systems," originally under the direction of Prof. Julia Meyer. The report includes an overview of the grant and the personnel involved, a list of publications acknowledging the grant, and a summary of the results and conclusions drawn from research supported by the grant.

  18. Final Technical Report for contract number DE-FG02-05ER15670

    Energy Technology Data Exchange (ETDEWEB)

    Glazebrook, Jane [Univ. of Minnesota, Minneapolis, MN (United States)

    2016-02-29

    This is the final technical report for contract number DE-FG02-05ER15670. The project is now complete, and results of the project have been published. Two papers were published based on work done in the last three-year funding period. The DOIs of these papers are included below. The abstracts of the papers, providing summaries of the work, are included in the body of the report.

  19. Test of the uplift of Tibetan Plateau by FG5 absolute gravimeter at Lhasa station

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The uplift of the Tibetan Plateau has been monitored by the FG5 absolute gravimeter, whose observing accuracy is as high as 2×10-8 m/s2. The analysis of the gravity observation results at the Lhasa station in 1999 and 1993 shows that the gravity value has decreased by 12×10-8 m/s2, and it is confirmed that the Lhasa region is uplifting at a rate of 10 mm/a.

  20. Thermo-electro-mechanical postbuckling of piezoelectric FG-CNTRC beams with geometric imperfections

    Science.gov (United States)

    Wu, Helong; Kitipornchai, Sritawat; Yang, Jie

    2016-09-01

    This paper presents thermo-electro-mechanical postbuckling analysis of geometrically imperfect functionally graded carbon nanotube-reinforced composite (FG-CNTRC) hybrid beams that are integrated with surface-bonded piezoelectric actuators. The material properties of FG-CNTRCs are assumed to be temperature-dependent and graded in the thickness direction. By using a generic imperfection function, various possible imperfections with different shapes and locations in the beam are considered. The theoretical formulations are based on the first-order shear deformation beam theory with von-Kármán nonlinearity. A differential quadrature approximation based iteration process is employed to obtain the postbuckling equilibrium path of piezoelectric FG-CNTRC hybrid beams under thermo-electro-mechanical loading. Parametric studies are conducted to examine the effect of geometric imperfection, distribution pattern and volume fraction of carbon nanotubes, temperature rise, actuator voltage, beam geometry and boundary conditions on the thermo-electro-mechanical postbuckling behaviour. The results show that the thermo-electro-mechanical postbuckling is considerably affected by the imperfection mode, half-wave number, location and amplitude, as well as the temperature rise and boundary conditions. The effect of applied actuator voltage is much less pronounced but tends to be relatively more noticeable as the slenderness ratio increases.

  1. Set standard deviation, repeatability and offset of absolute gravimeter A10-008

    Science.gov (United States)

    Schmerge, D.; Francis, O.

    2006-01-01

    The set standard deviation, repeatability and offset of absolute gravimeter A10-008 were assessed at the Walferdange Underground Laboratory for Geodynamics (WULG) in Luxembourg. Analysis of the data indicates that the instrument performed within the specifications of the manufacturer. For A10-008, the average set standard deviation was (1.6 0.6) ??Gal (1Gal ??? 1 cm s -2), the average repeatability was (2.9 1.5) ??Gal, and the average offset compared to absolute gravimeter FG5-216 was (3.2 3.5) ??Gal. ?? 2006 BIPM and IOP Publishing Ltd.

  2. FG020326-1oaded nanoparticle with PEG and PDLLA improved pharma-codynamics of reversing multidrug resistance in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Wen-jing DENG; Xiao-qiang YANG; Yong-ju LIANG; Li-ming CHEN; Yan-yan YAN; Xin-tao SHUAI; Li-wu FU

    2007-01-01

    Aim: FG020326, a novel imidazole derivative, is a potent multidrug-resistance (MDR) modulator in vitro and in vivo. However, FG020326 is insoluble. PEDLLA-FG020326 is a FG020326-loaded nanoparticle formed with diblock eopolymers of poly (ethylene glycol)-bloek-poly (D,L-lactic acid) (PEG:PDLLA, PEDLLA) that can solubilize FG020326. This work was intended to evaluate the pharmacody-namics of PEDLLA-FG020326 on reversing MDR in vitro and in vivo.Methods: Cytotoxicity was determined by tetrazolium assay. The intraceUular accumulation and efflux of doxorubicin (Dox) were detected by fluorescence spectrophotometry.The function of P-glycoprotein was examined by Rhodamine 123 (Rh 123) accumu-lation detected by flow cytometry. The KBv200 cell xenograft model was estab-lished to investigate the effect of PEDLLA-FG020326 on reversing MDR in vivo.Results: PEDLLA-FG020326 and FG020326 exhibited 56.4- and 35.9-fold activity in reversing KBv200 cells to vincristine (VCR) resistance, respectively and 14.98-and 7.64-fold to Dox resistance, respectively. PEDLLA-FG020326 was much stron-ger than FG020326, resulting in the increase of Dox and Rh123 accumulation and the decrease of intracellular Dox extrusion in KBv200 cells. Importantly, PEDLLA-FG020326 exhibited more powerful activity than FG020326 in enhancing the effect of VCR against KBv200 cell xenografts in nude mice, but did not appear more toxic.Conclusion: The pharmacodynamics of FG020326 was improved by incorporating it into a micellar nanoparticle formed with PEG-block-PDLLA copolymers.

  3. Quantum repeated games revisited

    CERN Document Server

    Frackiewicz, Piotr

    2011-01-01

    We present a scheme for playing quantum repeated 2x2 games based on the Marinatto and Weber's approach to quantum games. As a potential application, we study twice repeated Prisoner's Dilemma game. We show that results not available in classical game can be obtained when the game is played in the quantum way. Before we present our idea, we comment on the previous scheme of playing quantum repeated games.

  4. Fusarium graminearum pyruvate dehydrogenase kinase 1 (FgPDK1 Is Critical for Conidiation, Mycelium Growth, and Pathogenicity.

    Directory of Open Access Journals (Sweden)

    Tao Gao

    Full Text Available Pyruvate dehydrogenase kinase (PDK is an important mitochondrial enzyme that blocks the production of acetyl-CoA by selectively inhibiting the activity of pyruvate dehydrogenase (PDH through phosphorylation. PDK is an effectively therapeutic target in cancer cells, but the physiological roles of PDK in phytopathogens are largely unknown. To address these gaps, a PDK gene (FgPDK1 was isolated from Fusarium graminearum that is an economically important pathogen infecting cereals. The deletion of FgPDK1 in F. graminearum resulted in the increase in PDH activity, coinciding with several phenotypic defects, such as growth retardation, failure in perithecia and conidia production, and increase in pigment formation. The ΔFgPDK1 mutants showed enhanced sensitivity to osmotic stress and cell membrane-damaging agent. Physiological detection indicated that reactive oxygen species (ROS accumulation and plasma membrane damage (indicated by PI staining, lipid peroxidation, and electrolyte leakage occurred in ΔFgPDK1 mutants. The deletion of FgPDK1 also prohibited the production of deoxynivalenol (DON and pathogenicity of F. graminearum, which may resulted from the decrease in the expression of Tri6. Taken together, this study firstly identified the vital roles of FgPDK1 in the development of phytopathogen F. graminearum, which may provide a potentially novel clue for target-directed development of agricultural fungicides.

  5. Domain analysis

    DEFF Research Database (Denmark)

    Hjørland, Birger

    2017-01-01

    The domain-analytic approach to knowledge organization (KO) (and to the broader field of library and information science, LIS) is outlined. The article reviews the discussions and proposals on the definition of domains, and provides an example of a domain-analytic study in the field of art studie....... Varieties of domain analysis as well as criticism and controversies are presented and discussed....

  6. Crystal structure of the G3BP2 NTF2-like domain in complex with a canonical FGDF motif peptide.

    Science.gov (United States)

    Kristensen, Ole

    2015-11-06

    The crystal structure of the NTF2-like domain of the human Ras GTPase SH3 Binding Protein (G3BP), isoform 2, was determined at a resolution of 2.75 Å in complex with a peptide containing a FGDF sequence motif. The overall structure of the protein is highly similar to the homodimeric N-terminal domains of the G3BP1 and Rasputin proteins. Recently, a subset of G3BP interacting proteins was recognized to share a common sequence motif, FGDF. The most studied binding partners, USP10 and viral nsP3, interfere with essential G3BP functions related to assembly of cellular stress granules. Reported molecular modeling suggested that FGDF-motif containing peptides bind in an extended conformation into a hydrophobic groove on the surface of the G3BP NTF2-like domain in a manner similar to the known binding of FxFG nucleoporin repeats. The results in this paper provide evidence for a different binding mode. The FGDF peptide binds and changes conformation of the protruding N-terminal residues by providing hydrophobic interactions to a symmetry related molecule that facilitated crystallization of the G3BP2 isoform.

  7. Shape, thermal and surface properties determination of a candidate spacecraft target asteroid (175706) 1996 FG3

    Science.gov (United States)

    Yu, LiangLiang; Ji, Jianghui; Wang, Su

    2014-04-01

    In this paper, a 3D convex shape model of (175706) 1996 FG3, which consists of 2040 triangle facets and 1022 vertices, is derived from the known light curves. The best-fitting orientation of the asteroid's spin axis is determined to be λ = 237.27° and β = -83.8° considering the observation uncertainties, and its rotation period is ˜3.5935 h. Using the derived shape model, we adopt the so-called advanced thermophysical model (ATPM) to fit three published sets of mid-infrared observations of 1996 FG3, so as to evaluate its surface properties. Assuming the primary and the secondary bear identical shape, albedo, thermal inertia and surface roughness, the best-fitting parameters are obtained from the observations. The geometric albedo and effective diameter of the asteroid are reckoned to be pv = 0.045 ± 0.002, D_eff=1.69^{+0.05}_{-0.02} km. The diameters of the primary and secondary are determined to be D1=1.63^{+0.04}_{-0.03} km and D2=0.45^{+0.04}_{-0.03} km, respectively. The surface thermal inertia Γ is derived to be a low value of 80 ± 40 Jm-2 s-0.5 K-1 with a roughness fraction fR of 0.8^{+0.2}_{-0.4}. This indicates that the primary possibly has a regolith layer on its surface, which is likely to be covered by a mixture of dust, fragmentary rocky debris and sand. The minimum regolith depth is estimated to be 5-20 mm from the simulations of subsurface temperature distribution, indicating that 1996 FG3 could be a very suitable target for a sample return mission.

  8. Establishing a core domain set to measure rheumatoid arthritis flares

    DEFF Research Database (Denmark)

    Bykerk, Vivian P; Lie, Elisabeth; Bartlett, Susan J;

    2014-01-01

    agenda for OMERACT 12. CONCLUSION: At OMERACT 11, a core domain set to measure RA flare was ratified and endorsed by attendees. Domain validation aligning with Filter 2.0 is ongoing in new randomized controlled clinical trials and longitudinal observational studies using existing and new instruments......OBJECTIVE: The OMERACT Rheumatoid Arthritis (RA) Flare Group (FG) is developing a data-driven, patient-inclusive, consensus-based RA flare definition for use in clinical trials, longterm observational studies, and clinical practice. At OMERACT 11, we sought endorsement of a proposed core domain set....... At OMERACT 11, breakout groups discussed key domains and instruments to measure them, and proposed a research agenda. Patients were active research partners in all focus groups and domain identification activities. Processes for domain selection and patient partner involvement were case studies for OMERACT...

  9. Reconfigurable multiport EPON repeater

    Science.gov (United States)

    Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

    2009-11-01

    An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

  10. Final Close-Out Report for DE-FG02-93ER40764

    Energy Technology Data Exchange (ETDEWEB)

    Gyulassy, Miklos [Columbia Univ., New York, NY (United States)

    2016-02-12

    This is a final close-out report for DOE contract DE-FG02-93ER40764 at Columbia University in New York that funded nuclear theory research at Columbia from 12/15/1992 to 12/14/2015. Highlight of research results from the last FY 2015 period, a list of all 12 PhD students trained through the whole grant, and a list of 201 original papers published from 1993-2015 with impact factor metrics are presented.

  11. The absolute gravity measurement by FG5 gravimeter at Great Wall Station, Antarctica

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Gravity measurement is of great importance to the height datum in Antarctica.The absolute gravity measurement was carried out at Great Wall Station, Antarctica, using FG5 absolute gravity instrument.The gravity data was processed with corrections of earth tide, ocean tide, polar motion and the atmospher, and the RMS is within +3 x 10 -s ms-2.The vertical and horizontal gravity gradients were measured using 2 LaCoaste & Romberg (LCR) gravimeters.The absolute gravity measurement provides the fundamental data for the validation and calibration of the satellite gravity projects such as CHAMP, GRACE and GOCE, and for the high accuracy geoid model.

  12. Stability analysis of some reconstructed cosmological models in f(G , T) gravity

    Science.gov (United States)

    Sharif, M.; Ikram, Ayesha

    2017-09-01

    The aim of this paper is to reconstruct and analyze the stability of some cosmological models against linear perturbations in f(G , T) gravity (G and T represent the Gauss-Bonnet invariant and trace of the energy-momentum tensor, respectively). We formulate the field equations for both general as well as particular cases in the context of isotropic and homogeneous universe model. We reproduce the cosmic evolution corresponding to de Sitter universe, power-law solutions and phantom/non-phantom eras in this theory using reconstruction technique. Finally, we study stability analysis of de Sitter as well as power-law solutions through linear perturbations.

  13. Structures of the autoproteolytic domain from the Saccharomyces cerevisiae nuclear pore complex component, Nup145

    Energy Technology Data Exchange (ETDEWEB)

    Sampathkumar, Parthasarathy; Ozyurt, Sinem A.; Do, Johnny; Bain, Kevin T.; Dickey, Mark; Rodgers, Logan A.; Gheyi, Tarun; Sali, Andrej; Kim, Seung Joong; Phillips, Jeremy; Pieper, Ursula; Fernandez-Martinez, Javier; Franke, Josef D.; Martel, Anne; Tsuruta, Hiro; Atwell, Shane; Thompson, Devon A.; Emtage, J. Spencer; Wasserman, Stephen R.; Rout, Michael P.; Sauder, J. Michael; Burley, Stephen K. (SLAC); (Rockefeller); (UCSF); (Lilly)

    2012-04-30

    Nuclear pore complexes (NPCs) are large, octagonally symmetric dynamic macromolecular assemblies responsible for exchange of proteins and RNAs between the nucleus and cytoplasm. NPCs are made up of at least 456 polypeptides from {approx}30 distinct nucleoporins. Several of these components, sharing similar structural motifs, form stable subcomplexes that form a coaxial structure containing two outer rings (the nuclear and cytoplasmic rings), two inner rings, and a membrane ring. The yeast (Saccharomyces cerevisiae) Nup145 and its human counterpart are unique among the nucleoporins, in that they undergo autoproteolysis to generate functionally distinct proteins. The human counterpart of Nup145 is expressed as two alternatively spliced mRNA transcripts. The larger 190 kDa precursor undergoes post-translational autoproteolysis at the Phe863-Ser864 peptide bond yielding the 92 kDa Nup98 and the 96 kDa Nup96. The smaller 98 kDa precursor is also autoproteolysed at an analogous site giving 92 kDa Nup98-N and a 6 kDa C-terminal fragment, which may form a noncovalent complex. The yeast Nup145 precursor [Fig. 1(A)] contains twelve repeats of a 'GLFG' peptide motif (FG repeats) at its N-terminus, an internal autoproteolytic domain (a region of high conservation with the homologous yeast nucleoporins Nup110 and Nup116, neither of which undergo autoproteolysis), followed by the C-terminal domain. Various forms of the FG repeats are present in nearly half of all nucleoporins; they form intrinsically disordered regions implicated in gating mechanisms that control passage of macromolecules through NPCs. Nup145 undergoes autoproteolysis at the Phe605-Ser606 peptide bond to generate two functionally distinct proteins, Nup145N and Nup145C. Subsequently, Nup145C associates with six other proteins to form the heptameric Y-complex, a component of the outer rings of the NPC. Nup145N, on the other hand, can shuttle between the NPC and the nuclear interior. It has been suggested

  14. Recursive quantum repeater networks

    CERN Document Server

    Van Meter, Rodney; Horsman, Clare

    2011-01-01

    Internet-scale quantum repeater networks will be heterogeneous in physical technology, repeater functionality, and management. The classical control necessary to use the network will therefore face similar issues as Internet data transmission. Many scalability and management problems that arose during the development of the Internet might have been solved in a more uniform fashion, improving flexibility and reducing redundant engineering effort. Quantum repeater network development is currently at the stage where we risk similar duplication when separate systems are combined. We propose a unifying framework that can be used with all existing repeater designs. We introduce the notion of a Quantum Recursive Network Architecture, developed from the emerging classical concept of 'recursive networks', extending recursive mechanisms from a focus on data forwarding to a more general distributed computing request framework. Recursion abstracts independent transit networks as single relay nodes, unifies software layer...

  15. Investigation on steam oxidation behaviour of TP347H FG Part I Exposure at 256 bar

    DEFF Research Database (Denmark)

    Jianmin, J; Montgomery, Melanie; Larsen, OH

    2005-01-01

    The stainless steel TP347H FG is a candidate material for the final stage tubing of superheater and reheater sections of ultra supercritical boilers operated at steam temperatures up to 620C in the mild corrosion environments of coal-firing. A series of field tests has been conducted with the afo......The stainless steel TP347H FG is a candidate material for the final stage tubing of superheater and reheater sections of ultra supercritical boilers operated at steam temperatures up to 620C in the mild corrosion environments of coal-firing. A series of field tests has been conducted...... with the aforementioned steel in coal-fired boilers and this paper focuses on the steam oxidation behaviour for specimens tested at various metal temperatures for exposure times of 7700, 23000 and 30000 hours as investigated by light optical and scanning electron microscopy. The oxide present on the specimens is a duplex......, where the larger the metal grain size, the thicker the oxidation scale. This gave the appearance of uneven inner oxides with a varying pit thickness. Comparison of the pit thickness measurement and oxide composition reveals that the oxidation rate is fast during the initial oxidation stage...

  16. Free vibration of shallow and deep curved FG nanobeam via nonlocal Timoshenko curved beam model

    Science.gov (United States)

    Hosseini, S. A. H.; Rahmani, O.

    2016-03-01

    A free vibration analysis of shallow and deep curved functionally graded (FG) nanobeam is presented. Differential equations and boundary conditions are obtained using Hamilton's principle, and then, nonlocal theory is employed to derive differential equations in small scale. Properties of the material are FG in radial direction. In order to investigate the effects of deep curved beam, extensional stiffness, bending-extension coupling stiffness, and bending stiffness are calculated in the deep case, analytically. By employing Navier method, an analytical solution is presented. Results are compared and validated with available studies, and a good agreement is seen. The influences of effective parameters such as geometrical deep term, nonlocal parameter, opening angle, aspect ratio, mode number, and gradient index are discussed in detail. It is found that the frequency of deep curved nanobeam is higher than that of shallow one, and the aspect ratio significantly affects this difference to decrease. Also, it is concluded that the opening angle, nonlocal parameter, and power gradient index can notably influence the amount of frequency.

  17. Involvement of a velvet protein FgVeA in the regulation of asexual development, lipid and secondary metabolisms and virulence in Fusarium graminearum.

    Directory of Open Access Journals (Sweden)

    Jinhua Jiang

    Full Text Available The velvet protein, VeA, is involved in the regulation of diverse cellular processes. In this study, we explored functions of FgVeA in the wheat head blight pathogen, Fusarium graminearum,using a gene replacement strategy. The FgVEA deletion mutant exhibited a reduction in aerial hyphae formation, hydrophobicity, and deoxynivalenol (DON biosynthesis. Deletion of FgVEA gene led to an increase in conidial production, but a delay in conidial germination. Pathogencity assays showed that the mutant was impaired in virulence on flowering wheat head. Sensitivity tests to various stresses exhibited that the FgVEA deletion mutant showed increased resistance to osmotic stress and cell wall-damaging agents, but increased sensitivity to iprodione and fludioxonil fungicides. Ultrastructural and histochemical analyses revealed that conidia of FgVeA deletion mutant contained an unusually high number of large lipid droplets, which is in agreement with the observation that the mutant accumulated a higher basal level of glycerol than the wild-type progenitor. Serial analysis of gene expression (SAGE in the FgVEA mutant confirmed that FgVeA was involved in various cellular processes. Additionally, six proteins interacting with FgVeA were identified by yeast two hybrid assays in current study. These results indicate that FgVeA plays a critical role in a variety of cellular processes in F. graminearum.

  18. Wave propagation analysis of quasi-3D FG nanobeams in thermal environment based on nonlocal strain gradient theory

    Science.gov (United States)

    Ebrahimi, Farzad; Barati, Mohammad Reza

    2016-09-01

    This article examines the application of nonlocal strain gradient elasticity theory to wave dispersion behavior of a size-dependent functionally graded (FG) nanobeam in thermal environment. The theory contains two scale parameters corresponding to both nonlocal and strain gradient effects. A quasi-3D sinusoidal beam theory considering shear and normal deformations is employed to present the formulation. Mori-Tanaka micromechanical model is used to describe functionally graded material properties. Hamilton's principle is employed to obtain the governing equations of nanobeam accounting for thickness stretching effect. These equations are solved analytically to find the wave frequencies and phase velocities of the FG nanobeam. It is indicated that wave dispersion behavior of FG nanobeams is significantly affected by temperature rise, nonlocality, length scale parameter and material composition.

  19. The NF-κB pathway: regulation of the instability of atherosclerotic plaques activated by Fg, Fb, and FDPs.

    Science.gov (United States)

    Cao, Yongjun; Zhou, Xiaomei; Liu, Huihui; Zhang, Yanlin; Yu, Xiaoyan; Liu, Chunfeng

    2013-11-01

    Recently, the molecular mechanism responsible for the instability of atherosclerotic plaques has gradually become a hot topic among researchers and clinicians. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play an important role in the processes of formation and development of atherosclerosis. In this study, we established and employed the transwell co-culture system of rabbit aortic endothelial cells and smooth muscle cells to explore the relationship between fibrin (Fb), fibrinogen (Fg), and/or their degradation products (FDPs) in relation to the instability of atherosclerotic plaques; meanwhile, we observed the effects of Fg, Fb, and FDPs on the mRNA levels of MMPs and VEGF as well as on the activation of nuclear factor-kappa B (NF-κB). We concluded that Fb, Fg, and FDPs are involved in the progression of the instability of atherosclerotic plaques via increasing the expression of MMPs and VEGF. This effect might be mediated by the NF-кB pathway.

  20. Steam oxidation of TP 347H FG. Laboratory exposures versus service conditions at the power plant

    Energy Technology Data Exchange (ETDEWEB)

    Hansson, Anette N. [DONG Energy A/S, Copenhagen (Denmark); Montgomery, Melanie [DONG Energy A/S, Copenhagen (Denmark); Technical Univ. of Denmark, Lyngby (Denmark). Dept. of Mechanical Engineering; Vattenfall Heat Nordic, Copenhagen (Denmark)

    2010-07-01

    TP347H FG is often used as final superheater tubing at Danish Power Plants. The oxidation behaviour of TP347H FG in steam was investigated both in laboratory conditions and field conditions. Short time exposures (336 hours) were performed in the laboratory at 500, 600 and 700 C in gasses with 8 or 46% H{sub 2}O and varying oxygen partial pressures. The shortest exposure time at the power plant was 7720 h, the temperature varied between 500 and 650 C. Surprisingly, thicker oxide layers formed within the laboratory facility at 600 and 700 C than during the long time exposures at the power plant. This could not be explained by spallation. Double-layered oxides developed during oxidation. The outer layer consist of Fe-oxides and the inner oxide contained Fe and the remaining alloy elements. Investigations with scanning electron microscopy (SEM) revealed that the morphology of the inner oxide was different for the two types of exposures. However, investigation using transmission electron microscopy (TEM) showed that the inner oxide in both cases consisted of particles of Fe-Mn-Cr spinel embedded in a metallic Fe-Ni matrix in the bulk of the (former) alloy grains and Cr-rich oxide layer along the (former) alloy grain boundaries. The main difference between the layers formed at the two locations is that the Cr-rich oxide layer is thicker for the samples exposed at the power plant than that for the samples exposed at the laboratory conditions. Furthermore, the depth of Cr depletion in the alloy adjacent the oxide layer is greater for the samples exposed at the power plant compared to those exposed in the laboratory. The microstructure investigation suggests that the slower oxidation rate of TP347H FG at the power plant as compared to the laboratory is due to a larger reservoir of Cr for the samples exposed at the power plant probably combined with a higher mobility of Cr within the alloy. (orig.)

  1. Repeating the Past

    Science.gov (United States)

    Moore, John W.

    1998-05-01

    As part of the celebration of the Journal 's 75th year, we are scanning each Journal issue from 25, 50, and 74 years ago. Many of the ideas and practices described are so similar to present-day "innovations" that George Santayana's adage (1) "Those who cannot remember the past are condemned to repeat it" comes to mind. But perhaps "condemned" is too strong - sometimes it may be valuable to repeat something that was done long ago. One example comes from the earliest days of the Division of Chemical Education and of the Journal.

  2. 锚蛋白重复和激酶域1基因多态性与精神分裂症的关联研究%Association study of schizophrenia and ankyrin repeat and kinase domain containing 1 gene polymorphism

    Institute of Scientific and Technical Information of China (English)

    郭娟; 陈元堂; 何长江; 张丽; 吴瑜; 行养玲; 敖磊

    2010-01-01

    目的 探讨锚蛋白重复和激酶域1(ANKK1)基因多态性与精神分裂症的相关性.方法 收集符合美国DSM-Ⅳ精神分裂症诊断标准的112个先证者及其父母组成的核心家系,运用聚合酶链反应扩增及单核苷酸多态性的分子生物学技术,对ANK K1基因的rs4938015、rs7118900、rs2734849、rs1800497多态性分型,进行精神分裂症与锚蛋白重复和激酶域1基因多态性的关联分析和单体型相对风险率分析.结果 rs2734849等位基因与精神分裂症相关联(P=0.026),其中等位基因T是保护因素(Z=-2.19),A为危险因素(Z=2.19);rs4938015、rs7118900、rs1800497与精神分裂症无关联.三种单体型rs7118900-rs2734849的G/A、rs 2734849-rs1800497的A/C、rs7118900-rs2734849-rs1800497中的G/A/C与精神分裂症有关联(P值分别为0.032,0.041,0.046,基因型频率分别为0.36,0.29,0.17).结论 ANKK1基因与精神分裂症相关联.%Objective To detect the genetic association between schizophrenia and polymorphism of Ankyrin repeat and kinase domain containing 1 ( ANKK1 ) gene. Methods Observed in a sample of 112 parent/offspring trios where the proband net the American Classification and diagnostic Criteria for Mental Disorders The Forth Revised Edition, criteria for schizophrenia using correlation analysis and haplotype relative risk analysis. The polymorphism of Ankyrin repeat and kinase domain containing 1 gene was detected with PCR methods and SNP typing in all nucleus families. Results The rs2734849 allele was connected with schizophrenia(P= 0. 026). Allele T was protective factor( Z= -2.19) and allele A was the hazard factor( Z=2. 19). The rs4938015,rs7118900 and rs1800497 allele were independence with schizophrenia. Three kinds haplotypes of G/A in the rs7118900 -rs2734849, A/C in the rs2734849 -rs1800497, G/A/C in the rs7118900 -rs2734849 -rs1800497 were associated with schizophrenia ( The P values were 0.032,0. 041,0.046, the genotype frequencies were 0. 36,0.29,0. 17

  3. Field test results for steam oxidation of TP347H FG - growth of inner oxide

    DEFF Research Database (Denmark)

    Montgomery, Melanie; Jianmin, Jia; Larsen, OH

    2005-01-01

    A series of field tests have been conducted with TP347H FG in test superheater loops in coal-fired and biomass fired boilers of steam pressure 256 and 91 bar respectively. The exposure times are from 3,500 to 30,000 hours and the temperature range is from 450-630¢XC. The morphology, composition...... inner oxide presumably due to the formation of a more chromium rich Fe-Cr-Ni oxide at grain boundaries. At temperatures over 610¢XC, there is a decrease in inner oxide thickness. A thicker inner oxide is observed at the lower pressures compared to similar temperature ranges at higher pressures....... The effect of temperature, exposure time and pressure are discussed....

  4. Final Technical Report for Grant DE-FG02-04ER54795

    Energy Technology Data Exchange (ETDEWEB)

    Merlino, Robert L [Univ. of Iowa, Iowa City, IA (United States)

    2015-10-02

    This is the final technical report for DOE Grant #DE-FG02-04ER54795-Experimental Investigations of Fundamental Processes in Dusty Plasmas. A plasma is an ionized gas, and a dusty plasmas is a plasma that contains, in addition to electrons and ions, micron-sized dust particles. The dust particles acquire and electric charge in the plasma by collecting electrons and ions. The electrons move more rapidly than the ions, so the dust charge is negative. A 1 micron dust particle in a typical low temperature plasma has a charge corresponding to approximately 2000 electrons. Dusty plasmas are naturally found in astrophysical plasmas, planetary rings, technological plasmas, and magnetic fusion plasmas. The goal of this project was to study in the laboratory, the basic physical processes that occur in dusty plasmas. This report provides a summary of the major scientific products and activities of this award.

  5. Quantum interference effects in a multidriven transition Fg = 3 (←→) Fe= 2

    Institute of Scientific and Technical Information of China (English)

    Dong Ya-Bin; Zhang Jun-Xiang; Wang Hai-Hong; Gao Jiang-Rui

    2006-01-01

    We have theoretically and experimentally studied the quantum coherence effects of a degenerate transition Fg =3 (←→)Fe = 2 system interacting with a weak linearly polarized (with σ± components) probe light and a strong linearly polarized (with σ± components) coupling field. Due to the competition between the drive Rabi frequency and the Zeeman splitting, electromagnetically induced transparency (EIT) and electromagnetically induced absorption (EIA)are present at the different values of applied magnetic field in the case where the Zeeman splitting of excited state △e is larger than the Zeeman splitting of ground state △g (i.e. △e >△g).

  6. Elastic Solution of a Constrained FG Short Cylinder Under Axially Variable Pressure

    Science.gov (United States)

    Arefi, Mohammad; Mohammad-Rezaei Bidgoli, Elyas

    2017-06-01

    Elastic analysis of a functionally graded thick cylinder under longitudinally variable mechanical loadings is studied in the present paper. The modulus of elasticity is graded along the thickness direction based on the power law function. The cylinder is subjected to variable pressure along the longitudinal direction. First order shear deformation theory is employed for description of a two dimensional displacement field. This is due to fully constrained boundary conditions of the cylinder. An analytical approach was proposed for solution of non homogenous system of differential equations and derivation of homogenous and particular solutions. This approach has capability to model different types of loading (constant, linear and other types) along the longitudinal direction. The effect of different constant and variable loads is considered on the elastic results of FG cylinder.

  7. All-optical repeater.

    Science.gov (United States)

    Silberberg, Y

    1986-06-01

    An all-optical device containing saturable gain, saturable loss, and unsaturable loss is shown to transform weak, distorted optical pulses into uniform standard-shape pulses. The proposed device performs thresholding, amplification, and pulse shaping as required from an optical repeater. It is shown that such a device could be realized by existing semiconductor technology.

  8. Bidirectional Manchester repeater

    Science.gov (United States)

    Ferguson, J.

    1980-01-01

    Bidirectional Manchester repeater is inserted at periodic intervals along single bidirectional twisted pair transmission line to detect, amplify, and transmit bidirectional Manchester 11 code signals. Requiring only 18 TTL 7400 series IC's, some line receivers and drivers, and handful of passive components, circuit is simple and relatively inexpensive to build.

  9. RepeatsDB 2.0: improved annotation, classification, search and visualization of repeat protein structures

    Science.gov (United States)

    Paladin, Lisanna; Hirsh, Layla; Piovesan, Damiano; Andrade-Navarro, Miguel A.; Kajava, Andrey V.; Tosatto, Silvio C.E.

    2017-01-01

    RepeatsDB 2.0 (URL: http://repeatsdb.bio.unipd.it/) is an update of the database of annotated tandem repeat protein structures. Repeat proteins are a widespread class of non-globular proteins carrying heterogeneous functions involved in several diseases. Here we provide a new version of RepeatsDB with an improved classification schema including high quality annotations for ∼5400 protein structures. RepeatsDB 2.0 features information on start and end positions for the repeat regions and units for all entries. The extensive growth of repeat unit characterization was possible by applying the novel ReUPred annotation method over the entire Protein Data Bank, with data quality is guaranteed by an extensive manual validation for >60% of the entries. The updated web interface includes a new search engine for complex queries and a fully re-designed entry page for a better overview of structural data. It is now possible to compare unit positions, together with secondary structure, fold information and Pfam domains. Moreover, a new classification level has been introduced on top of the existing scheme as an independent layer for sequence similarity relationships at 40%, 60% and 90% identity. PMID:27899671

  10. Multi-domain proteins in the three kingdoms of life: orphan domains and other unassigned regions.

    Science.gov (United States)

    Ekman, Diana; Björklund, Asa K; Frey-Skött, Johannes; Elofsson, Arne

    2005-04-22

    Comparative studies of the proteomes from different organisms have provided valuable information about protein domain distribution in the kingdoms of life. Earlier studies have been limited by the fact that only about 50% of the proteomes could be matched to a domain. Here, we have extended these studies by including less well-defined domain definitions, Pfam-B and clustered domains, MAS, in addition to Pfam-A and SCOP domains. It was found that a significant fraction of these domain families are homologous to Pfam-A or SCOP domains. Further, we show that all regions that do not match a Pfam-A or SCOP domain contain a significantly higher fraction of disordered structure. These unstructured regions may be contained within orphan domains or function as linkers between structured domains. Using several different definitions we have re-estimated the number of multi-domain proteins in different organisms and found that several methods all predict that eukaryotes have approximately 65% multi-domain proteins, while the prokaryotes consist of approximately 40% multi-domain proteins. However, these numbers are strongly dependent on the exact choice of cut-off for domains in unassigned regions. In conclusion, all eukaryotes have similar fractions of multi-domain proteins and disorder, whereas a high fraction of repeating domain is distinguished only in multicellular eukaryotes. This implies a role for repeats in cell-cell contacts while the other two features are important for intracellular functions.

  11. The MADS-box transcription factor FgMcm1 regulates cell identity and fungal development in Fusarium graminearum.

    Science.gov (United States)

    Yang, Cui; Liu, Huiquan; Li, Guotian; Liu, Meigang; Yun, Yingzi; Wang, Chenfang; Ma, Zhonghua; Xu, Jin-Rong

    2015-08-01

    In eukaryotic cells, MADS-box genes are known to play major regulatory roles in various biological processes by combinatorial interactions with other transcription factors. In this study, we functionally characterized the FgMCM1 MADS-box gene in Fusarium graminearum, the causal agent of wheat and barley head blight. Deletion of FgMCM1 resulted in the loss of perithecium production and phialide formation. The Fgmcm1 mutant was significantly reduced in virulence, deoxynivalenol biosynthesis and conidiation. In yeast two-hybrid assays, FgMcm1 interacted with Mat1-1-1 and Fst12, two transcription factors important for sexual reproduction. Whereas Fgmcm1 mutants were unstable and produced stunted subcultures, Fgmcm1 mat1-1-1 but not Fgmcm1 fst12 double mutants were stable. Furthermore, spontaneous suppressor mutations occurred frequently in stunted subcultures to recover growth rate. Ribonucleic acid sequencing analysis indicated that a number of sexual reproduction-related genes were upregulated in stunted subcultures compared with the Fgmcm1 mutant, which was downregulated in the expression of genes involved in pathogenesis, secondary metabolism and conidiation. We also showed that culture instability was not observed in the Fvmcm1 mutants of the heterothallic Fusarium verticillioides. Overall, our data indicate that FgMcm1 plays a critical role in the regulation of cell identity, sexual and asexual reproduction, secondary metabolism and pathogenesis in F. graminearum.

  12. Significance of the class II hydrophobin FgHyd5p for the life cycle of Fusarium graminearum.

    Science.gov (United States)

    Minenko, Ekaterina; Vogel, Rudi F; Niessen, Ludwig

    2014-04-01

    Hydrophobins are small secreted proteins ubiquitously found in filamentous fungi. Some hydrophobins were shown to have functions in fungal development, while others lack known function. Class II hydrophobins from Fusarium graminearum and Fusarium culmorum are characterized by formation of low stability aggregates and their solubility in organic solvents. They are economically relevant to the brewing industry because they can induce beer gushing. Since cellular functions of Hyd5p's are still unknown, we analyzed the influence of FgHyd5p on growth and morphology of F. graminearum using FgΔhyd5 knock-out mutants expressing sGFP under the control of the hyd5 promoter and compared them with the performance of the parent wild type strain. Results demonstrate that FgHyd5p does not affect the colony and hyphal morphology. FgHyd5p affects the hydrophobicity of aerial mycelia but had no obvious function in penetration of hyphae through the water air interface. The hydrophobin affects the morphology of conidia, but not their fitness. Different sources of carbon and nitrogen as well as different pH have no effect on the expression of the hyd5 gene, which was demonstrated to be expressed upon growth of F. graminearum on hydrophobic surfaces.

  13. Effects of the beta-carboline, FG 7142, in the social interaction test of anxiety and the holeboard: correlations between behaviour and plasma concentrations.

    Science.gov (United States)

    File, S E; Pellow, S; Braestrup, C

    1985-06-01

    The behavioural effects of the beta-carboline FG 7142 were investigated in the social interaction test of anxiety and the holeboard test of exploration and locomotor activity. FG 7142 (5-20 mg/kg) produced a significant decrease in the time spent in social interaction by pairs of rats, without an accompanying decrease in motor activity. This anxiogenic effect was highly correlated with the plasma concentrations of FG 7142 for the rats receiving 5 and 10 mg/kg doses, but not for those receiving the 20 mg/kg dose. In the holeboard, FG 7142 had no effect on exploratory head-dipping at the doses tested, but selectively reduced locomotor activity and the number of rears. The profile of FG 7142 in these tests is compared with those of the beta-carbolines, B-CCE and B-CCP.

  14. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-01-01

    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

  15. The cyclase-associated protein FgCap1 has both protein kinase A-dependent and -independent functions during deoxynivalenol production and plant infection in Fusarium graminearum.

    Science.gov (United States)

    Yin, Tao; Zhang, Qiang; Wang, Jianhua; Liu, Huiquan; Wang, Chenfang; Xu, Jin-Rong; Jiang, Cong

    2017-01-31

    Fusarium graminearum is a causal agent of wheat scab and a producer of the trichothecene mycotoxin deoxynivalenol (DON). The expression of trichothecene biosynthesis (TRI) genes and DON production are mainly regulated by the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway and two pathway-specific transcription factors (TRI6 and TRI10). Interestingly, deletion mutants of TRI6 show reduced expression of several components of cAMP signalling, including the FgCAP1 adenylate-binding protein gene that has not been functionally characterized in F. graminearum. In this study, we show that FgCap1 interacts with Fac1 adenylate cyclase and that deletion of FgCAP1 reduces the intracellular cAMP level and PKA activity. The Fgcap1 deletion mutant is defective in vegetative growth, conidiogenesis and plant infection. It also shows significantly reduced DON production and TRI gene expression, which can be suppressed by exogenous cAMP, indicating a PKA-dependent regulation of DON biosynthesis by FgCap1. The wild-type, but not tri6 mutant, shows increased levels of intracellular cAMP and FgCAP1 expression under DON-producing conditions. Furthermore, the promoter of FgCAP1 contains one putative Tri6-binding site that is important for its function during DON biosynthesis, but is dispensable for hyphal growth, conidiogenesis and pathogenesis. In addition, FgCap1 shows an actin-like localization to the cortical patches at the apical region of hyphal tips. Phosphorylation of FgCap1 at S353 was identified by phosphoproteomics analysis. The S353A mutation in FgCAP1 has no effect on its functions during vegetative growth, conidiation and DON production. However, expression of the FgCAP1(S353A) allele fails to complement the defects of the Fgcap1 mutant in plant infection, indicating the importance of the phosphorylation of FgCap1 at S353 during pathogenesis. Taken together, our results suggest that FgCAP1 is involved in the regulation of DON production via cAMP signalling

  16. Zinc-finger directed double-strand breaks within CAG repeat tracts promote repeat instability in human cells.

    Science.gov (United States)

    Mittelman, David; Moye, Christopher; Morton, Jason; Sykoudis, Kristen; Lin, Yunfu; Carroll, Dana; Wilson, John H

    2009-06-16

    Expanded triplet repeats have been identified as the genetic basis for a growing number of neurological and skeletal disorders. To examine the contribution of double-strand break repair to CAG x CTG repeat instability in mammalian systems, we developed zinc finger nucleases (ZFNs) that recognize and cleave CAG repeat sequences. Engineered ZFNs use a tandem array of zinc fingers, fused to the FokI DNA cleavage domain, to direct double-strand breaks (DSBs) in a site-specific manner. We first determined that the ZFNs cleave CAG repeats in vitro. Then, using our previously described tissue culture assay for identifying modifiers of CAG repeat instability, we found that transfection of ZFN-expression vectors induced up to a 15-fold increase in changes to the CAG repeat in human and rodent cell lines, and that longer repeats were much more sensitive to cleavage than shorter ones. Analysis of individual colonies arising after treatment revealed a spectrum of events consistent with ZFN-induced DSBs and dominated by repeat contractions. We also found that expressing a dominant-negative form of RAD51 in combination with a ZFN, dramatically reduced the effect of the nuclease, suggesting that DSB-induced repeat instability is mediated, in part, through homology directed repair. These studies identify a ZFN as a useful reagent for characterizing the effects of DSBs on CAG repeats in cells.

  17. Repeatability of Cryogenic Multilayer Insulation

    Science.gov (United States)

    Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

    2017-01-01

    Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between multiple identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five GRC provided coupons with 25 layers was shown to be +/- 8.4 whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0. A second group of 10 coupons have been fabricated by Yetispace and tested by Florida State University, through the first 4 tests, the repeatability has been shown to be +/- 16. Based on detailed statistical analysis, the data has been shown to be statistically significant.

  18. Biodegradation of Phenol by Using Immobilized Cells of Acinetobacter sp. XA05 and Sphingomonas sp. FG03%固定化Acinetobacter sp. XA05和Sphingomonas sp. FG03降解苯酚

    Institute of Scientific and Technical Information of China (English)

    李华; 刘永军; 刘金光

    2010-01-01

    从活性污泥和受苯酚污染的土壤中分离出的菌株XA05和FG03均具有很强的苯酚生物降解能力.16s rDNA序列分析表明,XA05和FG03菌株分别属于不动杆菌属(Acinetobacter sp.)和鞘氨醇单胞菌属(Sphingomonas sp.).实验结果表明,在苯酚初始质量浓度为800.0 mg/L、培养时间为35 h的条件下,自由悬浮细胞和固定化细胞的苯酚降解率均高于95.0%.

  19. FG5/240绝对重力仪成套设备的检定测量分析%Analysis of the Calibration Measurements of the Whole-Set Absolute Gravimeter FG5/240

    Institute of Scientific and Technical Information of China (English)

    纪立东; 张宏伟; 王应建; 肖凡; 李建国

    2012-01-01

    详细介绍了FG5/240绝对重力仪的技术特点、测量原理和白家疃的试验观测,并就相配套的用于测量梯度的2台CG5相对重力仪(442、444)的检定项目和结果进行说明和分析,结果表明:2台CG5相对重力仪完全满足规范要求,FG5/240绝对重力仪的试验测量结果的标准偏差优于士2.0×10^-8ms^-2,能够用于陆态网络工程任务中部分基准站的绝对重力测量。%In the paper the technological features, measuring principle and the test observations at Baijiatong were introduced in detail. At the same time, the calibration items along with the calibrations of two more relative gravimeters for gradient measurement, CG5/442 and CG5/444, which are applied to form a complete set of the absolute gravimeter, were also described and analyzed. Results show that, 2 sets of CG5 can fully satisfy the demands of specifications, and the standard deviation of FG5 test measurements is better than 2.0 ×10^-8ms^-2, which means that the whole set of the FG5 absolute gra vimeter can be applied in the absolute gravimetry of a part of bench stations in the Land Gravity Network Project.

  20. 拒水拒油剂FG-410对涤纶织物整理工艺探讨%Discussion on finishing technology of water-repellent and oil-repellent finishing agent FG-410 on polyester fabrics

    Institute of Scientific and Technical Information of China (English)

    王健; 江里友

    2011-01-01

    采用国产含氟拒水拒油整理剂FG-410,通过正交试验探讨了整理剂用量、交联剂用量、催化剂用量及焙烘温度等因素对拒水拒油整理效果的影响,优化工艺条件为:FG-410整理剂用量20g/L,FBA交联剂用量16g/L,催化剂MgCl2用量8g/L,155℃焙烘.整理后织物具有良好的拒水拒油性能及耐水洗性,且整理工艺对织物强力及透气性无明显影响.%Polyester fabrics were finished with homemade water-repellent and oil-repellent agent fluorinecontained FG-410.Through orthogonal test, the effects of the dosage of water-repellent and oil-repellent agent,the dosage of crosslinking agent and catalyst, and cure temperature on the properties of water-repellence and oil-repellence were investigated.The optimum technology conditions were as follows: 20 g/L of finishing agent FG-410, 16 g/L of crosslinking agent FBA, 8 g/L of catalyst MgC12, cured at 155 ℃.The finished fabric showed superior water-repellent and oil-repellent properties and durable laundries.And the finishing had unobvious change on the broken strength and the air permeability of the fabrics.

  1. Detection of 75+ pulsation frequencies in the Delta Scuti star FG Vir

    CERN Document Server

    Breger, M; Antoci, V; Guggenberger, E; Shobbrook, R R; Handler, G; Ngwato, B; Rodler, F; Rodríguez, E; De Coca, P L; Rolland, A; Costa, V

    2005-01-01

    Extensive photometric multisite campaigns of the Delta Scuti variable FG Vir are presented. For the years 2003 and 2004, 926 hours of photometry at the millimag precision level were obtained. The combinations with earlier campaigns lead to excellent frequency resolution and high signal/noise. A multifrequency analysis yields 79 frequencies. This represents a new record for this type of star. The modes discovered earlier were confirmed. Pulsation occurs over a wide frequency band from 5.7 to 44.3 c/d with amplitudes of 0.2 mmag or larger. Within this wide band the frequencies are not distributed at random, but tend to cluster in groups. A similar feature is seen in the power spectrum of the residuals after 79 frequencies are prewhitened. This indicates that many additional modes are excited. The interpretation is supported by a histogram of the photometric amplitudes, which shows an increase of modes with small amplitudes. The old question of the 'missing modes' may be answered now: the large number of detecte...

  2. FUNCTIONAL RELATIONSHIPS FOR Teff AND log g IN F-G SUPERGIANTS FROM uvby - B PHOTOMETRY

    Directory of Open Access Journals (Sweden)

    A. Arellano Ferro

    2010-01-01

    Full Text Available A partir de datos fotoeléctricos en el sistema uvby - y de valores precisos sintéticos y espectroscópicos de Teff y log g en 50 supergigantes de tipos espectrales F-G, hemos calculado relaciones funcionales que permiten la estimación inicial de la temperatura efectiva y la gravedad en este tipo de estrellas. Se demuestra que aunque las calibraciones de Teff fueron calculadas con los datos de estrellas supergigantes jóvenes y masivas, también son válidas para estrellas evolucionadas post-AGB y RV Tau de temperaturas similares. La gravedad superficial también puede calcularse a partir del índice [c1] con una precisión de 0.26 dex. Aunque se puede distinguir una correlación entre MV y [c1], no hemos encontrado una correlación que prediga MV de manera suficientemente precisa.

  3. Photospheric carbon and oxygen abundances of F-G type stars in the Pleiades cluster

    CERN Document Server

    Takeda, Yoichi; Honda, Satoshi

    2016-01-01

    In order to investigate the carbon-to-oxygen ratio of the young open cluster M45 (Pleiades), the C and O abundances of selected 32 F-G type dwarfs (in the effective temperature range of Teff~5800-7600K and projected rotational velocity range of vesini~10-110km/s) belonging to this cluster were determined by applying the synthetic spectrum-fitting technique to C I 5380 and O I 6156-8 lines. The non-LTE corrections for these C I and O I lines were found to be practically negligible (less than a few hundredths dex). The resulting C and O abundances (along with the Fe abundance) turned out nearly uniform without any systematic dependence upon Teff or vesini. We found, however, in spite of almost solar Fe abundance ([Fe/H]~0), carbon turned out to be slightly subsolar ([C/H]~-0.1) while oxygen slightly supersolar ([O/H]~+0.1). This lead to a conclusion that [C/O] ratio was moderately subsolar (~-0.2) in the primordial gas from which these Pleiades stars were formed ~120--130 Myr ago. Interestingly, similarly young...

  4. Final Technical Report for Award DE-FG02-98ER41080

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Alan

    2014-11-14

    The prime motivation of the project at McMaster University was to carry out the critical evaluation and compilation of Nuclear Structure and Decay data, and of nuclear astrophysics data with continued participation in the United States Nuclear Data Program (US-NDP). A large body of evaluated and compiled structure data were supplied for databases such as ENSDF, XUNDL, NSR, etc. residing on webpage of National Nuclear Data Center of the Brookhaven National Laboratory, Upton, New York, USA. Thermonuclear reaction rates of importance to stellar explosions, such as novae, x-ray bursts and supernovae, were evaluated as well. This effort was closely coupled to our ongoing experimental effort, which took advantage of radioactive ion beam and stable beam facilities worldwide to study these key reaction rates. This report contains brief descriptions of the various activities together with references to all the publications in peer-reviewed journals which were the result of work carried out with the award DE-FG02-98-ER41080, during 1998-2013.

  5. The Delta Scuti star FG Vir. V. The 2002 photometric multisite campaign

    CERN Document Server

    Breger, M; Pretorius, M L; Martin-Ruiz, S; Amado, P J; Costa, V; Garrido, R; De Coca, P L; Olivares, I; Rodríguez, E; Rolland, A; Tshenye, T; Handler, G; Poretti, E; Sareyan, J P; Alvarez, M; Kilmartin, P M; Zima, W

    2004-01-01

    A high-accuracy multisite campaign was carried out from 2002 January to May with a photometric coverage of 398 hours at five observatories. The concentration on a few selected sites gives better consistency and accuracy than collecting smaller amounts from a larger number of sites. 23 frequencies were detected with a high statistical significance. 6 of these are new. The 17 frequencies found in common with the 1992-1995 data are the modes with highest amplitudes. This indicates that the pulsation spectrum of FG Vir is relatively stable over the ten-year period. Two frequencies have variable amplitudes and phases from year to year as well as during 2002. These were both found to be double modes with close frequencies. For the mode at 12.15 c/d this leads to an apparent modulation with a time scale of about 129d. The close frequencies at 12.15 c/d are composed of a radial and a nonradial mode, suggesting a similarity with the Blazhko Effect seen in RR Lyrae stars.

  6. Sodium pump distribution is not reversed in the DBA/2FG-pcy, polycystic kidney disease model mouse.

    Science.gov (United States)

    Kawa, G; Nagao, S; Yamamoto, A; Omori, K; Komatz, Y; Takahashi, H; Tashiro, Y

    1994-06-01

    Recently, it has been reported that Na,K-ATPase in the renal epithelia of human autosomal dominant polycystic kidney disease and cpk mouse, a murine model of autosomal recessive polycystic kidney disease, mislocates to apical plasma membrane and that mislocated Na,K-ATPase causes the cyst formation. Whether the DBA/2FG-pcy mice, which are presumably a suitable model for autosomal dominant polycystic kidney disease, also exhibit the reversal polarity of Na,K-ATPase localization was examined. Kidneys of newborn DBA/2FG-pcy mice, and those at early and late stages of cyst development were examined by immunohistochemical techniques. At any stage, abnormal distribution of Na,K-ATPase on the apical membranes of tubular epithelial cells could not be detected. It is suggested that cysts can be formed without reversed polarity of Na,K-ATPase distribution in pcy mice.

  7. Trusted Domain

    DEFF Research Database (Denmark)

    Hjorth, Theis Solberg; Torbensen, Rune

    2012-01-01

    that enables secure end-to-end communication with home automation devices, and it supports device revocations as well as a structure of intersecting sets of nodes for scalability. Devices in the Trusted Domain are registered in a list that is distributed using a robust epidemic protocol optimized...

  8. Domain crossing

    DEFF Research Database (Denmark)

    Schraefel, M. C.; Rouncefield, Mark; Kellogg, Wendy

    2012-01-01

    In CSCW, how much do we need to know about another domain/culture before we observe, intersect and intervene with designs. What optimally would that other culture need to know about us? Is this a “how long is a piece of string” question, or an inquiry where we can consider a variety of contexts a...

  9. Evaluation of cytotoxicity, genotoxicity and embryotoxicity of insecticide propoxur using flounder gill (FG) cells and zebrafish embryos.

    Science.gov (United States)

    Pandey, Manish Raj; Guo, Huarong

    2014-04-01

    Cytotoxicity, genotoxicity and embryotoxicity of carbamate insecticide propoxur were evaluated using flounder gill (FG) cells and zebrafish embryos. The cytotoxicity of propoxur in FG cells was analyzed by MTT, neutral red uptake (NRU), lactate dehydrogenase (LDH) release and Hoechst 33342 and propidium iodide double staining, and acute cytotoxic effects were observed in a concentration-dependent manner. The 24h-IC50 values of 89.96 ± 1.04, 103.4 ± 1.14 and 86.59 ± 1.13 μg/ml propoxur were obtained by MTT, NRU and LDH assays, respectively. The lethal effects were induced in FG cells mainly through necrosis but not apoptosis as evidenced by double fluorescence staining. Comet assay showed weak genotoxic effects and statistically significant DNA damages were recorded in the cells exposed to highest tested concentration of 75 μg/ml propoxur (p<0.05). Propoxur exerted obvious acute toxic effects on the survival, spontaneous movement, hatching and heart rate, and development (yolk and pericardial sac edema) of zebrafish embryos in both time- and concentration-dependent manner only at ⩾ 100 μg/ml. The corresponding 24h-, 48 h- and 96 h-LC50 values of propoxur in zebrafish embryos were 166.4 ± 1.06, 146.3 ± 1.07 and 134.8 ± 1.06 μg/ml, respectively. The above data obtained suggest a low acute toxicity of propoxur to the in vitro cultured FG cells and zebrafish embryos.

  10. Final Report. DOE Computational Nanoscience Project DE-FG02-03ER46096: Integrated Multiscale Modeling of Molecular Computing Devices

    Energy Technology Data Exchange (ETDEWEB)

    Cummings, Peter [Vanderbilt University

    2009-11-15

    The document is the final report of the DOE Computational Nanoscience Project DE-FG02-03ER46096: Integrated Multiscale Modeling of Molecular Computing Devices. It included references to 62 publications that were supported by the grant.

  11. The anxiogenic action of FG 7142 in the social interaction test is reversed by chlordiazepoxide and Ro 15-1788 but not by CGS 8216.

    Science.gov (United States)

    File, S E; Pellow, S

    1984-10-01

    The effects of FG 7142 were examined in the social interaction test, alone and in combination with chlordiazepoxide, Ro 15-1788 and CGS 8216. The anxiogenic action of FG 7142 (5 mg/kg) was reversed by chlordiazepoxide (5 mg/kg) and by Ro 15-1788 (10 mg/kg), but not by CGS 8216 (10 mg/kg). The profile of FG 7142 in this test and the pattern of its interactions with other compounds is similar to that of beta-CCE, but can be distinguished from that of Ro 15-1788 and CGS 8216. It is concluded that FG 7142, Ro 15-1788 and CGS 8216 may act via different sites to produce their anxiogenic effects.

  12. CRISPR/Cas9系统在腺样囊性癌细胞中编辑纤连蛋白基因EDA片段的研究%Knocking-out extra domain A alternative splice fragment of fibronectin using a clustered regularly interspaced short palindromic repeats/associated proteins 9 system

    Institute of Scientific and Technical Information of China (English)

    杨月; 王海丞; 许舒宇; 彭靖; 江久汇; 李翠英

    2015-01-01

    目的 利用成簇的规律间隔的短回文重复序列(clustered regularly interspaced short palindromic repeats,CRISPR)/常间回文重复序列丛集关联蛋白系统(associated proteins,Cas)编辑纤连蛋白(fibronectin)基因抑制其可变剪接片段基因外显子A(extra domain A,EDA),并观察对腺样囊性癌(adenoid cystic carcinoma,ACC)的促肿瘤作用.方法 根据纤连蛋白序列设计两段互补于EDA上游和一段与下游互补的引导RNA (single guide RNA,sgRNA,20 bp),分别连接至PX330质粒的U6启动子下游.质粒转染至ACC细胞系SACC-83,PCR扩增基因组并测序验证其定点敲除EDA结果及效率.质粒转染后的细胞进行稳定株的筛选及鉴定,将筛选后的稳定株作为EDA敲除实验组,SACC-83细胞为对照组,进行CCK-8细胞增殖和Transwell侵袭能力检测,每组实验重复3次.结果 sgRNA连接至PX330质粒U6启动子下游,成功构建了质粒敲除模型;SACC-83的基因组EDA外显子被敲除,敲除效率达70%以上,但纤连蛋白总量未发生明显变化.筛选出3株EDA敲除稳定株(A+C-2、A+C-6、B+C-10),并通过PCR鉴定证实其可靠性.划痕实验中实验组细胞运动速率[A+C-2 (21.67±1.87) μm/h;A+C-6(12.22±2.13) μm/h;B+C-10(20.00±2.56) μm/h]相对对照组[(27.78±3.20) μm/h]降低;增殖实验显示EDA敲除组细胞倍增时间增加[对照组SACC-83 (38.52±4.26)h,实验组A+C-2(62.05±5.80)h,A+C-6(46.32±6.35)h,B+C-10(40.7±3.88)h].结论 在sgRNA的引导下,CRISPR/Cas系统能简洁、高效地敲除细胞基因组中的EDA可变剪接外显子,EDA敲除对肿瘤细胞运动和侵袭有明显抑制作用.%Objective To investigate the effect of the fibronectin extra domain A on the aggressiveness of salivary adenoid cystic carcinoma (SACC) cells,via the clustered regularly interspaced short palindromic repeats (CRISPR)/associated proteins (Cas) system.Methods One sgRNA was designed to target the upstream of the genome sequences of extra domain A

  13. N-Methyl-beta-carboline-3-carboxamide (FG 7142): An anxiogenic agent in cigarette smoke condensate and its mechanism of formation.

    Science.gov (United States)

    Manabe, S; Juan, Y; Wada, O; Ueki, A; Kanai, Y

    1995-01-01

    beta-Carboline-3-carboxylic acid methylamide (FG 7142), an anxiogenic agent has been found in cigarette smoke condensate, but not in the cigarette itself. When a cigarette, except its filter portion, was immersed in 20 ml of potassium phosphate buffer, pH 7.4, then heated at 60 degrees C for 2 days with or without presence of methylamine, FG 7142 was detected only in the mixture containing methylamine. Furthermore, when the mixtures of beta-carboline derivatives and various amounts of methylamine hydrochloride were heated at 60 degrees C for 5 days, FG 7142 was formed only in the mixtures containing methylamine and 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-caroxylic acid (MTCA) or 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (TCCA). FG 7142 was also produced in the mixture of glucose, l-tryptophan and methylamine when heated at 200 degrees C in a dry condition. These observations suggest that FG 7142 is formed through the smoking process and that methylamine in cigarette smoke may play an important role in the formation of FG 7142.

  14. Studying the influence of surface effects on vibration behavior of size-dependent cracked FG Timoshenko nanobeam considering nonlocal elasticity and elastic foundation

    Science.gov (United States)

    Ghadiri, Majid; Soltanpour, Mahdi; Yazdi, Ali; Safi, Mohsen

    2016-05-01

    Free transverse vibration of a size-dependent cracked functionally graded (FG) Timoshenko nanobeam resting on a polymer elastic foundation is investigated in the present study. Also, all of the surface effects: surface density, surface elasticity and residual surface tension are studied. Moreover, satisfying the balance condition between the nanobeam and its surfaces was discussed. According to the power-law distribution, it is supposed that the material properties of the FG nanobeam are varying continuously across the thickness. Considering the small-scale effect, the Eringen's nonlocal theory is used; accounting the effect of polymer elastic foundation, the Winkler model is proposed. For this purpose, the equations of motion of the FG Timoshenko nanobeam and boundary conditions are obtained using Hamilton's principle. To find the analytical solutions for equations of motion of the FG nanobeam, the separation of variables method is employed. Two cases of boundary conditions, i.e., simply supported-simply supported (SS) and clamped-clamped (CC) are investigated in the present work. Numerical results are demonstrating a good agreement between the results of the present study and some available cases in the literature. The emphasis of the present study is on investigating the effect of various parameters such as crack severity, crack position, gradient index, mode number, nonlocal parameter, elastic foundation parameter and nanobeam length. It is clearly revealed that the vibrational behavior of a FG nanobeam is depending significantly on these effects. Also, these numerical results can be serving as benchmarks for future studies of FG nanobeams.

  15. PILER-CR: Fast and accurate identification of CRISPR repeats

    Directory of Open Access Journals (Sweden)

    Edgar Robert C

    2007-01-01

    Full Text Available Abstract Background Sequencing of prokaryotic genomes has recently revealed the presence of CRISPR elements: short, highly conserved repeats separated by unique sequences of similar length. The distinctive sequence signature of CRISPR repeats can be found using general-purpose repeat- or pattern-finding software tools. However, the output of such tools is not always ideal for studying these repeats, and significant effort is sometimes needed to build additional tools and perform manual analysis of the output. Results We present PILER-CR, a program specifically designed for the identification and analysis of CRISPR repeats. The program executes rapidly, completing a 5 Mb genome in around 5 seconds on a current desktop computer. We validate the algorithm by manual curation and by comparison with published surveys of these repeats, finding that PILER-CR has both high sensitivity and high specificity. We also present a catalogue of putative CRISPR repeats identified in a comprehensive analysis of 346 prokaryotic genomes. Conclusion PILER-CR is a useful tool for rapid identification and classification of CRISPR repeats. The software is donated to the public domain. Source code and a Linux binary are freely available at http://www.drive5.com/pilercr.

  16. Identification and Analysis of Novel Amino-Acid Sequence Repeats in Bacillus anthracis str. Ames Proteome Using Computational Tools

    Directory of Open Access Journals (Sweden)

    D. Satyanarayana Rao

    2007-02-01

    Full Text Available We have identified four repeats and ten domains that are novel in proteins encoded by the Bacillus anthracis str. Ames proteome using automated in silico methods. A “repeat” corresponds to a region comprising less than 55-amino-acid residues that occur more than once in the protein sequence and sometimes present in tandem. A “domain” corresponds to a conserved region with greater than 55-amino-acid residues and may be present as single or multiple copies in the protein sequence. These correspond to (1 57-amino-acid-residue PxV domain, (2 122-amino-acid-residue FxF domain, (3 111-amino-acid-residue YEFF domain, (4 109-amino-acid-residue IMxxH domain, (5 103-amino-acid-residue VxxT domain, (6 84-amino-acid-residue ExW domain, (7 104-amino-acid-residue NTGFIG domain, (8 36-amino-acid-residue NxGK repeat, (9 95-amino-acid-residue VYV domain, (10 75-amino-acid-residue KEWE domain, (11 59-amino-acid-residue AFL domain, (12 53-amino-acid-residue RIDVK repeat, (13 (a 41-amino-acid-residue AGQF repeat and (b 42-amino-acid-residue GSAL repeat. A repeat or domain type is characterized by specific conserved sequence motifs. We discuss the presence of these repeats and domains in proteins from other genomes and their probable secondary structure.

  17. DWI Repeaters and Non-Repeaters: A Comparison.

    Science.gov (United States)

    Weeber, Stan

    1981-01-01

    Discussed how driving-while-intoxicated (DWI) repeaters differed signigicantly from nonrepeaters on 4 of 23 variables tested. Repeaters were more likely to have zero or two dependent children, attend church frequently, drink occasionally and have one or more arrests for public intoxication. (Author)

  18. To Repeat or Not to Repeat a Course

    Science.gov (United States)

    Armstrong, Michael J.; Biktimirov, Ernest N.

    2013-01-01

    The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

  19. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  20. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  1. All-photonic quantum repeaters

    Science.gov (United States)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-01-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

  2. Microstructural investigation of the oxide formed on TP 347H FG during long-term steam oxidation

    DEFF Research Database (Denmark)

    Hansson, Anette Nørgaard; Danielsen, Hilmar Kjartansson; Grumsen, Flemming Bjerg

    2010-01-01

    The long-term oxidation behaviour of TP347H FG in ultra supercritical steam conditions was assessed by exposing the steel in test superheater loops in a Danish coal-fired power plant and characterising the oxide layer with reflective light and electron microscopy. Double layered oxide scales formed...... during steam oxidation. TEM investigations reveal that the inner oxide layer consists of particles of metallic Ni/Fe and Fe-Cr spinel in the interior of the former alloy grains and a compact layer of Fe-Cr spinel and Cr2O3 along the former alloy grain boundaries. The morphology suggests that the inner...

  3. Final Report for DOE grant project FG02-07ER41458 [Dense Quark Matter in Magnetic Fields

    Energy Technology Data Exchange (ETDEWEB)

    Incera, Vivian

    2012-01-24

    Final Report for DOE grant DE-FG02-07ER41458. This grant was originally a three-year project. However, this final report summarizes the results of the first two years, as at the end of the second year of the grant the PIs moved to a new university and the grant was closed. The work done under the first two years of the DOE grant led to several papers and presentations. It also served to train one undergraduate and three graduate students.

  4. Synthesis and Mesophase Properties of Intraanular Functionized Shape-persistent Macrocycles Containing Dibenzo [fg,op] naphthacenes

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    On the basis of the C-C coupling reactions of dibenzo [ fg, op ] naphthacene bistriflate, which was obtained by the condensation of phenylacetates with 4-aryl-2,6-bis(2-bromo-4-methoxy-phenyl) pyrylium salts followed by palladium-catalyzed dehydrohalogenation, three shape-persistent macrocycles with dibenzonaphthacene corner pieces, a nanometer interior void, and intraanular oligoalkyl side groups were synthesized by the oxidative cyclization of the corresponding bisacetylenes under high-dilution conditions. Their thermotropic liquid crystalline properties were investigated by using polarizing microscopy and differential scanning calorimetry. All the three compounds showed nematic mesophases and belonged to discotic liquid crystals with inverted topology.

  5. RTVue傅里叶光学相干断层扫描仪测量角膜参数的重复性和准确性评价%Repeatability and accuracy of corneal parameters measured by RTVue Fourier-domain optical coherence topography

    Institute of Scientific and Technical Information of China (English)

    华焱军; 黄锦海; 潘超; 王勤美

    2013-01-01

    膜地形图仪略大;RTVue FD-OCT获得的Rposterior/Ranterior比Gullstrand模型眼小,可能为建立更准确的标准化模型眼提供依据.%Background Corneal parameters (such as curvature,thickness,etc) are essential to the diagnosis of corneal related diseases,contact lenses fitting and corneal refractive surgery.Objective The aim of this study was to assess the repeatability and accuracy of corneal parameters obtained by RTVue Fourier-domain optical coherence topography (FD-OCT).Methods In this prospective study,77 eyes of 43 subjects with the refraction from-1.25 D to-10.00 D and astigmatism <2 D were enrolled in keratorefractive surgery center,Eye Hospital of Wenzhou Medical College.The anterior and posterior corneal curvature in 3 mm central zone (Ranterior and Rposterior),the ratio of posterior and anterior curvature (Rposterior/Ranterior),corneal central thickness (CCT),total corneal power(Knet),the simulated corneal power (Sim K),the anterior and posterior corneal power (Kanterior,Kposterior)were measured by FD-OCT.Corneal power (Km) was obtained by Topolyzer topography based on Placido ring.Three consecutive scans were acquired in every tested eye.Repeatability of FD-OCT measurement was assessed using the coefficient of variation CV),Cronbach Alpha and intra-class correlation coefficient (ICC).Repeated measure ANOVA was used to analyze the differences among SimK,Knet and Km.Pearson correlation analysis was used to analysis the correlation between SimK and K Knet and Km,SimK and Km.The agreement between Sim K and K Knet and Km,SimK and Km was assessed by Bland-Altman plots analysis.All the subjects understood the purpose of this investigation and written informed consent was obtained prior to the medical examination.Results The Ranterior,Rposterior,Rposterior/Ranterior,Kanterior,Kposterior,Sim K,Knet and CCT were (7.691 ±0.302) mm,(6.532±0.276) mm,0.849±0.014,(48.97±1.92)D,(-6.13±0.26)D,(43.95±1.72) D,(42.95±1.68) D and (545.20± 35.04) μm,respectively.The CV of all

  6. Filamin repeat segments required for photosensory signalling in Dictyostelium discoideum

    Directory of Open Access Journals (Sweden)

    Ahmed Afsar U

    2007-11-01

    Full Text Available Abstract Background Filamin is an actin binding protein which is ubiquitous in eukaryotes and its basic structure is well conserved – an N-terminal actin binding domain followed by a series of repeated segments which vary in number in different organisms. D. discoideum is a well established model organism for the study of signalling pathways and the actin cytoskeleton and as such makes an excellent organism in which to study filamin. Ddfilamin plays a putative role as a scaffolding protein in a photosensory signalling pathway and this role is thought to be mediated by the unusual repeat segments in the rod domain. Results To study the role of filamin in phototaxis, a filamin null mutant, HG1264, was transformed with constructs each of which expressed wild type filamin or a mutant filamin with a deletion of one of the repeat segments. Transformants expressing the full length filamin to wild type levels completely rescued the phototaxis defect in HG1264, however if filamin was expressed at lower than wild type levels the phototaxis defect was not restored. The transformants lacking any one of the repeat segments 2–6 retained defective phototaxis and thermotaxis phenotypes, whereas transformants expressing filaminΔ1 exhibited a range of partial complementation of the phototaxis phenotype which was related to expression levels. Immunofluorescence microscopy showed that filamin lacking any of the repeat segments still localised to the same actin rich areas as wild type filamin. Ddfilamin interacts with RasD and IP experiments demonstrated that this interaction did not rely upon any single repeat segment or the actin binding domain. Conclusion This paper demonstrates that wild type levels of filamin expression are essential for the formation of functional photosensory signalling complexes and that each of the repeat segments 2–6 are essential for filamins role in phototaxis. By contrast, repeat segment 1 is not essential provided the mutated

  7. FG 7142 specifically reduces meal size and the rate and regularity of sustained feeding in female rats: evidence that benzodiazepine inverse agonists reduce food palatability.

    Science.gov (United States)

    Cottone, Pietro; Sabino, Valentina; Steardo, Luca; Zorrilla, Eric P

    2007-05-01

    Benzodiazepine receptor inverse agonists reduce food intake in males, but their actions in females, in whom stress-related eating disorders are more common, as well as their behavioral mode of action remain unclear. The consummatory effects of benzodiazepine receptor ligands have alternately been hypothesized to reflect changes in the hedonic evaluation of food or secondary effects of anxiety-related or cognitive properties. To test the anorectic mode of action of benzodiazepine inverse agonists, the effects of FG 7142 on feeding microstructure were studied in nondeprived female Wistar rats (n=32). Microstructure analysis used a novel meal definition that recognizes prandial drinking. On pharmacologically synchronized diestrus I, rats were pretreated (-30 min dark onset) with the benzodiazepine partial inverse agonist FG 7142 (i.p. 0, 3.75, 7.5, 15 mg/kg) in a between-subjects design. FG 7142 delayed the onset of (16-541%), decreased the amount eaten (36-52%) and drunk (63-87%), and reduced the time spent drinking (59-87%) within the first nocturnal meal. Dose-dependent incremental anorexia continued 6 h into the dark cycle, whereas FG 7142 did not suppress the quantity, duration or rate of drinking past the first meal. Treated rats ate smaller meals (17-42%) of normal duration. This reflected that FG 7142 slowed feeding within meals (9-38%) by decreasing the regularity and maintenance of feeding from pellet-to-pellet. FG 7142 did not influence postprandial satiety; meal frequency and inter-meal intervals were unaffected. FG 7142 anorexia was blocked by the benzodiazepine receptor antagonist flumazenil in a 2:1 molar ratio (n=17 rats). The very early, nonspecific (+10 min), but not subsequent (2.5, 4.5 h) feeding-specific phase, of FG 7142 anorexia was mirrored by anxiogenic-like behavior in FG 7142-treated (7.5 mg/kg) female rats (n=48) in the elevated plus-maze. Thus, benzodiazepine receptor inverse agonists preferentially lessen the maintenance of feeding in

  8. .Gov Domains API

    Data.gov (United States)

    General Services Administration — This dataset offers the list of all .gov domains, including state, local, and tribal .gov domains. It does not include .mil domains, or other federal domains outside...

  9. Effects of Repeated Practice and Contextual-Writing Experiences on College Students' Writing Skills.

    Science.gov (United States)

    Johnstone, Karla M.; Ashbaugh, Hollis; Warfield, Terry D.

    2002-01-01

    Examined the effects of both general and task-specific writing experiences on college students' writing-skill development. As predicted, repeated practice was associated with superior writing skills and after controlling for repeated practice, writing within a specific test domain was associated with superior writing skills. Implications for…

  10. An Xq22.3 duplication detected by comparative genomic hybridization microarray (Array-CGH) defines a new locus (FGS5) for FG syndrome.

    Science.gov (United States)

    Jehee, Fernanda Sarquis; Rosenberg, Carla; Krepischi-Santos, Ana Cristina; Kok, Fernando; Knijnenburg, Jeroen; Froyen, Guy; Vianna-Morgante, Angela M; Opitz, John M; Passos-Bueno, Maria Rita

    2005-12-15

    FG syndrome is an X-linked multiple congenital anomalies (MCA) syndrome. It has been mapped to four distinct loci FGS1-4, through linkage analysis (Xq13, Xp22.3, and Xp11.4-p11.3) and based on the breakpoints of an X chromosome inversion (Xq11:Xq28), but so far no gene has been identified. We describe a boy with FG syndrome who has an inherited duplication at band Xq22.3 detected by comparative genomic hybridization microarray (Array-CGH). These duplication maps outside all four loci described so far for FG syndrome, representing therefore a new locus, which we propose to be called FGS5. MID2, a gene closely related to MID1, which is known to be mutated in Opitz G/BBB syndrome, maps within the duplicated segment of our patient. Since FG and Opitz G/BBB syndromes share many manifestations we considered MID2 a candidate gene for FG syndrome. We also discuss the involvement of other potential genes within the duplicated segment and its relationship with clinical symptoms of our patient, as well as the laboratory abnormalities found in his mother, a carrier of the duplication.

  11. In-plane vibration of FG micro/nano-mass sensor based on nonlocal theory under various thermal loading via differential transformation method

    Science.gov (United States)

    Rahmani, O.; Mohammadi Niaei, A.; Hosseini, S. A. H.; Shojaei, M.

    2017-01-01

    In the present study, free vibration model of a cantilever functionally graded (FG) nanobeam with an attached mass at tip and under various thermal loading and two types of material distribution is introduced. The vibration performance is considered using nonlocal Euler-Bernoulli beam theory. Two types of thermal loading, namely, uniform and nonlinear temperature rises through the thickness direction are considered. Thermo-mechanical properties of FG nano mass sensor are supposed to vary smoothly and continuously throughout the thickness based on power-law and Mori Tanaka distributions of material properties. Eringen non-local elasticity theory is exploited to describe the size dependency of FG nanobeam. The governing equations of the system with both axial and transverse displacements are derived based on Hamilton's principle and solved utilizing the differential transformation method (DTM) to find the non-dimensional natural frequencies. The results have good agreements with those discussing in the literature. After validation of the present model, the effect of various parameters such as mass and position of the attached nano particle, FG power-law exponent, thermal load type, material distribution type and nonlocal parameter on the frequency of nano sensor are studied. It is shown that the present model produces results of high accuracy, and it can be used as a benchmark in future studies of the free vibration of FG Nano-Mass Sensors.

  12. HIV-1CRF07_BC毒株gp41NHR结构域N51的表达及结构分析%Expression, structure and antigenicity analysis of N51 derived from the N-terminal heptad repeat domain in gp41 of HIV-1 CRF07_BC strain

    Institute of Scientific and Technical Information of China (English)

    邵继平; 姜世勃; 刘叔文

    2012-01-01

    Objective To express N51 derived from the N-terminal heptad repeat (NHR) domain in gp41 of the HIV-1 CRF07_BC strain and analyze its molecular structure and antigenicity. Methods Overlapping PCR was used to amplify the DNA fragment encoding N51Fd gene, which was then subcloned into the vector pFUSE-hIgGl-Fc2. The construct was confirmed by DNA sequencing. The structure and antigenicity of the recombinant protein N51FdFc-BC were analyzed using bioinformatic software, circular dichroism, and Western blotting. Results A recombinant expression vector pFUSE/N51Fd-BC was successfully constructed. N51FdFc-BC recombinant protein with a relative molecular mass of about 35 000 was effectively expressed in mammalian 293T cells and could be recognized by rabbit antibodies against HIV-1 gp41 N/C peptides as shown by Western blotting. Bioinformatic analysis showed that the recombinant protein N51FdFc-BC, with a relative molecular mass of 34 315.1 and a PI of 7.59, formed a secondary structure of random coil to allow its interactions as an antigen with antibodies. Circular dichroism measurement confirmed the random coil structure of N51FdFc-BC protein. Conclusion The recombinant protein N51FdFc-BC has a random coil structure and can be used as an immunogen for development of HIV-1 subunit vaccine.%目的 对来源于HIV-1中国流行株CRF07 BC的包膜糖蛋白gp41 NHR结构域的N51进行表达和结构及抗原性分析.方法 运用重叠延伸PCR方法扩增出N51Fd基因,将其插入真核表达载体pFUSE-hIgG1-Fc2,并进行核苷酸序列测定.利用生物信息学软件、圆二色谱法、免疫印迹法对表达的N51FdFc-BC重组蛋白进行结构和抗原性分析.结果 成功构建pFUSE/N51Fd-BC表达载体,并在真核表达体系实现了目的蛋白的高效表达.免疫印迹结果显示该重组蛋白大小约为35 000,可与抗HIV-1 gp41 N/C多肽的抗体反应.生物信息学分析显示N51 FdFc-BC重组蛋白相对分子质量为34 315.1,等电点PI为7

  13. FG020326 Sensitized Multidrug Resistant Cancer Cells to Docetaxel-Mediated Apoptosis via Enhancement of Caspases Activation

    Directory of Open Access Journals (Sweden)

    Li-Wu Fu

    2012-05-01

    Full Text Available Apoptotic resistance is the main obstacle for treating cancer patients with chemotherapeutic drugs. Multidrug resistance (MDR is often characterized by the expression of P-glycoprotein (P-gp, a 170-KD ATP-dependent drug efflux protein. Functional P-gp can confer resistance to activate caspase-8 and -3 dependent apoptosis induced by a range of different stimuli, including tumor necrosis and chemotherapeutic drugs such as docetaxel and vincristine. We demonstrated here that comparison of sensitive KB cells, P-gp positive (P-gp+ve KBv200 cells were extremely resistant to apoptosis induced by docetaxel. FG020326, a pharmacological inhibitor of P-gp function, could enhance concentration-dependently the effect of docetaxel on cell apoptosis and sensitize caspase-8, -9 and -3 activation in P-gp overexpressing KBv200 cells, but not in KB cells. Therefore, the enhancement of caspase-8, -9 and -3 activation induced by docetaxel may be one of the key mechanisms of the reversal of P-gp mediated docetaxel resistance by FG020326.

  14. Additional spectra of asteroid 1996 FG3, backup target of the ESA MarcoPolo-R mission

    CERN Document Server

    de Leon, J; Ali-Lagoa, V; Licandro, J; Pinilla-Alonso, N; Campins, H

    2013-01-01

    Near-Earth binary asteroid (175706) 1996 FG3 is the current backup target of the ESA MarcoPolo-R mission, selected for the study phase of ESA M3 missions. It is a primitive (C-type) asteroid that shows significant variation in its visible and near-infrared spectra. Here we present new spectra of 1996 FG3 and we compare our new data with other published spectra, analysing the variation in the spectral slope. The asteroid will not be observable again over the next three years at least. We obtained the spectra using DOLORES and NICS instruments at the Telescopio Nazionale Galileo (TNG), a 3.6m telescope located at El Roque de los Muchachos Observatory in La Palma, Spain. To compare with other published spectra of the asteroid, we computed the spectral slope S', and studied any plausible correlation of this quantity with the phase angle (alpha). In the case of visible spectra, we find a variation in spectral slope of Delta S' = 0.15 +- 0.10 %/10^3 A/degree for 3 < alpha < 18 degrees, in good agreement with ...

  15. FgFlbD regulates hyphal differentiation required for sexual and asexual reproduction in the ascomycete fungus Fusarium graminearum.

    Science.gov (United States)

    Son, Hokyoung; Kim, Myung-Gu; Chae, Suhn-Kee; Lee, Yin-Won

    2014-11-01

    Fusarium graminearum is a filamentous fungal plant pathogen that infects major cereal crops. The fungus produces both sexual and asexual spores in order to endure unfavorable environmental conditions and increase their numbers and distribution across plants. In a model filamentous fungus, Aspergillus nidulans, early induction of conidiogenesis is orchestrated by the fluffy genes. The objectives of this study were to characterize fluffy gene homologs involved in conidiogenesis and their mechanism of action in F. graminearum. We characterized five fluffy gene homologs in F. graminearum and found that FlbD is the only conserved regulator for conidiogenesis in A. nidulans and F. graminearum. Deletion of fgflbD prevented hyphal differentiation and the formation of perithecia. Successful interspecies complementation using A. nidulans flbD demonstrated that the molecular mechanisms responsible for FlbD functions are conserved in F. graminearum. Moreover, abaA-wetA pathway is positively regulated by FgFlbD during conidiogenesis in F. graminearum. Deleting fgflbD abolished morphological effects of abaA overexpression, which suggests that additional factors for FgFlbD or an AbaA-independent pathway for conidiogenesis are required for F. graminearum conidiation. Importantly, this study led to the construction of a genetic pathway of F. graminearum conidiogenesis and provides new insights into the genetics of conidiogenesis in fungi.

  16. The binary near-Earth asteroid (175706) 1996 FG3 - An observational constraint on its orbital stability

    CERN Document Server

    Scheirich, P; Jacobson, S A; Ďurech, J; Kušnirák, P; Hornoch, K; Mottola, S; Mommert, M; Hellmich, S; Pray, D; Polishook, D; Krugly, Yu N; Inasaridze, R Ya; Kvaratskhelia, O I; Ayvazian, V; Slyusarev, I; Pittichová, J; Jehin, E; Manfroid, J; Gillon, M; Galád, A; Pollock, J; Licandro, J; Alí-Lagoa, V; Brinsfield, J; Molotov, I E

    2014-01-01

    Using our photometric observations taken between April 1996 and January 2013 and other published data, we derive properties of the binary near-Earth asteroid (175706) 1996 FG3 including new measurements constraining evolution of the mutual orbit with potential consequences for the entire binary asteroid population. We also refined previously determined values of parameters of both components, making 1996 FG3 one of the most well understood binary asteroid systems. We determined the orbital vector with a substantially greater accuracy than before and we also placed constraints on a stability of the orbit. Specifically, the ecliptic longitude and latitude of the orbital pole are 266{\\deg} and -83{\\deg}, respectively, with the mean radius of the uncertainty area of 4{\\deg}, and the orbital period is 16.1508 +\\- 0.0002 h (all uncertainties correspond to 3sigma). We looked for a quadratic drift of the mean anomaly of the satellite and obtained a value of 0.04 +\\- 0.20 deg/yr^2, i.e., consistent with zero. The drif...

  17. Analysis of repeated measures data

    CERN Document Server

    Islam, M Ataharul

    2017-01-01

    This book presents a broad range of statistical techniques to address emerging needs in the field of repeated measures. It also provides a comprehensive overview of extensions of generalized linear models for the bivariate exponential family of distributions, which represent a new development in analysing repeated measures data. The demand for statistical models for correlated outcomes has grown rapidly recently, mainly due to presence of two types of underlying associations: associations between outcomes, and associations between explanatory variables and outcomes. The book systematically addresses key problems arising in the modelling of repeated measures data, bearing in mind those factors that play a major role in estimating the underlying relationships between covariates and outcome variables for correlated outcome data. In addition, it presents new approaches to addressing current challenges in the field of repeated measures and models based on conditional and joint probabilities. Markov models of first...

  18. Computational study of the human dystrophin repeats: interaction properties and molecular dynamics.

    Science.gov (United States)

    Legrand, Baptiste; Giudice, Emmanuel; Nicolas, Aurélie; Delalande, Olivier; Le Rumeur, Elisabeth

    2011-01-01

    Dystrophin is a large protein involved in the rare genetic disease Duchenne muscular dystrophy (DMD). It functions as a mechanical linker between the cytoskeleton and the sarcolemma, and is able to resist shear stresses during muscle activity. In all, 75% of the dystrophin molecule consists of a large central rod domain made up of 24 repeat units that share high structural homology with spectrin-like repeats. However, in the absence of any high-resolution structure of these repeats, the molecular basis of dystrophin central domain's functions has not yet been deciphered. In this context, we have performed a computational study of the whole dystrophin central rod domain based on the rational homology modeling of successive and overlapping tandem repeats and the analysis of their surface properties. Each tandem repeat has very specific surface properties that make it unique. However, the repeats share enough electrostatic-surface similarities to be grouped into four separate clusters. Molecular dynamics simulations of four representative tandem repeats reveal specific flexibility or bending properties depending on the repeat sequence. We thus suggest that the dystrophin central rod domain is constituted of seven biologically relevant sub-domains. Our results provide evidence for the role of the dystrophin central rod domain as a scaffold platform with a wide range of surface features and biophysical properties allowing it to interact with its various known partners such as proteins and membrane lipids. This new integrative view is strongly supported by the previous experimental works that investigated the isolated domains and the observed heterogeneity of the severity of dystrophin related pathologies, especially Becker muscular dystrophy.

  19. Computational study of the human dystrophin repeats: interaction properties and molecular dynamics.

    Directory of Open Access Journals (Sweden)

    Baptiste Legrand

    Full Text Available Dystrophin is a large protein involved in the rare genetic disease Duchenne muscular dystrophy (DMD. It functions as a mechanical linker between the cytoskeleton and the sarcolemma, and is able to resist shear stresses during muscle activity. In all, 75% of the dystrophin molecule consists of a large central rod domain made up of 24 repeat units that share high structural homology with spectrin-like repeats. However, in the absence of any high-resolution structure of these repeats, the molecular basis of dystrophin central domain's functions has not yet been deciphered. In this context, we have performed a computational study of the whole dystrophin central rod domain based on the rational homology modeling of successive and overlapping tandem repeats and the analysis of their surface properties. Each tandem repeat has very specific surface properties that make it unique. However, the repeats share enough electrostatic-surface similarities to be grouped into four separate clusters. Molecular dynamics simulations of four representative tandem repeats reveal specific flexibility or bending properties depending on the repeat sequence. We thus suggest that the dystrophin central rod domain is constituted of seven biologically relevant sub-domains. Our results provide evidence for the role of the dystrophin central rod domain as a scaffold platform with a wide range of surface features and biophysical properties allowing it to interact with its various known partners such as proteins and membrane lipids. This new integrative view is strongly supported by the previous experimental works that investigated the isolated domains and the observed heterogeneity of the severity of dystrophin related pathologies, especially Becker muscular dystrophy.

  20. Comparison of the in vitro and in vivo toxic effects of three sizes of zinc oxide (ZnO) particles using flounder gill (FG) cells and zebrafish embryos

    Science.gov (United States)

    Han, Li; Zhai, Yanan; Liu, Yang; Hao, Linhua; Guo, Huarong

    2017-02-01

    Nano-sized zinc oxide (nZnO) particles are one kind of the most commonly used metal oxide nanoparticles (NPs). This study compared the cytotoxic and embryotoxic effects of three increasing sized ZnO particles (ϕ 30 nm, 80-150 nm and 2 μm) in the flounder gill (FG) cells and zebrafish embryos, and analyzed the contribution of size, agglomeration and released Zn2+ to the toxic effects. All the tested ZnO particles were found to be highly toxic to both FG cells and zebrafish embryos. They induced growth inhibition, LDH release, morphological changes and apoptosis in FG cells in a concentration-, size- and time-dependent manner. Moreover, the release of LDH from the exposed FG cells into the medium occurred before the observable morphological changes happened. The ultrasonication treatment and addition of serum favored the dispersion of ZnO particles and alleviated the agglomeration, thus significantly increased the corresponding cytotoxicity. The released Zn2+ ions from ZnO particles into the extracellular medium only partially contributed to the cytotoxicity. All the three sizes of ZnO particles tested induced developmental malformations, decrease of hatching rates and lethality in zebrafish embryos, but size- and concentration- dependent toxic effects were not so obvious as in FG cells possibly due to the easy aggregation of ZnO particles in freshwater. In conclusion, both FG cells and zebrafish embryos are sensitive bioassay systems for safety assessment of ZnO particles and the environmental release of ZnO particles should be closely monitored as far as the safety of aquatic organisms is concerned.

  1. DE-FG02-08ER64658 (OASIS) - Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Sharman, Jonathan

    2013-09-05

    Project OASIS (Operation of Advanced Structures, Interfaces and Sub-components for MEAs) was a 12 month project that ran from 1st September 2008 to 31st August 2009, and was managed by the Department of Energy Office of Science, Chicago Office, as Award No DE-FG02-08ER64658, with Johnson Matthey Fuel Cells Inc. as the sole contractor. The project was completed on schedule, with technical successes (details below) and payment of the full grant award made by DOE. The aim of the project was the development of membrane electrode assemblies (MEAs) for H2/air polymer electrolyte membrane (PEM) fuel cells that would give higher performance under hot/dry and dry operating conditions, ideally with no loss of performance under wet conditions. Reducing or eliminating the need for humidifying the incoming gases will allow significant system cost and size reduction for many fuel cell applications including automotive, stationary and back-up power, and portable systems. Portable systems are also of particular interest in military markets. In previous work Johnson Matthey Fuel Cells had developed very stable, corrosion-resistant catalysts suitable for resisting degradation by carbon corrosion in particular. These materials were applied within the OASIS project as they are considered necessary for systems such as automotive where multiple start-stop events are experienced. These catalysts were contrasted with more conventional materials in the design of catalyst layers and novel microporous layers (MPLs) and gas diffusion layer (GDL) combinations were also explored. Early on in the work it was shown how much more aggressive high temperature operation is than dry operation. At the same humidity, tests at 110?C caused much more dehydration than tests at 80?C and the high temperature condition was much more revealing of improvements made to MEA design. Alloy catalysts were introduced and compared with Pt catalysts with a range of particle sizes. It was apparent that the larger

  2. Study on the correlation of plasma fibrinogen levels and Fg Bβ-455A gene polymorphisms to the acute cerebral infarction%急性脑梗死与血浆Fg水平以及FgBβ-455G/A多态性的相关性研究

    Institute of Scientific and Technical Information of China (English)

    张海霞; 杨美荣; 张江; 陈乃耀; 王大力

    2011-01-01

    Objective To investigate the correlation of plasma fibrinogen level and Fg Bβ-455 A gene polymorphisms with the acute cerebral infarction. Methods A total of 90 patients with acute cerebral infarction and 102 healthy subjects as case-control group were selected. The plasma fibrinogen levels in the two groups were compared, and the relationship analysis was performed among the plasma fibrinogen levels, the Fg Bβ-455A gene polymorphisms and the acute cerebral infarction. Results The plasma fibrinogen level in the acute cerebral infarction group was higher than that in control group (P < 0.05 ). The plasma fibrinogen level in gene-455A carrier, gene-455AA especially, was significantly higher than that in gene-455G carrier. Through Logisitic analysis, the increasing of fibrinogen concentrations and Fg Bβ-455G/A were independent risk factors in the acute cerebral infarction. Conclusion The alleles of Fg Bβ-455A are associated with fibrinogen concentrations. The increasing of fibrinogen concentrations and Fg Bβ-455G/A are independent risk factors of cerebral infarction.%目的 探讨急性脑梗死与血浆纤维蛋白原(Fg)水平及Fg Bβ-455G/A多态性的相关性.方法 选择急性脑梗死患者90例及同期门诊体检的健康者102例,比较两组间血浆Fg水平,对血浆Fg、Fg Bβ-455G/A基因多态性与急性脑梗死做相关性分析.结果 病例组血浆Fg水平高于对照组;突变基因-455A(AA、GA基因型)携带者的血浆Fg水平均高于非-455A携带者(GG型);以脑梗死为因变量经过多因素非条件的Logistic回归分析显示,血浆Fg水平、-455GA+AA进入回归方程.结论 Fg Bβ-455G/A多态性与血浆Fg水平具有相关性,血浆Fg浓度、FgBβ-455G/A是急性脑梗死发生的独立危险因素.

  3. Limitations on quantum key repeaters.

    Science.gov (United States)

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-23

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  4. Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

    Energy Technology Data Exchange (ETDEWEB)

    Provenzano, Virgil [National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States); Della Torre, Edward; Bennett, Lawrence H. [Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052 (United States); ElBidweihy, Hatem, E-mail: Hatem@gwmail.gwu.edu [Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052 (United States)

    2014-02-15

    The Gd{sub 5}Ge{sub 2}Si{sub 2} alloy and the off-stoichiometric Ni{sub 50}Mn{sub 35}In{sub 15} Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd{sub 5}Ge{sub 2}Si{sub 2} and Ni{sub 50}Mn{sub 35}In{sub 15} alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

  5. Final Technical Report, Grant DE-FG02-87ER13714, "Fundamental Studies of Metastable Liquids"

    Energy Technology Data Exchange (ETDEWEB)

    Pablo G. Debenedetti

    2009-03-09

    Grant DE-FG02-87ER13714 supported fundamental work on the physical properties of metastable liquids from 6/1/87 to 4/30/08. Renewal proposals were submitted every three years (1990, 1993, 1996, 1999, 2002, 2005), and included, in every case, a detailed Final Technical Report on the previous three years. Accordingly, the bulk of this report covers the final 2-year period 5/1/06 to 4/30/08 of this grant, which is not covered in any of the previous Final Technical Reports. This is preceded by a brief overview of the main research objectives and principal accomplishments during these very fruitful and productive 21 years of DOE-funded research.

  6. Supernova, baryon acoustic oscillations, and CMB surface distance constraints on f(G) higher order gravity models

    CERN Document Server

    Moldenhauer, Jacob; Thompson, John; Easson, Damien A

    2010-01-01

    We consider recently proposed higher order gravity models where the action is built from the Einstein-Hilbert action plus a function f(G) of the Gauss-Bonnet invariant. The models were previously shown to pass physical acceptability conditions as well as solar system tests. In this paper, we compare the models to combined data sets of supernovae, baryon acoustic oscillations, and constraints from the CMB surface of last scattering. We find that the models provide fits to the data that are close to those of the LCDM concordance model. The results provide a pool of higher order gravity models that pass these tests and need to be compared to constraints from large scale structure and full CMB analysis.

  7. Molecular phylogeny of the kelch-repeat superfamily reveals an expansion of BTB/kelch proteins in animals

    Directory of Open Access Journals (Sweden)

    Adams Josephine C

    2003-09-01

    Full Text Available Abstract Background The kelch motif is an ancient and evolutionarily-widespread sequence motif of 44–56 amino acids in length. It occurs as five to seven repeats that form a β-propeller tertiary structure. Over 28 kelch-repeat proteins have been sequenced and functionally characterised from diverse organisms spanning from viruses, plants and fungi to mammals and it is evident from expressed sequence tag, domain and genome databases that many additional hypothetical proteins contain kelch-repeats. In general, kelch-repeat β-propellers are involved in protein-protein interactions, however the modest sequence identity between kelch motifs, the diversity of domain architectures, and the partial information on this protein family in any single species, all present difficulties to developing a coherent view of the kelch-repeat domain and the kelch-repeat protein superfamily. To understand the complexity of this superfamily of proteins, we have analysed by bioinformatics the complement of kelch-repeat proteins encoded in the human genome and have made comparisons to the kelch-repeat proteins encoded in other sequenced genomes. Results We identified 71 kelch-repeat proteins encoded in the human genome, whereas 5 or 8 members were identified in yeasts and around 18 in C. elegans, D. melanogaster and A. gambiae. Multiple domain architectures were identified in each organism, including previously unrecognised forms. The vast majority of kelch-repeat domains are predicted to form six-bladed β-propellers. The most prevalent domain architecture in the metazoan animal genomes studied was the BTB/kelch domain organisation and we uncovered 3 subgroups of human BTB/kelch proteins. Sequence analysis of the kelch-repeat domains of the most robustly-related subgroups identified differences in β-propeller organisation that could provide direction for experimental study of protein-binding characteristics. Conclusion The kelch-repeat superfamily constitutes a

  8. Investigation of stress intensity factor for internal cracks in FG cylinders under static and dynamic loading

    Directory of Open Access Journals (Sweden)

    Mahmoud Shariati

    2017-01-01

    Full Text Available his paper investigates the variations of mode I stress intensity factor (KI for inner penny-shaped and circumferential cracks in functionally graded solid and hollow thick walled cylinders, respectively with the changes of crack geometry, material gradation and loading conditions. The functionally graded material of cylinders consists of epoxy and glass. It is assumed that the mechanical properties vary with a power law in the radial direction of cylinders. Micromechanical models for conventional composites are used to estimate the material properties of functionally graded cylinders. The equations of motion obtained from the extended finite element discretization are solved by the Newmark method in the time domain. The interaction integral method is employed to calculate the mode I stress intensity factor (KI. The MATLAB programming environment was implemented to solve the problem.

  9. Final Report for Award DE-FG02-09ER16008

    Energy Technology Data Exchange (ETDEWEB)

    Somerville, Chris

    2014-04-26

    The research objectives of this project was to characterize the factors that regulate the pattern, amount and quality of cellulose deposition in higher plants. We pursued this goal in four ways: (1) by searching for proteins that interact with the cellulose synthase complex using novel bioinformatics tools to identify genes which exhibit gene expression patterns that are highly correlated with cellulose synthase components, (2) by using cellulose synthase domains as bait in 2-hybrid screens, and then characterizing any proteins that are identified by both gene expression network analysis and 2-hybrid screens (3) by testing the function of all known post-translational modifications, (4) by identifying and characterizing kinases that carry out most of the known post-translational modification of cellulose synthase components.

  10. Material problems related to large scale firing of biomass. Steam oxidation of TP 347H FG and X20

    Energy Technology Data Exchange (ETDEWEB)

    Noergaard Hansson, A.

    2009-07-01

    TP 347 H and X20 is often used as construction material in biomass-fired boilers. The corrosion rate of the alloys is affected by the metal temperature. In this project, the oxidation behaviour of TP 347H FG and X20 is studied by field-testing, laboratory exposures, and thermodynamic/kinetic modelling. The long term oxidation behaviour of TP 347H FG at ultra supercritical steam conditions was assessed by exposing the steel in 4 test superheater loops in a coal-fired power plant. The steel was exposed for 7720, 22985, 29588, and 57554 h at metal temperatures between 499 and 650 deg. C. In the laboratory furnace, the oxidation behaviour of TP 347H FG, TP 347H CG, and X20 was studied in water vapour containing environments (8 or 46%) in the temperature range 500-700 deg. C. Air, Ar and Ar+7% H{sub 2} were used as carrier gas. The microstructure of the oxide layer and the subjacent alloy was investigated with X-ray diffraction (XRD), reflective light microscopy (RLM), scanning electron microscopy (SEM) equipped with energy dispersive spectroscopy (EDS), and transmission electron microscopy (TEM) equipped with electron diffraction (ED) and EDS. Double-layered oxides developed during steam oxidation of TP 347H FG both during field-testing and during laboratory exposures. TEM investigation suggested that the interior of the alloy grain was oxidised internally, forming particles of metallic Ni/Fe and Fe-Cr spinel. A FeCr{sub 2}O{sub 4} layer developed along the former alloy grain boundaries. Cr{sub 2}O{sub 3} developed in between this layer and the alloy during field-testing, and its formation was promoted by higher temperature. The morphology of the inner layer for the samples oxidised below and above approx. 585 deg. C looked very different in SEM (field-testing). It is suggested that more Cr is incorporated into the oxide layer at higher temperature, gradually transforming the morphology of the inner oxide layer. The alloy beneath the oxide layer was depleted in Cr

  11. Material problems related to large scale firing of biomass. Steam oxidation of TP 347H FG and X20

    Energy Technology Data Exchange (ETDEWEB)

    Noergaard Hansson, A.

    2009-07-01

    TP 347 H and X20 is often used as construction material in biomass-fired boilers. The corrosion rate of the alloys is affected by the metal temperature. In this project, the oxidation behaviour of TP 347H FG and X20 is studied by field-testing, laboratory exposures, and thermodynamic/kinetic modelling. The long term oxidation behaviour of TP 347H FG at ultra supercritical steam conditions was assessed by exposing the steel in 4 test superheater loops in a coal-fired power plant. The steel was exposed for 7720, 22985, 29588, and 57554 h at metal temperatures between 499 and 650 deg. C. In the laboratory furnace, the oxidation behaviour of TP 347H FG, TP 347H CG, and X20 was studied in water vapour containing environments (8 or 46%) in the temperature range 500-700 deg. C. Air, Ar and Ar+7% H{sub 2} were used as carrier gas. The microstructure of the oxide layer and the subjacent alloy was investigated with X-ray diffraction (XRD), reflective light microscopy (RLM), scanning electron microscopy (SEM) equipped with energy dispersive spectroscopy (EDS), and transmission electron microscopy (TEM) equipped with electron diffraction (ED) and EDS. Double-layered oxides developed during steam oxidation of TP 347H FG both during field-testing and during laboratory exposures. TEM investigation suggested that the interior of the alloy grain was oxidised internally, forming particles of metallic Ni/Fe and Fe-Cr spinel. A FeCr{sub 2}O{sub 4} layer developed along the former alloy grain boundaries. Cr{sub 2}O{sub 3} developed in between this layer and the alloy during field-testing, and its formation was promoted by higher temperature. The morphology of the inner layer for the samples oxidised below and above approx. 585 deg. C looked very different in SEM (field-testing). It is suggested that more Cr is incorporated into the oxide layer at higher temperature, gradually transforming the morphology of the inner oxide layer. The alloy beneath the oxide layer was depleted in Cr

  12. Family group conferencing in youth care : characteristics of the decision making model, implementation and effectiveness of the Family Group (FG) plans

    NARCIS (Netherlands)

    Asscher, Jessica J.; Dijkstra, Sharon; Stams, Geert Jan J. M.; Dekovic, Maja; Creemers, Hanneke E.

    2014-01-01

    Background: The model of Family group-conferencing (FG-c) for decision making in child welfare has rapidly spread over the world during the past decades. Its popularity is likely to be caused by its philosophy, emphasizing participation and autonomy of families, rather than based on positive researc

  13. Final Report for Grant DE-FG02-91ER40690 for the period 12/1/2010 to 4/30/2014

    Energy Technology Data Exchange (ETDEWEB)

    Durkin, Stan [The Ohio State Uiniversity, Columbus, OH (United States); Hill, Chris [The Ohio State Uiniversity, Columbus, OH (United States); Kass, Richard [The Ohio State Uiniversity, Columbus, OH (United States); Braaten, Eric [The Ohio State Uiniversity, Columbus, OH (United States); Mathur, Samir [The Ohio State Uiniversity, Columbus, OH (United States); Raby, Stuart [The Ohio State Uiniversity, Columbus, OH (United States); Shigemitsu, Junko [The Ohio State Uiniversity, Columbus, OH (United States); Gan, K. K. [The Ohio State Uiniversity, Columbus, OH (United States); Kagan, Harris [The Ohio State Uiniversity, Columbus, OH (United States); Hughes, Richard E. [The Ohio State Uiniversity, Columbus, OH (United States); Winer, Brian L. [The Ohio State Uiniversity, Columbus, OH (United States); Honscheid, Klaus [The Ohio State Uiniversity, Columbus, OH (United States)

    2014-07-22

    This is the final report for The Ohio State University high energy physics grant DE-FG02- 91ER40690. The activities of the various Tasks are briefy summarized over the previous grant period. The support from the Department of Energy is greatly appreciated.

  14. FgLPMO9A from Fusarium graminearum cleaves xyloglucan independently of the backbone substitution pattern

    DEFF Research Database (Denmark)

    Nekiunaite, Laura; Petrović, Dejan M.; Westereng, Bjørge

    2016-01-01

    Lytic polysaccharide monooxygenases (LPMOs) are important for the enzymatic conversion of biomass and seem to play a key role in degradation of the plant cell wall. In this study, we characterize an LPMO from the fungal plant pathogen Fusarium graminearum (FgLPMO9A) that catalyzes the mixed C1/C4...

  15. EAMJ Dec. Repeatability.indd

    African Journals Online (AJOL)

    2008-12-12

    Dec 12, 2008 ... Results:Kappa values for four-week repeatability for the wheeze and asthma questions were 0.61 ... for logistic, cultural and ethical reasons, to use ... individual with baseline forced expiratory volume in .... period is likely to also include the effects of true ... data, the writing of the manuscript or the decision.

  16. Potential Role of the Last Half Repeat in TAL Effectors Revealed by a Molecular Simulation Study

    Directory of Open Access Journals (Sweden)

    Hua Wan

    2016-01-01

    Full Text Available TAL effectors (TALEs contain a modular DNA-binding domain that is composed of tandem repeats. In all naturally occurring TALEs, the end of tandem repeats is invariantly a truncated half repeat. To investigate the potential role of the last half repeat in TALEs, we performed comparative molecular dynamics simulations for the crystal structure of DNA-bound TALE AvrBs3 lacking the last half repeat and its modeled structure having the last half repeat. The structural stability analysis indicates that the modeled system is more stable than the nonmodeled system. Based on the principle component analysis, it is found that the AvrBs3 increases its structural compactness in the presence of the last half repeat. The comparison of DNA groove parameters of the two systems implies that the last half repeat also causes the change of DNA major groove binding efficiency. The following calculation of hydrogen bond reveals that, by stabilizing the phosphate binding with DNA at the C-terminus, the last half repeat helps to adopt a compact conformation at the protein-DNA interface. It further mediates more contacts between TAL repeats and DNA nucleotide bases. Finally, we suggest that the last half repeat is required for the high-efficient recognition of DNA by TALE.

  17. Potential Role of the Last Half Repeat in TAL Effectors Revealed by a Molecular Simulation Study

    Science.gov (United States)

    Wan, Hua; Chang, Shan; Hu, Jian-ping; Tian, Xu-hong

    2016-01-01

    TAL effectors (TALEs) contain a modular DNA-binding domain that is composed of tandem repeats. In all naturally occurring TALEs, the end of tandem repeats is invariantly a truncated half repeat. To investigate the potential role of the last half repeat in TALEs, we performed comparative molecular dynamics simulations for the crystal structure of DNA-bound TALE AvrBs3 lacking the last half repeat and its modeled structure having the last half repeat. The structural stability analysis indicates that the modeled system is more stable than the nonmodeled system. Based on the principle component analysis, it is found that the AvrBs3 increases its structural compactness in the presence of the last half repeat. The comparison of DNA groove parameters of the two systems implies that the last half repeat also causes the change of DNA major groove binding efficiency. The following calculation of hydrogen bond reveals that, by stabilizing the phosphate binding with DNA at the C-terminus, the last half repeat helps to adopt a compact conformation at the protein-DNA interface. It further mediates more contacts between TAL repeats and DNA nucleotide bases. Finally, we suggest that the last half repeat is required for the high-efficient recognition of DNA by TALE. PMID:27803930

  18. The autolytic activity of the recombinant amidase of Staphylococcus saprophyticus is inhibited by its own recombinant GW repeats.

    Science.gov (United States)

    Hell, Wolfgang; Reichl, Sylvia; Anders, Agnes; Gatermann, Sören

    2003-10-10

    The Aas (autolysin/adhesin of Staphylococcus saprophyticus) is a multifunctional surface protein containing two enzymatic domains an N-acetyl-muramyl-L-alanine amidase, an endo-beta-N-acetyl-D-glucosaminidase, and two different regions of repetitive sequences, an N-terminal and a C-terminal repetitive domain. The C-terminal repetitive domain is built up by the repeats R1, R2 and R3, which interconnect the putative active centers of the amidase and glucosaminidase. To investigate the influence of the C-terminal repeats and the N-terminal repeats on the amidase activity, the repetitive domains and fragments of them were cloned and expressed in Escherichia coli. The influence of the different fragments on the activity of the recombinant amidase of the Aas, consisting of the active center of the enzyme and repeat R1, was investigated in a turbidimetric microassay. The different fragments derived from the C-terminal repeats inhibited the amidase activity, while the N-terminal repeats did not influence the activity of the enzyme. The inhibiting activity increased with the number of GW repeats the recombinant fragment contained. Thus we conclude, that the C-terminal GW repeats and not the N-terminal repeats are necessary for the cell wall targeting and the autolytic function of the amidase.

  19. Directionality switchable gain stabilized linear repeater

    Science.gov (United States)

    Ota, Takayuki; Ohmachi, Tadashi; Aida, Kazuo

    2004-10-01

    We propose a new approach to realize a bidirectional linear repeater suitable for future optical internet networks and fault location in repeater chain with OTDR. The proposed approach is the linear repeater of simple configuration whose directionality is rearranged dynamically by electrical control signal. The repeater is composed of a magneto-optical switch, a circulator, a dynamically gain stabilized unidirectional EDFA, and control circuits. The repeater directionality is rearranged as fast as 0.1ms by an electrical control pulse. It is experimentally confirmed that OTDR with the directionality switchable repeater is feasible for repeater chain. The detailed design and performance of the repeater are also discussed, including the multi-pass interference (MPI) which may arise in the proposed repeater, the effect of the MPI on SNR degradation of the repeater chain and the feed-forward EDFA gain control circuit.

  20. Protein domain prediction

    NARCIS (Netherlands)

    Ingolfsson, Helgi; Yona, Golan

    2008-01-01

    Domains are considered to be the building blocks of protein structures. A protein can contain a single domain or multiple domains, each one typically associated with a specific function. The combination of domains determines the function of the protein, its subcellular localization and the interacti

  1. Measurement-based quantum repeaters

    CERN Document Server

    Zwerger, M; Briegel, H J

    2012-01-01

    We introduce measurement-based quantum repeaters, where small-scale measurement-based quantum processors are used to perform entanglement purification and entanglement swapping in a long-range quantum communication protocol. In the scheme, pre-prepared entangled states stored at intermediate repeater stations are coupled with incoming photons by simple Bell-measurements, without the need of performing additional quantum gates or measurements. We show how to construct the required resource states, and how to minimize their size. We analyze the performance of the scheme under noise and imperfections, with focus on small-scale implementations involving entangled states of few qubits. We find measurement-based purification protocols with significantly improved noise thresholds. Furthermore we show that already resource states of small size suffice to significantly increase the maximal communication distance. We also discuss possible advantages of our scheme for different set-ups.

  2. A Repeating Fast Radio Burst

    CERN Document Server

    Spitler, L G; Hessels, J W T; Bogdanov, S; Brazier, A; Camilo, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J; Ferdman, R D; Freire, P C C; Kaspi, V M; Lazarus, P; Lynch, R; Madsen, E C; McLaughlin, M A; Patel, C; Ransom, S M; Seymour, A; Stairs, I H; Stappers, B W; van Leeuwen, J; Zhu, W W

    2016-01-01

    Fast Radio Bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measures (i.e. integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of the fast radio bursts has led several authors to hypothesise that they originate in cataclysmic astrophysical events. Here we report the detection of ten additional bursts from the direction of FRB121102, using the 305-m Arecibo telescope. These new bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and wh...

  3. Repeatability of Harris Corner Detector

    Institute of Scientific and Technical Information of China (English)

    HU Lili

    2003-01-01

    Interest point detectors are commonly employed to reduce the amount of data to be processed. The ideal interest point detector would robustly select those features which are most appropriate or salient for the application and data at hand. This paper shows that interest points are geometrically stable under different transformations.This property makes interest points very successful in the context of image matching. To measure this property quantatively, we introduce a evaluation criterion: repeatability rate.

  4. Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster.

    Science.gov (United States)

    Vognsen, Tina; Kristensen, Ole

    2012-03-30

    The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7Å resolution. The overall structure is highly similar to nuclear transport factor 2: It is a homodimer comprised of a β-sheet and three α-helices forming a cone-like shape. However, known binding sites for RanGDP and FxFG containing peptides show electrostatic and steric differences compared to nuclear transport factor 2. A HEPES molecule bound in the structure suggests a new, and possibly physiologically relevant, ligand binding site.

  5. Membrane binding domains

    OpenAIRE

    Hurley, James H.

    2006-01-01

    Eukaryotic signaling and trafficking proteins are rich in modular domains that bind cell membranes. These binding events are tightly regulated in space and time. The structural, biochemical, and biophysical mechanisms for targeting have been worked out for many families of membrane binding domains. This review takes a comparative view of seven major classes of membrane binding domains, the C1, C2, PH, FYVE, PX, ENTH, and BAR domains. These domains use a combination of specific headgroup inter...

  6. Modified extrinsic information feedback mechanism based on FG-turbo equalization%改进的基于因子图Turbo均衡的外信息反馈机制

    Institute of Scientific and Technical Information of China (English)

    王忠勇; 吕素; 段琳琳; 张传宗

    2012-01-01

    This paper uses the factor graph and sum-product algorithm to discuss the turbo equalization principle, compares the performances of FG-turbo equalization algorithm in the sparse and non-sparse channels, and proposes a new FG-turbo equalization extrinsic information feedback mechanism in the non-sparse channel. Simulation results show that in sparse channel, the performance of the FG-turbo equalization is very close to the performance of the MAP-turbo equalization after several iterations, and the improvement of the modified extrinsic information feedback mechanism makes FG-turbo equalization obtain better performance gain.%讨论了基于因子图与和积算法的turbo均衡算法,并对稀疏和非稀疏两种不同信道下的性能进行了比较,提出了稀疏信道下基于因子图的turbo (FG-turbo)均衡改进外信息反馈机制.仿真结果表明,在稀疏信道下,经过若干次迭代FG-turbo均衡的性能逼近MAP-turbo均衡.提出的外信息反馈机制给FG-turbo均衡带来了较大的性能增益.

  7. Structure and carboxyl-terminal domain (CTD) binding of the Set2 SRI domain that couples histone H3 Lys36 methylation to transcription.

    Science.gov (United States)

    Vojnic, Erika; Simon, Bernd; Strahl, Brian D; Sattler, Michael; Cramer, Patrick

    2006-01-06

    During mRNA elongation, the SRI domain of the histone H3 methyltransferase Set2 binds to the phosphorylated carboxyl-terminal domain (CTD) of RNA polymerase II. The solution structure of the yeast Set2 SRI domain reveals a novel CTD-binding fold consisting of a left-handed three-helix bundle. NMR titration shows that the SRI domain binds an Ser2/Ser5-phosphorylated CTD peptide comprising two heptapeptide repeats and three flanking NH2-terminal residues, whereas a single CTD repeat is insufficient for binding. Residues that show strong chemical shift perturbations upon CTD binding cluster in two regions. Both CTD tyrosine side chains contact the SRI domain. One of the tyrosines binds in the region with the strongest chemical shift perturbations, formed by the two NH2-terminal helices. Unexpectedly, the SRI domain fold resembles the structure of an RNA polymerase-interacting domain in bacterial sigma factors (domain sigma2 in sigma70).

  8. Parental magma of the Skaergaard intrusion: constraints from melt inclusions in primitive troctolite blocks and FG-1 dykes

    Science.gov (United States)

    Jakobsen, Jakob K.; Tegner, Christian; Brooks, C. Kent; Kent, Adam J. R.; Lesher, Charles E.; Nielsen, Troels F. D.; Wiedenbeck, Michael

    2010-01-01

    Troctolite blocks with compositions akin to the Hidden Zone are exposed in a tholeiitic dyke cutting across the Skaergaard intrusion, East Greenland. Plagioclase in these blocks contains finely crystallised melt inclusions that we have homogenised to constrain the parental magma to 47.4-49.0 wt.% SiO2, 13.4-14.9 wt.% Al2O3 and 10.7-14.1 wt.% FeOT. These compositions are lower in FeOT and higher in SiO2 than previous estimates and have distinct La/SmN and Dy/YbN ratios that link them to the lowermost volcanic succession (Milne Land Formation) of the regional East Greenland flood basalt province. New major- and trace element compositions for the FG-1 dyke swarm, previously taken to represent Skaergaard magmas, overlap with the entire range of the regional flood basalt succession and do not form a coherent suite of Skaergaard like melts. These dykes are therefore re-interpreted as feeder dykes throughout the main phase of flood basalt volcanism.

  9. Transcellular activation of the human immunodeficiency virus type 1 long terminal repeat in cocultured lymphocytes.

    Science.gov (United States)

    Marcuzzi, A; Weinberger, J; Weinberger, O K

    1992-01-01

    One of the unexplained aspects of the progression of AIDS is that immunological abnormalities are detectable before CD4+ T-helper cell depletion occurs (A.R. Gruters, F.G. Terpstra, R. De Jong, C.J.M. Van Noesel, R.A.W. Van Lier, and F. Miedema, Eur. J. Immunol. 20:1039-1044, 1990; F. Miedema, A.J. Chantal-Petit, F.G. Terpstra, J.K.M.E. Schattenkerk, F. de Wolf, B.J.M. Al, M. Roos, J.M.A. Lang, S.A. Danner, J. Goudsmit, and P.T.A. Schellekens, J. Clin. Invest. 82:1908-1914, 1988; G.M. Shearer, D.C. Bernstein, K.S. Tung, C.S. Via, R. Redfield, S.Z. Salahuddin, and R.C. Gallo, J. Immunol. 137:2514-2521, 1986). In this report, we describe a mechanism by which human immunodeficiency virus type 1 (HIV-1)-infected cells can influence neighboring HIV-1-infected T lymphocytes and uninfected T cells as well. We have examined the interaction of T-cell and macrophage cell lines that are transfected with HIV-1 DNA by using cocultured lymphocytes. The HIV-1 constructs we used lack a functional pol gene and therefore do not produce infectious virus. Cocultivation results in the transcellular activation of the HIV long terminal repeat in the cocultured T cells. This transcellular activation is evident in as little as 3 h of cocultivation, at ratios of HIV-expressing cells to target cells as low as 1:1,000, and is dependent on the Tat-responsive element. The demonstration that a small number of HIV-expressing cells can affect a large number of uninfected bystander cells in a short period of time suggests a mechanism by which global immune dysfunction can precede the high prevalence of infected cells. Images PMID:1602543

  10. Improving repeatability by improving quality

    Energy Technology Data Exchange (ETDEWEB)

    Ronen, Shuki; Ackers, Mark; Schlumberger, Geco-Prakla; Brink, Mundy

    1998-12-31

    Time lapse (4-D) seismic is a promising tool for reservoir characterization and monitoring. The method is apparently simple: to acquire data repeatedly over the same reservoir, process and interpret the data sets, then changes between the data sets indicate changes in the reservoir. A problem with time lapse seismic data is that reservoirs are a relatively small part of the earth and important reservoir changes may cause very small differences to the time lapse data. The challenge is to acquire and process economical time lapse data such that reservoir changes can be detected above the noise of varying acquisition and environment. 7 refs., 9 figs.

  11. Coordinated hybrid automatic repeat request

    KAUST Repository

    Makki, Behrooz

    2014-11-01

    We develop a coordinated hybrid automatic repeat request (HARQ) approach. With the proposed scheme, if a user message is correctly decoded in the first HARQ rounds, its spectrum is allocated to other users, to improve the network outage probability and the users\\' fairness. The results, which are obtained for single- and multiple-antenna setups, demonstrate the efficiency of the proposed approach in different conditions. For instance, with a maximum of M retransmissions and single transmit/receive antennas, the diversity gain of a user increases from M to (J+1)(M-1)+1 where J is the number of users helping that user.

  12. Domains via Graphs

    Institute of Scientific and Technical Information of China (English)

    ZHANG Guoqiang; CHEN Yixiang

    2001-01-01

    This paper provides a concrete and simple introduction to two pillars of domain theory: (1) solving recursive domain equations, and (2) universal and saturated domains. Our exposition combines Larsen and Winskel's idea on solving domain equations using information systems with Girard's idea of stable domain theory in the form of coherence spaces, or graphs.Detailed constructions are given for universal and even homogeneous objects in two categories of graphs: one representing binary complete, prime algebraic domains with complete primes covering the bottom; the other representing ω-algebraic, prime algebraic lattices. The backand-forth argument in model theory helps to enlighten the constructions.

  13. Polarization discrimination between repeater false-target and radar target

    Institute of Scientific and Technical Information of China (English)

    SHI LongFei; WANG XueSong; XIAO ShunPing

    2009-01-01

    High fidelity repeater false-target badly affects a radar system's detecting, tracking, and data processing. It is an available approach of confronting false-target for radar that discriminates firstly and then eliminates. Whereas for the technique progress about the repeater false-target jam, it is more and more difficult to discriminate this jam in the time-domain, frequency-domain, or space-domain. The technique using polarization information to discriminate the target and false-target is discussed in this paper. With the difference that false-target signal vector's polarization ratio is fixed and target echo signal vector's polarization ratio is variational along with radar transmission signal's polarization, we transform the discrimination problem to beeline distinguish problem in the 2-dim complex space. The distributing characteristic expression of the false-target discrimination statistic is constructed, with which the discrimination ratio of false-target is analyzed. For the target case, the decomposed model of target scattering matrix and the concept of distinguish quantity are proposed. Then, the discrimination ratio of target can be forecasted according to target distinguish quantity. Thus, the performance of discrimination method has been analyzed integrally. The simulation results demonstrate the method in this paper is effective on the discrimination of target and false-target.

  14. Crowding by a repeating pattern.

    Science.gov (United States)

    Rosen, Sarah; Pelli, Denis G

    2015-01-01

    Theinability to recognize a peripheral target among flankers is called crowding. For a foveal target, crowding can be distinguished from overlap masking by its sparing of detection, linear scaling with eccentricity, and invariance with target size.Crowding depends on the proximity and similarity of the flankers to the target. Flankers that are far from or dissimilar to the target do not crowd it. On a gray page, text whose neighboring letters have different colors, alternately black and white, has enough dissimilarity that it might escape crowding. Since reading speed is normally limited by crowding, escape from crowding should allow faster reading. Yet reading speed is unchanged (Chung & Mansfield, 2009). Why? A recent vernier study found that using alternating-color flankers produces strong crowding (Manassi, Sayim, & Herzog, 2012). Might that effect occur with letters and reading? Critical spacing is the minimum center-to-center target-flanker spacing needed to correctly identify the target. We measure it for a target letter surrounded by several equidistant flanker letters of the same polarity, opposite polarity, or mixed polarity: alternately white and black. We find strong crowding in the alternating condition, even though each flanker letter is beyond its own critical spacing (as measured in a separate condition). Thus a periodic repeating pattern can produce crowding even when the individual elements do not. Further, in all conditions we find that, once a periodic pattern repeats (two cycles), further repetition does not affect critical spacing of the innermost flanker.

  15. Photon-activated charge domain in high-gain photoconductive switches

    Institute of Scientific and Technical Information of China (English)

    Wei Shi(施卫); Huiying Dai(戴慧莹); Xiaowei Sun(孙小卫)

    2003-01-01

    We report our experimental observation of charge domain oscillation in semi-insulating GaAs photoconductive semiconductor switches (PCSSs). The high-gain PCSS is intrinsically a photon-activated charge domain device. It is the photon-activated carriers that satisfy the requirement of charge domain formation on carrier concentration and device length product of 1012 cm-2. We also show that, because of the repeated process of domain formation, the domain travels with a compromised speed of electron saturation velocity and the speed of light. As a result, the transit time of charge domains in PCSS is much shorter than that of traditional Gunn domains.

  16. Automatization and familiarity in repeated checking

    NARCIS (Netherlands)

    Dek, Eliane C P; van den Hout, Marcel A.; Giele, Catharina L.; Engelhard, Iris M.

    2014-01-01

    Repeated checking paradoxically increases memory uncertainty. This study investigated the underlying mechanism of this effect. We hypothesized that as a result of repeated checking, familiarity with stimuli increases, and automatization of the checking procedure occurs, which should result in decrea

  17. CDC Vital Signs: Preventing Repeat Teen Births

    Science.gov (United States)

    ... file Error processing SSI file Preventing Repeat Teen Births Recommend on Facebook Tweet Share Compartir On this ... Too many teens, ages 15–19, have repeat births. Nearly 1 in 5 births to teens, ages ...

  18. Domains of laminin

    DEFF Research Database (Denmark)

    Engvall, E; Wewer, U M

    1996-01-01

    Extracellular matrix molecules are often very large and made up of several independent domains, frequently with autonomous activities. Laminin is no exception. A number of globular and rod-like domains can be identified in laminin and its isoforms by sequence analysis as well as by electron...... microscopy. Here we present the structure-function relations in laminins by examination of their individual domains. This approach to viewing laminin is based on recent results from several laboratories. First, some mutations in laminin genes that cause disease have affected single laminin domains, and some...... laminin isoforms lack particular domains. These mutants and isoforms are informative with regard to the activities of the mutated and missing domains. These mutants and isoforms are informative with regard to the activities of the mutated and missing domains. Second, laminin-like domains have now been...

  19. Expanded complexity of unstable repeat diseases

    OpenAIRE

    Polak, Urszula; McIvor, Elizabeth; Dent, Sharon Y.R.; Wells, Robert D.; Napierala, Marek.

    2012-01-01

    Unstable Repeat Diseases (URDs) share a common mutational phenomenon of changes in the copy number of short, tandemly repeated DNA sequences. More than 20 human neurological diseases are caused by instability, predominantly expansion, of microsatellite sequences. Changes in the repeat size initiate a cascade of pathological processes, frequently characteristic of a unique disease or a small subgroup of the URDs. Understanding of both the mechanism of repeat instability and molecular consequen...

  20. The FgNot3 Subunit of the Ccr4-Not Complex Regulates Vegetative Growth, Sporulation, and Virulence in Fusarium graminearum.

    Directory of Open Access Journals (Sweden)

    Duc-Cuong Bui

    Full Text Available The Ccr4-Not complex is evolutionarily conserved and important for multiple cellular functions in eukaryotic cells. In this study, the biological roles of the FgNot3 subunit of this complex were investigated in the plant pathogenic fungus Fusarium graminearum. Deletion of FgNOT3 resulted in retarded vegetative growth, retarded spore germination, swollen hyphae, and hyper-branching. The ΔFgnot3 mutants also showed impaired sexual and asexual sporulation, decreased virulence, and reduced expression of genes related to conidiogenesis. Fgnot3 deletion mutants were sensitive to thermal stress, whereas NOT3 orthologs in other model eukaryotes are known to be required for cell wall integrity. We found that FgNot3 functions as a negative regulator of the production of secondary metabolites, including trichothecenes and zearalenone. Further functional characterization of other components of the Not module of the Ccr4-Not complex demonstrated that the module is conserved. Each subunit primarily functions within the context of a complex and might have distinct roles outside of the complex in F. graminearum. This is the first study to functionally characterize the Not module in filamentous fungi and provides novel insights into signal transduction pathways in fungal development.

  1. 47 CFR 97.205 - Repeater station.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Repeater station. 97.205 Section 97.205... SERVICE Special Operations § 97.205 Repeater station. (a) Any amateur station licensed to a holder of a Technician, General, Advanced or Amateur Extra Class operator license may be a repeater. A holder of...

  2. 47 CFR 22.1015 - Repeater operation.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Repeater operation. 22.1015 Section 22.1015... Offshore Radiotelephone Service § 22.1015 Repeater operation. Offshore central stations may be used as repeater stations provided that the licensee is able to maintain control of the station, and in...

  3. ProtRepeatsDB: a database of amino acid repeats in genomes

    Directory of Open Access Journals (Sweden)

    Chauhan Virander S

    2006-07-01

    Full Text Available Abstract Background Genome wide and cross species comparisons of amino acid repeats is an intriguing problem in biology mainly due to the highly polymorphic nature and diverse functions of amino acid repeats. Innate protein repeats constitute vital functional and structural regions in proteins. Repeats are of great consequence in evolution of proteins, as evident from analysis of repeats in different organisms. In the post genomic era, availability of protein sequences encoded in different genomes provides a unique opportunity to perform large scale comparative studies of amino acid repeats. ProtRepeatsDB http://bioinfo.icgeb.res.in/repeats/ is a relational database of perfect and mismatch repeats, access to which is designed as a resource and collection of tools for detection and cross species comparisons of different types of amino acid repeats. Description ProtRepeatsDB (v1.2 consists of perfect as well as mismatch amino acid repeats in the protein sequences of 141 organisms, the genomes of which are now available. The web interface of ProtRepeatsDB consists of different tools to perform repeat s; based on protein IDs, organism name, repeat sequences, and keywords as in FASTA headers, size, frequency, gene ontology (GO annotation IDs and regular expressions (REGEXP describing repeats. These tools also allow formulation of a variety of simple, complex and logical queries to facilitate mining and large-scale cross-species comparisons of amino acid repeats. In addition to this, the database also contains sequence analysis tools to determine repeats in user input sequences. Conclusion ProtRepeatsDB is a multi-organism database of different types of amino acid repeats present in proteins. It integrates useful tools to perform genome wide queries for rapid screening and identification of amino acid repeats and facilitates comparative and evolutionary studies of the repeats. The database is useful for identification of species or organism specific

  4. Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila

    OpenAIRE

    Shieh, Shin-Yi; Bonini, Nancy M.

    2011-01-01

    Spinocerebellar ataxia type 3 is one of the polyglutamine (polyQ) diseases, which are caused by a CAG-repeat expansion within the coding region of the associated genes. The CAG repeat specifies glutamine, and the expanded polyQ domain mutation confers dominant toxicity on the protein. Traditionally, studies have focused on protein toxicity in polyQ disease mechanisms. Recent findings, however, demonstrate that the CAG-repeat RNA, which encodes the toxic polyQ protein, also contributes to the ...

  5. Solution properties of the archaeal CRISPR DNA repeat-binding homeodomain protein Cbp2

    DEFF Research Database (Denmark)

    Kenchappa, Chandra; Heiðarsson, Pétur Orri; Kragelund, Birthe;

    2013-01-01

    in facilitating high affinity DNA binding of Cbp2 by tethering the two domains. Structural studies on mutant proteins provide support for Cys(7) and Cys(28) enhancing high thermal stability of Cbp2(Hb) through disulphide bridge formation. Consistent with their proposed CRISPR transcriptional regulatory role, Cbp2......Clustered regularly interspaced short palindromic repeats (CRISPR) form the basis of diverse adaptive immune systems directed primarily against invading genetic elements of archaea and bacteria. Cbp1 of the crenarchaeal thermoacidophilic order Sulfolobales, carrying three imperfect repeats, binds...... specifically to CRISPR DNA repeats and has been implicated in facilitating production of long transcripts from CRISPR loci. Here, a second related class of CRISPR DNA repeat-binding protein, denoted Cbp2, is characterized that contains two imperfect repeats and is found amongst members of the crenarchaeal...

  6. Solution properties of the archaeal CRISPR DNA repeat-binding homeodomain protein Cbp2

    DEFF Research Database (Denmark)

    Kenchappa, Chandra; Heiðarsson, Pétur Orri; Kragelund, Birthe

    2013-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) form the basis of diverse adaptive immune systems directed primarily against invading genetic elements of archaea and bacteria. Cbp1 of the crenarchaeal thermoacidophilic order Sulfolobales, carrying three imperfect repeats, binds...... specifically to CRISPR DNA repeats and has been implicated in facilitating production of long transcripts from CRISPR loci. Here, a second related class of CRISPR DNA repeat-binding protein, denoted Cbp2, is characterized that contains two imperfect repeats and is found amongst members of the crenarchaeal...... in facilitating high affinity DNA binding of Cbp2 by tethering the two domains. Structural studies on mutant proteins provide support for Cys(7) and Cys(28) enhancing high thermal stability of Cbp2(Hb) through disulphide bridge formation. Consistent with their proposed CRISPR transcriptional regulatory role, Cbp2...

  7. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS1018 in the Gulf of Mexico and North Atlantic Ocean from 2010-10-12 to 2010-10-16 (NCEI Accession 0140567)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0140567 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS1018 in the Gulf of Mexico and North Atlantic Ocean...

  8. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS0623 in the Gulf of Mexico and North Atlantic Ocean from 2006-10-30 to 2006-11-06 (NCEI Accession 0140564)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0140564 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS0623 in the Gulf of Mexico and North Atlantic Ocean...

  9. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS0618 in the Gulf of Mexico and North Atlantic Ocean from 2006-08-04 to 2006-08-14 (NCEI Accession 0140563)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0140563 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS0618 in the Gulf of Mexico and North Atlantic Ocean...

  10. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS0814 in the North Atlantic Ocean from 2008-10-17 to 2008-10-23 (NCEI Accession 0129855)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0129855 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS0814 in the North Atlantic Ocean from 2008-10-17 to...

  11. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS0914 in the Gulf of Mexico and North Atlantic Ocean from 2009-08-24 to 2009-08-28 (NCEI Accession 0129858)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0129858 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS0914 in the Gulf of Mexico and North Atlantic Ocean...

  12. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS1202 in the Gulf of Mexico and North Atlantic Ocean from 2012-02-27 to 2012-03-02 (NCEI Accession 0129868)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0129868 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS1202 in the Gulf of Mexico and North Atlantic Ocean...

  13. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS1102 in the Gulf of Mexico and North Atlantic Ocean from 2011-02-21 to 2011-02-25 (NCEI Accession 0129864)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0129864 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS1102 in the Gulf of Mexico and North Atlantic Ocean...

  14. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS0802 in the Gulf of Mexico and North Atlantic Ocean from 2008-02-08 to 2008-02-13 (NCEI Accession 0129853)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0129853 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS0802 in the Gulf of Mexico and North Atlantic Ocean...

  15. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS1106 in the Gulf of Mexico and North Atlantic Ocean from 2011-04-04 to 2011-04-08 (NCEI Accession 0129865)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0129865 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS1106 in the Gulf of Mexico and North Atlantic Ocean...

  16. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS1116 in the Gulf of Mexico and North Atlantic Ocean from 2011-10-17 to 2011-10-22 (NCEI Accession 0129867)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0129867 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS1116 in the Gulf of Mexico and North Atlantic Ocean...

  17. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS1004 in the Gulf of Mexico and North Atlantic Ocean from 2010-03-08 to 2010-03-12 (NCEI Accession 0129861)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0129861 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS1004 in the Gulf of Mexico and North Atlantic Ocean...

  18. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS1015 in the Gulf of Mexico and North Atlantic Ocean from 2010-08-16 to 2010-08-20 (NCEI Accession 0129863)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0129863 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS1015 in the Gulf of Mexico and North Atlantic Ocean...

  19. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS1113 in the Gulf of Mexico and North Atlantic Ocean from 2011-08-02 to 2011-08-07 (NCEI Accession 0129866)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0129866 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS1113 in the Gulf of Mexico and North Atlantic Ocean...

  20. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS0919 in the Gulf of Mexico and North Atlantic Ocean from 2009-10-26 to 2009-10-30 (NCEI Accession 0129859)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0129859 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS0919 in the Gulf of Mexico and North Atlantic Ocean...

  1. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS0906 in the Gulf of Mexico and North Atlantic Ocean from 2009-04-20 to 2009-04-23 (NCEI Accession 0129857)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0129857 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS0906 in the Gulf of Mexico and North Atlantic Ocean...

  2. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS1007 in the Gulf of Mexico and North Atlantic Ocean from 2010-05-03 to 2010-05-07 (NCEI Accession 0129862)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0129862 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS1007 in the Gulf of Mexico and North Atlantic Ocean...

  3. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS0603 in the Gulf of Mexico and North Atlantic Ocean from 2006-01-17 to 2006-01-25 (NCEI Accession 0140561)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0140561 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS0603 in the Gulf of Mexico and North Atlantic Ocean...

  4. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS0612 in the Gulf of Mexico and North Atlantic Ocean from 2006-05-02 to 2006-05-10 (NCEI Accession 0140562)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0140562 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS0612 in the Gulf of Mexico and North Atlantic Ocean...

  5. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS0718 in the Gulf of Mexico and North Atlantic Ocean from 2007-07-08 to 2007-07-14 (NCEI Accession 0140566)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0140566 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS0718 in the Gulf of Mexico and North Atlantic Ocean...

  6. Physical and profile data collected aboard the F.G. Walton Smith during cruise WS1207 in the Gulf of Mexico and North Atlantic Ocean from 2012-06-04 to 2012-06-08 (NCEI Accession 0129869)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0129869 includes physical and profile data collected aboard the F.G. Walton Smith during cruise WS1207 in the Gulf of Mexico and North Atlantic Ocean...

  7. Pentatricopeptide repeat proteins in plants.

    Science.gov (United States)

    Barkan, Alice; Small, Ian

    2014-01-01

    Pentatricopeptide repeat (PPR) proteins constitute one of the largest protein families in land plants, with more than 400 members in most species. Over the past decade, much has been learned about the molecular functions of these proteins, where they act in the cell, and what physiological roles they play during plant growth and development. A typical PPR protein is targeted to mitochondria or chloroplasts, binds one or several organellar transcripts, and influences their expression by altering RNA sequence, turnover, processing, or translation. Their combined action has profound effects on organelle biogenesis and function and, consequently, on photosynthesis, respiration, plant development, and environmental responses. Recent breakthroughs in understanding how PPR proteins recognize RNA sequences through modular base-specific contacts will help match proteins to potential binding sites and provide a pathway toward designing synthetic RNA-binding proteins aimed at desired targets.

  8. Two-dimensional quantum repeaters

    Science.gov (United States)

    Wallnöfer, J.; Zwerger, M.; Muschik, C.; Sangouard, N.; Dür, W.

    2016-11-01

    The endeavor to develop quantum networks gave rise to a rapidly developing field with far-reaching applications such as secure communication and the realization of distributed computing tasks. This ultimately calls for the creation of flexible multiuser structures that allow for quantum communication between arbitrary pairs of parties in the network and facilitate also multiuser applications. To address this challenge, we propose a two-dimensional quantum repeater architecture to establish long-distance entanglement shared between multiple communication partners in the presence of channel noise and imperfect local control operations. The scheme is based on the creation of self-similar multiqubit entanglement structures at growing scale, where variants of entanglement swapping and multiparty entanglement purification are combined to create high-fidelity entangled states. We show how such networks can be implemented using trapped ions in cavities.

  9. General benchmarks for quantum repeaters

    CERN Document Server

    Pirandola, Stefano

    2015-01-01

    Using a technique based on quantum teleportation, we simplify the most general adaptive protocols for key distribution, entanglement distillation and quantum communication over a wide class of quantum channels in arbitrary dimension. Thanks to this method, we bound the ultimate rates for secret key generation and quantum communication through single-mode Gaussian channels and several discrete-variable channels. In particular, we derive exact formulas for the two-way assisted capacities of the bosonic quantum-limited amplifier and the dephasing channel in arbitrary dimension, as well as the secret key capacity of the qubit erasure channel. Our results establish the limits of quantum communication with arbitrary systems and set the most general and precise benchmarks for testing quantum repeaters in both discrete- and continuous-variable settings.

  10. Hungarian repeat station survey, 2010

    Directory of Open Access Journals (Sweden)

    Péter Kovács

    2013-03-01

    Full Text Available The last Hungarian repeat station survey was completed between October 2010 and February 2011. Declination, inclination and the total field were observed using one-axial DMI fluxgate magnetometer mounted on Zeiss20A theodolite and GSM 19 Overhauser magnetometer. The magnetic elements of the sites were reduced to the epoch of 2010.5 on the basis of the continuous recordings of Tihany Geophysical Observatory. In stations located far from the reference observatory, the observations were carried out in the morning and afternoon in order to decrease the effect of the distant temporal correction. To further increase the accuracy, on-site dIdD variometer has also been installed near the Aggtelek station, in the Baradla cave, during the survey of the easternmost sites. The paper presents the technical details and the results of our last campaign. The improvement of the accuracy of the temporal reduction by the use of the local variometer is also reported.

  11. Quality control during repeated fryings

    Directory of Open Access Journals (Sweden)

    Cuesta, C.

    1998-08-01

    Full Text Available Most of the debate ¡s about how the slow or frequent turnover of fresh fat affects the deterioration, of fat used in frying. Then, the modification of different oils used in repeated fryings of potatoes without or with turnover of fresh oil, under similar frying conditions, was evaluated by two criteria: by measuring the total polar component isolated by column chromatography and by the evaluation of the specific compounds related to thermoxidative and hydrolytic alteration by High Performance Size Exclusion Chromatography (HPSEC. The results indicate that with frequent turnover of fresh oil, the critical level of 25% of polar material is rarely reached, and there are fewer problems with fat deterioration because the frying tended to increase the level of polar material and thermoxidative compounds (polymers and dimers of triglycerides and oxidized triglycerides in the fryer oil during the first fryings, followed by minor changes and a tendency to reach a near-steady state in successive fryings. However, in repeated frying of potatoes using a null turnover the alteration rate was higher being linear the relationship found between polar material or the different thermoxidative compounds and the number of fryings. On the other hand chemical reactions produced during deep-fat frying can be minimized by using proper oils. In addition the increased level of consumers awareness toward fat composition and its impact on human health could had an impact on the selection of fats for snacks and for industry. In this way monoenic fats are the most adequate from a nutritional point of view and for its oxidative stability during frying.

  12. A novel Hartman Shack-based topography system: repeatability and agreement for corneal power with Scheimpflug+Placido topographer and rotating prism auto-keratorefractor.

    Science.gov (United States)

    Prakash, Gaurav; Srivastava, Dhruv; Choudhuri, Sounak

    2015-12-01

    The purpose of this study is to analyze the repeatability and agreement of corneal power using a new Hartman type topographer in comparison to Scheimpflug+Placido and autorefractor devices. In this cross sectional, observational study performed at the cornea services of a specialty hospital, 100 normal eyes (100 consecutive candidates) without any previous ocular surgery or morbidity except refractive error were evaluated. All candidates underwent three measurements each on a Full gradient, Hartman type topographer (FG) (iDesign, AMO), Scheimpflug+Placido topographer (SP) (Sirius, CSO) and rotating prism auto-keratorefractor (AR) (KR1, Nidek). The parameters assessed were flat keratometry (K1), steep keratometry (K2), steep axis (K2 axis), mean K, J 0 and J 45. Intra-device repeatability and inter-device agreement were evaluated. On repeatability analysis, the intra-device means were not significantly different (ANOVA, p > 0.05). Intraclass correlations (ICC) were >0.98 except for J 0 and J 45. In terms of intra-measurement standard deviation (Sw), the SP and FG groups fared better than AR group (p 0.05, R (2) 0.05). ICC ranged from 0.92 to 0.99 (p < 0.001). Regression fits on Bland-Altman plots suggested no clinically significant effect of average values over difference in means. The repeatability of Hartman type topographer in normal eyes is comparable to SP combination device and better than AR. The agreement between the three devices is good. However, we recommend against interchanging these devices between follow-ups or pooling their data.

  13. Rational design of alpha-helical tandem repeat proteins with closed architectures

    Science.gov (United States)

    Doyle, Lindsey; Hallinan, Jazmine; Bolduc, Jill; Parmeggiani, Fabio; Baker, David; Stoddard, Barry L.; Bradley, Philip

    2015-01-01

    Tandem repeat proteins, which are formed by repetition of modular units of protein sequence and structure, play important biological roles as macromolecular binding and scaffolding domains, enzymes, and building blocks for the assembly of fibrous materials1,2. The modular nature of repeat proteins enables the rapid construction and diversification of extended binding surfaces by duplication and recombination of simple building blocks3,4. The overall architecture of tandem repeat protein structures – which is dictated by the internal geometry and local packing of the repeat building blocks – is highly diverse, ranging from extended, super-helical folds that bind peptide, DNA, and RNA partners5–9, to closed and compact conformations with internal cavities suitable for small molecule binding and catalysis10. Here we report the development and validation of computational methods for de novo design of tandem repeat protein architectures driven purely by geometric criteria defining the inter-repeat geometry, without reference to the sequences and structures of existing repeat protein families. We have applied these methods to design a series of closed alpha-solenoid11 repeat structures (alpha-toroids) in which the inter-repeat packing geometry is constrained so as to juxtapose the N- and C-termini; several of these designed structures have been validated by X-ray crystallography. Unlike previous approaches to tandem repeat protein engineering12–20, our design procedure does not rely on template sequence or structural information taken from natural repeat proteins and hence can produce structures unlike those seen in nature. As an example, we have successfully designed and validated closed alpha-solenoid repeats with a left-handed helical architecture that – to our knowledge – is not yet present in the protein structure database21. PMID:26675735

  14. Rational design of α-helical tandem repeat proteins with closed architectures.

    Science.gov (United States)

    Doyle, Lindsey; Hallinan, Jazmine; Bolduc, Jill; Parmeggiani, Fabio; Baker, David; Stoddard, Barry L; Bradley, Philip

    2015-12-24

    Tandem repeat proteins, which are formed by repetition of modular units of protein sequence and structure, play important biological roles as macromolecular binding and scaffolding domains, enzymes, and building blocks for the assembly of fibrous materials. The modular nature of repeat proteins enables the rapid construction and diversification of extended binding surfaces by duplication and recombination of simple building blocks. The overall architecture of tandem repeat protein structures--which is dictated by the internal geometry and local packing of the repeat building blocks--is highly diverse, ranging from extended, super-helical folds that bind peptide, DNA, and RNA partners, to closed and compact conformations with internal cavities suitable for small molecule binding and catalysis. Here we report the development and validation of computational methods for de novo design of tandem repeat protein architectures driven purely by geometric criteria defining the inter-repeat geometry, without reference to the sequences and structures of existing repeat protein families. We have applied these methods to design a series of closed α-solenoid repeat structures (α-toroids) in which the inter-repeat packing geometry is constrained so as to juxtapose the amino (N) and carboxy (C) termini; several of these designed structures have been validated by X-ray crystallography. Unlike previous approaches to tandem repeat protein engineering, our design procedure does not rely on template sequence or structural information taken from natural repeat proteins and hence can produce structures unlike those seen in nature. As an example, we have successfully designed and validated closed α-solenoid repeats with a left-handed helical architecture that--to our knowledge--is not yet present in the protein structure database.

  15. Production of Slit2 LRR domains in mammalian cells for structural studies and the structure of human Slit2 domain 3.

    Science.gov (United States)

    Morlot, Cecile; Hemrika, Wieger; Romijn, Roland A; Gros, Piet; Cusack, Stephen; McCarthy, Andrew A

    2007-09-01

    Slit2 and Roundabout 1 (Robo1) provide a key ligand-receptor interaction for the navigation of commissural neurons during the development of the central nervous system. Slit2 is a large multidomain protein containing an unusual domain organization of four tandem leucine-rich repeat (LRR) domains at its N-terminus. These domains are well known to mediate protein-protein interactions; indeed, the Robo1-binding region has been mapped to the concave face of the second LRR domain. It has also been shown that the fourth LRR domain may mediate Slit dimerization and that both the first and second domains can bind heparin. Thus, while roles have been ascribed for three of the LRR domains, there is still no known role for the third domain. Each of the four LRR domains from human Slit2 have now been successfully expressed in milligram quantities using expression in mammalian cells. Here, the crystallization of the second and third LRR domains and the structure of the third LRR domain are presented. This is the first structure of an LRR domain from human Slit2, which has an extra repeat compared with the Drosophila homologue. It is proposed that a highly conserved patch of surface residues on the concave face may mediate any protein-protein interactions involving this LRR domain, a result that will be useful in guiding further studies on Slit2.

  16. Translation domains in multiferroics

    OpenAIRE

    Meier, D; Leo, N; Jungk, T.; Soergel, E.; Becker, P.; Bohaty, L.; Fiebig, M.

    2010-01-01

    Translation domains differing in the phase but not in the orientation of the corresponding order parameter are resolved in two types of multiferroics. Hexagonal (h-) YMnO$_3$ is a split-order-parameter multiferroic in which commensurate ferroelectric translation domains are resolved by piezoresponse force microscopy whereas MnWO$_4$ is a joint-order-parameter multiferroic in which incommensurate magnetic translation domains are observed by optical second harmonic generation. The pronounced ma...

  17. Frustratingly Easy Domain Adaptation

    CERN Document Server

    Daumé, Hal

    2009-01-01

    We describe an approach to domain adaptation that is appropriate exactly in the case when one has enough ``target'' data to do slightly better than just using only ``source'' data. Our approach is incredibly simple, easy to implement as a preprocessing step (10 lines of Perl!) and outperforms state-of-the-art approaches on a range of datasets. Moreover, it is trivially extended to a multi-domain adaptation problem, where one has data from a variety of different domains.

  18. Staggered domain wall fermions

    CERN Document Server

    Hoelbling, Christian

    2016-01-01

    We construct domain wall fermions with a staggered kernel and investigate their spectral and chiral properties numerically in the Schwinger model. In some relevant cases we see an improvement of chirality by more than an order of magnitude as compared to usual domain wall fermions. Moreover, we present first results for four-dimensional quantum chromodynamics, where we also observe significant reductions of chiral symmetry violations for staggered domain wall fermions.

  19. Characterization of rDNAs and Tandem Repeats in the Heterochromatin of Brassica rapa

    NARCIS (Netherlands)

    Lim, K.B.; Jong, de J.H.S.G.M.; Yang, T.J.; Park, J.Y.; Kwon, S.J.; Kim, J.S.; Lim, M.H.; Kim, J.A.; Jin, M.; Jin, Y.M.; Kim, S.H.; Lim, Y.P.; Bang, J.W.; Kim, H.I.; Park, B.S.

    2005-01-01

    We describe the morphology and molecular organization of heterochromatin domains in the interphase nuclei, and mitotic and meiotic chromosomes, of Brassica rapa, using DAPI staining and fluorescence in situ hybridization (FISH) of rDNA and pericentromere tandem repeats. We have developed a simple me

  20. The evolution and function of protein tandem repeats in plants.

    Science.gov (United States)

    Schaper, Elke; Anisimova, Maria

    2015-04-01

    Sequence tandem repeats (TRs) are abundant in proteomes across all domains of life. For plants, little is known about their distribution or contribution to protein function. We exhaustively annotated TRs and studied the evolution of TR unit variations for all Ensembl plants. Using phylogenetic patterns of TR units, we detected conserved TRs with unit number and order preserved during evolution, and those TRs that have diverged via recent TR unit gains/losses. We correlated the mode of evolution of TRs to protein function. TR number was strongly correlated with proteome size, with about one-half of all TRs recognized as common protein domains. The majority of TRs have been highly conserved over long evolutionary distances, some since the separation of red algae and green plants c. 1.6 billion yr ago. Conversely, recurrent recent TR unit mutations were rare. Our results suggest that the first TRs by far predate the first plants, and that TR appearance is an ongoing process with similar rates across the plant kingdom. Interestingly, the few detected highly mutable TRs might provide a source of variation for rapid adaptation. In particular, such TRs are enriched in leucine-rich repeats (LRRs) commonly found in R genes, where TR unit gain/loss may facilitate resistance to emerging pathogens.

  1. Pragmatic circuits frequency domain

    CERN Document Server

    Eccles, William

    2006-01-01

    Pragmatic Circuits: Frequency Domain goes through the Laplace transform to get from the time domain to topics that include the s-plane, Bode diagrams, and the sinusoidal steady state. This second of three volumes ends with a-c power, which, although it is just a special case of the sinusoidal steady state, is an important topic with unique techniques and terminology. Pragmatic Circuits: Frequency Domain is focused on the frequency domain. In other words, time will no longer be the independent variable in our analysis. The two other volumes in the Pragmatic Circuits series include titles on DC

  2. Persistent Mappings in Cross-Domain Analogical Learning of Physics Domains

    Science.gov (United States)

    2009-01-01

    ms. What is the value of I? (Problem 21-37, Giancoli 1991). This problem is represented by a case of 14 facts, defining the entities, events...domains. For example, Giancoli (1991) introduces rotational motion over an entire chapter, coming back to the analogy with linear motion repeatedly...retrieval? 6.1 Materials The problems were selected from a variety of physics resources, (Shearer et al. 1971; Giancoli 1991; Ogata 1997; Fogiel

  3. 高效液相色谱-质谱联用测定小鼠血浆中FG-4592浓度及其药动学研究%Determination of FG-4592 in mice plasma and pharmacokinetic study by LC-MS/MS method

    Institute of Scientific and Technical Information of China (English)

    张璇; 郑兆浠; 郑剑斌; 李慧; 周薇

    2016-01-01

    目的 建立LC-MS/MS法检测小鼠血浆内FG-4592的浓度,研究FG-4592在小鼠体内的药代动力学.方法 KM小鼠腹腔注射FG-4592 5 mg/kg,不同时间点采集血浆,样品经甲醇沉淀.选用Agilent Zorbax SB-Aq-C18色谱柱(2.1 mm× 100 mm,3.5 μm),柱温25℃,流动相为甲醇-水(含5 mmol/L甲酸铵,0.1%甲酸)(90∶10),流速0.35 mL/min.采用ESI离子源,正离子模式多反应监测,离子通道分别为m/z 353.1→m/z278.1(FG-4592)和m/z294.9→m/z 235.0(内标物).结果 测定血浆中FG-4592的线性范围为1~1000 ng/mL,日内及日间精密度均<10%,准确度在90%~105%范围内,方法学考察均符合生物样品的分析要求.药代动力学参数:Cmax为(22.80±0.36)μg/mL,AUC(0-72)为(31.64±0.97)(μg·h)/mL,t1/2为8.81 h.结论 本研究建立的FG-4592血药浓度测定方法可行,该药物在血液中吸收良好,测定结果可为药物的基础研究提供依据.

  4. A versatile palindromic amphipathic repeat coding sequence horizontally distributed among diverse bacterial and eucaryotic microbes

    Directory of Open Access Journals (Sweden)

    Glass John I

    2010-07-01

    Full Text Available Abstract Background Intragenic tandem repeats occur throughout all domains of life and impart functional and structural variability to diverse translation products. Repeat proteins confer distinctive surface phenotypes to many unicellular organisms, including those with minimal genomes such as the wall-less bacterial monoderms, Mollicutes. One such repeat pattern in this clade is distributed in a manner suggesting its exchange by horizontal gene transfer (HGT. Expanding genome sequence databases reveal the pattern in a widening range of bacteria, and recently among eucaryotic microbes. We examined the genomic flux and consequences of the motif by determining its distribution, predicted structural features and association with membrane-targeted proteins. Results Using a refined hidden Markov model, we document a 25-residue protein sequence motif tandemly arrayed in variable-number repeats in ORFs lacking assigned functions. It appears sporadically in unicellular microbes from disparate bacterial and eucaryotic clades, representing diverse lifestyles and ecological niches that include host parasitic, marine and extreme environments. Tracts of the repeats predict a malleable configuration of recurring domains, with conserved hydrophobic residues forming an amphipathic secondary structure in which hydrophilic residues endow extensive sequence variation. Many ORFs with these domains also have membrane-targeting sequences that predict assorted topologies; others may comprise reservoirs of sequence variants. We demonstrate expressed variants among surface lipoproteins that distinguish closely related animal pathogens belonging to a subgroup of the Mollicutes. DNA sequences encoding the tandem domains display dyad symmetry. Moreover, in some taxa the domains occur in ORFs selectively associated with mobile elements. These features, a punctate phylogenetic distribution, and different patterns of dispersal in genomes of related taxa, suggest that the

  5. Structure and Notch receptor binding of the tandem WWE domain of Deltex.

    Science.gov (United States)

    Zweifel, Mark E; Leahy, Daniel J; Barrick, Doug

    2005-11-01

    Deltex is a cytosolic effector of Notch signaling thought to bind through its N-terminal domain to the Notch receptor. Here we report the structure of the Drosophila Deltex N-terminal domain, which contains two tandem WWE sequence repeats. The WWE repeats, which adopt a novel fold, are related by an approximate two-fold axis of rotation. Although the WWE repeats are structurally distinct, they interact extensively and form a deep cleft at their junction that appears well suited for ligand binding. The two repeats are thermodynamically coupled; this coupling is mediated in part by a conserved segment that is immediately C-terminal to the second WWE domain. We demonstrate that although the Deltex WWE tandem is monomeric in solution, it forms a heterodimer with the ankyrin domain of the Notch receptor. These results provide structural and functional insight into how Deltex modulates Notch signaling, and how WWE modules recognize targets for ubiquitination.

  6. Strengthening concept learning by repeated testing.

    Science.gov (United States)

    Wiklund-Hörnqvist, Carola; Jonsson, Bert; Nyberg, Lars

    2014-02-01

    The aim of this study was to examine whether repeated testing with feedback benefits learning compared to rereading of introductory psychology key-concepts in an educational context. The testing effect was examined immediately after practice, after 18 days, and at a five-week delay in a sample of undergraduate students (n = 83). The results revealed that repeated testing with feedback significantly enhanced learning compared to rereading at all delays, demonstrating that repeated retrieval enhances retention compared to repeated encoding in the short- and the long-term. In addition, the effect of repeated testing was beneficial for students irrespectively of working memory capacity. It is argued that teaching methods involving repeated retrieval are important to consider by the educational system.

  7. Final Report for Project DE-FG02-05ER15718 Fluoropolymers, Electrolytes, Composites and Electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Creager, Stephen [Clemson Univ., SC (United States)

    2017-05-24

    This report is for a project that was initiated under the title “New Proton-Conducting Fluoropolymer Electrolytes for PEM Fuel Cells”, as part of the DOE program titled “Basic Research for the Hydrogen Fuel Cell Initiative”, Program Notice DE-FG01-04ER04-20. The project received 750,000 dollars in initial funding for a three-year term with a start date of August 15, 2005. Creager was PI and co-PIs were DesMarteau and Smith, all from Clemson. The project was renewed for a second three-year term with a start date of June 15 2008, again for 750,000 dollars, with the new title, “Fluoropolymers, Electrolytes, Composites and Electrodes”. Shortly after the renewal was put in place, co-PI Smith left Clemson to accept a position at the University of Texas at Dallas. After a period of no-cost extension the project was renewed on January 1 2013 for another three-year term, this time for a smaller amount ($525,000) and with Thrasher, a new senior hire at Clemson, as co-PI in place of Smith. DesMarteau had retired from Clemson by this time but was retained as a project advisor. After a final one-year no-cost extension for calendar year 2016, the project ended on December 31, 2016, giving it an active period of eleven and one-half years, from August 15 2005 to December 31 2016. The overall objective of this research project has been to create and understand the behavior of new fluoropolymer-based electrolytes and electrodes suitable for use in electrochemical energy storage and conversion devices. The objective was pursued via research on new fluorinated monomers, new polymers and polyelectrolytes (also known as ionomers), and new electrocatalyst supports that in some cases include chemically grafted electrolytes to promote rapid ion transport to electrocatalytically active sites (usually platinum nanoparticles) on the support. The research involved synthesis and characterization of new materials, and creation and use of new measurement techniques that address key

  8. Visualizing domain wall and reverse domain superconductivity.

    Science.gov (United States)

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

    2014-08-28

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

  9. Repeat concussions in the national football league.

    Science.gov (United States)

    Casson, Ira R; Viano, David C; Powell, John W; Pellman, Elliot J

    2011-01-01

    Repeat concussion is an important issue in the National Football League (NFL). An initial description of repeat injuries was published for 6 years (1996-2001). The characteristics and frequency of repeat concussion in the NFL have not changed in the subsequent 6 years (2002-2007). Case control. From 1996 to 2007, concussions were reported using a standardized form documenting signs and symptoms, loss of consciousness and medical action taken. Data on repeat concussions were analyzed for the 12 years and compared between the 2 periods. In 2002-2007, 152 players had repeat concussions (vs 160 in 1996-2001); 44 had 3+ head injuries (vs 52). The positions most often associated with repeat concussion in 2002-2007 were the defensive secondary, kick unit, running back, and linebacker. The odds for repeat concussion were elevated for wide receivers, tight ends, and linebackers but lower than in the earlier period. During 2002-2007, over half of players with repeat concussion were removed from play, and fewer immediately returned (vs 1996-2001). The average duration between concussions was 1.25 years for 2002-2007 and 1.65 years for the 12-year period. Over 12 years, 7.6% of all repeat concussions occurred within 2 weeks of the prior concussion. The defensive secondary, kick unit, running back, and linebacker have the highest incidence of repeat concussion. During 2002-2007, more than half of players with repeat concussion were removed from play, and only a fraction immediately returned. Although concussion was managed more conservatively by team physicians in the recent 6 years, repeat concussions occurred at similar rates during both periods.

  10. Automated quality checks on repeat prescribing.

    OpenAIRE

    Rogers, Jeremy E; Wroe, Christopher J; Roberts, Angus; Swallow, Angela; Stables, David; Cantrill, Judith A; Rector, Alan L.

    2003-01-01

    BACKGROUND: Good clinical practice in primary care includes periodic review of repeat prescriptions. Markers of prescriptions that may need review have been described, but manually checking all repeat prescriptions against the markers would be impractical. AIM: To investigate the feasibility of computerising the application of repeat prescribing quality checks to electronic patient records in United Kingdom (UK) primary care. DESIGN OF STUDY: Software performance test against benchmark manual...

  11. Short Tandem Repeat DNA Internet Database

    Science.gov (United States)

    SRD 130 Short Tandem Repeat DNA Internet Database (Web, free access)   Short Tandem Repeat DNA Internet Database is intended to benefit research and application of short tandem repeat DNA markers for human identity testing. Facts and sequence information on each STR system, population data, commonly used multiplex STR systems, PCR primers and conditions, and a review of various technologies for analysis of STR alleles have been included.

  12. Production of Slit2 LRR domains in mammalian cells for structural studies and the structure of human Slit2 domain 3

    NARCIS (Netherlands)

    Morlot, C.; Hemrika, W.; Romijn, R.A.; Gros, P.; Cusack, S.; McCarthy, A.A.

    2007-01-01

    Slit2 and Roundabout 1 (Robo1) provide a key ligand-receptor interaction for the navigation of commissural neurons during the development of the central nervous system. Slit2 is a large multidomain protein containing an unusual domain organization of four tandem leucine-rich repeat (LRR) domains at

  13. Replication Stalling and Heteroduplex Formation within CAG/CTG Trinucleotide Repeats by Mismatch Repair

    KAUST Repository

    Viterbo, David

    2016-03-16

    Trinucleotide repeat expansions are responsible for at least two dozen neurological disorders. Mechanisms leading to these large expansions of repeated DNA are still poorly understood. It was proposed that transient stalling of the replication fork by the repeat tract might trigger slippage of the newly-synthesized strand over its template, leading to expansions or contractions of the triplet repeat. However, such mechanism was never formally proven. Here we show that replication fork pausing and CAG/CTG trinucleotide repeat instability are not linked, stable and unstable repeats exhibiting the same propensity to stall replication forks when integrated in a yeast natural chromosome. We found that replication fork stalling was dependent on the integrity of the mismatch-repair system, especially the Msh2p-Msh6p complex, suggesting that direct interaction of MMR proteins with secondary structures formed by trinucleotide repeats in vivo, triggers replication fork pauses. We also show by chromatin immunoprecipitation that Msh2p is enriched at trinucleotide repeat tracts, in both stable and unstable orientations, this enrichment being dependent on MSH3 and MSH6. Finally, we show that overexpressing MSH2 favors the formation of heteroduplex regions, leading to an increase in contractions and expansions of CAG/CTG repeat tracts during replication, these heteroduplexes being dependent on both MSH3 and MSH6. These heteroduplex regions were not detected when a mutant msh2-E768A gene in which the ATPase domain was mutated was overexpressed. Our results unravel two new roles for mismatch-repair proteins: stabilization of heteroduplex regions and transient blocking of replication forks passing through such repeats. Both roles may involve direct interactions between MMR proteins and secondary structures formed by trinucleotide repeat tracts, although indirect interactions may not be formally excluded.

  14. Identification of Genes Controlled by the Essential YycFG Two-Component System Reveals a Role for Biofilm Modulation in Staphylococcus epidermidis.

    Science.gov (United States)

    Xu, Tao; Wu, Yang; Lin, Zhiwei; Bertram, Ralph; Götz, Friedrich; Zhang, Ying; Qu, Di

    2017-01-01

    Biofilms play a crucial role in the pathogenicity of Staphylococcus epidermidis, while little is known about whether the essential YycFG two-component signal transduction system (TCS) is involved in biofilm formation. We used antisense RNA (asRNA) to silence the yycFG TCS in order to study its regulatory functions in S. epidermidis. Strain 1457 expressing asRNA yycF exhibited a significant delay (~4-5 h) in entry to log phase, which was partially complemented by overexpressing ssaA. The expression of asRNA yycF and asRNA yycG resulted in a 68 and 50% decrease in biofilm formation at 6 h, respectively, while they had no significant inhibitory effect on 12 h biofilm formation. The expression of asRNA yycF led to a ~5-fold increase in polysaccharide intercellular adhesion (PIA) production, but it did not affect the expression of accumulation-associated protein (Aap) or the release of extracellular DNA. Consistently, quantitative real-time PCR showed that silencing yycF resulted in an increased transcription of biofilm-related genes, including icaA, arlR, sarA, sarX, and sbp. An in silico search of the YycF regulon for the conserved YycF recognition pattern and a modified motif in S. epidermidis, along with additional gel shift and DNase I footprinting assays, showed that arlR, sarA, sarX, and icaA are directly regulated by YycF. Our data suggests that YycFG modulates S. epidermidis biofilm formation in an ica-dependent manner.

  15. The enterprise engineering domain

    CSIR Research Space (South Africa)

    De Vries, M

    2015-06-01

    Full Text Available representation of the EE domain within the emerging EE discipline. We used a questionnaire to gather the views of EE and enterprise architecture (EA) researchers and practitioners on the EE domain. The main contributions of this article include: (1...

  16. Domain wall filters

    CERN Document Server

    Bär, O; Neuberger, H; Witzel, O; Baer, Oliver; Narayanan, Rajamani; Neuberger, Herbert; Witzel, Oliver

    2007-01-01

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

  17. Domain Walls on Singularities

    CERN Document Server

    Halyo, Edi

    2009-01-01

    We describe domain walls that live on $A_2$ and $A_3$ singularities. The walls are BPS if the singularity is resolved and non--BPS if it is deformed and fibered. We show that these domain walls may interpolate between vacua that support monopoles and/or vortices.

  18. Domains of Learning.

    Science.gov (United States)

    Gagne, Robert M.

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

  19. A Domain Analysis Bibliography

    Science.gov (United States)

    1990-06-01

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

  20. Domain Modeling: NP_001092096.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_001092096.1 chr19 Solution structure of the tandem four zf-C2H2 domain repeats o...f murine GLI-Kruppel family member HKR3 c2dlqa_ chr19/NP_001092096.1/NP_001092096.1_holo_175-290.pdb blast 3

  1. Domain Modeling: NP_085116.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_085116.2 chr5 Solution structure of the tandem four zf-C2H2 domain repeats of mu...rine GLI-Kruppel family member HKR3 c2dlqa_ chr5/NP_085116.2/NP_085116.2_holo_209-322.pdb blast 216C,218E,21

  2. Domain Modeling: NP_940886.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_940886.1 chr3 Solution structure of the tandem four zf-C2H2 domain repeats of mu...rine GLI-Kruppel family member HKR3 c2dlqa_ chr3/NP_940886.1/NP_940886.1_holo_320-436.pdb psi-blast 321C,323

  3. Domain Modeling: NP_852466.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_852466.1 chr3 Solution structure of the tandem four zf-C2H2 domain repeats of mu...rine GLI-Kruppel family member HKR3 c2dlqa_ chr3/NP_852466.1/NP_852466.1_holo_673-813.pdb blast 926R,928P,92

  4. Domain Modeling: NP_056154.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_056154.1 chr20 Solution structure of the tandem four zf-C2H2 domain repeats of m...urine GLI-Kruppel family member HKR3 c2dlqa_ chr20/NP_056154.1/NP_056154.1_holo_623-739.pdb psi-blast 624C,6

  5. Domain Modeling: NP_065184.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_065184.2 chr1 Solution structure of the tandem four zf-C2H2 domain repeats of mu...rine GLI-Kruppel family member HKR3 c2dlqa_ chr1/NP_065184.2/NP_065184.2_holo_267-376.pdb psi-blast 274A,276

  6. Domain Modeling: NP_066971.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_066971.2 chr7 Solution structure of the tandem four zf-C2H2 domain repeats of mu...rine GLI-Kruppel family member HKR3 c2dlqa_ chr7/NP_066971.2/NP_066971.2_holo_341-454.pdb blast 348C,350E,35

  7. Domain Modeling: NP_006291.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_006291.2 chr19 Solution structure of the tandem four zf-C2H2 domain repeats of m...urine GLI-Kruppel family member HKR3 c2dlqa_ chr19/NP_006291.2/NP_006291.2_holo_163-276.pdb blast 170C,172E,

  8. Domain Modeling: NP_071911.3 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_071911.3 chr10 Solution structure of the tandem four zf-C2H2 domain repeats of m...urine GLI-Kruppel family member HKR3 c2dlqa_ chr10/NP_071911.3/NP_071911.3_holo_111-217.pdb psi-blast 112C,1

  9. Domain Modeling: NP_775751.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_775751.1 chr19 Solution structure of the tandem four zf-C2H2 domain repeats of m...urine GLI-Kruppel family member HKR3 c2dlqa_ chr19/NP_775751.1/NP_775751.1_holo_331-443.pdb blast 338C,340H,

  10. Domain Modeling: NP_064562.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_064562.1 chr5 The Crystal Structure of a Partial Mouse Notch-1 Ankyrin Domain: Repeats 4 Through 7 Preser...ve an Ankyrin Fold p1ympb_ chr5/NP_064562.1/NP_064562.1_apo_474-612.pdb psi-blast 0 ...

  11. Domain Modeling: NP_065070.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_065070.1 chr4 The Crystal Structure of a Partial Mouse Notch-1 Ankyrin Domain: Repeats 4 Through 7 Preser...ve an Ankyrin Fold p1ympb_ chr4/NP_065070.1/NP_065070.1_apo_969-1098.pdb blast 0 ...

  12. Domain Modeling: NP_149417.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_149417.1 chr6 The Crystal Structure of a Partial Mouse Notch-1 Ankyrin Domain: Repeats 4 Through 7 Preser...ve an Ankyrin Fold p1ympb_ chr6/NP_149417.1/NP_149417.1_apo_1-124.pdb psi-blast 0 ...

  13. Domain Modeling: NP_060314.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_060314.2 chr2 The Crystal Structure of a Partial Mouse Notch-1 Ankyrin Domain: Repeats 4 Through 7 Preser...ve an Ankyrin Fold p1ympb_ chr2/NP_060314.2/NP_060314.2_apo_19-138.pdb psi-blast 0 ...

  14. Domain Modeling: NP_075392.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_075392.2 chr2 The Crystal Structure of a Partial Mouse Notch-1 Ankyrin Domain: Repeats 4 Through 7 Preser...ve an Ankyrin Fold p1ympb_ chr2/NP_075392.2/NP_075392.2_apo_402-524.pdb psi-blast 0 ...

  15. Domain Modeling: NP_653309.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_653309.2 chr2 The Crystal Structure of a Partial Mouse Notch-1 Ankyrin Domain: Repeats 4 Through 7 Preser...ve an Ankyrin Fold p1ympb_ chr2/NP_653309.2/NP_653309.2_apo_357-481.pdb psi-blast 0 ...

  16. Domain Modeling: NP_064562.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_064562.1 chr5 The Crystal Structure of a Partial Mouse Notch-1 Ankyrin Domain: Repeats 4 Through 7 Preser...ve an Ankyrin Fold p1ympb_ chr5/NP_064562.1/NP_064562.1_apo_314-468.pdb psi-blast 0 ...

  17. Domain Modeling: NP_932326.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_932326.2 chr10 The Crystal Structure of a Partial Mouse Notch-1 Ankyrin Domain: Repeats 4 Through 7 Prese...rve an Ankyrin Fold p1ympb_ chr10/NP_932326.2/NP_932326.2_apo_230-367.pdb psi-blast 0 ...

  18. Domain Modeling: NP_060405.3 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_060405.3 chr4 The Crystal Structure of a Partial Mouse Notch-1 Ankyrin Domain: Repeats 4 Through 7 Preser...ve an Ankyrin Fold p1ympb_ chr4/NP_060405.3/NP_060405.3_apo_653-782.pdb psi-blast 0 ...

  19. Domain Modeling: NP_569058.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_569058.1 chr3 The Crystal Structure of a Partial Mouse Notch-1 Ankyrin Domain: Repeats 4 Through 7 Preser...ve an Ankyrin Fold p1ympb_ chr3/NP_569058.1/NP_569058.1_apo_128-246.pdb psi-blast 0 ...

  20. Domain Modeling: NP_064562.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_064562.1 chr5 The Crystal Structure of a Partial Mouse Notch-1 Ankyrin Domain: Repeats 4 Through 7 Preser...ve an Ankyrin Fold p1ympb_ chr5/NP_064562.1/NP_064562.1_apo_174-308.pdb psi-blast 0 ...

  1. Domain Modeling: NP_004534.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_004534.2 chr2 The Crystal Structure of a Partial Mouse Notch-1 Ankyrin Domain: Repeats 4 Through 7 Preser...ve an Ankyrin Fold p1ympb_ chr2/NP_004534.2/NP_004534.2_apo_2171-2302.pdb psi-blast 0 ...

  2. Domain Modeling: NP_001007472.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_001007472.2 chr9 Crystal Structure of the Ankyrin Repeat Domain of Trpv1 p2pnna_ chr9/NP_001007472....2/NP_001007472.2_holo_484-756.pdb psi-blast 491L,536Y,539V,540R,570Y,575T,578R,583Y,586L,587F,607R ATP 0 ...

  3. Domain Modeling: NP_057199.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_057199.1 chr2 The Crystal Structure of a Partial Mouse Notch-1 Ankyrin Domain: Repeats 4 Through 7 Preser...ve an Ankyrin Fold p1ympb_ chr2/NP_057199.1/NP_057199.1_apo_239-364.pdb psi-blast 0 ...

  4. Domain Modeling: NP_037512.3 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_037512.3 chr19 Solution structure of the tandem four zf-C2H2 domain repeats of m...urine GLI-Kruppel family member HKR3 c2dlqa_ chr19/NP_037512.3/NP_037512.3_holo_542-655.pdb blast 549C,551E,

  5. Domain Modeling: NP_060142.3 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_060142.3 chr15 Crystal structure of the ankyrin repeat domain of TRPV2 p2etcb_ chr15/NP_060142.3.../NP_060142.3_apo_483-742.pdb p2etba_ chr15/NP_060142.3/NP_060142.3_holo_483-742.pdb psi-blas

  6. Domain Modeling: NP_001098547.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_001098547.2 chr3 Solution structure of the tandem four zf-C2H2 domain repeats of... murine GLI-Kruppel family member HKR3 c2dlqa_ chr3/NP_001098547.2/NP_001098547.2_holo_540-654.pdb psi-blast

  7. Domain Modeling: NP_954871.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_954871.1 chr17 Solution structure of three tandem repeats of zf-C2H2 domains fro...m human Kruppel-like factor 5 p2ebta_ chr17/NP_954871.1/NP_954871.1_holo_244-338.pdb blast 256C,258I,261C,26

  8. Domain Modeling: NP_001074421.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_001074421.1 chr6 Solution structure of the tandem four zf-C2H2 domain repeats of... murine GLI-Kruppel family member HKR3 c2dlqa_ chr6/NP_001074421.1/NP_001074421.1_holo_6-118.pdb blast 6C,8L

  9. Domain Modeling: NP_006201.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_006201.1 chr19 Solution structure of the tandem four zf-C2H2 domain repeats of m...urine GLI-Kruppel family member HKR3 c2dlqa_ chr19/NP_006201.1/NP_006201.1_holo_165-272.pdb psi-blast 1308P,

  10. Domain Modeling: NP_899051.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_899051.1 chr17 Solution structure of the tandem four zf-C2H2 domain repeats of m...urine GLI-Kruppel family member HKR3 c2dlqa_ chr17/NP_899051.1/NP_899051.1_holo_199-297.pdb psi-blast 200L,2

  11. Repeatability & Workability Evaluation of SIGMOD 2009

    KAUST Repository

    Manegold, Stefan

    2010-12-15

    SIGMOD 2008 was the first database conference that offered to test submitters\\' programs against their data to verify the repeatability of the experiments published [1]. Given the positive feedback concerning the SIGMOD 2008 repeatability initiative, SIGMOD 2009 modified and expanded the initiative with a workability assessment.

  12. Association of condensin with chromosomes depends on DNA binding by its HEAT-repeat subunits.

    Science.gov (United States)

    Piazza, Ilaria; Rutkowska, Anna; Ori, Alessandro; Walczak, Marta; Metz, Jutta; Pelechano, Vicent; Beck, Martin; Haering, Christian H

    2014-06-01

    Condensin complexes have central roles in the three-dimensional organization of chromosomes during cell divisions, but how they interact with chromatin to promote chromosome segregation is largely unknown. Previous work has suggested that condensin, in addition to encircling chromatin fibers topologically within the ring-shaped structure formed by its SMC and kleisin subunits, contacts DNA directly. Here we describe the discovery of a binding domain for double-stranded DNA formed by the two HEAT-repeat subunits of the Saccharomyces cerevisiae condensin complex. From detailed mapping data of the interfaces between the HEAT-repeat and kleisin subunits, we generated condensin complexes that lack one of the HEAT-repeat subunits and consequently fail to associate with chromosomes in yeast and human cells. The finding that DNA binding by condensin's HEAT-repeat subunits stimulates the SMC ATPase activity suggests a multistep mechanism for the loading of condensin onto chromosomes.

  13. Reward modulation of contextual cueing: Repeated context overshadows repeated target location.

    Science.gov (United States)

    Sharifian, Fariba; Contier, Oliver; Preuschhof, Claudia; Pollmann, Stefan

    2017-08-07

    Contextual cueing can be enhanced by reward. However, there is a debate if reward is associated with the repeated target-distractor configurations or with the repeated target locations that occur in both repeated and new displays. Based on neuroimaging evidence, we hypothesized that reward becomes associated with the target location only in new displays, but not in repeated displays, where the repeated target location is overshadowed by the more salient repeated target-distractor configuration. To test this hypothesis, we varied the reward value associated with the same target location in repeated and new displays. The results confirmed the overshadowing hypothesis in that search facilitation in repeated target-distractor configurations was modulated by the variable value associated with the target location. This effect was observed mainly in early learning.

  14. Childhood experiences and repeated suicidal behavior

    DEFF Research Database (Denmark)

    Krarup, Gertrud; Nielsen, Bent; Rask, P

    1991-01-01

    The aim of this study was to elucidate the influence of various events in childhood on suicidal behavior in adult age. For this purpose, 99 patients admitted to the Department of Psychiatry of Odense University Hospital after making a suicide attempt were followed for 5 years, to register repeated...... suicidal behavior. The results showed that three fourths of the patients attempted suicide more than once (62% nonfatal and 14% fatal outcome). The sex distribution was about the same among the first-evers as among the repeaters. Most repeaters were younger people in their twenties and thirties......, and the first-evers on average were past the age of 40. Somewhat unexpectedly, significantly more repeaters than first-evers had grown up with both their parents. However, the results also showed that significantly more repeaters than first-evers had had an unhappy childhood. This indicates...

  15. UK 2009-2010 repeat station report

    Directory of Open Access Journals (Sweden)

    Thomas J.G. Shanahan

    2013-03-01

    Full Text Available The British Geological Survey is responsible for conducting the UK geomagnetic repeat station programme. Measurements made at the UK repeat station sites are used in conjunction with the three UK magnetic observatories: Hartland, Eskdalemuir and Lerwick, to produce a regional model of the local field each year. The UK network of repeat stations comprises 41 stations which are occupied at approximately 3-4 year intervals. Practices for conducting repeat station measurements continue to evolve as advances are made in survey instrumentation and as the usage of the data continues to change. Here, a summary of the 2009 and 2010 UK repeat station surveys is presented, highlighting the measurement process and techniques, density of network, reduction process and recent results.

  16. Discovery, Characterization, and Functional Study of a Novel MEF2D CAG Repeat in Duck (Anas platyrhynchos).

    Science.gov (United States)

    Wang, Yushi; Wang, Jiwen; Liu, Hehe; Zhang, Rongping; Zhang, Tao; Gan, Xiang; Huang, Huilan; Chen, Da; Li, Liang

    2016-08-01

    Myocyte enhancer transcription factor 2D (MEF2D) is an important transcription factor for promoting the growth and development of muscle. CAG repeats have been found in the coding sequence (CDS) of avian MEF2D; however, their functions remain unknown and require further investigation. Here, we examined the characteristics and functional role of MEF2D CAG repeat in duck. The full-length CDS of duck MEF2D was cloned for the first time, and a novel CAG repeat was identified and located in exon 9. Sequence analysis indicated that the protein domains of duck MEF2D are highly conserved relative to other vertebrates, whereas MEF2D CAG repeats with variable repeat numbers are specific to avian species. Furthermore, sequencing has revealed polymorphisms in MEF2D CAG repeat at both DNA and mRNA levels. Four MEF2D CAG repeat genotypes and 10 MEF2D cDNA variants with different CAG repeat numbers were detected in two duck populations. A t-test showed that the expanded CAG repeat generated significantly longer transcription products (p analysis demonstrated positive correlations between the expansion of the CAG repeat and five muscle-related traits. By using protein structure prediction, we suggested that the polymorphisms of the CAG repeat affect protein structures within protein domains. Taken together, these findings reveal that duck MEF2D CAG repeat is a potential functional element with polymorphisms and may cause differences in MEF2D function between duck and other vertebrate species.

  17. Thermal stability of chicken brain {alpha}-spectrin repeat 17: a spectroscopic study

    Energy Technology Data Exchange (ETDEWEB)

    Brenner, Annette K. [University of Bergen, Department of Chemistry (Norway); Kieffer, Bruno [Ecole Superieure de Biotechnologie de Strasbourg, IGBMC Biomolecular NMR Group, CNRS UMR 7104 (France); Trave, Gilles [Ecole Superieure de Biotechnologie de Strasbourg, Equipe Oncoproteines, IREBS, UMR 7242 (France); Froystein, Nils Age [University of Bergen, Department of Chemistry (Norway); Raae, Arnt J., E-mail: arnt.raae@mbi.uib.no [University of Bergen, Department of Molecular Biology (Norway)

    2012-06-15

    Spectrin is a rod-like multi-modular protein that is mainly composed of triple-helical repeats. These repeats show very similar 3D-structures but variable conformational and thermodynamical stabilities, which may be of great importance for the flexibility and dynamic behaviour of spectrin in the cell. For instance, repeat 17 (R17) of the chicken brain spectrin {alpha}-chain is four times less stable than neighbouring repeat 16 (R16) in terms of Increment G. The structure of spectrin repeats has mainly been investigated by X-ray crystallography, but the structures of a few repeats, e.g. R16, have also been determined by NMR spectroscopy. Here, we undertook a detailed characterization of the neighbouring R17 by NMR spectroscopy. We assigned most backbone resonances and observed NOE restraints, relaxation values and coupling constants that all indicated that the fold of R17 is highly similar to that of R16, in agreement with previous X-ray analysis of a tandem repeat of the two domains. However, {sup 15}N heteronuclear NMR spectra measured at different temperatures revealed particular features of the R17 domain that might contribute to its lower stability. Conformational exchange appeared to alter the linker connecting R17 to R16 as well as the BC-loop in close proximity. In addition, heat-induced splitting was observed for backbone resonances of a few spatially related residues including V99 of helix C, which in R16 is replaced by the larger hydrophobic tryptophan residue that is relatively conserved among other spectrin repeats. These data support the view that the substitution of tryptophan by valine at this position may contribute to the lower stability of R17.

  18. Chromatin structure of repeating CTG/CAG and CGG/CCG sequences in human disease.

    Science.gov (United States)

    Wang, Yuh-Hwa

    2007-05-01

    In eukaryotic cells, chromatin structure organizes genomic DNA in a dynamic fashion, and results in regulation of many DNA metabolic processes. The CTG/CAG and CGG/CCG repeating sequences involved in several neuromuscular degenerative diseases display differential abilities for the binding of histone octamers. The effect of the repeating DNA on nucleosome assembly could be amplified as the number of repeats increases. Also, CpG methylation, and sequence interruptions within the triplet repeats exert an impact on the formation of nucleosomes along these repeating DNAs. The two most common triplet expansion human diseases, myotonic dystrophy 1 and fragile X syndrome, are caused by the expanded CTG/CAG and CGG/CCG repeats, respectively. In addition to the expanded repeats and CpG methylation, histone modifications, chromatin remodeling factors, and noncoding RNA have been shown to coordinate the chromatin structure at both myotonic dystrophy 1 and fragile X loci. Alterations in chromatin structure at these two loci can affect transcription of these disease-causing genes, leading to disease symptoms. These observations have brought a new appreciation that a full understanding of disease gene expression requires a knowledge of the structure of the chromatin domain within which the gene resides.

  19. The different roles of aggrecan interaction domains

    DEFF Research Database (Denmark)

    Aspberg, Anders

    2012-01-01

    is vital in that it binds the proteoglycan to hyaluronan in ternary complex with link protein, retaining the proteoglycan in the tissue. The importance of the C-terminal G3 domain interactions has recently been emphasized by two different human hereditary disorders: autosomal recessive aggrecan......The aggregating proteoglycans of the lectican family are important components of extracellular matrices. Aggrecan is the most well studied of these and is central to cartilage biomechanical properties and skeletal development. Key to its biological function is the fixed charge of the many......-type spondyloepimetaphyseal dysplasia and autosomal dominant familial osteochondritis dissecans. In these two conditions, different missense mutations in the aggrecan C-type lectin repeat have been described. The resulting amino acid replacements affect the ligand interactions of the G3 domain, albeit with widely different...

  20. Preliminary study on preparation of human coagulation factor Ⅷ using ion exchange chromatography with FG TMAE%以强阴离子交换剂FG TMAE为介质的离子交换层析制备人凝血因子Ⅷ的初探

    Institute of Scientific and Technical Information of China (English)

    费梅芳; 是翡; 吴志韡; 吴云涛; 夏祯; 许静

    2015-01-01

    Objective To explore preparation of human coagulation factor Ⅷ (FⅧ)using ion exchange chromatography (ICE) with a strong anion exchanger FG TMAE as separating medium.Methods The initial conditions of ICE were identified by linear gradient elution using eluent containing different concentrations of NaCl.Ionic strength and pH value of the wash solution and eluentand and temperature of the sample were optimized to finally identify the optimum conditions of ICE with FG TMAE.Results When ICE was carried out using wash solution containing 220 mmol/L NaCl and eluent containing 450 mmol/L NaCl at pH7.0 in room temperature (20-25 ℃),recoveries (77.53%) and specific activity (24.67 IU/mg) of FⅧ were both high.Conclusion FⅧ preparation using ICE with FG TMAE is feasible.%目的 初步探索以强阴离子交换剂FG TMAE为介质进行离子交换层析来制备人凝血因子Ⅷ.方法 以含不同氯化钠浓度的洗脱液进行线性梯度来初步确定离子交换层析的条件,并优化离子交换层析的洗涤液和洗脱液的离子强度和pH值以及样品的温度,最终确定以强阴离子交换剂FGTMAE为介质进行离子交换层析的最适条件.结果 在室温(20~25℃)条件下,以pH 7.0的含220 mmol/L氯化钠的洗涤液和pH 7.0的含450 mmol/L氯化钠的洗脱液进行离子交换层析,可使人凝血因子Ⅷ的回收率(77.53%)和比活性(24.67 IU/mg)均较高.结论 以强阴离子交换剂FG TMAE为介质进行离子交换层析制备人凝血因子Ⅷ是可行的.

  1. Domain-Specific Multimodeling

    DEFF Research Database (Denmark)

    Hessellund, Anders

    Enterprise systems are complex artifacts. They are hard to build, manage, understand, and evolve. Existing software development paradigms fail to properly address challenges such as system size, domain complexity, and software evolution when development is scaled to enterprise systems. We propose...... domain-specific multimodeling as a development paradigm to tackle these challenges in a language-oriented manner. The different concerns of a system are conceptually separated and made explicit as independent domain-specific languages. This approach increases productivity and quality by raising...... the overall level of abstraction. It does, however, also introduce a new problem of coordinating multiple different languages in a single system. We call this problem the coordination problem. In this thesis, we present the coordination method for domain-specific multimodeling that explicitly targets...

  2. Conserved Domain Database (CDD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — CDD is a protein annotation resource that consists of a collection of well-annotated multiple sequence alignment models for ancient domains and full-length proteins.

  3. Identification of conserved, centrosome-targeting ASH domains in TRAPPII complex subunits and TRAPPC8

    DEFF Research Database (Denmark)

    Schou, Kenneth Bødtker; Morthorst, Stine Kjær; Christensen, Søren Tvorup;

    2014-01-01

    , and -13 as novel ASH domain-containing proteins. In addition to a C-terminal ASH domain region, we predict that the N-terminus of TRAPPC8, -9, -10, and -11, as well as their yeast counterparts, consists of an alpha-solenoid bearing stretches of multiple tetratricopeptide (TPR) repeats. Immunofluorescence...

  4. Length variations amongst protein domain superfamilies and consequences on structure and function.

    Directory of Open Access Journals (Sweden)

    Sankaran Sandhya

    Full Text Available BACKGROUND: Related protein domains of a superfamily can be specified by proteins of diverse lengths. The structural and functional implications of indels in a domain scaffold have been examined. METHODOLOGY: In this study, domain superfamilies with large length variations (more than 30% difference from average domain size, referred as 'length-deviant' superfamilies and 'length-rigid' domain superfamilies (<10% length difference from average domain size were analyzed for the functional impact of such structural differences. Our delineated dataset, derived from an objective algorithm, enables us to address indel roles in the presence of peculiar structural repeats, functional variation, protein-protein interactions and to examine 'domain contexts' of proteins tolerant to large length variations. Amongst the top-10 length-deviant superfamilies analyzed, we found that 80% of length-deviant superfamilies possess distant internal structural repeats and nearly half of them acquired diverse biological functions. In general, length-deviant superfamilies have higher chance, than length-rigid superfamilies, to be engaged in internal structural repeats. We also found that approximately 40% of length-deviant domains exist as multi-domain proteins involving interactions with domains from the same or other superfamilies. Indels, in diverse domain superfamilies, were found to participate in the accretion of structural and functional features amongst related domains. With specific examples, we discuss how indels are involved directly or indirectly in the generation of oligomerization interfaces, introduction of substrate specificity, regulation of protein function and stability. CONCLUSIONS: Our data suggests a multitude of roles for indels that are specialized for domain members of different domain superfamilies. These specialist roles that we observe and trends in the extent of length variation could influence decision making in modeling of new superfamily

  5. Modification of fibrin network ultrastructure by Fab fragments specific for different domain of fibrinogen.

    Science.gov (United States)

    Cierniewski, C S; Janiak, A; Wyroba, E

    1986-01-01

    Kinetics of inhibition of fibrin monomer polymerization produced by Fab fragments prepared from immunochemically purified monospecific antibodies to the surface epitopes of different domains of fibrinogen molecule has been correlated with electron microscopic observations of resulting specimens. Fab fragments prepared from anti FgD antisera were the most efficient inhibitors of thrombin-catalysed conversion of fibrinogen to fibrin; polymerization of fibrin monomers as detected spectrophotometrically was abolished at 2:1 molar ratio of anti FgD Fab fragments to fibra monomer. These Fab fragments acting as a steric hindrance of polymerization sites inhibited the first stage of fibrin monomer aggregation. Interaction of Fab fragments derived from antibodies specific for alpha 239-476 with corresponding segment of fibrinogen molecule resulted in a weak inhibition of fibrin monomer polymerization. However, fibrin obtained in the presence of these Fab fragments was significantly modified and showed no periodicity. This observation may suggest that anti alpha 239-476 Fab impaired the course of the second stage of fibrin monomer polymerization, i.e. lateral association of fibrin fibrils.

  6. The child accident repeater: a review.

    Science.gov (United States)

    Jones, J G

    1980-04-01

    The child accident repeater is defined as one who has at least three accidents that come to medical attention within a year. The accident situation has features in common with those of the child who has a single accident through simple "bad luck", but other factors predispose him to repeated injury. In the child who has a susceptible personality, a tendency for accident repetition may be due to a breakdown in adjustment to a stressful environment. Prevention of repeat accidents should involve the usual measures considered appropriate for all children as well as an attempt to provide treatment of significant maladjustment and modification of a stressful environment.

  7. Cardiac ankyrin repeat protein and atherosclerosis%心锚重复蛋白与冠状动脉粥样硬化

    Institute of Scientific and Technical Information of China (English)

    周丹

    2010-01-01

    @@ 心锚重复蛋白(cardiac ankyrin repeat protein,CARP)也常被称为ANKRD1蛋白(cardiac ankyrin repeat domain1protein),其他别名有C-193、MCARP等,是1985年发现的一个核转录辅助因子,属于锚蛋白(ANK)重复序列蛋白家族(muscle ankyrin repeat proteins,MARP)的保守基因.

  8. Telomere and ribosomal DNA repeats are chromosomal targets of the bloom syndrome DNA helicase

    Directory of Open Access Journals (Sweden)

    Paric Enesa

    2003-10-01

    Full Text Available Abstract Background Bloom syndrome is one of the most cancer-predisposing disorders and is characterized by genomic instability and a high frequency of sister chromatid exchange. The disorder is caused by loss of function of a 3' to 5' RecQ DNA helicase, BLM. The exact role of BLM in maintaining genomic integrity is not known but the helicase has been found to associate with several DNA repair complexes and some DNA replication foci. Results Chromatin immunoprecipitation of BLM complexes recovered telomere and ribosomal DNA repeats. The N-terminus of BLM, required for NB localization, is the same as the telomere association domain of BLM. The C-terminus is required for ribosomal DNA localization. BLM localizes primarily to the non-transcribed spacer region of the ribosomal DNA repeat where replication forks initiate. Bloom syndrome cells expressing the deletion alleles lacking the ribosomal DNA and telomere association domains have altered cell cycle populations with increased S or G2/M cells relative to normal. Conclusion These results identify telomere and ribosomal DNA repeated sequence elements as chromosomal targets for the BLM DNA helicase during the S/G2 phase of the cell cycle. BLM is localized in nuclear bodies when it associates with telomeric repeats in both telomerase positive and negative cells. The BLM DNA helicase participates in genomic stability at ribosomal DNA repeats and telomeres.

  9. Telomere and ribosomal DNA repeats are chromosomal targets of the bloom syndrome DNA helicase.

    Science.gov (United States)

    Schawalder, James; Paric, Enesa; Neff, Norma F

    2003-10-27

    Bloom syndrome is one of the most cancer-predisposing disorders and is characterized by genomic instability and a high frequency of sister chromatid exchange. The disorder is caused by loss of function of a 3' to 5' RecQ DNA helicase, BLM. The exact role of BLM in maintaining genomic integrity is not known but the helicase has been found to associate with several DNA repair complexes and some DNA replication foci. Chromatin immunoprecipitation of BLM complexes recovered telomere and ribosomal DNA repeats. The N-terminus of BLM, required for NB localization, is the same as the telomere association domain of BLM. The C-terminus is required for ribosomal DNA localization. BLM localizes primarily to the non-transcribed spacer region of the ribosomal DNA repeat where replication forks initiate. Bloom syndrome cells expressing the deletion alleles lacking the ribosomal DNA and telomere association domains have altered cell cycle populations with increased S or G2/M cells relative to normal. These results identify telomere and ribosomal DNA repeated sequence elements as chromosomal targets for the BLM DNA helicase during the S/G2 phase of the cell cycle. BLM is localized in nuclear bodies when it associates with telomeric repeats in both telomerase positive and negative cells. The BLM DNA helicase participates in genomic stability at ribosomal DNA repeats and telomeres.

  10. Strongly Semicontinuous Domains and Semi-FS Domains

    Directory of Open Access Journals (Sweden)

    Qingyu He

    2014-01-01

    Full Text Available We are mainly concerned with some special kinds of semicontinuous domains and relationships between them. New concepts of strongly semicontinuous domains, meet semicontinuous domains and semi-FS domains are introduced. It is shown that a dcpo L is strongly semicontinuous if and only if L is semicontinuous and meet semicontinuous. It is proved that semi-FS domains are strongly semicontinuous. Some interpolation properties of semiway-below relations in (strongly semicontinuous bc-domains are given. In terms of these properties, it is proved that strongly semicontinuous bc-domains, in particular strongly semicontinuous lattices, are all semi-FS domains.

  11. Domains in Ferroelectric Nanostructures

    Science.gov (United States)

    Gregg, Marty

    2010-03-01

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

  12. The Moral Maturity of Repeater Delinquents.

    Science.gov (United States)

    Petronio, Richard J.

    1980-01-01

    Differences in moral development (as conceived by Kohlberg) were examined in a sample of delinquent teenagers. The repeater group was not found, as had been hypothesized, to be lower on moral maturity than those who engaged in less delinquency. (GC)

  13. Star repeaters for fiber optic links.

    Science.gov (United States)

    McMahon, D H; Gravel, R L

    1977-02-01

    A star repeater combines the functions of a passive star coupler and a signal regenerating amplifier. By more effectively utilizing the light power radiated by a light emitting diode, the star repeater can, when used with small diameter channels, couple as much power to all receivers of a multiterminal link as would be coupled to the single receiver of a simple point-to-point link.

  14. Digital repeat analysis; setup and operation.

    Science.gov (United States)

    Nol, J; Isouard, G; Mirecki, J

    2006-06-01

    Since the emergence of digital imaging, there have been questions about the necessity of continuing reject analysis programs in imaging departments to evaluate performance and quality. As a marketing strategy, most suppliers of digital technology focus on the supremacy of the technology and its ability to reduce the number of repeats, resulting in less radiation doses given to patients and increased productivity in the department. On the other hand, quality assurance radiographers and radiologists believe that repeats are mainly related to positioning skills, and repeat analysis is the main tool to plan training needs to up-skill radiographers. A comparative study between conventional and digital imaging was undertaken to compare outcomes and evaluate the need for reject analysis. However, digital technology still being at its early development stages, setting a credible reject analysis program became the major task of the study. It took the department, with the help of the suppliers of the computed radiography reader and the picture archiving and communication system, over 2 years of software enhancement to build a reliable digital repeat analysis system. The results were supportive of both philosophies; the number of repeats as a result of exposure factors was reduced dramatically; however, the percentage of repeats as a result of positioning skills was slightly on the increase for the simple reason that some rejects in the conventional system qualifying for both exposure and positioning errors were classified as exposure error. The ability of digitally adjusting dark or light images reclassified some of those images as positioning errors.

  15. Quantum Key Distribution over Probabilistic Quantum Repeaters

    CERN Document Server

    Amirloo, Jeyran; Majedi, A Hamed

    2010-01-01

    A feasible route towards implementing long-distance quantum key distribution (QKD) systems relies on probabilistic schemes for entanglement distribution and swapping as proposed in the work of Duan, Lukin, Cirac, and Zoller (DLCZ) [Nature 414, 413 (2001)]. Here, we calculate the conditional throughput and fidelity of entanglement for DLCZ quantum repeaters, by accounting for the DLCZ self-purification property, in the presence of multiple excitations in the ensemble memories as well as loss and other sources of inefficiency in the channel and measurement modules. We then use our results to find the generation rate of secure key bits for QKD systems that rely on DLCZ quantum repeaters. We compare the key generation rate per logical memory employed in the two cases of with and without a repeater node. We find the cross-over distance beyond which the repeater system outperforms the non-repeater one. That provides us with the optimum inter-node distancing in quantum repeater systems. We also find the optimal exci...

  16. Remarkable selective constraints on exonic dinucleotide repeats.

    Science.gov (United States)

    Haasl, Ryan J; Payseur, Bret A

    2014-09-01

    Long dinucleotide repeats found in exons present a substantial mutational hazard: mutations at these loci occur often and generate frameshifts. Here, we provide clear and compelling evidence that exonic dinucleotides experience strong selective constraint. In humans, only 18 exonic dinucleotides have repeat lengths greater than six, which contrasts sharply with the genome-wide distribution of dinucleotides. We genotyped each of these dinucleotides in 200 humans from eight 1000 Genomes Project populations and found a near-absence of polymorphism. More remarkably, divergence data demonstrate that repeat lengths have been conserved across the primate phylogeny in spite of what is likely considerable mutational pressure. Coalescent simulations show that even a very low mutation rate at these loci fails to explain the anomalous patterns of polymorphism and divergence. Our data support two related selective constraints on the evolution of exonic dinucleotides: a short-term intolerance for any change to repeat length and a long-term prevention of increases to repeat length. In general, our results implicate purifying selection as the force that eliminates new, deleterious mutants at exonic dinucleotides. We briefly discuss the evolution of the longest exonic dinucleotide in the human genome--a 10 x CA repeat in fibroblast growth factor receptor-like 1 (FGFRL1)--that should possess a considerably greater mutation rate than any other exonic dinucleotide and therefore generate a large number of deleterious variants. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  17. Dynamic combinatorial libraries of artificial repeat proteins.

    Science.gov (United States)

    Eisenberg, Margarita; Shumacher, Inbal; Cohen-Luria, Rivka; Ashkenasy, Gonen

    2013-06-15

    Repeat proteins are found in almost all cellular systems, where they are involved in diverse molecular recognition processes. Recent studies have suggested that de novo designed repeat proteins may serve as universal binders, and might potentially be used as practical alternative to antibodies. We describe here a novel chemical methodology for producing small libraries of repeat proteins, and screening in parallel the ligand binding of library members. The first stage of this research involved the total synthesis of a consensus-based three-repeat tetratricopeptide (TPR) protein (~14 kDa), via sequential attachment of the respective peptides. Despite the effectiveness of the synthesis and ligation steps, this method was found to be too demanding for the production of proteins containing variable number of repeats. Additionally, the analysis of binding of the individual proteins was time consuming. Therefore, we designed and prepared novel dynamic combinatorial libraries (DCLs), and show that their equilibration can facilitate the formation of TPR proteins containing up to eight repeating units. Interestingly, equilibration of the library building blocks in the presence of the biologically relevant ligands, Hsp90 and Hsp70, induced their oligomerization into forming more of the proteins with large recognition surfaces. We suggest that this work presents a novel simple and rapid tool for the simultaneous screening of protein mixtures with variable binding surfaces, and for identifying new binders for ligands of interest.

  18. Just how versatile are domains?

    Directory of Open Access Journals (Sweden)

    Bornberg-Bauer Erich

    2008-10-01

    Full Text Available Abstract Background Creating new protein domain arrangements is a frequent mechanism of evolutionary innovation. While some domains always form the same combinations, others form many different arrangements. This ability, which is often referred to as versatility or promiscuity of domains, its a random evolutionary model in which a domain's promiscuity is based on its relative frequency of domains. Results We show that there is a clear relationship across genomes between the promiscuity of a given domain and its frequency. However, the strength of this relationship differs for different domains. We thus redefine domain promiscuity by defining a new index, DV I ("domain versatility index", which eliminates the effect of domain frequency. We explore links between a domain's versatility, when unlinked from abundance, and its biological properties. Conclusion Our results indicate that domains occurring as single domain proteins and domains appearing frequently at protein termini have a higher DV I. This is consistent with previous observations that the evolution of domain re-arrangements is primarily driven by fusion of pre-existing arrangements and single domains as well as loss of domains at protein termini. Furthermore, we studied the link between domain age, defined as the first appearance of a domain in the species tree, and the DV I. Contrary to previous studies based on domain promiscuity, it seems as if the DV I is age independent. Finally, we find that contrary to previously reported findings, versatility is lower in Eukaryotes. In summary, our measure of domain versatility indicates that a random attachment process is sufficient to explain the observed distribution of domain arrangements and that several views on domain promiscuity need to be revised.

  19. Data repeatability and acquisition techniques for Time-Domain Spectral Induced Polarization

    DEFF Research Database (Denmark)

    Legaz, Aurélie; Fiandaca, Gianluca; Pedersen, Jesper Bjergsted;

    2013-01-01

    A direct current (DC) resistivity and time domaininduced polarization (TDIP) survey was undertaken at a decommissionedlandfill site situated in Hørløkke, Denmark,for the purpose of mapping the waste deposits and to discriminateimportant geological units that control the hydrology ofthe surroundin...

  20. MO-FG-BRA-04: Leveraging the Abscopal Effect Via New Design Radiotherapy Biomaterials Loaded with Immune Checkpoint Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Y; Cifter, G; Altundal, Y; Moreau, M; Sajo, E [Univ Massachusetts Lowell, Lowell, MA (United States); Sinha, N [Wentworth Institute of Technology, Boston, MA (United States); Makrigiorgos, G [Dana Farber Cancer Institute, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Ngwa, W [Univ Massachusetts Lowell, Lowell, MA (United States); Dana Farber Cancer Institute, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)

    2015-06-15

    Purpose: Studies show that stereotactic body radiation therapy (SBRT) of a primary tumor in combination with immune checkpoint inhibitors (ICI) could Result in an immune-mediated regression of metastasis outside the radiation field, a phenomenon known as abscopal effect. However toxicities due to repeated systematic administration of ICI have been shown to be a major obstacle in clinical trials. Towards overcoming these toxicity limitations, we investigate a potential new approach whereby the ICI are administered via sustained in-situ release from radiotherapy (RT) biomaterials (e.g. fiducials) coated with a polymer containing the ICI. Methods: New design RT biomaterials were prepared by coating commercially available spacers/fiducials with a biocompatible polymer (PLGA) film containing fluorescent nanoparticles of size needed to load the ICI. The release of the nanoparticles was investigated in-vitro. Meanwhile, an experimentally determined in- vivo nanoparticle diffusion coefficient was employed in analytic calculations based on Fick’s second law to estimate the time for achieving the concentrations of ICI in the tumor draining lymph node (TDLN) that are needed to engender the abscopal effect during SBRT. The ICI investigated here was anti-CTLA-4 antibody (ipilimumab) at approved FDA concentrations. Results: Our in -vitro study results showed that RT biomaterials could be designed to achieve burst release of nanoparticles within one day. Meanwhile, our calculations indicate that for a 2 to 4 cm tumor it would take 4–22 days, respectively, following burst release, for the required concentration of ICI nanoparticles to accumulate in the TDLN during SBRT. Conclusion: Current investigations combining RT and immunotherapy involve repeated intravenous administration of ICI leading to significant systemic toxicities. Our preliminary results highlight a potential new approach for sustained in-situ release of the ICI from new design RT biomaterials. These results

  1. Axion domain wall baryogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Daido, Ryuji; Kitajima, Naoya [Department of Physics, Tohoku University,Sendai 980-8578 (Japan); Takahashi, Fuminobu [Department of Physics, Tohoku University,Sendai 980-8578 (Japan); Kavli IPMU, TODIAS, University of Tokyo,Kashiwa 277-8583 (Japan)

    2015-07-28

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

  2. Automated genotyping of dinucleotide repeat markers

    Energy Technology Data Exchange (ETDEWEB)

    Perlin, M.W.; Hoffman, E.P. [Carnegie Mellon Univ., Pittsburgh, PA (United States)]|[Univ. of Pittsburgh, PA (United States)

    1994-09-01

    The dinucleotide repeats (i.e., microsatellites) such as CA-repeats are a highly polymorphic, highly abundant class of PCR-amplifiable markers that have greatly streamlined genetic mapping experimentation. It is expected that over 30,000 such markers (including tri- and tetranucleotide repeats) will be characterized for routine use in the next few years. Since only size determination, and not sequencing, is required to determine alleles, in principle, dinucleotide repeat genotyping is easily performed on electrophoretic gels, and can be automated using DNA sequencers. Unfortunately, PCR stuttering with these markers generates not one band for each allele, but a pattern of bands. Since closely spaced alleles must be disambiguated by human scoring, this poses a key obstacle to full automation. We have developed methods that overcome this obstacle. Our model is that the observed data is generated by arithmetic superposition (i.e., convolution) of multiple allele patterns. By quantitatively measuring the size of each component band, and exploiting the unique stutter pattern associated with each marker, closely spaced alleles can be deconvolved; this unambiguously reconstructs the {open_quotes}true{close_quotes} allele bands, with stutter artifact removed. We used this approach in a system for automated diagnosis of (X-linked) Duchenne muscular dystrophy; four multiplexed CA-repeats within the dystrophin gene were assayed on a DNA sequencer. Our method accurately detected small variations in gel migration that shifted the allele size estimate. In 167 nonmutated alleles, 89% (149/167) showed no size variation, 9% (15/167) showed 1 bp variation, and 2% (3/167) showed 2 bp variation. We are currently developing a library of dinucleotide repeat patterns; together with our deconvolution methods, this library will enable fully automated genotyping of dinucleotide repeats from sizing data.

  3. Measuring the Activity of Leucine-Rich Repeat Kinase 2: A Kinase Involved in Parkinson's Disease

    Science.gov (United States)

    Lee, Byoung Dae; Li, Xiaojie; Dawson, Ted M.; Dawson, Valina L.

    2015-01-01

    Mutations in the LRRK2 (Leucine-Rich Repeat Kinase 2) gene are the most common cause of autosomal dominant Parkinson's disease. LRRK2 has multiple functional domains including a kinase domain. The kinase activity of LRRK2 is implicated in the pathogenesis of Parkinson's disease. Developing an assay to understand the mechanisms of LRRK2 kinase activity is important for the development of pharmacologic and therapeutic applications. Here, we describe how to measure in vitro LRRK2 kinase activity and its inhibition. PMID:21960214

  4. LRIG1 extracellular domain: structure and function analysis.

    Science.gov (United States)

    Xu, Yibin; Soo, Priscilla; Walker, Francesca; Zhang, Hui Hua; Redpath, Nicholas; Tan, Chin Wee; Nicola, Nicos A; Adams, Timothy E; Garrett, Thomas P; Zhang, Jian-Guo; Burgess, Antony W

    2015-05-22

    We have expressed and purified three soluble fragments of the human LRIG1-ECD (extracellular domain): the LRIG1-LRR (leucine-rich repeat) domain, the LRIG1-3Ig (immunoglobulin-like) domain, and the LRIG1-LRR-1Ig fragment using baculovirus vectors in insect cells. The two LRIG1 domains crystallised so that we have been able to determine the three-dimensional structures at 2.3Å resolution. We developed a three-dimensional structure for the LRIG1-ECD using homology modelling based on the LINGO-1 structure. The LRIG1-LRR domain and the LRIG1-LRR-1Ig fragment are monomers in solution, whereas the LRIG1-3Ig domain appears to be dimeric. We could not detect any binding of the LRIG1 domains or the LRIG1-LRR-1Ig fragment to the EGF receptor (EGFR), either in solution using biosensor analysis or when the EGFR was expressed on the cell surface. The FLAG-tagged LRIG1-LRR-1Ig fragment binds weakly to colon cancer cells regardless of the presence of EGFRs. Similarly, neither the soluble LRIG1-LRR nor the LRIG1-3Ig domains nor the full-length LRIG1 co-expressed in HEK293 cells inhibited ligand-stimulated activation of cell-surface EGFR.

  5. IN VITRO STUDY ON CYTOTOXIC EFFECTS OF THE ORGANOPHO-SPHOROUS PESTICIDE PROFENOFOS ON THE GILL CELL LINE, FG-9307, OF THE FLOUNDER (PARALICHTHYS OLIVACEUS)

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The FG-9307 cell line derived from the gill of flounder Paralichthys olivaceus was used in the present study to determine the acute cytotoxic effects of the organophosphorous pesticide, profenofos. It was found that the cell growth rate was markedly reduced by profenofos at the concentrations of 2.5, 5 and 7.5 mg/L tested; and that the fine structures of the cells were also altered by profenofos, as evidenced by dilation of nuclear membranes and mitochondria cristae, and presence of enlarged lysosomes with engulfed organelles and numerous vacuoles in the cytoplasm. Probably, mitochondria, the cell energy-generating sites, are the most prominent sites of profenofos cytotoxity in the cells. This seems to be the first report of the use of marine fish cell line for evaluation of the acute in vitro cytotoxicity of organophosphorus pesticide.

  6. Økologisk risikovurdering af genmodificeret dobbelt herbicidtolerant sojabønne linie FG72 i anmeldelse vedr. markedsføring under Forordning 1829/2003/EF

    DEFF Research Database (Denmark)

    Kjellsson, Gøsta; Damgaard, Christian; Sørensen, Jesper Givskov

    2012-01-01

    i Danmark, da de klimatiske forhold udelukker dette. En markedsføring af sojabønnen kan derfor ikke have nogen uøn-skede økologiske konsekvenser i Danmark. I dyrkningsområderne i Sydeuropa kan der ved uheld ske en iblanding af GM-sojabønnefrø i frø til udsæd af ikke-GM soja. En eventuel tilfældig...... spredning af GM-soja vurderes dog ikke at få nogen uønskede økologi-ske konsekvenser. BIOSCIENCE vurderer samlet, at der ikke kan forventes nogen uønskede økologiske konsekvenser for dyre- og planteliv ved markedsføring af den genmodificerede herbicidtolerante FG72-4-sojabønne til andre for-mål end dyrkning...

  7. Structure and organization of the mitochondrial DNA control region with tandemly repeated sequence in the Amazon ornamental fish.

    Science.gov (United States)

    Terencio, Maria Leandra; Schneider, Carlos Henrique; Gross, Maria Claudia; Feldberg, Eliana; Porto, Jorge Ivan Rebelo

    2013-02-01

    Tandemly repeated sequences are a common feature of vertebrate mitochondrial DNA control regions. However, questions still remain about their mode of evolution and function. To better understand patterns of variation in length and to explore the existence of previously described domain, we have characterized the control region structure of the Amazonian ornamental fish Nannostomus eques and Nannostomus unifasciatus. The control region ranged from 1121 to 1142 bp in length and could be separated into three domains: the domain associated with the extended terminal associated sequences, the central conserved domain, and the conserved sequence blocks domain. In the first domain, we encountered a sequence repeated 10 times in tandem (variable number tandem repeat (VNTR)) that could adopt an "inverted repetitions" type structural conformation. The results suggest that the VNTR pattern encountered in both N. eques and N. unifasciatus is consistent with the prerequisites of the illegitimate elongation model in which the unequal pairing of the chains near the 5'-end of the control region favors the formation of repetitions.

  8. Hybrid time/frequency domain modeling of nonlinear components

    DEFF Research Database (Denmark)

    Wiechowski, Wojciech Tomasz; Lykkegaard, Jan; Bak, Claus Leth

    2007-01-01

    model is used as a basis for its implementation. First, the linear network part is replaced with an ideal voltage source and a time domain (EMT) simulation is performed. During the initial oscillations, harmonic content of the converter currents is calculated at every period by a fast Fourier transform...... and the periodic steady state is identified. Obtained harmonic currents are assigned to current sources and used in the frequency domain calculation in the linear network. The obtained three-phase bus voltage is then inverse Fourier transformed and assigned to the voltage source and the time domain simulation...... is performed again. This process is repeated until the change in the magnitudes and phase angles of the fundamental and low order characteristic harmonics of the bus voltage is smaller then predefined precision indexes. The method is verified against precise time domain simulation. The convergence properties...

  9. On Binding Domains

    NARCIS (Netherlands)

    Everaert, M.B.H.

    2005-01-01

    In this paper I want to explore reasons for replacing Binding Theory based on the anaphor-pronoun dichotomy by a Binding Theory allowing more domains restricting/defining anaphoric dependencies. This will, thus, have consequences for the partitioning of anaphoric elements, presupposing more types of

  10. Cellulose binding domain proteins

    Science.gov (United States)

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

    1998-01-01

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

  11. Domain: Labour market

    NARCIS (Netherlands)

    Oude Mulders, J.; Wadensjö, E.; Hasselhorn, H.M.; Apt, W.

    This domain chapter is dedicated to summarize research on the effects of labour market contextual factors on labour market participation of older workers (aged 50+) and identify research gaps. While employment participation and the timing of (early) retirement is often modelled as an individual

  12. Normed Domains of Holomorphy

    Directory of Open Access Journals (Sweden)

    Steven G. Krantz

    2010-01-01

    Full Text Available We treat the classical concept of domain of holomorphy in ℂn when the holomorphic functions considered are restricted to lie in some Banach space. Positive and negative results are presented. A new view of the case n=1 is considered.

  13. Domain: Labour market

    NARCIS (Netherlands)

    Oude Mulders, J.; Wadensjö, E.; Hasselhorn, H.M.; Apt, W.

    2015-01-01

    This domain chapter is dedicated to summarize research on the effects of labour market contextual factors on labour market participation of older workers (aged 50+) and identify research gaps. While employment participation and the timing of (early) retirement is often modelled as an individual deci

  14. The relationship between circulating tumor cells counting and Cyfra21 -1,CEA,Fg%循环肿瘤细胞数目与血清中 Cyfra21-1、CEA、Fg 表达水平的关系

    Institute of Scientific and Technical Information of China (English)

    陈可绪; 陈东杰; 李毅斌; 张昱; 汪森明

    2015-01-01

    目的:探讨肿瘤患者外周血循环肿瘤细胞(CTCs)与常用的肿瘤指标细胞角质素19可溶片段(Cy-fra21-1)、癌胚抗原(CEA)及凝血功能指标纤维蛋白原(Fg)表达水平的关系,比较 CTCs 阳性组和阴性组转移灶数目差异。方法:采集66例进展期晚期肺癌住院患者治疗前7.5ml 外周血,保存于4℃冰箱中,24小时内由益善生物技术公司使用“免疫去除结合纳米过滤法”行 CTCs 检测。同时检测血清中 Cyfra21-1、CEA、Fg水平,收集并分析 CTCs 数目与转移灶数目、临床 T 分期、转移淋巴结的关系。结果:纳入患者中 CTCs 检出率为86.4%。CTCs 数目与 Cyfra21-1水平有相关关系,相关系数为0.365(P =0.003);CTCs 数目与 Fg 水平相关,相关系数为0.330(P =0.007);CEA 与 CTCs 两变量无明显相关性。两组患者的肿瘤转移器官数目大于3个的比例有显著差异。结论:两组患者 Cyfra21-1异常增高率有显著差异,且 CTCs 数目与 Cyfra21-1表达水平正相关,可由 Cyfra21-1初步估计 CTCs 水平。而外周血中 Fg 异常增高率无显著差异,但二者表达水平呈明显正相关,因此分析 CTCs 数目需要考虑 Fg 表达水平的影响。%Objective:To investigate the relevance between circulating tumor cells(CTCs)counting and the fol-lowing tumor markers:Cyfra21 -1,CEA,Fg,and compare the survival,sites of metastasis organs among patients strati-fied by CTCs counting.Methods:We selected 66 histologically diagnosed advanced lung cancer patients of progression period,applied CanpotrolTM,which developed by SurExam biotechnology company to detect CTCs in the blood,7. 5ml blood was needed before treatment for CTCs test.All the samples were stored at 4 cent degree after collection,and samples were tested within 24h.Serum concentration of Cyfra21 -1,CEA,Fg were detected to investigate the correla-tion of CTCs counting and tumor

  15. The effects of cholesterol concentration in lipid packing and domain registration in ternary mixture lipid multilayer

    Science.gov (United States)

    Ma, Yicong; Ghosh, Sajal; Connelly, Laura; Lal, Ratneshwar; Sinha, Sunil

    2013-03-01

    The effects of cholesterol in membrane rafts formation remain a mystery even until today. In our study of model membrane multilayer systems consisting of DPPC/DOPC/Cholesterol, we have characterized the morphology changes using AFM and optical microscopy, and the bilayer electron density profile using X-ray reflectivity, as a function of cholesterol concentration. In this presentation, we shall discuss how the cholesterol concentration affects the lipid packing within the bilayer, as well as the interlayer coupling of phase separated domains. X-ray scattering, AFM and optical microscopy which look at different length scales would constitute a complete picture. Our results may shed new light on the understanding of the role of cholesterol in raft formation in biological membranes. This work is supported by a grant from the Biomolecular Materials Program, Division of Materials Science and Engineering, Basic Energy Sciences, US Department of Energy under Award no. DE-FG02-04ER46173.

  16. An innovative browser-based data exploration tool with simultaneous scrolling in time and wavelength domains

    Science.gov (United States)

    Slater, Gregory L.; Schiff, David; De Pontieu, Bart; Tarbell, Theodore D.; Freeland, Samuel L.

    2017-08-01

    We present Cruiser, a new web tool for the precision interactive blending of image series across time and wavelength domains. Scrolling in two dimensions enables discovery and investigation of similarities and differences in structure and evolution across multiple wavelengths. Cruiser works in the latest versions of standards compliant browsers on both desktop and IOS platforms. Co-aligned data cubes have been generated for AIA, IRIS, and Hinode SOT FG, and image data from additional instruments, both space-based and ground-based, can be data sources. The tool has several movie playing and image adjustment controls which will be described in the poster and demonstrated on a MacOS notebook and iPad.

  17. Mining of simple sequence repeats in the Genome of Gentianaceae

    Directory of Open Access Journals (Sweden)

    R Sathishkumar

    2011-01-01

    Full Text Available Simple sequence repeats (SSRs or short tandem repeats are short repeat motifs that show high level of length polymorphism due to insertion or deletion mutations of one or more repeat types. Here, we present the detection and abundance of microsatellites or SSRs in nucleotide sequences of Gentianaceae family. A total of 545 SSRs were mined in 4698 nucleotide sequences downloaded from the National Center for Biotechnology Information (NCBI. Among the SSR sequences, the frequency of repeat type was about 429 -mono repeats, 99 -di repeats, 15 -tri repeats, and 2 --hexa repeats. Mononucleotide repeats were found to be abundant repeat types, about 78%, followed by dinucleotide repeats (18.16% among the SSR sequences. An attempt was made to design primer pairs for 545 identified SSRs but these were found only for 169 sequences.

  18. Human mitochondrial mTERF wraps around DNA through a left-handed superhelical tandem repeat.

    Science.gov (United States)

    Jiménez-Menéndez, Nereida; Fernández-Millán, Pablo; Rubio-Cosials, Anna; Arnan, Carme; Montoya, Julio; Jacobs, Howard T; Bernadó, Pau; Coll, Miquel; Usón, Isabel; Solà, Maria

    2010-07-01

    The regulation of mitochondrial DNA (mtDNA) processes is slowly being characterized at a structural level. We present here crystal structures of human mitochondrial regulator mTERF, a transcription termination factor also implicated in replication pausing, in complex with double-stranded DNA oligonucleotides containing the tRNA(Leu)(UUR) gene sequence. mTERF comprises nine left-handed helical tandem repeats that form a left-handed superhelix, the Zurdo domain.

  19. PolyQ repeat expansions in ATXN2 associated with ALS are CAA interrupted repeats.

    Directory of Open Access Journals (Sweden)

    Zhenming Yu

    Full Text Available Amyotrophic lateral sclerosis (ALS is a devastating, rapidly progressive disease leading to paralysis and death. Recently, intermediate length polyglutamine (polyQ repeats of 27-33 in ATAXIN-2 (ATXN2, encoding the ATXN2 protein, were found to increase risk for ALS. In ATXN2, polyQ expansions of ≥ 34, which are pure CAG repeat expansions, cause spinocerebellar ataxia type 2. However, similar length expansions that are interrupted with other codons, can present atypically with parkinsonism, suggesting that configuration of the repeat sequence plays an important role in disease manifestation in ATXN2 polyQ expansion diseases. Here we determined whether the expansions in ATXN2 associated with ALS were pure or interrupted CAG repeats, and defined single nucleotide polymorphisms (SNPs rs695871 and rs695872 in exon 1 of the gene, to assess haplotype association. We found that the expanded repeat alleles of 40 ALS patients and 9 long-repeat length controls were all interrupted, bearing 1-3 CAA codons within the CAG repeat. 21/21 expanded ALS chromosomes with 3CAA interruptions arose from one haplotype (GT, while 18/19 expanded ALS chromosomes with <3CAA interruptions arose from a different haplotype (CC. Moreover, age of disease onset was significantly earlier in patients bearing 3 interruptions vs fewer, and was distinct between haplotypes. These results indicate that CAG repeat expansions in ATXN2 associated with ALS are uniformly interrupted repeats and that the nature of the repeat sequence and haplotype, as well as length of polyQ repeat, may play a role in the neurological effect conferred by expansions in ATXN2.

  20. Repeatability of peripheral aberrations in young emmetropes.

    Science.gov (United States)

    Baskaran, Karthikeyan; Theagarayan, Baskar; Carius, Staffan; Gustafsson, Jörgen

    2010-10-01

    The purpose of this study is to assess the intrasession repeatability of ocular aberration measurements in the peripheral visual field with a commercially available Shack-Hartmann aberrometer (complete ophthalmic analysis system-high definition-vision research). The higher-order off-axis aberrations data in young healthy emmetropic eyes are also reported. The aberrations of the right eye of 18 emmetropes were measured using an aberrometer with an open field of view that allows peripheral measurements. Five repeated measures of ocular aberrations were obtained and assessed in steps of 10° out to ±40° in the horizontal visual field (nasal + and temporal -) and -20° in the inferior visual field. The coefficient of repeatability, coefficient of variation, and the intraclass correlation coefficient were calculated as a measure of intrasession repeatability. In all eccentric angles, the repeatability of the third- and fourth-order aberrations was better than the fifth and sixth order aberrations. The coefficient of variation was coefficient was >0.90 for the third and fourth order but reduced gradually for higher orders. There was no statistical significant difference in variance of total higher-order root mean square between on- and off-axis measurements (p > 0.05). The aberration data in this group of young emmetropes showed that the horizontal coma (C(3)(1)) was most positive at 40° in the temporal field, decreasing linearly toward negative values with increasing off-axis angle into the nasal field, whereas all other higher-order aberrations showed little or no change. The complete ophthalmic analysis system-high definition-vision research provides fast, repeatable, and valid peripheral aberration measurements and can be used efficiently to measure off-axis aberrations in the peripheral visual field.

  1. Safety of Repeated Yttrium-90 Radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Lam, Marnix G. E. H.; Louie, John D. [Stanford University School of Medicine, Division of Interventional Radiology (United States); Iagaru, Andrei H.; Goris, Michael L. [Stanford University School of Medicine, Division of Nuclear Medicine (United States); Sze, Daniel Y., E-mail: dansze@stanford.edu [Stanford University School of Medicine, Division of Interventional Radiology (United States)

    2013-10-15

    Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

  2. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Aubuchon, Adam C., E-mail: acaubuchon@gmail.com [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Chan, Michael D. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Lovato, James F. [Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Balamucki, Christopher J. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC (United States); McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States)

    2011-11-15

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  3. Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila.

    Science.gov (United States)

    Shieh, Shin-Yi; Bonini, Nancy M

    2011-12-15

    Spinocerebellar ataxia type 3 is one of the polyglutamine (polyQ) diseases, which are caused by a CAG-repeat expansion within the coding region of the associated genes. The CAG repeat specifies glutamine, and the expanded polyQ domain mutation confers dominant toxicity on the protein. Traditionally, studies have focused on protein toxicity in polyQ disease mechanisms. Recent findings, however, demonstrate that the CAG-repeat RNA, which encodes the toxic polyQ protein, also contributes to the disease in Drosophila. To provide insights into the nature of the RNA toxicity, we extracted brain-enriched RNA from flies expressing a toxic CAG-repeat mRNA (CAG100) and a non-toxic interrupted CAA/G mRNA repeat (CAA/G105) for microarray analysis. This approach identified 160 genes that are differentially expressed specifically in CAG100 flies. Functional annotation clustering analysis revealed several broad ontologies enriched in the CAG100 gene list, including iron ion binding and nucleotide binding. Intriguingly, transcripts for the Hsp70 genes, a powerful suppressor of polyQ and other human neurodegenerative diseases, were also upregulated. We therefore tested and showed that upregulation of heat shock protein 70 mitigates CAG-repeat RNA toxicity. We then assessed whether other modifiers of the pathogenic, expanded Ataxin-3 polyQ protein could also modify the CAG-repeat RNA toxicity. This approach identified the co-chaperone Tpr2, the transcriptional regulator Dpld, and the RNA-binding protein Orb2 as modifiers of both polyQ protein toxicity and CAG-repeat RNA-based toxicity. These findings suggest an overlap in the mechanisms of RNA and protein-based toxicity, providing insights into the pathogenicity of the RNA in polyQ disease.

  4. Copy number of tandem direct repeats within the inverted repeats of Marek's disease virus DNA.

    Science.gov (United States)

    Kanamori, A; Nakajima, K; Ikuta, K; Ueda, S; Kato, S; Hirai, K

    1986-12-01

    We previously reported that DNA of the oncogenic strain BC-1 of Marek's disease virus serotype 1 (MDV1) contains three units of tandem direct repeats with 132 base pair (bp) repeats within the inverted repeats of the long regions of the MDV1 genome, whereas the attenuated, nononcogenic viral DNA contains multiple units of tandem direct repeats (Maotani et al., 1986). In the present study, the difference in the copy numbers of 132 bp repeats of oncogenic and nononcogenic MDV1 DNAs in other strains of MDV1 was investigated by Southern blot hybridization. The main copy numbers in different oncogenic MDV1 strains differed: those of BC-1, JM and highly oncogenic Md5 were 3, 5 to 12 and 2, respectively. The viral DNA population with two units of repeats was small, but detectable, in cells infected with either the oncogenic BC-1 or JM strain. The MDV1 DNA in various MD cell lines contained either two units or both two and three units of repeats. The significance of the copy number of repeats in oncogenicity of MDV1 is discussed.

  5. Transition-Region/Coronal Signatures of Penumbral Microjets: Hi-C, SDO/AIA and Hinode (SOT/FG) Observations

    Science.gov (United States)

    Tiwari, Sanjiv K.; Alpert, Shane E.; Moore, Ronald L.; Winebarger, Amy R.

    2014-01-01

    Penumbral microjets are bright, transient features seen in the chromosphere of sunspot penumbrae. Katsuaka et al. (2007) noted their ubiquity and characterized them using the Ca II H-line filter on Hinode's Solar Optical Telescope (SOT). The jets are 1000{4000 km in length, 300{400 km in width, and last less than one minute. It was proposed that these penumbral microjets could contribute to the transition-region and coronal heating above sunspots. We examine whether these microjets appear in the transition-region (TR) and/or corona or are related{ temporally and spatially{ to similar brightenings in the TR and/or corona. First, we identify penumbral microjets with the SOT's Ca II H-line filter. The chosen sunspot is observed on July 11, 2012 from 18:50:00 UT to 20:00:00 UT at approx. 14 inches, -30 inches. We then examine the sunspot in the same field of view and at the same time in other wavelengths. We use the High Resolution Coronal Imager Telescope (Hi-C) at 193A and the 1600A, 304A, 171A, 193A, and 94A passbands of the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamic Observatory. We include examples of these jets and where they should appear in the other passbands, but find no signifcant association, except for a few jets with longer lifetimes and bigger sizes seen at locations in the penumbra with repeated stronger brightenings. We conclude that the normal microjets are not heated to transition-region/coronal temperatures, but the larger jets are.

  6. Time Domain Induced Polarization

    DEFF Research Database (Denmark)

    Fiandaca, Gianluca; Auken, Esben; Christiansen, Anders Vest

    2012-01-01

    Time-domain-induced polarization has significantly broadened its field of reference during the last decade, from mineral exploration to environmental geophysics, e.g., for clay and peat identification and landfill characterization. Though, insufficient modeling tools have hitherto limited the use...... of time-domaininduced polarization for wider purposes. For these reasons, a new forward code and inversion algorithm have been developed using the full-time decay of the induced polarization response, together with an accurate description of the transmitter waveform and of the receiver transfer function......%. Furthermore, the presence of low-pass filters in time-domain-induced polarization instruments affects the early times of the acquired decays (typically up to 100 ms) and has to be modeled in the forward response to avoid significant loss of resolution. The developed forward code has been implemented in a 1D...

  7. Expression of Anaplasma marginale ankyrin repeat-containing proteins during infection of the mammalian host and tick vector

    Science.gov (United States)

    Using searches of the NCBI conserved domain database and SMART genomic architecture analysis, we identified three ankyrin repeat-containing genes in Anaplasma marginale: AM705, AM926 and AM638. Recombinant protein was used to immunize mice and generate fusion hybridomas secreting protein-specific mo...

  8. Structural Determinants at the Interface of the ARC2 and LRR Domains Control the Activation of the NB-LRR Plant Immune Receptors Rx1 and Gpa2

    NARCIS (Netherlands)

    Slootweg, E.J.; Spiridon, L.N.; Roosien, J.; Butterbach, P.B.E.; Pomp, H.; Westerhof, L.B.; Wilbers, R.H.P.; Bakker, E.H.; Bakker, J.; Petrescu, A.J.; Smant, G.; Goverse, A.

    2013-01-01

    Many plant and animal immune receptors have a modular NB-LRR architecture in which a nucleotide-binding switch domain (NB-ARC) is tethered to a leucine-rich repeat sensor domain (LRR). The cooperation between the switch and sensor domains, which regulates the activation of these proteins, is poorly

  9. Scientific/Technical Report Science Literacy Project Award number-DE-FG02-06ER64286

    Energy Technology Data Exchange (ETDEWEB)

    Nasseh, Bizhan

    2011-02-28

    Ball State University (BSU) was the recipient of a U.S. Department of Energy award to develop educational games teaching science and math. The Science Media Program will merge Ball State University’s nationally recognized capabilities in education, technology, and communication to develop new, interactive, game-based media for the teaching and learning of science and scientific principles for K-12 students. BSU established a team of educators, researchers, scientists, animators, designers, technology specialists, and hired a professional media developer company (Outside Source Design) from Indianapolis. After six months discussions and assessments the project team selected the following 8 games in Math, Physics, Chemistry, and Biology, 2 from each discipline. The assembled teams were innovative and unique. This new model of development and production included a process that integrated all needed knowledge and expertise for the development of high quality science and math games for K-12 students. This new model has potential to be used by others for the development of the educational games. The uniqueness of the model is to integrate domain experts’ knowledge with researchers/quality control group, and combine a professional development team from the game development company with the academic game development team from Computer Science and Art departments at Ball State University. The developed games went through feasibility tests with selected students for improvement before use in the research activities.

  10. Y Se Repite = And It Repeats Itself

    Science.gov (United States)

    Katzew, Adriana

    2010-01-01

    In this article, the author discusses Y Se Repite [And It Repeats Itself], a project she conceptualized due to the growing number of Latino/a Mexican migrant workers in dairy farms in the state of Vermont. In 2006, approximately 2,000 Latinos/as--most of them undocumented Mexican migrant workers--worked throughout the state's dairy farms, yet…

  11. Repeater For A Digital-Communication Bus

    Science.gov (United States)

    Torres-Guzman, Esteban; Olson, Stephen; Heaps, Tim

    1993-01-01

    Digital repeater circuit designed to extend range of communication on MIL-STD-1553 bus beyond original maximum allowable length of 300 ft. Circuit provides two-way communication, one way at time, and conforms to specifications of MIL-STD-1553. Crosstalk and instability eliminated.

  12. Episodes of repeated sudden deafness following pregnancies.

    Science.gov (United States)

    Pawlak-Osinska, Katarzyna; Burduk, Pawel K; Kopczynski, Andrzej

    2009-04-01

    Sex hormones influence and provoke changes in hearing levels. Sudden deafness is rarely observed in pregnant women. The effective treatment of sudden deafness in pregnant women is a challenging problem. We present a case of repeatable, completely regressed sudden deafness in a woman during her first and second pregnancies.

  13. Repeated sprint training in normobaric hypoxia.

    Science.gov (United States)

    Galvin, Harvey M; Cooke, Karl; Sumners, David P; Mileva, Katya N; Bowtell, Joanna L

    2013-12-01

    Repeated sprint ability (RSA) is a critical success factor for intermittent sport performance. Repeated sprint training has been shown to improve RSA, we hypothesised that hypoxia would augment these training adaptations. Thirty male well-trained academy rugby union and rugby league players (18.4 ± 1.5 years, 1.83 ± 0.07 m, 88.1 ± 8.9 kg) participated in this single-blind repeated sprint training study. Participants completed 12 sessions of repeated sprint training (10 × 6 s, 30 s recovery) over 4 weeks in either hypoxia (13% FiO₂) or normoxia (21% FiO₂). Pretraining and post-training, participants completed sports specific endurance and sprint field tests and a 10 × 6 s RSA test on a non-motorised treadmill while measuring speed, heart rate, capillary blood lactate, muscle and cerebral deoxygenation and respiratory measures. Yo-Yo Intermittent Recovery Level 1 test performance improved after RS training in both groups, but gains were significantly greater in the hypoxic (33 ± 12%) than the normoxic group (14 ± 10%, prepeated aerobic high intensity workout than an equivalent normoxic training. Performance gains are evident in the short term (4 weeks), a period similar to a preseason training block.

  14. Adaptation and complexity in repeated games

    DEFF Research Database (Denmark)

    Maenner, Eliot Alexander

    2008-01-01

    The paper presents a learning model for two-player infinitely repeated games. In an inference step players construct minimally complex inferences of strategies based on observed play, and in an adaptation step players choose minimally complex best responses to an inference. When players randomly ...

  15. A Structured Group Program for Repeat Dieters.

    Science.gov (United States)

    McNamara, Kathleen

    1989-01-01

    Describes a structured group program for women who repeatedly diet and may be at risk of developing more serious eating disorders. Discusses sessions focusing on eating behavior as well as internal factors that contribute to low body esteem and food and weight preoccupation. Evaluates effectiveness of program by self-reports of members of two…

  16. Why Do Students Repeat Admissions Tests?

    Science.gov (United States)

    Jones, Martha S.

    Attitudes and beliefs about the admissions process, especially the role of standardized testing in admissions, were examined for students who took a standardized admissions test more than once. Their attitudes were compared with those of students who did not repeat the test. About 200 preveterinary students who had taken the Veterinary Aptitude…

  17. The Effect of Repeaters on Equating

    Science.gov (United States)

    Kim, HeeKyoung; Kolen, Michael J.

    2010-01-01

    Test equating might be affected by including in the equating analyses examinees who have taken the test previously. This study evaluated the effect of including such repeaters on Medical College Admission Test (MCAT) equating using a population invariance approach. Three-parameter logistic (3-PL) item response theory (IRT) true score and…

  18. Triggering of repeating earthquakes in central California

    Science.gov (United States)

    Wu, Chunquan; Gomberg, Joan; Ben-Naim, Eli; Johnson, Paul

    2014-01-01

    Dynamic stresses carried by transient seismic waves have been found capable of triggering earthquakes instantly in various tectonic settings. Delayed triggering may be even more common, but the mechanisms are not well understood. Catalogs of repeating earthquakes, earthquakes that recur repeatedly at the same location, provide ideal data sets to test the effects of transient dynamic perturbations on the timing of earthquake occurrence. Here we employ a catalog of 165 families containing ~2500 total repeating earthquakes to test whether dynamic perturbations from local, regional, and teleseismic earthquakes change recurrence intervals. The distance to the earthquake generating the perturbing waves is a proxy for the relative potential contributions of static and dynamic deformations, because static deformations decay more rapidly with distance. Clear changes followed the nearby 2004 Mw6 Parkfield earthquake, so we study only repeaters prior to its origin time. We apply a Monte Carlo approach to compare the observed number of shortened recurrence intervals following dynamic perturbations with the distribution of this number estimated for randomized perturbation times. We examine the comparison for a series of dynamic stress peak amplitude and distance thresholds. The results suggest a weak correlation between dynamic perturbations in excess of ~20 kPa and shortened recurrence intervals, for both nearby and remote perturbations.

  19. A Repeater in the Language Laboratory

    Science.gov (United States)

    Griffiths, B. T.

    1969-01-01

    Discusses the feasilility of the use of repeater devices in the language laboratory in order to enable the student to "recapitulate effortlessly and and indefinitely any utterance of any length which is causing him difficulty or is of special interest. (FWB)

  20. The Differential Effects of Repeating Kindergarten

    Science.gov (United States)

    Burkam, David T.; LoGerfo, Laura; Ready, Doug; Lee, Valerie E.

    2007-01-01

    We use the Early Childhood Longitudinal Study to investigate national patterns addressing (a) who repeats kindergarten, and (b) the subsequent cognitive effects of this event. Using OLS regression techniques, we investigate 1st-time kindergartners who are promoted, 1st-time kindergartners who are retained, and children who are already repeating…

  1. Preventing Repeat Teen Births PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2013-04-02

    This 60 second public service announcement is based on the April 2013 CDC Vital Signs report, which discusses repeat teen births and ways teens, parents and guardians, health care providers, and communities can help prevent them.  Created: 4/2/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 4/2/2013.

  2. Epigenetics and triplet repeat neurological diseases

    Directory of Open Access Journals (Sweden)

    Sathiji eNageshwaran

    2015-12-01

    Full Text Available The term ‘junk DNA’ has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterchromatinised resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions frequently exist as dinucleotide, trinucleotide and tetranucleotide repeats. The association between repetitive regions and disease was emphasised following the discovery of abnormal trinucleotide repeats underlying spinal and bulbar muscular atrophy (Kennedy’s disease and fragile X syndrome of mental retardation (FRAXA in 1991. In this review we provide a brief overview of epigenetic mechanisms and then focus on several diseases caused by DNA triplet-repeat expansions, which exhibit diverse epigenetic effects. It is clear that the emerging field of epigenetics is already generating novel potential therapeutic avenues for this group of largely incurable diseases.

  3. Costly renegotiation in repeated Bertand games

    DEFF Research Database (Denmark)

    Andersson, Ola; Wengström, Erik Roland

    2010-01-01

    This paper extends the concept of weak renegotiation-proof equilibrium (WRP) to allow for costly renegotiation and shows that even small renegotiation costs can have dramatic effects on the set of equilibria. More specifically, the paper analyzes the infinitely repeated Bertrand game. It is shown...

  4. EVOLUTION AND RECOMBINATION OF BOVINE DNA REPEATS

    NARCIS (Netherlands)

    JOBSE, C; BUNTJER, JB; HAAGSMA, N; BREUKELMAN, HJ; BEINTEMA, JJ; LENSTRA, JA

    The history of the abundant repeat elements in the bovine genome has been studied by comparative hybridization and PCR. The Bov-A and Bov-B SINE elements both emerged just after the divergence of the Camelidae and the true ruminants. A 31-bp subrepeat motif in satellites of the Bovidae species

  5. Building Fluency through the Repeated Reading Method

    Science.gov (United States)

    Cohen, Joshua

    2011-01-01

    For the last two years the author has used Repeated Reading (RR) to teach reading fluency in English as a Foreign Language classrooms in colleges and universities in Japan. RR is a method where the student reads and rereads a text silently or aloud from two to four times to reach a predetermined level of speed, accuracy, and comprehension. RR…

  6. History repeats itself: genomic divergence in copepods.

    Science.gov (United States)

    Renaut, Sébastien; Dion-Côté, Anne-Marie

    2016-04-01

    Press stop, erase everything from now till some arbitrary time in the past and start recording life as it evolves once again. Would you see the same tape of life playing itself over and over, or would a different story unfold every time? The late Steven Jay Gould called this experiment replaying the tape of life and argued that any replay of the tape would lead evolution down a pathway radically different from the road actually taken (Gould 1989). This thought experiment has puzzled evolutionary biologists for a long time: how repeatable are evolutionary events? And if history does indeed repeat itself, what are the factors that may help us predict the path taken? A powerful means to address these questions at a small evolutionary scale is to study closely related populations that have evolved independently, under similar environmental conditions. This is precisely what Pereira et al. (2016) set out to do using marine copepods Tigriopus californicus, and present their results in this issue of Molecular Ecology. They show that evolution can be repeatable and even partly predictable, at least at the molecular level. As expected from theory, patterns of divergence were shaped by natural selection. At the same time, strong genetic drift due to small population sizes also constrained evolution down a similar evolutionary road, and probably contributed to repeatable patterns of genomic divergence.

  7. Costly renegotiation in repeated Bertand games

    DEFF Research Database (Denmark)

    Andersson, Ola; Wengström, Erik Roland

    2010-01-01

    This paper extends the concept of weak renegotiation-proof equilibrium (WRP) to allow for costly renegotiation and shows that even small renegotiation costs can have dramatic effects on the set of equilibria. More specifically, the paper analyzes the infinitely repeated Bertrand game. It is shown...

  8. Photometric Repeatability of Scanned Imagery: UVIS

    Science.gov (United States)

    Shanahan, Clare E.; McCullough, Peter; Baggett, Sylvia

    2017-08-01

    We provide the preliminary results of a study on the photometric repeatability of spatial scans of bright, isolated white dwarf stars with the UVIS channel of the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope (HST). We analyze straight-line scans from the first pair of identical orbits of HST program 14878 to assess if sub 0.1% repeatability can be attained with WFC3/UVIS. This study is motivated by the desire to achieve better signal-to-noise in the UVIS contamination and stability monitor, in which observations of standard stars in staring mode have been taken from the installation of WFC3 in 2009 to the present to assess temporal photometric stability. Higher signal to noise in this program would greatly benefit the sensitivity to detect contamination, and to better characterize the observed small throughput drifts over time. We find excellent repeatability between identical visits of program 14878, with sub 0.1% repeatability achieved in most filters. These! results support the initiative to transition the staring mode UVIS contamination and photometric stability monitor from staring mode images to spatial scans.

  9. Repeat surgery after failed midurethral slings

    DEFF Research Database (Denmark)

    Foss Hansen, Margrethe; Lose, Gunnar; Kesmodel, Ulrik Schiøler

    2016-01-01

    MUS from 1998 through 2007. The outcome was repeat surgery with any subsequent procedure code for urinary incontinence within a 5-year period of the first procedure. RESULTS: A total of 5,820 women (mean age 55.4 years, ± 12.1) were registered with a synthetic MUS, and 354 (6 %) underwent reoperation...

  10. EVOLUTION AND RECOMBINATION OF BOVINE DNA REPEATS

    NARCIS (Netherlands)

    JOBSE, C; BUNTJER, JB; HAAGSMA, N; BREUKELMAN, HJ; BEINTEMA, JJ; LENSTRA, JA

    1995-01-01

    The history of the abundant repeat elements in the bovine genome has been studied by comparative hybridization and PCR. The Bov-A and Bov-B SINE elements both emerged just after the divergence of the Camelidae and the true ruminants. A 31-bp subrepeat motif in satellites of the Bovidae species cattl

  11. Multivariate linear models and repeated measurements revisited

    DEFF Research Database (Denmark)

    Dalgaard, Peter

    2009-01-01

    Methods for generalized analysis of variance based on multivariate normal theory have been known for many years. In a repeated measurements context, it is most often of interest to consider transformed responses, typically within-subject contrasts or averages. Efficiency considerations leads...

  12. On balanced minimal repeated measurements designs

    Directory of Open Access Journals (Sweden)

    Shakeel Ahmad Mir

    2014-10-01

    Full Text Available Repeated Measurements designs are concerned with scientific experiments in which each experimental unit is assigned more than once to a treatment either different or identical. This class of designs has the property that the unbiased estimators for elementary contrasts among direct and residual effects are obtainable. Afsarinejad (1983 provided a method of constructing balanced Minimal Repeated Measurements designs p < t , when t is an odd or prime power, one or more than one treatment may occur more than once in some sequences and  designs so constructed no longer remain uniform in periods. In this paper an attempt has been made to provide a new method to overcome this drawback. Specifically, two cases have been considered                RM[t,n=t(t-t/(p-1,p], λ2=1 for balanced minimal repeated measurements designs and  RM[t,n=2t(t-t/(p-1,p], λ2=2 for balanced  repeated measurements designs. In addition , a method has been provided for constructing              extra-balanced minimal designs for special case RM[t,n=t2/(p-1,p], λ2=1.

  13. Comparison of the domain and frequency domain state feedbacks

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, S.Y.

    1986-01-01

    In this paper, we present explicitly the equivalence of the time domain and frequency domain state feedbacks, as well as the dynamic state feedback and a modified frequency domain state feedback, from the closed-loop transfer function point of view. The difference of the two approaches is also shown.

  14. An examination of the origin and evolution of additional tandem repeats in the mitochondrial DNA control region of Japanese sika deer (Cervus Nippon).

    Science.gov (United States)

    Ba, Hengxing; Wu, Lang; Liu, Zongyue; Li, Chunyi

    2016-01-01

    Tandem repeat units are only detected in the left domain of the mitochondrial DNA control region in sika deer. Previous studies showed that Japanese sika deer have more tandem repeat units than its cousins from the Asian continent and Taiwan, which often have only three repeat units. To determine the origin and evolution of these additional repeat units in Japanese sika deer, we obtained the sequence of repeat units from an expanded dataset of the control region from all sika deer lineages. The functional constraint is inferred to act on the first repeat unit because this repeat has the least sequence divergence in comparison to the other units. Based on slipped-strand mispairing mechanisms, the illegitimate elongation model could account for the addition or deletion of these additional repeat units in the Japanese sika deer population. We also report that these additional repeat units could be occurring in the internal positions of tandem repeat regions, possibly via coupling with a homogenization mechanism within and among these lineages. Moreover, the increased number of repeat units in the Japanese sika deer population could reflect a balance between mutation and selection, as well as genetic drift.

  15. Domains of Disoriented Chiral Condensate

    CERN Document Server

    Amado, R D; Lu, Yang

    1996-01-01

    The probability distribution of neutral pion fraction from independent domains of disoriented chiral condensate is characterized. The signal for the condensate is clear for a small number of domains but is greatly reduced for more than three.

  16. 47 CFR 80.1179 - On-board repeater limitations.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false On-board repeater limitations. 80.1179 Section... On-board repeater limitations. When an on-board repeater is used, the following limitations must be met: (a) The on-board repeater antenna must be located no higher than 3 meters (10 feet) above...

  17. Summarization by domain ontology navigation

    DEFF Research Database (Denmark)

    Andreasen, Troels; Bulskov, Henrik

    2013-01-01

    of the subject. In between these two extremes, conceptual summaries encompass selected concepts derived using background knowledge. We address in this paper an approach where conceptual summaries are provided through a conceptualization as given by an ontology. The ontology guiding the summarization can...... be a simple taxonomy or a generative domain ontology. A domain ontology can be provided by a preanalysis of a domain corpus and can be used to condense improved summaries that better reflects the conceptualization of a given domain....

  18. Genome cartography through domain annotation.

    Science.gov (United States)

    Ponting, C P; Dickens, N J

    2001-01-01

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

  19. Ligand binding by PDZ domains

    OpenAIRE

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

    2012-01-01

    The postsynaptic density protein-95/disks large/zonula occludens-1 (PDZ) protein domain family is one of the most common proteinprotein interaction modules in mammalian cells, with paralogs present in several hundred human proteins. PDZ domains are found in most cell types, but neuronal proteins, for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, s...

  20. Structural Studies of a Four-MBT Repeat Protein MBTD1

    Energy Technology Data Exchange (ETDEWEB)

    Eryilmaz, Jitka; Pan, Patricia; Amaya, Maria F.; Allali-Hassani, Abdellah; Dong, Aiping; Adams-Cioaba, Melanie A.; MacKenzie, Farrell; Vedadi, Masoud; Min, Jinrong; (Toronto); (Toronto)

    2010-08-17

    The Polycomb group (PcG) of proteins is a family of important developmental regulators. The respective members function as large protein complexes involved in establishment and maintenance of transcriptional repression of developmental control genes. MBTD1, Malignant Brain Tumor domain-containing protein 1, is one such PcG protein. MBTD1 contains four MBT repeats. We have determined the crystal structure of MBTD1 (residues 130-566aa covering the 4 MBT repeats) at 2.5 {angstrom} resolution by X-ray crystallography. The crystal structure of MBTD1 reveals its similarity to another four-MBT-repeat protein L3MBTL2, which binds lower methylated lysine histones. Fluorescence polarization experiments confirmed that MBTD1 preferentially binds mono- and di-methyllysine histone peptides, like L3MBTL1 and L3MBTL2. All known MBT-peptide complex structures characterized to date do not exhibit strong histone peptide sequence selectivity, and use a 'cavity insertion recognition mode' to recognize the methylated lysine with the deeply buried methyl-lysine forming extensive interactions with the protein while the peptide residues flanking methyl-lysine forming very few contacts. Nevertheless, our mutagenesis data based on L3MBTL1 suggested that the histone peptides could not bind to MBT repeats in any orientation. The four MBT repeats in MBTD1 exhibits an asymmetric rhomboid architecture. Like other MBT repeat proteins characterized so far, MBTD1 binds mono- or dimethylated lysine histones through one of its four MBT repeats utilizing a semi-aromatic cage.

  1. Anterior segment biometry: a study and review of resolution and repeatability data.

    Science.gov (United States)

    Reinstein, Dan Z; Gobbe, Marine; Archer, Timothy J

    2012-07-01

    To obtain comparable resolution and repeatability data for a selection of anterior segment imaging devices. A standard letter of request was sent in May 2008 to each device manufacturer requesting resolution and repeatability data for its device to be provided according to specific definitions and protocol; if this was not already published in the peer-reviewed domain, compliant raw data were required. Where applicable, repeatability data were reported for corneal vertex corneal thickness; epithelial and flap thickness; minimum corneal thickness; corneal, epithelial and flap thickness mapping for the central 6-mm diameter; minimum residual stromal thickness; angle-to-angle diameter; sulcus-to-sulcus diameter; and anterior chamber depth. To summarize published repeatability data, a complete review of the peer-reviewed literature waas performed. Nine of the 13 manufacturers contacted agreed to take part and provided the data requested: Pentacam HD (Oculus Optikgeräte GmbH), Galilei (Ziemer), Visante OCT (Carl Zeiss Meditec), SL-OCT (Haag-Streit), RTVue (Optovue), Artemis (ArcScan), Vumax (Sonomed), HiScan (Opticon), and Eye Cubed (Ellex/Innovative). Only one (Carl Zeiss Meditec) of 9 manufacturers was able to provide the data directly upon request, without performing a prospective study. Five of the 9 manufacturers were able to provide a complete set of repeatability data for all parameters measurable with their device; the remaining 4 manufacturers admitted that repeatability of some parameters was unknown. Both literature and manufacturers' data on file were lacking and required the study to be performed. This report provides an imperfect, but most comprehensive to date, resolution and repeatability data review of biometric devices intended for surgical planning. Copyright 2012, SLACK Incorporated.

  2. Tandem repeat markers as novel diagnostic tools for high resolution fingerprinting of Wolbachia

    Directory of Open Access Journals (Sweden)

    Riegler Markus

    2012-01-01

    Full Text Available Abstract Background Strains of the endosymbiotic bacterium Wolbachia pipientis are extremely diverse both genotypically and in terms of their induced phenotypes in invertebrate hosts. Despite extensive molecular characterisation of Wolbachia diversity, little is known about the actual genomic diversity within or between closely related strains that group tightly on the basis of existing gene marker systems, including Multiple Locus Sequence Typing (MLST. There is an urgent need for higher resolution fingerprinting markers of Wolbachia for studies of population genetics, horizontal transmission and experimental evolution. Results The genome of the wMel Wolbachia strain that infects Drosophila melanogaster contains inter- and intragenic tandem repeats that may evolve through expansion or contraction. We identified hypervariable regions in wMel, including intergenic Variable Number Tandem Repeats (VNTRs, and genes encoding ankyrin (ANK repeat domains. We amplified these markers from 14 related Wolbachia strains belonging to supergroup A and were successful in differentiating size polymorphic alleles. Because of their tandemly repeated structure and length polymorphism, the markers can be used in a PCR-diagnostic multilocus typing approach, analogous to the Multiple Locus VNTR Analysis (MLVA established for many other bacteria and organisms. The isolated markers are highly specific for supergroup A and not informative for other supergroups. However, in silico analysis of completed genomes from other supergroups revealed the presence of tandem repeats that are variable and could therefore be useful for typing target strains. Conclusions Wolbachia genomes contain inter- and intragenic tandem repeats that evolve through expansion or contraction. A selection of polymorphic tandem repeats is a novel and useful PCR diagnostic extension to the existing MLST typing system of Wolbachia, as it allows rapid and inexpensive high-throughput fingerprinting of

  3. Chaotic domains: A numerical investigation

    OpenAIRE

    Cross, M. C.; Meiron, D.; Tu, Yuhai

    1994-01-01

    We study the chaotic domain state in rotating convection using a model equation that allows for a continuous range of roll orientations as in the experimental system. Methods are developed for extracting the domain configuration from the resulting patterns that should be applicable to a wide range of domain states. Comparison with the truncated three mode amplitude equation description is made.

  4. Gershgorin domains for partitioned matrices

    NARCIS (Netherlands)

    Sluis, A. van der

    1979-01-01

    Inclusion domains for the eigenvalues of a partitioned matrix are specified in terms of perturbations of its diagonal blocks. The size of such perturbations is measured using the Kantorovitch-Robert-Deutsch vectorial norms. The inclusion domains obtained thereby are compared with inclusion domains o

  5. Feature-level domain adaptation

    DEFF Research Database (Denmark)

    Kouw, Wouter M.; Van Der Maaten, Laurens J P; Krijthe, Jesse H.

    2016-01-01

    Domain adaptation is the supervised learning setting in which the training and test data are sampled from different distributions: training data is sampled from a source domain, whilst test data is sampled from a target domain. This paper proposes and studies an approach, called feature...

  6. Classification of Noncommutative Domain Algebras

    CERN Document Server

    Arias, Alvaro

    2012-01-01

    Noncommutative domain algebras are noncommutative analogues of the algebras of holomorphic functions on domains of $\\C^n$ defined by holomorphic polynomials, and they generalize the noncommutative Hardy algebras. We present here a complete classification of these algebras based upon techniques inspired by multivariate complex analysis, and more specifically the classification of domains in hermitian spaces up to biholomorphic equivalence.

  7. CTCF regulates the local epigenetic state of ribosomal DNA repeats

    Directory of Open Access Journals (Sweden)

    van de Nobelen Suzanne

    2010-11-01

    Full Text Available Abstract Background CCCTC binding factor (CTCF is a highly conserved zinc finger protein, which is involved in chromatin organization, local histone modifications, and RNA polymerase II-mediated gene transcription. CTCF may act by binding tightly to DNA and recruiting other proteins to mediate its various functions in the nucleus. To further explore the role of this essential factor, we used a mass spectrometry-based approach to screen for novel CTCF-interacting partners. Results Using biotinylated CTCF as bait, we identified upstream binding factor (UBF and multiple other components of the RNA polymerase I complex as potential CTCF-interacting partners. Interestingly, CTCFL, the testis-specific paralog of CTCF, also binds UBF. The interaction between CTCF(L and UBF is direct, and requires the zinc finger domain of CTCF(L and the high mobility group (HMG-box 1 and dimerization domain of UBF. Because UBF is involved in RNA polymerase I-mediated ribosomal (rRNA transcription, we analyzed CTCF binding to the rDNA repeat. We found that CTCF bound to a site upstream of the rDNA spacer promoter and preferred non-methylated over methylated rDNA. DNA binding by CTCF in turn stimulated binding of UBF. Absence of CTCF in cultured cells resulted in decreased association of UBF with rDNA and in nucleolar fusion. Furthermore, lack of CTCF led to reduced binding of RNA polymerase I and variant histone H2A.Z near the rDNA spacer promoter, a loss of specific histone modifications, and diminished transcription of non-coding RNA from the spacer promoter. Conclusions UBF is the first common interaction partner of CTCF and CTCFL, suggesting a role for these proteins in chromatin organization of the rDNA repeats. We propose that CTCF affects RNA polymerase I-mediated events globally by controlling nucleolar number, and locally by regulating chromatin at the rDNA spacer promoter, similar to RNA polymerase II promoters. CTCF may load UBF onto rDNA, thereby forming

  8. Structural Studies of Metastable and Ground State Vortex Lattice Domains in MgB2

    Science.gov (United States)

    de Waard, E. R.; Kuhn, S. J.; Rastovski, C.; Eskildsen, M. R.; Leishman, A.; Dewhurst, C. D.; Debeer-Schmitt, L.; Littrell, K.; Karpinski, J.; Zhigadlo, N. D.

    2015-03-01

    Small-angle neutron scattering (SANS) studies of the vortex lattice (VL) in the type-II superconductor MgB2 have revealed an unprecedented degree of metastability that is demonstrably not due to vortex pinning, [C. Rastovski et al . , Phys. Rev. Lett. 111, 107002 (2013)]. Application of an AC magnetic field to drive the VL to the ground state revealed a two-step power law behavior, indicating a slow nucleation of ground state domains followed by a faster growth. The dependence on the number of applied AC cycles is reminiscent of jamming of soft, frictionless spheres. Here, we report on detailed structural studies of both metastable and ground state VL domains. These include measurements of VL correlation lengths as well as spatially resolved SANS measurements showing the VL domain distribution within the MgB2 single crystal. We discuss these results and how they may help to resolve the mechanism responsible for stabilizing the metastable VL phases. This work is supported by the U.S. Department of Energy, Office of Basic Energy Sciences under Award DE-FG02-10ER46783.

  9. Stability of dental waxes following repeated heatings.

    Science.gov (United States)

    Kotsiomiti, E; McCabe, J F

    1995-02-01

    The flow and strength properties of dental waxes were examined following excessive and repeated heatings of the materials. For one product, the flow at 40 +/- 0.5 degrees C was reduced by 25.3% following heating above 200 degrees C. A decrease of the elastic modulus at 20 +/- 1 degree C by approximately 66% was observed in some cases after the heating temperature had been increased to 300 degrees C. Property variations were related to compositional changes, which were investigated by infrared spectoscopy and thermal analysis. Exposure of dental waxes to temperatures higher than 200 degrees C, particularly if it is repeated, may affect the composition and properties, resulting in inferior materials.

  10. Learning with repeated-game strategies.

    Science.gov (United States)

    Ioannou, Christos A; Romero, Julian

    2014-01-01

    We use the self-tuning Experience Weighted Attraction model with repeated-game strategies as a computer testbed to examine the relative frequency, speed of convergence and progression of a set of repeated-game strategies in four symmetric 2 × 2 games: Prisoner's Dilemma, Battle of the Sexes, Stag-Hunt, and Chicken. In the Prisoner's Dilemma game, we find that the strategy with the most occurrences is the "Grim-Trigger." In the Battle of the Sexes game, a cooperative pair that alternates between the two pure-strategy Nash equilibria emerges as the one with the most occurrences. In the Stag-Hunt and Chicken games, the "Win-Stay, Lose-Shift" and "Grim-Trigger" strategies are the ones with the most occurrences. Overall, the pairs that converged quickly ended up at the cooperative outcomes, whereas the ones that were extremely slow to reach convergence ended up at non-cooperative outcomes.

  11. Learning With Repeated-Game Strategies

    Directory of Open Access Journals (Sweden)

    Christos A. Ioannou

    2014-07-01

    Full Text Available We use the self-tuning Experience Weighted Attraction model with repeated-game strategies as a computer testbed to examine the relative frequency, speed of convergence and progression of a set of repeated-game strategies in four symmetric 2x2 games: Prisoner's Dilemma, Battle of the Sexes, Stag-Hunt, and Chicken. In the Prisoner's Dilemma game, we fi□nd that the strategy with the most occurrences is the Grim-Trigger. In the Battle of the Sexes game, a cooperative pair that alternates between the two pure-strategy Nash equilibria emerges as the one with the most occurrences. In the Stag-Hunt and Chicken games, the Win-Stay, Lose-Shift and Grim-Trigger strategies are the ones with the most occurrences. Overall, the pairs that converged quickly ended up at the cooperative outcomes, whereas the ones that were extremely slow to reach convergence ended up at non-cooperative outcomes.

  12. Quantum repeaters with entangled coherent states

    CERN Document Server

    Sangouard, Nicolas; Gisin, Nicolas; Laurat, Julien; Tualle-Brouri, Rosa; Grangier, Philippe

    2009-01-01

    Entangled coherent states can be prepared remotely by subtracting non-locally a single photon from two quantum superpositions of coherent states, the so-called "Schroedinger's cat" state. Such entanglement can further be distributed over longer distances by successive entanglement swapping operations using linear optics and photon-number resolving detectors. The aim of this paper is to evaluate the performance of this approach to quantum repeaters for long distance quantum communications. Despite many attractive features at first sight, we show that, when using state-of-the-art photon counters and quantum memories, they do not achieve higher entanglement generation rates than repeaters based on single-photon entanglement. We discuss potential developments which may take better advantage of the richness of entanglement based on continuous variables, including in particular efficient parity measurements.

  13. Quantum repeaters based on heralded qubit amplifiers

    CERN Document Server

    Minář, Jiří; Sangouard, Nicolas

    2011-01-01

    We present a quantum repeater scheme based on the recently proposed qubit amplifier [N. Gisin, S. Pironio and N. Sangouard, Phys. Rev. Lett. 105, 070501 (2010)]. It relies on a on-demand entangled-photon pair source which uses on-demand single-photon sources, linear optical elements and atomic ensembles. Interestingly, the imperfections affecting the states created from this source, caused e.g. by detectors with non-unit efficiencies, are systematically purified from an entanglement swapping operation based on a two-photon detection. This allows the distribution of entanglement over very long distances with a high fidelity, i.e. without vacuum components and multiphoton errors. Therefore, the resulting quantum repeater architecture does not necessitate final postselections and thus achieves high entanglement distribution rates. This also provides unique opportunities for device-independent quantum key distribution over long distances with linear optics and atomic ensembles.

  14. Nonparametric additive regression for repeatedly measured data

    KAUST Repository

    Carroll, R. J.

    2009-05-20

    We develop an easily computed smooth backfitting algorithm for additive model fitting in repeated measures problems. Our methodology easily copes with various settings, such as when some covariates are the same over repeated response measurements. We allow for a working covariance matrix for the regression errors, showing that our method is most efficient when the correct covariance matrix is used. The component functions achieve the known asymptotic variance lower bound for the scalar argument case. Smooth backfitting also leads directly to design-independent biases in the local linear case. Simulations show our estimator has smaller variance than the usual kernel estimator. This is also illustrated by an example from nutritional epidemiology. © 2009 Biometrika Trust.

  15. Repeat-PPM Super-Symbol Synchronization

    Science.gov (United States)

    Connelly, J.

    2016-11-01

    To attain a wider range of data rates in pulse position modulation (PPM) schemes with constrained pulse durations, the sender can repeat a PPM symbol multiple times, forming a super-symbol. In addition to the slot and symbol synchronization typically required for PPM, the receiver must also properly align the noisy super-symbols. We present a low-complexity approximation of the maximum-likelihood method for performing super-symbol synchronization without use of synchronization sequences. We provide simulation results demonstrating performance advantage when PPM symbols are spread by a pseudo-noise sequence, as opposed to simply repeating. Additionally, the results suggest that this super-symbol synchronization technique requires signal levels below those required for reliable communication. This validates that the PPM spreading approach proposed to CCSDS can work properly as part of the overall scheme.

  16. High-bandwidth hybrid quantum repeater.

    Science.gov (United States)

    Munro, W J; Van Meter, R; Louis, Sebastien G R; Nemoto, Kae

    2008-07-25

    We present a physical- and link-level design for the creation of entangled pairs to be used in quantum repeater applications where one can control the noise level of the initially distributed pairs. The system can tune dynamically, trading initial fidelity for success probability, from high fidelity pairs (F=0.98 or above) to moderate fidelity pairs. The same physical resources that create the long-distance entanglement are used to implement the local gates required for entanglement purification and swapping, creating a homogeneous repeater architecture. Optimizing the noise properties of the initially distributed pairs significantly improves the rate of generating long-distance Bell pairs. Finally, we discuss the performance trade-off between spatial and temporal resources.

  17. Do Gamma-Ray Burst Sources Repeat?

    OpenAIRE

    Meegan, Charles A.; Hartmann, Dieter H.; Brainerd, J. J.; Briggs, Michael S.; Paciesas, William S.; Pendleton, Geoffrey; Kouveliotou, Chryssa; Fishman, Gerald; Blumenthal, George; Brock, Martin

    1995-01-01

    The demonstration of repeated gamma-ray bursts from an individual source would severely constrain burst source models. Recent reports (Quashnock and Lamb 1993; Wang and Lingenfelter 1993) of evidence for repetition in the first BATSE burst catalog have generated renewed interest in this issue. Here, we analyze the angular distribution of 585 bursts of the second BATSE catalog (Meegan et al. 1994). We search for evidence of burst recurrence using the nearest and farthest neighbor statistic and...

  18. 2D Metals by Repeated Size Reduction.

    Science.gov (United States)

    Liu, Hanwen; Tang, Hao; Fang, Minghao; Si, Wenjie; Zhang, Qinghua; Huang, Zhaohui; Gu, Lin; Pan, Wei; Yao, Jie; Nan, Cewen; Wu, Hui

    2016-10-01

    A general and convenient strategy for manufacturing freestanding metal nanolayers is developed on large scale. By the simple process of repeatedly folding and calendering stacked metal sheets followed by chemical etching, free-standing 2D metal (e.g., Ag, Au, Fe, Cu, and Ni) nanosheets are obtained with thicknesses as small as 1 nm and with sizes of the order of several micrometers.

  19. Repeatability and Workability Evaluation of SIGMOD 2011

    DEFF Research Database (Denmark)

    Bonnet, Philippe

    2011-01-01

    SIGMOD has offered, since 2008, to verify the experiments published in the papers accepted at the conference. This year, we have been in charge of reproducing the experiments provided by the authors (repeatability), and exploring changes to experiment parameters (workability). In this paper, we a...... find that most experiments are distributed as Linux packages accompanied by instructions on how to setup and run the experiments. We are still far from the vision of executable papers...

  20. Repeatability of Response to Asthma Medications

    Science.gov (United States)

    Wu, Ann; Tantisira, Kelan; Li, Lingling; Schuemann, Brooke; Weiss, Scott

    2010-01-01

    Background Pharmacogenetic studies of drug response in asthma assume that patients respond consistently to a treatment but that treatment response varies across patients, however, no formal studies have demonstrated this. Objective To determine the repeatability of commonly used outcomes for treatment response to asthma medications: bronchodilator response, forced expiratory volume in 1 second (FEV1), and provocative concentration of methacholine producing a 20% decline in FEV1 (PC20). Methods The Childhood Asthma Management Program (CAMP) was a multi-center clinical trial of children randomized to receiving budesonide, nedocromil, or placebo. We determined the intraclass correlation coefficient (ICC) for each outcome over repeated visits over four years in CAMP using mixed effects regression models. We adjusted for the covariates: age, race/ethnicity, height, family income, parental education, and symptom score. We incorporated each outcome for each child as repeated outcome measurements and stratified by treatment group. Results The ICC for bronchodilator response was 0.31 in the budesonide group, 0.35 in the nedocromil group, and 0.40 in the placebo group, after adjusting for covariates. The ICC for FEV1 was 0.71 in the budesonide group, 0.60 in the nedocromil group, and 0.69 in the placebo group, after adjusting for covariates. The ICC for PC20 was 0.67 in the budesonide and placebo groups and 0.73 in the nedocromil group, after adjusting for covariates. Conclusion The within treatment group repeatability of FEV1 and PC20 are high; thus these phenotypes are heritable. FEV1 and PC20 may be better phenotypes than bronchodilator response for studies of treatment response in asthma. PMID:19064281

  1. Repeated extraction of DNA from FTA cards

    DEFF Research Database (Denmark)

    Stangegaard, Michael; Ferrero, Laura; Børsting, Claus

    2011-01-01

    Extraction of DNA using magnetic bead based techniques on automated DNA extraction instruments provides a fast, reliable and reproducible method for DNA extraction from various matrices. However, the yield of extracted DNA from FTA-cards is typically low. Here, we demonstrate that it is possible...... to repeatedly extract DNA from the processed FTA-disk. The method increases the yield from the nanogram range to the microgram range....

  2. Repeated extraction of DNA from FTA cards

    OpenAIRE

    Stangegaard, Michael; Ferrero, Laura; Børsting, Claus; Frank-Hansen, Rune; Hansen, Anders Johannes; Morling, Niels

    2011-01-01

    Extraction of DNA using magnetic bead based techniques on automated DNA extraction instruments provides a fast, reliable and reproducible method for DNA extraction from various matrices. However, the yield of extracted DNA from FTA-cards is typically low. Here, we demonstrate that it is possible to repeatedly extract DNA from the processed FTA-disk. The method increases the yield from the nanogram range to the microgram range.

  3. Repeated extraction of DNA from FTA cards

    DEFF Research Database (Denmark)

    Stangegaard, Michael; Ferrero, Laura; Børsting, Claus

    2011-01-01

    Extraction of DNA using magnetic bead based techniques on automated DNA extraction instruments provides a fast, reliable and reproducible method for DNA extraction from various matrices. However, the yield of extracted DNA from FTA-cards is typically low. Here, we demonstrate that it is possible...... to repeatedly extract DNA from the processed FTA-disk. The method increases the yield from the nanogram range to the microgram range....

  4. A Central Limit Theorem for Repeating Patterns

    CERN Document Server

    Abrams, Aaron; Landau, Henry; Landau, Zeph; Pommersheim, James

    2012-01-01

    This note gives a central limit theorem for the length of the longest subsequence of a random permutation which follows some repeating pattern. This includes the case of any fixed pattern of ups and downs which has at least one of each, such as the alternating case considered by Stanley in [2] and Widom in [3]. In every case considered the convergence in the limit of long permutations is to normal with mean and variance linear in the length of the permutations.

  5. Repeatability and Workability Evaluation of SIGMOD 2011

    DEFF Research Database (Denmark)

    Bonnet, Philippe

    2011-01-01

    SIGMOD has offered, since 2008, to verify the experiments published in the papers accepted at the conference. This year, we have been in charge of reproducing the experiments provided by the authors (repeatability), and exploring changes to experiment parameters (workability). In this paper, we a...... find that most experiments are distributed as Linux packages accompanied by instructions on how to setup and run the experiments. We are still far from the vision of executable papers...

  6. Epigenetics and Triplet-Repeat Neurological Diseases

    OpenAIRE

    Nageshwaran, Sathiji; Festenstein, Richard

    2015-01-01

    The term “junk DNA” has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterochromatinized resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions f...

  7. Epigenetics and triplet repeat neurological diseases

    OpenAIRE

    Sathiji eNageshwaran; Richard eFestenstein

    2015-01-01

    The term ‘junk DNA’ has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterchromatinised resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions fr...

  8. Ultraviolet to near-infrared spectroscopy of the potentially hazardous, low delta-V asteroid (175706) 1996 FG3. Backup target of the sample return mission MarcoPolo-R

    Science.gov (United States)

    Perna, D.; Dotto, E.; Barucci, M. A.; Fornasier, S.; Alvarez-Candal, A.; Gourgeot, F.; Brucato, J. R.; Rossi, A.

    2013-07-01

    Context. Primitive near-Earth asteroids (NEAs) are important subjects of study for current planetary research. Their investigation can provide crucial information on topics such as the formation of the solar system, the emergence of life, and the mitigation of the risk of asteroid impact. Sample return missions from primitive asteroids have been scheduled or are being studied by space agencies, including the MarcoPolo-R mission selected for the assessment study phase of ESA M3 missions. Aims: We want to improve our knowledge of the surface composition and physical nature of the potentially hazardous, low delta-V asteroid (175706) 1996 FG3, backup target of MarcoPolo-R. This intriguing object shows an as-yet unexplained spectral variability. Methods: We performed spectroscopic observations of 1996 FG3 using the visible spectrograph DOLORES at the Telescopio Nazionale Galileo (TNG), and the UV-to-NIR X-Shooter instrument at the ESO Very Large Telescope (VLT). Results: We find featureless spectra and we classify 1996 FG3 as a primitive Xc-type in the Bus-DeMeo taxonomy. Based on literature comparison, we confirm the spectral variability of this object at near-infrared (NIR) wavelengths, and find that spectral variations exist also for the visible spectral region. Phase reddening cannot explain such variations. Obtained with the same observational conditions for the whole 0.3-2.2 μm range, our X-Shooter spectrum allowed a proper comparison with the RELAB meteorite database. A very good fit is obtained with the very primitive C2 Tagish Lake carbonaceous chondrite (pressed powder), confirming 1996 FG3 as a suitable target for a sample return mission from primitive NEAs. Conclusions: We hypothesize a compacted/cemented surface for 1996 FG3, like that observed by the Hayabusa mission on (25143) Itokawa, with the possible presence of regions showing different degrees of surface roughness. This variegation could be related to the binary nature of 1996 FG3, but to check this

  9. Chromatin domains and prediction of MAR sequences.

    Science.gov (United States)

    Boulikas, T

    1995-01-01

    Polynuceosomes are constrained into loops or domains and are insulated from the effects of chromatin structure and torsional strain from flanking domains by the cross-complexation of matrix-attached regions (MARs) and matrix proteins. MARs or SARs have an average size of 500 bp, are spaced about every 30 kb, and are control elements maintaining independent realms of gene activity. A fraction of MARs may cohabit with core origin replication (ORIs) and another fraction might cohabit with transcriptional enhancers. DNA replication, transcription, repair, splicing, and recombination seem to take place on the nuclear matrix. Classical AT-rich MARs have been proposed to anchor the core enhancers and core origins complexed with low abundancy transcription factors to the nuclear matrix via the cooperative binding to MARs of abundant classical matrix proteins (topoisomerase II, histone H1, lamins, SP120, ARBP, SATB1); this creates a unique nuclear microenvironment rich in regulatory proteins able to sustain transcription, replication, repair, and recombination. Theoretical searches and experimental data strongly support a model of activation of MARs and ORIs by transcription factors. A set of 21 characteristics are deduced or proposed for MAR/ORI sequences including their enrichment in inverted repeats, AT tracts, DNA unwinding elements, replication initiator protein sites, homooligonucleotide repeats (i.e., AAA, TTT, CCC), curved DNA, DNase I-hypersensitive sites, nucleosome-free stretches, polypurine stretches, and motifs with a potential for left-handed and triplex structures. We are establishing Banks of ORI and MAR sequences and have undertaken a large project of sequencing a large number of MARs in an effort to determine classes of DNA sequences in these regulatory elements and to understand their role at the origins of replication and transcriptional enhancers.

  10. Repeated-sprint ability and aerobic fitness.

    Science.gov (United States)

    Thébault, Nicolas; Léger, Luc A; Passelergue, Philippe

    2011-10-01

    The purpose of this study was to reinvestigate the relationship between aerobic fitness and fatigue indices of repeated-sprint ability (RSA), with special attention to methodological normalization. Soldiers were divided into low (n = 10) and high (n = 9) fitness groups according to a preset maximal aerobic speed (MAS) of 17 km·h(-1) (∼60 ml O2·kg(-1)·min) measured with the University of Montreal Track Test (UMTT). Subjects' assessment included the RSA test (3 sets of 5 40-m sprints with 1-minute rest between sprints and 1.5 minutes between sets), a 40-m sprint (criterion test used in the computation of fatigue indices for the RSA test), strength and power measurement of the lower limbs, and the 20-m shuttle run test (20-m SRT) and the UMTT, which are measures of maximal aerobic power. The highest correlation with the RSA fatigue indices was obtained with the 20-m SRT (r = 0.90, p = 0.0001, n = 19), a test with 180° direction changes and accelerations and decelerations. The lower correlation (r = 0.66, p repeated sprints and achieved better recovery between series. A MAS of at least 17 km·h(-1) favors constant and high speed level during repeated sprints. From a practical point of view, a high aerobic fitness is a precious asset in counteracting fatigue in sports with numerous sprint repetitions.

  11. Histone deacetylase complexes promote trinucleotide repeat expansions.

    Directory of Open Access Journals (Sweden)

    Kim Debacker

    2012-02-01

    Full Text Available Expansions of DNA trinucleotide repeats cause at least 17 inherited neurodegenerative diseases, such as Huntington's disease. Expansions can occur at frequencies approaching 100% in affected families and in transgenic mice, suggesting that specific cellular proteins actively promote (favor expansions. The inference is that expansions arise due to the presence of these promoting proteins, not their absence, and that interfering with these proteins can suppress expansions. The goal of this study was to identify novel factors that promote expansions. We discovered that specific histone deacetylase complexes (HDACs promote CTG•CAG repeat expansions in budding yeast and human cells. Mutation or inhibition of yeast Rpd3L or Hda1 suppressed up to 90% of expansions. In cultured human astrocytes, expansions were suppressed by 75% upon inhibition or knockdown of HDAC3, whereas siRNA against the histone acetyltransferases CBP/p300 stimulated expansions. Genetic and molecular analysis both indicated that HDACs act at a distance from the triplet repeat to promote expansions. Expansion assays with nuclease mutants indicated that Sae2 is one of the relevant factors regulated by Rpd3L and Hda1. The causal relationship between HDACs and expansions indicates that HDACs can promote mutagenesis at some DNA sequences. This relationship further implies that HDAC3 inhibitors being tested for relief of expansion-associated gene silencing may also suppress somatic expansions that contribute to disease progression.

  12. Landauer's Principle in Repeated Interaction Systems

    Science.gov (United States)

    Hanson, Eric P.; Joye, Alain; Pautrat, Yan; Raquépas, Renaud

    2017-01-01

    We study Landauer's Principle for Repeated Interaction Systems (RIS) consisting of a reference quantum system S in contact with a structured environment E made of a chain of independent quantum probes; S interacts with each probe, for a fixed duration, in sequence. We first adapt Landauer's lower bound, which relates the energy variation of the environment E to a decrease of entropy of the system S during the evolution, to the peculiar discrete time dynamics of RIS. Then we consider RIS with a structured environment E displaying small variations of order {T^{-1}} between the successive probes encountered by S, after {n ˜eq T} interactions, in keeping with adiabatic scaling. We establish a discrete time non-unitary adiabatic theorem to approximate the reduced dynamics of S in this regime, in order to tackle the adiabatic limit of Landauer's bound. We find that saturation of Landauer's bound is related to a detailed balance condition on the repeated interaction system, reflecting the non-equilibrium nature of the repeated interaction system dynamics. This is to be contrasted with the generic saturation of Landauer's bound known to hold for continuous time evolution of an open quantum system interacting with a single thermal reservoir in the adiabatic regime.

  13. Metaphors, domains and embodiment

    Directory of Open Access Journals (Sweden)

    M.E. Botha

    2005-07-01

    Full Text Available Investigations of metaphorical meaning constitution and meaning (in- variance have revealed the significance of semantic and semiotic domains and the contexts within which they function as basis for the grounding of metaphorical meaning. In this article some of the current views concerning the grounding of metaphorical meaning in experience and embodiment are explored. My provisional agreement with Lakoff, Johnson and others about the “conceptual” nature of metaphor rests on an important caveat, viz. that this bodily based conceptual structure which lies at the basis of linguistic articulations of metaphor, is grounded in a deeper ontic structure of the world and of human experience. It is the “metaphorical” (actually “analogical” ontological structure of this grounding that is of interest for the line of argumentation followed in this article. Because Johnson, Lakoff and other’s proposal to ground metaphorical meaning in embodiment and neural processes is open to being construed as subjectivist and materialist, I shall attempt to articulate the contours of an alternative theory of conceptual metaphor, meaning and embodiment which counteracts these possibilities. This theory grounds metaphorical meaning and meaning change in an ontological and anthropological framework which recognises the presence and conditioning functioning of radially ordered structures for reality. These categorisations in which humankind, human knowledge and reality participate, condition and constrain (ground analogical and metaphorical meaning transfer, cross-domain mappings, and blends in cognition and in language, provide the basis for the analogical concepts found in these disciplines.

  14. Repeatability and reproducibility of corneal thickness using SOCT Copernicus HR.

    Science.gov (United States)

    Vidal, Silvia; Viqueira, Valentín; Mas, David; Domenech, Begoña

    2013-05-01

    The aim of this study is to determine the reliability of corneal thickness measurements derived from SOCT Copernicus HR (Fourier domain OCT). Thirty healthy eyes of 30 subjects were evaluated. One eye of each patient was chosen randomly. Images were obtained of the central (up to 2.0 mm from the corneal apex) and paracentral (2.0 to 4.0 mm) cornea. We assessed corneal thickness (central and paracentral) and epithelium thickness. The intra-observer repeatability data were analysed using the intra-class correlation coefficient (ICC) for a range of 95 per cent within-subject standard deviation (S(W)) and the within-subject coefficient of variation (C(W)). The level of agreement by Bland-Altman analysis was also represented for the study of the reproducibility between observers and agreement between methods of measurement (automatic versus manual). The mean value of the central corneal thickness (CCT) was 542.4 ± 30.1 μm (SD). There was a high intra-observer agreement, finding the best result in the central sector with an intra-class correlation coefficient of 0.99, 95 per cent CI (0.989 to 0.997) and the worst, in the minimum corneal thickness, with an intra-class correlation coefficient of 0.672, 95 per cent CI (0.417 to 0.829). Reproducibility between observers was very high. The best result was found in the central sector thickness obtained both manually and automatically with an intra-class correlation coefficient of 0.990 in both cases and the worst result in the maximum corneal thickness with an intra-class correlation coefficient of 0.827. The agreement between measurement methods was also very high with intra-class correlation coefficient greater than 0.91. On the other hand the repeatability and reproducibility for epithelial measurements was poor. Pachymetric mapping with SOCT Copernicus HR was found to be highly repeatable and reproducible. We found that the device lacks an appropriate ergonomic design as proper focusing of the laser beam onto the

  15. A Unified Model for Repeating and Non-repeating Fast Radio Bursts

    Science.gov (United States)

    Bagchi, Manjari

    2017-04-01

    The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

  16. Ligand binding by PDZ domains

    DEFF Research Database (Denmark)

    Chi, Celestine N.; Bach, Anders; Strømgaard, Kristian

    2012-01-01

    The postsynaptic density protein-95/disks large/zonula occludens-1 (PDZ) protein domain family is one of the most common protein-protein interaction modules in mammalian cells, with paralogs present in several hundred human proteins. PDZ domains are found in most cell types, but neuronal proteins......, for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well...

  17. Domain-specific enhancement of metacognitive ability following meditation training.

    Science.gov (United States)

    Baird, Benjamin; Mrazek, Michael D; Phillips, Dawa T; Schooler, Jonathan W

    2014-10-01

    Contemplative mental practices aim to enable individuals to develop greater awareness of their own cognitive and affective states through repeated examination of first-person experience. Recent cross-sectional studies of long-term meditation practitioners suggest that the subjective reports of such individuals are better calibrated with objective indices; however, the impact of mental training on metacognitive ability has not yet been examined in a randomized controlled investigation. The present study evaluated the impact of a 2-week meditation-training program on introspective accuracy in the domains of perception and memory. Compared with an active control group that elicited no change, we found that a 2-week meditation program significantly enhanced introspective accuracy, quantified by metacognitive judgments of cognition on a trial-by-trial basis, in a memory but not a perception domain. Together, these data suggest that, in at least some domains, the human capacity to introspect is plastic and can be enhanced through training.

  18. Technical Report for DE-FG02-03ER46029 Sugar-Coated PPEs, Novel Nanomaterials and Sensing Modules for Disease and Bioterrorism Related Threats

    Energy Technology Data Exchange (ETDEWEB)

    Uwe Bunz

    2003-08-27

    The detection and sensing of biological warfare agents (Ricin, Anthrax toxin), of disease agents (cholera, botulinum and tetanus toxins, influenza virus etc) and of biologically active species is important for national security and disease control. A premiere goal would be the simple colorimetric or fluorimetric detection of such toxins by a dipstick test. It would be desirable to sense 5,000-10,000 toxin molecules, i.e. 10-100 fg of a toxin contained 1-5 mL of sample. Fluorescent conjugated polymers should be particularly interesting in this regard, because they can carry multiple identical and/or different recognition units. Such an approach is particularly valuable for the detection of lectin toxins, because these bind to oligomeric carbohydrate displays. Lectins bind multivalently to sugars, i.e. several covalently connected sugar moieties have to be exposed to the lectin at the same time to obtain binding. The requirement of multivalency of the lectin-sugar interactions should allow a very sensitive detection of lectins with sugar coated conjugated polymers in an agglutination type assay, where the fluorescence of the PPEs disappears upon binding to the lectins. High molecular weights of the used PPEs would mean high sensitivity. Herein we present our progress towards that goal up to date.

  19. Coherent Hole-burning, Mollow Absorption Effect, and Four-wave Mixing in Cycling Transition Fe=0(←→)Fg=1 Subject to a Magnetic Field

    Institute of Scientific and Technical Information of China (English)

    古英; 孙庆青; 龚旗煌

    2004-01-01

    @@ We investigate the quantum coherence effects of a cycling transition Fe=0(←→)Fg=1, which is saturated and probed by the circular polarized fields, and is subject to a linearly polarized field and a magnetic field.Saturation field is applied in the case of the maximum coherence between the drive Rabi frequency and magnetic field, corresponding to the electromagnetically induced absorption (EIA) with negative dispersion found by Gu et al.In a small saturation Rabi frequency, the holes are burned in two Autler-Towns peaks outside two symmetric electromagnetically induced transparency (EIT) windows due to the two-photon resonance.When the saturation Rabi frequency is comparable with the drive Rabi frequency, the holes caused by the coherent population oscillation appear in the EIA spectrum.Continuing to increase the saturation Rabi frequency, we observe several emission peaks due to the Mollow absorption effects.Simultaneously, four-wave mixing (FWM) effects in this process are discussed.In the picture of dressed states, we explain the multi-peaks of quantum efficiency of FWM in terms of the multi-photon resonance conditions.We also find a good agreement between the absorption peaks and the FMW peaks.Finally, whenever EIA, EIT, or Mollow absorption happens, the dispersion at the pump-probe detuning center is kept to be negative with increasing the saturation Rabi frequency.It means that this point is suitable to perform the superluminal light propagation experiments.

  20. Repetition as one of the lexical and syntactic means of creation the integrity of syntactic period in verse translations of F.G. Lorca

    Directory of Open Access Journals (Sweden)

    Radchenko Galina Ivanovna

    2016-03-01

    Full Text Available In the article on the examples of translation of Spanish poems by the poet F.G. Lorca into Russian addresses the conservation of melody and rhythm of the original in the translation. In connection with membership of the Spanish and Russian languages to the Indo-European group we have ample opportunity to compare syntactic text-forming tools. One of syntactic means to recreate the rhythm of verse is the translations of a period. The period is usually based on the lexical and syntactic parallelism and repetition is made as a complex sentence. Our study showed that in the period of construction, connection parts and members of both Spanish and Russian versions are multilevel repetitive. Although it is possible the construction period and without the use of repetitions based on intonation and the sense of unity of its parts. Different versions can be a syntactic structure and semantic content, which range from the clear superiority of the first part to the harmony parts.